Role of Doppler ultrasound at time of diagnosis of late-onset fetal growth restriction in predicting adverse perinatal outcome: prospective cohort study.

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >−11 mEq/mL, or neonatal intensive care unit admission). Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512–0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507–0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.

Introduction: Fetal growth restriction (FGR) is a major obstetric complication associated with an increased risk of adverse perinatal outcomes. Objectives: This study aimed to evaluate the relationship between Doppler parameters, including the cerebroplacental ratio (CPR), umbilicocerebral ratio (UCR), and cerebro-placental-uterine ratio (CPUR), with adverse perinatal outcomes in singleton pregnancies complicated by FGR. Patients and Methods: This was a prospective study of 100 women with a singleton pregnancy 28 and 36.8 weeks of gestation was complicated by FGR and mild abnormalities. Feto-maternal Doppler examinations were conducted by the CPR, UCR, and CPUR parameters. Adverse outcomes were defined as Apgar score &lt;7 at 5 minutes, preterm birth &lt;37-week, neonatal intensive care unit (NICU) admission, fetal distress, and emergency cesarean section. These outcome parameters were checked with the results of the last ultrasound which performed 1-2 weeks before delivery. Results: Mean umbilical artery pulsatility index (UA-PI) (1.18±0.31 versus 1.04±0.21, P=0.010) and mean uterine arteries (UtAs)-PI (1.18±0.45 versus 0.96±0.36, P=0.20) were significantly higher in pregnancies that experienced adverse perinatal outcomes than those that did not experience them. Mean CPUR (1.82±1.03 versus 2.25±0.83, P=0.039) was significantly lower in pregnancies that experienced adverse perinatal outcomes versus those that did not. In binary multivariate logistic regression analysis, CPR, UCR, and CPUR parameters were evaluated with adverse perinatal outcomes. Only CPUR had a significant relationship with adverse perinatal outcomes. CPUR had a substantial relationship with Apgar score &lt;7 at 5 minutes (OR: 0.13; 95% CI: 0.02-0.63; P=0.012). Conclusion: CPUR is a new Doppler ratio associated with adverse perinatal outcomes in FGR pregnancies with minimal abnormalities.

Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies

This study aimed to validate the Prince of Songkla University (PSU) risk-scoring model for predicting adverse perinatal outcomes in pregnancies with an antenatal diagnosis of fetal growth restriction (FGR) in an independent cohort. A retrospective study was conducted on 121 non-anomalous singleton pregnancies affected by FGR between July 2022 and April 2024. The predictive performance of the PSU risk-scoring model, which combines maternal factors and simple ultrasound measurements to predict adverse perinatal outcomes in FGR, was evaluated by applying the original model to this independent cohort. Model variables included a history of hypertensive disorders of pregnancy (HDP) (1 point), chronic hypertension (3 points), HDP (2 points), maternal weight gain <8 kg (1 point), early-onset FGR (1 point), estimated fetal weight < 5th percentile (2 points), amniotic fluid index <5 cm (3 points), and abnormal umbilical artery Doppler (2 points). Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC). Sensitivity and specificity were calculated at different cut-off values. Median (interquartile range) gestational age at FGR diagnosis was 29 (22-39) weeks. Adverse perinatal outcomes occurred in 35 cases (28.9%). A cut-off score of 2 provided the highest sensitivity (85.7%) with a specificity of 51.2% for predicting adverse perinatal outcomes, with an AUC of 0.809 (95% confidence interval 0.714-0.905). This study confirms the predictive performance of the PSU risk-scoring model for adverse perinatal outcomes in FGR pregnancies, highlighting its potential to identify at-risk patients for referral, particularly in low-resource settings.

ABSTRACTObjectivesFirst, to compare published Doppler reference charts of the ratios of flow in the fetal middle cerebral and umbilical arteries (i.e. the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR)). Second, to assess the association of thresholds of CPR and UCR based on these charts with short‐term composite adverse perinatal outcome in a cohort of pregnancies considered to be at risk of late preterm fetal growth restriction.MethodsStudies presenting reference charts for CPR or UCR were searched for in PubMed. Formulae for plotting the median and the 10th percentile (for CPR) or the 90th percentile (for UCR) against gestational age were extracted from the publication or calculated from the published tables. Data from a prospective European multicenter observational cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks' gestation, in which fetal arterial Doppler measurements were collected longitudinally, were used to compare the different charts. Specifically, the association of UCR and CPR thresholds (CPR < 10th percentile or UCR ≥ 90th percentile and multiples of the median (MoM) values) with composite adverse perinatal outcome was analyzed. The association was also compared between chart‐based thresholds and absolute thresholds. Composite adverse perinatal outcome comprised both abnormal condition at birth and major neonatal morbidity.ResultsTen studies presenting reference charts for CPR or UCR were retrieved. There were large differences between the charts in the 10th and 90th percentile values of CPR and UCR, respectively, while median values were more similar. In the gestational‐age range of 28–36 weeks, there was no relationship between UCR or CPR and gestational age. From the prospective observational study, 856 pregnancies at risk of late‐onset preterm fetal growth restriction were included in the analysis. The association of abnormal UCR or CPR with composite adverse perinatal outcome was similar for percentile thresholds or MoM values, as calculated from the charts, and for absolute thresholds, both on univariable analysis and after adjustment for gestational age at measurement, estimated fetal weight MoM and pre‐eclampsia. The adjusted odds ratio for composite adverse perinatal outcome was 3.3 (95% CI, 1.7–6.4) for an absolute UCR threshold of ≥ 0.9 or an absolute CPR threshold of < 1.11 (corresponding to ≥ 1.75 MoM), and 1.6 (95% CI, 0.9–2.9) for an absolute UCR threshold of ≥ 0.7 to < 0.9 or an absolute CPR threshold of ≥ 1.11 to < 1.43 (corresponding to ≥ 1.25 to < 1.75 MoM).ConclusionsIn the gestational‐age range of 32 to 36 weeks, adjustment of CPR or UCR for gestational age is not necessary when assessing the risk of adverse outcome in pregnancies at risk of fetal growth restriction. The adoption of absolute CPR or UCR thresholds, independent of reference charts, is feasible and makes clinical assessment simpler than if using percentiles or other gestational‐age normalized units. The high variability in percentile threshold values among the commonly used UCR and CPR reference charts hinders reliable diagnosis and clinical management of late preterm fetal growth restriction. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

This study aims to evaluate the clinical utility of the Middle Cerebral Artery Diastolic Deceleration Area (MCA DDA) as a novel Doppler parameter for predicting hypoxia and adverse perinatal outcomes in pregnancies complicated by Fetal Growth Restriction (FGR). A prospective observational study was conducted at the Perinatology Clinic of Ankara Bilkent City Hospital between November 2023 and November 2024. A total of 102 singleton pregnancies were enrolled, including 51 FGR cases and 51 gestational age-matched controls. All participants underwent comprehensive ultrasonographic and Doppler assessments at 34 weeks of gestation. Doppler parameters, including Umbilical Artery Pulsatility Index (UA PI), Middle Cerebral Artery Pulsatility Index (MCA PI), Cerebroplacental Ratio (CPR), Cerebroplacental-Uterine Ratio (CPUR), and the novel MCA DDA, were recorded. Receiver Operating Characteristic (ROC) analysis was performed to evaluate the predictive performance of these parameters for composite adverse perinatal outcomes (CAPO), which included NICU admission, 5-min Apgar score < 7, umbilical artery pH < 7.20, and perinatal mortality. MCA DDA was significantly higher in the FGR group (9.26 ± 2.31) compared to controls (7.49 ± 2.98, p < 0.001). ROC analysis revealed that MCA DDA had an area under the curve (AUC) of 0.63 (95% CI: 0.52-0.75, p = 0.023) with an optimal cut-off value of 8.43 (sensitivity 63.6%, specificity 61.0%). In comparison, CPR demonstrated superior predictive performance with an AUC of 0.71 (95% CI: 0.59-0.82, p = 0.001), while CPUR showed an AUC of 0.66 (95% CI: 0.55-0.78, p = 0.006). The FGR group had significantly higher rates of CAPO (80%) and NICU admissions (42.2%) compared to the control group (p < 0.001). While MCA DDA is significantly elevated in FGR cases and provides valuable insights into cerebral diastolic blood flow, its predictive ability for adverse perinatal outcomes is moderate compared to traditional Doppler indices like CPR and CPUR. Integrating MCA DDA with established parameters may enhance fetal surveillance and improve perinatal outcome prediction in pregnancies complicated by FGR.

Middle Cerebral Artery–to–Uterine Artery Pulsatility Index Ratio and Cerebroplacental Ratio Independently Predict Adverse Perinatal Outcomes in Pregnancies at Term

Introduction: Our objective was to evaluate the strength of association and diagnostic performance of cerebroplacental ratio (CPR) in predicting the outcome of pregnancies complicated by pre- and gestational diabetes mellitus. Methods: PubMed, Embase, Cochrane, and Google Scholar databases were searched. Inclusion criteria were pregnancies complicated by gestational or pregestational diabetes undergoing ultrasound assessment of CPR. The primary outcome was a composite score of perinatal mortality and morbidity as defined by the original publication. The secondary outcomes included preterm birth gestational age (GA) at birth, mode of delivery, fetal growth restriction (FGR) or small for GA (SGA) newborn, neonatal birthweight, perinatal death (PND), Apgar score <7 at 5 min, abnormal acid-base status, neonatal hypoglycemia, admission to neonatal intensive care unit (NICU). Furthermore, we aimed to perform a number of sub-group analyses according to the type of diabetes (gestational and pregestational), management adopted (diet insulin or oral hypoglycemic agents), metabolic control (controlled vs. non-controlled diabetes), and fetal weight (FGR, normally grown, and large for GA fetuses). Head-to-head meta-analyses were used to directly compare the risk of each of the explored outcomes. For those outcomes found to be significant, computation of diagnostic performance of CPR was assessed using bivariate model. Results: Six studies (2,743 pregnancies) were included. The association between low CPR and adverse composite perinatal outcome was not statistically significant (p = 0.096). This result did not change when stratifying the analysis using CPR cut-off below 10th (p = 0.079) and 5th (p = 0.545) centiles. In pregnancies complicated by GDM, fetuses with a low CPR had a significantly higher risk of birthweight <10th percentile (OR: 5.83, 95% confidence interval [CI] 1.98–17.12) and this association remains significant when using a CPR <10th centile (p < 0.001). Fetuses with low CPR had also a significantly higher risk of PND (OR: 6.15, 95% CI 1.01–37.23, p < 0.001) and admission to NICU (OR 3.32, 95% CI 2.21–4.49, p < 0.001), but not of respiratory distress syndrome (p = 0.752), Apgar score <7 at 5 min (p = 0.920), abnormal acid-base status (p = 0.522), or neonatal hypoglycemia (p = 0.005). These results were confirmed when stratifying the analysis including only studies with CPR <10th centile as a cut-off to define abnormal CPR. However, CPR showed a low diagnostic accuracy for detecting perinatal outcomes. Conclusion: CPR is associated but not predictive of adverse perinatal outcome in pregnancies complicated by gestational diabetes. The findings from this systematic review do not support the use of CPR as a universal screening for pregnancy complication in women with diabetes.

To explore the predictive capacity of fetoplacental Doppler at 37 weeks' gestation in identifying small-for-gestational-age (SGA) neonates, fetal growth restriction (FGR) and adverse perinatal outcome. This was a prospective cohort study of low-risk singleton pregnancies undergoing ultrasound assessment at 37 weeks. At study inclusion, biometry for estimated fetal weight (EFW), and fetoplacental Doppler variables (uterine artery pulsatility index (UtA-PI), cerebroplacental ratio (CPR) and umbilical vein blood flow (UVBF) normalized by EFW) were measured. SGA was defined as a customized birth weight between the 3rd and 10th centiles, and FGR was defined as a birth weight < 3rd centile, according to local standards. Adverse perinatal outcomes included emergency Cesarean section for non-reassuring fetal status, 5-min Apgar score < 7 and neonatal acidosis at birth. A total of 946 pregnancies were included in the study. Of these, 89 (9.4%) were classified as SGA and 40 (4.2%) as FGR, with an overall rate of adverse perinatal outcome of 4.9%. At a fixed 10% false-positive rate (FPR), the detection rate of SGA by EFW, UtA-PI, CPR, UVBF and by a combination of Doppler variables (UtA-PI and CPR) and EFW was 59.2%, 10.5%, 13.7%, 3.2% and 61.0%, respectively. At a fixed 10% FPR, the detection rate of FGR by EFW, UtA-PI, CPR, UVBF and a combination of CPR and EFW centile was 83.3%, 13.9%, 27.8%, 13.9% and 88.6%, respectively. At a fixed 10% FPR, the detection rate of adverse perinatal outcome by EFW, UtA-PI, CPR and UVBF was 19.2%, 9.2%, 23.1% and 16.9%, respectively, while combining EFW with Doppler variables (including CPR and UVBF normalized by EFW) improved the detection rate to nearly 30%. In low-risk pregnancies, Doppler evaluation at 37 weeks' gestation did not improve the prediction of SGA and FGR compared with that given by EFW alone, however, combining Doppler variables with EFW improved the prediction of adverse perinatal outcomes given by these parameters alone, although not markedly. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term. Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36+0 and 37+6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data. In all, 600 consecutive singleton pregnancies from 36weeks of gestation were included in the study. Mean MCA PI (1.1± 0.2 vs 1.5± 0.4, P<0.001) and cerebroplacental ratio (1.4± 0.4 vs 1.9± 0.6, P<0.001) were lower, whereas uterine arteries PI (0.8±0.2 vs 0.7±0.3, P=0.001) was higher in pregnancies experiencing than in those not experiencing composite adverse outcome. Conversely, there was no difference in either UA PI (P=0.399) or estimated fetal weight centile (P=0.712) between the two groups, but AC centile was lower in fetuses experiencing composite adverse outcome (45.4 vs 53.2, P=0.040). At logistic regression analysis, MCA PI (odds ratio [OR] 0.1, 95% CI 0.01-.2, P=0.001), uterine arteries PI (OR 1.4, 95% CI 1.2-1.6, P=0.001), abdominal circumference centile (OR 1.12, 95% CI 1.1-1.4, P=0.001) and gestational age at birth (OR 1.6, 95% CI 1.2-2.1, P=0.004) were independently associated with composite adverse outcome. Despite this, the diagnostic accuracy of Doppler in predicting adverse pregnancy outcome at term was poor. MCA PI and cerebroplacental ratio are associated with adverse perinatal outcome at term. However, their predictive accuracy for perinatal compromise is poor, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.

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. This was a retrospective cohort study of 3437 African-American women. Population-based (Hadlock, INTERGROWTH-21st , 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 < 10th and > 90th 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. 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 < 10th percentile varied from 6.8% (NICHD) to 24.4% (FMF). EFW < 10th 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 < 10th 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 < 10th 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-21st 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 > 90th percentile were also at risk for any adverse perinatal outcome according to the INTERGROWTH-21st (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 > 90th percentile, rather than EFW < 10th percentile, in screening by these standards. Fetuses with EFW < 10th percentile or EFW > 90th 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 < 10th 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-21st ) 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.

Diagnosis and management of fetal growth restriction: the ISUOG guideline and comparison with the SMFM guideline.

We thank Prof. Lees et al. for their comments regarding our study1 in which we endeavored to apply the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)2 and Society for Maternal–Fetal Medicine (SMFM)3 definitions of fetal growth restriction (FGR) to a pre-existing cohort of patients with the aim to compare their performance in predicting neonatal small-for-gestational age (SGA) and composite adverse neonatal outcome. As outlined in the Discussion, our study has limitations. In table S1 of the study, we report that six of the 53 fetuses with late-onset FGR according to the ISUOG definition had estimated fetal weight (EFW) or fetal abdominal circumference (AC) crossing centiles of more than 2 quartiles on growth centiles. Our group has previously compared the ability of the Delphi criteria for FGR (including AC or EFW crossing > 2 quartiles) with that of EFW < 10th percentile for gestational age to predict neonatal SGA, and did not find the Delphi criteria to be a better predictor4. Furthermore, other studies have shown that the addition of fetal growth velocity between 20 and 36 weeks' gestation does not improve the ability of EFW at 35–37 weeks to predict delivery of a SGA neonate5. Lees et al. also questioned the utilization of neonatal SGA as a proxy for FGR. We agree with the authors that most fetuses with EFW or AC < 10th percentile but > 3rd percentile for gestational age and normal fetal surveillance (umbilical artery Doppler, non-stress test or biophysical profile) are less likely to have poor perinatal outcome. However, the optimal way to incorporate Doppler evaluation of the middle cerebral artery, uterine artery and ductus venosus, or the cerebroplacental ratio, in the management of early- and late-onset FGR is not yet clear6-8. We also agree that labeling more fetuses as being growth restricted may not reflect an increase in the detection of those fetuses that truly have placental pathology and would benefit from early intervention. Nevertheless, in our study, we aimed to compare the performance of the different diagnostic criteria for FGR of the two leading governing bodies in fetal medicine. Lastly, we agree that the prediction of adverse outcome in FGR pregnancies, especially those with late-onset FGR, is poor by both definitions of FGR. Unfortunately, the optimal definition and management protocol for FGR remains elusive and we acknowledge that some of the guidelines developed by both the SMFM and ISUOG for the diagnosis and management of FGR are not supported by high-level evidence. However, the simplicity of the SMFM diagnostic criteria, which are based on only AC and/or EFW, makes easier their implementation across the globe.

To develop and validate an index predictive of adverse perinatal outcome (APO) in pregnancies meeting the consensus-based criteria for fetal growth restriction (FGR) endorsed by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). This was a retrospective analysis of consecutive singleton non-anomalous gestations meeting the ISUOG-endorsed criteria for FGR at a single tertiary care center from November 2010 to August 2020. The dataset was divided randomly into a development set (two-thirds) and a validation set (one-third). The primary composite APO comprised one or more of: perinatal demise, Grade III-IV intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), seizures, hypoxic ischemic encephalopathy (HIE), necrotizing enterocolitis (NEC), sepsis, bronchopulmonary dysplasia (BPD) and length of stay in the neonatal intensive care unit (NICU) > 7 days. Regression analysis incorporated clinical factors readily available at the time of FGR diagnosis. The sum of β coefficient-based weights yielded an index score, the performance of which was assessed in the validation set. Score cut-offs were selected to identify 'high-risk' and 'low-risk' ranges for which positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios were calculated. Of the 875 consecutive pregnancies that met the criteria for FGR and were included in the study cohort, 405 (46%) were complicated by one or more components of the composite APO, including 54 (6%) perinatal deaths, 22 (3%) neonates with Grade III-IV IVH and/or PVL, nine (1%) with seizures and/or HIE, 91 (10%) with BPD, 57 (7%) with sepsis, 21 (2%) with NEC, and 361 (41%) who remained in the NICU > 7 days. In addition, 270 (31%) pregnancies were delivered by Cesarean section for non-reassuring fetal status, 43 (5%) were admitted to the NICU for < 7 days, 79 (9%) had 5-min Apgar score < 7, 125/631 (20%) had a cord gas pH ≤ 7.1 and 35/631 (6%) had a base excess ≥ 12 mmol/L. The predictive index we developed included seven factors available at the time of FGR diagnosis: hypertensive disorder of pregnancy (HDP) (+8 points), chronic hypertension without HDP (+4 points), gestational age ≤ 32 weeks (+5 points), absent or reversed end-diastolic flow in the umbilical artery (+8 points), prepregnancy body mass index ≥ 35 kg/m2 (+3 points), isolated abdominal circumference < 3rd percentile (-4 points) and non-Hispanic black race (-2 points). The bias-corrected bootstrapped (1000 replicates) area under the receiver-operating-characteristics curve (AUC) of the predictive index for composite APO in the validation group was 0.88 (95% CI, 0.84-0.92), which was similar to that in the development group (AUC, 0.86 (95% CI, 0.82-0.89); P = 0.34). In the total cohort, 40% of pregnancies had a low-risk index score (≤ 2), associated with a NPV of 85% (95% CI, 81-88%) and a LR- of 0.21 (95% CI, 0.16-0.27), and 23% had a high-risk index score (≥ 10), associated with a PPV of 96% (95% CI, 93-98%) and a LR+ of 27.36 (95% CI, 14.33-52.23). Of the remaining pregnancies that had an intermediate-risk score, 50% were complicated by composite APO. An easy-to-use index incorporating seven clinical factors readily available at the time of FGR diagnosis is predictive of APO and may prove useful in counseling and management of pregnancies meeting the ISUOG-endorsed criteria for FGR. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.