Outcomes in very preterm infants receiving an exclusive human milk diet, or their own mother's milk supplemented with preterm formula.

Background: An infant's Own Mother's Milk (OMM) is the mainstay of very preterm nutrition. When a supplement is required, preterm formula and pasteurised human donor milk (pHDM), are options. Which is optimal is unknown.

Aims And Outcome Measures: Comparison of "survival to 34 weeks postmenstrual age (PMA) without surgery for necrotising enterocolitis (NEC)" and other outcomes, in infants receiving OMM supplemented with pHDM without bovine macronutrient fortification (exclusive human milk diet), and infants receiving OMM supplemented with preterm formula.

Design: Cohort analysis of observational data from the National Neonatal Research Database; data-adaptive Super Learner approach with Targeted Maximum Likelihood Estimation to calculate Adjusted Risk Differences (ARD) between the groups.

Participants: Infants born below 32 weeks gestation admitted to neonatal units in England and Wales between 01 and 06-2017 and 31-05-2022.

Results: Compared to the formula supplemented group (n = 7133), infants receiving an exclusive human milk diet (n = 1007), had lower survival to 34 weeks PMA without NEC surgery (ARD -98 %, 95%CI -114 to -82), higher all-cause (107 %, 91 to 122) and NEC-related mortality (10 %, 04 to 15), and lower rates of treated retinopathy of prematurity (-28 %, -34 to -23) and bronchopulmonary dysplasia (-121 %, -140 to -101).

Conclusions: The lower survival to 34 weeks PMA without NEC surgery in infants receiving an exclusive human milk diet is unexpected. We adjusted for factors that influence outcomes but cannot exclude the possibility of confounding, hence our data justify a randomised controlled trial to identify optimal supplementary feeds for very preterm infants.