Contribution of Preterm Birth to Mortality Among Neonates With Birth Defects
Authors: Benjamin Renata H. , Canfield Mark A. , Marengo Lisa K. , Agopian A. J. 
Published: August 2023

ABSTRACT
Birth defects are an important cause of death among infants who die within their first year. Among other complications associated with birth defects, mothers are at higher risk for preterm delivery, which is also associated with infant mortality. Some previous research has shown that in a population of infants with birth defects, those born at term are 3 to 4 times more likely to survive as their preterm peers. This study aimed to clarify the relationship between birth defects, infant mortality, and preterm birth using the population attributable fraction (PAF), examining the mortality risk attributable to preterm birth in infants with birth defects.
Data for this study came from the Texas Birth Defects Registry, which includes live births, still births, and pregnancy terminations with a structural birth defect or chromosomal abnormality. The sample included live-born infants with 1 or more major birth defects between January 1, 1999 and December 31, 2014. Exclusion criteria were infants with a chromosomal abnormality or diagnosed syndrome, infants missing data on gestational age or with a gestational age less than 24 weeks, and anencephaly. The final sample included 169,148 infants; of these, 40,872 were preterm (<37 weeks), 128,276 were term, and 2715 died as neonates.
Distributions of maternal and infant characteristics were significantly different between the 2 groups (P < 0.01), with more mothers of preterm infants experiencing diabetes, hypertension, multiple gestation pregnancies, or cesarean delivery. In addition, more preterm infants had multiple birth defects or congenital heart defects than their term peers. Analysis of the data included estimates of PAF for infant mortality risk attributed to 31 different birth defects, with results ranging from 12.5% to 71.9%. Highest PAF estimates were observed for anotia or microtia (71.9%; CI, 41.1–86.6), hypospadias (69.4%; CI, 53.9–79.7), talipes equinovarus (69.4%; CI, 60.0–76.6), and stenosis or atresia of the large intestine, rectum, or anal canal (69.1%; CI, 56.3–78.1). On the other hand, lowest PAF estimates included hypoplastic left heart syndrome (12.5%; CI, 8.7–16.1), coarctation of the aorta (19.7%; CI, 9.8–28.4), diaphragmatic hernia (23.8%; CI, 19.2–28.2), and holoprosencephaly (26.0%; CI, 14.5–35.9). For each defect associated with a higher PAF, a large percentage of infant deaths were those born preterm. Infants with defects that had a high PAF estimate were 11.4–17.8 times more likely to die if born preterm than term, and those with a low PAF estimate were only 1.9–2.3 times more likely to die if born preterm as opposed to full term. Overall, analysis showed that 51.7% of neonatal mortality in infants with birth defects is attributable to preterm birth. Stratified analyses performed to reduce confounders showed similar results.
The relationship between birth defects and other factors contributing to preterm delivery and infant mortality is complex, and thus this study is unable to fully characterize these relationships. The associations revealed in this analysis indicate that preterm birth is a significant contributor to infant mortality in infants with birth defects, and further research can more fully characterize this association by attempting interventions both to mitigate preterm birth and to reduce infant mortality after preterm birth. Further research might also focus on particular types of birth defects and how rates of preterm birth might be reduced in specific cases of either infant or maternal risks.