OBJECTIVE: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation.
DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions.
STUDY SELECTION: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death.
DATA EXTRACTION AND SYNTHESIS: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses.
MAIN OUTCOMES AND MEASURES: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death.
RESULTS: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%).
CONCLUSIONS AND RELEVANCE: Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.
OBJECTIVES: This study aimed to explore factors associated with blood DHA and AA concentrations of very preterm infants receiving standard care, in the days following birth.
METHODS: We examined the fatty acid composition of whole blood samples collected on cards at 0-6 d after birth, from a cross-sectional study of 1174 infants born <29 weeks of gestation in Australia, New Zealand, and Singapore.
RESULTS: Considerable variation was observed in the proportions of blood AA (1.4%-18.0%) and DHA (0.4%-5.7%) concentrations. Infant blood DHA status was not associated with gestational age at birth, but AA was lower by 0.11% for each week of gestation (95% CI: -0.07%, 0.15%). There was an inverse relationship between age of sampling after birth and DHA (0.07% lower per day; 95% CI: 0.04%, 0.09%) and AA (0.09% lower; 95% CI: 0.04%, 0.14%). A concomitant positive relationship was observed between days after birth and the fatty acids present in the intravenous lipid emulsion administered: ω-6 linoleic acid (range: 2.1%-35.1%) and ω-9 oleic acid (range: 12.2%-52.9%).
CONCLUSIONS: Preterm infants whose blood was sampled later after birth have lower DHA and AA status relative to those sampled earlier after birth; samples taken at later timepoints are concurrently higher in the fatty acids of linoleic acid and oleic acid, which are the major compositional components of intravenous lipid emulsions routinely administered to preterm infants. The results support calls to develop intravenous feeds closely matching the fatty acid composition of infant blood at birth. The N3RO Trial is registered at the Australian New Zealand Clinical Trial Registry as ACTRN12612000503820 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000503820).