Time-related bias when studying perinatal complications after maternal injuries: Application to maternal injuries and preterm birth

Background: Some studies examining associations between maternal injuries and preterm birth reported null or counterintuitive protective effects, especially for 3 rd -trimester injuries, likely due to time-related biases. Methods: This retrospective cohort study comprised all births occurring at Atrium Health Wake Forest Baptist health system between 2018 and 2024. We ascertained maternal injuries using validated diagnostic codes and defined preterm birth as gestational age at delivery <37 weeks. We estimated associations between maternal injuries and preterm birth with two approaches. We used logistic regression for time-fixed analysis (injury at any point in pregnancy yes/no and preterm birth yes/no) and Cox proportional hazards models for time-varying analysis (i.e., time-varying injury definition, restricted follow-up to periods when pregnancies were at risk of preterm birth). Results: Among 58,897 births, 1,801 women (3.1%) experienced maternal injuries during pregnancy. With the time-varying approach, maternal injuries were associated with increased risk of preterm birth (adjusted hazard ratio (HR): 1.16 (95% CI: 1.01, 1.32). Trimester-specific analyses showed positive associations for all trimesters, with higher effect estimates observed for 2 nd and 3 rd trimester injuries (adjusted HRs: 1.17 (95% CI: 0.97, 1.42) and 1.22 (95% CI: 0.92, 1.61), respectively). With time-fixed analyses, associations for any injury were underestimated, compared to time-varying analyses, and results for 3 rd trimester injuries showed counterintuitive negative associations (adjusted odds ratio: 0.73 (0.54, 0.98)). Conclusion(s): Time-related biases typically underestimate associations between maternal injuries and preterm birth, particularly for 3 rd trimester injuries. Rigorous study design and analytical methods that account for time-related biases are crucial in studies investigating adverse outcomes after maternal injuries.