PC1112: Associations of an Exclusive Human Milk Diet with Morbidity and Mortality in ELBW Infants Born Weighing <750 Grams: An Individual Participant Data Meta-analysis

Background: Advances in medical interventions have pushed the age of viability younger resulting in improved survival rates of ELBW infants. Yet, survival without major comorbidities remains very low among these infants. Further interventions are needed to improve their long-term quality of life. An exclusive human milk diet (EHMD) has shown promising results in clinical trials to reduce health complications of prematurity in infants weighing ≤1250 g compared to traditionally used cow milk-based fortifiers or preterm infant formulas. We hypothesized that this reduction in complications were extended to the smallest ELBW infants, born weighing < 750 g.

Methods: We conducted a systematic review with individual participant data meta-analysis on existing EHMD clinical studies. Authors from eligible studies were invited to contribute their data for infants born weighing < 750 g. The meta-analysis included RCT and observational cohort studies with control groups comprising infants fed cow milk-based nutritional products. Sensitivity analyses compared infants fed an EHMD (human milk fortified with human milk-based fortifiers from Prolacta Bioscience®) and infants fed a base diet of human milk fortified with cow milk-based fortifiers. Risk ratios and adjusted risk ratios (aRR) reported are from complete cases.

Results: To date, data from 5 unique studies have been contributed, totaling 795 infants born weighing < 750 g between 2007-2015. Of these, 401 infants received an EHMD; 394 received a diet containing cow milk-based nutritional products which may have included preterm infant formula (CMBD+f); 50 infants received a base diet of human milk fortified with cow milk-based fortifiers excluding preterm infant formula (CMBD-f). Infants fed an EHMD had significantly lower risks of RoP (stage 3/4), BPD, sepsis, morbidity/mortality index, NEC, and NEC surgery compared to infants fed CMBD+f. Compared to a diet without formula (CMBD-f), infants fed an EHMD had a 76% reduced risk of severe RoP (aRR, 0.24; 95% CI, 0.17-0.36), a 63% reduced risk of NEC (aRR, 0.37; 95% CI, 0.22-0.66), and 65% reduced risk of NEC surgery (aRR, 0.35; 95% CI, 0.20-0.67). These outcomes remained significant after adjustment for race, infant sex, and gestational age.

Conclusion: An EHMD was associated with a reduced risk of several major comorbidities in ELBW infants born weighing < 750 g compared to cow milk-based nutritional products even with a base diet of human milk.