Main research findings

Doxylamine-pyridoxine (D-P) combination (Diclectin) is the only antiemetic drug approved for use in pregnancy in Canada. The standard recommended dose is up to 4 tablets a day, regardless of body weight or severity of symptoms. 7 . This study aimed to determine the incidence of adverse maternal and fetal effects and pregnancy outcome in 225 women taking Diclectin at the recommended (n = 123) or higher than recommended (n = 102) doses. In this observational, prospective study, one-third (33.6%) of women reported having adverse effects (sleepiness, tiredness, and/or drowsiness) temporally related to the medication. There was no association between the dose per kg and rates of reported maternal adverse effects with doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets). 7 . Nausea and vomiting of pregnancy (NVP) was reported as severe by the majority (75.8%) of women. Mean birth weight (BW) was 3,400 g and gestational age (GA) 39 weeks. Multivariate analysis revealed that only prepregnancy weight and GA predicted lower BW, not the dose of D-P or the severity of NVP. 7 . There were two pregnancies with major malformation, a finding that is consistent with the rates of birth defects in the general population. 7 . It was concluded that the higher than standard dose of Diclectin, when calculated per kg of body weight, does not affect either the incidence of maternal adverse effects or pregnancy outcome. If needed, Diclectin can be given at doses higher than 4 tablets/day to normalize for body weight or optimize efficacy. 7 .

Another study found that among 3,835 women exposed to Bendectin while pregnant, in this group of 13,346 births, 13 had infants who developed pyloric stenosis. In comparison, among 9,511 women not exposed to Bendectin, 13 had infants who developed pyloric stenosis, resulting in a risk ratio estimate of 2.5 (95% confidence interval (CI) 1.2-5.2). 12 . The risk ratio increased from 1.2 (95% CI 0.4-4.4) in women who filled only one prescription to 7.6 (95% CI 4.9-11.6) in women who filled five or more prescriptions for Bendectin during their pregnancy. 12 .

A prospective study examined the relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). 13 . Three of the 58 categories of congenital malformations were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). 13 . However, these associations were considered to be due to chance. An independent study (the Collaborative Perinatal Project) found that two of these three malformations (microcephaly and cataract) were strongly associated with vomiting during pregnancy, even without Bendectin use. 13 . The authors concluded that there was no overall increase in the rate of major malformations after exposure to Bendectin and the three observed associations between Bendectin and individual malformations are unlikely to be causal. 13 .

Benefits and Risks

Benefit Summary

Doxylamine-pyridoxine combination is an effective treatment for nausea and vomiting in pregnancy. There is no evidence of increased risk of adverse effects to the mother or the fetus, even when the standard dose is exceeded. 7 . This could help improve the health and well-being of both mother and fetus by effectively managing pregnancy-related nausea and vomiting. 7 .

Risk Summary

The most common side effect of doxylamine-pyridoxine combination is sleepiness, tiredness, or drowsiness. 7 . These side effects are usually mild and tend to go away with time. 7 . Additionally, there might be a risk of birth defects in the fetus when taken during pregnancy, although this risk is comparable to the incidence of birth defects in the general population. 12 . 7 .

Study Comparison

Study Commonalities

Multiple studies suggest that doxylamine-pyridoxine combination is an effective treatment for nausea and vomiting in pregnancy and that the incidence of adverse effects to the mother and the fetus is low. 7 . These studies also indicate that the dosage can be adjusted to accommodate body weight. 7 .

Study Differences

Some studies have suggested an association between doxylamine-pyridoxine combination exposure and congenital malformations. 12 . However, other studies have shown no such association between the drug and birth defects. 13 . The discrepancies in the findings might be due to differences in study design, sample size, and data analysis methods.

Consistency and Contradictions of Results

Several studies suggest an association between exposure to doxylamine-pyridoxine combination and congenital malformations. 12 . However, other studies show no such association between the drug and birth defects. 13 . The discrepancies in the findings could be attributed to differences in study design, sample size, and data analysis methods.

Considerations for Applying Results in Real Life

If considering doxylamine-pyridoxine combination for nausea and vomiting in pregnancy, consult with a healthcare professional to understand the risks and benefits. Nausea and vomiting are common during pregnancy, often managed with lifestyle changes and home remedies. 5 . However, if the symptoms are severe and interfere with daily life, seeking medical advice is essential. 7 . Your doctor can determine the underlying cause of your nausea and vomiting and recommend appropriate treatment. Treatment for pregnancy-related nausea and vomiting may involve dietary adjustments, medication, or a combination of both. 7 . Dietary adjustments include eating smaller, more frequent meals, staying hydrated, and avoiding high-fat foods. 7 . Medications that may be prescribed include vitamin B6, doxylamine, and metoclopramide. 7 . Nausea and vomiting in pregnancy typically start in the first trimester and improve by the second trimester. 7 . However, if the symptoms persist into the second trimester or begin in the third trimester, consult your doctor. 7 . Nausea and vomiting in pregnancy can be a serious condition that affects both the mother and the fetus. 7 . Therefore, seek medical advice if symptoms are severe and interfere with your daily life. 7 .

Limitations of Current Research

The limitations of these studies include the fact that they were observational, prospective studies. This means that they cannot prove cause and effect. 7 . These studies were also conducted in Canada, so the results may not be generalizable to other countries. 7 .

Future Research Needs

Future research should include randomized controlled trials to investigate the safety and efficacy of doxylamine-pyridoxine combination in greater detail. 7 . These studies should be conducted in different countries to ensure generalizability. 7 .

Conclusion

These studies suggest that doxylamine-pyridoxine combination could be an effective treatment for nausea and vomiting during pregnancy. 7 . However, it is important to understand the risks and benefits associated with its use. 7 . If you have questions about treating nausea and vomiting during pregnancy, consult with your doctor. 7 .