Morning Sickness and Hyperemesis gravidarum

Morning Sickness is understood to be an evolved trait that protects the fetus against toxins ingested by the mother.[1][2][3] 

In the fetus, these defenses are not yet fully developed, and even small doses of plant toxins that have negligible effects on the adult can be harmful or lethal to the embryo.[1][4]

There is considerable evidence to support this theory, including:[1][5][6]

• ·        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.[1][7]  This may be because such women are more likely to ingest substances that are harmful to the fetus.[1][8]

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.[1][9]

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.[1][10]

In the United States and Canada, the doxylamine-pyridoxine combination is the only approved pregnancy category "A" prescription treatment for nausea and vomiting of pregnancy.[1][11][12]

There is tentative evidence that ginger may be useful.[1][13] However, safety concerns have been raised regarding its anticoagulant properties.[1][14][15]

Thalidomide

Baby born to a mother who had taken
thalidomide while pregnant.[16]

First marketed in West Germany in 1957, thalidomide claimed to cure “anxiety, insomnia, gastritis, and tension";[16][17] and came to be prescribed as a treatment for nausea associated with morning sickness in pregnant women. 

In the late 1950's and early 1960's, more than 10,000 children in 46 countries were born with deformities such as phocomelia* as a consequence of thalidomide use.[16][18][19] Other birth defects included dysmelia*, bone underdevelopment, and other congenital defects affecting the ear, heart, or internal organs.[16][20][21] The negative effects of thalidomide led to the development of more structured drug regulations and control over drug use and development.[16][22]

*Dysmelia is a congenital disorder of a limb resulting from a disturbance in embryonic development.[23]

*Phocomelia is an extremely rare congenital disorder involving malformation of the limbs.[24]

Despite the side effects, thalidomide was sold in pharmacies in Canada until 1962; Canada was the last country to end sales of the drug.[25][26][41]

In the United Kingdom, the drug was licensed in 1958 and withdrawn in 1961. Of the approximately 2,000 babies born with defects, around half died within a few months and 466 survived to at least 2010.[27][41]

Although thalidomide was never approved for sale in the United States, at the time, millions of tablets had been distributed to physicians during a clinical testing program.[28][41]

Hyperemesis gravidarum

Hyperemesis gravidarum (HG) is a complication of pregnancy characterized by intractable nausea, vomiting, and dehydration. It is estimated to affect 0.5–2.0% of pregnant women.[30][31][41] 

Catherine, Duchess of Cambridge was hospitalized due to hyperemesis gravidarum during her first pregnancy, and is being treated for a similar condition for her second pregnancy.[32][41]

When hyperemesis gravidarum is severe or inadequately treated, it may result in the following:[30][41]

• ·        Loss of 5% or more of pre-pregnancy body weight
• ·        Dehydration, causing ketosis,[34] and constipation
• ·        Nutritional disorders such as vitamin B1 (thiamine) deficiency, vitamin B6 deficiency or vitamin B12 deficiency
• ·        Metabolic imbalances such as metabolic ketoacidosis[30] or thyrotoxicosis[41]  
• ·        Physical and emotional stress of pregnancy on the body
• ·        Difficulty with activities of daily living

Hyperemesis gravidarum tends to occur in the first trimester of pregnancy[34][41] and lasts significantly longer than morning sickness.

It is thought that HG is due to a combination of factors which may vary between women and include: genetics,[30] body chemistry, and overall health.[33][41]

One factor is an adverse reaction to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic gonadotropin (hCG).[35][36][41] 

Another postulated cause of HG is an increase in maternal levels of estrogens (decreasing intestinal motility and gastric emptying leading to nausea/vomiting).[30][41]

Dry bland food and oral re-hydration are first-line treatments.[37][41]  

If oral nutrition is insufficient, intravenous nutritional support may be needed.[32][41] 

For women who require hospital admission, thromboembolic stockings or low-molecular-weight heparin may be used as measures to prevent the formation of a blood clot.[38][41]

If HG is inadequately treated, anemia,[30]  hyponatremia (a condition that occurs when the level of sodium in your blood is abnormally low),[30][42] Wernicke's encephalopathy,(serious neurologic disorder),[30][43] renal failure, coagulopathy (clotting disorder),[44] atrophy, Mallory-Weiss tears (gastro-esophageal laceration syndrome),[30][45] hypoglycemia, jaundice, malnutrition, deep vein thrombosis, and pulmonary embolism are among the possible consequences. 

Depression is a common secondary complication of HG.[30][41]

The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother.[38][41] 

Infants of women with severe hyperemesis who gain less than 7 kg (15.4 lb) during pregnancy tend to be of lower birth weight, small for gestational age, and born before 37 weeks gestation.[34][41] 

In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7 kg appear similar to infants from uncomplicated pregnancies.[40][42]  

There is no significant difference in the neonatal death rate in infants born to mothers with HG compared to infants born to mothers who do not have HG.[30][41]

References:

[1] http://en.wikipedia.org/wiki/Morning_sickness

[2] Hook, E. B. (1976). "Changes in tobacco smoking and ingestion of alcohol and caffeinated beverages during early pregnancy: are these consequences, in part, of feto-protective mechanisms diminishing maternal exposure to embryotoxins?". In Kelly, S. Birth Defects: Risks and Consequences. Academic Press. pp. 173–181.

[3]  Profet, Margie (1992). "Pregnancy Sickness as Adaptation: A Deterrent to Maternal Ingestion of Teratogens". In Barkow, John; Cosmides, Jerome; Tooby, Leda. The Adapted Mind: Evolutionary Psychology and the Generation of Culture. Oxford University Press. pp. 327–365.

[4] Beck, F. (1973). Human Embryology and Genetics. Blackwell Scientific.

[5] Nesse, Randolphe M; Williams, George C (1996). Why We Get Sick (First ed.). New York: Vintage Books. p. 290.

[6] Pepper GV, Craig Roberts S (October 2006). "Rates of nausea and vomiting in pregnancy and dietary characteristics across populations". Proceedings of the Royal Society B 273 (1601): 2675–2679. doi:10.1098/rsbp.2006.3633. PMC 1635459.PMID 17002954.

[7] Chan, Ronna L. et al.; Olshan, A. F.; Savitz, D. A.; Herring, A. H.; Daniels, J. L.; Peterson, H. B.; Martin, S. L. (Sep 22, 2010). "Severity and duration of nausea and vomiting symptoms in pregnancy and spontaneous abortion". Human Reproduction 25(11): 2907–12. doi:10.1093/humrep/deq260. PMC 3140259. PMID 20861299.

[8] Sherman, Paul W.; Flaxman, Samuel M. (2002). "Nausea and vomiting of pregnancy in an evolutionary perspective". Am J Obstet Gynecol 186 (5): S190–S197.doi:10.1067/mob.2002.122593. PMID 12011885.

[9] Haig, David (October 1993). "Genetic conflicts in human pregnancy". Quarterly Review of Biology 68 (4): 495–532. doi:10.1086/418300. PMID 8115596.

[10] Flaxman, Samuel M.; Sherman, Paul W. (June 2000). "Morning sickness: a mechanism for protecting mother and embryo". Quarterly Review of Biology 75 (2): 113–148.doi:10.1086/393377. PMID 10858967.

[11] Jarvis, S; Nelson-Piercy, C (Jun 17, 2011). "Management of nausea and vomiting in pregnancy.". BMJ (Clinical research ed.) 342: d3606. doi:10.1136/bmj.d3606.PMID 21685438.

[12] Clark SM, Dutta E, Hankins GD (September 2014). "The outpatient management and special considerations of nausea and vomiting in pregnancy". Semin Perinatol. S0146-0005 (14): 00102–5. doi:10.1053/j.semperi.2014.08.014. PMID 25267280.

[13] Matthews, A; Dowswell, T; Haas, DM; Doyle, M; O'Mathúna, DP (September 2010). "Interventions for nausea and vomiting in early pregnancy.". The Cochrane database of systematic reviews (9): CD007575. doi:10.1002/14651858.CD007575.pub2.PMID 20824863.

[14] Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA (2005). "Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting". Obstetrics and gynecology 105 (4): 849–56. doi:10.1097/01.AOG.0000154890.47642.23.PMID 15802416.

[15] Tiran, Denise (Feb 2012). "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. doi:10.1016/j.ctcp.2011.08.007. ISSN 1744-3881.

[16] http://en.wikipedia.org/wiki/Thalidomide

[17]  Miller, Marylin T. (1991). "Thalidomide Embryopathy: A Model for the Study of Congenital Incomitant Horizontal Strabismus". Transaction of the American Ophthalmological Society81: 623–674.

[18]  Zimmer C (March 15, 2010). "Answers Begin to Emerge on How Thalidomide Caused Defects". New York Times. Retrieved 2010-03-21. As they report in the current issue of Science, a protein known as cereblon latched on tightly to the thalidomide

[19]  Bren L (2001-02-28). "Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History". FDA Consumer (U.S. Food and Drug Administration).

[20] Cuthbert, Alan (2001, 2003). The Oxford Companion to the Body. Oxford University Press. Retrieved 26 February 2012

[21] Franks ME, Macpherson GR, Figg WD (May 2004). "Thalidomide". Lancet 363(9423): 1802–11. doi:10.1016/S0140-6736(04)16308-3. PMID 15172781.

[22] Heaton, C. A. (1994). The Chemical Industry. Springer. p. 40. ISBN 0-7514-0018-1.

[23] http://en.wikipedia.org/wiki/Dysmelia

[24] http://en.wikipedia.org/wiki/Phocomelia

[25] Webb JF (November 1963). "Canadian Thalidomide Experience". Can Med Assoc J 89: 987–92. PMC 1921912. PMID 14076167.

[26] "Turning Points of History–Prescription for Disaster". History Television.

[27] "Apology for thalidomide survivors". BBCNews:Health (BBC News). 14 January 2010.

[28] Mekdeci, Betty. "How a Commonly Used Drug Caused Birth Defects".

[29] http://en.wikipedia.org/wiki/Hyperemesis_gravidarum

[30] Summers, A (July 2012). "Emergency management of hyperemesis gravidarum.". Emergency nurse 20 (4): 24–28.doi:10.7748/en2012.07.20.4.24.c9206. PMID 22876404.

[31] Goodwin, TM (September 2008). "Hyperemesis gravidarum.". Obstetrics and gynecology clinics of North America 35 (3): 401–17, viii. doi:10.1016/j.ogc.2008.04.002.PMID 18760227.

[32] Cohen, (Ed.) Wayne R. (2000). Cherry and Merkatz's complications of pregnancy. (5th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 124. ISBN 9780683016734.

[33] "HG Theories & Research". helpher.org. Retrieved 25 December 2012.

[34] Ahmed KT, Almashhrawi AA, Rahman RN, Hammoud GM, Ibdah JA; Almashhrawi; Rahman; Hammoud; Ibdah (November 2013). "Liver diseases in pregnancy: diseases unique to pregnancy". World J Gastroenterol 19 (43): 7639–46.doi:10.3748/wjg.v19.i43.7639. PMC 3837262. PMID 24282353.

[35] Cole, LA (August 2010). "Biological functions of hCG and hCG-related molecules".Reproductive biology and endocrinology 8 (102): 102. doi:10.1186/1477-7827-8-102.PMC 2936313. PMID 20735820.

[36]  Hershman JM (June 2004). "Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid". Best Pract. Res. Clin. Endocrinol. Metab.18 (2): 249–65. doi:10.1016/j.beem.2004.03.010. PMID 15157839.

[37] Office on Women's Health (2010). "Pregnancy Complications". U.S. Department of Health and Human Services. Retrieved 27 October 2013.

[38] Handbook of early pregnancy care. London: Informa Healthcare. 2006. pp. 149–154. ISBN 9781842143230.

[39] Matthews, Anne; Haas, David M; O'Mathúna, Dónal P; Dowswell, Therese; Doyle, Mary; Matthews, Anne (2014). "Cochrane Database of Systematic Reviews".doi:10.1002/14651858.CD007575.pub3.

[40] Dodds L, Fell DB, Joseph KS, Allen VM, Butler B.; Fell; Joseph; Allen; Butler (2006). "Outcomes of pregnancies complicated by hyperemesis gravidarum". Obstet Gynecol. 107(2 Pt 1): 285–92. doi:10.1097/01.AOG.0000195060.22832.cd. PMID 16449113.

[41] http://en.wikipedia.org/wiki/Thalidomide

[42] http://www.mayoclinic.org/diseases-conditions/hyponatremia/basics/definition/con-20031445

[43] http://emedicine.medscape.com/article/794583-overview

[44] http://en.wikipedia.org/wiki/Coagulopathy

[45] http://en.wikipedia.org/wiki/Mallory%E2%80%93Weiss_syndrome

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