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.

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.

Comparison of cardiac morphology and function in small for gestational age fetuses and fetuses with late-onset fetal growth retardation.

OBJECTIVES: To compare cardiac structural and functional findings of fetuses with fetal growth restriction (FGR) and small for gestational age (SGA). METHODS: In this prospective cohort study, patients were classified into three groups using Delphi procedure according to fetal weight, umbilical, uterine artery Doppler and cerebroplacental ratio. Fetal cardiac ultrasonographic morphology and Doppler examination was performed to all pregnant women at 36 weeks of gestation. RESULTS: Seventy three patients were included in the study. There were one (6.7%) patient in the control group, 2 (13.3%) in the SGA group and 12 (80%) in the FGR group who needed neonatal intensive care unit (NICU) and NICU requirement was significantly higher in FGR fetuses (p<0.001). Left spherical index was found to be lower only among FGR fetuses (p=0.046). Left ventricular wall thickness was decreased and the right/left ventricular wall ratio was increased in FGR fetuses (p=0.006, p<0.001). Tricuspid/mitral valve ratio and mitral annular plane systolic excursion value was lower in FGR fetuses (p=0.034, p=0.024 respectively). Also, myocardial performance index was remarkably higher in FGR group (p=0.002). CONCLUSIONS: We detected cardiac morphological changes in cases of both SGA and FGR-more pronounced in the FGR cases. Findings related to morphological changes on the left side in FGR cases were considered secondary to volume increase in FGR cases as an indicator of a brain-protective effect. In the FGR group, both systolic and diastolic dysfunctions were detected in the left heart.

Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with increased nuchal translucency, tricuspid regurgitation and abnormal flow in ductus venosus.

OBJECTIVE: To examine the association between fetal major heart defects and increased nuchal translucency thickness (NT), tricuspid regurgitation and abnormal flow in the ductus venosus in a large population of singleton pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation. METHODS: This was a retrospective study of prospectively collected data from singleton pregnancies attending for a routine ultrasound scan at 11-13 weeks' gestation, which included examination of fetal anatomy, measurement of NT and assessment of blood flow across the tricuspid valve and in the ductus venosus, according to a standardized protocol. The incidence of fetal NT ≥ 95th and ≥ 99th percentiles, tricuspid regurgitation and reversed a-wave in the ductus venosus in fetuses with and those without a major heart defect was determined and the performance of each marker and their combination in the detection of major heart defects was calculated. RESULTS: The study population of 93 209 pregnancies with no apparent chromosomal abnormality included 211 (0.23%) with a fetal major heart defect and 92 998 morphologically normal neonates. In 113 (53.6%) cases with a major heart defect, the diagnosis was made at the 11-13-week scan, in 82 (38.9%) at the 18-24-week scan, in 10 (4.7%) at the third-trimester scan and in six (2.8%) postnatally. At the 11-13-week scan, we diagnosed all cases of tricuspid or pulmonary atresia and polyvalvular dysplasia, > 90% of cases of hypoplastic left heart syndrome or atrioventricular septal defect, about 60% of complex heart defects and cases of left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), 30-40% of cases of tetralogy of Fallot and arch abnormalities, 25% of tricuspid valve abnormalities and about 15% of cases of transposition of the great arteries, but none of aortic or pulmonary stenosis or common arterial trunk. Fetal NT ≥ 95th or ≥ 99th percentile, tricuspid regurgitation or abnormal ductus venosus flow was observed in 77 (36.5%), 45 (21.3%), 61 (28.9%) and 58 (27.5%) fetuses with a major heart defect, respectively, and in 5678 (6.1%), 857 (0.9%), 1136 (1.2%) and 1644 (1.8%) of those without a heart defect. Any one of NT ≥ 95th percentile, tricuspid regurgitation or abnormal flow in the ductus venosus was found in 117 (55.5%; 95% CI, 48.5-62.3%) fetuses with a heart defect and in 8166 (8.8%; 95% CI, 8.6-9.0%) of those without a heart defect. Any one of NT ≥ 99th percentile or the other two markers was found in 99 (46.9%; 95% CI, 40.0-53.9%) fetuses with a heart defect and in 3517 (3.8%; 95% CI, 3.7-3.9%) of those without a heart defect. CONCLUSION: At 11-13 weeks' gestation, measurement of fetal NT and assessment of flow across the tricuspid valve and in the ductus venosus can lead to early diagnosis of major heart defect. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Doppler changes in umbilical artery and ductus venosus during fetoscopic prenatal surgical repair of myelomeningocele.

OBJECTIVE: Cardiac dysfunction has been described in 60% of fetuses undergoing open myelomeningocele (MMC) repair. Routine Doppler evaluation of the umbilical artery (UA) and ductus venosus (DV) is challenging during fetal surgery. The aim of this study was to describe Doppler changes in the UA and DV in a cohort of fetuses during fetoscopic MMC repair. METHODS: This was a retrospective study of fetuses that underwent fetoscopic repair of MMC at a single institution between 2014 and 2017. Ultrasound images taken intraoperatively were analyzed to describe the changes in Doppler parameters of the UA and DV during fetoscopic MMC repair. The timing of Doppler changes was matched with the phase of surgery to determine whether a pattern to their appearance could be ascertained. RESULTS: Of the thirty-five cases of fetoscopic MMC repair performed during the study period, Doppler data were available for 15. Of these, UA Doppler data were obtained in 12 cases, and DV Doppler data were obtained in 13 cases. Of the 12 cases for which there were UA data, nine (75%) showed transient absence of end-diastolic flow (EDF), with five (41.7%) of them progressing to reversal of EDF. Of the 13 cases for which there were DV data, nine had elevated pulsatility index; however, none of them had absent or reversed blood flow during atrial contraction. Of the nine cases with absent EDF in the UA, this abnormality first appeared during fetoscopic repair in five (55.6%), after uterus exteriorization but before CO2 insufflation in two (22.2%), after uterus replacement but before skin closure in one (11.1%) and after CO2 insufflation but before the start of the MMC repair in one (11.1%). Doppler abnormalities in four fetuses with reversed EDF and in three with absent EDF resolved during surgery. Follow-up examination 1 day after surgery demonstrated resolution of UA and DV Doppler abnormalities in all fetuses. CONCLUSION: Transient Doppler abnormalities of the UA, without significant changes in the DV, can be seen during fetoscopic MMC repair. The clinical significance of these Doppler findings remains unclear due to their transient and intermittent nature. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks.

OBJECTIVES: To develop a model for the prediction of stillbirth that is based on a combination of maternal characteristics and medical history with first-trimester biochemical and biophysical markers and to evaluate the performance of screening with this model for all stillbirths and those due to impaired placentation and unexplained causes. METHODS: This was a prospective screening study of 76 897 singleton pregnancies, including 76 629 live births and 268 (0.35%) antepartum stillbirths; 157 (59%) were secondary to impaired placentation and 111 (41%) were due to other or unexplained causes. Multivariable logistic regression analysis was used to determine if there was a significant contribution to prediction of stillbirth from the maternal factor-derived a-priori risk, fetal nuchal translucency thickness, ductus venosus pulsatility index for veins (DV-PIV), uterine artery pulsatility index (UtA-PI) and maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A (PAPP-A). The significant contributors were used to derive a model for first-trimester prediction of stillbirth. RESULTS: Significant contribution to prediction of stillbirth was provided by maternal factors, PAPP-A, UtA-PI and DV-PIV. A model combining these variables predicted 40% of all stillbirths and 55% of those due to impaired placentation, at a false-positive rate of 10%. Within the impaired-placentation group, the detection rate of stillbirth < 32 weeks' gestation was higher than that of stillbirth ≥ 37 weeks (64% vs 42%). CONCLUSIONS: A model based on maternal factors and first-trimester biomarkers can potentially predict more than half of subsequent stillbirths that occur due to impaired placentation. The extent to which such stillbirths could be prevented remains to be determined. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Obstetric outcomes in pregnancies with normal nuchal translucency and abnormal ductus venosus Doppler in the first trimester ultrasonography.

In the present case-control study, we evaluated obstetric outcomes of pregnancies with normal nuchal translucency (NT) and abnormal ductus venosus (DV) Doppler findings in the first trimester combined screening test for chromosomal abnormalities. All study patients underwent DV Doppler examination, concurrent with the combined screening test. DV Doppler revealed pathologic findings in 14 pregnant women despite normal NT after the elimination of lost to follow-up and foetal anomaly. Obstetric outcomes of the case patients were compared with a control group that were matched for mean gestational age, and Crown-rump length with normal NT and DV Doppler measurements was selected comprising 88 pregnant women. Regarding maternal outcomes, women with abnormal DV Doppler findings had a higher rate of placental abruption, delivered at an earlier mean gestational age (preterm delivery). Interestingly, a higher rate of spontaneous vaginal delivery rate was observed in these patients. From the foetal perspective, pregnancies with abnormal DV Doppler had lower birth weight and received lower Apgar scores. In conclusion, an abnormal DV Doppler test in the first trimester was associated with poor maternal and foetal obstetric outcomes. These findings should be elucidated in future studies.

Ductus Venosus Doppler Flow Velocity after Transplacental and Non-transplacental Amniocentesis during Midtrimester.

OBJECTIVE: We aimed to evaluate ductus venosus Doppler waveforms before and after amniocentesis in order to investigate any effect of amniocentesis on fetal myocardial hemodynamics. We also evaluated the umbilical artery, uterine artery and fetal mid-cerebral artery Doppler waveforms in order to investigate any relationship with ductus venosus Doppler changes. METHODS: The study population consisted of 56 singleton pregnancies having genetic amniocentesis. Twenty seven of them had transplacental needle insertion; whereas 29 of them had non-transplacental amniocentesis. Uterine artery, umbilical artery, mid-cerebral artery and ductus venosus pulsatiliy index and resistance index were measured just before and after amniocentesis. RESULTS: Amniocentesis does not cause any significant changes in fetal ductus venosus Doppler waveforms. There is also no significant changes in uterine artery, umbilical artery, mid-cerebral artery pulsatility and resistance index. CONCLUSION: Amniocentesis-whether transplacental or not- does not cause any significant effect on fetal myocardial hemodynamics.

The pre-eclampsia, growth restriction, and ductus venosus doppler (GRADED) study: An observational study of early-onset fetal growth restriction and pre-eclampsia.

OBJECTIVE: To assess the feasibility of using ductus venosus Doppler (DVD) to time delivery in early-onset fetal growth restriction (FGR) and pre-eclampsia in a resource-constrained setting. METHODS: This was a prospective, observational study of pregnancies affected by early-onset FGR and pre-eclampsia. Patient characteristics, risk factors, ultrasound findings, and pregnancy outcomes were entered into a data collection tool. The association of these variables with perinatal and maternal outcomes were determined using binary logistic regression analysis. RESULTS: The study had 61 participants. Most patients were delivered at 29-31+6 weeks of pregnancy (67%). Neonates with an estimated fetal weight on ultrasound of less than 800 g had the highest incidence of perinatal mortality (63%). There was a near six-fold increase in risk of major neonatal morbidity in patients with abnormal DVD (odds ratio 5.9, 95% confidence interval [CI] 1.8-19.0). Absent flow in the DVD a-wave carried a higher risk of perinatal mortality (OR 23.8, 95% CI 1.7-334.8); 22% of patients with an abnormal DVD a-wave experienced placental abruption. CONCLUSION: Having an abnormal DVD in the background of pre-eclampsia was related to increased perinatal morbidity and mortality, with increased risk of placental abruption.

Routine Doppler ultrasound in twin pregnancy.

Doppler ultrasound when used appropriately is an invaluable tool in monitoring high risk twin pregnancy. There are no recent multicentre randomised controlled trials examining the value of routine umbilical artery doppler (UA), middle cerebral artery doppler (MCA), cerebroplacental ratio (CPR), uterine artery doppler (UtA) and ductus venosus doppler in uncomplicated twins. Thus, there is lack of international consensus in relation to incorporation of doppler ultrasound in the routine surveillance of uncomplicated multiples. In this chapter we will discuss how twins differ from singletons in their growth trajectories and progression of doppler abnormalities. International clinical guidelines are reviewed. Recommendations for doppler surveillance (routine or selective) with reference to recent studies are made.

Twin reversed arterial perfusion (TRAP) sequence: A case report and a brief literature review.

Twin reversed arterial perfusion (TRAP) sequence is rare in monochorionic twin pregnancies. TRAP sequence is distinct from other multifetal pregnancies in that one of the twins has normal anatomy while the other twin has a varied amount of characteristic abnormal features. In the literature, mortality is reported 100% in the abnormal twin. We report 1 case of TRAP sequence at our institution in which the diagnosis of TRAP sequence was missed in the first trimester at another hospital. The patient, a 33-year-old G1P0A0, did not have any follow-up after her first scan until the routine second-trimester ultrasound at our institution. Both the radiologist and the sonographer did not appreciate the differential diagnosis of TRAP sequence in their clinical decision-making. The TRAP diagnosis was established after the ultrasound performed at the fetal assessment unit in our hospital. Radiofrequency ablation (RFA) procedure was performed to give the normal twin a chance to survive, but unfortunately, the prognosis was poor in this case. We conclude that diagnosing a TRAP sequence is very important early in the pregnancy for a positive outcome in the normal twin. A robust collaboration among radiologists and obstetricians is vital for the best outcome of the normal twin.

The significance of reverse flow in ductus venosus between sixteen and twenty weeks' gestation.

OBJECTIVE: To evaluate the correlation between reversed a-wave in ductus venosus at 16-20 weeks' gestation and trisomy 21 and adverse perinatal outcomes. MATERIALS AND METHODS: Our study included 174 pregnant women who were under follow-up at a tertiary center between May and September 2010. Ductus venosus Doppler (DVD) measurements were obtained throughout the 6-month period from women who underwent amniocentesis procedures due to increased risk for trisomy 21 in terms of first or second trimester screening test results. These women were followed up for enrollment of subsequent data about perinatal outcomes. RESULTS: In 13 of 174 cases, Doppler studies indicated a reversed a-wave in the ductus venosus. Of these fetuses, 3 were diagnosed as having trisomy 21 after amniocentesis, which related to 60% (3 of 5 fetuses) of all fetuses with trisomy 21. The pregnant women with reversed a-wave in DVD also had an increased rate of preeclampsia (15%) and gestational diabetes mellitus (GDM) (23%) in late pregnancy. CONCLUSION: Reversed a-wave in ductus venosus between 16-20 weeks' gestation is associated with increased risk of trisomy 21, preeclampsia, and GDM. If further prospective studies confirm its utility, DVD interrogation for trisomy 21 may be extended until 20 weeks' gestation.

Early onset fetal growth restriction.

Fetal growth restriction remains a challenging entity with significant variations in clinical practice around the world. The different etiopathogenesis of early and late fetal growth restriction with their distinct progression of fetal severity and outcomes, compounded by doctors and patient anxiety adds to the quandary involving its management. This review summarises the literature around diagnosing and monitoring early onset fetal growth restriction (early onset FGR) with special emphasis on optimal timing of delivery as guided by recent research advances.

Can the ductus venosus doppler predict the hemoglobinopathies?

OBJECTIVE: The aim of our study was to investigate the ductus venosus doppler between 11-13+6 (week-day) in pregnant women with hemoglobinopaties and its relation with fetal outcomes. MATERIAL AND METHODS: A total of 100 pregnant women with hemoglobinopathies and 100 healthy pregnant women were included in our study. Ultrasonography (USG) was performed to all pregnant women and the ductus venosus doppler (DVD) flows were evaluated. The results were statistically analyzed. RESULTS: The mean hemoglobin level was significantly lower in hemoglobinopathy group (9.7 ± 0.7) than control group (10.67 ± 0.82) (P<0.001). There was a significant relationship between Vmax, Vmin, S/D and reverse 'a' wave in fetuses with hemoglobinopathies. Vmax, Vmin and S/D parameters were higher in the group of hemoglobinopathies (respectively mean value, 31.3 ± 1.66, 8.90 ± 0.81, 2.97 ± 0.49). Reverse 'a' wave was detected especially in all fetuses with sickle cell anemia. There was no significantly relationship between the groups in terms of PI, RI and HR. In a logistic regression analyses, fetal hemoglobinopathy was independently associated with Vmin (ß = 1.07, P = 0.001), S/D (ß = 2.61, P = 0.001) and reverse 'a' wave (ß = 2.46, P = 0.004). CONCLUSION: Pregnant women with hemoglobinopathies had changed ductus venosus doppler values in compared to normal pregnant women. Maternal anemia may cause this doppler changes. Furthermore all fetuses with sickle cell anemia (n = 5) had abnormal ductus venosus doppler findings. Further studies are needed to investigate the relationship between abnormal ductus venosus doppler findings and fetuses diagnosed with sickle cell anemia.

Antenatal tests of fetal wellbeing.

In current obstetric practice, there is frequently a need to assess fetal wellbeing. This is particularly so in those fetuses at risk, including the small-for-gestational-age fetus or the fetus of a mother who presents with reduced fetal movements or who has an obstetric complication such as pre-eclampsia. It is important that the clinician is able to assess fetal wellbeing in such cases, especially in preterm gestations, when inappropriate delivery could have serious adverse consequences. In this paper, we review the current evidence for the use and the limitations of widely used methods of antenatal monitoring including the use of cardiotocography, biophysical profile, and ultrasound-derived parameters including umbilical artery, middle cerebral artery, and ductus venosus Doppler flow.

Clinical efficiency of the measurement of fetal nuchal translucency and Doppler examination of ductus venosus as a screening tool for chromosomal abnormalities / 대한산부인과학회지

OBJECTIVE: To evaluate the efficiency of the measurement of fetal nuchal translucency (FNT) and ductus venosus Doppler examination (DV Doppler) as a screening tool for chromosomal abnormalities. METHODS: FNT measurement and DV Doppler wereperformed in 950 pregnancies between 11(+0)~13(+6) weeks' gestation. Chromosomal analysis was done when FNT was more than 3 mm and DV Doppler showed absent flow or reversed flow. The numbers of cases with increased FNT and abnormal DV Doppler were counted in the groups of abnormal and normal karyotype. RESULTS: Data were available in 912 pregnancies. 11 pregnancies showed abnormal karyotype (1.2%). In the 11 cases with abnormal karyotype,increased FNT was found in 8 cases with 72.7% sensitivity and abnormal DV Doppler was found in 5 cases with 45.4% sensitivity. In the 901 cases withnormal karyotype, increased FNT was found in 33 cases with 96.3% specificity and abnormal DV Doppler was found in 12 cases with 98.7% specificity. Positive predictive value was 19.5% in cases of increased FNT, 29.4% in cases of abnormal DV Doppler, and 44.4% in cases of increased FNT and abnormal DV Doppler both. CONCLUSION: There is no improvement in general screening for chromosomal abnormalities when FNT measurement and DV Doppler were performed together. But better specificity and positive predictive value for chromosomal abnormalities were found.