Prediction of adverse perinatal outcome by fetal biometry: comparison of customized and population-based standards

Abstract

Objective: To compare the predictive performance of estimated fetal weight (EFW) percentiles, according to eight growth standards, to detect fetuses at risk for adverse perinatal outcome.

Methods: This was a retrospective cohort study of 3437 African-American women. Population-based (Hadlock, INTERGROWTH-21^st , World Health Organization (WHO), Fetal Medicine Foundation (FMF)), ethnicity-specific (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)), customized (Gestation-Related Optimal Weight (GROW)) and African-American customized (Perinatology Research Branch (PRB)/NICHD) growth standards were used to calculate EFW percentiles from the last available scan prior to delivery. Prediction performance indices and relative risk (RR) were calculated for EFW < 10^th and > 90^th percentiles, according to each standard, for individual and composite adverse perinatal outcomes. Sensitivity at a fixed (10%) false-positive rate (FPR) and partial (FPR < 10%) and full areas under the receiver-operating-characteristics curves (AUC) were compared between the standards.

Results: Ten percent (341/3437) of neonates were classified as small-for-gestational age (SGA) at birth, and of these 16.4% (56/341) had at least one adverse perinatal outcome. SGA neonates had a 1.5-fold increased risk of any adverse perinatal outcome (P < 0.05). The screen-positive rate of EFW < 10^th percentile varied from 6.8% (NICHD) to 24.4% (FMF). EFW < 10^th percentile, according to all standards, was associated with an increased risk for each of the adverse perinatal outcomes considered (P < 0.05 for all). The highest RRs associated with EFW < 10^th percentile for each adverse outcome were 5.1 (95% CI, 2.1-12.3) for perinatal mortality (WHO); 5.0 (95% CI, 3.2-7.8) for perinatal hypoglycemia (NICHD); 3.4 (95% CI, 2.4-4.7) for mechanical ventilation (NICHD); 2.9 (95% CI, 1.8-4.6) for 5-min Apgar score < 7 (GROW); 2.7 (95% CI, 2.0-3.6) for neonatal intensive care unit (NICU) admission (NICHD); and 2.5 (95% CI, 1.9-3.1) for composite adverse perinatal outcome (NICHD). Although the RR CIs overlapped among all standards for each individual outcome, the RR of composite adverse perinatal outcome in pregnancies with EFW < 10^th percentile was higher according to the NICHD (2.46; 95% CI, 1.9-3.1) than the FMF (1.47; 95% CI, 1.2-1.8) standard. The sensitivity for composite adverse perinatal outcome varied substantially between standards, ranging from 15% for NICHD to 32% for FMF, due mostly to differences in FPR; this variation subsided when the FPR was set to the same value (10%). Analysis of AUC revealed significantly better performance for the prediction of perinatal mortality by the PRB/NICHD standard (AUC = 0.70) compared with the Hadlock (AUC = 0.66) and FMF (AUC = 0.64) standards. Evaluation of partial AUC (FPR < 10%) demonstrated that the INTERGROWTH-21^st standard performed better than the Hadlock standard for the prediction of NICU admission and mechanical ventilation (P < 0.05 for both). Although fetuses with EFW > 90^th percentile were also at risk for any adverse perinatal outcome according to the INTERGROWTH-21^st (RR = 1.4; 95% CI, 1.0-1.9) and Hadlock (RR = 1.7; 95% CI, 1.1-2.6) standards, many times fewer cases (2-5-fold lower sensitivity) were detected by using EFW > 90^th percentile, rather than EFW < 10^th percentile, in screening by these standards.

Conclusions: Fetuses with EFW < 10^th percentile or EFW > 90^th percentile were at increased risk of adverse perinatal outcomes according to all or some of the eight growth standards, respectively. The RR of a composite adverse perinatal outcome in pregnancies with EFW < 10^th percentile was higher for the most-stringent (NICHD) compared with the least-stringent (FMF) standard. The results of the complementary analysis of AUC suggest slightly improved detection of adverse perinatal outcome by more recent population-based (INTERGROWTH-21^st ) and customized (PRB/NICHD) standards compared with the Hadlock and FMF standards. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

Keywords: customized fetal growth standards; estimated fetal weight; growth restriction; mechanical ventilation; neonatal intensive care unit admission; perinatal morbidity; perinatal mortality.

Figure 1:

Association between an EFW<10th percentile and adverse perinatal outcomes. Relative risk and 95% confidence intervals are shown using a forest plot. Estimated fetal weight (EFW) and percentile values are calculated as described in the Methods section.

Figure 2:

Sensitivity at fixed false-positive rate. For standards providing an exact percentile value, the test positive is based on a cut-off chosen so that the false-positive rate is 10% for each outcome considered. Sensitivity and 95% confidence intervals are shown using a forest plot.

Figure 3:

Receiver Operating Characteristic (ROC) curves for prediction of adverse neonatal outcomes. The ROC curves are constructed from the percentile values derived from each standard, and the area under the curves (AUC) is shown in the legend. The following outcomes are considered: A – Composite adverse perinatal outcomes; B – Perinatal mortality; C – NICU admission; D – Apgar score <7 at 5 minutes; E – Hypoglycemia; F – Mechanical ventilation.

Figure 3:

Receiver Operating Characteristic (ROC) curves for prediction of adverse neonatal outcomes. The ROC curves are constructed from the percentile values derived from each standard, and the area under the curves (AUC) is shown in the legend. The following outcomes are considered: A – Composite adverse perinatal outcomes; B – Perinatal mortality; C – NICU admission; D – Apgar score <7 at 5 minutes; E – Hypoglycemia; F – Mechanical ventilation.

Figure 3:

Receiver Operating Characteristic (ROC) curves for prediction of adverse neonatal outcomes. The ROC curves are constructed from the percentile values derived from each standard, and the area under the curves (AUC) is shown in the legend. The following outcomes are considered: A – Composite adverse perinatal outcomes; B – Perinatal mortality; C – NICU admission; D – Apgar score <7 at 5 minutes; E – Hypoglycemia; F – Mechanical ventilation.

Figure 3:

Receiver Operating Characteristic (ROC) curves for prediction of adverse neonatal outcomes. The ROC curves are constructed from the percentile values derived from each standard, and the area under the curves (AUC) is shown in the legend. The following outcomes are considered: A – Composite adverse perinatal outcomes; B – Perinatal mortality; C – NICU admission; D – Apgar score <7 at 5 minutes; E – Hypoglycemia; F – Mechanical ventilation.

Figure 3:

Receiver Operating Characteristic (ROC) curves for prediction of adverse neonatal outcomes. The ROC curves are constructed from the percentile values derived from each standard, and the area under the curves (AUC) is shown in the legend. The following outcomes are considered: A – Composite adverse perinatal outcomes; B – Perinatal mortality; C – NICU admission; D – Apgar score <7 at 5 minutes; E – Hypoglycemia; F – Mechanical ventilation.

Figure 3:

Receiver Operating Characteristic (ROC) curves for prediction of adverse neonatal outcomes. The ROC curves are constructed from the percentile values derived from each standard, and the area under the curves (AUC) is shown in the legend. The following outcomes are considered: A – Composite adverse perinatal outcomes; B – Perinatal mortality; C – NICU admission; D – Apgar score <7 at 5 minutes; E – Hypoglycemia; F – Mechanical ventilation.