1. In a large cohort of infants with birth defects, the population attributable fraction (PAF) of preterm birth for risk of neonatal death was 51.7%.
2. PAF varied substantially by specific birth defect, from 26.1% for hypoplastic left heart syndrome to 76.2% for anotia/microtia.
Evidence Rating Level: 2 (Good)
Study Rundown: Birth defects are associated with an increased risk of neonatal mortality, defined as death within 28 days of birth. The population attributable fraction (PAF) is a useful metric that assesses the role a specific exposure plays in the development of a particular outcome. In this study, the PAF of prematurity was calculated for neonatal mortality in a large cohort of about 169,000 infants with birth defects. 24.2% of these infants were born preterm. The PAF of preterm birth for neonatal mortality was 51.7% overall in infants with birth defects, indicating that about half of mortality risk was attributable to prematurity. The PAF for individual birth defects ranged from 26.1% for hypoplastic left heart syndrome to 76.1% for hypospadias and 76.2% for anotia or microtia. In general, more severe birth defects associated with higher overall mortality risk, including critical heart defects, were associated with a lower PAF of prematurity, while for less critical defects, mortality risk was more attributable to prematurity. This relationship is intuitive but had not been previously reported. Though the overall benefit of preventing preterm delivery is widely known, this study further supports efforts to avoid preterm delivery in infants with birth defects to decrease the risk of neonatal mortality.
In-Depth [retrospective cohort]: Infants born alive at 24 weeks or more gestation between 1999 and 2014 who were part of the Texas Birth Defects Registry were included. Infants with anencephaly, chromosomal abnormalities, or diagnosed syndromes were excluded. Multiple birth defects were present in 30.6% of preterm infants compared to 24.1% of term. Congenital heart defects were also more prevalent in preterm infants at 46.7% versus 34.1%. PAF was calculated using prevalence of neonatal death in the relevant group as well as the risk ratio for mortality between preterm and term infants. The 95% confidence interval (CI) for the PAF in birth defects overall was 49.4-54.0%. PAF was 19.2% for all infants born at 24-28 weeks gestation, 13.9% for 28-32 weeks, and 18.7% for 32-37 weeks.
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