Senior scientist Leibniz Institute for Prevention Research and Epidemiology - BIPS Bremen, Germany
Background: Treatment with inhibitors of the renin-angiotensin-aldosterone system (RAAS-I) after gestational week (GW) 20 can result in severe fetotoxic effects including oligohydramnios, renal damage and lung hypoplasia. RAAS fetotoxicity might also lead to functional defects that manifest late postnatally, e.g. as hypertension or renal disease. So far there are no studies examining the long-term effects of RAAS-I in children without diagnosed fetopathy in the first weeks of live.
Objectives: To describe the long-term outcomes of children exposed to RAAS-I after GW 20 with no fetopathy in the first 180 days after birth.
Methods: We used a previously established cohort in the German Pharmacoepidemiological Research Database (GePaRD), which included children born to women who were exposed to RAAS-I or, as comparator, metoprolol or methyldopa (HYP, recommended antihypertensives during pregnancy) after GW 20 between 2006 and 2019. We excluded children with a diagnosis (in the child or the mother) indicating a fetotoxic effect, i.e. renal failure, pulmonary hypoplasia, thrombosis of vena cava inferior, contractures or effects of oligohydramnios coded during pregnancy or in the first 180 days after birth. Starting with day 181, we followed up included children until death, the end of continuous insurance or the end of the study period (31.12.2019) and described the occurrence of indicators for renal disease or hypertension (diagnosis of renal disease or hypertension, antihypertensive treatment, dialysis). Other factors such as (pre)eclampsia, diabetes, obesity, use of antidiabetics and diuretics, socioeconomic status, multiples, gestational age at birth and malformations were also assessed.
Results: We included 195 children exposed to RAAS-I and 29,346 children exposed to HYP after GW 20. Median follow-up was 4.0 years in both groups. Codes indicating renal disease were found in no child exposed to RAAS-I and in 16 children (0.1%) exposed to HYP. Among children exposed to RAAS-I, three children (1.5%) had hypertension (one with diagnosis, two with antihypertensive treatment). These children also had major congenital malformations (two with ventricular septal defect, one with hypoplastic left heart syndrome). Among children exposed to HYP, 193 children (0.66%) had hypertension (23 diagnosis, 123 treatment, 17 both) and about half of these 193 children also had a diagnosis of a major congenital malformations.
Conclusions: Our study does not suggest that fetal exposure to RAAS-I after GW 20 leads to late postnatal functional defects such as hypertension or renal disease but the low sample size and the mere descriptive nature of our study should be considered in the interpretation of our findings.
