OP 27 Methyldopa during the first trimester and pregnancy outcome – A prospective observational cohort study

Introduction An increased risk of congenital malformations in offspring of mothers with chronic hypertension is discussed. Although methyldopa is recommended as first line treatment for hypertensive disorders in pregnancy in most countries, published experience on 1st trimester exposure is still limited. Objectives The primary aim of our study was to analyze the risk of birth defects and spontaneous abortions in women treated with methyldopa during the first trimester. Patients and methods The pattern of antihypertensive drug regimen during the first trimester was analyzed in 1152 prospectively ascertained pregnancies reported to the German Embryotox pharmacovigilance institute. Pregnancy outcomes were then evaluated in a subgroup of women treated with methyldopa ( n  = 261) and compared to a non-hypertensive comparison group ( n  = 526). Results At conception 51% of women were treated with beta-blockers, 47% with RAAS-inhibitors and only 14% with methyldopa; monotherapy with one antihypertensive drug occured in 66% of pregnancies. The rate of major birth defects among women exposed to methyldopa during 1st trimester was not significantly increased compared to non-hypertensive women (3.7% vs. 2.5%; ORadj 1.24, 95% CI 0.4–4.0). There was a tendency towards a higher rate of spontaneous abortions in methyldopa exposed women. The risk of preterm birth was significantly higher and adjusted birth weight scores were significantly lower in the methyldopa group. Head circumferences were significantly reduced in exposed boys only. In a sensitivity analysis comparing pregnancies methyldopa monotherapy to metoprolol monotherapy, there was neither evidence for an increased risk for birth defects or early pregnancy loss nor for growth restriction or a reduced head circumference. However, the significantly increased risk of preterm birth in methyldopa treated pregnancies was confirmed. Conclusions Our study supports the evidence of safety of methyldopa during pregnancy. Further studies are needed to clarify the influence of hypertension and treatment with antihypertensives on preterm birth and intrauterine growth. This work was performed with financial support from the German Ministry of Health (BMG) and the German Federal Institute for Drugs and Medical Devices (BfArM).