Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge.
Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies. To determine if the addition of a multinutrient human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge is possible and whether it influences first-year growth.
                Of a cohort of 320 infants (gestational age: 24-32 weeks; birth weight: 535-2255 g), breastfed infants (65% [n = 207]) were randomly assigned shortly before hospital discharge to receive either unfortified (n = 102, group A) or fortified (n = 105, group B) mother's milk until 4 months' corrected age (CA). The remaining infants were bottle-fed with a preterm formula (group C). Follow-up was performed at term and at 2, 4, 6, and 12 months' CA.
                Mean duration of breastfeeding after term was not significantly different between groups A and B (11.8 and 10.6 weeks, respectively). Weight, length, and head circumference were not significantly different between groups A and B at 12 months' CA. Compared with groups A and B, infants in group C had a higher increase in weight z score until term and in length z score until 6 months' CA. At 12 months' CA, boys in group C were significantly longer and heavier compared with those in groups A and B, whereas girls in group C were longer and heavier compared with those in group A only. A higher protein intake was related to a higher serum urea nitrogen level and growth.
                Fortification of mother's milk after hospital discharge while breastfeeding very preterm infants was possible without influencing breastfeeding duration but did not significantly influence growth parameters at 1 year of age compared with unfortified mother's milk.
The limited available data do not provide convincing evidence that feeding preterm infants with multinutrient fortified breast milk compared with unfortified breast milk following hospital discharge affects important outcomes including growth rates during infancy. There are no data on long-term growth. Since fortifying breast milk for infants fed directly from the breast is logistically difficult and has the potential to interfere with breast feeding, it is important to determine if mothers would support further trials of this intervention.