Drugs, Pregnancy & Lactation

Consider neurodevelopmental impacts of hyperemesis gravidarum


 

Hyperemesis gravidarum (HG) affects just 1%-2% of pregnant women, but it’s clinical consequences are significant, with excess vomiting and dehydration, hospitalization, and the need for intravenous fluids being common in that group. In extreme cases, repeated vomiting has led to tears in the esophagus and severe dehydration has caused acute renal failure. All of that leaves aside the obvious suffering and distress it causes for women with the condition.

While studies continue to support the long-held theory that mild-to-moderate nausea and vomiting has a protective effect in pregnancy, that does not appear to be true for HG. Rather, the medical literature shows that HG is associated with small-for-gestational-age neonates, low birth weight, higher rates of preterm birth, and lower Apgar scores at 5 minutes.

Dr. Gideon Koren

Dr. Gideon Koren

What is even more concerning is what is happening to these children developmentally. In the last few years, controlled studies have emerged looking at long-term neurological development following pregnancy with HG.

I was one of the investigators on a study that prospectively followed more than 200 women with nausea and vomiting in pregnancy from 2006 to 2012. We found that children whose mothers were hospitalized for their symptoms – 22 in all – had significantly lower IQ scores at 3.5 years to 7 years, compared with children whose mothers were not hospitalized. Verbal IQ scores were 107.2 points vs. 112.7 (P = .04), performance IQ scores were 105.6 vs. 112.3 (P = .03), and full scale IQ was 108.7 vs. 114.2 (P = .05).

The study cohort included three groups: women treated with more than four tablets per day of doxylamine/pyridoxine (Diclegis); women treated with up to four tablets per day of the drug; and women who did not receive pharmacotherapy (Obstet Gynecol. 2015. doi: 10.1097/01.AOG.0000463229.81803.1a).

Hospitalized women in the study received antiemetics about a week later, experienced more severe symptoms, and were more likely to report depression. Overall, we found that duration of hospitalization, maternal depression, and maternal IQ all were significant predictors for these outcomes. However, daily antiemetic therapy was not associated with adverse outcomes.

nauseous pregnant woman ©monkeybusinessimages/thinkstockphotos.com
These findings led my colleagues and I to conclude that timely preventive antiemetics and depression control could help prevent hospitalization and the associated worsened outcomes in child neurodevelopment.

Another study, published the same year, found that children exposed to HG had a more than three times increased risk for a neurodevelopmental diagnosis, including attention disorders, speech and language delays, and sensory disorders. The changes were more prevalent when women experienced symptoms early in pregnancy – prior to 5 weeks of gestation (Eur J Obstet Gynecol Reprod Biol. 2015 Jun;189:79-84).

The study compared neurodevelopmental outcomes for 312 children from 203 women with HG, with 169 children from 89 unaffected mothers. The findings are similar to those of our study, despite the differences in methodologies. Both studies found that the antiemetics were not associated with adverse outcomes, but the symptoms of HG appear to be the culprit.

While more research is needed to confirm these findings, it makes sense that the nutritional deficiencies created by excess vomiting and inability to eat are having an impact on the fetus.

It also raises an important question for the ob.gyn. about when to intervene in these women. Often, clinicians take a wait-and-see approach to nausea and vomiting in pregnancy, but the developing research suggests that earlier intervention would lead to better outcomes for mother and baby. One guide to determining that preventive antiemetics are necessary is to consider whether your patient has had HG in a previous pregnancy or if her mother or sister has experienced HG.

Another consideration is treating the nutritional deficiency that develops in women whose HG symptoms persist. These women are not simply in need of fluids and electrolytes but are missing essential vitamins and proteins. This is an area where much more research is needed, but clinicians can take a proactive approach by providing team care that includes consultation with a dietitians or nutritionist.

Finally, we cannot forget that maternal depression also appears to be significant predictor of poor fetal outcomes, so providing appropriate psychiatric treatment is essential.

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. Dr. Koren was a principal investigator in the U.S. study that resulted in the approval of Diclegis, marketed by Duchesnay USA, and has served as a consultant to Duchesnay.

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