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Objective: To examine the performance of a model combining maternal risk factors, uterine artery pulsatility index (UtA-PI) and estimated fetal weight (EFW) at 19-24 weeks' gestation, for predicting all antepartum stillbirths and those due to impaired placentation, in a training dataset used for development of the model and in a validation dataset.Methods: The data for this study were derived from prospective screening for adverse obstetric outcome in women with singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation. The study population was divided into a training dataset used to develop prediction models for placental dysfunction-related antepartum stillbirth and a validation dataset to which the models were then applied. Multivariable logistic regression analysis was used to develop a model based on a combination of maternal risk factors, EFW Z-score and UtA-PI multiples of the normal median. We examined the predictive performance of the model by, first, the ability of the model to discriminate between the stillbirth and live-birth groups, using the area under the receiver-operating-characteristics curve (AUC) and the detection rate (DR) at a fixed false-positive rate (FPR) of 10%, and, second, calibration by measurements of calibration slope and intercept.Results: The study population of 131 514 pregnancies included 131 037 live births and 477 (0.36%) stillbirths. There are four main findings of this study. First, 92.5% (441/477) of stillbirths were antepartum and 7.5% (36/477) were intrapartum, and 59.2% (261/441) of antepartum stillbirths were observed in association with placental dysfunction and 40.8% (180/441) were unexplained or due to other causes. Second, placental dysfunction accounted for 80.1% (161/201) of antepartum stillbirths at < 32 weeks' gestation, 54.2% (52/96) at 32 + 0 to 36 + 6 weeks and 33.3% (48/144) at ≥ 37 weeks. Third, the risk of placental dysfunction-related antepartum stillbirth increased with increasing maternal weight and decreasing maternal height, was 3-fold higher in black than in white women, was 5.5-fold higher in parous women with previous stillbirth than in those with previous live birth, and was increased in smokers, in women with chronic hypertension and in parous women with a previous pregnancy complicated by pre-eclampsia and/or birth of a small-for-gestational-age baby. Fourth, in screening for placental dysfunction-related antepartum stillbirth by a combination of maternal risk factors, EFW and UtA-PI in the validation dataset, the DR at a 10% FPR was 62.3% (95% CI, 57.2-67.4%) and the AUC was 0.838 (95% CI, 0.799-0.878); these results were consistent with those in the dataset used for developing the algorithm and demonstrate high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 1.029 and the intercept was -0.009, demonstrating good agreement between the predicted risk and observed incidence of placental dysfunction-related antepartum stillbirth. The performance of screening was better for placental dysfunction-related antepartum stillbirth at < 37 weeks' gestation compared to at term (DR at a 10% FPR, 69.8% vs 29.2%).Conclusions: Screening at mid-gestation by a combination of maternal risk factors, EFW and UtA-PI can predict a high proportion of placental dysfunction-related stillbirths and, in particular, those that occur preterm. Such screening provides poor prediction of unexplained stillbirth or stillbirth due to other causes. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether in fetuses with open spina bifida (OSB) the tentorium can be seen to be displaced downwards and vertically oriented by the time of the 11-13-week scan and whether this is reflected in an alteration of the brainstem-tentorium (BST) angle.Methods: The study population was recruited between 2015 and 2020 from three fetal medicine referral centers and comprised a control group and a study group of pregnancies with OSB. The control group was recruited prospectively and included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome. The study group was selected retrospectively and included all cases with OSB between 2015 and 2020. All cases underwent detailed ultrasound assessment at 11 + 0 to 13 + 6 weeks' gestation. The position of the torcular Herophili (TH) was identified in the midsagittal view of the fetal brain with the use of color Doppler and was considered as a proxy for the insertion of the tentorium on the fetal skull. The BST angle was calculated in the same view and was compared between the two groups.Results: Sixty normal fetuses were included in the control group and 22 fetuses with OSB in the study group. In both groups, the BST angle was found to be independent of gestational age or crown-rump length (P = 0.8815, R2  = 0.0003861 in the controls, and P = 0.2665, R2  = 0.00978 in the OSB group). The mean BST angle was 48.7 ± 7.8° in controls and 88.1 ± 1.18°, i.e. close to 90°, in fetuses with OSB. Comparison of BST-angle measurements between the control group and cases with OSB showed a statistically significant difference (P = 0.0153). In all fetuses with OSB, the downward displacement of the TH and tentorium was clearly visible at the 11-13-week scan.Conclusions: In fetuses with OSB, the BST angle is significantly larger than in normal controls, with the tentorium being almost perpendicular to the brainstem. This sign confirms the inferior displacement of the tentorium cerebelli with respect to its normal insertion on the occipital clivus as early as the first trimester of pregnancy and is useful in the diagnosis of Chiari-II malformation at this early stage. In fetuses with OSB, the low position of the tentorium and TH is clearly visible, even subjectively, at the 11-13-week scan. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in combination with the established biomarkers of pre-eclampsia (PE), including mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE.Methods: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at any time and at < 3 weeks after assessment by a combination of maternal demographic characteristics and medical history with biomarkers. The area under the receiver-operating-characteristics curve and detection rate (DR) of delivery with PE, at a 10% false-positive rate (FPR), in screening by combinations of maternal factors with ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio), MAP, UtA-PI, serum PlGF and serum sFlt-1 were determined. The modeled performance of screening for PE was also estimated.Results: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The PSV ratio improved the prediction of PE with delivery at any stage after assessment provided by maternal factors alone (from 25.4% to 50.6%), maternal factors and MAP (54.3% to 62.7%), maternal factors, MAP and PlGF (68.3% to 70.8%) and maternal factors, MAP, PlGF and sFlt-1 (75.7% to 76.7%), at a FPR of 10%. The PSV ratio also improved the prediction of PE with delivery at < 3 weeks after assessment provided by maternal factors alone (from 31.0% to 69.4%), maternal factors and MAP (74.1% to 83.4%), maternal factors, MAP and UtA-PI (77.1% to 85.0%) and maternal factors, MAP and PlGF (84.8% to 88.6%). The empirical results for DR at a 10% FPR were consistent with the modeled results. Screening by a combination of maternal factors with MAP and PSV ratio also detected 59.4% (95% CI, 58.6-82.5%) of cases of gestational hypertension with delivery at any stage after assessment, and 86.7% (95% CI, 82.4-100%) of those with delivery at < 3 weeks after assessment.Conclusion: Ophthalmic artery Doppler could potentially improve the performance of screening for PE at 35-37 weeks, especially imminent PE with delivery within 3 weeks after assessment, but further studies are needed to validate this finding. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To assess whether repeat cervical-length (CL) measurement in women discharged from hospital after their first episode of threatened preterm labor can predict their risk of spontaneous preterm birth.Methods: This was a secondary analysis of a randomized controlled trial of maintenance tocolysis, in which CL was measured on transvaginal ultrasound at the time of hospital discharge and after 2, 4, 8 and 12 weeks, in women who remained undelivered after their first episode of threatened preterm labor. After univariate analysis, multivariate logistic regression analysis was used to assess whether CL < 10 mm at the time of hospital discharge or at any follow-up evaluation could predict spontaneous delivery prior to 37 weeks of gestation.Results: Of 226 women discharged after a diagnosis of threatened preterm labor, 57 (25.2%) delivered spontaneously prior to 37 weeks' gestation. The risk of spontaneous preterm birth was higher among women with CL < 10 mm at hospital discharge compared to those with CL ≥ 10 mm (adjusted odds ratio (aOR), 3.3; 95% CI, 1.2-9.2). Moreover, spontaneous preterm delivery was more common when CL < 10 mm was detected up to 2 weeks (aOR, 2.9; 95% CI, 1.1-7.3) or up to 4 weeks (aOR, 7.3; 95% CI, 2.3-22.8) post discharge, as compared with when CL was persistently ≥ 10 mm. The association was not significant when considering CL measurements at 8 weeks, and there was insufficient information to assess the effect of measurements obtained at 12 weeks.Conclusions: Women who remain undelivered after their first episode of threatened preterm labor continue to be at high risk of spontaneous preterm birth if their CL is below 10 mm at the time of hospital discharge or at any follow-up visit up to 4 weeks later. CL measurement could be included in the antenatal care of these women in order to stratify their risk of preterm birth, rationalize resource utilization and help clinicians improve pregnancy outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS).Methods: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial.Results: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher).Conclusions: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 11-13 weeks' gestation are reduced in pregnancies with fetal trisomy and in those that subsequently develop pre-eclampsia (PE). In screening for trisomy, the established biochemical marker is PAPP-A, whereas in screening for PE, the preferred marker is PlGF. The objective of this study was to examine the impact of replacing PAPP-A by PlGF in first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency thickness (NT) and free β-human chorionic gonadotropin (β-hCG).Methods: This was a prospective screening study in singleton pregnancies for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT and serum PAPP-A and free β-hCG at 11-13 weeks' gestation in which we also measured PlGF. Multiples of the median (MoM) values were calculated for PAPP-A, free β-hCG and PlGF. The dataset was split randomly into training and test datasets of roughly equal size, and the parameters for PlGF obtained from the training dataset were used in risk calculation for the test dataset. Standardized detection rates were computed by obtaining the likelihood ratios for biochemistry and fetal NT for trisomy-21, -18 and -13 pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific detection rates. These were then weighted according to the maternal age distributions of trisomy-21, -18 and -13 pregnancies in England and Wales in 2018. Similarly, standardized false-positive rates (FPR) were computed by obtaining the likelihood ratios for biochemistry and NT, as appropriate, in normal pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific FPRs. A modeling approach was used to assess the performance of screening according to gestational age at biochemical testing.Results: The study population of 71 266 pregnancies included 70 858 (99.4%) with normal fetal karyotype or birth of a phenotypically normal neonate and 263 with trisomy 21, 109 with trisomy 18 and 36 with trisomy 13. There are five main findings of this study. First, the performance of screening for trisomy by the first-trimester combined test or the combined test in which PAPP-A is replaced by PlGF is substantially better at 11 than at 13 weeks' gestation; for example, the detection rates of trisomy 21 by the combined test were 94%, 90% and 84%, at 5% FPR, when testing was carried out at 11, 12 and 13 weeks, respectively, and the corresponding values in screening by a test in which PAPP-A is replaced by PlGF were 90%, 87% and 86%, respectively. Second, in trisomy-21 pregnancies, the deviation of median PAPP-A MoM from normal decreases with increasing gestational age, whereas the deviation in PlGF does not change with gestational age. Third, the performance of screening for trisomy 21 during the 11th and 12th gestational weeks is superior if screening includes PAPP-A rather than PlGF, whereas during the 13th week the performance is slightly higher with the use of PlGF rather than PAPP-A. Fourth, in our population with mean gestational age at testing of 12.7 weeks, screening by maternal age, fetal NT, serum free β-hCG and serum PAPP-A predicted 88%, 96% and 97% of cases of fetal trisomies 21, 18 and 13, respectively, at a FPR of 5%; the respective values in screening by a test in which PAPP-A is replaced by PlGF were 85%, 96% and 96%. Fifth, addition of serum PlGF does not improve the prediction of trisomy provided by maternal age, fetal NT and serum free β-hCG and PAPP-A.Conclusion: In first-trimester screening for trisomy, the preferred biochemical marker is PAPP-A rather than PlGF, especially when biochemical testing is carried out during the 11th week of gestation or earlier. However, if PlGF was to be used rather than PAPP-A, the same detection rate can be achieved but at a higher FPR. This may be an acceptable compromise to minimize cost and achieve effective screening for both trisomy and PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: First-trimester screening for pre-eclampsia (PE) is useful because treatment of the high-risk group with aspirin reduces the rate of early PE with delivery at < 34 weeks' gestation by about 80% and that of preterm PE with delivery at < 37 weeks by 60%. In previous studies, we reported that the best way of identifying the high-risk group is by a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). An alternative biochemical marker is pregnancy-associated plasma protein-A (PAPP-A), which is used widely as part of early screening for trisomy. The objective of this study was to examine the additive value of PlGF and PAPP-A in first-trimester screening for preterm PE by maternal factors, MAP and UtA-PI and define the risk cut-off and screen-positive rate to achieve a desired detection rate of PE if PAPP-A rather than PlGF was to be used for first-trimester screening.Methods: This was a non-intervention screening study. The data were derived from prospective screening for adverse obstetric outcomes in women with singleton pregnancy attending for a routine first-trimester hospital visit. Patient-specific risks of delivery with PE at < 37 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median (MoM) values of MAP, UtA-PI, PlGF and PAPP-A. The performance of screening in the total population and in subgroups of women of white and black racial origin was estimated. McNemar's test was used to compare the detection rate, for a fixed screen-positive rate, of screening with and without PlGF and PAPP-A. Risk cut-offs and screen-positive rates to achieve desired detection rates of preterm PE were determined in screening with and without PlGF and PAPP-A.Results: The study population was composed of 60 875 singleton pregnancies, including 1736 (2.9%) that developed PE. There are three main findings of this study. First, the performance of first-trimester screening for PE by a combination of maternal factors, MAP, UtA-PI and PlGF is superior to that of screening by maternal factors, MAP, UtA-PI and PAPP-A; for example, in screening by maternal factors, MAP, UtA-PI and PlGF, at a screen-positive rate of 10%, the detection rate of PE with delivery at < 37 weeks' gestation was 74.1%, which was 7.1% (95% CI, 3.8-10.6%) higher than in screening by maternal factors, MAP, UtA-PI and PAPP-A. Second, addition of serum PAPP-A does not improve the prediction of PE provided by maternal factors, MAP, UtA-PI and PlGF. Third, the risk cut-off and screen-positive rate to achieve a given fixed detection rate of preterm PE vary according to the racial composition of the study population and whether the biomarkers used for screening are MAP, UtA-PI and PlGF or MAP, UtA-PI and PAPP-A. For example, in screening by a combination of maternal factors, MAP, UtA-PI and PlGF in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 136 and the screen-positive rate would be 14.1%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 29 and the screen-positive rate would be 12.5%. In screening by a combination of maternal factors, MAP, UtA-PI and PAPP-A in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 140 and the screen-positive rate would be 16.9%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 44 and the screen-positive rate would be 19.3%.Conclusion: In first-trimester screening for PE, the preferred biochemical marker is PlGF rather than PAPP-A. However, if PAPP-A was to be used rather than PlGF, the same detection rate can be achieved but at a higher screen-positive rate. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To examine the performance of the routine 11-13-week scan in detecting fetal defects in twin pregnancies and to examine if, in pregnancies with a fetal defect, compared to those with normal fetuses, there is increased incidence of nuchal translucency thickness (NT) ≥ 95th and ≥ 99th percentiles or intertwin discordance in crown-rump length (CRL) ≥ 10% and ≥ 15%.Methods: This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11-13 weeks' gestation between 2002 and 2019. Pregnancies with known chromosomal abnormality were excluded. The final diagnosis of fetal defect was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal defects was determined.Results: The study population of 6366 twin pregnancies with two live fetuses at 11-13 weeks' gestation included 4979 (78.2%) dichorionic (DC) and 1387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than in DC twins (2.8% vs 1.3%); second, the proportion of defects diagnosed in the first trimester was higher in MC than in DC twins (52.6% vs 27.1%); third, the pattern of defects in relation to detectability at the 11-13-week scan (always detectable, sometimes detectable and never detectable) was similar to that reported previously in singleton pregnancies; fourth, always-detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body-stalk anomaly, twin reversed arterial perfusion sequence and conjoined twins; fifth, the incidence of fetal NT ≥ 95th percentile was higher in those with than in those without a defect (16.5% vs 4.5% in DC twins and 19.2% vs 5.9% in MC twins) and this was also true for NT ≥ 99th percentile (8.3% vs 1.0% in DC twins and 15.4% vs 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥ 10% was higher in those with than in those without a defect (20.2% vs 7.9% in DC twins and 33.8% vs 9.3% in MC twins) and this was also true for CRL discordance ≥ 15% (10.1% vs 1.9% in DC twins and 28.2% vs 2.8% in MC twins).Conclusions: First, fetal defects are more common in MC than in DC twin pregnancies. Second, first-trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies. Third, first-trimester detectability of defects in MC twins is higher than in DC twins. Fourth, in twin pregnancies with a fetal defect, there is higher intertwin discordance in CRL and incidence of increased NT, but the predictive performance of screening by these markers is poor. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy.Methods: This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling.Results: First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling.Conclusions: First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To develop enhanced prediction models to update the QUiPP App prototype, a tool providing individualized risk of spontaneous preterm birth (sPTB), for use in women with symptoms of threatened preterm labor (TPTL), incorporating risk factors, transvaginal ultrasound assessment of cervical length (CL) and cervicovaginal fluid quantitative fetal fibronectin (qfFN) test results.Methods: Participants were pregnant women between 23 + 0 and 34 + 6 weeks' gestation with symptoms of TPTL, recruited as part of four prospective cohort studies carried out at 16 UK hospitals between October 2010 and October 2017. The training set comprised all women whose outcomes were known in May 2017 (n = 1032). The validation set comprised women whose outcomes were gathered between June 2017 and March 2018 (n = 506). Parametric survival models were developed for three combinations of predictors: risk factors plus qfFN test results alone, risk factors plus CL alone, and risk factors plus both qfFN and CL. The best models were selected using the Akaike and Bayesian information criteria. The estimated probability of sPTB < 30, < 34 or < 37 weeks' gestation and within 1 or 2 weeks of testing was calculated and receiver-operating-characteristics (ROC) curves were created to demonstrate the diagnostic ability of the prediction models.Results: Predictive statistics were similar between the training and the validation sets at most outcome time points and for each combination of predictors. Areas under the ROC curves (AUC) demonstrated that all three algorithms had good accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1 and 2 weeks' post-testing in the validation set, particularly the model combining risk factors plus qfFN alone (AUC: 0.96 at < 30 weeks; 0.85 at < 34 weeks; 0.77 at < 37 weeks; 0.91 at < 1 week from testing; and 0.92 at < 2 weeks from testing).Conclusions: Validation of the new prediction models suggests that the QUiPP App v.2 can reliably calculate risk of sPTB in women with TPTL. Use of the QUiPP App in practice could lead to better targeting of intervention, while providing reassurance and avoiding unnecessary intervention in women at low risk. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Accurate mid-pregnancy prediction of spontaneous preterm birth (sPTB) is essential to ensure appropriate surveillance of high-risk women. Advancing the QUiPP App prototype, QUiPP App v.2 aimed to provide individualized risk of delivery based on cervical length (CL), quantitative fetal fibronectin (qfFN) or both tests combined, taking into account further risk factors, such as multiple pregnancy. Here we report development of the QUiPP App v.2 predictive models for use in asymptomatic high-risk women, and validation using a distinct dataset in order to confirm the accuracy and transportability of the QUiPP App, overall and within specific clinically relevant time frames.Methods: This was a prospective secondary analysis of data of asymptomatic women at high risk of sPTB recruited in 13 UK preterm birth clinics. Women were offered longitudinal qfFN testing every 2-4 weeks and/or transvaginal ultrasound CL measurement between 18 + 0 and 36 + 6 weeks' gestation. A total of 1803 women (3878 visits) were included in the training set and 904 women (1400 visits) in the validation set. Prediction models were created based on the training set for use in three groups: patients with risk factors for sPTB and CL measurement alone, with risk factors for sPTB and qfFN measurement alone, and those with risk factors for sPTB and both CL and qfFN measurements. Survival analysis was used to identify the significant predictors of sPTB, and parametric structures for survival models were compared and the best selected. The estimated overall probability of delivery before six clinically important time points (< 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks after testing) was calculated for each woman and analyzed as a predictive test for the actual occurrence of each event. This allowed receiver-operating-characteristics curves to be plotted, and areas under the curve (AUC) to be calculated. Calibration was performed to measure the agreement between expected and observed outcomes.Results: All three algorithms demonstrated high accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks of testing, with AUCs between 0.75 and 0.90 for the use of qfFN and CL combined, between 0.68 and 0.90 for qfFN alone, and between 0.71 and 0.87 for CL alone. The differences between the three algorithms were not statistically significant. Calibration confirmed no significant differences between expected and observed rates of sPTB within 4 weeks and a slight overestimation of risk with the use of CL measurement between 22 + 0 and 25 + 6 weeks' gestation.Conclusions: The QUiPP App v.2 is a highly accurate prediction tool for sPTB that is based on a unique combination of biomarkers, symptoms and statistical algorithms. It can be used reliably in the context of communicating to patients the risk of sPTB. Whilst further work is required to determine its role in identifying women requiring prophylactic interventions, it is a reliable and convenient screening tool for planning follow-up or hospitalization for high-risk women. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To report the rate of additional central nervous system (CNS) anomalies detected exclusively on prenatal magnetic resonance imaging (MRI) in fetuses diagnosed with isolated mild or moderate ventriculomegaly (VM) on ultrasound, according to the type of ultrasound protocol adopted (dedicated neurosonography vs standard assessment of the fetal brain), and to explore whether the diagnostic performance of fetal MRI in detecting such anomalies is affected by gestational age at examination and laterality and degree of ventricular dilatation.Methods: MEDLINE, EMBASE, CINAHL and Clinicaltrials.gov were searched for studies reporting on the prenatal MRI assessment of fetuses diagnosed with isolated mild or moderate VM (ventricular dilatation of 10-15 mm) on ultrasound. Additional anomalies detected only on MRI were classified as callosal, septal, posterior fossa, white matter, intraventricular hemorrhage, cortical, periventricular heterotopia, periventricular cysts or complex malformations. The rate of additional anomalies was compared between fetuses diagnosed on dedicated neurosonography, defined as a detailed assessment of the fetal brain, according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines, and those diagnosed on standard fetal brain assessment. The rate of additional CNS anomalies missed on prenatal MRI and detected only at birth was calculated and compared between fetuses that had early (at or before 24 weeks' gestation) and those that had late (after 24 weeks) MRI. Subanalysis was performed according to the laterality (uni- vs bilateral) and degree (mild vs moderate, defined as ventricular dilatation of 10-12 and 13-15 mm, respectively) of ventricular dilatation. Whether MRI assessment led to a significant change in prenatal management was explored. Random-effects meta-analysis of proportions was used.Results: Sixteen studies (1159 fetuses) were included in the systematic review. Overall, MRI detected an anomaly not identified on ultrasound in 10.0% (95% CI, 6.2-14.5%) of fetuses. However, when stratifying the analysis according to the type of ultrasound assessment, the rate of associated anomalies detected only on MRI was 5.0% (95% CI, 3.0-7.0%) when dedicated neurosonography was performed compared with 16.8% (95% CI, 8.3-27.6%) in cases that underwent a standard assessment of the fetal brain in the axial plane. The overall rate of an additional anomaly detected only at birth and missed on prenatal MRI was 0.9% (95% CI, 0.04-1.5%) (I2 , 0%). There was no difference in the rate of an associated anomaly detected only after birth when fetal MRI was carried out before, compared with after, 24 weeks of gestation (P = 0.265). The risk of detecting an associated CNS abnormality on MRI was higher in fetuses with moderate than in those with mild VM (odds ratio, 8.1 (95% CI, 2.3-29.0); P = 0.001), while there was no difference in those presenting with bilateral, compared with unilateral, dilatation (P = 0.333). Finally, a significant change in perinatal management, mainly termination of pregnancy owing to parental request, following MRI detection of an associated anomaly, was observed in 2.9% (95% CI, 0.01-9.8%) of fetuses undergoing dedicated neurosonography compared with 5.1% (95% CI, 3.2-7.5%) of those having standard assessment.Conclusions: In fetuses undergoing dedicated neurosonography, the rate of a CNS anomaly detected exclusively on MRI is lower than that reported previously. Early MRI has an excellent diagnostic performance in identifying additional CNS anomalies, although the findings from this review suggest that MRI performed in the third trimester may be associated with a better detection rate for some types of anomaly, such as cortical, white matter and intracranial hemorrhagic anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and nature of copy number variants (CNVs) identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses with isolated increased nuchal translucency thickness (NT) ≥ 3.5 mm.Methods: This was a retrospective, multicenter study, including 11 French hospitals, of data from the period between April 2012 and December 2015. In total, 720 fetuses were analyzed by rapid aneuploidy test and the fetuses identified as euploid underwent CMA. CNVs detected were evaluated for clinical significance and classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs not related to the phenotype (i.e. incidental findings).Results: In 121 (16.8%) fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53 (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic, including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599 (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%) were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the reason for referral diagnosis (i.e. an incidental finding) and the remaining 21 were benign CNVs, without clinical consequence. Interestingly, we identified five genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with congenital heart defects.Conclusion: Our study demonstrates the benefit of CMA in the etiological diagnosis of fetuses with isolated increased NT. It is worth noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To propose a clinical score for the optimal antenatal diagnosis of fetal lower urinary tract obstruction (LUTO) in the second and third trimesters of pregnancy, as an alternative to the commonly used ultrasound triad of megacystis, keyhole sign and hydronephrosis.Methods: This was a national retrospective study carried out at the eight tertiary fetal medicine units (FMUs) in The Netherlands. Only cases referred for megacystis from the second trimester onwards and with a clear postnatal diagnosis were included in the study. At referral, data were collected on amniotic fluid volume, renal cortical appearance, bladder volume, hydronephrosis, fetal ascites, ureteral size, keyhole sign, fetal sex and gestational age. Multivariate analysis was performed, starting by including all antenatal variables, and then excluding the weakest predictors using the backward stepwise strategy.Results: Over a 7-year period, 312 fetuses with a diagnosis of megacystis were referred to the eight Dutch tertiary FMUs. A final diagnosis was achieved in 143 cases, including 124 of LUTO and 19 reclassified after birth as non-obstructive megacystis. The optimal bladder volume cut-off for prediction of LUTO was 35 cm3 (area under the curve (AUC) = 0.7, P = 0.03). The clinical score formulated on the basis of the multivariate analysis included fetal sex, degree of bladder distension, ureteral size, oligo- or anhydramnios and gestational age at referral. The combination of these five variables demonstrated good accuracy in discriminating LUTO from non-obstructive megacystis (AUC = 0.84, P < 0.001), compared with the poor performance of the ultrasound triad (AUC = 0.63, P = 0.07).Conclusions: We propose a clinical score that combines five antenatal variables for the prospective diagnosis of congenital LUTO. This score showed good discriminative capacity in predicting LUTO, and better diagnostic accuracy compared with that of the classic ultrasound triad. Future studies to validate these results should be carried out in order to refine antenatal management of LUTO and prevent inappropriate fetal interventions. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of chronic hypertension (CH), with and without superimposed pre-eclampsia (PE), on the incidence of a small-for-gestational-age (SGA) neonate and to explore the possible mechanism for such association.Methods: Data for this study were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11-13 weeks' gestation, which included recording of maternal characteristics and medical history and measurement of mean arterial pressure (MAP). Birth-weight Z-score, adjusted for gestational age and maternal and pregnancy characteristics, and incidence of SGA were compared between those with and those without CH in the total population and in the subgroups of pregnancies with and without PE. Regression analysis was used to examine the relationship between MAP and birth-weight Z-score and incidence of SGA and PE in those with and those without CH.Results: The study population constituted 74 226 pregnancies, including 1052 (1.4%) with CH and 73 174 without CH. PE developed in 233 (22.1%) cases of the group with CH and in 1662 (2.3%) of those without CH. In the group that developed PE, there was no significant difference for either median birth-weight Z-score or incidence of SGA between those with CH and those without CH. In the group without PE, the incidence of SGA was twice as high in those with CH than in those without. There was a significant association between log10 MAP multiples of the median and incidence of SGA and PE, which was more marked in those with CH than in those without.Conclusion: CH is associated with an increased risk of SGA and PE and this is related to MAP at 11-13 weeks' gestation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the application of non-invasive prenatal testing (NIPT) as an alternative to invasive diagnostic prenatal testing in pregnancies with abnormal ultrasound findings.Methods: This was a retrospective analysis of 251 singleton and multiple pregnancies at high risk for fetal chromosomal abnormality based on findings at sonographic examination, in which NIPT was performed as a first-tier genetic test. NIPT was performed by massively parallel sequencing of cell-free DNA in maternal plasma, allowing genome-wide detection of whole-chromosome, as well as partial, autosomal aneuploidy. Sex chromosomes were not analyzed, according to the current protocol in Dutch laboratories.Results: NIPT was performed at a median gestational age of 20 weeks, indicated by the presence of multiple congenital anomalies (n = 13), isolated structural anomalies (n = 57), increased nuchal translucency ≥ 3.5 mm (n = 58), soft markers (n = 73), growth restriction (n = 40) and other anomalies (n = 10). NIPT results were normal in 224 (89.2%) pregnancies, inconclusive in one (0.4%) and abnormal in 26 (10.4%). Most genetic aberrations detected by NIPT were common whole-chromosome aneuploidies: trisomy 21 (n = 13), trisomy 18 (n = 6) and trisomy 13 (n = 3). Four further NIPT results were abnormal; one was suspected of being confined placental mosaicism and one was of maternal origin. In those with normal NIPT results, sonographic follow-up or examination of the newborn indicated the need for diagnostic genetic testing in 33/224 (14.7%) pregnancies. Clinically relevant genetic aberrations were revealed in 7/224 (3.1%) cases, two of which were whole-chromosome aneuploidies: trisomy 13 and monosomy X. As sex chromosomal aberrations are not included in NIPT analysis, the latter cannot be considered a false-negative result. Other discordant findings were subchromosomal aberrations (< 20 megabases, n = 2) and monogenic aberrations (n = 3).Conclusions: NIPT should not be recommended for genetic evaluation of the etiology of ultrasound anomalies, as both resolution and sensitivity, or negative predictive value, are inferior to those of conventional karyotyping and microarray analysis. Nonetheless, some pregnant women consider NIPT to be an acceptable alternative to invasive diagnostic testing. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To determine the accuracy of fetal and newborn growth charts for the prediction of small-for-gestational age (SGA) at birth (birth weight < 10th centile).Methods: This was a prospective cohort study performed within a UK specialist fetal growth clinic. A total of 105 consecutive pregnant women referred for a suspected SGA fetus were included. All pregnancies were managed according to a standard protocol using estimated fetal weight (EFW) plotted on customized Gestation Related Optimal Weight (GROW) charts. The last antenatal estimates of EFW (according to charts of GROW, Hadlock et al. and Mikolajczyk et al.), abdominal circumference (AC) (according to charts of Hadlock et al., INTERGROWTH-21st Project and Chitty et al.) or change in AC over time (calculated according to Pregnancy Outcome Prediction (POP) study) were compared against four birth-weight charts (GROW, INTERGROWTH-21st , Mikolajczyk et al. and World Health Organization (WHO)). The ability of each antenatal test to predict adverse perinatal outcome (APO) was assessed.Results: Birth weight < 10th centile was assigned in 62 (59%) neonates using the GROW chart, 57 (54%) using the Mikolajczyk et al. chart, 55 (52%) using the INTERGROWTH-21st chart and 51 (49%) using the WHO chart. AC-Hadlock had the best negative likelihood ratio (range, 0.3-0.4) and sensitivity (range, 74%-82%) for predicting SGA as defined by all four postnatal birth-weight charts. AC-INTERGROWTH-21st had the best positive likelihood ratio (range, 5.9-10.9) and specificity (94%-96%). For prediction of APO, AC-Hadlock and EFW-GROW had the best sensitivities (57% and 52%, respectively), whereas AC-POP had the best positive likelihood ratio (2.2) and specificity (88%). Antenatal prediction of APO increased to a sensitivity of 61% when AC-POP and EFW-GROW were combined; however, specificity was only 56%.Conclusions: We have identified wide variation in the diagnostic accuracy of various antenatal tools for the prediction of both SGA and APO, dependent on the choice of chart. Suboptimal diagnostic accuracy of commonly used antenatal tests may lead to increasing medicalization without prevention of APO. Researchers should focus their attention on a combination of fetal biometry and biomarkers for better prediction of SGA and prevention of APO. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To assess potential differences in fetal size between the French population and the international population from the INTERGROWTH-21st (IG-21st ) Project and to measure the impact of switching to the IG-21st reference standards for fetal size.Methods: This was a nationwide cross-sectional study of fetal ultrasound biometry. Low-risk singleton pregnancies were recruited prospectively within the network of the national French College of Fetal Ultrasound, CFEF, over a 6-week period. Further selection was performed based on the criteria of the IG-21st Project in order to obtain a comparable population. Head circumference (HC) was used as the main fat-free skeletal measure of growth for comparison of French fetal size with that of the IG-21st population. The impact of switching to the IG-21st fetal growth standards was quantified by comparing Z-scores calculated using the IG-21st standards with those calculated using locally derived reference ranges for HC, abdominal circumference (AC) and femur length (FL).Results: Following selection, 4858 cases were analyzed. The distribution of HC demonstrated clear similarity between our French population and the IG-21st population: our observed centile curves closely matched those of IG-21st and the Z-scores were close to 0 across gestational age. The IG-21st standards performed as well as did locally derived charts in terms of screening for small-for-gestational age by AC, while they identified significantly fewer small FL values than were expected and than did the locally derived charts.Conclusions: Under strict selection criteria, fetal size in France is similar to that of the international population used in the IG-21st Project. The discrepancies in FL are unlikely to impact on prenatal management. Therefore, switching from locally derived reference ranges to the IG-21st standards appears to be a safe option. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To develop an objective method for visualizing and measuring the fetal optic chiasm (OC) using transvaginal two-dimensional (2D) ultrasound in the coronal plane and to report measurements in fetuses with agenesis of the septum pellucidum (SP).Methods: This was a prospective cross-sectional study of 115 morphologically normal fetuses in low-risk pregnancies, between 21 and 30 weeks' gestation. The OC was measured in a coronal plane at the level of the third ventricle and was seen as a horizontally aligned dumbbell-shaped structure of moderate echogenicity. In addition, OC measurements from eight fetuses with agenesis of the SP and complete follow-up were compared with the reference range.Results: OC measurements were obtained in 110/115 normal fetuses and showed that OC increases linearly with gestational age. Our method of measurement demonstrated good intraobserver repeatability and excellent interobserver reproducibility. Among the eight fetuses with agenesis of the SP, five had normal OC measurements and five had normal vision postnatally. Pregnancy continued to term in all cases and the follow-up period varied from 6 months to 7 years.Conclusion: Our study demonstrates that it is possible to visualize and measure the OC directly on a 2D ultrasound coronal plane. In fetuses with agenesis of the SP, the morphology and width of the OC visual pathway could prove a relevant tool for assessing its development. It would also help in the difficult task of providing antenatal counseling when faced with the diagnosis of agenesis of the SP. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Inclusion of the three vessels and trachea view in the routine assessment of the fetal heart at the 18-20-week morphology scan improves recognition of a right-sided aortic arch (RAA). We report our experience of RAA diagnosed in an unselected population of pregnant women attending for a routine morphology scan.Methods: The obstetric imaging databases of two ultrasound centers were reviewed retrospectively to identify all routine fetal morphology scans performed at 18-22 weeks' gestation between January 2011 and December 2014. A review of postnatal charts was conducted to ascertain findings at birth, neonatal complications and the anatomical findings at any neonatal echocardiographic or surgical procedure. Parents of older infants were contacted by phone to assess their wellbeing and identify any respiratory or feeding difficulties.Results: In the 48-month study period, 43 083 routine anomaly scans were performed. Twenty-three cases of isolated RAA were identified, a prevalence of 0.05%. Nineteen (83%) cases of isolated RAA had a left-sided arterial duct and four (17%) had a right-sided duct. Postnatal follow-up data were obtained in all cases. The prevalence of a symptomatic vascular ring due to a double aortic arch was 13% (3/23). One (4%) case was diagnosed with DiGeorge syndrome.Conclusions: RAA can be identified easily on a routine fetal anomaly scan, however the prevalence of RAA is low in an unselected population. Antenatally diagnosed cases should be referred for detailed fetal echocardiography and the patient should be made aware of the association with DiGeorge syndrome and the symptoms associated with a vascular ring. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of an ultrasound-based scoring system for diagnosing morbidly adherent placenta (MAP).Methods: This study included pregnant women referred to our ultrasound unit during 2013-2015 because of suspected MAP on a previous ultrasound examination or because they had at least one previous Cesarean delivery. All women were assessed using a scoring system based on the following: number and size of placental lacunae; obliteration of the demarcation between the uterus and placenta; placental location; color Doppler signals within placental lacunae; hypervascularity of the placenta-bladder and/or uteroplacental interface zone; and number of previous Cesarean deliveries. Each criterion was assigned 0, 1 or 2 points and the sum of points yielded the final score. Patients were classified into low, moderate or high probability for MAP based on the final score. The presence of MAP was determined by the surgeon at delivery and clinical descriptions were documented in the electronic patient file. Pathological diagnoses were available only in cases that underwent hysterectomy.Results: In total, 258 pregnant women were included in the study, of whom 23 (8.9%) were diagnosed with MAP. There was a statistically significant difference in the prevalence of MAP when women were grouped according to the scoring system, with 0.9%, 29.4% and 84.2% in the low, moderate and high probability groups, respectively (P < 0.0001). All sonographic criteria of the scoring system were significantly associated with MAP (P < 0.0001). Receiver-operating characteristics (ROC) curves for prediction of MAP using the number of placental lacunae and obliteration of the uteroplacental demarcation yielded an area under the ROC curve of 0.94 (95% CI, 0.86-1.00).Conclusions: Our proposed scoring system is highly predictive of MAP in patients at risk. This allows an adequate multidisciplinary team approach for the planning and timing of delivery in such cases. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: The antenatal diagnosis of twin anemia-polycythemia sequence (TAPS) in monochorionic-diamniotic (MCDA) twin pregnancies is based on elevated peak systolic velocity in the middle cerebral artery (MCA-PSV) in the donor twin and decreased MCA-PSV in the recipient twin. However, the association between these parameters and polycythemia has not yet been established. The aim of this study was to determine whether MCA-PSV can predict polycythemia in MCDA pregnancies.Methods: This was a prospective cohort study of MCDA pregnancies recruited at 14-18 weeks' gestation from a single tertiary care center between January 2011 and June 2014. Fetal MCA Doppler waveforms were recorded every 2 weeks from 18 weeks' gestation until delivery. Only those with an MCA-PSV measurement within 1 week of delivery were included in the analysis. Neonatal hematocrit level was determined in all twins from venous blood obtained within 4 h of delivery. Polycythemia was defined as a hematocrit of > 65%, and anemia as a hematocrit of < 45%. TAPS was diagnosed when an intertwin hemoglobin difference of > 8 g/dL and reticulocyte count ratio of > 1.7 were observed.Results: Of 162 MCDA pregnancies followed during the study period, 69 had an MCA-PSV measurement within 1 week of delivery and were included in the study. Twenty-five neonates were diagnosed with polycythemia and nine twin pairs met the criteria for TAPS. In a pooled analysis, MCA-PSV was negatively correlated with neonatal hematocrit (P = 0.017, r = -0.215) and was significantly higher in anemic fetuses than in normal controls (1.15 multiples of the median (MoM) vs 1.02 MoM, respectively; P = 0.001). However, MCA-PSV was similar among polycythemic and normal fetuses (0.95 MoM vs 1.02 MoM, respectively; P = 0.47). Intertwin difference in MCA-PSV (delta MCA-PSV) was positively correlated with intertwin hematocrit difference (P = 0.002, r = 0.394). Moreover, twin pregnancies with an intertwin hematocrit difference of > 24% had a significantly greater delta MCA-PSV than did those with an intertwin hematocrit difference of ≤ 24% (delta MCA-PSV, 19 vs 5 cm/s; P < 0.001).Conclusions: MCA-PSV is not significantly decreased in polycythemic MCDA twins. However, delta MCA-PSV is associated with a large intertwin difference in hematocrit, and its use may be better than conventional methods for the risk assessment of TAPS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To analyze whether the frequency of autism spectrum disorder (ASD) in a cohort of Swedish children differs between those exposed to ultrasound in the 12(th) week and those exposed to ultrasound in the 18(th) week of gestation.Methods: The study cohort consisted of approximately 30 000 children born between 1999 and 2003 to mothers who had been randomized to a prenatal ultrasound examination at either 12 or 18 weeks' gestation as part of the framework for a study on nuchal translucency screening. The outcome measure in the present study was the rate of ASD diagnoses among the children. Information on ASD diagnoses was based on data from the Swedish social insurance agency concerning childcare allowance granted for ASD.Results: Between 1999 and 2003, a total of 14 726 children were born to women who underwent a 12-week ultrasound examination and 14 596 to women who underwent an 18-week ultrasound examination. Of these, 181 (1.2%) and 176 (1.2%) children, respectively, had been diagnosed with ASD. There was no difference in ASD frequency between the early and late ultrasound groups.Conclusions: Women subjected to at least one prenatal ultrasound examination at either 12 or 18 weeks' gestation had children with similar rates of ASD. However, this result reflects routine care 10-15 years ago in Sweden. Today, higher intensity ultrasound scans are performed more frequently, at earlier stages during pregnancy and for non-medical purposes, implying longer exposure time for the fetus. This change in the use of ultrasound necessitates further follow-up study of the possible effects that high exposure to ultrasound during the gestational period has on the developing brain. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: A prenatal ultrasound examination and a postmortem examination provide the basis for correct diagnosis in fetuses terminated due to congenital anomalies. The aim of this study was to correlate fetal anomalies detected by ultrasound examination with those identified at autopsy following termination of pregnancy (TOP) over a 30-year period, and to evaluate the correlation between findings at different gestational ages and assess these trends over time.Methods: The study group consisted of 1029 TOPs performed over a 30-year period, from 1985 to 2014. The gestational age ranged between 11 and 33 weeks. Prenatal ultrasound examinations were performed at the National Center for Fetal Medicine, St Olavs Hospital, Trondheim, Norway. Autopsies were performed at the Department of Pathology and Medical Genetics at the same hospital or a collaborating hospital.Results: There was full agreement between ultrasound and autopsy findings in 88.1% (907/1029) of TOPs, and the main diagnosis was correct in 97.9% (1007/1029). When comparing the 15-year period of 2000-2014 with that of 1985-1999, the difference in the rates of full agreement and agreement in the main diagnosis was statistically significant. In 1.3% (13/1029) of cases, ultrasound findings were not confirmed at autopsy. There were no false-positive diagnoses leading to TOP. Throughout the 30-year period, there was an increase in early TOPs, whereas late TOPs declined.Conclusions: Our study demonstrates that there is a clear correlation between ultrasound and autopsy findings, which is continuously improving. Despite this high correlation, there is reason to continue the practice of validation to ensure the safety of the diagnostic process leading to TOP. The trend towards an earlier termination emphasizes the necessity of such a practice. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To describe the timing of the ultrasound appearance of olfactory sulci in normal fetuses, according to gestational age.Methods: Olfactory sulci were assessed prospectively in the coronal plane on routine brain ultrasound examination in 100 normal fetuses between 22 and 31 + 6 weeks' gestation. Examinations were divided into five groups according to gestational age: Group 1, 22 to 23 + 6 weeks (n = 22); Group 2, 24 to 25 + 6 weeks (n = 9); Group 3, 26 to 27 + 6 weeks (n = 25); Group 4, 28 to 29 + 6 weeks (n = 22) and Group 5, 30 to 31 + 6 weeks (n = 22). For each fetus, olfactory sulci were assessed as absent, developing or formed.Results: Developing sulci appeared as primitive smooth depressions in the frontal lobe, which evolved into deep sharp complete sulci in later pregnancy. It was possible to assess the development of sulci in all cases. Olfactory sulci were consistently absent in Group 1. In Group 2, 44.4% of fetuses had absent olfactory sulci and 55.6% had developing sulci. In Group 3, the olfactory sulci were still developing in 21 (84.0%) fetuses and were completely formed in four (16.0%). Sulci were completely formed in all fetuses in Groups 4 and 5.Conclusions: Fetal brain ultrasound can visualize developing olfactory sulci from as early as 24 weeks' gestation. After 26 weeks, fetuses have detectable olfactory sulci and, after 28 weeks, they are completely formed. Abnormal development of olfactory sulci is a key feature of CHARGE syndrome. These results may help to improve the prenatal diagnosis of CHARGE syndrome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging.Methods: MEDLINE and EMBASE were searched electronically utilizing combinations of relevant medical subject headings for 'posterior fossa' and 'outcome'. The posterior fossa anomalies analyzed were Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes observed were rate of chromosomal abnormalities, additional anomalies detected at prenatal magnetic resonance imaging (MRI), additional anomalies detected at postnatal imaging and concordance between prenatal and postnatal diagnoses. Only isolated cases of posterior fossa anomalies - defined as having no cerebral or extracerebral additional anomalies detected on ultrasound examination - were included in the analysis. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. We used meta-analyses of proportions to combine data and fixed- or random-effects models according to the heterogeneity of the results.Results: Twenty-two studies including 531 fetuses with posterior fossa anomalies were included in this systematic review. The prevalence of chromosomal abnormalities in fetuses with isolated DWM was 16.3% (95% CI, 8.7-25.7%). The prevalence of additional central nervous system (CNS) abnormalities that were missed at ultrasound examination and detected only at prenatal MRI was 13.7% (95% CI, 0.2-42.6%), and the prevalence of additional CNS anomalies that were missed at prenatal imaging and detected only after birth was 18.2% (95% CI, 6.2-34.6%). Prenatal diagnosis was not confirmed after birth in 28.2% (95% CI, 8.5-53.9%) of cases. MCM was not significantly associated with additional anomalies detected at prenatal MRI or detected after birth. Prenatal diagnosis was not confirmed postnatally in 7.1% (95% CI, 2.3-14.5%) of cases. The rate of chromosomal anomalies in fetuses with isolated BPC was 5.2% (95% CI, 0.9-12.7%) and there was no associated CNS anomaly detected at prenatal MRI or only after birth. Prenatal diagnosis of BPC was not confirmed after birth in 9.8% (95% CI, 2.9-20.1%) of cases. The rate of chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI, 0.8-17.1%) and there were no additional anomalies detected at prenatal MRI (0% (95% CI, 0.0-45.9%)). The proportions of cerebral anomalies detected only after birth was 14.2% (95% CI, 2.9-31.9%). Prenatal diagnosis was not confirmed after birth in 32.4% (95% CI, 18.3-48.4%) of cases.Conclusions: DWM apparently isolated on ultrasound imaging is a condition with a high risk for chromosomal and associated structural anomalies. Isolated MCM and BPC have a low risk for aneuploidy or associated structural anomalies. The small number of cases with isolated VH prevents robust conclusions regarding their management from being drawn. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart.Methods: In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated.Results: One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance.Conclusions: In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject.Methods: We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression.Results: The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (β = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (β = 10.6, P = 0.04 and β = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (β = -14.7, P = 0.03).Conclusion: In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence and impact of extracardiac anomalies on the prognosis of fetuses with heterotaxy syndrome. Methods: All fetuses diagnosed with heterotaxy syndrome by three experienced examiners over a period of 14 years (1999-2013) were reviewed retrospectively. Results: In total, 165 fetuses with heterotaxy syndrome were diagnosed in the study period. One hundred and fifty (90.9%) had cardiac defects; extracardiac anomalies that did not involve the spleen were present in 26/165 (15.8%) cases. Of the total study cohort, termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were alive at the latest follow-up, resulting in a total perinatal and pediatric mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac anomalies with significant impact on the postnatal course: one neonate died following repair of an encephalocele, six had successful treatment for various types of intestinal malrotation and/or atresia and one underwent hiatal hernia repair; the remaining seven had biliary atresia, of which five died and the two survivors are awaiting liver transplantation. The status of the spleen was assessed in 93/105 liveborn children and was found to be abnormal in 84/93 (90.3%). There were three cases of lethal sepsis, all associated with asplenia. Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an extracardiac cause and in two (5.2%) the reason was uncertain. Conclusions: Although the leading causes of death in fetuses and children with heterotaxy syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with significant impact on outcome. These anomalies often escape prenatal detection, and therefore neonates at risk should be monitored for bowel obstruction, biliary atresia and immune dysfunction in order to allow timely intervention through a multidisciplinary approach. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population.Methods: Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery ≥ 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks.Results: Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a-posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11).Conclusion: A strategy of selecting 50% of the study population to undergo third-trimester ultrasound examination, based on accrued risk in the second trimester, proved equivalent to routine third-trimester ultrasound scanning in predicting late FGR. [ABSTRACT FROM AUTHOR]

Objective: To describe the anatomical structures that form the anterior (AC) and posterior (PC) complexes of the fetal brain and to categorize their anomalies in fetuses with cerebral abnormalities.Methods: We analyzed retrospectively volume datasets from 100 normal fetuses between 20 and 30 weeks' gestation. On the axial transventricular plane, our analysis of the AC included the interhemispheric fissure (IHF), the callosal sulcus (CS), the genu of the corpus callosum (CC), the cavum septi pellucidi (CSP) and the anterior horns (AH) of the lateral ventricles. The PC included the splenium of the CC, the medial wall of the lateral ventricles, the CS and the parieto-occipital fissure (POF). We then categorized AC/PC findings in 32 fetuses with agenesis of the septi pellucidi, schizencephaly, callosal dysgenesis, cortical malformation and hypoxic-ischemic brain injury.Results: The structures forming the AC and PC were visible in 100% and 92%, respectively, of normal cases. In the AC, the CSP was square-shaped in 73% of cases and it was triangular in 27%; the AH was comma-shaped in 92% of cases and triangular in the remainder. In the PC, the splenium of the CC interrupted and bridged the midline and was delimited posteriorly by the CS and the IHF. The POF was visible posteriorly. We categorized AC and PC abnormalities according to the main deviation from normality in their anatomical structures. The AC was abnormal in 30/32 cases and the PC was abnormal in 16/32 cases. In the two cases with normal AC, the PC was abnormal.Conclusion: Normal appearance of AC and PC seems to be a strong indicator of fetal central nervous system normality. Morphological abnormalities in both complexes are robust markers of midline defects, but not exclusively so. The majority of fetuses with cortical malformations showed a defect in the AC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of combined screening by maternal characteristics and medical history, fetal biometry and biophysical and biochemical markers at 19-24 weeks' gestation, for prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE), and examine the potential value of such assessment in deciding whether the third-trimester scan should be at 32 and/or 36 weeks' gestation.Methods: This was a screening study in 7816 singleton pregnancies, including 389 (5.0%) that delivered SGA neonates with birth weight < 5(th) percentile (SGA < 5(th) ), in the absence of PE. Multivariable logistic regression analysis was used to determine if screening by a combination of maternal factors, fetal biometry, uterine artery pulsatility index (UtA-PI) and maternal serum concentrations of placental growth factor (PlGF) and α-fetoprotein (AFP) had significant contribution in predicting SGA neonates. A model was developed for selecting the gestational age for third-trimester assessment, at 32 and/or 36 weeks, based on the results of screening at 19-24 weeks.Results: Significant independent contributions to the prediction of SGA < 5(th) were provided by maternal factors, fetal biometry, UtA-PI and serum PlGF and AFP. The detection rate (DR) of such combined screening at 19-24 weeks was 100%, 78% and 42% for SGA < 5(th) delivering < 32, at 32-36 and ≥ 37 weeks' gestation, respectively, at a false-positive rate (FPR) of 10%. In a hypothetical model, it was estimated that if the desired objective of prenatal screening is to predict about 80% of the cases of SGA < 5(th) , it would be necessary to select 11% of the population at the 19-24-week assessment to be reassessed at 32 weeks and 44% to be reassessed at 36 weeks; 57% would not require a third-trimester scan.Conclusion: Prenatal prediction of a high proportion of SGA neonates necessitates the undertaking of screening in the third trimester of pregnancy, in addition to assessment in the second trimester, and the timing of such screening, at 32 and/or 36 weeks, should be contingent on the results of the assessment at 19-24 weeks. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential value of combined screening by maternal characteristics and medical history (maternal factors), estimated fetal weight (EFW), uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP) and serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-34 weeks' gestation in the prediction of delivery of small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE).Methods: This was a screening study in 9472 singleton pregnancies at 30-34 weeks' gestation, comprising 469 that delivered SGA neonates and 9003 cases unaffected by SGA, PE or gestational hypertension. Multivariable logistic regression analysis was used to determine if UtA-PI, MAP and serum PlGF or sFlt-1, individually or in combination, improved the prediction of SGA neonates provided from screening by maternal factors and EFW.Results: Compared to the normal group, mean log10 multiples of the median (MoM) values of UtA-PI, MAP and serum sFlt-1 were significantly higher and log10 MoM PlGF was lower in the SGA group. Multivariable logistic regression analysis demonstrated that in the prediction of SGA neonates with a birth weight < 5(th) percentile, delivering < 5 weeks and ≥ 5 weeks after assessment, there were significant independent contributions from maternal factors, EFW, UtA-PI, MAP, and serum PlGF and sFlt-1, but the best performance was provided by a combination of maternal factors, EFW, UtA-PI, MAP and serum PlGF, excluding sFlt-1. Combined screening predicted, at a 10% false-positive rate, 89%, 94%, 96% of SGA neonates delivering at 32-36 weeks' gestation with birth weight < 10(th) , < 5(th) and < 3(rd) percentiles, respectively; the respective detection rates of combined screening for SGA neonates delivering ≥ 37 weeks were 57%, 65% and 72%.Conclusion: Combined screening by maternal factors and biophysical and biochemical markers at 30-34 weeks' gestation could identify a high proportion of pregnancies that will deliver SGA neonates. [ABSTRACT FROM AUTHOR]

The article offers information on the study that examines the role of fetal magnetic resonance imaging (MRI) in the prenatal diagnosis of facial clefts. It notes that 34 pregnant women with a mean gestational age of 26 weeks who underwent in utero MRI were the subjects in the study. The study finds that MRI offers better detection and classification of facial clefts than ultrasound alone.

The article presents a study that identifies the sonographic dimensions of the facial profile of the fetus in normal pregnancy. The study was undertaken through a cross-sectional study of 397 normal healthy fetus at 14-33 weeks of gestation. Results of the study showed that there was a significant linear correlation between the gestational age (GA) of the fetus and the distance from the tip of its nose to its mouth which can be used as a tool for the diagnosis of abnormal fetal facial pressure.

Objectives The aim of this study was to describe a novel three-dimensional (3D) ultrasound rendering technique to examine the normal fetal posterior palate and to assess its correspondence with the real fetal anatomy. Methods A prospective longitudinal study was conducted from January to October 2005 and included 100 fetuses in a low-risk population. Fetal ultrasound examinations were performed at 17, 22, 27 and 32 weeks' gestation to determine the normal 3D ultrasound view of the fetal palate at different gestational ages. The ultrasound scans were performed using the strict anterior axial plane of the starting reconstruction volume and the underside 3D view of the fetal palate. The 3D view of the fetal palate was compared with the normal anatomical view of the fetal palate obtained by surgical fetopathological examination of fetuses at the same gestational ages. The sonographic visualization rates of seven defined anatomical landmarks of the fetal palate were computed for each gestational age. The visualization rates across gestational ages were compared by use of the Cochrane Q test. The reliability of detection of each anatomical landmark across gestational ages was determined by Cronbach's Alpha. Results In all cases a 3D ultrasound view of the fetal maxilla and secondary palate was obtained at each period of gestation and corresponded well to the fetal anatomical specimens. The seven defined anatomical landmarks of the fetal palate were identified in 42–100% of cases. The visualization rates across gestational ages were significantly different in five of these anatomical landmarks. These differences can be explained by different developmental processes of these anatomical structures. The overall reliability of visualization across the gestational ages for the anatomical landmarks was medium to very high (0.73–0.96), except for the landmark interpalatal suture which was low (0.48). Conclusions This technique of anterior axial 3D view reconstruction of the fetal palate seen by an underside view can provide unique diagnostic information on the integrity of the secondary palate. This innovative, simple and rapid technique may become the reference technique in ultrasound investigation of the fetal palate, and should be of value in diagnosing isolated secondary cleft palate or palatal involvement when cleft lip and alveolus are diagnosed. [ABSTRACT FROM AUTHOR]

Objective The widely applied transcerebellar diameter (TCD) obtained at axial cranial imaging, measures the distance between the lateral aspects of the cerebellum and incorporates the width of the cerebellar vermis. Our objective was to create reference ranges of axial fetal cerebellar hemisphere circumference (CHC) and area (CHA), independent of the cerebellar vermis, throughout gestation. Methods This cross-sectional study involved pregnant patients between 14 and 41 weeks of gestation. Inclusion criteria consisted of well-established dates (confirmed by early ultrasound), non-anomalous singleton fetuses and intact amniotic membranes. Sonographic measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), humerus length (HL), TCD, and estimated fetal weight (EFW). Values of axial fetal CHC and CHA were each calculated as the mean of three separate measurements. The 5th, 50th and 95th centiles were estimated at each week of gestational age (GA) by least-squares regression for the mean and standard deviation (SD) of the CHC and CHA as functions of GA. r² and associated P-values for the relationships of CHC and CHA with other sonographic biometric measurements were calculated. Results The study included 651 consecutive patients. All attempts at obtaining axial fetal CHC and CHA were successful. Mean maternal age was 27.3 ± 6.7 years, median gravidity was 1 (range 1–16), and median parity was 1 (range 0–6). Mean CHC (cm) throughout gestation was modeled as -2.091 + 0.2563 × GA (weeks) (SD = -0.075 + 0.0164 × GA), and mean CHA (cm²) was modeled as 0.245–0.0765 × GA + 0.00506 × GA² (SD = 1.167∸0.1565 × GA + 0.006785 × GA² ∸ 0.00008028 × GA³). Fetal axial CHC and CHA correlated significantly and strongly with BPD, HC, AC, HL, FL, TCD and EFW (all R2 values were ± 0.95, and all P-values were < 0.001). Conclusion Nomograms of axial fetal cerebellar hemisphere circumference and area throughout gestation, independent of the cerebellar vermis, have been provided. [ABSTRACT FROM AUTHOR]

Objectives: To assess the use of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of the fetal kidney and to estimate age-dependent changes in the apparent diffusion coefficient (ADC) of normal and pathological fetal kidneys.Methods: DW-MRI was performed on a 1.5-T machine at 23-38 gestational weeks in 51 pregnant women in whom the fetal kidneys were normal and in 10 whose fetuses had renal pathology (three with suspected nephropathy, three with renal tract dilatation, one with unilateral renal venous thrombosis, and three with twin-twin transfusion syndrome (TTTS)). The ADC was measured in an approximately 1-cm2 region of interest within the renal parenchyma.Results: ADC values in normal renal parenchyma ranged from 1.1 to 1.8 10(-3) mm2 s-1. There was no significant age-dependent change in the ADC of normal kidneys. In cases of nephropathy, the ADC value was not always pathological but an ADC map could show abnormal findings. In cases of dilatation, the ADC value was difficult to determine when the dilatation was huge. In cases of TTTS, the ADC of the donor twin was higher than that of the recipient twin and the difference seemed to be related to the severity of the syndrome.Conclusion: Evaluation of the ADC for fetal kidneys is feasible. Fetal measurement of the ADC value and ADC maps may be useful tools with which to explore the fetal kidney when used in conjunction with current methods. DW-MR images, ADC value and ADC map seem to be useful in cases of suspected nephropathy (hyperechoic kidneys), dilated kidney and vascular pathology (renal venous thrombosis, TTTS). [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility and clinical potential of 4D volume rendering of the atrioventricular (AV) valve junction, to standardize the acquisition method, and to display the AV valve junction morphology in normal fetuses and in those with a complete atrioventricular septal defect (AVSD). Methods: We performed sonography in 40 normal fetuses and 10 fetuses with complete AVSD, and volume datasets were acquired from apical and lateral four-chamber views. The render box was placed systematically. First, it included the AV valves, with the reference dot at the level of the crux of the heart. Then, it included the papillary muscles, with the reference dot in the interventricular septum at the level of the distal opening of the tricuspid valve leaflet. Results: Volume acquisition and rendering were technically possible in all cases. Volume rendering of the left ventricle showed the position of the anterolateral and posteromedial papillary muscles in 36/40 normal fetuses (90%). At the level of the right ventricle, the septal, anterior and posterior papillary muscles were visualized in 33/40 normal fetuses (82%). In cases of complete AVSD, the AV valve has five leaflets, with anterosuperior and posteroinferior bridging leaflets straddling the septa. The morphology of the anterosuperior bridging leaflets and the abnormal position of the papillary muscles could be displayed in all cases. Conclusions: Our study suggests that some of the components of the AV junction can be reconstructed easily from sonographic volumes acquired from an apical or lateral four-chamber view. This new technique may have a role in obtaining views that are not easily accessible by standard sonography, enabling a rapid complementary assessment of normal and abnormal intracardiac anatomy. [ABSTRACT FROM AUTHOR]

Objective: To analyze the most relevant anomalies, seen in a sequential segmental transverse views approach to imaging the fetal heart, that provide clues to the diagnosis of complete transposition of the great arteries (TGA). Methods: We reviewed retrospectively all the cases of isolated TGA diagnosed in our center or submitted for a second opinion through the spatio-temporal image correlation (STIC) telemedicine (TELE-STIC) program. Only transverse cardiac sweeps were obtained. Digital video clips and STIC volumes were reviewed. The abnormal features on four-chamber, five-chamber, three-vessel (3V) and three vessels and trachea (3VT) views were analyzed. Results: The study population consisted of eight fetuses with TGA with normal extracardiac anatomy. The gestational age ranged from 13 to 32 (mean, 23) weeks. The maternal age ranged from 25 to 42 (mean, 32) years. A normal four-chamber view was seen in seven cases. Only one case demonstrated a significant ventricular septal defect. At the level of the five-chamber view a straight course arterial vessel arose from the left ventricle with lateral branches in all fetuses. In the 3V view, the ascending aorta was seen reaching more anteriorly than was the pulmonary artery in six cases. At the level of the 3VT view, two vessels (transverse aortic arch and superior vena cava) rather than three were seen in all cases. Conclusion: Our proposed sequential segmental approach to imaging the fetal heart apparently allows, in five-chamber and 3VT views, clear and confident signs to be detected that aid diagnosis of TGA. [ABSTRACT FROM AUTHOR]

Objective: We have reported previously that valve dilation enhances growth of cardiac structures and may prevent hypoplastic left heart syndrome (HLHS) in fetuses with critical aortic stenosis. We aimed to investigate maternal/fetal factors which may affect the technical success of fetal valvuloplasty, and to describe perinatal complications of the procedure. Methods: This was a descriptive series of 22 fetuses diagnosed with critical aortic stenosis developing into HLHS which underwent intervention by valvuloplasty. Initially this was attempted using a percutaneous approach; reassessment after our first five attempts, only one of which was successful, led to the introduction of the option of laparotomy. Technical success was defined as balloon inflation across the aortic annulus and a broader jet through the aortic valve as assessed by Doppler. Data collected included body mass index, demographic variables, ultrasound findings and postprocedure interventions. Results: Technical success increased significantly if maternal laparotomy was an option (83.3% vs. 20.0%, P = 0.017). Laparotomy was performed in 66.6% (12/18) of cases. There was a learning curve that showed an increase in success rate and decrease in need for laparotomy over the 3-year study period. Neither the need for laparotomy nor the chances of technical success were predictable by gestational age, body mass index or placental location. Tocolysis was limited to perioperative prophylaxis; one woman experienced wound infection and fluid overload. Postoperatively, three fetuses died and two delivered prematurely, 2 and 7 weeks after intervention. Conclusion: Fetal aortic valvuloplasty can be performed with technical success, with low fetal loss rate and few maternal complications. While the need for laparotomy cannot be predicted, having it available as an option improves the technical success rate. [ABSTRACT FROM AUTHOR]

Objectives: To assess the reliability of two-dimensional gray-scale (2D) and color Doppler echocardiography in the study of the size and anatomy of the central pulmonary arteries and of the sources of pulmonary blood flow in a case series of fetuses with pulmonary atresia and ventricular septal defect (PA-VSD), and to evaluate whether the use of 4D ultrasound with B-flow imaging and spatio-temporal image correlation (STIC) can improve prenatal diagnostic accuracy. Methods: The study population comprised a group of seven PA-VSD fetuses that had been examined by 2D and color Doppler echocardiography exclusively, and a group of five additional cases identified initially by conventional echocardiography and examined further by 4D ultrasound, for all of which a thorough postnatal or autopsy study of the size and anatomy of the pulmonary arteries and blood supply was available. Results: 2D and color Doppler echocardiography failed to assess the anatomy of the central pulmonary arteries and the source of the pulmonary blood supply in 33% and 25% of the 12 cases, respectively. 4D ultrasound with B-flow imaging and STIC assessed successfully the anatomy of the pulmonary arteries and the source of pulmonary blood supply in all five fetuses examined. Conclusions: The prognosis of PA-VSD is influenced by the anatomy of the pulmonary arteries and the sources of the pulmonary blood supply, and by coexisting extracardiac and genetic anomalies. Our findings, although limited to a small sample size, suggest that 4D echocardiography with B-flow imaging and STIC, unlike 2D ultrasound, can provide thorough visualization of very small vessels and of the arterial blood supply to the lungs of fetuses with PA-VSD. 4D ultrasound may be used in the future to improve and help to detail the diagnosis of other fetal cardiac defects. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the spatio-temporal image correlation (STIC) acquisition technique can be taught to a general obstetrician by e-mail; whether STIC volume datasets can be transmitted over the Internet; and whether STIC volume datasets analyzed offline at a remote setting can be used to confirm or exclude major cardiac defects (TELE-STIC). Methods: This was a prospective study involving 50 pregnant women with gestational ages ranging between 20 and 36 weeks. These patients were selected by two general obstetricians (operators) working in geographically remote areas of Chile. Although both obstetricians were users of equipment capable of four-dimensional (4D) ultrasound with STIC, they lacked skill in the performance of fetal cardiac examination. A dedicated web disk was created to upload the acquired volume datasets using an Internet broadband connection. Offline analysis was performed by a single investigator experienced in fetal echocardiography (the administrator). Results: A telemedicine link via the Internet was possible in all cases. Seventy-seven volume datasets were sent to the web server. A complete cardiac examination according to set criteria was achieved by the administrator in 86% of the cases scanned by one operator and 95% of the cases scanned by the other operator. Three patients had cardiac defects confirmed postnatally, two fetuses had extracardiac anomalies and one fetus had a suspected cardiac defect unconfirmed by second-opinion TELE-STIC. There were two isolated major congenital heart defects. Both patients were given advice by e-mail and teleconference using a web camera about the likely outcome and benefits of scheduling in utero transport to a tertiary care center. Conclusions: STIC volumes can be obtained by operators inexperienced in fetal echocardiography, transmitted via the Internet, and their analysis enables recognition of most of the structures and views necessary to assess fetal cardiac anatomy. The preliminary use of TELE-STIC allowed us to demonstrate that some intracardiac anomalies can be ruled out and others confirmed, allowing perinatal management to be tailored accordingly. [ABSTRACT FROM AUTHOR]

A case of mixed intrahepatic arteriovenous shunts in a fetus diagnosed at 35 weeks' gestation is presented. Color Doppler ultrasonography in the fetal liver demonstrated complicated vascular connections fed by the hepatic arterial branches and drained into the portal and middle hepatic veins. Pulsed Doppler ultrasonography identified a high cardiac output state by the detection of increased flow velocities of the great vessels. The contribution of Doppler ultrasonography to hemodynamic changes is highlighted. The management is briefly discussed. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to investigate whether the prenatal diagnosis of a ‘lean’ umbilical cord in otherwise normal fetuses identifies fetuses at risk of being small for gestational age (SGA) at birth and of having distress in labor. The umbilical cord was defined as lean when its cross-sectional area on ultrasound examination was below the 10th centile for gestational age. Method Pregnant women undergoing routine sonographic examination were included in the study. Inclusion criteria were gestational age greater than 20 weeks, intact membranes, and singleton gestation. The sonographic cross-sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. Umbilical artery Doppler waveforms were recorded during fetal apnea and fetal anthropometric parameters were measured. Results During the study period, 860 patients met the inclusion criteria, of whom 3.6% delivered a SGA infant. The proportion of SGA infants was higher among fetuses who had a lean umbilical cord on ultrasound examination than among those with a normal umbilical cord (11.5% vs. 2.6%, p < 0.05). Fetuses with a lean cord had a risk 4.4-fold higher of being SGA at birth than those with a normal umbilical cord. After 25 weeks of gestation, this risk was 12.4 times higher when the umbilical cord was lean than when it was of normal size. The proportion of fetuses with meconium-stained amniotic fluid at delivery was higher among fetuses with a lean cord than among those with a normal umbilical cord (14.6% vs. 3.1%, p < 0.001). The proportion of infants who had a 5-min Apgar score < 7 was higher among those who had a lean cord than among those with normal umbilical cord (5.2% vs. 1.3%, p < 0.05). Considering only patients admitted in labor with intact membranes and who delivered an appropriate-for-gestational-age infant, the proportion of fetuses who had oligohydramnios at the time of delivery was higher among those who h... [ABSTRACT FROM AUTHOR]

Standard sonographic views of the brain obtained along the axial planes at mid-gestation failed to identify absence of the septum pellucidum in two consecutive fetuses. It was presumably the close proximity of the walls of the lateral ventricles that generated an artifact resembling a normal cavum septi pellucidi. In one of these fetuses, septo-optic dysplasia was confirmed by magnetic resonance demonstration of hypoplastic optic tracts. In the other fetus, isolated absence of the septum pellucidum was the final diagnosis. Standard axial scans are unreliable in predicting absence of the septum pellucidum in the mid-trimester fetus when the lateral ventricles are normal in size. [ABSTRACT FROM AUTHOR]