Bias in comparisons of mortality among very preterm births: A cohort study

Background Several studies of prenatal determinants and neonatal morbidity and mortality among very preterm births have resulted in unexpected and paradoxical findings. We aimed to compare perinatal death rates among cohorts of very preterm births (24-31 weeks) with rates among all births in these groups (>= 24 weeks), using births-based and fetuses-at-risk formulations. Methods We conducted a cohort study of singleton live births and stillbirths >= 24 weeks' gestation using population-based data from the United States and Canada (2006-2015). We contrasted rates of perinatal death between women with or without hypertensive disorders, between maternal races, and between births in Canada vs the United States. Results Births-based perinatal death rates at 24-31 weeks were lower among hypertensive than among non-hypertensive women (rate ratio [RR] 0.67, 95% CI 0.65-0.68), among Black mothers compared with White mothers (RR 0.94, 95%CI 0.92-0.95) and among births in the United States compared with Canada (RR 0.74, 95%CI 0.71-0.75). However, overall (>= 24 weeks) perinatal death rates were higher among births to hypertensive vs non-hypertensive women (RR 2.14, 95%CI 2.10-2.17), Black vs White mothers (RR 1.86, 95%CI 184-1.88;) and births in the United States vs Canada (RR 1.08, 95%CI 1.05-1.10), as were perinatal death rates based on fetuses-at-risk at 24-31 weeks (RR for hypertensive disorders: 2.58, 95%CI 2.53-2.63; RR for Black vs White ethnicity: 2.29, 95%CI 2.25-2.32; RR for United States vs Canada: 1.27, 95%CI 1.22-1.30). Conclusion Studies of prenatal risk factors and between-centre or between-country comparisons of perinatal mortality bias causal inferences when restricted to truncated cohorts of very preterm births.