Objective: The objective of our study is to assess the impact of triptan exposure on pregnancy outcome. Methods: We performed a prospective observational cohort study with 432 pregnant women exposed to triptans and enrolled by the German Embryotox system. Pregnancy outcomes were compared with a migraine and a non-migraine comparison cohort. Primary objectives were major birth defects and spontaneous abortion; secondary endpoints were preterm delivery, birth weight, pregnancy complications and the rate of electively terminated pregnancies. Results: Compared to a non-migraine cohort the rates of major birth defects (OR_adj 0.84; 95% CI 0.4–1.9), spontaneous abortions (OR_adj 1.20; 95% CI 0.9–1.7), preterm delivery (OR_adj 1.01; 95% CI 0.7–1.5), and preeclampsia (OR_adj 1.33; 95% CI 0.7–2.5) were not increased in triptan-exposed pregnancies. Conclusions: Our findings support the evidence that triptans are not major teratogens. When compellingly needed during pregnancy, sumatriptan as the best studied triptan appears an acceptable treatment option. A detailed fetal ultrasound should be offered in cases of first trimester exposure to less well-studied triptans. Trial registration number in German Clinical Trials Register: DRKS00007660

Background: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used to treat pain, fever and inflammatory conditions. Due to evidenced fetotoxicity, treatment with NSAID and metamizole should be avoided in the 3rd trimester of pregnancy. There is an ongoing debate on fetotoxic risk of 2nd trimester use which is why we have conducted this study. Methods: In this observational cohort study outcome of pregnancies with NSAID and/or metamizole exposure in the 2nd and/or 3rd trimester (study cohort n = 1092) was compared with pregnancies exposed to NSAID and/or metamizole in the 1st trimester only (comparison cohort, n = 1154). The WHO-UMC system was used to assess causality between study medication and study endpoints. Prenatal study endpoints were constriction of ductus arteriosus Botalli, oligohydramnios, late spontaneous abortion (SAB) or stillbirth. Postnatal study endpoints were patent ductus arteriosus (PDA), anomalies of the right heart ventricle, primary pulmonary hypertension (PPHT), and neonatal impairment of kidney function. Results: Ductus arteriosus constriction was diagnosed in 5/1092 (0.5%) in the study cohort versus 0/1154 pregnancies in the comparison cohort. In one fetus, ductus arteriosus constriction and oligohydramnios occurred already in the late 2nd trimester after long-term NSAID exposure. Oligohydramnios was diagnosed in 41/1092 (3.8%) in the study cohort versus 29/1154 (2.5%) cases in the comparison cohort [RR, 1.5 (95% CI 0.9–2.4)]. Limited to 2nd trimester, oligohydramnios occurred in 8/904 (0.9%) versus 2/1154 (0.2%) pregnancies [RR, 5.1 (95% CI 1.1–24.0)]. At least in four of the 2nd trimester exposed pregnancies NSAID exposure lasted several weeks. Late SAB or stillbirth occurred in 14/1092 (1.3%) versus 17/1154 (1.5%). Postnatal cardiovascular or renal pathology did not differ between the cohorts. Conclusions: NSAID use in the 2nd trimester limited to a few days does not appear to pose a relevant risk. Use for longer periods in the advanced 2nd trimester, however, may cause oligohydramnios and ductus arteriosus constriction similar to effects observed after 3rd trimester use.

Aims: Angiotensin‐II receptor 1 antagonists (AT₁‐antagonists) may cause severe and even lethal fetopathy in late pregnancy. However, exposure still occurs in spite of warnings in package leaflets. This study aimed to assess the risk of fetopathy, the sensitive time window, and possible new symptoms in prospective as well as retrospective cases with AT₁‐antagonist treatment during the second or third trimester of pregnancy.Methods: Patients were enrolled by the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy between 1999 and 2011 through risk consultation. Symptoms defined as indicative of AT₁‐antagonist fetopathy were: oligo‐/anhydramnios, renal insufficiency, lung hypoplasia, joint contractures, skull hypoplasia and fetal/neonatal death.Results: In 5/29 (17%) prospectively enrolled cases with AT₁‐antagonist exposure beyond the first trimester oligo‐/anhydramnios was diagnosed. Two infants showed additional symptoms of fetopathy. The risk is more than 30% if treatment continues beyond the 20th week of pregnancy. Oligo‐/anhydramnios was reversible after AT₁‐antagonist withdrawal. Among 16 retrospective case reports, three infants presented with a thrombosis of the inferior vena cava in the vicinity of the renal veins. Four out of 13 live births did not survive.Conclusions: Our survey suggests that the risk increases with duration of AT₁‐antagonist treatment into late pregnancy and oligo‐/anhydramnios may be reversible after AT₁‐antagonist discontinuation. Thrombosis of inferior vena cava may be a new feature of AT₁‐antagonist fetopathy. AT₁‐antagonist medication during pregnancy constitutes a considerable risk and must be discontinued immediately. In case of indicative diagnostic findings in either the fetus or newborn, previous maternal AT₁‐antagonist exposure should be considered.