Developmental Impact of NICU Exposures (DINE)

Background: Each year in the United States, over 300,000 preterm infants are admitted to neonatal intensive care units (NICUs) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. Many life-saving and supportive respiratory, nutritional, hematologic and pharmaceutical therapies in the NICU expose preterm infants to potentially harmful chemicals during a life stage analogous to the third trimester of gestation. The NIH-funded DINE study capitalizes on the infrastructure, biorepositories, and extensive clinical databases of four existing preterm cohorts to explore the hypothesis that early life exposure to phthalates adversely impacts neurodevelopment, lung function, growth, adiposity, and pubertal development in childhood. The scientific premise of the DINE study is that early life exposure to phthalates, a class of chemical plasticizers ubiquitous in the NICU, has long-lasting harmful effects on child health and development, and that these harmful effects are magnified in children born preterm. This premise is based on strong evidence of multisystem adverse health effects in term-born children who are exposed to phthalates in utero during the third trimester of pregnancy or in early infancy. In preterm infants, however, rigorously obtained data on the health effects of phthalates are scant. Dermal, inhalational and intravenous exposures to phthalates are widespread in some NICUs, where preterm infants are cared for during the sensitive "third trimester" developmental window. Moreover, premature infants experience a high prevalence of the adverse health effects that are associated with early life exposures to phthalates in term-born children, including altered neurodevelopment, poor pulmonary function, and maladapted growth. A rigorous, well-designed, sufficiently powered study of NICU-based phthalate exposures and long-term health outcomes of preterm infants has the potential to change care practices, promote regulatory policy changes and lead to mitigation of phthalate exposures in the NICU. Significance: The proposed research is expected to identify modifiable sources of developmental risk for NICU patients that can inform and improve hospital care and long-term outcome. Moreover, our findings could lead to relatively inexpensive NICU interventions, such as use of non-phthalate containing medical materials, dosing guidelines for elemental metals and guidance for parents and staff on infant stress-reduction, and policy changes (e.g. regulation of the phthalates used in medical devices or changes to the trace metal content of parenteral nutrition) with significant positive potential impacts on life-long morbidities common among NICU graduates. Information gleaned from studying our highly-exposed, highly-vulnerable population may elucidate health impacts of early life exposures that translate to risk reduction in the general population.