title: What is the basis for a genetic approach in neonatal disorders?
abstract: Gene-environment interactions likely account for some degree of the variance in response rates that are clinically observed with antenatal corticosteroids, breast milk prophylaxis, surfactant administration, early recognition and treatment of sepsis, utility of non-invasive ventilation, and judicious exposure to supplemental oxygen. While these therapies and practice guidelines have significantly decreased overall neonatal mortality in the NICU, they have not made a marked impact on the frequency and severity of conditions such as bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and periventricular leukomalacia. One possible explanation is that genetic factors in the neonate modulate response to external intervention or preventative agents, culminating in variable levels of injury and different degrees of resolution and repair. Gene-environment explanations are supported by the observed heritability of BPD in twin studies, but they do not differentiate the interactions between neonate and offending toxin or pathogen, from interactions between neonate and intervention or therapeutic agent. Likely, both kinds of interactions are important in determining outcome.
authors.affiliation: Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT; Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT. Electronic address: Vineet.bhandari@drexelmed.edu.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.affiliation: Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT; Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT; Department of Genetics, Yale University School of Medicine, New Haven, CT; Department of Investigative Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D059647:Gene-Environment Interaction; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases; D007234:Infant, Premature; D015931:Intensive Care, Neonatal; D007385:Intermittent Positive-Pressure Ventilation; D008297:Male; D008895:Milk, Human / Q000187:drug effects / Q000276:immunology*; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000009:adverse effects; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D012178:Retinopathy of Prematurity / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011663:Pulmonary Surfactants
keywords: BPD; IVH; NEC; PDA; RDS; ROP; Twin studies; apnea of prematurity; neonatal sepsis; premature newborn