(A-319) Assessing the Risk of Neurodevelopmental Disorders in Children Prenatally Exposed to β-Lactam Antibiotics

Background: β-lactam antibiotics are commonly prescribed for most bacterial infections during pregnancy due to their well-established safety profile. However, the potential risk of neurodevelopmental disorders (NDDs) in children associated with prenatal β-lactam exposure remains unclear.

Objectives: We aimed to assess the risk of NDDs in children prenatally exposed to different classes of β-lactams during specific gestational periods to determine the effect of in-utero β-lactam exposure on fetal neurodevelopment.

Methods: This retrospective cohort study utilized administrative claims data spanning the years 2012 to 2024, and included pregnant women aged 12 to 55 years and their live-born infants, identified using validated algorithms. The incidence of NDDs, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), developmental coordination disorder (DCD), speech and language disorder (SLD), and behavioral disorder (BD), was compared between children exposed to β-lactam antibiotics and those with no antibiotic exposure during early pregnancy (≤20 weeks), late pregnancy (>20 weeks), and the entire pregnancy period. Cox proportional hazard regression analyses were performed using inverse probability weighting to adjust for confounding variables. Sensitivity analyses were conducted to address potential biases and evaluate the robustness of the findings across various subgroups.

Results: Among the 16,076 livebirths included in the study, 1,964 (12.2%) were exposed to β-lactams. Penicillin β-lactams were the most commonly dispensed class, constituting 72% (n=1,414) of the β-lactams. Compared to children with no antibiotic exposure, there was no significant risk of NDDs in those exposed to any β-lactams during gestation. However, there was a higher risk of ADHD (HR: 2.26; 95% CI: 1.02 – 5.00) and BD (HR: 2.07; 95% CI: 1.10 – 3.92) in children exposed to penicillin β-lactams compared to those with no antibiotic exposure during late pregnancy. Additionally, a higher risk of DCD was observed in children exposed to non-penicillin β-lactams compared to those with no antibiotic exposure during the entire (HR: 3.82; 95% CI: 2.01 – 7.29) and early (HR: 4.36; 95% CI: 2.37 – 8.02) pregnancy periods, while late pregnancy exposure was associated with a higher risk of SLD (HR: 2.10; 95% CI: 1.32 – 3.34).

Conclusions: While overall β-lactam antibiotic exposure during pregnancy was not associated with NDDs, our results suggest that specific β-lactam classes and gestational timing of exposure may influence neurodevelopmental outcomes in children. Further research is warranted to confirm these associations, investigate underlying biological mechanisms, and refine clinical guidelines for β-lactam antibiotic use during pregnancy.