Human Milk and Recurrent Wheeze in Black Infants Born Preterm

Background: Early childhood wheeze is a well-described consequence of preterm birth. Studies in term infants have demonstrated that human milk decreases rates of recurrent wheeze in the first year of life. The current study aims to investigate the association between human milk feeding and recurrent wheeze in black infants born between 28 0/7 and 36 6/7 weeks gestation. This population is notable in that black preterm-born infants exhibit higher rates of recurrent wheeze than their white counterparts, higher rates of prematurity, and demonstrate low rates of exclusive human milk feeding at NICU discharge. We hypothesize that human milk exerts a dose-dependent effect against recurrent wheezing phenotypes in black infants born preterm.

Methods: This is a secondary analysis of existing data from the Wheezing in Black Preterm Infants: Impact of Vitamin D Supplementation Strategy (D-Wheeze) Study. Our primary outcome is to determine the association between human milk exposure and number of wheezing episodes in infancy for black infants born between 28 0/7 and 36 6/7 weeks gestation. Secondary outcomes include the number and severity of medically attended respiratory illnesses, respiratory medication use, and recurrent wheeze. Parents completed respiratory questionnaires at 3, 6, 9, and 12 months corrected gestational age as well as monthly diet screens. We analyzed data from 277 infants. Breastfeeding status at 3 months corrected gestational age was classified as exclusive, partial, or none. The primary outcome was number of wheezing episodes at 12 months corrected gestational age. Secondary outcomes were number of medically attended respiratory illnesses, severity of medical attended respiratory illness (pediatrician vs. emergency department vs. hospitalization), and respiratory medication use. The association between breastfeeding status at 3 months of corrected gestational age and outcomes was examined by generalized linear models with adjustment for a number of key covariates and clustered analyses to account for the non-independence of twins.

Results: In adjusted linear models, there was a significant decrease in number of wheezing episodes per year for exclusively human milk fed infants as compared to infants fed exclusively formula (RR 0.260, CI 0.078-0.859). Partial human milk feeding also decreased wheezing episodes, although this effect was not significant (RR 0.742, 95% CI [0.355, 1.551]). Furthermore, exclusive human milk feeding was significantly associated with decrease in medically attended respiratory illnesses (RR 0.140, 95% CI [0.028, 0.702]).

Conclusion: There is an association between exclusive human milk feeding and decreased number of wheezing episodes in the first year of life in black infants form between 28 0/7 and 36 6/7 weeks gestational age. This association is attenuated in infants who receive formula in additional to human milk. Future analyses will explore associations between short-term exposure to human milk (i.e. in the inpatient setting only) and wheeze.