View source for Medicine:Preterm birth

{{short description|Birth at less than a specified gestational age}}
{{Infobox medical condition (new)
| name          = Preterm birth
| pronounce     = 
| synonyms      = Premature birth, preemies, premmies
| image         = Premature infant with ventilator.jpg
| alt           = 
| caption       = [[Medicine:Medical ventilator|Intubated]] preterm baby in an incubator
| field         = Neonatology, [[Medicine:Pediatrics|Pediatrics]], [[Medicine:Obstetrics|Obstetrics]]
| symptoms      = [[Biology:Birth|Birth]] of a baby at younger than 37 weeks' gestational age<ref name=NIH2014Def/>
| complications = [[Medicine:Cerebral palsy|Cerebral palsy]], delays in development, hearing problems, [[Medicine:Visual impairment|sight problems]]<ref name=NIH2014Def/>
| onset         = 
| duration      = 
| types         = 
| causes        = Often unknown<ref name=WHO2014/>
| risks         = [[Medicine:Diabetes mellitus|Diabetes]], high blood pressure, [[Biology:Multiple birth|Multiple gestation]], obesity or underweight, a number of vaginal infections, celiac disease, [[Chemistry:Tobacco smoking|tobacco smoking]], [[Medicine:Psychological stress|psychological stress]]<ref name=WHO2014/><ref name=NIH2014Risk/><ref name=SacconeBerghella2015/>
| diagnosis     = 
| differential  = 
| prevention    = [[Chemistry:Progesterone|Progesterone]]<ref name=NIH2014Pre/>
| treatment     = Corticosteroids, keeping the baby warm through skin-to-skin contact, supporting [[Social:Breastfeeding|breastfeeding]], treating [[Medicine:Infection|infection]]s, supporting breathing<ref name=WHO2014/><ref name=NIH2013Mg/>
| medication    = 
| prognosis     = 
| frequency     = ~15 million a year (12% of deliveries)<ref name=WHO2014/>
| deaths        = 805,800<ref name=GBD2015De/>
}}
<!-- Definition and symptoms -->
'''Preterm birth''', also known as '''premature birth''', is the [[Medicine:Childbirth|birth]] of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks.<ref name="NIH2014Def">{{cite web|title=Preterm Labor and Birth: Condition Information|url=http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/default.aspx|website=[[Organization:National Institutes of Health|National Institutes of Health]]|access-date=7 March 2015|date=3 November 2014|url-status=live|archive-url=https://web.archive.org/web/20150402111534/http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/default.aspx|archive-date=2 April 2015}}</ref> Extreme preterm<ref name="WHO2014" /> is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 34 weeks, late preterm birth is between 34 and 36 weeks' gestation.<ref>{{cite journal | vauthors = Brown HK, Speechley KN, Macnab J, Natale R, Campbell MK | title = Neonatal morbidity associated with late preterm and early term birth: the roles of gestational age and biological determinants of preterm birth | journal = International Journal of Epidemiology | volume = 43 | issue = 3 | pages = 802–814 | date = June 2014 | pmid = 24374829 | pmc = 4052131 | doi = 10.1093/ije/dyt251 }}</ref> These babies are also known as '''premature babies''' or colloquially '''preemies''' (American English)<ref>{{cite web|url=https://www.oxfordlearnersdictionaries.com/definition/english/preemie?q=preemie |title=preemie noun – Definition, pictures, pronunciation and usage notes &#124; Oxford Advanced Learner's Dictionary at |publisher=Oxfordlearnersdictionaries.com |date= |access-date=2022-05-06}}</ref> or '''premmies''' (Australian English).<ref>{{cite web|url=https://dictionary.cambridge.org/dictionary/english/premmie|title = Premmie}}</ref> Symptoms of preterm labor include [[Medicine:Uterine contraction|uterine contraction]]s which occur more often than every ten minutes and/or the leaking of fluid from the [[Biology:Vagina|vagina]] before 37 weeks.<ref name="NIH2015Prelab">{{cite web|title=What are the symptoms of preterm labor?|url=http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/symptoms.aspx|website=[[Organization:National Institutes of Health|National Institutes of Health]]|access-date=7 March 2015|date=11 June 2013|url-status=live|archive-url=https://web.archive.org/web/20150402154200/http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/symptoms.aspx|archive-date=2 April 2015}}</ref><ref name="Vink_2018">{{cite journal | vauthors = Vink J, Myers K | title = Cervical alterations in pregnancy | journal = Best Practice & Research. Clinical Obstetrics & Gynaecology | volume = 52 | pages = 88–102 | date = October 2018 | pmid = 30314740 | pmc = 6282836 | doi = 10.1016/j.bpobgyn.2018.03.007 | series = Biological Basis and Prevention of Preterm Birth Treatment }}</ref> Premature infants are at greater risk for [[Medicine:Cerebral palsy|cerebral palsy]], delays in development, hearing problems and problems with their [[Medicine:Visual impairment|vision]].<ref name="NIH2014Def" /> The earlier a baby is born, the greater these risks will be.<ref name="NIH2014Def" /><!-- Causes -->

The cause of spontaneous preterm birth is often not known.<ref name=WHO2014/> Risk factors include [[Medicine:Diabetes mellitus|diabetes]], high blood pressure, [[Biology:Multiple birth|multiple gestation]] (being pregnant with more than one baby), being either obese or underweight, vaginal infections, [[Earth:Air pollution|air pollution]] exposure, [[Chemistry:Tobacco smoking|tobacco smoking]], and [[Medicine:Psychological stress|psychological stress]].<ref name=WHO2014/><ref name=NIH2014Risk>{{cite web|title=What are the risk factors for preterm labor and birth?|url=http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/who_risk.aspx|website=[[Organization:National Institutes of Health|National Institutes of Health]]|access-date=7 March 2015|date=3 November 2014|url-status=live|archive-url=https://web.archive.org/web/20150405075659/http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/who_risk.aspx|archive-date=5 April 2015}}</ref><ref name=Kor2017>{{cite journal | vauthors = Korten I, Ramsey K, Latzin P | title = Air pollution during pregnancy and lung development in the child | journal = Paediatric Respiratory Reviews | volume = 21 | pages = 38–46 | date = January 2017 | pmid = 27665510 | doi = 10.1016/j.prrv.2016.08.008 }}</ref> For a healthy pregnancy, medical [[Medicine:Labor induction|induction of labor]] or cesarean section are not recommended before 39 weeks unless required for other medical reasons.<ref name=WHO2014/> There may be certain medical reasons for early delivery such as preeclampsia.<ref>{{cite web|title=What causes preterm labor and birth?|url=http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/causes.aspx|website=[[Organization:National Institutes of Health|National Institutes of Health]]|access-date=7 March 2015|date=3 November 2014|url-status=live|archive-url=https://web.archive.org/web/20150402165739/http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/causes.aspx|archive-date=2 April 2015}}</ref>

<!-- Prevention and treatment -->
Preterm birth may be prevented in those at risk if the hormone [[Chemistry:Progesterone|progesterone]] is taken during [[Medicine:Pregnancy|pregnancy]].<ref name=NIH2014Pre/> Evidence does not support the usefulness of [[Medicine:Bed rest|bed rest]].<ref name=NIH2014Pre>{{cite web|title=What treatments are used to prevent preterm labor and birth?|url=http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/treatments.aspx |publisher=[[Organization:National Institutes of Health|National Institutes of Health]]|access-date=7 March 2015|date=3 November 2014|url-status=live|archive-url=https://web.archive.org/web/20150402122124/http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/treatments.aspx|archive-date=2 April 2015}}</ref><ref>{{cite journal | vauthors = Sosa CG, Althabe F, Belizán JM, Bergel E | title = Bed rest in singleton pregnancies for preventing preterm birth | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 3 | pages = CD003581 | date = March 2015 | pmid = 25821121 | pmc = 7144825 | doi = 10.1002/14651858.CD003581.pub3 }}</ref> It is estimated that at least 75% of preterm infants would survive with appropriate treatment, and the survival rate is highest among the infants born the latest in gestation.<ref name=WHO2014/> In women who might deliver between 24 and 37 weeks, corticosteroid treatment may improve outcomes.<ref name=NIH2013Mg>{{cite web|title=What treatments can reduce the chances of preterm labor & birth?|url=http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/reduce.aspx|website=[[Organization:National Institutes of Health|National Institutes of Health]]|access-date=7 March 2015|date=11 June 2013|url-status=live|archive-url=https://web.archive.org/web/20150402102224/http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/Pages/reduce.aspx|archive-date=2 April 2015}}</ref><ref name=ACOG2016>{{cite web|title=Antenatal Corticosteroid Therapy for Fetal Maturation|url=http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Antenatal-Corticosteroid-Therapy-for-Fetal-Maturation|website=ACOG|access-date=27 September 2016|date=October 2016|url-status=live|archive-url=https://web.archive.org/web/20160929153101/http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Antenatal-Corticosteroid-Therapy-for-Fetal-Maturation|archive-date=29 September 2016}}</ref> A number of medications, including [[Chemistry:Nifedipine|nifedipine]], may delay delivery so that a mother can be moved to where more medical care is available and the corticosteroids have a greater chance to work.<ref>{{cite journal | vauthors = Haram K, Mortensen JH, Morrison JC | title = Tocolysis for acute preterm labor: does anything work | journal = The Journal of Maternal-Fetal & Neonatal Medicine | volume = 28 | issue = 4 | pages = 371–378 | date = March 2015 | pmid = 24990666 | doi = 10.3109/14767058.2014.918095 | s2cid = 20078137 }}</ref> Once the baby is born, care includes keeping the baby warm through skin-to-skin contact or incubation, supporting [[Social:Breastfeeding|breastfeeding]] and/or formula feeding, treating [[Medicine:Infection|infection]]s, and supporting breathing.<ref name=WHO2014/> Preterm babies sometimes require [[Medicine:Intubation|intubation]].<ref name="WHO2014" />

<!-- Epidemiology and prognosis -->
Preterm birth is the most common cause of death among infants worldwide.<ref name=NIH2014Def/> About 15 million babies are preterm each year (5% to 18% of all deliveries).<ref name=WHO2014/> Late preterm birth accounts for 75% of all preterm births.<ref>{{cite journal | vauthors = Trilla CC, Medina MC, Ginovart G, Betancourt J, Armengol JA, Calaf J | title = Maternal risk factors and obstetric complications in late preterm prematurity | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 179 | pages = 105–109 | date = August 2014 | pmid = 24965989 | doi = 10.1016/j.ejogrb.2014.05.030 }}</ref> This rate is inconsistent across countries. In the United Kingdom 7.9% of babies are born pre-term and in the United States 12.3% of all births are before 37 weeks gestation.<ref>{{cite journal | vauthors = Chow YH, Dattani N | title = Estimating conception statistics using gestational age information from NHS Numbers for Babies data | journal = Health Statistics Quarterly | volume = 41 | issue = 41 | pages = 21–27 | date = 2009-02-26 | pmid = 19320250 | doi = 10.1057/hsq.2009.5 | s2cid = 23996035 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mathews TJ, Miniño AM, Osterman MJ, Strobino DM, Guyer B | title = Annual summary of vital statistics: 2008 | journal = Pediatrics | volume = 127 | issue = 1 | pages = 146–157 | date = January 2011 | pmid = 21173001 | pmc = 4079290 | doi = 10.1542/peds.2010-3175 }}</ref> Approximately 0.5% of births are extremely early periviable births (20–25 weeks of gestation), and these account for most of the deaths.<ref name="Ecker_2017">{{cite journal | vauthors = Ecker JL, Kaimal A, Mercer BM, Blackwell SC, deRegnier RA, Farrell RM, Grobman WA, Resnik JL, Sciscione AC | display-authors = 6 | collaboration = American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine | title = Obstetric Care consensus No. 6: Periviable Birth | journal = Obstetrics and Gynecology | volume = 130 | issue = 4 | pages = e187–e199 | date = October 2017 | pmid = 28937572 | doi = 10.1097/AOG.0000000000002352 }}</ref> In many countries, rates of premature births have increased between the 1990s and 2010s.<ref name=WHO2014>{{cite web |url=https://www.who.int/mediacentre/factsheets/fs363/en/ |title=Preterm birth Fact sheet N°363 |author=World Health Organization |work=who.int |date=November 2014 |access-date=6 March 2015 |url-status=live |archive-url=https://web.archive.org/web/20150307050438/http://www.who.int/mediacentre/factsheets/fs363/en/ |archive-date=7 March 2015}}</ref> Complications from preterm births resulted in 0.81 million deaths in 2015, down from 1.57 million in 1990.<ref name=GBD2015De>{{cite journal | vauthors = Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, etal | collaboration = BD 2015 Mortality and Causes of Death Collaborators | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 }}</ref><ref name="GDB2013">{{cite journal | vauthors = Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, etal | collaboration = GBD 2013 Mortality and Causes of Death Collaborators | title = Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 | journal = Lancet | volume = 385 | issue = 9963 | pages = 117–171 | date = January 2015 | pmid = 25530442 | pmc = 4340604 | doi = 10.1016/S0140-6736(14)61682-2 }}</ref> The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72%.<ref name=Clo2016>{{cite book |title=Cloherty and Stark's Manual of Neonatal Care |date=2016 |publisher=Lippincott Williams & Wilkins |isbn=9781496367495 |page=161 |edition=8th}}</ref>{{Update inline|date=June 2023}} The chances of survival without any long-term difficulties are lower.<ref name=Jar2015>{{cite journal | vauthors = Jarjour IT | title = Neurodevelopmental outcome after extreme prematurity: a review of the literature | journal = Pediatric Neurology | volume = 52 | issue = 2 | pages = 143–152 | date = February 2015 | pmid = 25497122 | doi = 10.1016/j.pediatrneurol.2014.10.027 }}</ref>

== Signs and symptoms ==
[[File:Mom and Premature Baby at Kapiolani.jpg|thumb|right|A new mother holds her premature baby at Kapiolani Medical Center NICU in Honolulu, Hawaii.]]
Signs and symptoms of preterm labor include four or more uterine contractions in one hour. In contrast to false labour, true labor is accompanied by [[Medicine:Cervical dilation|cervical dilation]] and [[Medicine:Cervical effacement|effacement]]. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection ([[Medicine:Chorioamnionitis|chorioamnionitis]]) is a serious threat to both [[Biology:Fetus|fetus]] and mother. In some cases, the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process.

== Causes ==
The main categories of causes of preterm birth are preterm [[Medicine:Labor induction|labor induction]] and spontaneous preterm labor.

=== Risk factors ===
The exact cause of spontaneous preterm birth is difficult to determine and it may be caused by many different factors at the same time as labor is a complex process.<ref>{{cite web | title = Preterm birth | publisher = World Health Organization | date = 19 February 2018 | url = https://www.who.int/news-room/fact-sheets/detail/preterm-birth | access-date = 20 May 2020}}</ref><ref>{{cite journal | vauthors = Frey HA, Klebanoff MA | title = The epidemiology, etiology, and costs of preterm birth | language = English | journal = Seminars in Fetal & Neonatal Medicine | volume = 21 | issue = 2 | pages = 68–73 | date = April 2016 | pmid = 26794420 | doi = 10.1016/j.siny.2015.12.011 }}</ref> The research available is limited with regard to the cervix and therefore is limited in discerning what is or is not normal.<ref name="Vink_2018" /> Four different pathways have been identified that can result in preterm birth and have considerable evidence: precocious fetal endocrine activation, uterine overdistension ([[Medicine:Placental abruption|placental abruption]]), decidual bleeding, and intrauterine inflammation or infection.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK11353/|title=Biological Pathways Leading to Preterm Birth| vauthors = Behrman RE, Butler AS | collaboration = Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes |date=2007|publisher=National Academies Press (US)|language=en}}</ref>

Identifying women at high risk of giving birth early would enable the health services to provide specialized care for these women and their babies, for example a hospital with a special care baby unit such as a [[Medicine:Neonatal intensive care unit|neonatal intensive care unit]] (NICU). In some instances, it may be possible to delay the birth. [[Risk score|Risk scoring systems]] have been suggested as an approach to identify those at higher risk, however, there is no strong research in this area so it is unclear whether the use of risk scoring systems for identifying mothers would prolong pregnancy and reduce the numbers of preterm births or not.<ref name="ReferenceB">{{cite journal | vauthors = Davey MA, Watson L, Rayner JA, Rowlands S | title = Risk-scoring systems for predicting preterm birth with the aim of reducing associated adverse outcomes | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 10 | pages = CD004902 | date = October 2015 | pmid = 26490698 | pmc = 7388653 | doi = 10.1002/14651858.CD004902.pub5 }}</ref>

====Maternal factors====
{|class="wikitable" style="float:right; margin-left:1em; font-size:88%"
! Risk factor !! [[Relative risk]]<ref name=Os2013>Unless otherwise given in boxes, reference is: {{cite journal | vauthors = Van Os M, Van Der Ven J, Kazemier B, Haak M, Pajkrt E, Mol BW, De Groot C | s2cid = 8036202 | title = Individualizing the risk for preterm birth: An overview of the literature | journal = Expert Review of Obstetrics & Gynecology | volume = 8 | issue = 5 | pages = 435–442 | year = 2013 | doi = 10.1586/17474108.2013.825481 }}</ref> !! 95% [[Confidence interval|confidence<br /> interval]]<ref name=Os2013/>
|-
| Fetal fibronectin || 4.0 || 2.9–5.5
|-
| Short cervical length || 2.9 || 2.1–3.9
|-
| Prenatal Care Absent<ref name="sciencedirect1254">{{cite journal | vauthors = Vintzileos AM, Ananth CV, Smulian JC, Scorza WE, Knuppel RA | title = The impact of prenatal care in the United States on preterm births in the presence and absence of antenatal high-risk conditions | journal = American Journal of Obstetrics and Gynecology | volume = 187 | issue = 5 | pages = 1254–1257 | date = November 2002 | pmid = 12439515 | doi = 10.1067/mob.2002.127140 }}</ref> || 2.9 || 2.8–3.0
|-
| [[Medicine:Chlamydia infection|Chlamydia]] || 2.2 || 1.0–4.8
|-
| Low socio-economic status || 1.9 || 1.7–2.2
|-
| Large or small pregnancy weight gain || 1.8 || 1.5–2.3
|-
| Short maternal height || 1.8 || 1.3–2.5
|-
| Periodontitis || 1.6 || 1.1–2.3
|-
| Celiac disease || 1.4<ref name="TersigniCastellani2014">{{cite journal | vauthors = Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N | display-authors = 6 | title = Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms | journal = Human Reproduction Update | volume = 20 | issue = 4 | pages = 582–593 | year = 2014 | pmid = 24619876 | doi = 10.1093/humupd/dmu007 | doi-access = free | hdl = 10807/56796 | hdl-access = free }}</ref> || 1.2–1.6<ref name="TersigniCastellani2014"/>
|-
| Asymptomatic bacteriuria || 1.1 || 0.8–1.5
|-
| High or low [[Body mass index|BMI]] || 0.96 || 0.66–1.4
|-
| || ''[[Odds ratio|odds ratio]]'' || 
|-
| History of spontaneous preterm birth || ''3.6'' || 3.2–4.0
|-
| [[Medicine:Bacterial vaginosis|Bacterial vaginosis]] || ''2.2'' || 1.5–3.1
|-
| Black ethnicity/race || ''2.0'' || 1.8–2.2 
|-
| Filipino ancestry<ref>{{cite web |url=http://health.hawaii.gov/mchb/files/2013/05/prematurity20101.pdf |title=Premature Birth Fact Sheet |access-date=2014-08-08 |url-status=live |archive-url=https://web.archive.org/web/20140808062311/http://health.hawaii.gov/mchb/files/2013/05/prematurity20101.pdf |archive-date=8 August 2014}}</ref> || ''1.7'' || 1.5–2.1
|-
| Unwanted pregnancy{{ r | UIP_Shah | p=1 | q=An unintended pregnancy was further classified as mistimed (not intended at that time) or unwanted (not desired at any time). ... There were statistically significantly increased odds of PTB among unintended (OR 1.31, 95% CI 1.09, 1.58), and unwanted (OR 1.50, 95% CI 1.41, 1.61) but not for mistimed (OR 1.36, 95% CI 0.96, 1.93) pregnancies. Unintended, unwanted, and mistimed pregnancies ending in a live birth are associated with a significantly increased risk of LBW and PTB. }} || ''1.5'' || 1.41–1.61
|-
| Unintended pregnancy{{ r | UIP_Shah | p=1 | q=An unintended pregnancy was further classified as mistimed (not intended at that time) or unwanted (not desired at any time). ... There were statistically significantly increased odds of PTB among unintended (OR 1.31, 95% CI 1.09, 1.58), and unwanted (OR 1.50, 95% CI 1.41, 1.61) but not for mistimed (OR 1.36, 95% CI 0.96, 1.93) pregnancies. Unintended, unwanted, and mistimed pregnancies ending in a live birth are associated with a significantly increased risk of LBW and PTB. }} || ''1.31'' || 1.09–1.58 
|-
| Being single/unmarried<ref name=Raatikainen2005/> || ''1.2'' || 1.03–1.28 
|}
[[File:Premature Births in England and Wales 2011 (cropped).png|thumb|upright=1.4|Percentage premature births in England and Wales 2011, by age of mother and whether single or multiple birth]]
Risk factors in the mother have been identified that are linked to a higher risk of a preterm birth. These include age (either very young or older),<ref name=Goldenberg2008>
{{cite journal | vauthors = Goldenberg RL, Culhane JF, Iams JD, Romero R | title = Epidemiology and causes of preterm birth | journal = Lancet | volume = 371 | issue = 9606 | pages = 75–84 | date = January 2008 | pmid = 18177778 | pmc = 7134569 | doi = 10.1016/S0140-6736(08)60074-4 }}</ref> high or low body mass index (BMI),<ref>{{cite web| vauthors = Moldenhauer JS |title=Risk factors present before pregnancy|url=http://www.merck.com/mmhe/sec22/ch258/ch258b.html|work=Merck Manual Home Edition|publisher=Merck Sharp & Dohme|url-status=live|archive-url=https://web.archive.org/web/20100817051002/http://www.merck.com/mmhe/sec22/ch258/ch258b.html|archive-date=17 August 2010}}</ref><ref>
{{cite journal | vauthors = Hendler I, Goldenberg RL, Mercer BM, Iams JD, Meis PJ, Moawad AH, MacPherson CA, Caritis SN, Miodovnik M, Menard KM, Thurnau GR, Sorokin Y | display-authors = 6 | title = The Preterm Prediction Study: association between maternal body mass index and spontaneous and indicated preterm birth | journal = American Journal of Obstetrics and Gynecology | volume = 192 | issue = 3 | pages = 882–886 | date = March 2005 | pmid = 15746686 | doi = 10.1016/j.ajog.2004.09.021 | url = https://zenodo.org/record/1258686 }}</ref> length of time between pregnancies,<ref>{{cite journal | vauthors = Smith GC, Pell JP, Dobbie R | title = Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study | journal = BMJ | volume = 327 | issue = 7410 | pages = 313–0 | date = August 2003 | pmid = 12907483 | pmc = 169644 | doi = 10.1136/bmj.327.7410.313 }}</ref> previous spontaneous (i.e., [[Medicine:Miscarriage|miscarriage]]) or surgical [[Medicine:Abortion|abortion]]s,<ref name="rcog-care">{{cite web| work = Evidence-based Clinical Guideline No. 7| publisher = Royal College of Obstetricians and Gynaecologists| title = The Care of Women Requesting Induced Abortion| pages = 44, 45| date = November 2011| access-date = 31 May 2013| url = http://www.rcog.org.uk/files/rcog-corp/Abortion%20guideline_web_1.pdf| archive-url = https://web.archive.org/web/20120529004416/http://www.rcog.org.uk/files/rcog-corp/Abortion%20guideline_web_1.pdf| url-status = dead| archive-date = 2012-05-29}}</ref><ref>
{{cite journal | vauthors = Virk J, Zhang J, Olsen J | title = Medical abortion and the risk of subsequent adverse pregnancy outcomes | journal = The New England Journal of Medicine | volume = 357 | issue = 7 | pages = 648–653 | date = August 2007 | pmid = 17699814 | doi = 10.1056/NEJMoa070445 | s2cid = 14975701 | doi-access = free }}</ref> unintended pregnancies,<ref name="UIP_Shah">{{cite journal | vauthors = Shah PS, Balkhair T, Ohlsson A, Beyene J, Scott F, Frick C | title = Intention to become pregnant and low birth weight and preterm birth: a systematic review | journal = Maternal and Child Health Journal | volume = 15 | issue = 2 | pages = 205–216 | date = February 2011 | pmid = 20012348 | doi = 10.1007/s10995-009-0546-2 | s2cid = 20441901 }}</ref> untreated or undiagnosed celiac disease,<ref name="TersigniCastellani2014" /><ref name="SacconeBerghella2015">{{cite journal | vauthors = Saccone G, Berghella V, Sarno L, Maruotti GM, Cetin I, Greco L, Khashan AS, McCarthy F, Martinelli D, Fortunato F, Martinelli P | display-authors = 6 | title = Celiac disease and obstetric complications: a systematic review and metaanalysis | journal = American Journal of Obstetrics and Gynecology | volume = 214 | issue = 2 | pages = 225–234 | date = February 2016 | pmid = 26432464 | doi = 10.1016/j.ajog.2015.09.080 }}</ref> fertility difficulties, heat exposure,<ref>{{cite journal| vauthors = Barreca A, Schaller J |year=2020|title=The impact of high ambient temperatures on delivery timing and gestational lengths|journal=Nature Climate Change|volume=10|pages=77–82|doi=10.1038/s41558-019-0632-4|issn=1758-6798|s2cid=208538820}}</ref> and genetic variables.<ref name="Bhattacharya_2010" />

Studies on type of work and physical activity have given conflicting results, but it is opined that stressful conditions, hard labor, and long hours are probably linked to preterm birth.<ref name="Goldenberg2008" /> Obesity does not directly lead to preterm birth;<ref>{{cite journal | vauthors = Tsur A, Mayo JA, Wong RJ, Shaw GM, Stevenson DK, Gould JB | title = 'The obesity paradox': a reconsideration of obesity and the risk of preterm birth | journal = Journal of Perinatology | volume = 37 | issue = 10 | pages = 1088–1092 | date = October 2017 | pmid = 28749482 | doi = 10.1038/jp.2017.104 | s2cid = 25566593 | author5-link = David K. Stevenson }}</ref> however, it is associated with diabetes and hypertension which are risk factors by themselves.<ref name="Goldenberg2008" /> To some degree those individuals may have underlying conditions (i.e., uterine malformation, hypertension, diabetes) that persist. Couples who have tried more than one year versus those who have tried less than one year before achieving a spontaneous conception have an adjusted [[Odds ratio|odds ratio]] of 1.35 (95% [[Confidence interval|confidence interval]] 1.22–1.50) of preterm birth.<ref name="Pinborg2013">{{cite journal | vauthors = Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Söderström-Anttila V, Nygren KG, Hazekamp J, Bergh C | display-authors = 6 | title = Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis | journal = Human Reproduction Update | volume = 19 | issue = 2 | pages = 87–104 | year = 2012 | pmid = 23154145 | doi = 10.1093/humupd/dms044 | doi-access = free }}</ref> Pregnancies after [[Biology:In vitro fertilisation|IVF]] confers a greater risk of preterm birth than spontaneous conceptions after more than one year of trying, with an adjusted odds ratio of 1.55 (95% CI 1.30–1.85).<ref name="Pinborg2013" />

Certain ethnicities may have a higher risk as well. For example, in the U.S. and the UK, [[Biography:Black people|Black]] women have preterm birth rates of 15–18%, more than double than that of the white population. Many Black women have higher preterm birth rates due to multiple factors but the most common is high amounts of chronic stress, which can eventually lead to premature birth.<ref name="Braveman_2017">{{cite journal | vauthors = Braveman P, Heck K, Egerter S, Dominguez TP, Rinki C, Marchi KS, Curtis M | title = Worry about racial discrimination: A missing piece of the puzzle of Black-White disparities in preterm birth? | journal = PLOS ONE | volume = 12 | issue = 10 | pages = e0186151 | date = 2017-10-11 | pmid = 29020025 | pmc = 5636124 | doi = 10.1371/journal.pone.0186151 | bibcode = 2017PLoSO..1286151B | doi-access = free | veditors = Ryckman KK }}</ref> Adult chronic disease is not always the case with premature birth in Black women, which makes the main factor of premature birth challenging to identify.<ref name="Braveman_2017" /> Filipinos are also at high risk of premature birth, and it is believed that nearly 11–15% of Filipinos born in the U.S. (compared to other Asians at 7.6% and whites at 7.8%) are premature.<ref name="hawaii.edu">{{cite web |url=http://www.hawaii.edu/news/2014/01/14/preterm-birth-by-filipino-women-linked-to-genetic-mutational-change/ |title=Preterm birth by Filipino women linked to genetic mutational change |date=14 January 2014 |access-date=2014-08-08 |url-status=live |archive-url=https://web.archive.org/web/20140811122154/http://www.hawaii.edu/news/2014/01/14/preterm-birth-by-filipino-women-linked-to-genetic-mutational-change/ |archive-date=11 August 2014}}</ref> Filipinos being a big risk factor is evidenced with the {{wipe|Philippines}} being the eighth-highest ranking in the world for preterm births, the only non-African country in the top 10.<ref>{{cite web |url=http://www.smartparenting.com.ph/community/news/unicef-philippines-has-one-of-the-highest-premature-birth-rates-in-the-world |title=Smart Parenting: The Filipino Parenting Authority |access-date=2014-08-09 |url-status=dead |archive-url=https://web.archive.org/web/20140814165910/http://www.smartparenting.com.ph/community/news/unicef-philippines-has-one-of-the-highest-premature-birth-rates-in-the-world |archive-date=14 August 2014}}</ref> This discrepancy is not seen in comparison to other Asian groups or Hispanic immigrants and remains unexplained.<ref name="Goldenberg2008" /> Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that help them be predisposed to premature births.<ref name="hawaii.edu" /> An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated.<ref name="Bhattacharya_2010">{{cite journal | vauthors = Bhattacharya S, Amalraj Raja E, Ruiz Mirazo E, Campbell DM, Lee AJ, Norman JE, Bhattacharya S | title = Inherited predisposition to spontaneous preterm delivery | journal = Obstetrics and Gynecology | volume = 115 | issue = 6 | pages = 1125–1133 | date = June 2010 | pmid = 20502281 | doi = 10.1097/AOG.0b013e3181dffcdb | hdl-access = free | s2cid = 10113798 | hdl = 2164/2233 }}
*{{lay source |template = cite news| url= http://news.bbc.co.uk/1/hi/health/8701628.stm|title =  Premature birth risk is genetic, researchers suspect |date = May 25, 2010 |website= BBC News }}</ref> No single gene has been identified.

Marital status is associated with risk for preterm birth. A study of 25,373 pregnancies in Finland revealed that unmarried mothers had more preterm deliveries than married mothers (P=0.001).<ref name="Raatikainen2005">{{cite journal | vauthors = Raatikainen K, Heiskanen N, Heinonen S | title = Marriage still protects pregnancy | journal = BJOG | volume = 112 | issue = 10 | pages = 1411–1416 | date = October 2005 | pmid = 16167946 | doi = 10.1111/j.1471-0528.2005.00667.x | s2cid = 13193685 | doi-access = free }}</ref> Pregnancy outside of marriage was associated overall with a 20% increase in total adverse outcomes, even at a time when Finland provided free maternity care. A study in Quebec of 720,586 births from 1990 to 1997 revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents.<ref>{{cite journal | vauthors = Luo ZC, Wilkins R, Kramer MS | title = Disparities in pregnancy outcomes according to marital and cohabitation status | journal = Obstetrics and Gynecology | volume = 103 | issue = 6 | pages = 1300–1307 | date = June 2004 | pmid = 15172868 | doi = 10.1097/01.AOG.0000128070.44805.1f | s2cid = 43892340 }}</ref>{{update inline| {{PMID|20690038}}|date=May 2013}}

====Factors during pregnancy====
Medications during pregnancy, living conditions, air pollution, smoking, illicit drugs or alcohol, infection, or physical trauma may also cause a preterm birth.

Air pollution: Living in an area with a high concentration of air pollution is a major risk factor for preterm labor, including living near major roadways or highways where vehicle emissions are high from traffic congestion or are a route for diesel trucks that tend to emit more pollution.<ref>{{Cite journal| vauthors = Currie J |date=October 2009|title=Traffic Congestion and Infant Health: Evidence from E-ZPass|url=https://www.nber.org/papers/w15413.pdf|journal=National Bureau of Economic Research}}</ref><ref>{{Cite news|url=https://www.cbc.ca/news/technology/air-pollution-study-1.5339472|title=Harmful air pollution 'definitely too high for the public' near city roads, study suggests| vauthors = Chung E |date=30 October 2019|publisher=CBC News|access-date=2 November 2019}}</ref><ref name="Kor2017" />

The use of [[Medicine:Fertility medication|fertility medication]] that stimulates the ovary to release multiple eggs and of [[Biology:In vitro fertilisation|IVF]] with [[Biology:Embryo transfer|embryo transfer]] of multiple embryos has been implicated as a risk factor for preterm birth. Often labor has to be induced for medical reasons; such conditions include high blood pressure,<ref name="Goldenberg1998">{{cite journal | vauthors = Goldenberg RL, Iams JD, Mercer BM, Meis PJ, Moawad AH, Copper RL, Das A, Thom E, Johnson F, McNellis D, Miodovnik M, Van Dorsten JP, Caritis SN, Thurnau GR, Bottoms SF | display-authors = 6 | title = The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network | journal = American Journal of Public Health | volume = 88 | issue = 2 | pages = 233–238 | date = February 1998 | pmid = 9491013 | pmc = 1508185 | doi = 10.2105/AJPH.88.2.233 }}</ref> [[Medicine:Pre-eclampsia|pre-eclampsia]],<ref name="Banhidy2007">
{{cite journal | vauthors = Bánhidy F, Acs N, Puhó EH, Czeizel AE | title = Pregnancy complications and birth outcomes of pregnant women with urinary tract infections and related drug treatments | journal = Scandinavian Journal of Infectious Diseases | volume = 39 | issue = 5 | pages = 390–397 | year = 2007 | pmid = 17464860 | doi = 10.1080/00365540601087566 | s2cid = 5159387 }}</ref> maternal diabetes,<ref name="Rosenberg2005">{{cite journal | vauthors = Rosenberg TJ, Garbers S, Lipkind H, Chiasson MA | title = Maternal obesity and diabetes as risk factors for adverse pregnancy outcomes: differences among 4 racial/ethnic groups | journal = American Journal of Public Health | volume = 95 | issue = 9 | pages = 1545–1551 | date = September 2005 | pmid = 16118366 | pmc = 1449396 | doi = 10.2105/AJPH.2005.065680 }}</ref> asthma, thyroid disease, and heart disease.

Certain medical conditions in the pregnant mother may also increase the risk of preterm birth. Some women have anatomical problems that prevent the baby from being carried to term. These include a weak or short [[Medicine:Cervix|cervix]] (the strongest predictor of premature birth).<ref>
{{cite journal | vauthors = To MS, Skentou CA, Royston P, Yu CK, Nicolaides KH | title = Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population-based prospective study | journal = Ultrasound in Obstetrics & Gynecology | volume = 27 | issue = 4 | pages = 362–367 | date = April 2006 | pmid = 16565989 | doi = 10.1002/uog.2773 | s2cid = 24970386 | doi-access = free }}</ref><ref name="Fonseca2007">
{{cite journal | vauthors = Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH | title = Progesterone and the risk of preterm birth among women with a short cervix | journal = The New England Journal of Medicine | volume = 357 | issue = 5 | pages = 462–469 | date = August 2007 | pmid = 17671254 | doi = 10.1056/NEJMoa067815 | s2cid = 14884358 | doi-access = free }}</ref><ref name="Romero2007">
{{cite journal | vauthors = Romero R | title = Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment | journal = Ultrasound in Obstetrics & Gynecology | volume = 30 | issue = 5 | pages = 675–686 | date = October 2007 | pmid = 17899585 | doi = 10.1002/uog.5174 | s2cid = 46366053 | doi-access = free }}</ref><ref name=Goldenberg1998/> Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or [[Medicine:Placental abruption|placental abruption]]—conditions that occur frequently preterm—even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate.<ref>
{{cite journal | vauthors = Krupa FG, Faltin D, Cecatti JG, Surita FG, Souza JP | title = Predictors of preterm birth | journal = International Journal of Gynaecology and Obstetrics | volume = 94 | issue = 1 | pages = 5–11 | date = July 2006 | pmid = 16730012 | doi = 10.1016/j.ijgo.2006.03.022 | s2cid = 41368575 }}</ref> Women with abnormal amounts of [[Biology:Amniotic fluid|amniotic fluid]], whether too much (polyhydramnios) or too little (oligohydramnios), are also at risk.<ref name=Goldenberg2008/> [[Medicine:Anxiety|Anxiety]] and depression have been linked as risk factors for preterm birth.<ref name="Goldenberg2008" /><ref name="Dole2003">
{{cite journal | vauthors = Dole N, Savitz DA, Hertz-Picciotto I, Siega-Riz AM, McMahon MJ, Buekens P | title = Maternal stress and preterm birth | journal = American Journal of Epidemiology | volume = 157 | issue = 1 | pages = 14–24 | date = January 2003 | pmid = 12505886 | doi = 10.1093/aje/kwf176 | url = http://171.66.121.65/cgi/reprint/157/1/14 | url-status = dead | s2cid = 44325654 | doi-access = free | archive-url = https://web.archive.org/web/20071008202838/http://171.66.121.65/cgi/reprint/157/1/14 | archive-date = 8 October 2007 }}</ref>

The use of [[Biology:Tobacco|tobacco]], [[Biology:Cocaine|cocaine]], and excessive [[Chemistry:Alcohol (drug)|alcohol]] during pregnancy increases the chance of preterm delivery. [[Chemistry:Tobacco smoking|Tobacco]] is the most commonly used drug during pregnancy and contributes significantly to low birth weight delivery.<ref>
{{cite journal | vauthors = Parazzini F, Chatenoud L, Surace M, Tozzi L, Salerio B, Bettoni G, Benzi G | title = Moderate alcohol drinking and risk of preterm birth | journal = European Journal of Clinical Nutrition | volume = 57 | issue = 10 | pages = 1345–1349 | date = October 2003 | pmid = 14506499 | doi = 10.1038/sj.ejcn.1601690 | s2cid = 27688375 | doi-access = free }}</ref> Babies with [[Medicine:Birth defect|birth defect]]s are at higher risk of being born preterm.<ref>
{{cite journal | vauthors = Dolan SM, Gross SJ, Merkatz IR, Faber V, Sullivan LM, Malone FD, Porter TF, Nyberg DA, Comstock CH, Hankins GD, Eddleman K, Dugoff L, Craigo SD, Timor-Tritsch I, Carr SR, Wolfe HM, Bianchi DW, D'Alton ME | display-authors = 6 | title = The contribution of birth defects to preterm birth and low birth weight | journal = Obstetrics and Gynecology | volume = 110 | issue = 2 Pt 1 | pages = 318–324 | date = August 2007 | pmid = 17666606 | doi = 10.1097/01.AOG.0000275264.78506.63 | s2cid = 32544532 }}</ref>

[[Earth:Passive smoking|Passive smoking]] and/or smoking before the pregnancy influences the probability of a preterm birth. The [[Organization:World Health Organization|World Health Organization]] published an international study in March 2014.<ref>The Lancet 28. März 2014: [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960082-9/abstract Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis]. This study is registered with PROSPERO, number CRD42013003522</ref>

Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an [[Odds ratio|odds ratio]] of 1.9 and 95% [[Confidence interval|confidence interval]] of 1.1–3.5.<ref>{{cite journal | vauthors = van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, Bisschop PH | title = Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review | journal = Human Reproduction Update | volume = 17 | issue = 5 | pages = 605–619 | year = 2011 | pmid = 21622978 | doi = 10.1093/humupd/dmr024 | doi-access = free }}</ref>

Intimate violence against the mother is another risk factor for preterm birth.<ref>{{cite journal | vauthors = Boy A, Salihu HM | title = Intimate partner violence and birth outcomes: a systematic review | journal = International Journal of Fertility and Women's Medicine | volume = 49 | issue = 4 | pages = 159–164 | year = 2004 | pmid = 15481481 }}</ref>

Physical trauma may case a preterm birth. The Nigerian cultural method of abdominal massage has been shown to result in 19% preterm birth among women in Nigeria, plus many other adverse outcomes for the mother and baby.<ref>
{{cite journal | vauthors = Ugboma HA, Akani CI | title = Abdominal massage: another cause of maternal mortality | journal = Nigerian Journal of Medicine | volume = 13 | issue = 3 | pages = 259–262 | year = 2004 | pmid = 15532228 }}</ref> This ought not be confused with massage therapy conducted by a fully trained and certified/licensed massage therapist or by significant others trained to provide massage during pregnancy, which—in a study involving pregnant females with prenatal depression—has been shown to have numerous positive results during pregnancy, including the reduction of preterm birth, less depression, lower cortisol, and reduced anxiety.<ref>{{cite journal | vauthors = Field T, Deeds O, Diego M, Hernandez-Reif M, Gauler A, Sullivan S, Wilson D, Nearing G | display-authors = 6 | title = Benefits of combining massage therapy with group interpersonal psychotherapy in prenatally depressed women | journal = Journal of Bodywork and Movement Therapies | volume = 13 | issue = 4 | pages = 297–303 | date = October 2009 | pmid = 19761951 | pmc = 2785018 | doi = 10.1016/j.jbmt.2008.10.002 }}</ref> In healthy women, however, no effects have been demonstrated in a controlled study.

====Infection====
The frequency of infection in preterm birth is inversely related to the gestational age. ''[[Biology:Mycoplasma genitalium|Mycoplasma genitalium]]'' infection is associated with increased risk of preterm birth, and spontaneous abortion.<ref name="LisRowhani-Rahbar2015">{{cite journal | vauthors = Lis R, Rowhani-Rahbar A, Manhart LE | title = Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis | journal = Clinical Infectious Diseases | volume = 61 | issue = 3 | pages = 418–426 | date = August 2015 | pmid = 25900174 | doi = 10.1093/cid/civ312 | doi-access = free | hdl = 1773/26479 | hdl-access = free }}</ref>

Infectious microorganisms can be ascending, hematogenous, iatrogenic by a procedure, or retrograde through the fallopian tubes. From the deciduae they may reach the space between the [[Biology:Amnion|amnion]] and [[Biology:Chorion|chorion]], the [[Biology:Amniotic fluid|amniotic fluid]], and the fetus. A [[Medicine:Chorioamnionitis|chorioamnionitis]] also may lead to [[Medicine:Sepsis|sepsis]] of the mother. Fetal infection is linked to preterm birth and to significant long-term disability including [[Medicine:Cerebral palsy|cerebral palsy]].<ref>{{cite journal | vauthors = Schendel DE | title = Infection in pregnancy and cerebral palsy | journal = Journal of the American Medical Women's Association | volume = 56 | issue = 3 | pages = 105–108 | year = 2001 | pmid = 11506145 }}</ref>

It has been reported that asymptomatic colonization of the decidua occurs in up to 70% of women at term using a DNA probe suggesting that the presence of micro-organism alone may be insufficient to initiate the infectious response.

As the condition is more prevalent in black women in the U.S. and the UK, it has been suggested to be an explanation for the higher rate of preterm birth in these populations. It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth. The condition known as aerobic vaginitis can be a serious risk factor for preterm labor; several previous studies failed to acknowledge the difference between aerobic vaginitis and bacterial vaginosis, which may explain some of the contradiction in the results.<ref>{{cite journal | vauthors = Donders G, Bellen G, Rezeberga D | title = Aerobic vaginitis in pregnancy | journal = BJOG | volume = 118 | issue = 10 | pages = 1163–1170 | date = September 2011 | pmid = 21668769 | doi = 10.1111/j.1471-0528.2011.03020.x | s2cid = 7789770 | doi-access = free }}</ref>

Untreated [[Medicine:Candidiasis|yeast]] infections are associated with preterm birth.<ref name=rob2015>{{cite journal | vauthors = Roberts CL, Algert CS, Rickard KL, Morris JM | title = Treatment of vaginal candidiasis for the prevention of preterm birth: a systematic review and meta-analysis | journal = Systematic Reviews | volume = 4 | issue = 1 | pages = 31 | date = March 2015 | pmid = 25874659 | pmc = 4373465 | doi = 10.1186/s13643-015-0018-2 | doi-access = free }}</ref>

A review into prophylactic antibiotics (given to prevent infection) in the second and third trimester of pregnancy (13–42 weeks of pregnancy) found a reduction in the number of preterm births in women with bacterial vaginosis. These antibiotics also reduced the number of waters breaking before labor in full-term pregnancies, reduced the risk of infection of the lining of the womb after delivery (endometritis), and rates of gonococcal infection. However, the women without bacterial vaginosis did not have any reduction in preterm births or pre-labor preterm waters breaking. Much of the research included in this review lost participants during follow-up so did not report the long-term effects of the antibiotics on mothers or babies. More research in this area is needed to find the full effects of giving antibiotics throughout the second and third trimesters of pregnancy.<ref name="ReferenceC">{{cite journal | vauthors = Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P, Ota E | title = Antibiotic prophylaxis during the second and third trimester to reduce adverse pregnancy outcomes and morbidity | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 6 | pages = CD002250 | date = June 2015 | pmid = 26092137 | pmc = 7154219 | doi = 10.1002/14651858.CD002250.pub3 | veditors = Thinkhamrop J }}</ref>

A number of maternal bacterial infections are associated with preterm birth including [[Medicine:Pyelonephritis|pyelonephritis]], asymptomatic [[Medicine:Bacteriuria|bacteriuria]], [[Medicine:Pneumonia|pneumonia]], and [[Medicine:Appendicitis|appendicitis]]. A review into giving antibiotics in pregnancy for asymptomatic bacteriuria (urine infection with no symptoms) found the research was of very low quality but that it did suggest that taking antibiotics reduced the numbers of preterm births and babies with low birth weight.<ref name="Smaill_2019">{{cite journal | vauthors = Smaill FM, Vazquez JC | title = Antibiotics for asymptomatic bacteriuria in pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 11 | date = November 2019 | pmid = 31765489 | pmc = 6953361 | doi = 10.1002/14651858.CD000490.pub4 }}</ref> Another review found that one dose of antibiotics did not seem as effective as a course of antibiotics but fewer women reported side effects from one dose.<ref>{{cite journal | vauthors = Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A | title = Duration of treatment for asymptomatic bacteriuria during pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 11 | pages = CD000491 | date = November 2015 | pmid = 26560337 | pmc = 7043273 | doi = 10.1002/14651858.CD000491.pub3 }}</ref> This review recommended that more research is needed to discover the best way of treating asymptomatic bacteriuria.<ref name="Smaill_2019"/>

A different review found that preterm births happened less for pregnant women who had routine testing for low genital tract infections than for women who only had testing when they showed symptoms of low genital tract infections.<ref name="ReferenceD">{{cite journal | vauthors = Sangkomkamhang US, Lumbiganon P, Prasertcharoensuk W, Laopaiboon M | title = Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 2 | pages = CD006178 | date = February 2015 | pmid = 25922860 | pmc = 8498019 | doi = 10.1002/14651858.CD006178.pub3 }}</ref> The women being routinely tested also gave birth to fewer babies with a low birth weight. Even though these results look promising, the review was only based on one study so more research is needed into routine screening for low genital tract infections.<ref name="ReferenceD"/>

Also [[Medicine:Periodontal disease|periodontal disease]] has been shown repeatedly to be linked to preterm birth.<ref>
{{cite journal | vauthors = Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP, Goldenberg RL, Hauth JC | title = Periodontal infection and preterm birth: results of a prospective study | journal = Journal of the American Dental Association | volume = 132 | issue = 7 | pages = 875–880 | date = July 2001 | pmid = 11480640 | doi = 10.14219/jada.archive.2001.0299 }}</ref><ref>{{cite web |url=https://www.unitedconcordia.com/dental-insurance/dental/conditions/pregnancy-oral-health/ |title=Pregnancy and Oral Health - United Concordia Dental |access-date=2015-01-19 |url-status=live |archive-url=https://web.archive.org/web/20150120074310/https://www.unitedconcordia.com/dental-insurance/dental/conditions/pregnancy-oral-health/ |archive-date=20 January 2015}}</ref> In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth.<ref name=Goldenberg2008/>

====Genetics====
There is believed to be a maternal genetic component in preterm birth.<ref name=Kistka2008>
{{cite journal | vauthors = Kistka ZA, DeFranco EA, Ligthart L, Willemsen G, Plunkett J, Muglia LJ, Boomsma DI | title = Heritability of parturition timing: an extended twin design analysis | journal = American Journal of Obstetrics and Gynecology | volume = 199 | issue = 1 | pages = 43.e1–43.e5 | date = July 2008 | pmid = 18295169 | doi = 10.1016/j.ajog.2007.12.014 }}</ref> Estimated heritability of timing-of-birth in women was 34%. However, the occurrence of preterm birth in families does not follow a clear inheritance pattern, thus supporting the idea that preterm birth is a non-Mendelian trait with a polygenic nature.<ref name="Zhang2017">{{cite journal | vauthors = Zhang G, Feenstra B, Bacelis J, Liu X, Muglia LM, Juodakis J, Miller DE, Litterman N, Jiang PP, Russell L, Hinds DA, Hu Y, Weirauch MT, Chen X, Chavan AR, Wagner GP, Pavličev M, Nnamani MC, Maziarz J, Karjalainen MK, Rämet M, Sengpiel V, Geller F, Boyd HA, Palotie A, Momany A, Bedell B, Ryckman KK, Huusko JM, Forney CR, Kottyan LC, Hallman M, Teramo K, Nohr EA, Davey Smith G, Melbye M, Jacobsson B, Muglia LJ | display-authors = 6 | title = Genetic Associations with Gestational Duration and Spontaneous Preterm Birth | journal = The New England Journal of Medicine | volume = 377 | issue = 12 | pages = 1156–1167 | date = September 2017 | pmid = 28877031 | pmc = 5561422 | doi = 10.1056/NEJMoa1612665 }}</ref>

====Prenatal care====
The absence of prenatal care has been associated with higher rates of preterm births. Analysis of 15,627,407 live births in the United States in 1995–1998 concluded that the absence of prenatal care carried a 2.9 (95%CI 2.8, 3.0) times higher risk of preterm births.<ref name="sciencedirect1254"/> This same study found statistically significant relative risks of maternal anemia, intrapartum fever, unknown bleeding, renal disease, placental previa, hydramnios, placenta abruption, and pregnancy-induced hypertension with the absence of prenatal care. All these prenatal risks were controlled for other high-risk conditions, maternal age, gravidity, marital status, and maternal education. The absence of prenatal care prior to and during the pregnancy is primarily a function of socioeconomic factors (low family income and education), access to medical consultations (large distance from the place of residence to the healthcare unit and transportation costs), quality of healthcare, and social support.<ref>{{cite journal | vauthors = Rosa CQ, Silveira DS, Costa JS | title = Factors associated with lack of prenatal care in a large municipality | journal = Revista de Saude Publica | volume = 48 | issue = 6 | pages = 977–984 | date = December 2014 | pmid = 26039401 | pmc = 4285828 | doi = 10.1590/S0034-8910.2014048005283 }}</ref> Efforts to decrease rates of preterm birth should aim to increase the deficits posed by the aforementioned barriers and to increase access to prenatal care.

==Diagnosis==
===Placental alpha microglobulin-1===
Placental alpha microglobulin-1 (PAMG-1) has been the subject of several investigations evaluating its ability to predict imminent spontaneous preterm birth in women with signs, symptoms, or complaints suggestive of preterm labor.<ref name="pmid17329514">{{cite journal | vauthors = Lee SE, Park JS, Norwitz ER, Kim KW, Park HS, Jun JK | title = Measurement of placental alpha-microglobulin-1 in cervicovaginal discharge to diagnose rupture of membranes | journal = Obstetrics and Gynecology | volume = 109 | issue = 3 | pages = 634–640 | date = March 2007 | pmid = 17329514 | doi = 10.1097/01.AOG.0000252706.46734.0a | s2cid = 20732037 }}</ref><ref>{{cite journal | vauthors = Lee SM, Lee J, Seong HS, Lee SE, Park JS, Romero R, Yoon BH | title = The clinical significance of a positive Amnisure test in women with term labor with intact membranes | journal = The Journal of Maternal-Fetal & Neonatal Medicine | volume = 22 | issue = 4 | pages = 305–310 | date = April 2009 | pmid = 19350444 | pmc = 2744034 | doi = 10.1080/14767050902801694 }}</ref><ref>{{cite journal |vauthors=Lee SM, Yoon BH, Park CW, Kim SM, Park JW | year = 2011 | title = Intra-amniotic inflammation in patients with a positive Amnisure test in preterm labor and intact membranes | journal = Am J Obstet Gynecol | volume = 204 | issue = 1| page = S209 | doi=10.1016/j.ajog.2010.10.543}}</ref><ref>{{cite journal | vauthors = Lee SM, Romero R, Park JW, Kim SM, Park CW, Korzeniewski SJ, Chaiworapongsa T, Yoon BH | display-authors = 6 | title = The clinical significance of a positive Amnisure test in women with preterm labor and intact membranes | journal = The Journal of Maternal-Fetal & Neonatal Medicine | volume = 25 | issue = 9 | pages = 1690–1698 | date = September 2012 | pmid = 22280400 | pmc = 3422421 | doi = 10.3109/14767058.2012.657279 }}</ref><ref>{{cite journal | vauthors = Sukchaya K, Phupong V | title = A comparative study of positive rate of placental α-microglobulin-1 test in pre-term pregnant women with and without uterine contraction | journal = Journal of Obstetrics and Gynaecology | volume = 33 | issue = 6 | pages = 566–568 | date = August 2013 | pmid = 23919851 | doi = 10.3109/01443615.2013.807786 | s2cid = 20265539 }}</ref><ref>{{cite journal | vauthors = Nikolova T, Bayev O, Nikolova N, Di Renzo GC | title = Evaluation of a novel placental alpha microglobulin-1 (PAMG-1) test to predict spontaneous preterm delivery | journal = Journal of Perinatal Medicine | volume = 42 | issue = 4 | pages = 473–477 | date = July 2014 | pmid = 24334429 | doi = 10.1515/jpm-2013-0234 | s2cid = 6547430 }}</ref> In one investigation comparing this test to [[Biology:Fetal fibronectin|fetal fibronectin]] testing and cervical length measurement via transvaginal ultrasound, the test for PAMG-1 (commercially known as the PartoSure test) has been reported to be the single best predictor of imminent spontaneous delivery within 7 days of a patient presenting with signs, symptoms, or complaints of preterm labor. Specifically, the PPV, or positive predictive value, of the tests were 76%, 29%, and 30% for PAMG-1, fFN and CL, respectively (P < 0.01).<ref>Nikolova T, Bayev O, Nikolova N, Di Renzo GC. Comparison of a novel test for placental alpha microglobulin-1 with fetal fibronectin and cervical length measurement for the prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor. J Perinat Med. 2015 Jan 6.</ref>

===Fetal fibronectin===
[[Biology:Fetal fibronectin|Fetal fibronectin]] (fFN) has become an important biomarker—the presence of this glycoprotein in the cervical or vaginal secretions indicates that the border between the chorion and decidua has been disrupted. A positive test indicates an increased risk of preterm birth, and a negative test has a high predictive value.<ref name=Goldenberg2008/> It has been shown that only 1% of women in questionable cases of preterm labor delivered within the next week when the test was negative.<ref>
{{cite journal | vauthors = Lu GC, Goldenberg RL, Cliver SP, Kreaden US, Andrews WW | title = Vaginal fetal fibronectin levels and spontaneous preterm birth in symptomatic women | journal = Obstetrics and Gynecology | volume = 97 | issue = 2 | pages = 225–228 | date = February 2001 | pmid = 11165586 | doi = 10.1016/S0029-7844(00)01130-3 | s2cid = 34818112 }}</ref>

===Ultrasound===
Obstetric ultrasound has become useful in the assessment of the [[Medicine:Cervix|cervix]] in women at risk for premature delivery. A short cervix preterm is undesirable: A cervical length of less than {{Convert|25|mm|abbr=on}} at or before 24 weeks of gestational age is the most common definition of cervical incompetence.<ref>[http://radiopaedia.org/articles/cervical_incompetence Cervical incompetence] {{webarchive|url=https://web.archive.org/web/20140307205141/http://radiopaedia.org/articles/cervical_incompetence |date=7 March 2014 }} from [[Medicine:Radiopaedia|Radiopaedia]]. Authors: Dr Praveen Jha and Dr Laughlin Dawes et al. Retrieved Feb 2014</ref>

=== Emerging Technologies ===
Technologies under research and development to facilitate earlier diagnosis of preterm births include sanitary pads that identify biomarkers such as fFN and PAMG-1 and others, when placed into the vagina. These devices then calculate a risk of preterm birth and send the findings to a smartphone.<ref>{{Cite web |last=Agency |first=Innosuisse-Swiss Innovation |title=Rea - a smart bandage for pregnant women |url=https://www.innosuisse.ch/inno/en/home/success-stories/projektbeispiele/start-up/rea.html |access-date=2023-09-05 |website=www.innosuisse.ch |language=en}}</ref> The notion that risk scoring systems are accurate in predicting preterm birth has been debated in multiple literature reviews.<ref>{{Cite journal |last1=Ferreira |first1=Amaro |last2=Bernardes |first2=João |last3=Gonçalves |first3=Hernâni |date=January 2023 |title=Risk Scoring Systems for Preterm Birth and Their Performance: A Systematic Review |journal=Journal of Clinical Medicine |language=en |volume=12 |issue=13 |pages=4360 |doi=10.3390/jcm12134360 |pmid=37445395 |pmc=10342801 |issn=2077-0383 |doi-access=free }}</ref><ref>{{Citation |last1=Davey |first1=Mary-Ann |title=Risk scoring systems for predicting preterm birth with the aim of reducing associated adverse outcomes |date=2010-01-20 |url=http://dx.doi.org/10.1002/14651858.cd004902.pub2 |work=Cochrane Database of Systematic Reviews |access-date=2023-09-05 |place=Chichester, UK |publisher=John Wiley & Sons, Ltd |last2=Watson |first2=Lyndsey |last3=Rayner |first3=Jo Anne |last4=Rowlands |first4=Shelley|editor-first1=Mary-Ann |editor-last1=Davey |doi=10.1002/14651858.cd004902.pub2 }}</ref>

===Classification===
[[File:Prenatal development table.svg|center|thumb|800px|Stages in [[Biology:Prenatal development|prenatal development]], with weeks and months numbered from last menstruation]]
In humans, the usual definition of preterm birth is birth before a gestational age of 37 complete weeks.<ref name=Steer2005>
{{cite journal | vauthors = Steer P | title = The epidemiology of preterm labour | journal = BJOG | volume = 112 | issue = Suppl 1 | pages = 1–3 | date = March 2005 | pmid = 15715585 | doi = 10.1111/j.1471-0528.2005.00575.x | s2cid = 33738952 | doi-access = free }}</ref> In the normal human fetus, several organ systems mature between 34 and 37 weeks, and the fetus reaches adequate maturity by the end of this period. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to mature in the womb; because of this, many premature babies spend the first days and weeks of their lives on [[Engineering:Ventilator|ventilator]]s. Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Preterm babies born near 37 weeks often have no problems relating to prematurity if their lungs have developed adequate [[Biology:Pulmonary surfactant|surfactant]], which allows the lungs to remain expanded between breaths. Sequelae of prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus, and to a greater extent by preventing preterm birth.

==Prevention==
Historically efforts have been primarily aimed to improve survival and health of preterm infants (tertiary intervention). Such efforts, however, have not reduced the incidence of preterm birth. Increasingly primary interventions that are directed at all women, and secondary intervention that reduce existing risks are looked upon as measures that need to be developed and implemented to prevent the health problems of premature infants and children.<ref name=Iams2008>
{{cite journal | vauthors = Iams JD, Romero R, Culhane JF, Goldenberg RL | title = Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth | journal = Lancet | volume = 371 | issue = 9607 | pages = 164–175 | date = January 2008 | pmid = 18191687 | doi = 10.1016/S0140-6736(08)60108-7 | s2cid = 8204299 }}</ref> Smoking bans are effective in decreasing preterm births.<ref>{{cite journal | vauthors = Been JV, Nurmatov UB, Cox B, Nawrot TS, van Schayck CP, Sheikh A | title = Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis | journal = Lancet | volume = 383 | issue = 9928 | pages = 1549–1560 | date = May 2014 | pmid = 24680633 | doi = 10.1016/S0140-6736(14)60082-9 | s2cid = 8532979 }}</ref> Different strategies are used in the administration of prenatal care, and future studies need to determine if the focus can be on screening for high-risk women, or widened support for low-risk women, or to what degree these approaches can be merged.<ref name="Iams2008" />

===Before pregnancy===
Adoption of specific professional policies can immediately reduce risk of preterm birth as the experience in assisted reproduction has shown when the number of embryos during embryo transfer was limited.<ref name=Iams2008/>
Many countries have established specific programs to protect pregnant women from hazardous or night-shift work and to provide them with time for prenatal visits and paid pregnancy-leave. The EUROPOP study showed that preterm birth is not related to type of employment, but to prolonged work (over 42 hours per week) or prolonged standing (over 6 hours per day).<ref>{{cite journal | vauthors = Saurel-Cubizolles MJ, Zeitlin J, Lelong N, Papiernik E, Di Renzo GC, Bréart G | title = Employment, working conditions, and preterm birth: results from the Europop case-control survey | journal = Journal of Epidemiology and Community Health | volume = 58 | issue = 5 | pages = 395–401 | date = May 2004 | pmid = 15082738 | pmc = 1732750 | doi = 10.1136/jech.2003.008029 }}</ref> Also, night work has been linked to preterm birth.<ref>
{{cite journal | vauthors = Pompeii LA, Savitz DA, Evenson KR, Rogers B, McMahon M | title = Physical exertion at work and the risk of preterm delivery and small-for-gestational-age birth | journal = Obstetrics and Gynecology | volume = 106 | issue = 6 | pages = 1279–1288 | date = December 2005 | pmid = 16319253 | doi = 10.1097/01.AOG.0000189080.76998.f8 | s2cid = 19518460 }}</ref> Health policies that take these findings into account can be expected to reduce the rate of preterm birth.<ref name=Iams2008/> Preconceptional intake of folic acid is recommended to reduce birth defects. There is also some evidence that folic acid supplement preconceptionally (before becoming pregnant) may reduce premature birth.<ref>{{cite journal | vauthors = Li B, Zhang X, Peng X, Zhang S, Wang X, Zhu C | title = Folic Acid and Risk of Preterm Birth: A Meta-Analysis | journal = Frontiers in Neuroscience | volume = 13 | pages = 1284 | date = 2019 | pmid = 31849592 | pmc = 6892975 | doi = 10.3389/fnins.2019.01284 | doi-access = free }}</ref> Reducing smoking is expected to benefit pregnant women and their offspring.<ref name=Iams2008/>

===During pregnancy===

Self-care methods to reduce the risk of preterm birth include proper nutrition, avoiding stress, seeking appropriate medical care, avoiding infections, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors).<ref>
{{cite journal | vauthors = Lamont RF, Jaggat AN | title = Emerging drug therapies for preventing spontaneous preterm labor and preterm birth | journal = Expert Opinion on Investigational Drugs | volume = 16 | issue = 3 | pages = 337–345 | date = March 2007 | pmid = 17302528 | doi = 10.1517/13543784.16.3.337 | s2cid = 11591970 }}</ref> Reducing physical activity during pregnancy has not been shown to reduce the risk of a preterm birth.<ref>{{cite journal | vauthors = Johnston M, Landers S, Noble L, Szucs K, Viehmann L | collaboration = Section on Breastfeeding | title = Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin Summary, Number 234 | journal = Obstetrics and Gynecology | volume = 138 | issue = 2 | pages = 320–323 | date = August 2021 | pmid = 34293768 | doi = 10.1097/AOG.0000000000004480 | s2cid = 236200411 }}</ref> Healthy eating can be instituted at any stage of the pregnancy including nutritional adjustments and consuming suggested vitamin supplements.<ref name=Iams2008/> Calcium supplementation in women who have low dietary calcium may reduce the number of negative outcomes including preterm birth, pre-eclampsia, and maternal death.<ref>{{cite journal | vauthors = Hofmeyr GJ, Lawrie TA, Atallah ÁN, Torloni MR | title = Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 10 | pages = CD001059 | date = October 2018 | pmid = 30277579 | pmc = 6517256 | doi = 10.1002/14651858.CD001059.pub5 }}</ref> The World Health Organization (WHO) suggests 1.5–2&nbsp;g of calcium supplements daily, for pregnant women who have low levels of calcium in their diet.<ref>{{cite book |title=Guideline: Calcium supplementation in pregnant women |date=2013 |publisher=World Health Organization |location=Geneva}}</ref> Supplemental intake of C and E vitamins have not been found to reduce preterm birth rates.<ref>{{cite journal | vauthors = Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS | title = Vitamins C and E and the risks of preeclampsia and perinatal complications | journal = The New England Journal of Medicine | volume = 354 | issue = 17 | pages = 1796–1806 | date = April 2006 | pmid = 16641396 | doi = 10.1056/NEJMoa054186 | hdl = 2440/23161 | doi-access = free | hdl-access = free }}</ref>

While periodontal infection has been linked with preterm birth, [[Randomized controlled trial|randomized trials]] have not shown that periodontal care during pregnancy reduces preterm birth rates.<ref name="Iams2008" /> Smoking cessation has also been shown to reduce the risk.<ref>{{cite journal | vauthors = Avşar TS, McLeod H, Jackson L | title = Health outcomes of smoking during pregnancy and the postpartum period: an umbrella review | journal = BMC Pregnancy and Childbirth | volume = 21 | issue = 1 | pages = 254 | date = March 2021 | pmid = 33771100 | pmc = 7995767 | doi = 10.1186/s12884-021-03729-1 | doi-access = free }}</ref> The use of personal at home uterine monitoring devices to detect contractions and possible preterm births in women at higher risk of having a preterm baby have been suggested.<ref name="Urquhart_2017">{{cite journal | vauthors = Urquhart C, Currell R, Harlow F, Callow L | title = Home uterine monitoring for detecting preterm labour | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 2 | pages = CD006172 | date = February 2017 | pmid = 28205207 | pmc = 6464057 | doi = 10.1002/14651858.CD006172.pub4 }}</ref> These home monitors may not reduce the number of preterm births, however, using these devices may increase the number of unplanned antenatal visits and may reduce the number of babies admitted to special care when compared with women receiving normal antenatal care.<ref name="Urquhart_2017" /> Support from medical professionals, friends, and family during pregnancy may be beneficial at reducing caesarean birth and may reduce prenatal hospital admissions, however, these social supports alone may not prevent preterm birth.<ref name="East2019">{{cite journal | vauthors = East CE, Biro MA, Fredericks S, Lau R | title = Support during pregnancy for women at increased risk of low birthweight babies | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 4 | pages = CD000198 | date = April 2019 | pmid = 30933309 | pmc = 6443020 | doi = 10.1002/14651858.CD000198.pub3 }}</ref>

====Screening during pregnancy====
Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth.<ref>
{{cite journal | vauthors = Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M | title = Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight | journal = Obstetrics and Gynecology | volume = 73 | issue = 4 | pages = 576–582 | date = April 1989 | pmid = 2927852 }}</ref> Extensive studies have been carried out to determine if other forms of screening in low-risk women followed by appropriate intervention are beneficial, including screening for and treatment of ''[[Biology:Ureaplasma urealyticum|Ureaplasma urealyticum]]'', group B streptococcus, ''Trichomonas vaginalis'', and bacterial vaginosis did not reduce the rate of preterm birth.<ref name="Iams2008" /> Routine ultrasound examination of the length of the cervix may identify women at risk of preterm labour and tentative evidence suggests ultrasound measurement of the length of the cervix in those with preterm labor can help adjust management and results in the extension of pregnancy by about four days.<ref>{{cite journal | vauthors = Berghella V, Saccone G | title = Cervical assessment by ultrasound for preventing preterm delivery | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 9 | pages = CD007235 | date = September 2019 | pmid = 31553800 | pmc = 6760928 | doi = 10.1002/14651858.CD007235.pub4 }}</ref> Screening for the presence of fibronectin in vaginal secretions is not recommended at this time in women at low risk of preterm birth.{{Medical citation needed|date=August 2021}}

===Reducing existing risks===
Women are identified to be at increased risk for preterm birth on the basis of their past obstetrical history or the presence of known risk factors. Preconception intervention can be helpful in selected patients in a number of ways. Patients with certain uterine anomalies may have a surgical correction (i.e. removal of a [[Medicine:Uterine septum|uterine septum]]), and those with certain medical problems can be helped by optimizing medical therapies prior to conception, be it for asthma, diabetes, hypertension, and others.

====Multiple pregnancies====
In multiple pregnancies, which often result from use of [[Engineering:Assisted reproductive technology|assisted reproductive technology]], there is a high risk of preterm birth. Selective reduction is used to reduce the number of fetuses to two or three.<ref name=ACOG2017>{{cite web |title=Opinion Number 719: Multifetal Pregnancy Reduction |url=https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Ethics/Multifetal-Pregnancy-Reduction |publisher=American College of Obstetricians and Gynecologists' Committee on Ethics. |date=September 2017 |access-date=26 October 2018 |archive-date=4 April 2019 |archive-url=https://web.archive.org/web/20190404072926/https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Ethics/Multifetal-Pregnancy-Reduction |url-status=dead }}</ref><ref name=Zipori2017>{{cite journal | vauthors = Zipori Y, Haas J, Berger H, Barzilay E | title = Multifetal pregnancy reduction of triplets to twins compared with non-reduced triplets: a meta-analysis | journal = Reproductive Biomedicine Online | volume = 35 | issue = 3 | pages = 296–304 | date = September 2017 | pmid = 28625760 | doi = 10.1016/j.rbmo.2017.05.012 | doi-access = free }}</ref><ref name=Evans2014>{{cite journal | vauthors = Evans MI, Andriole S, Britt DW | title = Fetal reduction: 25 years' experience | journal = Fetal Diagnosis and Therapy | volume = 35 | issue = 2 | pages = 69–82 | year = 2014 | pmid = 24525884 | doi = 10.1159/000357974 | doi-access = free }}</ref>

====Reducing indicated preterm birth====
A number of agents have been studied for the secondary prevention of indicated preterm birth. Trials using low-dose [[Chemistry:Aspirin|aspirin]], fish oil, vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-dose aspirin was used.<ref name=Iams2008/> Even if agents such as calcium or [[Biology:Antioxidant|antioxidant]]s were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed.<ref name=Iams2008/>

====Reducing spontaneous preterm birth====
Reduction in activity by the mother—pelvic rest, limited work, bed rest—may be recommended although there is no evidence it is useful with some concerns it is harmful.<ref>{{cite journal | vauthors = McCall CA, Grimes DA, Lyerly AD | title = "Therapeutic" bed rest in pregnancy: unethical and unsupported by data | journal = Obstetrics and Gynecology | volume = 121 | issue = 6 | pages = 1305–1308 | date = June 2013 | pmid = 23812466 | doi = 10.1097/aog.0b013e318293f12f | s2cid = 9069311 }}</ref> Increasing medical care by more frequent visits and more education has not been shown to reduce preterm birth rates.<ref name="East2019"/> Use of nutritional supplements such as omega-3 [[Chemistry:Polyunsaturated fatty acid|polyunsaturated fatty acid]]s is based on the observation that populations who have a high intake of such agents are at low risk for preterm birth, presumably as these agents inhibit production of proinflammatory cytokines. A randomized trial showed a significant decline in preterm birth rates,<ref>
{{cite journal | vauthors = Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C | title = Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team | journal = BJOG | volume = 107 | issue = 3 | pages = 382–395 | date = March 2000 | pmid = 10740336 | doi = 10.1111/j.1471-0528.2000.tb13235.x | s2cid = 30837582 | doi-access = free }}</ref> and further studies are in the making.

=====Antibiotics=====

While antibiotics can get rid of bacterial vaginosis in pregnancy, this does not appear to change the risk of preterm birth.<ref>{{cite journal | vauthors = Brocklehurst P, Gordon A, Heatley E, Milan SJ | title = Antibiotics for treating bacterial vaginosis in pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD000262 | date = January 2013 | pmid = 23440777 | pmc = 4164464 | doi = 10.1002/14651858.CD000262.pub4 }}</ref> It has been suggested that chronic chorioamnionitis is not sufficiently treated by antibiotics alone (and therefore they cannot ameliorate the need for preterm delivery in this condition).<ref name=Iams2008/>

=====Progestogens=====

[[Biology:Progestogen|Progestogen]]s—often given in the form of vaginal<ref>{{cite web |date=July 2017|title=Progesterone: Use in the second and third trimester of pregnancy for the prevention of preterm birth|url=https://ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Progesterone-use-in-the-second-and-third-trimester-(C-Obs-29b)-Review-July-2017.pdf?ext=.pdf|access-date=2021-01-29|website=The Royal Australian and New Zealand College of Obstetricians and Gynaecologists}}</ref> [[Chemistry:Progesterone (medication)|progesterone]] or [[Biology:Hydroxyprogesterone caproate|hydroxyprogesterone caproate]]—relax the uterine musculature, maintain cervical length, and possess anti-inflammatory properties; all of which invoke physiological and anatomical changes considered to be beneficial in reducing preterm birth. Two meta-analyses demonstrated a reduction in the risk of preterm birth in women with recurrent preterm birth by 40–55%.<ref>{{cite journal | vauthors = Dodd JM, Jones L, Flenady V, Cincotta R, Crowther CA | title = Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD004947 | date = July 2013 | pmid = 23903965 | doi = 10.1002/14651858.CD004947.pub3 | s2cid = 43862120 }}</ref><ref>
{{cite journal | vauthors = Mackenzie R, Walker M, Armson A, Hannah ME | title = Progesterone for the prevention of preterm birth among women at increased risk: a systematic review and meta-analysis of randomized controlled trials | journal = American Journal of Obstetrics and Gynecology | volume = 194 | issue = 5 | pages = 1234–1242 | date = May 2006 | pmid = 16647905 | doi = 10.1016/j.ajog.2005.06.049 }}</ref>

Progestogen supplementation also reduces the frequency of preterm birth in pregnancies where there is a short cervix.<ref name="Iams2014">{{cite journal | vauthors = Iams JD | title = Clinical practice. Prevention of preterm parturition | journal = The New England Journal of Medicine | volume = 370 | issue = 3 | pages = 254–261 | date = January 2014 | pmid = 24428470 | doi = 10.1056/NEJMcp1103640 | s2cid = 29480873 }}</ref> A short cervix is one that is less than 25mm, as detected during a transvaginal cervical length assessment in the midtrimester.<ref>{{cite journal | vauthors = Romero R, Nicolaides KH, Conde-Agudelo A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Hassan SS | display-authors = 6 | title = Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study | journal = Ultrasound in Obstetrics & Gynecology | volume = 48 | issue = 3 | pages = 308–317 | date = September 2016 | pmid = 27444208 | pmc = 5053235 | doi = 10.1002/uog.15953 }}</ref> However, progestogens are not effective in all populations, as a study involving twin gestations failed to see any benefit.<ref>{{cite journal |vauthors=Caritis S, Rouse D |year=2006 |title=A randomized controlled trial of 17-hydroxyprogesterone caproate (17-OHPC) for the prevention of preterm birth in twins |journal=American Journal of Obstetrics & Gynecology |volume=195 |issue=6 |pages=S2 |doi=10.1016/j.ajog.2006.10.003 |url=https://zenodo.org/record/1258694 |doi-access=free }}</ref> Despite extensive research related to progestogen effectiveness, uncertainties remain concerning types of progesterone and routes of administration.<ref>{{cite journal | vauthors = Stewart LA, Simmonds M, Duley L, Dietz KC, Harden M, Hodkinson A, Llewellyn A, Sharif S, Walker R, Wright K | display-authors = 6 | title = Evaluating progestogens for prevention of preterm birth international collaborative (EPPPIC) individual participant data (IPD) meta-analysis: protocol | journal = Systematic Reviews | volume = 6 | issue = 1 | pages = 235 | date = November 2017 | pmid = 29183399 | pmc = 5706301 | doi = 10.1186/s13643-017-0600-x | doi-access = free }}</ref>

=====Cervical cerclage=====

In preparation for [[Medicine:Childbirth|childbirth]], the woman's [[Medicine:Cervix|cervix]] shortens. Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. [[Medicine:Cervical cerclage|Cervical cerclage]] is a surgical intervention that places a suture around the cervix to prevent its shortening and widening. Numerous studies have been performed to assess the value of cervical cerclage and the procedure appears helpful primarily for women with a short cervix and a history of preterm birth.<ref name=Iams2014/><ref>
{{cite journal | vauthors = Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM | title = Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data | journal = Obstetrics and Gynecology | volume = 106 | issue = 1 | pages = 181–189 | date = July 2005 | pmid = 15994635 | doi = 10.1097/01.AOG.0000168435.17200.53 | s2cid = 22742373 }}</ref> Instead of a prophylactic cerclage, women at risk can be monitored during pregnancy by sonography, and when shortening of the cervix is observed, the cerclage can be performed.<ref name=Iams2008/>

==Treatment==
[[File:Premature birth Alberta, Canada.jpg|thumb|Preterm birth at 32 weeks 4 days, with a weight of 2,000&nbsp;g attached to medical equipment]]
Tertiary interventions are aimed at women who are about to go into preterm labor, or rupture the membranes or bleed preterm. The use of the [[Biology:Fetal fibronectin|fibronectin test]] and ultrasonography improves the diagnostic accuracy and reduces false-positive diagnosis. While treatments to arrest early labor where there is progressive cervical dilatation and effacement will not be effective to gain sufficient time to allow the fetus to grow and mature further, it may defer delivery sufficiently to allow the mother to be brought to a specialized center that is equipped and staffed to handle preterm deliveries.<ref>
{{cite journal | vauthors = Phibbs CS, Baker LC, Caughey AB, Danielsen B, Schmitt SK, Phibbs RH | title = Level and volume of neonatal intensive care and mortality in very-low-birth-weight infants | journal = The New England Journal of Medicine | volume = 356 | issue = 21 | pages = 2165–2175 | date = May 2007 | pmid = 17522400 | doi = 10.1056/NEJMsa065029 | s2cid = 8083107 | doi-access = free }}</ref> In a hospital setting women are hydrated via intravenous infusion (as dehydration can lead to premature uterine contractions).<ref>{{cite journal | vauthors = Stan CM, Boulvain M, Pfister R, Hirsbrunner-Almagbaly P | title = Hydration for treatment of preterm labour | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD003096 | date = November 2013 | pmid = 24190310 | doi = 10.1002/14651858.CD003096.pub2 }}</ref>

If a baby has [[Medicine:Cardiac arrest|cardiac arrest]] at birth and is less than 22 to 24 weeks gestational age, attempts at resuscitation are not generally indicated.<ref>{{cite journal | vauthors = Aziz K, Lee HC, Escobedo MB, Hoover AV, Kamath-Rayne BD, Kapadia VS, Magid DJ, Niermeyer S, Schmölzer GM, Szyld E, Weiner GM, Wyckoff MH, Yamada NK, Zaichkin J | display-authors = 6 | title = Part 5: Neonatal Resuscitation: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 142 | issue = 16_suppl_2 | pages = S524–S550 | date = October 2020 | pmid = 33081528 | doi = 10.1161/CIR.0000000000000902 | s2cid = 224826008 | doi-access = free }}</ref>

===Steroids===
Severely premature infants may have underdeveloped lungs because they are not yet producing their own [[Biology:Pulmonary surfactant|surfactant]]. This can lead directly to [[Medicine:Infant respiratory distress syndrome|respiratory distress syndrome]], also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, an [[Chemistry:Antenatal steroid|antenatal steroid]] that crosses the placental barrier and stimulates the production of surfactant in the lungs of the baby.<ref name=ACOG2016/> Steroid use up to 37 weeks is also recommended by the American Congress of Obstetricians and Gynecologists.<ref name=ACOG2016/> Typical glucocorticoids that would be administered in this context are [[Chemistry:Betamethasone|betamethasone]] or [[Biology:Dexamethasone|dexamethasone]], often when the pregnancy has reached viability at 23 weeks.{{Citation needed|date=May 2023}}

In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There are still some concerns about the efficacy and side effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk. A 2015 [[Organization:Cochrane (organisation)|Cochrane]] review (updated in 2022) supports the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course.<ref>{{cite journal | vauthors = Walters A, McKinlay C, Middleton P, Harding JE, Crowther CA | title = Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 4 | pages = CD003935 | date = April 2022 | pmid = 35377461 | pmc = 8978608 | doi = 10.1002/14651858.CD003935.pub5 }}</ref>

A Cochrane review from 2020 recommends the use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and respiratory distress syndrome and probably reduces the risk of IVH.<ref>{{cite journal | vauthors = McGoldrick E, Stewart F, Parker R, Dalziel SR | title = Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | pages = CD004454 | date = December 2020 | pmid = 33368142 | pmc = 8094626 | doi = 10.1002/14651858.CD004454.pub4 | publication-date = Dec 25, 2020 }}</ref>

Concerns about adverse effects of prenatal corticosteroids include increased risk for maternal infection, difficulty with diabetic control, and possible long-term effects on neurodevelopmental outcomes for the infants. There is ongoing discussion about when steroids should be given (i.e. only antenatally or postnatally too) and for how long (i.e. single course or repeated administration). Despite these unknowns, there is a consensus that the benefits of a single course of prenatal glucocorticosteroids vastly outweigh the potential risks.<ref>{{cite web |url=https://consensus.nih.gov/1994/1994AntenatalSteroidPerinatal095html.htm |title=The National Institutes of Health (NIH) Consensus Development Program: The Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes |access-date=2017-07-18 |url-status=live |archive-url=https://web.archive.org/web/20170709174327/https://consensus.nih.gov/1994/1994antenatalsteroidperinatal095html.htm |archive-date=9 July 2017}}</ref><ref>{{cite web |url=https://consensus.nih.gov/2000/2000AntenatalCorticosteroidsRevisted112html.htm |title=The National Institutes of Health (NIH) Consensus Development Program: Antenatal Corticosteroids Revisited: Repeat Courses |access-date=2017-07-18 |url-status=live |archive-url=https://web.archive.org/web/20170118011125/https://consensus.nih.gov/2000/2000AntenatalCorticosteroidsRevisted112html.htm |archive-date=18 January 2017}}</ref><ref name="pmid28786098">{{cite journal | vauthors = Shepherd E, Salam RA, Middleton P, Makrides M, McIntyre S, Badawi N, Crowther CA | title = Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 8 | pages = CD012077 | date = August 2017 | pmid = 28786098 | pmc = 6483544 | doi = 10.1002/14651858.CD012077.pub2 }}</ref>

=== Antibiotics ===
The routine administration of antibiotics to all women with threatened preterm labor reduces the risk of the baby being infected with [[Biology:Streptococcus agalactiae|group B streptococcus]] and has been shown to reduce related mortality rates.<ref>{{cite journal | vauthors = Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A | title = Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC | journal = MMWR. Recommendations and Reports | volume = 51 | issue = RR-11 | pages = 1–22 | date = August 2002 | pmid = 12211284 }}</ref>

When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Prophylactic antibiotic administration has been shown to prolong pregnancy and reduced neonatal morbidity with rupture of membranes at less than 34 weeks.<ref name="Kenyon2001">{{cite journal | vauthors = Kenyon SL, Taylor DJ, Tarnow-Mordi W | title = Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group | journal = Lancet | volume = 357 | issue = 9261 | pages = 989–994 | date = March 2001 | pmid = 11293641 | doi = 10.1016/S0140-6736(00)04233-1 | s2cid = 205936902 }}</ref> Because of concern about [[Medicine:Necrotizing enterocolitis|necrotizing enterocolitis]], [[Chemistry:Amoxicillin|amoxicillin]] or [[Chemistry:Erythromycin|erythromycin]] has been recommended but not amoxicillin + clavulanic acid (co-amoxiclav).<ref name="Kenyon2001"/>

===Tocolysis===
A number of medications may be useful to delay delivery including: [[Chemistry:Nonsteroidal anti-inflammatory drug|nonsteroidal anti-inflammatory drug]]s, [[Chemistry:Calcium channel blocker|calcium channel blocker]]s, [[Chemistry:Beta2-adrenergic agonist|beta mimetics]], and [[Chemistry:Atosiban|atosiban]].<ref>{{cite journal | vauthors = Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ | title = Tocolytic therapy for preterm delivery: systematic review and network meta-analysis | journal = BMJ | volume = 345 | pages = e6226 | date = October 2012 | pmid = 23048010 | pmc = 4688428 | doi = 10.1136/bmj.e6226 }}</ref> [[Medicine:Tocolytic|Tocolysis]] rarely delays delivery beyond 24–48 hours.<ref name=Simham2007>
{{cite journal | vauthors = Simhan HN, Caritis SN | title = Prevention of preterm delivery | journal = The New England Journal of Medicine | volume = 357 | issue = 5 | pages = 477–487 | date = August 2007 | pmid = 17671256 | doi = 10.1056/NEJMra050435 }}</ref> This delay, however, may be sufficient to allow the pregnant woman to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and [[Chemistry:Beta2-adrenergic agonist|β2-agonist]] drugs delay by 48 hours but carry more side effects.<ref name=Iams2008/><ref>{{cite journal | vauthors = Li X, Zhang Y, Shi Z | title = Ritodrine in the treatment of preterm labour: a meta-analysis | journal = The Indian Journal of Medical Research | volume = 121 | issue = 2 | pages = 120–127 | date = February 2005 | pmid = 15756046 }}</ref> [[Chemistry:Magnesium sulfate|Magnesium sulfate]] does not appear to be useful to prevent preterm birth.<ref>{{cite journal | vauthors = Crowther CA, Brown J, McKinlay CJ, Middleton P | title = Magnesium sulphate for preventing preterm birth in threatened preterm labour | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD001060 | date = August 2014 | pmid = 25126773 | doi = 10.1002/14651858.CD001060.pub2 }}</ref> Its use before delivery, however, does appear to decrease the risk of [[Medicine:Cerebral palsy|cerebral palsy]].<ref>{{cite journal | vauthors = Crowther CA, Middleton PF, Voysey M, Askie L, Duley L, Pryde PG, Marret S, Doyle LW | display-authors = 6 | title = Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis | journal = PLOS Medicine | volume = 14 | issue = 10 | pages = e1002398 | date = October 2017 | pmid = 28976987 | pmc = 5627896 | doi = 10.1371/journal.pmed.1002398 | doi-access = free }}</ref>

=== Mode of delivery ===
The routine use of [[Medicine:Caesarean section|caesarean section]] for early delivery of infants expected to have very low [[Medicine:Birth weight|birth weight]] is controversial,<ref>{{cite journal | vauthors = Alfirevic Z, Milan SJ, Livio S | title = Caesarean section versus vaginal delivery for preterm birth in singletons | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 9 | pages = CD000078 | date = September 2013 | pmid = 24030708 | pmc = 7052739 | doi = 10.1002/14651858.CD000078.pub3 }}</ref> and a decision concerning the route and time of delivery probably needs to be made on a case-by-case basis.

===Neonatal care===
[[File:Couveuse pour prématuré.jpg|thumb|upright=1.3|Incubator for preterm baby]]
In developed countries premature infants are usually cared for in a [[Medicine:Neonatal intensive care unit|neonatal intensive care unit]] (NICU). The physicians who specialize in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and [[Biology:Electroencephalography|brain activity]]. After delivery, plastic wraps or warm mattresses are useful to keep the infant warm on their way to the NICU.<ref>{{cite journal | vauthors = McCall EM, Alderdice F, Halliday HL, Vohra S, Johnston L | title = Interventions to prevent hypothermia at birth in preterm and/or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 2 | pages = CD004210 | date = February 2018 | pmid = 29431872 | pmc = 6491068 | doi = 10.1002/14651858.CD004210.pub5 }}</ref> Treatments may include fluids and nutrition through [[Chemistry:Intravenous therapy|intravenous]] catheters, [[Chemistry:Oxygen|oxygen]] supplementation, [[Medicine:Mechanical ventilation|mechanical ventilation]] support, and medications.<ref>{{cite journal | vauthors = Bruschettini M, O'Donnell CP, Davis PG, Morley CJ, Moja L, Calevo MG | title = Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 3 | pages = CD004953 | date = March 2020 | pmid = 32187656 | pmc = 7080446 | doi = 10.1002/14651858.CD004953.pub4 }}</ref> In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as ''[[Engineering:Kangaroo care|kangaroo care]]'' (skin to skin warming), encouraging [[Social:Breastfeeding|breastfeeding]], and basic infection control measures can significantly reduce preterm morbidity and mortality. Kangaroo mother care (KMC) can decrease the risk of neonatal sepsis, hypothermia, hypoglycemia and increase exclusive breastfeeding.<ref>{{cite journal | vauthors = Boundy EO, Dastjerdi R, Spiegelman D, Fawzi WW, Missmer SA, Lieberman E, Kajeepeta S, Wall S, Chan GJ | display-authors = 6 | title = Kangaroo Mother Care and Neonatal Outcomes: A Meta-analysis | journal = Pediatrics | volume = 137 | issue = 1 | date = January 2016 | pmid = 26702029 | pmc = 4702019 | doi = 10.1542/peds.2015-2238 }}</ref> Bili lights may also be used to treat [[Medicine:Neonatal jaundice|newborn jaundice]] (hyperbilirubinemia).

Water can be carefully provided to prevent dehydration but not so much to increase risks of side effects.<ref>{{cite journal | vauthors = Bell EF, Acarregui MJ | title = Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 12 | pages = CD000503 | date = 4 December 2014 | pmid = 25473815 | pmc = 7038715 | doi = 10.1002/14651858.CD000503.pub3 }}</ref>

==== Breathing support ====
In terms of respiratory support, there may be little or no difference in the risk of death or chronic lung disease between high flow nasal cannulae (HFNC) and continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NPPV).<ref>{{cite journal | vauthors = Hodgson KA, Wilkinson D, De Paoli AG, Manley BJ | title = Nasal high flow therapy for primary respiratory support in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 5 | pages = CD006405 | date = May 2023 | pmid = 37144837 | pmc = 10161968 | doi = 10.1002/14651858.CD006405.pub4 | pmc-embargo-date = May 5, 2024 }}</ref> For extremely preterm babies (born before 28 weeks' gestation), targeting a higher versus a lower oxygen saturation range makes little or no difference overall to the risk of death or major disability.<ref>{{cite journal | vauthors = Askie LM, Darlow BA, Davis PG, Finer N, Stenson B, Vento M, Whyte R | title = Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD011190 | date = April 2017 | pmid = 28398697 | pmc = 6478245 | doi = 10.1002/14651858.CD011190.pub2 }}</ref> Babies born before 32 weeks have been shown to have a lower risk of death from bronchopulmonary dysplasia if they have CPAP immediately after being born, compared to receiving either supportive care or assisted ventilation.<ref>{{cite journal |last1=Subramaniam |first1=P |last2=Ho |first2=JJ |last3=Davis |first3=PG |title=Prophylactic or very early initiation of continuous positive airway pressure (CPAP) for preterm infants. |journal=The Cochrane Database of Systematic Reviews |date=18 October 2021 |volume=2021 |issue=10 |pages=CD001243 |doi=10.1002/14651858.CD001243.pub4 |pmid=34661278 |pmc=8521644 |ref=CochraneCPAP}}</ref>

There is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding).<ref>{{cite journal | vauthors = Lai NM, Foong SC, Foong WC, Tan K | title = Co-bedding in neonatal nursery for promoting growth and neurodevelopment in stable preterm twins | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD008313 | date = April 2016 | pmid = 27075527 | pmc = 6464533 | doi = 10.1002/14651858.CD008313.pub3 }}</ref>

===Nutrition===
Meeting the appropriate nutritional needs of preterm infants is important for long-term health. Optimal care may require a balance of meeting nutritional needs and preventing complications related to feeding. The ideal growth rate is not known, however, preterm infants usually require a higher energy intake compared to babies who are born at term.<ref name="Abiramalatha_2021">{{cite journal | vauthors = Abiramalatha T, Thomas N, Thanigainathan S | title = High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 3 | pages = CD012413 | date = March 2021 | pmid = 33733486 | pmc = 8092452 | doi = 10.1002/14651858.CD012413.pub3 }}</ref> The recommended amount of milk is often prescribed based on approximated nutritional requirements of a similar aged fetus who is not compromised.<ref name="Walsh_2020">{{cite journal | vauthors = Walsh V, Brown JV, Copperthwaite BR, Oddie SJ, McGuire W | title = Early full enteral feeding for preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 12 | pages = CD013542 | date = December 2020 | pmid = 33368149 | pmc = 8094920 | doi = 10.1002/14651858.CD013542.pub2 }}</ref> An immature [[Biology:Gastrointestinal tract|gastrointestinal tract]] (GI tract), medical conditions (or [[Medicine:Comorbidity|co-morbidities]]), risk of aspirating milk, and [[Medicine:Necrotizing enterocolitis|necrotizing enterocolitis]] may lead to difficulties in meeting this high nutritional demand and many preterm infants have nutritional deficits that may result in growth restrictions.<ref name="Walsh_2020" /> In addition, very small preterm infants cannot coordinate sucking, swallowing, and breathing.<ref name="Sadrudin Premji_2021">{{cite journal | vauthors = Sadrudin Premji S, Chessell L, Stewart F | title = Continuous nasogastric milk feeding versus intermittent bolus milk feeding for preterm infants less than 1500 grams | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 6 | pages = CD001819 | date = June 2021 | pmid = 34165778 | pmc = 8223964 | doi = 10.1002/14651858.CD001819.pub3 }}</ref> Tolerating a full enteral feeding (the prescribed volume of milk or formula) is a priority in neonatal care as this reduces the risks associated with venous catheters including infection, and may reduce the length of time the infant requires specialized care in the hospital.<ref name="Walsh_2020" /> Different strategies can be used to optimize feeding for preterm infants. The type of milk/formula and fortifiers, route of administration (by mouth, tube feeding, venous catheter), timing of feeding, quantity of milk, continuous or intermittent feeding, and managing gastric residuals are all considered by the neonatal care team when optimizing care. The evidence in the form of high quality randomized trials is generally fairly weak in this area, and for this reason different neonatal intensive care units may have different practices and this results in a fairly large variation in practice. The care of preterm infants also varies in different countries and depends on resources that are available.<ref name="Walsh_2020" />

==== Human breast milk and formula ====
The American Academy of Pediatrics recommended feeding preterm infants [[Social:Breastfeeding|human milk]], finding "significant short- and long-term beneficial effects," including lower rates of [[Medicine:Necrotizing enterocolitis|necrotizing enterocolitis]] (NEC).<ref>{{cite journal | title = Breastfeeding and the use of human milk | journal = Pediatrics | volume = 129 | issue = 3 | pages = e827–e841 | date = March 2012 | pmid = 22371471 | doi = 10.1542/peds.2011-3552 | quote = Meta-analyses of 4 randomized clinical trials performed over the period 1983 to 2005 support the conclusion that feeding preterm infants human milk is associated with a significant reduction (58%) in the incidence of NEC. | doi-access = free | last1 = Eidelman | first1 = Arthur I. | last2 = Schanler | first2 = Richard J. | last3 = Johnston | first3 = Margreete | last4 = Landers | first4 = Susan | last5 = Noble | first5 = Larry | last6 = Szucs | first6 = Kinga | last7 = Viehmann | first7 = Laura }}</ref> In the absence of evidence from randomised controlled trials about the effects of feeding preterm infants with formula compared with mother's own breast milk, data collected from other types of studies suggest that mother's own breast milk is likely to have advantages over formula in terms of the baby's growth and development.<ref>{{cite journal | vauthors = Brown JV, Walsh V, McGuire W | title = Formula versus maternal breast milk for feeding preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD002972 | date = August 2019 | pmid = 31452191 | pmc = 6710607 | doi = 10.1002/14651858.CD002972.pub3 }}</ref><ref name="Abiramalatha_2021" /> A recent (2019) large review of evidence suggests that feeding preterm infants with formula rather than donor breast milk is associated with faster rates of growth, but with a near‐doubling of the risk of developing NEC.<ref>{{cite journal | vauthors = Quigley M, Embleton ND, McGuire W | title = Formula versus donor breast milk for feeding preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD002971 | date = July 2019 | pmid = 31322731 | pmc = 6640412 | doi = 10.1002/14651858.CD002971.pub5 }}</ref>

===== Fortified human breast milk and preterm/term formula =====
Breast milk or formula alone may not be sufficient to meet the nutritional needs of some preterm infants. Fortification of breast milk or formula by adding extra nutrients is an approach often taken for feeding preterm infants, with the goal of meeting the high nutritional demand.<ref name="Abiramalatha_2021" /> High quality randomized controlled trials are needed in this field to determine the effectiveness of fortification.<ref name="Brown_2016" /> It is unclear if fortification of breast milk improves outcomes in preterm babies, though it may speed growth.<ref name="Brown_2016">{{cite journal | vauthors = Brown JV, Embleton ND, Harding JE, McGuire W | title = Multi-nutrient fortification of human milk for preterm infants | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD000343 | date = May 2016 | pmid = 27155888 | doi = 10.1002/14651858.CD000343.pub3 }}</ref> Supplementing human milk with extra protein may increase short-term growth but the longer-term effects on body composition, growth and brain development are uncertain.<ref>{{cite journal | vauthors = Amissah EA, Brown J, Harding JE | title = Protein supplementation of human milk for promoting growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 9 | pages = CD000433 | date = September 2020 | pmid = 32964431 | pmc = 8094919 | doi = 10.1002/14651858.CD000433.pub3 }}</ref><ref>{{cite journal | vauthors = Gao C, Miller J, Collins CT, Rumbold AR | title = Comparison of different protein concentrations of human milk fortifier for promoting growth and neurological development in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 11 | pages = CD007090 | date = November 2020 | pmid = 33215474 | pmc = 8092673 | doi = 10.1002/14651858.CD007090.pub2 }}</ref> Higher protein formula (between 3 and 4 grams of protein per kilo of body weight) may be more effective than low protein formula (less than 3 grams per kilo per day) for weight gain in formula-fed low-birth-weight infants.<ref>{{cite journal | vauthors = Fenton TR, Al-Wassia H, Premji SS, Sauve RS | title = Higher versus lower protein intake in formula-fed low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD003959 | date = June 2020 | pmid = 32573771 | pmc = 7387284 | doi = 10.1002/14651858.CD003959.pub4 }}</ref> There is insufficient evidence about the effect on preterm babies' growth of supplementing human milk with carbohydrate,<ref>{{cite journal | vauthors = Amissah EA, Brown J, Harding JE | title = Carbohydrate supplementation of human milk to promote growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD000280 | date = September 2020 | pmid = 32898300 | pmc = 8094174 | doi = 10.1002/14651858.CD000280.pub3 }}</ref> fat,<ref>{{cite journal | vauthors = Amissah EA, Brown J, Harding JE | title = Fat supplementation of human milk for promoting growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD000341 | date = August 2020 | pmid = 32842164 | pmc = 8236752 | doi = 10.1002/14651858.CD000341.pub3 }}</ref><ref>{{cite journal | vauthors = Perretta L, Ouldibbat L, Hagadorn JI, Brumberg HL | title = High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 2 | pages = CD002777 | date = February 2021 | pmid = 33620090 | pmc = 8094384 | doi = 10.1002/14651858.CD002777.pub2 }}</ref> and branched-chain amino acids.<ref>{{cite journal | vauthors = Amari S, Shahrook S, Namba F, Ota E, Mori R | title = Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 10 | pages = CD012273 | date = October 2020 | pmid = 33006765 | pmc = 8078205 | doi = 10.1002/14651858.CD012273.pub2 }}</ref> Conversely, there is some indication that preterm babies who cannot breastfeed may do better if they are fed only with diluted formula compared to full strength formula but the clinical trial evidence remains uncertain.<ref>{{cite journal | vauthors = Basuki F, Hadiati DR, Turner T, McDonald S, Hakimi M | title = Dilute versus full-strength formula in exclusively formula-fed preterm or low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD007263 | date = June 2019 | pmid = 31246272 | pmc = 6596360 | doi = 10.1002/14651858.CD007263.pub3 }}</ref>

Individualizing the nutrients and quantities used to fortify enteral milk feeds in infants born with very low birth weight may lead to better short-term weight gain and growth but the evidence is uncertain for longer term outcomes and for the risk of serious illness and death.<ref name="Fabrizio_2020">{{cite journal | vauthors = Fabrizio V, Trzaski JM, Brownell EA, Esposito P, Lainwala S, Lussier MM, Hagadorn JI | title = Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD013465 | date = November 2020 | pmid = 33226632 | pmc = 8094236 | doi = 10.1002/14651858.CD013465.pub2 }}</ref> This includes targeted fortification (adjusting the level of nutrients in response to the results of a test on the breast milk) and adjustable fortification (adding nutrients based on testing the infant).<ref name="Fabrizio_2020" />

Multi-nutrient fortifier used to fortify human milk and formula has traditionally been derived from bovine milk.<ref name="Premkumar_2019">{{cite journal | vauthors = Premkumar MH, Pammi M, Suresh G | title = Human milk-derived fortifier versus bovine milk-derived fortifier for prevention of mortality and morbidity in preterm neonates | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 11 | date = November 2019 | pmid = 31697857 | pmc = 6837687 | doi = 10.1002/14651858.CD013145.pub2 }}</ref> Fortifier derived from humans is available, however, the evidence from clinical trials is uncertain and it is not clear if there are any differences between human-derived fortifier and bovine-derived fortifier in terms of neonatal weight gain, feeding intolerance, infections, or the risk of death.<ref name="Premkumar_2019" />

==== Timing of feeds ====
For very preterm infants, most neonatal care centres start milk feeds gradually, rather than starting with a full enteral feeding right away, however, is not clear if starting full enteral feeding early effects the risk of necrotising enterocolitis.<ref name="Walsh_2020" /> In these cases, the preterm infant would be receiving the majority of their nutrition and fluids intravenously. The milk volume is usually gradually increased over the following weeks.<ref name="Walsh_2020" /> Research into the ideal timing of enteral feeding and whether delaying enteral feeding or gradually introducing enteral feeds is beneficial at improving growth for preterm infants or low birth weight infants is needed.<ref name="Walsh_2020" /> In addition, the ideal timing of enteral feeds to prevent side effects such as necrotising enterocolitis or mortality in preterm infants who require a packed red blood cell transfusion is not clear.<ref>{{cite journal | vauthors = Yeo KT, Kong JY, Sasi A, Tan K, Lai NM, Schindler T | title = Stopping enteral feeds for prevention of transfusion-associated necrotising enterocolitis in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 10 | date = October 2019 | pmid = 31684689 | pmc = 6815687 | doi = 10.1002/14651858.CD012888.pub2 }}</ref> Potential disadvantages of a more gradual approach to feeding preterm infants associated with less milk in the gut and include slower GI tract secretion of hormones and gut motility and slower microbial colonization of the gut.<ref name="Walsh_2020" />

Regarding the timing of starting fortified milk, preterm infants are often started on fortified milk/formula once they are fed 100&nbsp;mL/kg of their body weight. Other some neonatal specialists feel that starting to feed a preterm infant fortified milk earlier is beneficial to improve intake of nutrients.<ref name="Thanigainathan_2020">{{cite journal | vauthors = Thanigainathan S, Abiramalatha T | title = Early fortification of human milk versus late fortification to promote growth in preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 7 | pages = CD013392 | date = July 2020 | pmid = 32726863 | pmc = 7390609 | doi = 10.1002/14651858.CD013392.pub2 }}</ref> The risks of feeding intolerance and necrotising enterocolitis related to early versus later fortification of human milk are not clear.<ref name="Thanigainathan_2020" /> Once the infant is able to go home from the hospital there is limited evidence to support prescribing a preterm (fortified) formula.<ref>{{cite journal | vauthors = Young L, Embleton ND, McGuire W | title = Nutrient-enriched formula versus standard formula for preterm infants following hospital discharge | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 12 | pages = CD004696 | date = December 2016 | pmid = 27958643 | pmc = 6463855 | doi = 10.1002/14651858.CD004696.pub5 }}</ref>

==== Intermittent feeding versus continuous feeding ====
For infants who weigh less than 1500 grams, tube feeding is usually necessary.<ref name="Sadrudin Premji_2021" /> Most often, neonatal specialists feed preterm babies intermittently with a prescribed amount of milk over a short period of time. For example, a feed could last 10–20 minutes and be given every 3 hours. This intermittent approach is meant to mimic conditions of normal bodily functions involved with feeding and allow for a cyclic pattern in the release of gastrointestinal tract hormones to promote development of the gastrointestinal system.<ref name="Sadrudin Premji_2021" /> In certain cases, continuous nasogastric feeding is sometimes preferred. There is low to very low certainty evidence to suggest that low birth weight babies who receive continuous nasogastic feeding may reach the benchmark of tolerating full enteral feeding later than babies fed intermittently and it is not clear if continuous feeding has any effect on weight gain or the number of interruptions in feedings.<ref name="Sadrudin Premji_2021" /> Continuous feeding may have little to no effect on length of body growth or head circumference and the effects of continuous feeding on the risk of developing necrotising enterocolitis is not clear.<ref name="Sadrudin Premji_2021" />

Since preterm infants with gastro-oesophageal reflux disease do not have a fully developed antireflux mechanism, deciding on the most effective approach for nutrition is important. It is not clear if continuous bolus intragastric tube feeding is more effective compared to intermittent bolus intragastric tube feeding for feeding preterm infants with [[Medicine:Gastroesophageal reflux disease|gastroesophageal reflux disease]].<ref>{{cite journal | vauthors = Richards R, Foster JP, Psaila K | title = Continuous versus bolus intermittent intragastric tube feeding for preterm and low birth weight infants with gastro-oesophageal reflux disease | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 8 | pages = CD009719 | date = August 2021 | pmid = 34355390 | pmc = 8407337 | doi = 10.1002/14651858.CD009719.pub3 }}</ref>

For infants who would benefit from intermittent bolus feeding, some infants may be fed using the "push feed" method using a syringe to gently push the milk or formula into the stomach of the infant. Others may be fed using a gravity feeding system where the syringe is attached directly to a tube and the milk or formula drips into the infant's stomach. It is not clear from medical studies which approach to intermittent bolus feeding is more effective or reduces adverse effects such as apnea, bradycardia, or oxygen desaturation episodes.<ref>{{cite journal | vauthors = Dawson JA, Summan R, Badawi N, Foster JP | title = Push versus gravity for intermittent bolus gavage tube feeding of preterm and low birth weight infants | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 8 | pages = CD005249 | date = August 2021 | pmid = 34346056 | pmc = 8407046 | doi = 10.1002/14651858.CD005249.pub3 }}</ref><ref>{{cite journal | vauthors = Akindolire A, Talbert A, Sinha I, Embleton N, Allen S | title = Evidence that informs feeding practices in very low birthweight and very preterm infants in sub-Saharan Africa: an overview of systematic reviews | journal = BMJ Paediatrics Open | volume = 4 | issue = 1 | pages = e000724 | date = 2020 | pmid = 32821859 | pmc = 7422638 | doi = 10.1136/bmjpo-2020-000724 }}</ref>

==== High volume feeds ====
High-volume (more than 180&nbsp;mL per kilogram per day) [[Medicine:Enteral administration|enteral]] feeds of fortified or non-fortified human breast milk or formula may improve weight gain while the pre-term infant is hospitalized, however, there is insufficient evidence to determine if this approach improves growth of the neonate and other clinical outcomes including length of hospital stay.<ref name="Abiramalatha_2021" /> The risks or adverse effects associated with high-volume enteral feeding of preterm infants including [[Medicine:Aspiration pneumonia|aspiration pneumonia]], [[Medicine:Gastroesophageal reflux disease|reflux]], apnea, and sudden oxygen desaturation episodes have not been reported in the trials considered in a 2021 [[Systematic review|systematic review]].<ref name="Abiramalatha_2021" />

==== Parenteral (intraveneous) nutrition ====
For preterm infants who are born after 34 weeks of gestation ("late preterm infants") who are critically ill and cannot tolerate milk, there is some weak evidence that the infant may benefit from including amino acids and fats in the intravenous nutrition at a later time point (72 hours or longer from hospital admission) versus early (less than 72 hours from admission to hospital), however further research is required to understand the ideal timing of starting intravenous nutrition.<ref>{{cite journal | vauthors = Moon K, Athalye-Jape GK, Rao U, Rao SC | title = Early versus late parenteral nutrition for critically ill term and late preterm infants | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 4 | pages = CD013141 | date = April 2020 | pmid = 32266712 | pmc = 7138920 | doi = 10.1002/14651858.CD013141.pub2 }}</ref>

==== Gastric residuals ====
For preterm infants in neonatal intensive care on gavage feeds, monitoring the volume and colour of gastric residuals, the milk and gastrointestinal secretions that remain in the stomach after a set amount of time, is common standard of care practice.<ref name="Abiramalatha_2023">{{cite journal |last1=Abiramalatha |first1=T |last2=Thanigainathan |first2=S |last3=Ramaswamy |first3=VV |last4=Rajaiah |first4=B |last5=Ramakrishnan |first5=S |title=Re-feeding versus discarding gastric residuals to improve growth in preterm infants. |journal=The Cochrane Database of Systematic Reviews |date=30 June 2023 |volume=2023 |issue=6 |pages=CD012940 |doi=10.1002/14651858.CD012940.pub3 |pmid=37387544 |pmc=10312053 |url=https://pubmed.ncbi.nlm.nih.gov/37387544/ |access-date=19 October 2023 |ref=Abiramalatha_2023 |pmc-embargo-date=June 30, 2024 }}</ref> Gastric residual often contains gastric acid, hormones, enzymes, and other substances that may help improve digestion and mobility of the gastrointestinal tract.<ref name="Abiramalatha_2023" /> Analysis of gastric residuals may help guide timing of feeds.<ref name="Abiramalatha_2023" /> Increased gastric residual may indicate feeding intolerance or it may be an early sign of necrotizing enterocolitis.<ref name="Abiramalatha_2023" /> Increased gastric residual may be caused by an underdeveloped gastrointestinal system that leads to slower gastric emptying or movement of the milk in the intestinal tract, reduced hormone or enzyme secretions from the gastrointestinal tract, duodenogastric [[Medicine:Gastroesophageal reflux disease|reflux]], formula, medications, and/or illness.<ref name="Abiramalatha_2023" /> The clinical decision to discard the gastric residuals (versus re-feeding) is often individualized based on the quantity and quality of the residual.<ref name="Abiramalatha_2023" /> Some experts also suggest replacing the fresh milk or curded milk and bile-stained aspirates, but not replacing haemorrhagic residual.<ref name="Abiramalatha_2023" /> Evidence to support or refute the practice of re-feeding preterm infants with gastric residuals is lacking.<ref name="Abiramalatha_2023" />

=== Hyponatraemia and hypernatraemia ===
Imbalances of sodium ([[Medicine:Hyponatremia|hyponatraemia]] and [[Medicine:Hypernatremia|hypernatraemia]]) are common in babies born preterm.<ref name=":0">{{Cite journal |last1=Diller |first1=Natasha |last2=Osborn |first2=David A |last3=Birch |first3=Pita |date=2023-10-12 |editor-last=Cochrane Neonatal Group |title=Higher versus lower sodium intake for preterm infants |journal=Cochrane Database of Systematic Reviews |language=en |volume=2023 |issue=10 |pages=CD012642 |doi=10.1002/14651858.CD012642.pub2 |pmc=10569379 |pmid=37824273 |pmc-embargo-date=October 12, 2024 }}</ref> Hypernatraemia (sodium levels in the serum of more than 145-150 mmol/L) is common early on in preterm babies and the risk of hyponatraemia (sodium levels of less than 135 nmol/L) increases after about a week of birth if left untreated and prevention approaches are not used.<ref name=":0" /> Preventing complications associated with sodium imbalances is part of standard of care for preterm infants and includes careful monitoring of water and sodium given to the infant.<ref name=":0" /> The optimal sodium dose given immediately after birth (first day) is not clear and further research is needed to understand the idea management approach.<ref name=":0" />

=== Hearing assessment===
The Joint Committee on Infant Hearing (JCIH) state that for preterm infants who are in the neonatal intensive care unit (NICU) for a prolonged time should have a diagnostic audiologic evaluation before they are discharged from the hospital.<ref name="Joint Committee on Infant Hearing_2007">{{cite journal | author = Joint Committee on Infant Hearing | title = Year 2007 position statement: Principles and guidelines for early hearing detection and intervention programs | journal = Pediatrics | volume = 120 | issue = 4 | pages = 898–921 | date = October 2007 | pmid = 17908777 | doi = 10.15142/fptk-b748 }}</ref> Well babies follow a 1-2-3-month benchmark timeline where they are screened, diagnosed, and receiving intervention for a hearing loss. However, very premature babies it might not be possible to complete a hearing screen at one month of age due to several factors. Once the baby is stable an audiologic evaluation should be performed. For premature babies in the NICU, auditory brainstem response (ABR) testing is recommended. If the infant does not pass the screen, they should be referred for an audiologic evaluation by an audiologist.<ref name="Joint Committee on Infant Hearing_2007"/> If the infant is on aminoglycosides such as gentamicin for less than five days they should be monitored and have a follow-up 6–7 months of being discharged from the hospital to ensure there is no late onset hearing loss due to the medication.<ref name="Joint Committee on Infant Hearing_2007"/>

==Outcomes and prognosis==
[[File:Preterm infants survival rates.svg|thumb|upright=1.4|Preterm infants survival rates<ref>{{cite journal | vauthors = Patel RM, Rysavy MA, Bell EF, Tyson JE | title = Survival of Infants Born at Periviable Gestational Ages | journal = Clinics in Perinatology | volume = 44 | issue = 2 | pages = 287–303 | date = June 2017 | pmid = 28477661 | pmc = 5424630 | doi = 10.1016/j.clp.2017.01.009 }}</ref><ref>{{cite journal | vauthors = Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES | title = Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies) | journal = BMJ | volume = 345 | pages = e7976 | date = December 2012 | pmid = 23212881 | pmc = 3514472 | doi = 10.1136/bmj.e7976 }}</ref><ref>{{cite journal | vauthors = Fellman V, Hellström-Westas L, Norman M, Westgren M, Källén K, Lagercrantz H, Marsál K, Serenius F, Wennergren M | display-authors = 6 | title = One-year survival of extremely preterm infants after active perinatal care in Sweden | journal = JAMA | volume = 301 | issue = 21 | pages = 2225–2233 | date = June 2009 | pmid = 19491184 | doi = 10.1001/jama.2009.771 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ancel PY, Goffinet F, Kuhn P, Langer B, Matis J, Hernandorena X, Chabanier P, Joly-Pedespan L, Lecomte B, Vendittelli F, Dreyfus M, Guillois B, Burguet A, Sagot P, Sizun J, Beuchée A, Rouget F, Favreau A, Saliba E, Bednarek N, Morville P, Thiriez G, Marpeau L, Marret S, Kayem G, Durrmeyer X, Granier M, Baud O, Jarreau PH, Mitanchez D, Boileau P, Boulot P, Cambonie G, Daudé H, Bédu A, Mons F, Fresson J, Vieux R, Alberge C, Arnaud C, Vayssière C, Truffert P, Pierrat V, Subtil D, D'Ercole C, Gire C, Simeoni U, Bongain A, Sentilhes L, Rozé JC, Gondry J, Leke A, Deiber M, Claris O, Picaud JC, Ego A, Debillon T, Poulichet A, Coliné E, Favre A, Fléchelles O, Samperiz S, Ramful D, Branger B, Benhammou V, Foix-L'Hélias L, Marchand-Martin L, Kaminski M | display-authors = 6 | title = Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study | journal = JAMA Pediatrics | volume = 169 | issue = 3 | pages = 230–238 | date = March 2015 | pmid = 25621457 | doi = 10.1001/jamapediatrics.2014.3351 | collaboration = EPIPAGE-2 Writing Group | doi-access = free }}</ref><ref>{{cite journal | vauthors = Boland RA, Davis PG, Dawson JA, Doyle LW | title = Outcomes of infants born at 22-27 weeks' gestation in Victoria according to outborn/inborn birth status | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 102 | issue = 2 | pages = F153–F161 | date = March 2017 | pmid = 27531224 | doi = 10.1136/archdischild-2015-310313 | s2cid = 7958596 }}</ref><ref>{{cite journal | vauthors = Chen F, Bajwa NM, Rimensberger PC, Posfay-Barbe KM, Pfister RE | title = Thirteen-year mortality and morbidity in preterm infants in Switzerland | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 101 | issue = 5 | pages = F377–F383 | date = September 2016 | pmid = 27059074 | doi = 10.1136/archdischild-2015-308579 | s2cid = 20567764 }}</ref>]]{{Main|Health outcomes for adults born prematurely}}
Preterm births can result in a range of problems including mortality and physical and mental delays.<ref name="SaigalDoyle2008">{{cite journal | vauthors = Saigal S, Doyle LW | title = An overview of mortality and sequelae of preterm birth from infancy to adulthood | journal = Lancet | volume = 371 | issue = 9608 | pages = 261–269 | date = January 2008 | pmid = 18207020 | doi = 10.1016/S0140-6736(08)60136-1 | s2cid = 17256481 }}</ref><ref name="BMJ">{{cite journal | vauthors = Phillips C, Velji Z, Hanly C, Metcalfe A | title = Risk of recurrent spontaneous preterm birth: a systematic review and meta-analysis | journal = BMJ Open | volume = 7 | issue = 6 | pages = e015402 | date = July 2017 | pmid = 28679674 | pmc = 5734267 | doi = 10.1136/bmjopen-2016-015402 }}</ref>

===Mortality and morbidity===
In the U.S. where many [[Medicine:Neonatal infection|neonatal infection]]s and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%.<ref>
{{cite journal|vauthors=Mathew TJ, MacDorman MF|year=2006|title=Infant Mortality Statistics from the 2003 Period Linked Birth/Infant Death Data Set|journal=National Vital Statistics Reports|volume=54|issue=16}}</ref> Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below.

The earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. As NICU care has improved over the last 40 years, the limit of viability has reduced to approximately 24 weeks.<ref name="Kaempf2006">
{{cite journal | vauthors = Kaempf JW, Tomlinson M, Arduza C, Anderson S, Campbell B, Ferguson LA, Zabari M, Stewart VT | display-authors = 6 | title = Medical staff guidelines for periviability pregnancy counseling and medical treatment of extremely premature infants | journal = Pediatrics | volume = 117 | issue = 1 | pages = 22–29 | date = January 2006 | pmid = 16396856 | doi = 10.1542/peds.2004-2547 | url = http://pediatrics.aappublications.org/cgi/content/full/117/1/22 | url-status = live | s2cid = 20495326 | archive-url = https://web.archive.org/web/20080318092852/http://pediatrics.aappublications.org/cgi/content/full/117/1/22 | archive-date = 18 March 2008 }} — in particular see [http://pediatrics.aappublications.org/cgi/content-nw/full/117/1/22/T1 TABLE 1 Survival and Neurologic Disability Rates Among Extremely Premature Infants] {{webarchive|url=https://web.archive.org/web/20080612205553/http://pediatrics.aappublications.org/cgi/content-nw/full/117/1/22/T1|date=12 June 2008}}</ref><ref name="Morgan2008">
{{cite journal | vauthors = Morgan MA, Goldenberg RL, Schulkin J | title = Obstetrician-gynecologists' practices regarding preterm birth at the limit of viability | journal = The Journal of Maternal-Fetal & Neonatal Medicine | volume = 21 | issue = 2 | pages = 115–121 | date = February 2008 | pmid = 18240080 | doi = 10.1080/14767050701866971 | s2cid = 27735824 }}</ref> Most newborns who die, and 40% of older infants who die, were born between 20 and 25.9 weeks (gestational age), during the second trimester.<ref name="Ecker_2017" />

As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are [[Medicine:Medical ethics|ethical]] controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the [[Medicine:Abortion|abortion]] debate.<ref name="Arzuaga2011">{{cite journal | vauthors = Arzuaga BH, Lee BH | title = Limits of human viability in the United States: a medicolegal review | journal = Pediatrics | volume = 128 | issue = 6 | pages = 1047–1052 | date = December 2011 | pmid = 22065266 | doi = 10.1542/peds.2011-1689 | s2cid = 31065615 | doi-access = free }}</ref>

===Specific risks for the preterm neonate===
Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result, they are at risk for numerous medical problems affecting different organ systems.
*Neurological problems can include apnea of prematurity, hypoxic-ischemic encephalopathy (HIE), [[Medicine:Retinopathy of prematurity|retinopathy of prematurity]] (ROP),<ref>{{Cite book| vauthors = Lambert SR, Lyons CJ |title=Taylor and Hoyt's pediatric ophthalmology and strabismus|date=2016-10-31|isbn=9780702066160|edition=Fifth|location=Edinburgh | publisher = Elsevier Health Sciences|oclc=960162637|name-list-style=vanc}}</ref> [[Social:Developmental disability|developmental disability]], transient hyperammonemia, [[Medicine:Cerebral palsy|cerebral palsy]], and [[Medicine:Intraventricular hemorrhage|intraventricular hemorrhage]], the latter affecting 25% of babies born preterm, usually before 32 weeks of pregnancy.<ref name="marchofdimes">[http://www.marchofdimes.org/loss/neonatal-death.aspx March of Dimes --> Neonatal Death] {{webarchive|url=https://web.archive.org/web/20141024114718/http://www.marchofdimes.org/loss/neonatal-death.aspx|date=24 October 2014}} Retrieved on 11 November 2014</ref> Mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death.<ref name="marchofdimes" /> Neurodevelopmental problems have been linked to lack of maternal thyroid hormones, at a time when their own [[Biology:Thyroid|thyroid]] is unable to meet postnatal needs.<ref>{{cite journal | vauthors = Berbel P, Navarro D, Ausó E, Varea E, Rodríguez AE, Ballesta JJ, Salinas M, Flores E, Faura CC, de Escobar GM | display-authors = 6 | title = Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity | journal = Cerebral Cortex | volume = 20 | issue = 6 | pages = 1462–1475 | date = June 2010 | pmid = 19812240 | pmc = 2871377 | doi = 10.1093/cercor/bhp212 }}</ref>
*Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (PDA).
*Respiratory problems are common, specifically the [[Medicine:Infant respiratory distress syndrome|respiratory distress syndrome]] (RDS or IRDS) (previously called hyaline membrane disease). Another problem can be [[Medicine:Bronchopulmonary dysplasia|chronic lung disease]] (previously called bronchopulmonary dysplasia or BPD).
*Gastrointestinal and metabolic issues can arise from neonatal hypoglycemia, feeding difficulties, [[Medicine:Rickets|rickets]] of prematurity, [[Medicine:Hypocalcemia|hypocalcemia]], inguinal hernia, and [[Medicine:Necrotizing enterocolitis|necrotizing enterocolitis]] (NEC).
*Hematologic complications include [[Medicine:Anemia of prematurity|anemia of prematurity]], [[Medicine:Thrombocytopenia|thrombocytopenia]], and hyperbilirubinemia (jaundice) that can lead to [[Medicine:Kernicterus|kernicterus]].
*Infection, including [[Medicine:Sepsis|sepsis]], [[Medicine:Pneumonia|pneumonia]], and [[Medicine:Urinary tract infection|urinary tract infection]] {{ref|1}}

=== Survival ===
The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72% as of 2016.<ref name="Clo2016" /> With extensive treatment up to 30% of those who survive birth at 22 weeks survive longer term as of 2019.<ref name="BAPM2019">{{cite web |title=New BAPM Framework on Extreme Preterm Birth Published {{!}} British Association of Perinatal Medicine |url=https://www.bapm.org/posts/109-new-bapm-framework-on-extreme-preterm-birth-published |website=www.bapm.org |access-date=25 October 2019 |archive-date=4 December 2020 |archive-url=https://web.archive.org/web/20201204175403/https://www.bapm.org/posts/109-new-bapm-framework-on-extreme-preterm-birth-published |url-status=dead }}</ref> The chances of survival without long-term difficulties is less.<ref name="Jar2015" /> Of those who survive following birth at 22 weeks 33% have severe disabilities.<ref name="BAPM2019" /> In the developed world, overall survival is about 90% while in low-income countries survival rates are about 10%.<ref name="WHO2015QA">{{cite web|date=November 2015|title=World Health Organization|url=https://www.who.int/features/qa/preterm_babies/en/|url-status=live|archive-url=https://web.archive.org/web/20160718231911/http://www.who.int/features/qa/preterm_babies/en/|archive-date=18 July 2016}}</ref>

Some children will adjust well during childhood and adolescence,<ref name="SaigalDoyle2008"/> although disability is more likely nearer the limits of viability. A large study followed children born between 22 and 25 weeks until the age of 6 years old. Of these children, 46% had moderate to severe disabilities such as cerebral palsy, vision or hearing loss and learning disabilities, 34% had mild disabilities, and 20% had no disabilities; 12% had disabling cerebral palsy.<ref name="msnbc.msn.com">{{cite web |date=6 January 2005 |title=Extreme preemies face long-term disabilities |url=http://www.nbcnews.com/id/6790571 |website=NBC News}}</ref> Up to 15% of premature infants have significant hearing loss.<ref>{{cite web |date=2017-06-19 |title=Why Do So Many Preemies Have Hearing Loss? |url=https://www.audiology.org/news/why-do-so-many-preemies-have-hearing-loss |access-date=2020-04-01 |website=Audiology}}</ref>

As survival has improved, the focus of interventions directed at the newborn has shifted to reduce long-term disabilities, particularly those related to brain injury.<ref name="SaigalDoyle2008"/> Some of the complications related to prematurity may not be apparent until years after the birth. A long-term study demonstrated that the risks of medical and social disabilities extend into adulthood and are higher with decreasing gestational age at birth and include [[Medicine:Cerebral palsy|cerebral palsy]], [[Medicine:Intellectual disability|intellectual disability]], disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and [[Medicine:Epilepsy|epilepsy]].<ref name=Moster2008>
{{cite journal | vauthors = Moster D, Lie RT, Markestad T | title = Long-term medical and social consequences of preterm birth | journal = The New England Journal of Medicine | volume = 359 | issue = 3 | pages = 262–273 | date = July 2008 | pmid = 18635431 | doi = 10.1056/NEJMoa0706475 | s2cid = 25921193 | doi-access = free }}</ref> Standard intelligence tests showed that 41% of children born between 22 and 25 weeks had moderate or severe learning disabilities when compared to the test scores of a group of similar classmates who were born at full term.<ref name="msnbc.msn.com"/> It is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth.<ref name=Moster2008/> People born prematurely may be more susceptible to developing depression as teenagers.<ref name=dunn>
{{cite news| title=Depression linked to premature birth| url=http://www.theage.com.au/articles/2004/05/03/1083436541757.html| access-date=2008-12-16| location=Melbourne| work=The Age| date=2004-05-04| url-status=live| archive-url=https://web.archive.org/web/20090408083313/http://www.theage.com.au/articles/2004/05/03/1083436541757.html| archive-date=8 April 2009}}</ref>
Some of these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes.<ref>
{{cite journal | vauthors = Böhm B, Katz-Salamon M, Institute K, Smedler AC, Lagercrantz H, Forssberg H | title = Developmental risks and protective factors for influencing cognitive outcome at 5 1/2 years of age in very-low-birthweight children | journal = Developmental Medicine and Child Neurology | volume = 44 | issue = 8 | pages = 508–516 | date = August 2002 | pmid = 12206615 | doi = 10.1017/S001216220100247X }}</ref> Studies of people born premature and investigated later with [[Physics:Magnetic resonance imaging|MRI brain imaging]], demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence.<ref name="Spencer2008">{{cite journal | vauthors = Spencer MD, Moorhead TW, Gibson RJ, McIntosh AM, Sussmann JE, Owens DG, Lawrie SM, Johnstone EC | display-authors = 6 | title = Low birthweight and preterm birth in young people with special educational needs: a magnetic resonance imaging analysis | journal = BMC Medicine | volume = 6 | issue = 1 | pages = 1 | date = January 2008 | pmid = 18234075 | pmc = 2241838 | doi = 10.1186/1741-7015-6-1 | doi-access = free }}</ref> Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.<ref name="SaigalDoyle2008"/> They are more likely to develop type 1 diabetes (roughly 1.2 times the rate) and type 2 diabetes (1.5 times).<ref>{{cite journal | vauthors = Li S, Zhang M, Tian H, Liu Z, Yin X, Xi B | title = Preterm birth and risk of type 1 and type 2 diabetes: systematic review and meta-analysis | journal = Obesity Reviews | volume = 15 | issue = 10 | pages = 804–811 | date = October 2014 | pmid = 25073871 | doi = 10.1111/obr.12214 | s2cid = 22685359 }}</ref>

Despite the neurosensory, mental and educational problems studied in school age and adolescent children born extremely preterm, the majority of preterm survivors born during the early years of neonatal intensive care are found to do well and to live fairly normal lives in young adulthood.<ref>{{cite journal | vauthors = Hack M | title = Adult outcomes of preterm children | journal = Journal of Developmental and Behavioral Pediatrics | volume = 30 | issue = 5 | pages = 460–470 | date = October 2009 | pmid = 19823140 | doi = 10.1097/dbp.0b013e3181ba0fba | s2cid = 205574669 }}</ref> Young adults born preterm seem to acknowledge that they have more health problems than their peers, yet feel the same degree of satisfaction with their quality of life.<ref>{{cite journal | vauthors = Saigal S | title = Quality of life of former premature infants during adolescence and beyond | journal = Early Human Development | volume = 89 | issue = 4 | pages = 209–213 | date = April 2013 | pmid = 23462550 | doi = 10.1016/j.earlhumdev.2013.01.012 }}</ref>

Beyond the neurodevelopmental consequences of prematurity, infants born preterm have a greater risk for many other health problems. For instance, children born prematurely have an increased risk for developing [[Medicine:Chronic kidney disease|chronic kidney disease]].<ref>{{cite journal | vauthors = Carmody JB, Charlton JR | title = Short-term gestation, long-term risk: prematurity and chronic kidney disease | journal = Pediatrics | volume = 131 | issue = 6 | pages = 1168–1179 | date = June 2013 | pmid = 23669525 | doi = 10.1542/peds.2013-0009 | s2cid = 8389988 }}</ref>

==Epidemiology==
[[File:Prematurity and low birth weight world map - DALY - WHO2004.svg|thumb|upright=1.2|[[Disability-adjusted life year]] for prematurity and low birth weight per 100,000 inhabitants in 2004.<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009 }}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|less than 120}}
{{legend|#fff200|120–240}}
{{legend|#ffdc00|240–360}}
{{legend|#ffc600|360–480}}
{{legend|#ffb000|480–600}}
{{legend|#ff9a00|600–720}}
{{legend|#ff8400|720–840}}
{{legend|#ff6e00|840–960}}
{{legend|#ff5800|960–1080}}
{{legend|#ff4200|1080–1200}}
{{legend|#ff2c00|1200–1500}}
{{legend|#cb0000|more than 1500}}
{{div col end}}]]
Preterm birth complicates 5–18% of births worldwide.<ref name=rob2015/> In Europe and many developed countries the preterm birth rate is generally 5–9%,<ref>{{cite journal | vauthors = Delnord M, Blondel B, Zeitlin J | title = What contributes to disparities in the preterm birth rate in European countries? | journal = Current Opinion in Obstetrics & Gynecology | volume = 27 | issue = 2 | pages = 133–142 | date = April 2015 | pmid = 25692506 | pmc = 4352070 | doi = 10.1097/GCO.0000000000000156 }}</ref> while in the U.S. from 2007 to 2022 the rate fluctuated from 9.6 to 10.5 per cent.<ref>{{cite web |title=Vital Statistics Rapid Release, Number 28 (June 2023) |url=https://www.cdc.gov/nchs/data/vsrr/vsrr028.pdf |website=cdc.gov }}</ref>

As weight is easier to determine than gestational age, the [[Organization:World Health Organization|World Health Organization]] tracks rates of low [[Medicine:Birth weight|birth weight]] (< 2,500 grams), which occurred in 16.5% of births in less developed regions in 2000.<ref>
{{cite web |title=Data and statistics |url=https://www.who.int/research/en/ |publisher=[[Organization:World Health Organization|World Health Organization]] |url-status=dead |archive-url=https://web.archive.org/web/20070216204220/http://www.who.int/research/en/ |archive-date=16 February 2007 }}</ref> It is estimated that one third of these low birth weight deliveries are due to preterm delivery. Weight generally correlates to gestational age; however, infants may be underweight for other reasons than a preterm delivery. Neonates of low birth weight (LBW) have a birth weight of less than {{Cvt|2500|g|lboz}} and are mostly but not exclusively preterm babies as they also include ''small for gestational age'' (SGA) babies. Weight-based classification further recognizes ''Very Low Birth Weight'' (VLBW) which is less than 1,500&nbsp;g, and ''Extremely Low Birth Weight'' (ELBW) which is less than 1,000 g.<ref name="SubramanianKNS">
{{cite web |author=Subramanian, KNS |date=18 June 2009 |title=Extremely Low Birth Weight Infant |url=http://www.emedicine.com/ped/topic2784.htm |publisher=[[Medicine:EMedicine|eMedicine]] |access-date=2009-08-26 |url-status=live |archive-url=https://web.archive.org/web/20081121011312/http://www.emedicine.com/ped/TOPIC2784.HTM |archive-date=21 November 2008}}</ref> Almost all neonates in these latter two groups are born preterm.

About 75% of nearly a million deaths due to preterm delivery would survive if provided warmth, breastfeeding, treatments for infection, and breathing support.<ref name="WHO2015QA" /> Complications from preterm births resulted in 740,000 deaths in 2013, down from 1.57 million in 1990.<ref name=GDB2013/>

==Society and culture==

===Economics===
Preterm birth is a significant cost factor in healthcare, not even considering the expenses of long-term care for individuals with disabilities due to preterm birth. A 2003 study in the U.S. determined neonatal costs to be $224,400 for a newborn at 500–700 g versus $1,000 at over 3,000 g. The costs increase exponentially with decreasing gestational age and weight.<ref>
{{cite journal | vauthors = Gilbert WM, Nesbitt TS, Danielsen B | title = The cost of prematurity: quantification by gestational age and birth weight | journal = Obstetrics and Gynecology | volume = 102 | issue = 3 | pages = 488–492 | date = September 2003 | pmid = 12962929 | doi = 10.1016/S0029-7844(03)00617-3 | s2cid = 9995272 }}</ref>
The 2007 Institute of Medicine report ''Preterm Birth''<ref>Richard E. Behrman, Adrienne Stith Butler, Editors, Committee on Understanding Premature Birth and Assuring Healthy Outcomes. [http://www.nap.edu/openbook.php?record_id=11622 Preterm Birth: Causes, Consequences, and Prevention] {{webarchive|url=https://web.archive.org/web/20110605011101/http://www.nap.edu/openbook.php?record_id=11622 |date=5 June 2011 }}. Institute of Medicine. The National Academies Press, 2007. Retrieved 2010-1-14.</ref> found that the 550,000 premature babies born each year in the U.S. run up about $26 billion in annual costs, mostly related to care in neonatal intensive care units, but the real tab may top $50 billion.<ref>Spencer E. Ante. [http://www.businessweek.com/magazine/content/08_25/b4089046084131.htm Million-Dollar Babies] {{webarchive|url=https://web.archive.org/web/20090531170243/http://www.businessweek.com/magazine/content/08_25/b4089046084131.htm |date=31 May 2009 }}. BusinessWeek. 12 June 2008. Retrieved 2010-1-24.</ref>

===Notable cases===
{{anchor|Notable preterm births}}
James Elgin Gill (born on 20 May 1987 in [[Place:Ottawa|Ottawa]], Ontario, Canada) was the earliest premature baby in the world, until that record was broken in 2004. He was 128 days premature, 21 weeks 5 days gestation, and weighed {{Convert|624|g|lboz|frac=4|abbr=on}}. He survived.<ref>{{cite web|url=http://www.canada.com/topics/bodyandhealth/story.html?id=db8f33ab-33e9-429f-bedc-b6ca80f61bdc|title=Miracle child|access-date=2007-11-28|url-status=live|archive-url=https://web.archive.org/web/20071209065838/http://www.canada.com/topics/bodyandhealth/story.html?id=db8f33ab-33e9-429f-bedc-b6ca80f61bdc|archive-date=9 December 2007}}</ref><ref>{{Cite book|title=Guinness World Records 2004|url=https://archive.org/details/guinnessworldrec2004guin|url-access=registration|publisher=Bantam Books|year=2004|isbn=9780553587128}}</ref>

In 2014, Lyla Stensrud, born in San Antonio, Texas, U.S., became the youngest premature baby in the world. She was born at 21 weeks 4 days and weighed 410 grams (less than a pound). Kaashif Ahmad resuscitated the baby after she was born. As of November 2018, Lyla was attending preschool. She had a slight delay in speech, but no other known medical issues or disabilities.<ref>{{Cite news|url=https://www.today.com/health/born-21-weeks-she-may-be-most-premature-surviving-baby-t118610|title='Miracle baby': Born at 21 weeks, she may be the most premature surviving infant|work=TODAY|access-date=2019-01-02}}</ref>

Amillia Taylor is also often cited as the most premature baby.<ref name="BBCAmillia">
{{cite news | url = http://news.bbc.co.uk/1/hi/world/americas/6384621.stm | title = Most-premature baby allowed home | work = BBC News | date = 2007-02-21 | access-date = 2007-05-05 | url-status = live | archive-url = https://web.archive.org/web/20070323131706/http://news.bbc.co.uk/1/hi/world/americas/6384621.stm | archive-date = 23 March 2007}}</ref> She was born on 24 October 2006 in Miami, Florida, U.S., at 21 weeks and 6 days' gestation.<ref>
{{cite web |url=http://210.245.61.173/en/detail.php |title=trithuc.thanhnienkhcn.org.vn |access-date=2007-11-28 |url-status=dead |archive-url=https://web.archive.org/web/20080124190429/http://210.245.61.173/en/detail.php |archive-date=24 January 2008}}</ref> This report has created some confusion as her gestation was measured from the date of conception (through ''in vitro'' fertilization) rather than the date of her mother's last menstrual period, making her appear 2 weeks younger than if gestation was calculated by the more common method. At birth, she was {{convert|9|in|cm|0|order=flip|
abbr=on}} long and weighed {{convert|10|oz|g|order=flip|abbr=on}}.<ref name="BBCAmillia"/> She had [[Biology:Digestion|digestive]] and respiratory problems, together with a [[Biology:Brain|brain]] [[Medicine:Bleeding|hemorrhage]]. She was discharged from the Baptist Children's Hospital on 20 February 2007.<ref name="BBCAmillia"/>

The record for the smallest premature baby to survive was held for a considerable amount of time by Madeline Mann, who was born in 1989 at 26 weeks, weighing {{convert|9.875|oz|g|order=flip|abbr=on}} and measuring {{convert|9.5|in|cm|0|order=flip|abbr=on}} long.<ref>
{{cite news |url=http://www.hindu.com/seta/2004/08/26/stories/2004082600411400.htm |title=A little miracle called Madeline |access-date=2007-11-28 |location=Chennai, India |date=2004-08-26 |url-status=dead |archive-url=https://web.archive.org/web/20071202081008/http://www.hindu.com/seta/2004/08/26/stories/2004082600411400.htm |work=The Hindu |archive-date=2 December 2007}}</ref> This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital, Loyola University Medical Center in Maywood, Illinois.<ref>
{{cite news |url=http://www.cbsnews.com/stories/2005/02/08/health/main672488.shtml |title=World's Smallest Baby Goes Home, Cellphone-Sized Baby Is Discharged From Hospital |publisher=CBS News |access-date=2007-11-28 |date=2005-02-08 |url-status=live |archive-url=https://web.archive.org/web/20080101060051/http://www.cbsnews.com/stories/2005/02/08/health/main672488.shtml |archive-date=1 January 2008}}</ref> at 25 weeks' gestation. At birth, she was {{convert|8|in|cm|0|order=flip|abbr=on}} long and weighed {{Convert|261|g|oz|abbr=on}}.<ref>{{Cite news|url=http://healthland.time.com/2011/12/12/worlds-tiniest-preterm-babies-are-doing-just-fine/|title=Incredibly, World's Tiniest Preterm Babies Are Doing Just Fine| vauthors = Rochman B |magazine=Time|access-date=2019-05-30|issn=0040-781X}}</ref> Her twin sister was also a small baby, weighing {{Convert|563|g|lboz|abbr=on}} at birth. During [[Medicine:Pregnancy|pregnancy]] their mother had [[Medicine:Pre-eclampsia|pre-eclampsia]], requiring birth by [[Medicine:Caesarean section|caesarean section]]. The larger twin left the hospital at the end of December, while the smaller remained there until 10 February 2005 by which time her weight had increased to {{convert|1.18|kg|lboz|abbr=on}}.<ref>{{cite news |publisher=CBS News |date=8 February 2005 |title=World's Smallest Baby Goes Home |url=http://www.cbsnews.com/stories/2005/02/08/health/main672488.shtml |url-status=live |archive-url=https://web.archive.org/web/20080101060051/http://www.cbsnews.com/stories/2005/02/08/health/main672488.shtml |archive-date=1 January 2008}}</ref> Generally healthy, the twins had to undergo [[Physics:Laser surgery|laser eye surgery]] to correct vision problems, a common occurrence among premature babies.

In May 2019, Sharp Mary Birch Hospital for Women & Newborns in San Diego announced that a baby nicknamed "Saybie" had been discharged almost five months after being born at 23 weeks' gestation and weighing {{Convert|244|g|oz|abbr=on}}. Saybie was confirmed by Dr. Edward Bell of the [[Organization:University of Iowa|University of Iowa]], which keeps the Tiniest Babies Registry, to be the new smallest surviving premature baby in that registry.<ref>{{Cite news|url=https://www.npr.org/2019/05/29/728118503/saybie-born-at-8-6-ounces-in-san-diego-is-now-the-worlds-tiniest-surviving-baby|title=Saybie, Born at 8.6 Ounces in San Diego, Is Now The World's Tiniest Surviving Baby|newspaper=NPR|date=29 May 2019|access-date=2019-05-30| vauthors = Allyn B }}</ref>

Born in February 2009, at Children's Hospitals and Clinics of Minnesota, Jonathon Whitehill was just 25 weeks' gestation with a weight of {{Convert|310|g|oz|abbr=on}}. He was hospitalized in a [[Medicine:Neonatal intensive care unit|neonatal intensive care unit]] for five months, and then discharged.<ref>{{cite web |url=http://www.medicine.uiowa.edu/tiniestbabies/bworder.asp?gender=Male |title=The Tiniest Babies |publisher=[[Organization:University of Iowa|University of Iowa]] |access-date=2010-07-22 |url-status=dead |archive-url=https://web.archive.org/web/20100610190309/http://www.medicine.uiowa.edu/tiniestbabies/bworder.asp?gender=Male |archive-date=10 June 2010}}</ref>

Richard Hutchinson was born at Children's Hospitals and Clinics of Minnesota in Minneapolis, Minnesota, on June 5, 2020, at 21 weeks 2 days gestation. At birth he weighed {{convert|12|oz|g|order=flip|abbr=on}}. He remained hospitalized until November 2020, when he was then discharged.<ref>{{cite web|date=2020-12-23|title=Baby Richard born at 21 weeks: One of the youngest babies to survive|url=http://www.childrensmn.org/2020/12/23/baby-richard-born-21-weeks-one-youngest-babies-survive/|access-date=2021-06-05|website=Children's Minnesota|language=en-US}}</ref><ref>{{cite web|date=2021-04-14|title=Miracle Baby Thrives After Being Given 0% Chance To Live Diagnosis|url=https://minnesota.cbslocal.com/2021/04/14/miracle-baby-thrives-after-being-given-0-chance-to-live-diagnosis/|access-date=2021-06-05|language=en-US}}</ref>

On 5 July 2020 Curtis Means was born at the [[Organization:University of Alabama at Birmingham|University of Alabama at Birmingham]] hospital at 21 weeks 1 day, and weighed {{convert|420|g|abbr=on}}. He was discharged in April 2021. {{as of|2023|3}}, he is the current world record holder.<ref>{{cite web|url=https://www.guinnessworldrecords.com/world-records/67461-most-premature-baby|title=Most premature baby|date=5 July 2020 |publisher=Guinness World Records|access-date=2023-03-15}}</ref>

Historical figures who were born prematurely include [[Biography:Johannes Kepler|Johannes Kepler]] (born in 1571 at seven months' gestation), [[Biography:Isaac Newton|Isaac Newton]] (born in 1642, small enough to fit into a [[Quart|quart]] mug, according to his mother), Winston Churchill (born in 1874 at seven months' gestation), and Anna Pavlova (born in 1885 at seven months' gestation).<ref>{{cite book |author=Raju, TNK |year=1980 |chapter=Some Famous "High Risk" Newborn Babies |chapter-url=http://www.neonatology.org/classics/mj1980/ch28.html |title=Historical Review and Recent Advances in Neonatal and Perinatal Medicine |url-status=live |archive-url=https://web.archive.org/web/20070911014841/http://www.neonatology.org/classics/mj1980/ch28.html |archive-date=11 September 2007}}</ref>

=== Effect of the coronavirus pandemic ===
During the COVID-19 pandemic, a drastic drop in the rate of premature births has been reported in many countries, ranging from a 20% reduction to a 90% drop in the starkest cases. Studies in Ireland and Denmark first noticed the phenomenon, and it has been confirmed elsewhere. There is no universally accepted explanation for this drop as of August 2020. Hypotheses include additional rest and support for expectant mothers staying at home, less air pollution due to shutdowns and reduced car fumes, and reduced likelihood of catching other diseases and viruses in general due to the lockdowns.<ref>{{cite news | vauthors = Preston E |date=July 19, 2020 |title=During Coronavirus Lockdowns, Some Doctors Wondered: Where Are the Preemies? |url=https://www.nytimes.com/2020/07/19/health/coronavirus-premature-birth.html |work=The New York Times |access-date=August 2, 2020 }}</ref>

== Research ==
Brain injury is common among preterms, ranging from [[Biology:White matter|white matter]] injury to intraventricular and cerebellar haemorrhages.<ref>{{cite journal | vauthors = Benders MJ, Kersbergen KJ, de Vries LS | title = Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage | journal = Clinics in Perinatology | volume = 41 | issue = 1 | pages = 69–82 | date = March 2014 | pmid = 24524447 | doi = 10.1016/j.clp.2013.09.005 }}</ref> The characteristic neuropathology of preterms has been described as the "encephalopathy of prematurity".<ref>{{cite journal | vauthors = Volpe JJ | title = The encephalopathy of prematurity--brain injury and impaired brain development inextricably intertwined | journal = Seminars in Pediatric Neurology | volume = 16 | issue = 4 | pages = 167–178 | date = December 2009 | pmid = 19945651 | pmc = 2799246 | doi = 10.1016/j.spen.2009.09.005 }}</ref> The number of preterms that receive special education is doubled compared to the general population. School marks are lower and so are verbal learning, executive function, language skills, and memory performance scores,<ref name="Grey and white matter distribution">{{cite journal | vauthors = Nosarti C, Giouroukou E, Healy E, Rifkin L, Walshe M, Reichenberg A, Chitnis X, Williams SC, Murray RM | display-authors = 6 | title = Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome | journal = Brain | volume = 131 | issue = Pt 1 | pages = 205–217 | date = January 2008 | pmid = 18056158 | doi = 10.1093/brain/awm282 | doi-access = free }}</ref><ref name="Preterm birth and structural brain">{{cite journal | vauthors = Nosarti C, Nam KW, Walshe M, Murray RM, Cuddy M, Rifkin L, Allin MP | title = Preterm birth and structural brain alterations in early adulthood | journal = NeuroImage. Clinical | volume = 6 | pages = 180–191 | date = 2014 | pmid = 25379430 | pmc = 4215396 | doi = 10.1016/j.nicl.2014.08.005 }}</ref><ref>{{cite journal | vauthors = Tanskanen P, Valkama M, Haapea M, Barnes A, Ridler K, Miettunen J, Murray GK, Veijola JM, Jones PB, Taanila AM, Isohanni MK | display-authors = 6 | title = Is prematurity associated with adult cognitive outcome and brain structure? | journal = Pediatric Neurology | volume = 44 | issue = 1 | pages = 12–20 | date = January 2011 | pmid = 21147382 | doi = 10.1016/j.pediatrneurol.2010.07.002 }}</ref><ref name="Cognitive Outcomes for Extremely Pr">{{cite journal | vauthors = Orchinik LJ, Taylor HG, Espy KA, Minich N, Klein N, Sheffield T, Hack M | title = Cognitive outcomes for extremely preterm/extremely low birth weight children in kindergarten | journal = Journal of the International Neuropsychological Society | volume = 17 | issue = 6 | pages = 1067–1079 | date = November 2011 | pmid = 21923973 | pmc = 3282051 | doi = 10.1017/S135561771100107X }}</ref> as well as IQ scores.<ref name="Preterm birth and structural brain"/><ref name="Cognitive Outcomes for Extremely Pr"/><ref name="White Matter and Cognition in Adult">{{cite journal | vauthors = Allin MP, Kontis D, Walshe M, Wyatt J, Barker GJ, Kanaan RA, McGuire P, Rifkin L, Murray RM, Nosarti C | display-authors = 6 | title = White matter and cognition in adults who were born preterm | journal = PLOS ONE | volume = 6 | issue = 10 | pages = e24525 | date = 12 October 2011 | pmid = 22022357 | pmc = 3192037 | doi = 10.1371/journal.pone.0024525 | s2cid = 3884637 | doi-access = free | bibcode = 2011PLoSO...624525A }}</ref><ref name="Cortical thickness and cognition in">{{cite journal | vauthors = Bjuland KJ, Løhaugen GC, Martinussen M, Skranes J | title = Cortical thickness and cognition in very-low-birth-weight late teenagers | journal = Early Human Development | volume = 89 | issue = 6 | pages = 371–380 | date = June 2013 | pmid = 23273486 | doi = 10.1016/j.earlhumdev.2012.12.003 }}</ref><ref name="Contribution of brain size to IQ an">{{cite journal | vauthors = Cheong JL, Anderson PJ, Roberts G, Burnett AC, Lee KJ, Thompson DK, Molloy C, Wilson-Ching M, Connelly A, Seal ML, Wood SJ, Doyle LW | display-authors = 6 | title = Contribution of brain size to IQ and educational underperformance in extremely preterm adolescents | journal = PLOS ONE | volume = 8 | issue = 10 | pages = e77475 | date = 2013 | pmid = 24130887 | pmc = 3793949 | doi = 10.1371/journal.pone.0077475 | doi-access = free | bibcode = 2013PLoSO...877475C }}</ref><ref name="Outcomes in young adulthood for ver">{{cite journal | vauthors = Hack M, Flannery DJ, Schluchter M, Cartar L, Borawski E, Klein N | title = Outcomes in young adulthood for very-low-birth-weight infants | journal = The New England Journal of Medicine | volume = 346 | issue = 3 | pages = 149–157 | date = January 2002 | pmid = 11796848 | doi = 10.1056/NEJMoa010856 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Weisglas-Kuperus N, Hille ET, Duivenvoorden HJ, Finken MJ, Wit JM, van Buuren S, van Goudoever JB, Verloove-Vanhorick SP | display-authors = 6 | title = Intelligence of very preterm or very low birthweight infants in young adulthood | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 94 | issue = 3 | pages = F196–F200 | date = May 2009 | pmid = 18805824 | doi = 10.1136/adc.2007.135095 | hdl = 1874/32813 | s2cid = 16930851 | url = https://research.vumc.nl/en/publications/c8d24d0a-a35a-42a3-8628-bd4ab1adac1d | hdl-access = free }}</ref> Behaviourally, adolescents who were born very preterm and/or very low birth weight have similar self-reports of quality of life, health status and self-esteem as term controls.<ref>{{cite journal | vauthors = Doyle LW, Cheong JL, Burnett A, Roberts G, Lee KJ, Anderson PJ | title = Biological and Social Influences on Outcomes of Extreme-Preterm/Low-Birth Weight Adolescents | journal = Pediatrics | volume = 136 | issue = 6 | pages = e1513–e1520 | date = December 2015 | pmid = 26553187 | doi = 10.1542/peds.2015-2006 | s2cid = 30594886 | doi-access = free }}</ref><ref>{{cite journal | vauthors = van Lunenburg A, van der Pal SM, van Dommelen P, van der Pal-de Bruin KM, Bennebroek Gravenhorst J, Verrips GH | title = Changes in quality of life into adulthood after very preterm birth and/or very low birth weight in the Netherlands | journal = Health and Quality of Life Outcomes | volume = 11 | issue = 1 | pages = 51 | date = March 2013 | pmid = 23531081 | pmc = 3618000 | doi = 10.1186/1477-7525-11-51 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Walther FJ, den Ouden AL, Verloove-Vanhorick SP | title = Looking back in time: outcome of a national cohort of very preterm infants born in The Netherlands in 1983 | journal = Early Human Development | volume = 59 | issue = 3 | pages = 175–191 | date = September 2000 | pmid = 10996273 | doi = 10.1016/S0378-3782(00)00094-3 }}</ref><ref>{{cite journal | vauthors = Zwicker JG, Harris SR | title = Quality of life of formerly preterm and very low birth weight infants from preschool age to adulthood: a systematic review | journal = Pediatrics | volume = 121 | issue = 2 | pages = e366–e376 | date = February 2008 | pmid = 18245409 | doi = 10.1542/peds.2007-0169 | s2cid = 11674158 }}</ref>

Various [[Physics:Magnetic resonance imaging|structural magnetic resonance]] studies found consistent reductions in whole brain volume.<ref name="Cognitive Outcomes for Extremely Pr"/><ref name="White Matter and Cognition in Adult"/><ref name="Contribution of brain size to IQ an"/><ref name="Outcomes in young adulthood for ver"/><ref>{{cite journal | vauthors = Martinussen M, Flanders DW, Fischl B, Busa E, Løhaugen GC, Skranes J, Vangberg TR, Brubakk AM, Haraldseth O, Dale AM | display-authors = 6 | title = Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight | journal = The Journal of Pediatrics | volume = 155 | issue = 6 | pages = 848–853.e1 | date = December 2009 | pmid = 19683725 | pmc = 5875423 | doi = 10.1016/j.jpeds.2009.06.015 }}</ref> The extensive list of particular regions with smaller volumes compared to controls includes many cortical areas (temporal, frontal, parietal, occipital and cingulate), the [[Biology:Hippocampus|hippocampal regions]], [[Biology:Thalamus|thalamus]], [[Biology:Basal ganglia|basal ganglia]], [[Medicine:Amygdala|amygdala]], brain stem, [[Biology:Internal capsule|internal capsule]], [[Biology:Corpus callosum|corpus callosum]], and [[Biology:Cerebellum|cerebellum]]. Brain volume reduction seems to be present throughout the whole brain. In contrast, larger volumes were found in some of the same areas including medial/anterior frontal, parietal and temporal cortex, cerebellum, [[Biology:Middle temporal gyrus|middle temporal gyrus]], [[Biology:Parahippocampal gyrus|parahippocampal gyrus]], and [[Biology:Fusiform gyrus|fusiform gyrus]], as well as larger lateral ventricles on average.<ref>{{cite journal | vauthors = Allin M, Henderson M, Suckling J, Nosarti C, Rushe T, Fearon P, Stewart AL, Bullmore ET, Rifkin L, Murray R | display-authors = 6 | title = Effects of very low birthweight on brain structure in adulthood | journal = Developmental Medicine and Child Neurology | volume = 46 | issue = 1 | pages = 46–53 | date = January 2004 | pmid = 14974647 | doi = 10.1111/j.1469-8749.2004.tb00433.x | s2cid = 221649350 | doi-access = free }}</ref> The cause of these inconsistencies are unknown. Additionally, reductions in cortical surface area/cortical thickness were found in the temporal lobes bilaterally and in left frontal and parietal areas.<ref name="Cortical thickness and cognition in" /><ref>{{cite journal | vauthors = Skranes J, Løhaugen GC, Martinussen M, Håberg A, Brubakk AM, Dale AM | title = Cortical surface area and IQ in very-low-birth-weight (VLBW) young adults | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 49 | issue = 8 | pages = 2264–2271 | date = September 2013 | pmid = 23845237 | doi = 10.1016/j.cortex.2013.06.001 | s2cid = 32770053 }}</ref> Thicker cortex was found bilaterally in the medial inferior and anterior parts of the frontal lobes and in the occipital lobes.
Gestational age was positively correlated with volumes of the temporal and fusiform gyri and sensorimotor cortex bilaterally, left [[Biology:Inferior parietal lobule|inferior parietal lobule]], brain stem, and various white matter tracts, as well as specific positive associations with the cerebellum and thalamus. Several structural brain alterations have been linked back to cognitive and behavioural outcome measures. For example, total brain tissue volume explained between 20 and 40% of the IQ and educational outcome differences between extremely preterm born adolescents and control adolescents.<ref name="Contribution of brain size to IQ an"/><ref name="Outcomes in young adulthood for ver"/> In another study, a 25% quartile decrease in white matter values in middle temporal gyrus was associated with a 60% increase in the risk of cognitive impairment.<ref name="Grey and white matter distribution"/> Nosarti and colleagues previously hypothesised that maturational patterns in preterm brains were consistent with the age-related stages typically observed in younger subjects. Their most recent study suggests, however, that their trajectory may not only be delayed but also fundamentally distinctive. Since both smaller and larger regional volumes were found in very preterm individuals compared to controls.<ref name="Preterm birth and structural brain"/>

The evidence to support the use of [[Unsolved:Osteopathy#Practice|osteopathic manipulations]] to provide benefit in neonatal care is weak.<ref>{{cite journal | vauthors = Lanaro D, Ruffini N, Manzotti A, Lista G | title = Osteopathic manipulative treatment showed reduction of length of stay and costs in preterm infants: A systematic review and meta-analysis | journal = Medicine | volume = 96 | issue = 12 | pages = e6408 | date = March 2017 | pmid = 28328840 | pmc = 5371477 | doi = 10.1097/MD.0000000000006408 }}</ref><ref>{{cite journal | vauthors = DeMarsh S, Huntzinger A, Gehred A, Stanek JR, Kemper KJ, Belsky JA | title = Pediatric Osteopathic Manipulative Medicine: A Scoping Review | journal = Pediatrics | volume = 147 | issue = 2 | pages = e2020016162 | date = February 2021 | pmid = 33500321 | doi = 10.1542/peds.2020-016162 | s2cid = 231730075 | doi-access = free }}</ref>

== See also ==
*Canadian Perinatal Network
*World Prematurity Day

== References ==
{{reflist}}

== External links ==

{{Medical resources
| ICD10          = {{ICD10|O|60|1|o|60}}, {{ICD10|P|07|3|p|05}} 
| ICD9           = {{ICD9|644}}, {{ICD9|765}} 
| ICDO           = 
| OMIM           = 
| MedlinePlus    = 001562 
| eMedicineSubj  = ped 
| eMedicineTopic = 1889 
| DiseasesDB     = 10589 
| MeshID         = D047928
}}
{{Certain conditions originating in the perinatal period}}

{{DEFAULTSORT:Preterm Birth}}
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Preterm birth}}