101 Trends in antenatal risk factors and the cumulative effect on outcomes of very preterm infants in Canada 2010-2023

Abstract Background Antenatal risk factors such as maternal diabetes, maternal hypertension, maternal age at birth and lower socioeconomic status (income and education) have been increasing over time in high-income countries. Antenatal factors are important contributors to neonatal outcomes of very preterm infants. Objectives This study aimed to evaluate the trends in antenatal risk factors and their cumulative effect on the risk of mortality/morbidity in very preterm infants. Design/Methods Retrospective cohort study of infants born 23-31 weeks’ gestation without major congenital anomalies and admitted in the Canadian Neonatal Network (CNN) database 2010-2023. Exposures includes advanced maternal age (AMA), maternal hypertension (HTN), maternal diabetes (DB), and maternal smoking (S). Primary composite outcome was mortality/morbidity (bronchopulmonary dysplasia, retinopathy of prematurity, severe brain injury and necrotizing enterocolitis). The effect of exposure to one, two, three and all four risk factors on the composite outcome was assessed using multivariable Poisson regression with robust error variance adjusted for confounders. Results Rate of mortality/morbidity was 40% (16,311/40,952). Overall, rate of exposure to risk factors was: none, 47% (19,366); one, 38% (15,667); two, 12% (4936); three, 2% (929); four 0.1% (54). Compared to not being exposed to any risk factors, significantly higher risk of mortality/morbidity was observed with exposure to one (adjusted RR [aRR] 1.94, 95% CI 1.02-1.06) and two risk factors (aRR 1.05, 95% CI 0.68-0.96) but not with three (aRR 1.02, 95% CI 0.94-1.11) and four (aRR 1.27, 95% CI 0.89-1.81). Maternal HTN (alone and in combination with other factors) was the most consistent risk factor for adverse outcomes. The proportion of neonates exposed ≥1 risk factor increased from 50% in 2010 to 55% in 2023. Conclusion The proportion of very preterm infants exposed to antenatal risk factors is increasing over time and exposure to a higher number of risk factors is associated with higher risk of adverse neonatal outcomes. This can help identify antenatal and postnatal interventions to mediate the risk of adverse neonatal outcomes.