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 (ß = -1.1; 95% CI, -2.2 to -0.02; P = .05) and language scores (ß = -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.

Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Use of SMOF lipid emulsion in very preterm infants does not affect the incidence of bronchopulmonary dysplasia-free survival.

BACKGROUND: We aim to assess whether the docosahexaenoic acid (DHA)-containing lipid emulsion (LE) SMOFlipid 20% (Fresenius Kabi Canada Ltd) is associated with bronchopulmonary dysplasia (BPD)-free survival at 36 weeks' postmenstrual age in very preterm infants. METHODS: This cohort study is nested in the MOBYDIck randomized clinical trial (NCT02371460), which investigated the effect of maternal DHA supplementation on BPD-free survival in breastfed very preterm infants born between 23 0/7 and 28 6/7 weeks' gestation in 16 Canadian neonatal intensive care units (2015-2018). Parenteral SMOF-LE was given to the infants according to the sites' routine care protocols. Relative risks (RRs) were estimated using a modified Poisson regression model with generalized estimating equations taking into account recruitment site, multiple birth, DHA supplementation, birth weight, sex, and gestational age. RESULTS: Among 528 infants (mean gestational age, 26.5 weeks [SD, 1.6]), 272 received SMOF-LE. Overall, 56.7% of the infants in the SMOF-LE group and 59.7% infants in the non-SMOF-LE group survived without BPD (adjusted RR, 0.94 [95% CI, 0.77-1.14]; P = 0.51). BPD rates were 39.3% in the SMOF-LE group vs 34.1% in the non-SMOF-LE group (adjusted RR, 1.10 [95% CI, 0.82-1.47]; P = 0.53). Severe BPD rates were 31.8% in the SMOF-LE group vs 28.8% in the non-SMOF-LE group (adjusted P = 0.59). Mortality was not significantly different between the SMOF-LE (6.7%) and non-SMOF-LE groups (9.5%; adjusted P = 0.40). CONCLUSION: In very preterm infants, intravenous DHA-containing SMOF-LE during the neonatal period was not associated with BPD-free survival.

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial.

INTRODUCTION: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. METHODS: Preterm infants' growth profile, growth velocity from birth to 36 weeks' postmenstrual age (PMA), and growth at 36 weeks' PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015-2018). Lactating mothers who delivered before 29 weeks' gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks' PMA. Analyses were performed using a linear regression model with generalized estimating equations. RESULTS: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks' PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5-80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6-6.2], p = 0.02). At 36 weeks' PMA, the weight of males in the DHA group was significantly smaller (MD, -88.9 g [95% CI: -166.2 to -11.6], p = 0.02). CONCLUSION: DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA.