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

Abstract

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.

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants

“…Alternatively, the use of a BPD definition, classified on its severity according to the mode of respiratory support regardless of the need for supplemental oxygen, may be a better outcome associated with early childhood morbidities in modern neonatal respiratory care . Results of this systematic review and meta-analysis did not detect an association between DHA and severe BPD, yet the inverse association of DHA with moderate-to-severe BPD warrants investigation to understand how to balance the potential adverse implications of DHA for BPD with the potential benefits of DHA for neurodevelopment …”

“…warrants investigation to understand how to balance the potential adverse implications of DHA for BPD with the potential benefits of DHA for neurodevelopment. [20][21][22] Two trials 19,31 reported an increased risk for BPD after DHA administration in more mature babies, resulting in a higher effect size in this category. However, stratification according to GA was inconclusive, with no subgroup differences found and high evidence of heterogeneity limited the interpretation of results.…”

“…Contrary to the aforementioned hypothesis, both trials reported an overall increase of BPD with the use of DHA but an inconsistent association with BPD-free survival in analysis by gestational age (GA) and mode of delivery. By contrast, early follow-ups of these trials provided some signals regarding neurodevelopment following such DHA supplementation …”

SMOFlipid Impact on Growth and Neonatal Morbidities in Very Preterm Infants

“…This effect may have been mediated by BPD. In its secondary analysis, the MOBYDIck trial found that giving DHA supplementation alone to mothers who breastfed their preterm infants is associated with improving the weight velocity in females, only with an opposite impact on males, and these influences are not mediated by BPD [ 33 ].…”

Effect of Docosahexaenoic Acid (DHA) Supplementation of Preterm Infants on Growth, Body Composition, and Blood Pressure at 7-Years Corrected Age: Follow-Up of a Randomized Controlled Trial

“…Infants born prematurely are deprived of this in utero accretion of DHA, contributing to their higher risk of developmental delay compared to infants born at term [ 3 , 5 ]. Clinical trials assessing higher doses of DHA in preterm infants have been designed to improve neurodevelopmental outcomes [ 6 , 7 , 8 , 9 , 10 , 11 ]. However, DHA can be a potent anti-inflammatory agent and may have other actions that affect other organ systems.…”