The most common bacterial infections during pregnancy include urinary tract infections, cellulitis and skin abscesses, upper and lower respiratory tract infections, and sexually transmitted diseases. Management of bacterial infections in pregnant women requires early antimicrobial treatment to prevent adverse maternal and pregnancy outcomes. As such, antibiotics are among the most commonly used medications in pregnancy – approximately six out of ten publicly insured and four out of ten commercially insured pregnant women fill at least one antibiotic prescription during pregnancy. To select the optimal antibiotic from the range of available options for specific infections, it is therefore crucial to understand the comparative safety of in utero exposure to specific antibiotics. Unfortunately, rigorous and comprehensive safety data to inform the risk-benefit trade-off are sparse and evidence is conflicting. The primary concern among potential risks associated with antibiotic use in pregnancy are congenital malformations, which are a leading cause of neonatal morbidity and mortality, and frequently cause lifelong disability. Additionally, some studies have pointed to an increased risk of spontaneous abortions and neonatal jaundice associated with some commonly used classes of antibiotics. Given that 45% of pregnancies in the US are unintended, understanding the comparative safety of antibiotics in early pregnancy may also inform the selection of antibiotics in women of reproductive age. The objective of the proposed studies is therefore to evaluate the comparative safety of antibiotics commonly used for the treatment of bacterial infections during pregnancy. To accomplish this, we will employ large pregnancy cohorts of publicly and privately insured pregnant women (N ≈ 4.5 million). For each of the most common bacterial infections, we will assess the comparative safety of available commonly used antibiotic treatment options and utilize the rich information in our data sources to control for potential confounding variables. The large study size will enable quantification of effects for the pre-specified outcomes (i.e., malformations overall, specific malformation types, spontaneous abortion, and neonatal jaundice) with great precision. In addition, to ensure a comprehensive evaluation of the comparative safety, we will utilize a novel signal detection method developed by members of our team, TreeScan, for simultaneous evaluation of a broad range of potential maternal, fetal and neonatal adverse outcomes. By harnessing the power of existing real-world data, this study will inform strategies for tailoring antibiotic treatment to optimize pregnancy outcomes in this vulnerable population. As such, the proposed study aligns well with the main goal of PAR-20-300. By defining the safest treatment options for women of reproductive age with bacterial infections, the findings of this study will have direct and immediate clinical impact.

Antibiotics are among the most commonly used medications in pregnancy, yet the potential of teratogenicity and fetal toxicity of antibiotics in humans remains an area largely devoid of evidence. To address this critical information gap, we propose to generate high-quality evidence on the comparative safety of antibiotic treatment options for common bacterial infections during pregnancy by leveraging existing data on over 4.5 million pregnancies. The findings from this research will directly inform the treatment decisions regarding antibiotics selection in pregnant women and women of reproductive age who may become pregnant.