Postnatal and long-term outcomes after in utero exposure to RAAS inhibitors: cohort study based on German claims data

Although use of inhibitors of the renin-angiotensin-aldosterone system (RAAS-I) is contraindicated in the second and third trimesters of pregnancy, a relevant number of pregnancies is still exposed. Fetopathy in children exposed after gestational week (GW) 20 is well described, but data on long-term outcomes are scarce. Our study aims to describe postnatal and long-term outcomes after fetal exposure to RAAS-I.

We included all pregnancies in the German Pharmacoepidemiological Research Database GePaRD (claims data; 20% of the total German population) with exposure to RAAS-I or the antihypertensives recommended during pregnancy, i.e., metoprolol or methyldopa (HYP) after GW 20. We assessed diagnoses characteristic of RAAS-I-related fetopathy in the first 180 days after birth and examined long-term outcomes of children with and without neonatal fetopathy, especially hypertension and kidney disease.

Overall, we identified 203 live born children exposed to RAAS-I, of whom 61 were exposed to angiotensin II receptor blockers (ARBs), and 29,674 live born children exposed to HYP. Diagnoses consistent with RAAS-I-related fetopathy were seen in eight of the RAAS-I exposed newborns (3.9%) and in seven of the 61 ARB-exposed newborns (11.5%). Median follow-up in children without fetopathy was 4.0 years in both exposure groups. Among non-fetopathy children exposed to RAAS-I, three (1.5%) were diagnosed with hypertension or received antihypertensive prescriptions, compared to 176 children (0.6%) exposed to HYP.

Risk of fetopathy is higher after fetal exposure to ARBs than to angiotensin-converting enzyme inhibitors. In a small proportion of children, sequelae of fetal RAAS-I exposure might only manifest in the years following birth.