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Background <p>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.</p> Methods <p>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&#xa0;days after birth and examined long-term outcomes of children with and without neonatal fetopathy, especially hypertension and kidney disease.</p> Results <p>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&#xa0;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.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

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  • 发表日期：

    2025年12月17日

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  • Tania Schink,
  • Malte Braitmaier,
  • Katarina Dathe,
  • Ulrike Haug,
  • Christof Schaefer,
  • Kathrin Thöne,
  • Marlies Onken

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Graphical Abstract