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

Abstract

OBJECTIVE-The protective role of breastfeeding against severe acute lung disease in infants is well established, but its mechanism is unclear. Most hypotheses assume that breastfeeding confers similar passive protection to every infant; however, a few observations have suggested that the benefits of breast milk against severe lung disease may differ according to gender. The objective of this study was to determine whether the effect of breastfeeding on susceptibility to severe acute lung disease among infants at high risk is different for girls and boys.METHODS-A cohort was analyzed prospectively by use of 2 different strategies: (1) predictors of first episode of rehospitalization by univariate and multivariate analyses using robust Poisson regression and (2) mean number of rehospitalizations between groups using multiple regression negative binomial models.RESULTS-A total of 119 high-risk, very low birth weight infants were enrolled. Breast milk protected girls but not boys against severe acute lung disease. The interaction between breastfeeding and gender was clinically and statistically significant, even after adjustment for variables that can Address correspondence to Fernando P. Polack, MD, Johns Hopkins University, 615 N Wolfe St, E5202, Baltimore, MD 21205. E-mail: fpolack@jhsph.edu PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Drs Klein and Bergel contributed equally to this work.The authors have indicated they have no financial relationships relevant to this article to disclose. What's Known on This SubjectThe protective role of breastfeeding against severe acute lung disease in infants is well established, but its mechanism is unclear. Most hypotheses assume that breastfeeding confers similar passive protection to every infant. What This Study AddsThis study reveals an unexpected gender-related difference in the protective effects of breast milk; suggests that severity of respiratory diseases in infancy may be amenable to modulation by a nonspecific mechanism; challenges the established dogma that the protective effect of breast milk is exerted by passive transfer of IgA; and contributes to redefine the populations of premature infants at highest risk for severe lung disease, in this case nonbreastfeeding girls. 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...

Human Rhinoviruses in Severe Respiratory Disease in Very Low Birth Weight Infants

“…In the meantime, our findings provide yet another reason to minimize risk factors for BPD. 30,[37][38][39] Infants with BPD had higher risks of HRV-associated ARI, bronchiolitis, and hospitalization. The suspected role of HRV in the inception of asthma 19,40 and the high rates of asthma in children who had BPD 1-3 stress the potentially severe predictive implications and pathologic consequences of this combination.…”

“…We gathered data prospectively by frequent and standardized clinical monitoring of all infants in the cohort, predefined criteria for evaluation of respiratory signs and symptoms and severity of illness, and monitored infants until resolution of symptoms. In addition, the seasonality of respiratory viruses in Buenos Aires resembles that of industrialized nations, 4,23,24,30 making certain generalizations possible.…”

“…29 Nasal secretions also were tested for the presence of RSV; human metapneumovirus; human parainfluenza viruses 1, 2, and 3; and influenza virus by reverse transcriptasepolymerase chain reaction by use of the Hexaplex Plus assay (Prodesse, Waukesha, WI), as described previously. 24,30 Statistical Analysis…”

Paramyxoviruses: Respiratory Syncytial Virus and Human Metapneumovirus

“…The results of epidemiologic studies on benefi t have been confl icting, although recent studies suggest that breast-feeding may have a strong protective effect only in girls [ 104 ]. The sex of the infant modulates the severity of RSV infection for additional reasons that are not fully understood.…”

Physical stature and biological living standards of girls and young women in the Netherlands, born between 1815 and 1865

“…2 A nice example illustrating interaction between environmental and biological factors comes from a study (Klein et al, 2008) showing that girls benefit more than boys from the protective effects of breast milk, but also that girls fed with baby formula are more likely to fall victim to a respiratory or lung infection than their siblings of opposite sex. The study population consisted of very low birth weight infants in the age of 30 weeks.…”