Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

Objective To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. Study design This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). Results Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (β = −1.1; 95% CI, −2.2 to −0.02; P = .05) and language scores (β = −2.1; 95% CI, −3.3 to −0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, −0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004). Conclusions Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. Trial registration Clinicaltrials.gov identifier: NCT02371460. To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (β = −1.1; 95% CI, −2.2 to −0.02; P = .05) and language scores (β = −2.1; 95% CI, −3.3 to −0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, −0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004). Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight.