Up to 80% of women experience morning sickness, and about 25% of them continue to experience symptoms through the second and third trimesters. The delayed-release combination of the antihistamine doxylamine and vitamin B6 (pyridoxine hydrochloride) is the only drug approved to treat nausea and vomiting in pregnancy (NVP) in the United States (Diclegis) and Canada (Diclectin). Despite Food and Drug Administration approval and solid evidence demonstrating that this antihistamine-based treatment is safe and effective during pregnancy, many women are afraid to take it due to misperception of risk.
What can help clinicians who are reassuring their pregnant patients to use medications when needed are the numerous studies documenting that NVP is associated with reduced rates of congenital malformations, prematurity, and miscarriage.
In a recent analysis of studies from Sweden, the United States, and Hungary – which measured different outcomes – we found a consistent, favorable effect of NVP on birth outcomes, including lower rates of miscarriages, congenital malformations, and prematurity, as well as neurodevelopmental outcomes.
These studies include a U.S. study of about 2,400 pregnant women between 2000 and 2004, which found that the miscarriage risk was reduced among most age groups of women who experienced NVP for at least half of their pregnancy, with the greatest effects (an 80% reduced risk) among the oldest women. Among those who did not have symptoms, the risk for miscarriage was increased by about threefold (Hum. Reprod. 2010;25:2907-12).
A prospective Swedish study that evaluated the effects of antihistamines in early pregnancy provides even stronger evidence for a protective effect of NVP. This study compared delivery outcomes in more than 17,000 women who took antihistamines early in pregnancy for allergies or for morning sickness. A protective effect was demonstrated in the group with NVP, with a significantly lower rate of preterm births, low birth weight, and small for gestational age among singletons. But in the group of women who took the medication for allergies, there was a neutral effect on delivery outcomes, with no protective effect observed (J. Matern. Fetal Neonatal Med. 2002;11:146-52).
Other studies include the following:
• In a prospective study of 849 pregnant women in Ecuador, the risk of miscarriage was significantly reduced by 55% among those with nausea only, and by 34% among those with nausea and vomiting (J. Perinat. Med. 2006;34: 115-22).
•A study using data from the Hungarian Case-Control Surveillance System of Congenital Abnormalities between 1980 and 1996 found that overall, mothers of babies with congenital abnormalities were 26% less likely to have experienced severe NVP in early pregnancy compared with the mothers of controls with no congenital abnormalities (Am. Med. Genet. A 2006;140:453-62). In another study of more than 38,000 women who were controls in this registry, who did not have babies with congenital abnormalities, 6.4% of those with medically documented and treated NVP had preterm births vs. 9.5% among those who did not have NVP (Paediatr. Perinat. Epidemiol. 2004;18:253-9).
• In a Swedish study, the rate of congenital malformations was 9% lower in a group of more than 16,000 women who said they had used meclozine (the antihistamine most often used for NVP in Sweden) early in pregnancy, compared with all women who gave birth. Rates of preterm birth, low birth weight, and small head circumference were lower among those who had taken meclozine (Eur. J. Epidemiol. 2003;18: 665-9).
• In a Motherisk study that compared the neurodevelopment of 121 children aged 3-7 years, those whose mothers had NVP scored higher in some areas compared with women not experiencing NVP. The severity of NVP and maternal IQ were predictors of improved results (J. Pediatr. 2009;155:45-50).
The underlying hypothesis is that the protective effect of NVP is related to a more favorable hormonal milieu during pregnancy. Although estrogen, progesterone and beta-HCG levels are increased during pregnancy, the effect cannot be attributed to any one hormone, and some believe it may be an as-of-yet unidentified hormone. Many women who have morning sickness until they deliver often say that symptoms entirely resolve within minutes of the delivery of the placenta, suggesting that a hormone – or another compound or combination of compounds – produced by the placenta causes these symptoms.
The Motherisk NVP Line (800-436-8477) encourages women who need pharmacotherapy that there are safe medications for this condition, and that the protective effect of NVP on pregnancy outcome should encourage them to effectively treat their symptoms.
Dr. Koren is professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto. He heads the Research Leadership for Better Pharmacotherapy During Pregnancy and Lactation at the Hospital for Sick Children, Toronto, where he is director of the Motherisk Program. He also holds the Ivey Chair in Molecular Toxicology at the department of medicine, University of Western Ontario, London. Dr. Koren was a principal investigator in the U.S. study that resulted in the approval of Diclegis, marketed by Duchesnay USA, and he has served as a consultant to Duchesnay. E-mail him at obnews@frontlinemedcom.com.