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Director's Challenge Study on Breastfeeding and Pulmonary Disease

By Eddy Ball
July 2008

Director's Challenge Grant Principal Investigator Steve Kleeberger
Director's Challenge Grant Principal Investigator Steve Kleeberger (Photo courtesy of Steve McCaw)

The June issue of Pediatrics includes the latest findings to emerge from research funded through the NIEHS Director's Challenge Program in Integrative Research awarded in October 2006. NIEHS Laboratory of Respiratory Biology (LRB) Chief Steven Kleeberger, Ph.D., is the principal investigator for the grant, which supports work at NIEHS, the Panamerican INFANT Network at Johns Hopkins University and Fundación INFANT in Buenos Aries, Argentina.

Although some previous research had suggested that gender played a greater role in the protective effect of breastfeeding, the study results were dramatic. Breast-fed females showed a significantly lower (6.5 per cent) rehospitalization rate than males, while formula-fed females experienced a 50 percent rate, pointing to a specific avoidable risk related to gender. For males, breastfeeding made little difference in the rehospitalization rate (18.9 per cent for breast fed versus 18.5 percent for formula-fed).

Johns Hopkins infectious disease specialist Fernando Polack, M.D., was the corresponding author for the Pediatrics study( Exit NIEHS Website, which was led by M. Inés Klein, M.D., an investigator at Fundación INFANT. The research team prospectively analyzed a cohort of 119 preterm infants and young children at high risk for pulmonary disease at two treatment sites in Buenos Aires between 2003 and 2005.

As Polack explained in the paper, the scientists were exploring "the role of gender and breastfeeding on susceptibility to severe acute lung disease among intensively monitored infants at high risk." The researchers were testing the widely held hypotheses that breastfeeding confers a similar passive protection against serious lung disease to each and every infant, regardless of gender, through transfer from mother to child of immunoglobulin A or of other molecules with specific anti-infective activity.

Writing for the team, Polack identified three important implications of the findings for pediatric research. "They strongly suggest that breast milk protection against acute respiratory infections is not universally conferred by passive transfer of humoral immunity" but in a gender-specific manner instead. They also point to the possibility that a nonspecific modulatory molecule may be involved in protecting infants from several different agents involved in respiratory disease, suggesting a breast milk-mediated critical pathway in the breast-fed girls.

Finally, the findings pinpoint a subset of infants at especially high risk of hospitalization and the strikingly different effects of breast feeding on boys and girls. Although the fomula-fed girls represented only 17 percent of infants in the study, they accounted for 48 percent of all hospitalizations during the first episode of acute respiratory disease.

Identifying this especially high-risk group could have an important public health application in prevention and impact infant morbidity in developing countries, where treatment resources can be limited and where hospitalization rates for very low birth-weight infants can be higher than 25 percent during the first year of life.

Now in the second year of a five-year grant, the Director's Challenge Project involves an interdisciplinary approach to understanding respiratory diseases such as bronchopulmonary dysplasia (BPD) among premature infants and the role of specific genes that increase susceptibility to oxidant-induced inflammatory diseases affecting several of the body's systems.

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