Gestational age at birth and body size from infancy through adolescence: findings from analyses of individual data on 253,810 singletons in 16 birth cohort studies

BackgroundPreterm birth is the leading cause of perinatal morbidity and mortality, and is associated with adverse developmental and long-term health outcomes, including several cardio-metabolic risk factors. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as proxy of prematurity rather than actual length of gestation. We investigated the association of gestational age at birth (GA) with body size from infancy through adolescence. Methods and FindingsWe conducted a two-stage Individual Participant Data (IPD) meta-analysis using data from 253,810 mother-children dyads from 16 general population-based cohort studies in Europe, North America and Australasia to estimate the association of GA with standardized Body Mass Index (BMI) and overweight (including obesity) adjusted for confounders. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately, and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0-0.5 years), late infancy (>0.5-2.0 years), early childhood (>2.0-5.0 years), mid-childhood (>5.0-9.0 years), late childhood (>9.0-14.0 years) and adolescence (>14.0-19.0 years). GA was positively associated with BMI in the first decade of life with mean differences in BMI z-score (0.01-0.02) per week of increase in GA, however preterm infants reached similar levels of BMI as term infants by adolescence. The association of GA with risk of overweight revealed a similar pattern of results from late infancy through mid-childhood with an increased odds of overweight (OR 1.01-1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with risk of overweight (OR 0.98 [95% CI: 0.97:1.00]) per week of increase in GA, and children born very preterm had increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08]) compared with term. The findings were consistent across cohorts and sensitivity analyses, despite considerable heterogeneity in cohort characteristics. ConclusionHigher GA is potentially clinically important for higher BMI in infancy, while the association attenuates consistently with age. By adolescence, preterm children have on average a similar mean BMI to those born term.