Preterm formulas that are available today have been designed to match the composition of human milk with respect to calories and nutrients that are needed for the growth and development of preterm infants. However, these synthesized formulas do not provide the non-nutrient components of human milk such as secretory IgA, lysozyme, oligosaccharides, polyunsaturated fatty acids, and platelet-activating factor (PAF)-acetylhydrolase. These non-nutrient components of human milk contribute to GI mucosal integrity, function, and boost immunity against various GI infections. The AAP policy statement in 2012 on breast feeding and the use of human milk recommends human milk for term, preterm and other high risk infants either by direct breastfeeding and or by expressed breast milk.5
The AAP statement also indicated that donor human milk might be a suitable alternative for infants whose mothers are unable or unwilling to provide their own milk.5
There is much data to suggest that human milk provides long-term benefits in term infants by lowering the incidence of sudden infant death syndrome, childhood infectious diseases (respiratory tract infections, otitis media, GI infection), allergic diseases, celiac disease, inflammatory bowel disease, obesity, etc.5
In addition to these long-term benefits, preterm infants may also benefit in the short-term from the non-nutritive components of human milk by reduced susceptibility to sepsis or to NEC. However, there are currently no randomized controlled studies comparing the effect of mother’s own milk (not donor milk) with formula on the incidence of NEC and mortality.6
Several randomized controlled trials have been done to study the effect of donor human milk versus formula on the incidence of NEC and mortality in preterm infants. Meta-analysis of five of those randomized controlled trials comparing donor milk versus formula feeds in preterm infants showed that preterm infants fed with formula had more than twice the incidence of NEC (relative risk of 2.5 [95 % CI:1.2 to 5.1], number needed to harm was 33 [95% CI:17 to 100]) compared to the preterm infants fed with human milk.7
The results of this meta-analysis underscore the importance of human milk intake in preterm infants.
Even though human milk intake reduces the risk of NEC, such reductions can only be achieved if preterm infants receive a certain minimal volume or proportion of their enteral feed as human milk. This dose-related benefit of human milk intake was evaluated in a secondary analysis of 1272 extremely low birth weight (ELBW) infants enrolled in the NICHD Glutamine Trial.8
In this study population, approximately 13 percent of ELBW infants died or developed NEC 14 days after birth. For each 10% increase in the proportion of total intake as human milk, there was a reduction in NEC or death after 14 days by a factor of 0.83 [95 % CI: 0.72 to 0.96].8
Similar results were also shown in a prospective cohort study by Sisk et al, in which 10 percent of VLBW infants who received less than 50 percent of their total enteral intake as human milk developed NEC whereas only 3 percent of infants who received more than 50 percent as human milk developed NEC.9
The odds of NEC decreased by 38% for every 25% increase in proportion of human milk in the first 14 days9
. Overall, after adjustment for gestational age, higher human milk intake was associated with a lower risk of NEC (OR 0.17 [95% CI: 0.04 to 0.68], P<0.01).9
Quality of Evidence (I)
Recommendation Grade (A):
The evidence is very strong in favor of human milk (donor) compared to artificial formula in reducing the incidence of NEC in preterm infants. Even though such benefit is yet to be proven for mother’s own milk by randomized controlled trials, we can strongly recommend based on existing evidence from donor human milk that the mother should be encouraged and persuaded to feed her preterm infant with preferably her own milk, or with donor human milk if she is unable or unwilling to feed with her own milk.