Abstract
The use of birthweight standards to define small for gestational age may fail to identify neonates affected by poor fetal growth as they include births associated with suboptimal fetal growth. This study aimed to compare intrauterine vs birthweight-derived standards to define newborn small for gestational age to predict neonatal morbidity and mortality. This was a secondary analysis of a multicenter observational study of 118,422 births. Live-born singleton, nonanomalous newborns born at 23 to 41 weeks of gestation were included. Those with missing gestational age estimation or without a first- or second-trimester ultrasound to confirm dating, birthweight, or neonatal outcome data were excluded. Birthweight percentile was computed using an intrauterine standard (Hadlock) and a birthweight-derived standard (Olsen). We compared the test characteristics of small for gestational age (birthweight of <10th percentile) by each standard to predict a composite neonatal morbidity and mortality outcome (death before discharge, neonatal intensive care unit admission >48 hours, respiratory distress syndrome, sepsis, necrotizing enterocolitis, grade 3 or 4 intraventricular hemorrhage, or seizures). Severe composite morbidity was analyzed as a secondary outcome and was defined as death, neonatal intensive care unit admission >7 days, necrotizing enterocolitis, grade 3 or 4 intraventricular hemorrhage, or seizures. The areas under the curve using receiver-operating characteristic methodology and proportions of the primary outcome by small for gestational age status were compared by gestational age category at birth (<34, 34 0/7 to 36 6/7, ≥37 weeks). Of 115,502 mother-newborn dyads in the parent study, 78,203 (67.7%) were included, with most exclusions occurring because of missing or inadequate dating information, multiple gestations, or delivery outside the gestational age range. The primary composite outcome occurred in 9.5% (95% confidence interval, 9.3-9.7), and the severe composite outcome occurred in 5.3% (95% confidence interval, 5.1-5.4). Small for gestational age was diagnosed by intrauterine and birthweight-derived standards in 14.8% and 7.4%, respectively (P<.001). Neonates considered small for gestational age only by the intrauterine standard experienced the primary outcome more than twice as often as those considered non-small for gestational age by both standards (18.4% vs 7.9%; P<.001). For the prediction of the primary outcome, small for gestational age by the intrauterine standard had higher sensitivity (29% vs 15%; P<.001) but lower specificity (87% vs 93%; P<.001) than by the birthweight standard. Both standards had weak performance overall, although the intrauterine standard had a higher area under the curve (0.58 vs 0.53; P<.001). When subanalyzed by gestational age at birth, the difference in areas under the curve was only present among preterm deliveries 34 to 36 competed weeks. Neither standard demonstrated any discrimination for morbidity prediction among term births (area under the curve, 0.50 for both). When the prediction of severe morbidity was compared, the intrauterine still had better overall prediction than the birthweight standard (areas under the curve, 0.65 vs 0.57; P<.001), although this also varied by gestational age at birth. Among nonanomalous neonates, neither intrauterine nor birthweight-derived standards for small for gestational age accurately predicted neonatal morbidity and mortality, with no discriminatory ability at term. Small for gestational age intrauterine standards performed better than birthweight standards.
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