PROJECT SUMMARY/ABSTRACT Multiple clinical studies have found an association between antibiotic exposures in infancy and atopic disorders. Studies have also demonstrated a reduced resistance to subsequent infections after antibiotic therapy for culture-negative infection. Past studies have focused on either prenatal antibiotics given to the mother during pregnancy, or on childhood antibiotics, with little investigation of perinatal antibiotic exposure given to mothers at the time of labor and to neonates immediately after birth. Antibiotic effect on childhood diseases is likely mediated by alteration of host microflora diversity, adversely impacting the development of immune responses. The immediate period after birth is a critical time for immune system interaction with key microflora taxa and alterations are most likely to have enduring effects. Perinatal antibiotics have been shown to cause significant changes in the neonatal gut microbiome that persist for weeks after birth. The increasing use of intrapartum and neonatal antibiotics to prevent early-onset neonatal bacterial infection means that ~30% of newborns are now exposed to antibiotics around the time of birth. This widespread use of perinatal antibiotics may have a significant effect of childhood outcomes of atopic and infectious diseases that has not yet been investigated. We hypothesize that perinatal antibiotic exposures will be associated with a higher incidence of atopic diseases and pediatric office visits due to physician-diagnosed infection. Our first specific aim will address the relationship of perinatal antibiotics to the clinical diagnosis of atopic disorders in the first five years of life. Our second specific aim is to measure the impact of perinatal antibiotics on non-preventative care office visits due to the commonest physician-diagnosed childhood infections. To achieve our aims, we will form a birth cohort of term infants delivered from 2007-2012 at the 2 main birthing centers referring newborns to The Children’s Hospital of Philadelphia (CHOP) pediatric care network. We will leverage CHOP’s large integrated electronic health records from over 31 centers to follow infants from their birthing admissions until 5 years of age and form a detailed longitudinal database spanning obstetrical, neonatal and childhood health care data. Using this database we will determine the difference in incidence of any atopic diagnosis and episodes of non-preventative health visits due to infections among infants with and without exposure to perinatal antibiotics. Perinatal antibiotic exposures are provided to mothers and their newborns with the assumption that they constitute safe approaches to the prevention of a neonatal infection, a low incidence but high morbidity disease. The results of our study may have a profound impact the perceived safety of early antibiotic exposures, and could result in a major revision of newborn clinical practice.