Childhood neurodevelopment after spontaneous versus indicated preterm birth

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: We performed 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 women 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, neonatal intensive care unit deaths, and deaths after discharge) or an abnormal Bayley II score by 2 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 or less, and neonatal morbidities associated with prematurity. Bivariate analyses of baseline characteristics by exposure were conducted. A logistic regression model was fitted to adjust for confounders.

Results: Of 1678 subjects, 1631 (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 weeks ± 7.8 versus 28.8 weeks ± 2.5, P = .07). A Psychomotor Developmental Index score 2 standard deviations or less below the mean or death occurred in 340 (20.9%) spontaneous preterm birth subjects and 17 (36.2%) indicated preterm birth subjects (P = .01). When adjusting for confounders, there remained an increased probability of a Psychomotor Developmental Index scores 2 standard deviations or less or death in indicated preterm birth subjects (P = .02). Although not statistically significant, indicated preterm birth was also associated with higher odds of Mental Developmental Index scores 2 standard deviations or less or death, Psychomotor Developmental scores 1 standard deviation or less or death, and Mental Developmental Index scores 1 standard deviation or less or death (1.76, 1.59, and 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 less or death remained significant higher in the indicated preterm birth group (adjusted odds ratio, 1.98; 95% confidence interval, 1.01-3.88).

Conclusion: In this cohort of pregnant women who delivered preterm, indicated deliveries were associated with worse psychomotor development than were spontaneous deliveries. Other outcomes appeared to be poor, but our numbers were limited. This finding should be confirmed in a larger cohort of women undergoing medically indicated preterm deliveries.