Enteral High-Dose Docosahexaenoic Acid and Neurodevelopment in Extremely Preterm Infants: A Systematic Review and...

Area of Science:

• Neonatal Medicine
• Neuroscience
• Nutritional Science

Background:

• Extremely preterm infants may require high-dose docosahexaenoic acid (DHA) for optimal neurodevelopment and cognition.
• Evidence supporting the efficacy of enteral high-dose DHA for neurodevelopment in this population is limited.

Purpose of the Study:

• To investigate the association between enteral high-dose DHA during the neonatal period and neurodevelopmental outcomes in infants born at or before 29 weeks of gestation.
• To synthesize evidence from randomized controlled trials (RCTs) on DHA supplementation and infant neurodevelopment.

Main Methods:

• A systematic literature search was conducted across multiple databases (CINAHL, Cochrane Library, Embase, Medline, Scopus, Web of Science) up to April 11, 2024.
• Eligible RCTs involved infants born ≤29 weeks gestation, assessing direct enteral DHA administration (≥ 40 mg/kg/d) or fortified breast milk/formula (≥ 0.60% total fatty acids).
• Data were pooled using meta-analyses, with global cognitive scores as the primary outcome.

Main Results:

• Three high-quality RCTs involving 2028 infants were included. Meta-analysis showed no significant difference in global cognition scores at corrected ages of 18-36 months or 5-7 years.
• However, the largest RCT using a direct enteral emulsion showed improved cognitive scores at 5 years (MD 3.45; 95% CI: 0.38, 6.52).
• High-dose DHA was associated with reduced mild motor and cognitive impairment, with no observed adverse effects.

Conclusions:

• Enteral high-dose DHA supplementation in extremely preterm infants did not demonstrate a significant effect on global cognitive scores via meta-analysis.
• A direct enteral emulsion form of DHA showed potential for improved cognitive outcomes.
• The findings support current recommendations for DHA supplementation in this vulnerable population.