Differential Gender Response to Respiratory Infections and to the Protective Effect of Breast Milk in Preterm Infants

Viral respiratory infections are the main pediatric cause of hospitalization in infants and young children during the winter worldwide.1 In particular, very low birth weight (VLBW) infants are at high risk for severe viral lung disease.2–4 Although respiratory infections are a serious threat to VLBW infants everywhere, the rate of severe presentations is higher in infants who live in developing countries.4,5 Unlike in industrialized nations,2–4 preterm infants in developing countries often lack access to prophylaxis against respiratory syncytial virus (RSV)5 and have low immunization rates against influenza virus.6 Virus-specific preventive interventions against other agents are not available. Hospitalization rates for VLBW infants in developing countries can exceed 25% during the first year of life.5,7 The protective role of breastfeeding against severe respiratory infections in healthy term infants is well established.8,9 In VLBW infants, a similar beneficial effect has been described.10 For all of these populations, the mechanism of breast milk–mediated protection is unclear. A widely accepted hypothesis attributes the effect of breast milk to neutralization of infectious agents by passively transferred secretory immunoglobulin A in the respiratory tract of exposed infants.9,11–13 Alternative theories attribute protection to the passive transfer of other molecules with anti-infective activity.14–16 All of these hypotheses assume that breastfeeding confers similar passive protection to each and every infant; however, a few observations in recent years suggested that the benefits of breast milk against acute lung disease may differ according to gender.17,18 If confirmed, then these gender differences could challenge the current theories that postulate a passive mechanism of breast milk–mediated protection and identify certain subgroups of infants who are at higher risk for severe disease (ie, those not protected by breast milk). We present the results of a prospective cohort study designed to determine the role of gender and breastfeeding on susceptibility to severe acute lung disease among intensively monitored infants at high risk.