Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

OBJECTIVES: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre-eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt-1/PlGF concentration ratio and the competing-risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. METHODS: This was a case-control study in which maternal serum GlyFn was measured in stored samples from a non-intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point-of-care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA-PI, PlGF and sFlt-1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA-PI, PlGF and sFlt-1 were converted to MoM. The competing-risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false-positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. RESULTS: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt-1) was 83.7% (95% CI, 70.3-92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8-87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA-PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4-78.3%); PE at any time: DR, 56.0% (95% CI, 45.7-65.9%)) or high sFlt-1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9-85.1%); PE at any time: DR, 63.0% (95% CI, 52.8-72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. CONCLUSION: GlyFn is a potentially useful biomarker in third-trimester screening for term PE and term GH, but the findings of this case-control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler and biomarkers of impaired placentation at 36 weeks' gestation in pregnancies with small fetuses.

OBJECTIVES: First, to compare ophthalmic artery peak systolic velocity (PSV) ratio and biomarkers of impaired placentation at 36 weeks' gestation in women who delivered a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate, in the absence of hypertensive disorder, with those of women who developed pre-eclampsia (PE) or gestational hypertension (GH) and of women unaffected by SGA, FGR, PE or GH. Second, to examine the associations of PSV ratio, uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) with birth-weight Z-score or percentile. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, UtA-PI, PlGF and sFlt-1. Values of PSV ratio, UtA-PI, PlGF and sFlt-1 were converted to multiples of the median (MoM) or delta values. Median MoM or deltas of these biomarkers in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, UtA-PI MoM, PlGF MoM and sFlt-1 MoM with birth-weight Z-score, after exclusion of PE and GH cases. RESULTS: The study population of 9033 pregnancies included 7696 (85.2%) that were not affected by FGR, SGA, PE or GH, 182 (2.0%) complicated by FGR in the absence of PE or GH, 698 (7.7%) with SGA in the absence of FGR, PE or GH, 236 (2.6%) with PE and 221 (2.4%) with GH. Compared with unaffected pregnancies, in the FGR and SGA groups, the PSV ratio delta and sFlt-1 MoM were increased and PlGF MoM was decreased; UtA-PI MoM was increased in the FGR group but not the SGA group. The magnitude of the changes in biomarker values relative to the unaffected group was smaller in the FGR and SGA groups than that in the PE and GH groups. In non-hypertensive pregnancies, there were significant inverse associations of PSV ratio delta and UtA-PI MoM with birth-weight Z-score, such that the values were increased in small babies and decreased in large babies. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small babies and high PlGF levels in large babies. There was no significant association between sFlt-1 MoM and birth-weight Z-score. CONCLUSIONS: Ophthalmic artery PSV ratio, reflective of peripheral vascular resistance, and UtA-PI, PlGF and sFlt-1, biomarkers of impaired placentation, are altered in pregnancies complicated by hypertensive disorder and, to a lesser extent, in non-hypertensive pregnancies delivering a SGA or FGR neonate. The associations between the biomarkers and birth-weight Z-score suggest the presence of a continuous physiological relationship between fetal size and peripheral vascular resistance and placentation, rather than a dichotomous relationship of high peripheral resistance and impaired placentation in small compared to non-small fetuses. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of angiogenic factors in prediction of growth-related neonatal morbidity at term and comparison with competing-risks model.

OBJECTIVES: First, to describe the distribution of biomarkers of impaired placentation in small-for-gestational-age (SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt-1/PlGF ratio or low PlGF with that of the competing-risks model for SGA in predicting growth-related neonatal morbidity. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt-1. The primary outcome was delivery within 4 weeks after assessment and at < 42 weeks' gestation of a SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt-1/PlGF ratio > 90th percentile, sFlt-1/PlGF ratio > 38 and the competing-risks model for SGA, using combinations of maternal risk factors and Z-scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt-1, were estimated. The detection rates by the different methods of screening were compared using McNemar's test. RESULTS: In the study population of 29 035 women, prediction of growth-related neonatal morbidity at term provided by the competing-risks model was superior to that of screening by low PlGF concentration or a high sFlt-1/PlGF concentration ratio. For example, at a screen-positive rate (SPR) of 13.1%, as defined by the sFlt-1/PlGF ratio > 38, the competing-risks model using maternal risk factors and EFW predicted 77.5% (95% CI, 71.7-83.3%) of SGA < 10th percentile and 89.3% (95% CI, 83.7-94.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 71.4% (95% CI, 56.5-86.4%) and 90.0% (95% CI, 76.9-100%). These were significantly higher than the respective values of 41.0% (95% CI, 34.2-47.8%) (P < 0.0001), 48.8% (95% CI, 39.9-57.7%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.035) achieved by the application of the sFlt-1/PlGF ratio > 38. At a SPR of 10.0%, as defined by PlGF < 10th percentile, the competing-risks model using maternal factors and EFW predicted 71.5% (95% CI, 65.2-77.8%) of SGA < 10th percentile and 84.3% (95% CI, 77.8-90.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95% CI, 53.1-83.9%) and 85.0% (95% CI, 69.4-100%). These were significantly higher than the respective values of 36.5% (95% CI, 29.8-43.2%) (P < 0.0001), 46.3% (95% CI, 37.4-55.2%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.021) achieved by the application of PlGF < 10th percentile. CONCLUSION: At 36 weeks' gestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt-1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal vascular indices at 36 weeks' gestation in small and growth restricted fetuses.

OBJECTIVE: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation, in pregnancies complicated by small for gestational age (SGA) fetuses and those with fetal growth restriction (FGR). METHODS: This was a prospective observational non-intervention study in women with singleton pregnancies attending for a routine hospital visit at 35+0 to 36+6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices and hemodynamic parameters obtained by a non-invasive operator independent device, including pulse wave velocity, augmention index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and fetal heart rate. Hypertensive disorders of pregnancy were excluded and the values in the SGA and FGR groups were compared between them and with unaffected pregnancies. Diagnosis of SGA was based on the birth of a baby with birthweight below the 10th percentile for gestational age. In FGR, in addition to a birthweight below the 10th percentile, at the 35-37 weeks scan Doppler studies had shown that the uterine artery or umbilical artery pulsatility index (PI) was above the 95th percentile for gestational age or the fetal middle cerebral artery PI was below the 5th percentile. RESULTS: In the 6,413 women included in the study there were 605 (9.4%) cases of SGA, 133 (2.1%) of FGR and 5,675 (88.5%) unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were also increased, whereas aortic stiffness assessed by pulse wave velocity and augmentation index did not differ between affected and unaffected pregnancies. In the FGR, compared to the SGA group, central systolic and diastolic blood pressure were higher, whereas, heart rate was lower. CONCLUSIONS: In SGA and FGR pregnancies there are deranged maternal hemodynamic responses when these are compared to normal pregnancies. Mothers with FGR babies have higher central blood pressure compared to SGA ones, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. This article is protected by copyright. All rights reserved.

Implication of third-trimester screening accuracy for small-for-gestational age and additive value of third-trimester growth-trajectory indicators in predicting severe adverse perinatal outcome in low-risk population: pragmatic secondary analysis of IRIS study.

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing-risks model.

OBJECTIVE: To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio, or the competing-risks model, which combines maternal risk factors with biomarkers to estimate patient-specific risk. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt-1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt-1/PlGF ratio (> 90th percentile); or (iii) the competing-risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt-1 ('double test') or PlGF, sFlt-1 and MAP ('triple test'). Risk cut-offs corresponded to a screen-positive rate of 10%. DRs were compared between tests. RESULTS: Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen-positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt-1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt-1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7-23.0%) and 12.4% (9.7-15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9-26.8%) and 12.9% (7.7-17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4-21.6%) and 5.4% (0.0-10.8%), respectively). The double test was superior to the sFlt-1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment. CONCLUSION: At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing-risks model triple test is superior to that of PlGF alone or the sFlt-1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Competing-risks model for prediction of small-for-gestational-age neonate at 36 weeks' gestation.

OBJECTIVES: To develop further a competing-risks model for the prediction of a small-for-gestational-age (SGA) neonate by including sonographically estimated fetal weight (EFW) and biomarkers of impaired placentation at 36 weeks' gestation, and to compare the performance of the new model with that of the traditional EFW < 10th percentile cut-off. METHODS: This was a prospective observational study in 29 035 women with a singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. A competing-risks model for the prediction of a SGA neonate was used. The parameters included in the prior-history model were provided in previous studies. An interaction continuous model was used for the EFW likelihood. A folded plane regression model was fitted to describe likelihoods of biomarkers of impaired placentation. Stratification plans were also developed. The new model was evaluated and compared with EFW percentile cut-offs. RESULTS: The performance of the model was better for predicting SGA neonates delivered closer to the point of assessment. The prediction provided by maternal factors alone was improved significantly by the addition of EFW, uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) but not by mean arterial pressure or soluble fms-like tyrosine kinase-1. At a 10% false-positive rate, maternal factors and EFW predicted 77.6% and 65.8% of SGA neonates < 10th percentile delivered before 38 and 42 weeks, respectively. The respective figures for SGA < 3rd percentile were 85.5% and 74.2%. Addition of UtA-PI and PlGF resulted in marginal improvement in prediction of SGA < 3rd percentile requiring imminent delivery. A competing-risks approach that combines maternal factors and EFW performed better when compared with fixed EFW percentile cut-offs at predicting a SGA neonate, especially with increasing time interval between assessment and delivery. The new model was well-calibrated. CONCLUSIONS: A competing-risks model provides effective risk stratification for a SGA neonate at 35 + 0 to 36 + 6 weeks' gestation and is superior to EFW percentile cut-offs. The use of biomarkers of impaired placentation in addition to maternal factors and fetal biometry results in small improvement of the predictive performance for a neonate with severe SGA. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of small-for-gestational-age neonates at 33-39 weeks' gestation in China: logistic regression modeling of the contributions of second- and third-trimester ultrasound data and maternal factors.

OBJECTIVES: A screening model for prediction of small-for-gestational-age (SGA) neonates (SGAp) was established by logistic regression using ultrasound data and maternal factors (MF). We aimed to evaluate the ability of SGAp as well as abdominal circumference (AC) and estimated fetal weight (EFW) measurements to predict SGA neonates at 33-39 weeks' gestation. METHODS: This retrospective study evaluated 5298 singleton pregnancies that had involved three ultrasound examinations at 21+0-27+6, 28+0-32+6, and 33+0-39+6 weeks. All ultrasound data were transformed to MoM values (multiple of the median). Multivariate logistic regression was used to analyze the correlation between SGA status and various variables (ultrasound data and MF) during pregnancy to build the SGAp model. EFW was calculated according to the Hadlock formula at 33-39 weeks of gestation. The predictive performance of SGAp, AC MoM value at 33+0-39+6 weeks (AC-M), EFW MoM value (EFW-M), EFW-M plus MF, AC value at 33+0-39+6 weeks (AC), AC growth velocity, EFW, and EFW plus MF was evaluated using ROC curves. The detection rate (DR) of SGA neonate with SGAp, AC-M, EFW-M, and EFW-M plus MF at false positive rate (FPR) of 5% and 10%, and the FPR at DR of 85%, 90%, and 95% were observed. RESULTS: The AUCs of SGAp, AC-M, EFW-M, EFW-M plus MF, AC, AC growth velocity, EFW, and EFW plus MF for SGA neonates screening were 0.933 (95%CI: 0.916-0.950), 0.906 (95%CI: 0.887-0.925), 0.920 (95%CI: 0.903-0.936), 0.925 (95%CI: 0.909-0.941), 0.818 (95%CI: 0.791-0.845), 0.786 (95%CI: 0.752-0.821), 0.810 (95%CI: 0.782-0.838), and 0.834 (95%CI: 0.807-0.860), respectively. The screening efficiency of SGAp, AC-M, EFW-M, and EFW-M plus MF are significantly higher than AC, AC growth velocity, EFW, and EFW plus MF. The DR of SGAp, AC-M, EFW-M, and EFW-M plus MF for SGA neonates were 80.4%, 69.6%, 73.8% and 74.3% at 10% FPR. The AUCs of SGAp, AC-M, EFW-M, and EFW-M plus MF 0.950 (95%CI: 0.932-0.967), 0.929 (95%CI: 0.909-0.948), 0.938 (95%CI: 0.921-0.956) and 0.941 (95%CI: 0.924-0.957), respectively for screening SGA neonates delivered within 2 weeks after the assessment. The DR for these births increased to 85.8%, 75.8%, 80.0%, and 82.5%, respectively. CONCLUSION: The rational use of ultrasound data can significantly improve the prediction of SGA statuses.

Routine Ultrasound at 30th-33rd weeks versus 30th-33rd and 35th-37th weeks in Low-Risk Pregnancies: A Randomized Trial.

INTRODUCTION: The aim of this study was to evaluate the accuracy of 35-37 weeks' ultrasound for fetal growth restriction (FGR) detection and the impact of 30th-33rd weeks versus 30th-33rd and 35th-37th weeks' ultrasound on perinatal outcomes. METHODS: This was a randomized controlled trial that enrolled 1,061 low-risk pregnant women: 513 in the control group (routine ultrasound performed at 30th-33rd weeks) and 548 in the study group (with an additional ultrasound at 35th-37th weeks). FGR was defined as a fetus with an estimated fetal weight (EFW) below the 10th percentile. p values < 0.05 were considered statistically significant. RESULTS: The ultrasound at 35-37 weeks had an overall accuracy of FGR screening of 94%. Spearman's correlation coefficient between EFW and birthweight centile was higher for at 35-37 weeks' ultrasound (ρ = 0.75) compared with 30-33 weeks' ultrasound (ρ = 0.44). The study group had a lower rate of operative vaginal deliveries (24.4% vs. 39.3%, p = 0.005) and cesarean deliveries for nonreassuring fetal status (16.8% vs. 38.8%, p < 0.001). DISCUSSION/CONCLUSION: A later ultrasound (35-37 weeks) had a high accuracy for detection of FGR and had a higher correlation between EFW and birthweight centiles. Furthermore, it was also associated with lower adverse perinatal outcomes compared to an earlier ultrasound.

Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of fetal abnormalities.

OBJECTIVE: To investigate the potential value of routine ultrasound examination at 35-37 weeks' gestation in the diagnosis of previously unknown fetal abnormalities. METHODS: This was a prospective study of 52 400 singleton pregnancies attending for a routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation; all pregnancies had a previous scan at 18-24 weeks and 47 214 also had a scan at 11-13 weeks. We included pregnancies resulting in live birth or stillbirth but excluded those with known chromosomal abnormality. Abnormalities were classified according to the affected major organ system, and the type and incidence of new abnormalities were determined. RESULTS: In the study population, the incidence of fetal abnormality was 1.9% (995/52 400), including 674 (67.7%) that had been diagnosed previously during the first and/or second trimester, 247 (24.8%) that were detected for the first time at 35-37 weeks and 74 (7.4%) that were detected for the first time postnatally. The most common abnormalities that were diagnosed during the first and/or second trimester and that were also observed at 35-37 weeks included ventricular septal defect, talipes, unilateral renal agenesis and/or pelvic kidney, hydronephrosis, duplex kidney, unilateral multicystic kidney, congenital pulmonary airway malformation, ventriculomegaly, cleft lip and palate, polydactyly and abdominal cyst or gastroschisis. The most common abnormalities first seen at 35-37 weeks were hydronephrosis, mild ventriculomegaly, ventricular septal defect, duplex kidney, ovarian cyst and arachnoid cyst. The incidence of abnormalities first seen at 35-37 weeks was 0.5% and those that were detected exclusively for the first time at this examination were ovarian cyst, microcephaly, achondroplasia, dacryocystocele and hematocolpos. The incidence of abnormalities first seen postnatally was 0.1% and the most common were isolated cleft palate, polydactyly or syndactyly and ambiguous genitalia or hypospadias; prenatal examination of the genitalia was not a compulsory part of the protocol. CONCLUSIONS: A high proportion of fetal abnormalities are detected for the first time during a routine ultrasound examination at 35-37 weeks' gestation. Such diagnosis and subsequent management, including selection of timing and place for delivery and postnatal investigations, could potentially improve postnatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ophthalmic artery Doppler in prediction of pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVES: First, to examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE), and, second, to examine the variability between repeat measurements in the same eye and variability in measurements between the two eyes. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history and assessment of flow velocity waveforms from the maternal ophthalmic artery. Waveforms were obtained in sequence from the right eye, left eye and again from the right and then left eye. We recorded the average of the four measurements, two from each eye, for the following four indices: first peak of systolic velocity; second peak of systolic velocity; pulsatility index; and the ratio of the second to first peak of systolic velocity (PSV ratio). The measurements of the four indices were standardized to remove the effects of maternal characteristics and elements from the medical history. The competing-risks model was used to determine the detection rate (DR) of delivery with PE at any time and at < 3 weeks after assessment, at a 10% false-positive rate (FPR), in screening by maternal factors alone and a combination of maternal factors and the adjusted value of each of the four ophthalmic artery indices. RESULTS: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The DR, at 10% FPR, of delivery with PE at any time after assessment by maternal factors was 25.0% (95% CI, 14.7-37.9%), and this increased by 25 percentage points to 50.0% (95% CI, 36.8-63.2%) with the addition of the adjusted PSV ratio (P = 0.005); the respective values for delivery with PE at < 3 weeks after assessment were 31.6% (95% CI, 12.6-56.6%) and 57.9% (95% CI, 33.5-79.8%). The other ophthalmic artery indices did not improve the prediction provided by maternal factors alone. There was good correlation between the first and second measurements of PSV ratio from the same eye (right eye r = 0.823, left eye r = 0.840), but poorer correlation in the first and second measurements between the two eyes (first measurement r = 0.690, second measurement r = 0.682). In screening by maternal factors and PSV ratio for PE with delivery at any stage after assessment, the estimated DR, at 10% FPR, was 50.0% when the average of four measurements was used (two from each eye), 49.1% when the average of one measurement from each eye was used, 47.3% when the average of two measurements from the same eye was used, and 45.8% when only one measurement was used. CONCLUSIONS: Ophthalmic artery PSV ratio at 35-37 weeks' gestation can predict subsequent delivery with PE, especially if this occurs within 3 weeks after assessment. In the assessment of ophthalmic artery Doppler, it is necessary to use the average of one measurement from each eye to minimize variability of measurements. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.

BACKGROUND: Third-trimester studies in selected high-risk pregnancies have reported that low cerebroplacental ratio, due to high pulsatility index in the umbilical artery, and or decreased pulsatility index in the fetal middle cerebral artery, is associated with increased risk of adverse perinatal outcomes. OBJECTIVE: To investigate the predictive performance of screening for adverse perinatal outcome by the cerebroplacental ratio measured routinely at 35-37 weeks' gestation. STUDY DESIGN: This was a prospective observational study in 47,211 women with singleton pregnancies undergoing routine ultrasound examination at 35+6 to 37+6 weeks' gestation, including measurement of umbilical artery-pulsatility index and middle cerebral artery-pulsatility index. The measured umbilical artery-pulsatility index and middle cerebral artery-pulsatility index and their ratio were converted to multiples of the median after adjustment for gestational age. Multivariable logistic regression analysis was used to determine whether umbilical artery-pulsatility index, middle cerebral artery-pulsatility index, and cerebroplacental ratio improved the prediction of adverse perinatal outcome that was provided by maternal characteristics, medical history, and obstetric factors. The following outcome measures were considered: (1) adverse perinatal outcome consisting of stillbirth, neonatal death, or hypoxic-ischemic encephalopathy grades 2 and 3; (2) presence of surrogate markers of perinatal hypoxia consisting of umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score <7, or admission to the neonatal intensive care unit for >24 hours; (3) cesarean delivery for presumed fetal compromise in labor; and (4) neonatal birthweight less than the third percentile for gestational age. RESULTS: First, the incidence of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, and cesarean delivery for presumed fetal compromise in labor was greater in pregnancies with small for gestational age neonates with birthweight <10th percentile compared with appropriate for gestational age neonates; however, 80%-85% of these adverse events occurred in the appropriate for gestational age group. Second, low cerebroplacental ratio <10th percentile was associated with increased risk of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, cesarean delivery for presumed fetal compromise in labor, and birth of neonates with birthweight less than third percentile. However, multivariable regression analysis demonstrated that the prediction of these adverse outcomes by maternal demographic characteristics and medical history was only marginally improved by the addition of cerebroplacental ratio. Third, the performance of low cerebroplacental ratio in the prediction of each adverse outcome was poor, with detection rates of 13%-26% and a false-positive rate of about 10%. Fourth, the detection rates of adverse outcomes were greater in small for gestational age than in appropriate for gestational age babies and in pregnancies delivering within 2 weeks rather than at any stage after assessment; however, such increase in detection rates was accompanied by an increase in the false-positive rate. Fifth, in appropriate for gestational age neonates, the predictive accuracy of cerebroplacental ratio was low, with positive and negative likelihood ratios ranging from 1.21 to 1.82, and 0.92 to 0.98, respectively; although the accuracy was better in small for gestational age neonates, this was also low with positive likelihood ratios of 1.31-2.26 and negative likelihood ratios of 0.69-0.92. Similar values were obtained in fetuses classified as small for gestational age and appropriate for gestational age according to the estimated fetal weight. CONCLUSIONS: In pregnancies undergoing routine antenatal assessment at 35-37 weeks' gestation, measurement of cerebroplacental ratio provides poor prediction of adverse perinatal outcome in both small for gestational age and appropriate for gestational age fetuses.

Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation.

BACKGROUND: Small for gestational age (SGA) neonates are at increased risk for perinatal mortality and morbidity; however, the risks can be substantially reduced if the condition is identified prenatally, because in such cases close monitoring and appropriate timing of delivery and prompt neonatal care can be undertaken. The traditional approach of identifying pregnancies with SGA fetuses is maternal abdominal palpation and serial measurements of symphysial-fundal height, but the detection rate of this approach is less than 30%. A higher performance of screening for SGA is achieved by sonographic fetal biometry during the third trimester; screening at 30-34 weeks' gestation identifies about 80% of SGA neonates delivering preterm but only 50% of those delivering at term, at a screen-positive rate of 10%. There is some evidence that routine ultrasound examination at 36 weeks' gestation is more effective than that at 32 weeks in predicting birth of SGA neonates. OBJECTIVE: To investigate the potential value of maternal characteristics and medical history, sonographically estimated fetal weight (EFW) and biomarkers of impaired placentation at 35+0- 36+6 weeks' gestation in the prediction of delivery of SGA neonates. MATERIALS AND METHODS: A dataset of 19,209 singleton pregnancies undergoing screening at 35+0-36+6 weeks' gestation was divided into a training set and a validation set. The training dataset was used to develop models from multivariable logistic regression analysis to determine whether the addition of uterine artery pulsatility index (UtA-PI), umbilical artery PI (UA-PI), fetal middle cerebral artery PI (MCA-PI), maternal serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT) would improve the performance of maternal factors and EFW in the prediction of delivery of SGA neonates. The models were then tested in the validation dataset to assess performance of screening. RESULTS: First, in the training dataset, in the SGA group, compared to those with birthweight in ≥10th percentile, the median multiple of the median (MoM) values of PlGF and MCA-PI were reduced, whereas UtA-PI, UA-PI, and sFLT were increased. Second, multivariable regression analysis demonstrated that in the prediction of SGA in <10th percentile there were significant contributions from maternal factors, EFW Z-score, UtA-PI MoM, MCA-PI MoM, and PlGF MoM. Third, in the validation dataset, prediction of 90% of SGA neonates delivering within 2 weeks of assessment was achieved by a screen-positive rate of 67% (95% confidence interval [CI], 64-70%) in screening by maternal factors, 23% (95% CI, 20-26%) by maternal factors, and EFW and 21% (95% CI, 19-24%) by the addition of biomarkers. Fourth, prediction of 90% of SGA neonates delivering at any stage after assessment was achieved by a screen-positive rate of 66% (95% CI, 65-67%) in screening by maternal factors, 32% (95% CI, 31-33%) by maternal factors and EFW and 30% (95% CI, 29-31%) by the addition of biomarkers. CONCLUSION: The addition of biomarkers of impaired placentation only marginally improves the predictive performance for delivery of SGA neonates achieved by maternal factors and fetal biometry at 35+0-36+6 weeks' gestation.

Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks.

OBJECTIVE: To assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of ultrasonographic estimated fetal weight (EFW) at 35 + 0 to 36 + 6 weeks' gestation for prediction of delivery of a small-for-gestational-age (SGA) neonate and adverse perinatal outcome. METHODS: This was a prospective study of 14 497 singleton pregnancies undergoing routine ultrasound examination at 30 + 0 to 34 + 6 and at 35 + 0 to 36 + 6 weeks' gestation. Multivariable logistic regression analysis was used to determine whether addition of growth velocity, defined as the difference in EFW Z-score or abdominal circumference (AC) Z-score between the early and late third-trimester scans divided by the time interval between the scans, improved the performance of EFW Z-score at 35 + 0 to 36 + 6 weeks in the prediction of, first, delivery of a SGA neonate with birth weight < 10th and < 3rd percentiles within 2 weeks and at any stage after assessment and, second, a composite of adverse perinatal outcome, defined as stillbirth, neonatal death or admission to the neonatal unit for ≥ 48 h. RESULTS: Multivariable logistic regression analysis demonstrated that significant contributors to the prediction of a SGA neonate were EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation, fetal growth velocity, by either AC Z-score or EFW Z-score, and maternal risk factors. The area under the receiver-operating characteristics curve (AUC) and detection rate (DR), at a 10% screen-positive rate, for prediction of a SGA neonate < 10th percentile born within 2 weeks after assessment achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks (AUC, 0.938 (95% CI, 0.928-0.947); DR, 80.7% (95% CI, 77.6-83.9%)) were not significantly improved by addition of EFW growth velocity and maternal risk factors (AUC, 0.941 (95% CI, 0.932-0.950); P = 0.061; DR, 82.5% (95% CI, 79.4-85.3%)). Similar results were obtained when growth velocity was defined by AC rather than EFW. Similarly, there was no significant improvement in the AUC and DR, at a 10% screen-positive rate, for prediction of a SGA neonate < 10th percentile born at any stage after assessment or a SGA neonate < 3rd percentile born within 2 weeks or at any stage after assessment, achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks by addition of maternal factors and either EFW growth velocity or AC growth velocity. Multivariable logistic regression analysis demonstrated that the only significant contributor to adverse perinatal outcome was maternal risk factors. Multivariable logistic regression analysis in the group with EFW < 10th percentile demonstrated that significant contribution to prediction of delivery of a neonate with birth weight < 10th and < 3rd percentiles and adverse perinatal outcome was provided by EFW Z-score at 35 + 0 to 36 + 6 weeks, but not by AC growth velocity < 1st decile. CONCLUSION: The predictive performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for delivery of a SGA neonate and adverse perinatal outcome is not improved by addition of estimated growth velocity between 32 and 36 weeks' gestation. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks.

OBJECTIVES: To evaluate the performance of ultrasonographic estimated fetal weight (EFW) at 35 + 0 to 36 + 6 weeks' gestation in the prediction of delivery of a small-for-gestational-age (SGA) neonate and assess the additive value of, first, maternal risk factors and, second, fetal growth velocity between 20 and 36 weeks' gestation in improving such prediction. METHODS: This was a prospective study of 44 043 singleton pregnancies undergoing routine ultrasound examination at 19 + 0 to 23 + 6 and at 35 + 0 to 36 + 6 weeks' gestation. Multivariable logistic regression analysis was used to determine whether addition of maternal risk factors and growth velocity, the latter defined as the difference in EFW Z-score or fetal abdominal circumference (AC) Z-score between the third- and second-trimester scans divided by the time interval between the scans, improved the performance of EFW Z-score at 35 + 0 to 36 + 6 weeks in the prediction of delivery of a SGA neonate with birth weight < 10th and < 3rd percentiles within 2 weeks and at any stage after assessment. RESULTS: Screening by EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation predicted 63.4% (95% CI, 62.0-64.7%) of neonates with birth weight < 10th percentile and 74.2% (95% CI, 72.2-76.1%) of neonates with birth weight < 3rd percentile born at any stage after assessment, at a screen-positive rate of 10%. The respective values for SGA neonates born within 2 weeks after assessment were 76.8% (95% CI, 74.4-79.0%) and 81.3% (95% CI, 78.2-84.0%). For a desired 90% detection rate of SGA neonate delivered at any stage after assessment, the necessary screen-positive rate would be 33.7% for SGA < 10th percentile and 24.4% for SGA < 3rd percentile. Multivariable logistic regression analysis demonstrated that, in the prediction of a SGA neonate with birth weight < 10th and < 3rd percentiles, there was a significant contribution from EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation, maternal risk factors and AC growth velocity, but not EFW growth velocity. However, the area under the receiver-operating characteristics curve for prediction of delivery of a SGA neonate by screening with maternal risk factors and EFW Z-score was not improved by addition of AC growth velocity. CONCLUSION: Screening for SGA neonates by EFW at 35 + 0 to 36 + 6 weeks' gestation and use of the 10th percentile as the cut-off predicts 63% of affected neonates. Prediction of 90% of SGA neonates necessitates classification of about 35% of the population as being screen positive. The predictive performance of EFW is not improved by addition of estimated growth velocity between the second and third trimesters of pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation.

BACKGROUND: Justification of prenatal screening for small-for-gestational-age (SGA) fetuses near term is based on, first, evidence that such fetuses/neonates are at increased risk of stillbirth and adverse perinatal outcome, and, second, the expectation that these risks can be reduced by medical interventions, such as early delivery. However, there are no randomized studies demonstrating that routine screening for SGA fetuses and appropriate interventions in the high-risk group can reduce adverse perinatal outcome. Before such meaningful studies can be undertaken, it is essential that the best approach for effective identification of SGA neonates is determined, and that the contribution of SGA neonates to the overall rate of adverse perinatal outcome is established. In a previous study of pregnancies undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation, we found that, first, screening by estimated fetal weight (EFW) < 10th percentile provided poor prediction of SGA neonates and, second, prediction of > 85% of SGA neonates requires use of EFW < 40th percentile. OBJECTIVES: To examine the contribution of SGA fetuses to the overall rate of adverse perinatal outcome and, to propose a two-stage approach for prediction of a SGA neonate at routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. METHODS: This was a prospective study of 45 847 singleton pregnancies undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. First, we examined the relationship between birth-weight percentile and adverse perinatal outcome, defined as stillbirth, neonatal death or admission to the neonatal unit for ≥ 48 h. Second, we used a two-stage approach for prediction of a SGA neonate and adverse perinatal outcome; in the first stage, fetal biometry was used to distinguish between pregnancies at very low risk (EFW ≥ 40th percentile) and those at increased risk (EFW < 40th percentile) and, in the second stage, the pregnancies with EFW < 40th percentile were stratified into high-, intermediate- and low-risk groups based on the results of EFW and pulsatility index in the uterine arteries, umbilical artery and fetal middle cerebral artery. Different percentiles of EFW and Doppler indices were used to define each risk category, and the performance of screening for a SGA neonate and adverse perinatal outcome in pregnancies delivered at ≤ 2, 2.1-4 and > 4 weeks after assessment was determined. We propose that the high-risk group would require monitoring from initial assessment to delivery, the intermediate-risk group would require monitoring from 2 weeks after initial assessment to delivery, the low-risk group would require monitoring from 4 weeks after initial assessment to delivery, and the very low-risk group would not require any further reassessment. RESULTS: First, although in neonates with low birth weight (< 10th percentile) the risk of adverse perinatal outcome is increased, 84% of adverse perinatal events occur in the group with birth weight ≥ 10th percentile. Second, in screening by EFW < 10th percentile, the predictive performance for a SGA neonate is modest for those born at ≤ 2 weeks after assessment (83% and 69% for neonates with birth weight < 3rd and < 10th percentiles, respectively), but poor for those born at 2.1-4 weeks (65% and 45%, respectively) and > 4 weeks (40% and 30%, respectively) after assessment. Third, improved performance of screening, especially for those delivered at > 2 weeks after assessment, is potentially achieved by a proposed new approach for stratifying pregnancies into management groups based on findings of EFW and Doppler indices (prediction of birth weight < 3rd and < 10th percentiles for deliveries at ≤ 2, 2.1-4 and > 4 weeks after assessment: 89% and 75%, 83% and 74%, and 88% and 82%, respectively). Fourth, the predictive performance for adverse perinatal outcome of EFW < 10th percentile is very poor (26%, 9% and 5% for deliveries at ≤ 2, 2.1-4 and > 4 weeks after assessment, respectively) and this is improved by the proposed new approach (31%, 22% and 29%, respectively). CONCLUSIONS: This study presents an approach for stratifying pregnancies undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation into four management groups based on findings of EFW and Doppler indices. This approach potentially has a higher predictive performance for a SGA neonate and adverse perinatal outcome than that of screening by EFW < 10th percentile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound.

OBJECTIVES: First, to evaluate and compare the performance of routine ultrasonographic estimated fetal weight (EFW) and fetal abdominal circumference (AC) at 31 + 0 to 33 + 6 and 35 + 0 to 36 + 6 weeks' gestation in the prediction of a large-for-gestational-age (LGA) neonate born at ≥ 37 weeks' gestation. Second, to assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for prediction of a LGA neonate. Third, to define the predictive performance for a LGA neonate of different EFW cut-offs on routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Fourth, to propose a two-stage strategy for identifying pregnancies with a LGA fetus that may benefit from iatrogenic delivery during the 38th gestational week. METHODS: This was a retrospective study. First, data from 21 989 singleton pregnancies that had undergone routine ultrasound examination at 31 + 0 to 33 + 6 weeks' gestation and 45 847 that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks were used to compare the predictive performance of EFW and AC for a LGA neonate with birth weight > 90th and > 97th percentiles born at ≥ 37 weeks' gestation. Second, data from 14 497 singleton pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation and had a previous scan at 30 + 0 to 34 + 6 weeks were used to determine, through multivariable logistic regression analysis, whether addition of growth velocity, defined as the difference in EFW Z-score or AC Z-score between the early and late third-trimester scans divided by the time interval between the scans, improved the performance of EFW at 35 + 0 to 36 + 6 weeks in the prediction of delivery of a LGA neonate at ≥ 37 weeks' gestation. Third, in the database of the 45 847 pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation, the screen-positive and detection rates for a LGA neonate born at ≥ 37 weeks' gestation and ≤ 10 days after the initial scan were calculated for different EFW percentile cut-offs between the 50th and 90th percentiles. RESULTS: First, the areas under the receiver-operating characteristics curves (AUC) of screening for a LGA neonate were significantly higher using EFW Z-score than AC Z-score and at 35 + 0 to 36 + 6 than at 31 + 0 to 33 + 6 weeks' gestation (P < 0.001 for all). Second, the performance of screening for a LGA neonate achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks was not significantly improved by addition of EFW growth velocity or AC growth velocity. Third, in screening by EFW > 90th percentile at 35 + 0 to 36 + 6 weeks' gestation, the predictive performance for a LGA neonate born at ≥ 37 weeks' gestation was modest (65% and 46% for neonates with birth weight > 97th and > 90th percentiles, respectively, at a screen-positive rate of 10%), but the performance was better for prediction of a LGA neonate born ≤ 10 days after the scan (84% and 71% for neonates with birth weight > 97th and > 90th percentiles, respectively, at a screen-positive rate of 11%). Fourth, screening by EFW > 70th percentile at 35 + 0 to 36 + 6 weeks' gestation predicted 91% and 82% of LGA neonates with birth weight > 97th and > 90th percentiles, respectively, born at ≥ 37 weeks' gestation, at a screen-positive rate of 32%, and the respective values of screening by EFW > 85th percentile for prediction of a LGA neonate born ≤ 10 days after the scan were 88%, 81% and 15%. On the basis of these results, it was proposed that routine fetal biometry at 36 weeks' gestation is a screening rather than diagnostic test for fetal macrosomia and that EFW > 70th percentile should be used to identify pregnancies in need of another scan at 38 weeks, at which those with EFW > 85th percentile should be considered for iatrogenic delivery during the 38th week. CONCLUSIONS: First, the predictive performance for a LGA neonate by routine ultrasonographic examination during the third trimester is higher if the scan is carried out at 36 than at 32 weeks, the method of screening is EFW than fetal AC, the outcome measure is birth weight > 97th than > 90th percentile and if delivery occurs within 10 days than at any stage after assessment. Second, prediction of a LGA neonate by EFW > 90th percentile is modest and this study presents a two-stage strategy for maximizing the prenatal prediction of a LGA neonate. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.