BALTIMORE – Starting treatment with a combination of doxylamine and pyridoxine before the onset of nausea and vomiting significantly reduced the incidence of severe nausea and vomiting of pregnancy, compared with starting treatment at the first sign of symptoms, in a study of 59 women with a history of severe nausea and vomiting of pregnancy, Caroline Maltepe reported.

In the prospective, randomized, open-label study of women with a history of nausea and vomiting of pregnancy (NVP), 30 women began taking the delayed-release combination of 10 mg of doxylamine and 10 mg of pyridoxine (vitamin B₆) as soon as they learned they were pregnant, before they started to experience nausea and vomiting (at a mean of 4 weeks’ gestation). Another 29 pregnant women started taking the combination when they started to experience symptoms, Ms. Maltepe said at the annual meeting of the Teratology Society.

Women in both groups started to experience NVP symptoms at a mean of about 5 to almost 6 weeks, said Ms. Maltepe, the lead author of the study, who is with the Motherisk Program at the Hospital for Sick Children in Toronto. The program conducts research and provides information about the safety of maternal exposure to drugs, chemicals, diseases, radiation, and environmental agents to the developing fetus or infant.

The women (mean age, 31-32 years) had experienced severe NVP or hyperemesis gravidarum (HG) in their previous pregnancy, and enrolled when they were planning a pregnancy or in early pregnancy at a point when they had not yet experienced any symptoms. Women in both groups took 2-9 tablets of the doxylamine-pyridoxine combination a day, and received counseling and follow-up calls.

In Canada, the combination is approved and marketed as Diclectin, by Duchesnay, and is the only drug labeled for treating NVP in Canada. There it is considered a first-line treatment and is taken at a standard dose of four tablets a day, said Ms. Maltepe, the coordinator of the NVP helpline at Motherisk.

Diclectin is a generic form of the drug Bendectin, which was marketed in the United States until 1983, when it was voluntarily withdrawn by its manufacturer, Merrell Dow Pharmaceuticals, after a series of lawsuits claiming it caused birth defects. For several years, Duchesnay has been working toward Food and Drug Administration clearance to market Diclectin in the United States, but it would be premature to predict when it would become available in the United States, a spokesman for the company said.

In the study, symptoms were evaluated using the PUQE (Pregnancy–Unique Quantification of Emesis and Nausea) score, a validated scoring system that takes into account the frequency of vomiting; the frequency of retching, gagging, or dry heaves; and the number of hours spent feeling nauseous over a 24-hour period. The score was developed by Dr. Gideon Koren, director of Motherisk and coauthor of this study, and his associates. A score of 7-12 is considered moderate; a score of 13 or higher is considered severe.

In the study, preemptive treatment was associated with 70% fewer cases of moderate to severe NVP during the first 3 weeks women experienced symptoms: 4 of the 26 (15%) evaluable women had a PUQE score of 11 or more during the first 3 weeks of NVP symptoms, compared with 9 of the 23 (39%) evaluable women in the control group, a significant difference. Of the 19 women in the preemptively treated group who had HG during the previous pregnancy, 6 (32%) experienced HG, compared with 6 of the 11 (55%) in the control group, also a significant difference. Some women who enrolled were not evaluable for reasons that included having a miscarriage.

NVP resolved before labor in significantly more of the women in the preemptively treated group than in the control group (almost 80% vs. about 50%), and there was a negative correlation between PUQE scores and a well-being score, indicating that treatment is associated with improved quality of life for these patients, Ms. Maltepe said.

In women who have experienced severe NVP or HG in a previous pregnancy, preemptive treatment with doxylamine-pyridoxine events can reduce the recurrence of NVP in subsequent pregnancies, and improve their quality of life during pregnancy, as well as reduce time off from work and the need for enteral and parenteral therapy, hospitalization, and other costs associated with severe NVP, she concluded.

The NVP helpline at Motherisk is the only dedicated NVP helpline in the world, according to Ms. Maltepe, who provides evidence-based recommendations on pharmaceutical and nonpharmaceutical approaches to treating NVP for pregnant women, their family members, and clinicians via the helpline (800-436-8477 in North America).

The study was funded by Duchesnay. Ms. Maltepe and her coauthors said they had no relevant conflict of interest to disclose.

The Motherisk site is available at www.motherisk.org/women/index.jsp.

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