Childhood neurodevelopment after spontaneous versus indicated preterm birth

Abstract Background Preterm birth is the leading cause of neonatal morbidity and mortality. Individuals who survive preterm birth are at a higher risk for many long-term adverse effects, including neurodevelopmental deficits. There are many well-established risk factors for worse neurologic outcomes spanning the prenatal and postnatal periods, however, investigators have yet to assess whether the cause of preterm birth has an impact on neurodevelopment. Objective Our objective was to assess whether neurologic outcomes differ by children born via indicated versus spontaneous preterm birth. Study Design Secondary analysis of a multicenter trial assessing magnesium for neuroprotection in women at risk for preterm delivery from 24 to 31 weeks. We included women with live, nonanomalous, singleton gestations who delivered preterm; we excluded those whose children were missing 2-year follow-up information for reasons other than perinatal demise. The primary exposure was type of preterm birth: 1) spontaneous if the child’s mother presented with preterm labor or ruptured membranes or 2) indicated if the child was delivered preterm iatrogenically. The primary outcome was death (including stillbirths, NICU deaths, and deaths after discharge) or an abnormal Bayley II score by two years of age, defined as a Mental Developmental Index score or Psychomotor Developmental Index score 2 standard deviations below the mean. Secondary outcomes included death or Mental Developmental Index and Psychomotor Developmental Index scores ≤1 standard deviation and neonatal morbidities associated with prematurity. Bivariate analyses of baseline characteristics by exposure were conducted. We fit a logistic regression model to adjust for confounders. Results Of 1,678 subjects 1,631 (97.2%) underwent spontaneous preterm birth and 47 (2.8%) underwent indicated preterm birth. Baseline maternal demographics and gestational age at delivery were similar between groups (29.6 wks ±7.8 v. 28.8 wks ±2.5, p=0.07). A Psychomotor Developmental Index score ≤2 standard deviations or death occurred in 340 (20.9%) spontaneous preterm birth subjects and 17 (36.2%) indicated preterm birth subjects (p=0.01). When adjusting for confounders, there remained an increased probability of a Psychomotor Developmental Index scores ≤2 standard deviations or death in indicated preterm birth subjects (p=0.02). Though not statistically significant, indicated preterm birth was also associated with higher odds of Mental Developmental Index scores ≤2 standard deviations or death, Psychomotor Developmental scores ≤1 standard deviation or death, and Mental Developmental Index scores ≤1 standard deviation or death (1.76, 1.59, 1.45, respectively). Limiting the analysis to small for gestational age infants, there was no difference in neurologic outcomes. The same was true for when we excluded small for gestational age infants from our analysis. However, after adjusting for small for gestational age, the odds of a Psychomotor Developmental Index score ≤2 standard deviations or death remained significant higher in the indicated preterm birth group (aOR 1.98, 95% CI 1.01, 3.88). Conclusion In this cohort of pregnancies who delivered preterm, indicated deliveries were associated with worse psychomotor development than spontaneous deliveries. Other outcomes appeared poor, but our numbers were limited. This finding should be confirmed in a larger cohort of women undergoing medically indicated preterm deliveries.