Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes.

BACKGROUND: Montelukast (Singulair) is a selective leukotriene receptor antagonist (LTRA) indicated for the maintenance treatment of asthma. Currently, there are limited prospective, comparative studies in the literature examining the safety of montelukast use in pregnancy. OBJECTIVES: The primary objective of this study was to determine whether exposure to montelukast during pregnancy increases the rate of major malformations above the 1­3% baseline risk or the rate of other adverse effects. METHODS: Pregnant women taking montelukast were enrolled in the study from six teratogen information services around the world. These women were compared to two other groups of women: (1) disease-matched, who used inhalers for a similar indication and (2) women not diagnosed with asthma and not exposed to any known teratogens. The primary outcome was major malformations and secondary endpoints included spontaneous abortion, fetal distress, gestational age at birth and birth weight. RESULTS: Out of 180 montelukast-exposed pregnancies, there were 160 live births including three sets of twins, 20 spontaneous abortions, 2 elective abortions and 1 major malformation reported. The mean birth weight was lower (3,214 ± 685 g) compared to controls [3,356 ± 657 (disease-matched) and 3,424 ± 551 (exposed to non-teratogens), P = 0.038] and the gestational age was shorter [37.8 ± 3.1 weeks (montelukast) and 37.6 ± 4.4 (disease-matched) versus 39.3 ± 2.4 weeks (exposed to non-teratogens), P = 0.045]. About 25% of the newborns had fetal distress, a higher rate than controls (P = 0.007). However, upon sub-analysis of women who continued the drug until delivery, only birth-weight difference (304 g) remained significant. CONCLUSIONS: Montelukast does not appear to increase the baseline rate of major malformations. The lower birth weight in both asthma groups is most likely associated with the severity of the maternal condition.

Pregnancy outcome after exposure to ranitidine and other H2-blockers. A collaborative study of the European Network of Teratology Information Services.

BACKGROUND: Published data on pregnancy outcome after exposure to H2-blockers is scarce. The aim of the present study was to evaluate the data collected by the memberships of the European Network of Teratology Information Services (ENTIS). METHODS: The patients were pregnant women who or whose doctor or midwife did contact a Teratology Information Service for risk assessment after the use of a H2-blocker in pregnancy. The data were prospectively collected, i.e. before the outcome of pregnancy was known. Standardized procedures for data collection were used by each centre. The data of the exposed women were compared to those of a control group exposed to non-teratogenic substances. RESULTS: Data on the outcome of 553 pregnancies with exposure to an H2-blocker were evaluated (ranitidine n=335; cimetidine n=113, famotidine n=75; nizatidine n=15, roxatidine n=15). Most of them had been exposed at least in the first trimester. The incidence of premature deliveries was higher in the exposed group compared to the control group. There was no increase in the incidence of major malformations. Two pregnancies with maternal use of famotidine in early pregnancy were terminated after the prenatal diagnosis of a neural tube defect. CONCLUSION: There is no indication for an increased risk of major malformations after the use of H2-blockers during pregnancy.

Topically applied minoxidil may cause fetal malformation: a case report.

BACKGROUND: Minoxidil is a K(+) channel opener able to cause relaxation of vascular smooth muscles and modify cell growth and cell fate or migration. It is now widely used for its hair growth promoting effects. When locally applied, it is absorbed through the skin and may have systemic pharmacological effects. CASE: A 28-year-old white pregnant woman daily applied minoxidil 2% to her scalp because of hair loss. At the 22nd gestational week, after a routine ultrasound test showing significant brain, heart, and vascular malformations of the fetus, pregnancy was interrupted. The placenta had numerous ischemic areas and a discrepancy between gestational age and villi maturation. In the villi, capillaries were increased in number, significantly enlarged, and excessively marginalized. The fetus' heart was increased in volume and had a globose shape, the aorta had a distal stenosis. The sigmoid colon was significantly increased in length and a mesentery commune was present. The brain had enlarged ventricles and abundant hemorrhages. Histological examination showed areas of demyelinization with gliosis, signs of excessive and inappropriate angiogenesis, and capillary rearrangement. CONCLUSIONS: Further knowledge on minoxidil-induced fetal toxicity would be beneficial before allowing its use in pregnant women.