Medicine:Morning sickness

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Short description: Nausea due to pregnancy
Morning sickness
Other namesNausea and vomiting of pregnancy, nausea gravidarum, emesis gravidarum, pregnancy sickness
SpecialtyObstetrics
SymptomsNausea, vomiting[1]
ComplicationsWernicke encephalopathy, esophageal rupture[1]
Usual onset4th week of pregnancy[2]
DurationUntil 16th week of pregnancy[2]
CausesUnknown[2]
Diagnostic methodBased on symptoms after other causes have been ruled out[3]
Differential diagnosisHyperemesis gravidarum[1]
PreventionPrenatal vitamins[3]
TreatmentDoxylamine and pyridoxine[3][4]
Frequency~75% of pregnancies[4][5]

Morning sickness, also called nausea and vomiting of pregnancy (NVP), is a symptom of pregnancy that involves nausea or vomiting.[1] Despite the name, nausea or vomiting can occur at any time during the day.[2] Typically the symptoms occur between the 4th and 16th week of pregnancy.[2] About 10% of women still have symptoms after the 20th week of pregnancy.[2] A severe form of the condition is known as hyperemesis gravidarum and results in weight loss.[1][6]

The cause of morning sickness is unknown but may relate to changing levels of the hormone human chorionic gonadotropin.[2] Some have proposed that morning sickness may be useful from an evolutionary point of view.[1] Diagnosis should only occur after other possible causes have been ruled out.[3] Abdominal pain, fever, or headaches are typically not present in morning sickness.[1]

Taking prenatal vitamins before pregnancy may decrease the risk.[3] Specific treatment other than a bland diet may not be required for mild cases.[2][6][3] If treatment is used the combination of doxylamine and pyridoxine is recommended initially.[3][4] There is limited evidence that ginger may be useful.[3][7] For severe cases that have not improved with other measures methylprednisolone may be tried.[3] Tube feeding may be required in women who are losing weight.[3]

Morning sickness affects about 70–80% of all pregnant women to some extent.[4][5] About 60% of women experience vomiting.[2] Hyperemesis gravidarum occurs in about 1.6% of pregnancies.[1] Morning sickness can negatively affect quality of life, result in decreased ability to work while pregnant, and result in health-care expenses.[3] Generally, mild to moderate cases have no effect on the fetus, and most severe cases also have normal outcomes.[1] Some women choose to have an abortion due to the severity of symptoms.[1] Complications such as Wernicke encephalopathy or esophageal rupture may occur, but very rarely.[1]

Signs and symptoms

About 66% of women have both nausea and vomiting while 33% have just nausea.[1] Symptoms of both nausea and vomiting will normally climax around 10 and 16 weeks of pregnancy, subsiding around 20 weeks.[8] However, after around 22 weeks, up to 10% of women continue to have lingering symptoms.[8]

Cause

The cause of morning sickness is unknown but may relate to changing levels of estrogen and the hormone human chorionic gonadotropin.[2][9] Some have proposed that morning sickness may be useful from an evolutionary point of view, arguing that morning sickness may protect both the pregnant woman and the developing embryo just when the fetus is most vulnerable.[1] Diagnosis should only occur after other possible causes have been ruled out.[3] Abdominal pain, fever, or headaches are typically not present in morning sickness.[1]

Nausea and vomiting may also occur with molar pregnancy.[10]

Morning sickness is related to diets low in cereals and high in sugars, oilcrops, alcohol and meat.[11]

Pathophysiology

Hormone changes

Pathophysiology of vomiting in pregnancy

Defense mechanism

Morning sickness may be an evolved trait that protects the fetus against toxins ingested by the mother. Independent Scholar-Biologist Margie Profet from Seattle was one of the first to investigate the morning sickness-mystery. She argued that nausea and food aversions during pregnancy evolved to impose dietary restrictions on the mother in the early weeks of pregnancy, when the mother and the embryo are most immunologically vulnerable, to minimize fetal exposure to toxins such as mutagens and teratogens.[15] A woman and her embryo are very vulnerable to toxins during pregnancy. By reducing exposure to such chemicals, morning sickness reduces impairments on normal embryonic development and increases the reproductive success of the mother and survival success of both the mother and her offspring. Evidence in support of this theory includes:[16][11]

  • Morning sickness is very common among pregnant women, which argues in favor of its being a functional adaptation and against the idea that it is a pathology.
  • Fetal vulnerability to toxins peaks at around 3 months, which is also the time of peak susceptibility to morning sickness.
  • There is a good correlation between toxin concentrations in foods, and the tastes and odors that cause revulsion.

Women who have no morning sickness are more likely to miscarry.[17][18] This may be because such women are more likely to ingest substances that are harmful to the fetus.[19]

In addition to protecting the fetus, morning sickness may also protect the mother. A pregnant woman's immune system is suppressed during pregnancy, presumably to reduce the chances of rejecting tissues of her own offspring.[20] Because of this, animal products containing parasites and harmful bacteria can be especially dangerous to pregnant women. There is evidence that morning sickness is often triggered by animal products including meat and fish.[21]

If morning sickness is a defense mechanism against the ingestion of toxins, the prescribing of anti-nausea medication to pregnant women may have the undesired side effect of causing birth defects or miscarriages by encouraging harmful dietary choices.[16]

Also, morning sickness is a defense mechanism because when analyzing embryonic growth, several critical periods are identified in which there is mass proliferation and cell division resulting in the development of the heart and central nervous system that are very sensitive. In that period, the fetus is most at risk from damage to toxins and mutagens. These developments occur through week 6-18 which is in the same time frame in which the most nausea and vomiting of pregnancy (NVP) occurs. This relationship between the time at which the embryo is most susceptible to toxins lines up exactly with when the most severe NVP symptoms are seen, suggesting that this NVP is an evolutionary response developed in the mother, to indicate the sensitivity of the fetus hence making her wary to her health and in turn protecting the fetus.[21]

Treatments

There is a lack of good evidence to support the use of any particular intervention for morning sickness.[7]

Medications

A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), metoclopramide, and phenothiazines (such as promethazine).[22][23] With respect to effectiveness it is unknown if one is superior to another.[22] In the United States and Canada, the doxylamine-pyridoxine combination (as Diclegis in US and Diclectin in Canada) is the only approved pregnancy category "A" prescription treatment for nausea and vomiting of pregnancy.[23]

Ondansetron may be beneficial, but there are some concerns regarding an association with cleft palate,[24] and there is little high quality data.[22] Metoclopramide is also used and relatively well tolerated.[25] Evidence for the use of corticosteroids is weak.[26]

Alternative medicine

Some studies support the use of ginger, but overall the evidence is limited and inconsistent.[3][7][9][27] Safety concerns have been raised regarding its anticoagulant properties.[9][28][29][30]

History

Thalidomide

Main page: Physics:Thalidomide scandal

In the late 1950s and early 1960s, the use of thalidomide in 46 countries by women who were pregnant or who subsequently became pregnant resulted in the "biggest man‐made medical disaster ever," with more than 10,000 children born with a range of severe deformities, such as phocomelia, as well as thousands of miscarriages.[31][32]

Thalidomide was introduced in 1953 as a tranquilizer, and was later marketed by the German pharmaceutical company Chemie Grünenthal under the trade name Contergan as a medication for anxiety, trouble sleeping, "tension", and morning sickness.[33][34] It was introduced as a sedative and medication for morning sickness without having been tested on pregnant women.[35] While initially deemed to be safe in pregnancy, concerns regarding birth defects were noted in 1961, and the medication was removed from the market in Europe that year.[33][36]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Practice Bulletin No. 153: Nausea and Vomiting of Pregnancy". Obstetrics and Gynecology 126 (3): e12–e24. September 2015. doi:10.1097/AOG.0000000000001048. PMID 26287788. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Nausea and vomiting in early pregnancy". BMJ Clinical Evidence 2009. June 2009. PMID 21726485. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 "Practice Bulletin Summary No. 153: Nausea and Vomiting of Pregnancy". Obstetrics and Gynecology 126 (3): 687–688. September 2015. doi:10.1097/01.aog.0000471177.80067.19. PMID 26287781. https://journals.lww.com/greenjournal/citation/2015/09000/practice_bulletin_summary_no__153__nausea_and.42.aspx. 
  4. ↑ 4.0 4.1 4.2 4.3 "Treating morning sickness in the United States--changes in prescribing are needed". American Journal of Obstetrics and Gynecology 211 (6): 602–606. December 2014. doi:10.1016/j.ajog.2014.08.017. PMID 25151184. 
  5. ↑ 5.0 5.1 "Prevalence of nausea and vomiting of pregnancy in the USA: a meta analysis". Journal of Population Therapeutics and Clinical Pharmacology 20 (2): e163–e170. 2013-01-01. PMID 23863545. 
  6. ↑ 6.0 6.1 "Pregnancy". September 27, 2010. http://www.womenshealth.gov/pregnancy/you-are-pregnant/pregnancy-complications.html. 
  7. ↑ 7.0 7.1 7.2 "Interventions for nausea and vomiting in early pregnancy". The Cochrane Database of Systematic Reviews 2015 (9): CD007575. September 2015. doi:10.1002/14651858.CD007575.pub4. PMID 26348534. 
  8. ↑ 8.0 8.1 "Nausea and vomiting of pregnancy". Gastroenterology Clinics of North America 40 (2): 309–34, vii. June 2011. doi:10.1016/j.gtc.2011.03.009. PMID 21601782. 
  9. ↑ 9.0 9.1 9.2 "A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting". Nutrition Journal 13: 20. March 2014. doi:10.1186/1475-2891-13-20. PMID 24642205. 
  10. ↑ "Hyperemesis gravidarum, a literature review". Human Reproduction Update 11 (5): 527–539. 2005. doi:10.1093/humupd/dmi021. PMID 16006438. 
  11. ↑ 11.0 11.1 "Rates of nausea and vomiting in pregnancy and dietary characteristics across populations". Proceedings. Biological Sciences 273 (1601): 2675–2679. October 2006. doi:10.1098/rspb.2006.3633. PMID 17002954. 
  12. ↑ "Nausea and vomiting in pregnancy in relation to prolactin, estrogens, and progesterone: a prospective study". Obstetrics and Gynecology 101 (4): 639–644. April 2003. doi:10.1016/s0029-7844(02)02730-8. PMID 12681864. 
  13. ↑ "Morning Sickness: Coping With The Worst". NY Metro Parents Magazine. http://www.nymetroparents.com/newarticle.cfm?colid=7114. 
  14. ↑ "Clinical practice. Nausea and vomiting in pregnancy". The New England Journal of Medicine 363 (16): 1544–1550. October 2010. doi:10.1056/NEJMcp1003896. PMID 20942670. 
  15. ↑ Why We Get Sick: The New Science of Darwinian Medicine.. Knopf Doubleday Publishing. April 1996. pp. 983. ISBN 978-0679746744. 
  16. ↑ 16.0 16.1 Why We Get Sick (1st ed.). New York: Vintage Books. 1996. pp. 290. 
  17. ↑ "Severity and duration of nausea and vomiting symptoms in pregnancy and spontaneous abortion". Human Reproduction 25 (11): 2907–2912. November 2010. doi:10.1093/humrep/deq260. PMID 20861299. 
  18. ↑ Collins, Dr Francis (2016-10-04). "Morning Sickness Associated with Lower Miscarriage Risk" (in en-US). https://directorsblog.nih.gov/2016/10/04/nausea-in-pregnancy-is-associated-with-lower-miscarriage-risk/. 
  19. ↑ "Nausea and vomiting of pregnancy in an evolutionary perspective". American Journal of Obstetrics and Gynecology 186 (5 Suppl Understanding): S190–S197. May 2002. doi:10.1067/mob.2002.122593. PMID 12011885. 
  20. ↑ "Genetic conflicts in human pregnancy". The Quarterly Review of Biology 68 (4): 495–532. December 1993. doi:10.1086/418300. PMID 8115596. http://nrs.harvard.edu/urn-3:HUL.InstRepos:3153297. 
  21. ↑ 21.0 21.1 "Morning sickness: a mechanism for protecting mother and embryo". The Quarterly Review of Biology 75 (2): 113–148. June 2000. doi:10.1086/393377. PMID 10858967. 
  22. ↑ 22.0 22.1 22.2 "Management of nausea and vomiting in pregnancy". The BMJ 342: d3606. June 2011. doi:10.1136/bmj.d3606. PMID 21685438. https://www.bmj.com/content/342/bmj.d3606. 
  23. ↑ 23.0 23.1 "The outpatient management and special considerations of nausea and vomiting in pregnancy". Seminars in Perinatology 38 (8): 496–502. December 2014. doi:10.1053/j.semperi.2014.08.014. PMID 25267280. https://www.sciencedirect.com/science/article/abs/pii/S0146000514001025. 
  24. ↑ "Is ondansetron safe for use during pregnancy?". Canadian Family Physician 58 (10): 1092–1093. October 2012. PMID 23064917. PMC 3470505. https://www.cfp.ca/content/58/10/1092. 
  25. ↑ "Contemporary approaches to hyperemesis during pregnancy". Current Opinion in Obstetrics & Gynecology 23 (2): 87–93. April 2011. doi:10.1097/GCO.0b013e328342d208. PMID 21297474. https://journals.lww.com/co-obgyn/abstract/2011/04000/contemporary_approaches_to_hyperemesis_during.6.aspx. 
  26. ↑ "BET 2: Steroid therapy in the treatment of intractable hyperemesis gravidarum". Emergency Medicine Journal 28 (10): 898–900. October 2011. doi:10.1136/emermed-2011-200636. PMID 21918097. https://emj.bmj.com/content/28/10/898.3. 
  27. ↑ "Effects of ginger for nausea and vomiting in early pregnancy: a meta-analysis". Journal of the American Board of Family Medicine 27 (1): 115–122. 2014. doi:10.3122/jabfm.2014.01.130167. PMID 24390893. https://www.jabfm.org/content/27/1/115. 
  28. ↑ "Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting". Obstetrics and Gynecology 105 (4): 849–856. April 2005. doi:10.1097/01.AOG.0000154890.47642.23. PMID 15802416. https://journals.lww.com/greenjournal/abstract/2005/04000/effectiveness_and_safety_of_ginger_in_the.27.aspx. 
  29. ↑ "Ginger to reduce nausea and vomiting during pregnancy: evidence of effectiveness is not the same as proof of safety". Complementary Therapies in Clinical Practice 18 (1): 22–25. February 2012. doi:10.1016/j.ctcp.2011.08.007. PMID 22196569. https://www.sciencedirect.com/science/article/abs/pii/S1744388111000739. 
  30. ↑ "Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis". The Journal of Maternal-Fetal & Neonatal Medicine 35 (1): 187–196. January 2022. doi:10.1080/14767058.2020.1712714. PMID 31937153. https://www.tandfonline.com/doi/full/10.1080/14767058.2020.1712714. 
  31. ↑ Vargesson, Neil. “Thalidomide-induced teratogenesis: history and mechanisms.” Birth defects research. Part C, Embryo today : reviews vol. 105,2 (2015): 140–56. doi:10.1002/bdrc.21096
  32. ↑ Bren L (28 February 2001). "Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History". FDA Consumer (U.S. Food and Drug Administration). http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/2001/201_kelsey.html. 
  33. ↑ 33.0 33.1 Miller, Marylin T. (1991). "Thalidomide Embryopathy: A Model for the Study of Congenital Incomitant Horizontal Strabismus". Transactions of the American Ophthalmological Society 81: 623–674. PMID 1808819. 
  34. ↑ Loue, Sana; Sajatovic, Martha (2004) (in en). Encyclopedia of Women's Health. Springer Science & Business Media. pp. 643–644. ISBN 9780306480737. https://books.google.com/books?id=LbHWgd-mDbsC&pg=PA644. 
  35. ↑ Sneader, Walter (2005). Drug discovery: a history (Rev. and updated ed.). Chichester: Wiley. p. 367. ISBN 978-0-471-89979-2. https://archive.org/details/drugdiscoveryhis00snea. 
  36. ↑ Cuthbert, Alan (2003). The Oxford Companion to the Body. Oxford University Press. p. 682. doi:10.1093/acref/9780198524038.001.0001. ISBN 9780198524038. https://archive.org/details/oxfordcompaniont0000unse_z0k4/page/682. 
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