(311) Risk of Neonatal and Maternal Adverse Events of Oral Anti-hypertensive Medications Used in Pregnancy: Evidence Synthesis from a Disproportionality Analysis

Background: Hypertensive disorders of pregnancy (HDP) are rising in prevalence and are associated with adverse maternal and infant health outcomes. Oral anti-hypertensives are acceptable first-line agents to treat HDP in outpatient settings. However, the maternal and neonatal safety of these drugs remains unclear.

Objectives: To identify the safety signals of oral anti-hypertensive medications used in pregnancy related to neonatal and maternal adverse events

Methods: We carried out a retrospective case/non-case study using spontaneous reports in the FDA Adverse Event Reporting System (FAERS) from the date of approval by the FDA to 30th December 2023. The study employed a disproportionality analysis, calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) to identify safety signals related to neonatal and maternal safety adverse events (if PRR ≥ 2, Lower Bound (LB) ROR > 1, and IC025 > 0) for anti-hypertensive drugs during the pregnancy. We also performed a signal refinement analysis by eliminating the confounding co-prescribed medications to identify the robustness of the findings.

Results: Using disproportionality analysis, 46 neonatal safety signals (Labetalol=27, Nifedipine=18, Amlodipine=1, Methyldopa=8, and hydralazine=2) of considerable strength such as neonatal respiratory distress syndrome and neonatal respiratory failure signals were observed for labetalol [PRR= 27.4 (χ2= 849.7), LB ROR= 19.6, IC025= 3.8; PRR= 15.5 (χ2= 40.3), LB ROR= 5.0, IC025= 0.3], and nifedipine [PRR= 14.9 (χ2= 802.8), LB ROR= 11.6, IC025= 3.3; PRR= 10.4 (χ2= 58.2), LB ROR= 4.9, IC025= 1.4]. Neonatal Intraventricular hemorrhage identified for methyldopa and amlodipine [PRR= 10.4 (χ2= 34.0), LB ROR= 3.9, IC025= 0.6; PRR= 3.8 (χ2= 160.9), LB ROR= 3.0, IC025=1.5]. Patent ductus arteriosus [PRR= 10.8 (χ2= 460.1), LB ROR= 8.2, IC025= 2.9] signal was identified in Nifedipine. Signals of considerable strength in maternal adverse events such as postpartum hemorrhage, pre-eclampsia signals were observed for labetalol [PRR= 22.3 (χ2= 160.3), LB ROR= 11.1, IC025= 2.1; PRR= 91.4 (χ2= 10179.8), LB ROR= 77.2, IC025= 5.7], and nifedipine [PRR= 4.7 (χ2= 17.5), LB ROR= 2.1, IC025= 0.5; PRR= 21.0 (χ2= 1791.2); LB ROR= 17.2, IC025= 3.9].

Conclusions: Our analysis uncovers notable safety signals for both neonatal and maternal outcomes associated with oral anti-hypertensive medications during pregnancy. Neonatal and maternal safety signals for labetalol and nifedipine emphasize the imperative for cautious prescription and close monitoring for adverse outcomes in hypertensive pregnant women.