Customized versus Population Growth Standards for Morbidity and Mortality Risk Stratification Using Ultrasonographic Fetal Growth Assessment at 22 to 29 Weeks' Gestation

Abstract

Objective: The aim of study is to compare the performance of ultrasonographic customized and population fetal growth standards for prediction adverse perinatal outcomes.

Study design: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, in which l data were collected at visits throughout pregnancy and after delivery. Percentiles were assigned to estimated fetal weights (EFWs) measured at 22 to 29 weeks using the Hadlock population standard and a customized standard (www.gestation.net). Areas under the curve were compared for the prediction of composite and severe composite perinatal morbidity using EFW percentile.

Results: Among 8,701 eligible study participants, the population standard diagnosed more fetuses with fetal growth restriction (FGR) than the customized standard (5.5 vs. 3.5%, p < 0.001). Neither standard performed better than chance to predict composite perinatal morbidity. Although the customized performed better than the population standard to predict severe perinatal morbidity (areas under the curve: 0.56 vs. 0.54, p = 0.003), both were poor. Fetuses considered FGR by the population standard but normal by the customized standard had morbidity rates similar to fetuses considered normally grown by both standards.The population standard diagnosed FGR among black women and Hispanic women at nearly double the rate it did among white women (p < 0.001 for both comparisons), even though morbidity was not different across racial/ethnic groups. The customized standard diagnosed FGR at similar rates across groups. Using the population standard, 77% of FGR cases were diagnosed among female fetuses even though morbidity among females was lower (p < 0.001). The customized model diagnosed FGR at similar rates in male and female fetuses.

Conclusion: At 22 to 29 weeks' gestation, EFW percentile alone poorly predicts perinatal morbidity whether using customized or population fetal growth standards. The population standard diagnoses FGR at increased rates in subgroups not at increased risk of morbidity and at lower rates in subgroups at increased risk of morbidity, whereas the customized standard does not.

Figure 1:. Study inclusion flow diagram

GA, gestational age.

Figure 2:. Overlap and discordance between population and customized ultrasound growth standards and perinatal morbidity.

Panel A: Growth status and overlap with composite morbidity; Panel B: growth status and overlap with severe morbidity. The circles and areas of overlap are proportional to their respective groups’ sizes and degrees to which they overlap, except where FGR and normal growth groups overlap, which is an artifact required to maintain each groups’ circular shape. Fetuses in the “normal growth” category are those with estimated fetal weights > 10^th percentile by both population and customized standards. FGR, fetal growth restriction; GROW, gestation-related optimal weight.

Figure 3.. Relative risk of composite morbidity and FGR by BMI category.

This figure demonstrates how the relative risk increases with increasing BMI category for all variables except for FGR by Hadlock. P values are for the distribution of proportions across groups (chi-square). Relative risks by ascending BMI category are as follows: for composite morbidity: 0.63, 1 (reference), 1.2, 1.4; for severe composite morbidity: 0.33, 1 (reference), 1.1, 1.9; for FGR by Hadlock: 1.5, 1 (reference), 0.8, 1.0; FGR by GROW: 0.35, 1 (reference); 1.1, 1.5. BMI, body mass index; FGR, fetal growth restriction; GROW, gestation-related optimal weight.

Figure 4.. Relative risk of composite morbidity and FGR diagnosis by race/ethnicity

This figure demonstrates how the relative risks are similar among race/ethnicity categories for all variables except for FGR by Hadlock. P values are for the distribution of proportions across groups (chi-square). The “other/missing” group is chosen as the reference group because it has the lowest rate of composite morbidity. Relative risks for “other/missin”, White, Hispanic, and Black groups, respectively, are as follows: for composite morbidity: 1, 1.0, 1.1, 1.1; for severe composite morbidity: 1, 1.0, 1.1, 1.1; for FGR by Hadlock: 1, 0.7, 1.2, 1.3; FGR by GROW: 1, 0.9, 1.0, 0.7. For FGR by Hadlock, p<0.03 for all pairwise comparisons of Hispanic, Black, and other/missing vs White. FGR, fetal growth restriction; GROW, gestation-related optimal weight. The number of Native Americans was too small (n=8) for sub-analysis and so are not included in this table.

Figure 5.. Relative risk of composite morbidity and FGR diagnosis by neonatal sex

This figure demonstrates how the relative risks of morbidity are higher for male than female fetuses, lower for FGR by Hadlock, and similar for FGR by GROW. P values are for the distribution of proportions between groups (chi-square). The female group is chosen as the reference group because it has the lowest rate of composite morbidity. Relative risks for female and male groups, respectively, are as follows: 1, 1.2; for severe composite morbidity: 1, 1.4; for FGR by Hadlock: 1, 0.5; FGR by GROW: 1, 1.0. FGR, fetal growth restriction; GROW, gestation-related optimal weight.