Among preeclamptic women (those with a sustained elevation of blood pressure [BP] of 140 mmHg systolic or 90 mmHg diastolic after 20 weeks' gestation, proteinuria, and edema1), detection of growth-restricted fetuses (weight less than 10th percentile for gestational age) is important because, with growth disturbances, mild diseases can become severe, fetal growth restriction (FGR) is associated with increased risk of poor perinatal outcome2 and neurodevelopmental delay,3 and conservative management of severe preeclampsia at 28 to 32 weeks' gestation depends on clinicians' ability to diagnose FGR. Fetal growth restriction can be a contraindication for expectant management of severe preeclampsia, especially very preterm disease. 4–6
Despite the importance of antenatal diagnosis of FGR among women with hypertensive disease, there is a paucity of reports on the diagnostic accuracy of identifying a growth-restricted fetus. The purpose of this case control study was to determine the accuracy of sonographic estimates of fetal weight to identify fetuses that will be born with weights below the 10th percentile to women with and without hypertensive disease of pregnancy.
Materials and Methods
During 2 years (1992–1994) at a tertiary center, subjects were identified prospectively with nonanomalous singleton gestations and vertex presentations, accurate assessment of gestational age made on the basis on sonographic examination before 24 weeks, hypertensive disease of pregnancy, and sonographic fetal measurements (biparietal diameter [BPD], femur length [FL], abdominal and head circumferences [AC, HC, respectively]) within 2 weeks of delivery. Control cases (1:1) consisted of the next women without preeclampsia but with similar gestational ages determined on the basis of early ultrasonographic examination. Patients with gestational glucose intolerance or preexisting chronic hypertension or diabetes mellitus were not excluded from analysis. The groups also were matched for those underlying complications. Subjects were recruited when admitted to the labor and delivery department.
Chronic hypertension was defined as a documented BP of 140/90 mmHg or more before 20 weeks' gestation or prescription of antihypertensive medications before conception. Superimposed preeclampsia was diagnosed if there was an elevation of 30 mmHg of systolic or 15 mmHg of diastolic pressure over the BP recorded in the first trimester with an increase in 24-hour proteinuria of 1 g or more. Women were considered preeclamptic if on two occasions at least 6 hours apart they had systolic BP of at least 140 mmHg or diastolic BP of at least 90 mmHg, and proteinuria of at least 300 mg in 24 hours. Severe preeclampsia was defined according to ACOG criteria.1 A parturient was diagnosed with eclampsia if she had grand mal seizures with other criteria of preeclampsia. Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome was defined according to the criteria of Martin and coworkers.7 Insulin-dependent diabetes (class A2) was diagnosed if patients prescribed 1800 kcal American Diabetic Association diets had fasting or 2-hour post-prandial glucose values more than 105 or 120 mg/dL, respectively. Diabetes mellitus diagnosed before pregnancy was categorized according to the White classification. Delivery before 37 weeks was considered pre-term. Fetal growth restriction and small for gestational age (SGA) were defined as sonographic predictions and actual birth weights, respectively, below the 10th percentile for gestational age.8
The accuracy of sonographically estimated fetal weights (EFWs) was measured by comparing the mean error (birth weight−the predicted weight in grams), mean standardized absolute error (absolute value of error in grams ÷ birth weight in kilograms × 1000), and percentage of predictions within 10% of birth weights. Assuming 55% of the sonographic estimates are within 10% of actual birth weight in the control group,9 275 patients were required in the two groups to detect a difference of 12% among preeclamptic women (α = .5, and β = .20). Paired or unpaired t tests or nonparametric tests (if the distribution was not Gaussian) were used and P < .05 was significant. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated; if there was one value of 0, then to make calculations possible, 0.5 was added to each cell. Sensitivity, specificity, test efficiency (portion of patients correctly assigned normal or abnormal), and positive and negative predictive values were determined.
Two hundred eighty-seven women with preeclampsia met the inclusion criteria. Among those, 145 (50.5%) had mild and 142 (49.5%) had severe preeclampsia. Both the study and control groups had 14 patients with chronic hypertension and 12 with diabetes mellitus. Table 1 shows the maternal and neonatal characteristics of the groups. The portion of nulliparas was similar in the study (103 of 287, 35.9%) and control (94 of 287, 32.5%; OR 1.15, 95% CI 0.81, 1.62) groups. In both groups, 19 (6.6%), 147 (51.2%), and 121 (42.2%) delivered before 28, between 28 and 36.9, and at 37 or more weeks, respectively. Although the sonographic estimates of the birth weights were similar between groups, actual birth weights were significantly different. In the two groups, mean error, mean standardized absolute error, and percentage of estimates within 10% of the actual weight were similar.
The incidence of SGA was significantly higher among preeclamptic women (Table 1). Of the 43 SGA infants in the study group, 63% were from pregnancies with severe preeclampsia (27 of 43), and 37% had mothers with mild disease (16 of 43). Preterm SGA infants were born significantly more often in the study (32 of 43, 74%) than in the control group (three of 13, 23%; OR 9.69 95% CI 2.25, 41.80). In the study group, sensitivity, specificity, test efficiency, and positive and negative predictive values of sonographic estimated fetal weights under 10%, to identify growth-restricted fetuses, were 10%, 98%, 84%, 50%, and 84%, respectively. The corresponding values in the control group were 0%, 99%, 94%, 0%, and 94%.
Table 2 shows the accuracy of sonographic prediction of birth weights among the two groups with and without SGA. Fetal growth restriction was detected more commonly among preeclamptic women than among controls (11.6% versus 0%; OR 4.74, 95% CI 0.25, 90.31). The mean standardized absolute error among the 43 preeclamptic women with SGA infants (158 ± 152 g/kg) was similar to that among the women with SGA infants in the control group (233 ± 206 g/kg; P = .21). Newborns with abnormal growth in the two groups had similar percentages of estimates within 10% of actual weight (51% versus 44%; OR 1.34, 95% CI 0.42, 4.27).
Parturients with preeclampsia and delivery within 28–32 weeks had significantly higher incidence of SGA infants (17%, 11 of 63) than did controls (0%; OR 27.82, 95% CI 1.60, 483.65). The sensitivity, specificity, test efficiency, and positive and negative predictive values of detecting growth-restricted fetuses were 18%, 96%, 83%, 50%, and 84%, respectively. The incidence of SGA births among severely preeclamptic women at 28–32 weeks was 23% (10 of 44), and within that group the sensitivity of detecting abnormal conditions was 20%, specificity 94%, test efficiency 77%, and positive and negative predictive values 50% and 80%, respectively. Because there were no fetuses with growth restriction in the control group, the predictive accuracy could not be calculated.
There were four major findings of this study. The incidence of FGR was significantly higher among hypertensive (15%) than among normotensive (6%) pregnancies, which is in agreement with the findings of Spinillo et al3 that among preeclamptic women the risk of having SGA infants is threefold higher than among normotensive controls. That was not surprising considering transvaginal uterine and umbilical artery Doppler studies at 12–16 weeks found high resistance in early pregnancy among those who subsequently developed hypertensive disease or delivered newborns with FGR.10 As reported by Roberts and Redman,11 among preeclamptic women, the placental abnormalities, termed atherosis, are completed by 20–22 weeks.
Among newborns of preeclamptic women, not only the AC, but BPD, HC, and FL were significantly lower among the SGA newborns than among those of normal weight (Table 2), which was surprising, considering gestational age was similar among hypertensive women with and without FGR, and with hypertensive disease, FGR is asymmetrical. A possible explanation for that finding is that FGR occurs early in gestation and affects all biometric characteristics. That hypothesis is consistent with the abnormal Doppler findings at 12–16 weeks10 among women who subsequently developed hypertensive disease, and the fact that atherosis in the placental vessel is present by 20–22 weeks.11
Overall accuracy of estimating birth weights sonographically was similar between the groups (Table 1) and among newborns with weights above the 10th percentile (Table 2). However, inaccuracy of fetal weight estimation is significantly higher among pregnancies with FGR than among those without (Table 2). Regardless of group, SGA fetuses had similar error, mean standardized absolute error, and percentage of estimates within 10% of birth weights, which indicated that the accuracy of sonographic estimates was related to growth abnormalities and not hypertension or preeclampsia. In the study and control groups, newborns with growth abnormalities had negative mean errors (−205 ± 365 and −286 ± 515 g, respectively) indicating that sonographic predictions were overestimates, whereas neonates with normal growth had positive mean errors (34 ± 413 and 62 ± 394 g, respectively) indicating underestimation. A possible reason for the higher inaccuracy among fetuses with growth below the 10th percentile is that regression equations, used to calculate the sonographic estimates of weight, were derived from fetuses with normal growth.12 Decreased soft tissue with FGR might render predictions of birth weight intrinsically inaccurate.
The most important finding of the study was that antenatal detection of FGR was poor. Overall, the sensitivity of sonographic estimates of fetal weights under 10% for gestational age to detect FGR was only 10%, with a positive predictive value of 50%. Among all preeclamptic women at 28–32 weeks, the corresponding values were 18% and 50%, respectively. For women with severe preeclampsia at 28–32 weeks, the sensitivity of detecting FGR was 20%, and the positive predictive value only 50%. The inability to reliably and consistently detect abnormal growth in a majority of cases was reported by other investigators. David et al13 found that the sensitivity of sonographically estimated fetal weights (derived from 26 models) below 10% for gestational age ranged from 0 to 57%. Using the model proposed by Hadlock et al,12 those authors found a sensitivity of 23%. The following observation also lends credence to the poor ability to identify FGR antenatally: Among 68 women with severe preeclampsia managed expectantly, Chari et al5 reported delivery of 15 (22%) newborns with weight below 10% and none of them were detected before delivery.
If sonographic estimation of birth weight is a poor means of detecting FGR, it is reasonable to ask if other methods have better accuracy. Chang et al14 did a 15-year review of English language journals to find the most appropriate ultrasonic measurement for predicting FGR. After analyzing 117 articles, the authors concluded that placental grading, decreased amniotic fluid volume, reduced total intrauterine volume, and Doppler waveform indices did not have as high a sensitivity or predictive accuracy as AC or estimated fetal weight under 10% for gestational age. Schucker et al6 recently reported that among 136 patients with severe preeclampsia managed expectantly for at least 48 hours, an amniotic fluid index no more than 5.0 cm on admission had a sensitivity of 14% for FGR detection. Thus, accurate antenatal diagnosis of FGR remains problematic.
There are several limitations of this study that should be acknowledged. One shortcoming is that residents, maternal-fetal fellows, and sonographers undertook ultrasonographic examinations. Although it is possible that estimates of sonographers were more accurate than those of physicians in training, prospective studies have not confirmed this.9 It is unlikely that even if sonographers performed all the biometric measurements the detection of FGR would have improved. We acknowledge that the definition of FGR is variable. Some investigators consider FGR to be birth weight below 5%,5 10%,4,6,13,14 or 15%.15 We selected the criterion of neonatal weight of less than 10% for FGR because it is used most commonly. It is unlikely our findings would be different if another threshold were chosen, although future studies are needed to confirm them. Clinical management schemes that presume antenatal diagnosis of FGR is reliable should be used with caution.
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