Donor Human Milk vs. Preterm Formula for Supplementation in Very Preterm Infants: Long-Term Neurodevelopment at 24 Months

Abstract

Introduction: When mother’s own milk is insufficient, donor human milk (DHM) or preterm formula (PF) are used as supplements for very preterm infants. Short-term benefits (lower NEC risk) favor DHM, but long-term neurodevelopmental outcomes are uncertain due to nutrient differences (DHM has lower protein, fat).

Methods: We conducted a systematic review of RCTs comparing DHM versus PF supplementation in very preterm (<32 weeks) or VLBW infants. Primary outcome: neurodevelopmental impairment (NDI) at 18–24 months corrected age (composite of cognitive, motor, or language delay). Secondary: Bayley-III cognitive score. MEDLINE, Embase, CENTRAL searched.

Results: Six RCTs (n=1,347 infants) were included. At 24 months, NDI occurred in 27% of DHM-supplemented vs. 29% of PF-supplemented infants (RR 0.93, 95% CI 0.77–1.12, p=0.45). Bayley-III cognitive scores were not different (mean difference 0.8 points, 95% CI –1.2 to 2.8). Subgroup analysis of infants exclusively fed DHM+mother’s milk (no PF) showed slightly lower NDI (RR 0.85, 95% CI 0.68–1.06, borderline). NEC was significantly lower with DHM (3.1% vs. 8.7%, p<0.001).

Discussion: DHM and PF produce comparable neurodevelopmental outcomes at 24 months despite nutrient composition differences. The NEC benefit favors DHM, while growth velocity was higher with PF (not analyzed due to heterogeneity). Longer-term follow-up (5–8 years) needed for subtle cognitive effects.

Conclusions: Donor human milk is a safe alternative to preterm formula for supplementation in very preterm infants, offering NEC protection without neurodevelopmental disadvantage at age 2 years.