Management of fetuses with apparent normal growth and abnormal cerebroplacental ratio: A risk-based approach near term.

INTRODUCTION: Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk-based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. MATERIAL AND METHODS: This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. RESULTS: Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The "a priori" risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. CONCLUSIONS: Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation.

Hepatic arterial buffer response: activation in donor fetuses and the effect of laser ablation of intertwin anastomosis.

OBJECTIVES: Hepatic arterial buffer response (HABR) is an important defence mechanism for maintaining liver blood flow. It is suspected that HABR is active in monochorionic diamniotic twins (MCDA) with twin-to-twin transfusion syndrome (TTTS) where donor compensates a setting of volume depletion and the recipient an overload. The present study investigates whether in TTTS, HABR is active in donor and/or recipient individually and try to determine if the activation of HABR is a direct response to TTTS. METHODS: Hepatic artery (HA) peak systolic velocity (PSV) was measured in normal MCDA fetuses and TTTS. Correlation with relevant fetal Dopplers and characteristics were determined. Z-scores for HA-PSV (HAV-Z) were calculated and its association with TTTS in donors and recipients were determined as well as changes in HAV-Z after laser treatment. RESULTS: In this study 118 MCDA were included, 61.9 % normal and 38.1 % TTTS. Of the TTTS 22 required laser treatment. A total of 382 scans were performed in normal group and 155 in TTTS. Our data demonstrates that in donors HAV-Z was 2.4 Z-scores higher compared to normal fetuses (ß=2.429 95 % CI 1.887, 2.971; p<0.001) and after laser treatment HAV-Z reduced (ß=-1.829 95 % CI -2.593, -1.064; p<0.001). There was no significant difference between recipients and normal (ß=-0.092 95 % CI -0.633, 0.449; p=0.738). CONCLUSIONS: HABR is active in TTTS, promoting an increased hepatic blood flow in donors. The activation is direct response to TTTS as shown by the reduction in HAV-Z after laser. This finding provides important insights into the pathophysiology of TTTS.

Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

OBJECTIVES: Monochorionic twins (MC) have higher risk of perinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. METHODS: sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. RESULTS: We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was -0.16 (±0.97). CONCLUSIONS: Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

Elevated Middle Cerebral Artery Peak Systolic Velocity in Non-Anemic Fetuses: Providing a Better Understanding of Enigmatic Middle Cerebral Artery Peak Systolic Velocity.

INTRODUCTION: Our aim was to investigate the incidence, comorbidities, and outcomes of fetuses with an elevated middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 multiples of median (MoM), despite normal hemoglobin (Hgb) levels on fetal blood sampling (FBS). METHODS: A single-center observational retrospective cohort study of all fetuses undergoing FBS and MCA-PSV >1.5 MoM. Only those fetuses with no or mild anemia were included. Indications for Doppler assessment, associated anomalies, and neonatal outcomes were collected. RESULTS: Overall, 383 fetuses had an MCA-PSV >1.5 MoM and underwent FBS. Twenty-three (6%) fetuses met our inclusion criteria and had no or only mild anemia. Associations with elevated MCA-PSV were elucidated in 12 of the 23 cases (52.2%) and included mild anemia (n = 2), intracranial hemorrhage (n = 3), genetic disease (n = 1), idiopathic nonimmune hydrops (NIH, n = 1), hypoxic-ischemic encephalopathy (n = 1), maternal and or fetal acidosis (n = 3), and fetal growth restriction (n = 1). Favorable perinatal outcomes were observed in truly unexplained 11 cases with no additional anomalies (47.8%). CONCLUSION: Elevated MCA-PSV >1.5 MoM with normal Hgb levels is seen in 6% of pregnancies undergoing FBS and is often associated with other significant maternal or fetal problems. Those with unexplained and isolated MCA-PSV elevation have normal outcomes.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction.

BACKGROUND: The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. OBJECTIVE: This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. STUDY DESIGN: This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. RESULTS: A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). CONCLUSION: Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Comparison of ductus venosus Doppler and cerebroplacental ratio for the prediction of adverse perinatal outcome in high-risk pregnancies before and after 34 weeks.

INTRODUCTION: The objective of the study was to compare the accuracy of the ductus venosus pulsatility index (DV PI) with that of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome at two gestational ages: <34 and ≥34 weeks' gestation. MATERIAL AND METHODS: This was a retrospective study of 169 high-risk pregnancies (72 < 34 and 97 ≥ 34 weeks) that underwent an ultrasound examination of CPR, DV Doppler and estimated fetal weight at 22-40 weeks. The CPR and DV PI were converted into multiples of the median, and the estimated fetal weight into centiles according to local references. Adverse perinatal outcome was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean delivery, 5' Apgar score <7, neonatal pH <7.10 and admission to neonatal intensive care unit. Values were plotted according to the interval to labor to evaluate progression of abnormal Doppler values, and their accuracy was evaluated at both gestational periods, alone and combined with clinical data, by means of univariable and multivariable models, using the Akaike information criteria (AIC) and the area under the curve (AUC). RESULTS: Prior to 34 weeks' gestation, DV PI was the latest parameter to become abnormal. However, it was a poor predictor of adverse perinatal outcome (AUC 0.56, 95% CI: 0.40-0.71, AIC 76.2, p > 0.05), and did not improve the predictive accuracy of CPR for adverse perinatal outcome (AUC 0.88, 95% CI: 0.79-0.97, AIC 52.9, p < 0.0001). After 34 weeks' gestation, the chronology of the DV PI and CPR anomalies overlapped, but again DV PI was a poor predictor for adverse perinatal outcome (AUC 0.62, 95% CI: 0.49-0.74, AIC 120.6, p > 0.05), that did not improve the CPR ability to predict adverse perinatal outcome (AUC 0.80, 95% CI: 0.67-0.92, AIC 106.8, p < 0.0001). The predictive accuracy of CPR prior to 34 weeks persisted when the gestational age at delivery was included in the model (AUC 0.91, 95% CI: 0.81-1.00, AIC 46.3, p < 0.0001, vs AUC 0.86, 95% CI: 0.72-1, AIC 56.1, p < 0.0001), and therefore was not determined by prematurity. CONCLUSIONS: CPR predicts adverse perinatal outcome better than DV PI, regardless of gestational age. Larger prospective studies are needed to delineate the role of ultrasound tools of fetal wellbeing assessment in predicting and preventing adverse perinatal outcome.

Chorioangioma: a single tertiary care center retrospective study.

OBJECTIVES: Chorioangioma represents a challenge due to the rarity of the condition, paucity of sufficient management guidelines, and controversies regarding the best invasive fetal therapy option; most of the scientific evidence for clinical treatment has been limited to case reports. The aim of this retrospective study was to review the natural antenatal history, maternal and fetal complications, and therapeutic modalities used in pregnancies complicated with placental chorioangioma at a single Center. METHODS: This retrospective study was conducted at King Faisal Specialist Hospital and Research Center (KFSH&RC) in Riyadh, Saudi Arabia. Our study population included all pregnancies with ultrasound features of chorioangioma, or histologically confirmed chorioangiomas, between January 2010 and December 2019. Data were collected from the patients' medical records, including the ultrasound reports and histopathology results. All subjects were kept anonymous; case numbers were used as identifiers. Data collected by the investigators were entered into Excel worksheets in an encrypted format. A MEDLINE database was used to retrieve 32 articles for literature review. RESULTS: Over a 10-year period between January 2010 and December 2019, 11 cases of chorioangioma were identified. Ultrasound remains the gold standard for diagnosis and follow-up of the pregnancy. Seven of the 11 cases were detected by ultrasound, allowing proper fetal surveillance and antenatal follow-up. Of the remaining six patients, one underwent radiofrequency ablation, two underwent intrauterine transfusion for fetal anemia due to placenta chorioangioma, one had vascular embolization with an adhesive material, and two were managed conservatively until term with ultrasound surveillance. CONCLUSIONS: Ultrasound remains the gold standard modality for prenatal diagnosis and follow-up of pregnancies with suspected chorioangiomas. Tumor size and vascularity play a significant role in the development of maternal-fetal complications and the success of fetal interventions. To determine the superior modality of fetal intervention mandates more data and research; nevertheless, Fetoscopic Laser Photocoagulation and embolization with adhesive material seem to be a lead choice, with reasonable fetal survival.

Hepatic arterial buffer response in monochorionic diamniotic pregnancies with twin-to-twin transfusion syndrome.

OBJECTIVES: Hepatic arterial buffer response (HABR) is an important regulatory process for hepatic blood flow. Its activity has been described in some fetal adverse conditions but in twin-to-twin transfusion syndrome (TTTS) it is unknown if such response is present. The aim of this study is to test the hypothesis that HABR operates in monochorionic diamniotic twins (MCDA) with TTTS. METHODS: Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured prospectively in 64 MCDA pregnancies. 43 without TTTS (group 1) and in 21 pregnancies with TTTS (group 2). We calculated ratios for PI (HAPI-ratio) and PSV (HAV-ratio) between recipient and donor in group 2 or bigger and smaller fetus in group 1 and compared groups. The association of HAV-ratio and HAPI ratio with TTTS, relation with other fetal Dopplers and reliability of measurement by a single operator were investigated. RESULTS: HAV-ratio and HAPI-ratio appears to be independent from fetal Dopplers, estimated weight and gestational age. In group 2, HAV-ratio is lower than group 1 (p<0.001, 95% CI 0.443-0.643). In group 1 the mean HAV-ratio is 1.014 (±0.021) while in group 2 is 0.47 (±0.035). HAPI-ratio is lower in group 2 than in group 1 although this difference was not significant (p=0.066, 95% CI -0.007-0.231). A good reliability of measurements of hepatic artery PSV and PI was demonstrated by intraclass correlation coefficient analysis (ICC 0.971 95% CI 0.963-0.977, p<0.001 and ICC 0.694 95% CI 0.596-0.772, p<0.001, respectively). CONCLUSIONS: Monochorionic pregnancies with TTTS are associated with lower HAV-ratios. This could be explained by an active HABR.

Angiogenic factors for planning fetal surveillance in fetal growth restriction and small-for-gestational-age fetuses: A prospective observational study.

OBJECTIVE: The aim of this study was to assess the added value of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio for adjusting the periodicity of ultrasound examinations in early-onset fetal growth restriction (FGR) and small for gestational age (SGA). DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. POPULATION: One hundred and thirty-four single pregnancies with ultrasonographic estimated fetal weight (EFW) below the 10th centile between 20+0 and 31+6  weeks of gestation with antegrade umbilical artery flow. METHODS: The time from Doppler and sFlt-1/PlGF assessment to delivery was recorded and classified into four ranges: <1, <2, <3 and <4 weeks. MAIN OUTCOME MEASURES: Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of sFlt-1/PlGF values to predict the time to delivery. RESULTS: In the SGA cohort, the NPV calculated for an sFlt-1/PlGF cut-off value of 38 was 100% for delivery before 3 weeks, and 98% for delivery before 4 weeks after diagnosis (95% CI 0.89-1.00). In the FGR cohort, the NPV calculated for an sFlt-1/PlGF cut-off value of 38 was 100% for delivery before 2 weeks after diagnosis (95% CI 0.92-1.00). By contrast, more than 50% of cases with an sFlt-1/PlGF value of >85 required an elective delivery before 1 week. CONCLUSIONS: sFlt-1/PlGF values in early-onset SGA and FGR are predictive of the time to delivery and could be used for planning fetal surveillance, by reducing the frequency of ultrasound in cases with sFlt-1/PlGF < 38 and by providing closer follow-up in cases with sFlt-1/PlGF >85. TWEETABLE ABSTRACT: sFlt-1/PlGF values in early-onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance.

Ultrasound predictors of adverse outcome in pregnancy complicated by pre-existing and gestational diabetes.

INTRODUCTION: Ultrasound assessment of fetuses subjected to hyperglycemia is recommended but, apart from increased size, little is known about its interpretation, and the identification of which large fetuses of diabetic pregnancy are at risk is unclear. Newer markers of adverse outcomes, abdominal circumference growth velocity and cerebro-placental ratio, help to predict risk in non-diabetic pregnancy. Our study aims to assess their role in pregnancies complicated by diabetes. MATERIAL AND METHODS: This is a retrospective analysis of a cohort of singleton, non-anomalous fetuses of women with pre-existing or gestational diabetes mellitus, and estimated fetal weight at the 10th centile or above. Gestational diabetes was diagnosed by selective screening of at risk groups. A universal ultrasound scan was offered at 20 and 36 weeks of gestation. Estimated fetal weight, abdominal circumference growth velocity, presence of polyhydramnios, and cerebro-placental ratio were evaluated at the 36-week scan. A composite adverse outcome was defined as the presence of one or more of perinatal death, arterial cord pH less than 7.1, admission to Neonatal Unit, 5-minute Apgar less than 7, severe hypoglycemia, or cesarean section for fetal compromise. A chi-squared test was used to test the association of estimated fetal weight at the 90th centile or above, polyhydramnios, abdominal circumference growth velocity at the 90th centile or above, and cerebro-placental ratio at the 5th centile or below with the composite outcome. Logistic regression was used to assess which ultrasound markers were independent risk factors. Odds ratios of composite adverse outcome with combinations of independent ultrasound markers were calculated. RESULTS: A total of 1044 pregnancies were included, comprising 87 women with pre-existing diabetes mellitus and 957 with gestational diabetes. Estimated fetal weight at the 90th centile or above, abdominal circumference growth velocity at the 90th centile or above, cerebro-placental ratio at the 5th centile or below, but not polyhydramnios, were significantly associated with adverse outcomes: odds ratios (95% confidence intervals) 1.85 (1.21-2.84), 1.54 (1.02-2.31), 1.92 (1.21-3.30), and 1.53 (0.79-2.99), respectively. Only estimated fetal weight at the 90th centile or above and cerebro-placental ratio at the 5th centile or below were independent risk factors. The greatest risk (odds ratio 6.85, 95% confidence interval 2.06-22.78) was found where both the estimated fetal weight is at the 90th centile or above and the cerebro-placental ratio is at the 5th centile or below. CONCLUSIONS: In diabetic pregnancies, a low cerebro-placental ratio, particularly in a macrosomic fetus, confers additional risk.

Current practice in the diagnosis and management of fetal growth restriction: An international survey.

INTRODUCTION: The aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries. MATERIAL AND METHODS: An e-questionnaire was sent via REDCap with "click thru" links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings. RESULTS: A total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from ≥32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (≤32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively. CONCLUSIONS: The diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynamics are less frequently assessed but more so in early rather than late fetal growth restriction. Further standardization is needed for the definition of cerebral blood flow redistribution.

Evaluating the predictive value of fetal Doppler indices and neonatal outcome in late-onset preeclampsia with severe features: a cross-sectional study in a resource-limited setting.

BACKGROUND: Preeclampsia constitutes a major health problem with substantial maternal and perinatal morbidity and mortality. The aim of this study was to detect the diagnostic efficacy of fetal Doppler in predicting adverse outcomes in severe late onset preeclampsia (LOP). METHODS: A prospective study was conducted among childbearing women who presented with severe LOP and matched controls. Umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) and cerebroplacental ratio (CPR) were measured. RESULTS: All UA indices were significantly higher in the case group compared to the controls (p < 0.001). UA PI and RI were significantly correlated with all neonatal adverse outcomes except cord pH status (p < 0.05). Abnormal CPR was the most sensitive index that positively correlated with intrauterine growth retardation (IUGR), low 5- minute Apgar score and neonatal intensive care unit admission (79, 72.8 and 73.3%, respectively). In the same context, Abnormal UA PI and RI represented the most specific tool for predicting IUGR, low 1- and 5- minutes Apgar score with positive predictive values were 52, 87 and 57%, respectively. CONCLUSION: In severe LOP, UA Doppler remains the preferential indicator for adverse birth outcomes with CPR is the best index that could be solely used for predicting such outcome.

Cerebroplacental Ratio Prediction of Intrapartum Fetal Compromise according to the Interval to Delivery.

INTRODUCTION: A controversy exists about the accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC). Our aim was to evaluate whether the interval to delivery modifies the accuracy of CPR either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO), and other clinical variables. METHODS: This was a multicenter retrospective study of 5,193 women with singleton pregnancies who underwent an ultrasound scan at 35+0-41+0 weeks and gave birth within 1 month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20, requiring urgent cesarean section. The diagnostic ability of CPR in multiples of the median (CPR MoM) was evaluated at different intervals to delivery, alone and combined with EFWc, TLO, and other pregnancy data such as maternal age, maternal body mass index, parity, and fetal sex, for the prediction of CS-IFC by means of ROC curves and logistic regression analysis. RESULTS: The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor and by adding information related to EFWc and TLO (AUC 0.71 [95% CI: 0.64-0.79], 0.73 [95% CI: 0.66-0.80], and 0.75 [95% CI: 0.69-0.81]; p < 0.0001). Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied. CONCLUSION: CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO.

Effect of SARS-CoV-2 infection during the second half of pregnancy on fetal growth and hemodynamics: A prospective study.

INTRODUCTION: Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MATERIAL AND METHODS: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups. Fetal growth was assessed by analyzing the growth velocity of head circumference, abdominal circumference, femur length, and estimated fetal weight between the second- and third-trimester scans. Similarly, changes in the pulsatility index of uterine, umbilical, and middle cerebral arteries, and their ratios were compared between the two study groups. RESULTS: Forty-nine consecutive pregnancies complicated, and 98 not complicated, by SARS-CoV-2 infection were included. General baseline and pregnancy characteristics were similar between pregnant women with and those without SARS-CoV-2 infection. There was no difference in head circumference, abdominal circumference, femur length, and estimated fetal weight z scores between pregnancies complicated and those not complicated by SARS-CoV-2 infection at both the second- and third-trimester scans. Likewise, there was no difference in the growth velocity of all these body parameters between the two study groups. Finally, there was no difference in the pulsatility index of both maternal and fetal Doppler scans throughout gestation between the two groups. CONCLUSIONS: Pregnancies complicated by SARS-CoV-2 infection are not at higher risk of developing fetal growth restriction through impaired placental function. The findings from this study do not support a policy of increased fetal surveillance in these women.

Assessment of fetal Doppler parameters in pregnant women with COVID-19 infection: a prospective case-control study.

OBJECTIVES: To investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on fetal Doppler parameters. METHODS: This was a prospective case-control study conducted in Ankara City Hospital with confirmed SARS-CoV-2 infected pregnants between August 1, 2020 and October 1, 2020. There were 54 COVID-19 confirmed pregnant women and 97 age-matched pregnant women as a control group between 28 and 39 weeks. Infection was confirmed based on positive real-time polymerase-chain reaction results. Demographic features, uterine artery (right, left), umblical artery, middle cerebral artery, ductus venosus, cerebro-placental ratio, and cerebral-placental-uterine ratio Doppler parameters were investigated in both groups. RESULTS: Two groups were similar in terms of demographic features and no difference was found for fetal Doppler parameters. CONCLUSIONS: COVID-19 seems to have no adverse effect on fetoplacental circulation in mild and moderate patients during the acute phase of the infection.

Doppler assessment of the fetus in pregnant women recovered from COVID-19.

OBJECTIVE: The aim of this study was to evaluate the maternal-fetal Doppler patterns in pregnant women recovered from COVID-19. METHODS: This prospective case-control study was conducted in Ankara City Hospital between July 1, 2020 and August 30, 2020. Thirty pregnant women who were diagnosed with COVID-19 and completed the quarantine process were compared with 40 healthy pregnant women in terms of the fetal Doppler parameters. All pregnant women diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were followed up in our clinic and their diagnoses have been confirmed in nasopharyngeal and oropharyngeal samples by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) method. Doppler ultrasonographic assessment of the uterine arteries (UtA) and middle cerebral artery (MCA) were used in addition to umbilical artery (UA) Doppler between 23 and 40 weeks of gestation. Also, cerebroplacental ratio (CPR) was calculated according to gestational age. RESULTS: The pulsatility and resistance indices of umbilical and UtA showed a significant increase in pregnant women in the study group compared to the control group (p < 0.05). Multivariable logistic regression analysis revealed that pulsatility and resistance indices of the mean UtA were independently associated with disease (OR > 1000, 95%CI 9.77 to >1000, p = 0.009; OR 0,000 95%CI 0,000-0,944, p = 0,049), respectively. Medical treatment was given to 16/30 (53%) of pregnant women diagnosed with COVID-19. CONCLUSION: In conclusion, uterine artery Doppler indices in the third trimester may have clinical value in pregnant women recovered from COVID-19.

Reference values for pulsatility index of fetal anterior and posterior cerebral arteries in prolonged pregnancy.

OBJECTIVE: To establish consistent normal reference values for fetal anterior cerebral artery (ACA) and posterior cerebral artery (PCA) pulsatility index (PI) in prolonged pregnancy. METHODS: This prospective cross-sectional observational study included singleton normal prolonged pregnancies into two study groups according to the gestational age: from 40 + 0 to 40 + 6 and from 41 + 0 to 41 + 6 weeks. The PI was assessed in both anatomical segments of ACA (ACA-S1 and ACA-S2) and of PCA (PCA-S1 and PCA-S2) with color Doppler imaging and pulsed Doppler examination, and reference centiles charts were generated. PI values from the two investigated segments of each vessel were also compared. RESULTS: Data were obtained in 771 patients: n = 448 in the 40 + 0 and 40 + 6 weeks group, and n = 323 in the 41 + 0 and 41 + 6 weeks group. A moderate decrease in PI was observed as pregnancy progressed. No differences in PI values were found between the two anatomical segments of ACA and PCA. CONCLUSION: This study provides Doppler reference values for the fetal ACA and PCA PI. It also shows that Doppler examination could be performed indifferently in one of the two anatomical segments of these arteries.

Does Uterine Doppler Add Information to the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome at the End of Pregnancy?

OBJECTIVE: To evaluate whether the addition of the mean uterine arteries pulsatility index (mUtA PI) to the cerebroplacental ratio (CPR) improves its ability to predict adverse perinatal outcome (APO) at the end of pregnancy. METHODS: This was a prospective study of 891 fetuses that underwent an ultrasound examination at 34-41 weeks. The CPR and the mUtA PI were converted into multiples of the median (MoM) and the estimated fetal weight (EFW) into centiles according to local references. APO was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5' Apgar score <7, neonatal pH <7.10 and admission to pediatric care units. The accuracies of the different parameters were evaluated alone and in combination with gestational characteristics using univariate and multivariate analyses by means of the Akaike Information Criteria (AIC) and the area under the curve (AUC). Finally, a comparison was similarly performed between the CPR and the cerebro-placental-uterine ratio (CPUR; CPR/mUtA PI) for the prediction of APO. RESULTS: The univariate analysis showed that CPR MoM was the best parameter predicting APO (AIC 615.71, AUC 0.675). The multivariate analysis including clinical data showed that the best prediction was also achieved with the CPR MoM (AIC 599.39, AUC 0.718). Moreover, when EFW centiles were considered, the addition of UtA PI MoM did not improve the prediction already obtained with CPR MoM (AIC 591.36, AUC 0.729 vs. AIC 589.86, AUC 0.731). Finally, the prediction by means of CPUR did not improve that of CPR alone (AIC 623.38, AUC 0.674 vs. AIC 623.27, AUC 0.66). CONCLUSION: The best prediction of APO at the end of pregnancy is obtained with CPR whatever is the combination of parameters. The addition of uterine Doppler to the information yielded by CPR does not result in any prediction improvement.

Diagnostic performance of third-trimester ultrasound for the prediction of late-onset fetal growth restriction: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the diagnostic performance of ultrasound screening for predicting late smallness for gestational age and/or fetal growth restriction. DATA SOURCES: A systematic search was performed to identify relevant studies published since 2007 in English, Spanish, French, Italian, or German, using the databases PubMed, ISI Web of Science, and SCOPUS. STUDY ELIGIBILITY CRITERIA: We used rrospective and retrospective cohort studies in low-risk or nonselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation. STUDY APPRAISAL AND SYNTHESIS METHODS: The estimated fetal weight and fetal abdominal circumference were assessed as index tests for the prediction of birthweight <10th (i.e. smallness for gestational age), less than the fifth, and less than the third centile and fetal growth restriction (estimated fetal weight less than the third or estimated fetal weight <10th plus Doppler signs). Quality of the included studies was independently assessed by 2 reviewers, using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. For the meta-analysis, hierarchical summary receiver-operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models. The sensitivity of the abdominal circumference <10th centile and estimated fetal weight <10th centile for a fixed 10% false-positive rate was derived from the corresponding hierarchical summary receiver-operating characteristic curves. Heterogeneity between studies was visually assessed using Galbraith plots, and publication bias was assessed by funnel plots and quantified by Deeks' method. RESULTS: A total of 21 studies were included. Observed pooled sensitivities of abdominal circumference and estimated fetal weight <10th centile for birthweight <10th centile were 35% (95% confidence interval, 20-52%) and 38% (95% confidence interval, 31-46%), respectively. Observed pooled specificities were 97% (95% confidence interval, 95-98%) and 95% (95% confidence interval, 93-97%), respectively. Modeled sensitivities of abdominal circumference and estimated fetal weight <10th centile for 10% false-positive rate were 78% (95% confidence interval, 61-95%) and 54% (95% confidence interval, 46-52%), respectively. The sensitivity of estimated fetal weight <10th centile was better when aimed to fetal growth restriction than to smallness for gestational age. Meta-regression analysis showed a significant increase in sensitivity when ultrasound evaluation was performed later in pregnancy (P = .001). CONCLUSION: Third-trimester abdominal circumference and estimated fetal weight perform similar in predicting smallness for gestational age. However, for a fixed 10% false-positive rate extrapolated sensitivity is higher for abdominal circumference. There is evidence of better performance when the scan is performed near term and when fetal growth restriction is the targeted condition.

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.