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Objectives: An increased nuchal translucency (NT) thickness of ≥ 3.5 mm is a well-established marker for congenital anomalies and adverse pregnancy outcome between 11 and 14 weeks' gestation, but little is known about its performance as a screening tool before 11 weeks. We aimed to investigate, in a prospective setting, whether fetuses with increased NT before 11 weeks are at risk for adverse pregnancy outcome., Methods: This was a prospective cohort study including pregnant women with a viable fetus with NT ≥ 2.5 mm and a crown-rump length (CRL) < 45 mm. All included women were referred to our fetal medicine unit (FMU) and scheduled for a follow-up scan where the NT was remeasured after 1 week when the CRL was > 45 mm. Two groups were evaluated: cases with a normalized NT (< 3.5 mm) and cases with persistently increased NT (≥ 3.5 mm). The cases were monitored until 4 weeks after delivery. The main outcome was a composite adverse outcome of aneuploidy, other genetic disorders, structural anomalies and pregnancy loss. We performed subgroup analyses of NT thickness at inclusion and normalized or persistently increased NT at follow-up., Results: The study included 109 cases, of which 39 (35.8%) had an adverse pregnancy outcome. Of these, 64.1% (25/39) were aneuploid, corresponding to 22.9% (25/109) of the total study population. In the subgroups of NT thickness at inclusion of 2.5-3.4 mm, 3.5-4.4 mm and ≥ 4.5 mm, an adverse outcome was reported in 22.0% (9/41), 40.0% (18/45) and 52.2% (12/23), respectively. In fetuses with a normalized NT and without ultrasound abnormalities at the follow-up scan, the incidence of adverse outcome was 8.5% (5/59), of which 5.1% (3/59) cases were aneuploid., Conclusions: Fetuses with an early increased NT thickness are at considerable risk of an adverse pregnancy outcome, even if the NT normalizes after 11 weeks. Not all congenital anomalies can be diagnosed with routine first-trimester screening, such as non-invasive prenatal testing and/or a first-trimester anomaly scan. Therefore, expectant parents should always be referred to a FMU for detailed ultrasonography. Invasive prenatal testing should be offered if an increased NT of ≥ 2.5 mm is observed before 11 weeks' gestation. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To determine whether implementation of cell-free DNA (cfDNA) testing for aneuploidy as a first-tier test and subsequent abolition of first trimester combined testing (FCT) affected the first trimester detection (<14 weeks) of certain fetal anomalies., Methods: We performed a geographical cohort study in two Fetal Medicine Units between 2011 and 2020, including 705 fetuses with prenatally detected severe brain, abdominal wall and congenital heart defects. Cases were divided into two groups: before (n = 396) and after (n = 309) cfDNA introduction. The primary outcome was the first trimester detection rate (<14 weeks) overall and for non-chromosomal anomalies solely., Results: Overall, gastroschisis, AVSD and HLHS were detected more often in the first trimester in the before group compared to the after group, respectively 54.5% versus 18.5% (p = 0.004), 45.9% versus 26.9% (p = 0.008) and 30% versus 3.4% (p = 0.005). After exclusion of chromosomal anomalies identifiable through cfDNA testing, the detection of AVSD remained higher in the before group (43.3% vs. 9.5%, p = 0.02), leading to a possible earlier gestation at termination. The termination of pregnancy (TOP) rate did not differ among the groups. In the after group, referrals for suspected anomalies following a dating scan between 11 and 14 weeks significantly increased from 17.4% to 29.1% (p < 0.001)., Conclusion: This study underscores the value of a scan dedicated to fetal anatomy in the first trimester as we observed a decline in the early detection of certain fetal anomalies (detectable in the first trimester) subsequent to the abolition of FCT., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objectives: Fetal premature atrial contractions (PAC) are usually benign but may be associated with congenital heart defect (CHD) and tachyarrhythmia, which in turn carry a risk of cardiac failure and fetal death. We aimed to explore the frequency of adverse outcome and to identify risk factors for tachyarrhythmia in pregnancies complicated by fetal PAC., Methods: This was a retrospective cohort study of fetuses diagnosed with PAC at two academic centers in Amsterdam, The Netherlands, between 2007 and 2022. Cases with a congenital anomaly and those with a prior diagnosis of CHD or other arrhythmias were excluded. M-mode and Doppler tracings were reanalyzed and the frequency of PAC was recorded. The incidence of the following adverse outcomes was examined: underlying CHD not identified at the 20-week fetal anomaly scan, tachyarrhythmia, other arrhythmia, administration of antiarrhythmic therapy and death. Risk factors for tachyarrhythmia were analyzed using odds ratios (OR)., Results: In 24.1% of 1439 referred cases, PAC resolved before confirmation at the fetal medicine unit (FMU). Of the 939 included cases with confirmed PAC, the total incidence of adverse outcome was 6.8% (64/939). CHD was diagnosed in 14 (1.5% (95% CI, 0.9-2.5%)) cases, of which eight were diagnosed prenatally and six postnatally. Compared with baseline, the incidence of CHD was higher in the presence of fetal PAC (OR, 1.8 (95% CI, 1.0-3.3); P = 0.034). Tachyarrhythmia occurred prenatally and/or postnatally in 32 (3.4%) cases, of which eight (25.0%) showed signs of cardiac failure, and in 23 (71.9%) cases, antiarrhythmic therapy was required. No cases of tachyarrhythmia led to fetal or infant death. Risk factors for tachyarrhythmia were PAC with short runs of supraventricular tachycardia (OR, 98.7), blocked PAC (OR, 30.3), PAC in bigeminy (OR, 21.8), frequent PAC (one per 5-10 beats) (OR, 6.9), signs of cardiac failure (OR, 14.2) and the presence of a foramen ovale aneurysm (OR, 5.0)., Conclusions: PAC are generally benign and often resolve spontaneously. However, fetuses with an irregular heart rhythm should be referred for advanced ultrasonography, which should focus on classifying the type of PAC and risk of adverse outcome. When risk factors for tachyarrhythmia are identified, weekly fetal heart-rate monitoring is advised until resolution of the PAC. In the absence of risk factors, standard obstetric care may be sufficient, with additional instructions to report reduced fetal movements. Should tachyarrhythmia or cardiac failure develop, referral back to the FMU is indicated. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To evaluate and compare the outcome of fetuses and neonates with congenital small bowel obstructions (SBO), evaluate the screening performance of prenatal ultrasound for SBO and identify possible risk factors for adverse outcomes., Methods: All cases referred to the Amsterdam University Medical Centers between 2007 and 2021 for a prenatal suspected SBO, supplemented by cases of postnatal diagnosis of SBO, were included. The primary outcome was survival after 24 weeks of gestation until the first year of life., Results: 147 cases of SBO were included with a survival rate of 86.2% (119/138) after 24 weeks of gestation until the first year of age. Additional structural or chromosomal anomalies were found to have an increased risk of adverse outcomes. Intrauterine fetal demise occurred in 10/147 (6.8%) cases and 9/147 (6.1%) cases died during postnatal follow-up. The overall positive predictive value of all prenatally diagnosed cases was 91.5%. Surgical correction was performed in 123/128 (96.0%) of the live-born cases., Conclusions: Congenital SBO has an overall favorable prognosis, but the outcome is negatively impacted by the possible presence of additional structural or chromosomal anomalies. Fetal monitoring in the early third trimester should be considered, since all cases of Intrauterine fetal demise occurred between 30 and 35 weeks of gestation., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objectives: Fetal motor assessment (FMA) in addition to structural anomaly scan enhances prenatal detection of arthrogryposis multiplex congenita (AMC). In the Amsterdam UMC, sonographers are trained to perform FMA. We examined the effect of motor assessment training by comparing sonographers with (SMA) and without this training (S) on their qualitative motor assessment in fetuses with normal (FNM) and abnormal motility (FAM) and their visual processing by eye-tracking., Methods: The study was performed from 2019 to 2020. Five SMA and five S observed five FNM and five FAM videos. Qualitative FMA consisted of six aspects of the general movement and the overall conclusion normal or abnormal. The visual processing aspects examined through eye-tracking were fixation duration, number of revisits per region of interest (ROI) and scanpaths of saccades between fixation points., Results: Quality assessment by SMA revealed more correct aspects in FNM than in FAM but overall conclusions were equally correct (92-96 %). S scored aspects of FNM better than in FAM, but overall conclusion correct only in half of FNM and three quarters of FAM. Eye-tracking of SMA and S showed fixation duration and revisits with similar distributions per ROIs for FNM and FAM, but SMA perform more trunk revisits in FNM. Scanpaths had smaller circumference, less outliers and more consistency in SMA than S., Conclusion: This modest population of qualified sonographers showed that additional FMA training improved qualitative motor assessment. Eye-tracking revealed differences in visual processing and stimulates continuous education for professionals active in the detection of these rare diseases., Competing Interests: Declaration of competing interest There were no competing interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the quality of fetal heart images, obtained during the second-trimester standard anomaly scan (SAS) in cases of CHD, to explore factors associated with a missed prenatal diagnosis., Methods: In this case-control study, all cases of a fetus born with isolated severe CHD in the Northwestern region of The Netherlands, between 2015 and 2016, were extracted from the PRECOR registry. Severe CHD was defined as need for surgical repair in the first year postpartum. Each cardiac view (four-chamber view (4CV), three-vessel (3V) view and left and right ventricular outflow tract (LVOT, RVOT) views) obtained during the SAS was scored for technical correctness on a scale of 0 to 5 by two fetal echocardiography experts, blinded to the diagnosis of CHD and whether it was detected prenatally. Quality parameters of the cardiac examination were compared between cases in which CHD was detected and those in which it was missed on the SAS. Regression analysis was used to assess the association of sonographer experience and of screening-center experience with the cardiac examination quality score., Results: A total of 114 cases of isolated severe CHD at birth were analyzed, of which 58 (50.9%) were missed and 56 (49.1%) were detected on the SAS. The defects comprised transposition of the great arteries (17%), aortic coarctation (16%), tetralogy of Fallot (10%), atrioventricular septal defect (6%), aortic valve stenosis (5%), ventricular septal defect (18%) and other defects (28%). No differences were found in fetal position, obstetric history, maternal age or body mass index (BMI) or gestational age at examination between missed and detected cases. Ninety-two cases had available cardiac images from the SAS. Compared with the detected group, the missed group had significantly lower cardiac examination quality scores (adequate score (≥ 12) in 32% vs 64%; P = 0.002), rate of proper use of magnification (58% vs 84%; P = 0.01) and quality scores for each individual cardiac plane (4CV (2.7 vs 3.9; P < 0.001), 3V view (3.0 vs 3.8; P = 0.02), LVOT view (1.9 vs 3.3; P < 0.001) and RVOT view (1.9 vs 3.3; P < 0.001)). In 49% of missed cases, the lack of detection was due to poor adaptational skills resulting in inadequate images in which the CHD was not clearly visible; in 31%, the images showed an abnormality (mainly septal defects and aortic arch anomalies) which had not been recognized at the time of the scan; and, in 20%, the cardiac planes had been obtained properly but showed normal anatomy. Multivariate regression analysis showed that the volume of SAS performed per year by each sonographer was associated significantly with quality score of the cardiac examination., Conclusions: A lack of adaptational skills when performing the SAS, as opposed to circumstantial factors such as BMI or fetal position, appears to play an important role in failure to detect CHD prenatally. The quality of the cardiac views was inadequate significantly more often in undetected compared with detected cases. Despite adequate quality of the images, CHD was not recognized in 31% of cases. A high volume of SAS performed by each sonographer in a large ultrasound center contributes significantly to prenatal detection. In 20% of undetected cases, CHD was not visible even though the quality of the images was good. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Neurodevelopmental delay is frequently encountered in children with a congenital heart defect (CHD). Fetuses with major CHD have a smaller head circumference (HC), irrespective of altered cerebral flow or brain oxygenation. This cohort study compared head growth in cases with isolated vs those with non-isolated CHD to evaluate the effect of additional pathology on head size in these fetuses., Method: All CHD cases diagnosed prenatally in the period January 2002-July 2014 were selected from our regional registry, PRECOR. Cases of multiple pregnancy, and those affected by maternal diabetes, severe fetal structural brain anomalies or functional CHD were excluded. Subjects were divided into groups according to whether the CHD was isolated, and the non-isolated group was subdivided into three groups: cases with genetic anomaly, extracardiac malformation or placental pathology. In both isolated and non-isolated CHD groups, CHDs were also grouped according to their potential effect on aortic flow and oxygen saturation. Mean HC Z-scores at 20 weeks and increase or decrease (Δ) of HC Z-scores over the course of pregnancy were compared between isolated and non-isolated groups, using mixed linear regression models., Results: Included were 916 cases of CHD diagnosed prenatally, of which 378 (41.3%) were non-isolated (37 with placental pathology, 217 with genetic anomaly and 124 with extracardiac malformation). At 20 weeks, non-isolated cases had significantly lower HC Z-scores than did isolated cases (Z-score = -0.70 vs -0.03; P < 0.001) and head growth over the course of pregnancy showed a larger decrease in this group (Δ HC Z-score = -0.03 vs -0.01 per week; P = 0.01). Cases with placental pathology had the lowest HC Z-score at 20 weeks (Z-score = -1.29) and the largest decrease in head growth (Δ HC Z-score = -0.06 per week). In CHD subjects with a genetic diagnosis (Z-score = -0.73; Δ HC Z-score = -0.04 per week) and in those with an extracardiac malformation (Z-score = -0.49; Δ HC Z-score = -0.02 per week), HC Z-scores were also lower compared with those in subjects with isolated CHD. CHDs that result in low oxygenation or flow to the brain were present more frequently in isolated than in non-isolated cases., Conclusions: Smaller HC in fetuses with CHD appears to be associated strongly with additional pathology. Placental pathology and genetic anomaly in particular seem to be important contributors to restricted head growth. This effect appears to be irrespective of altered hemodynamics caused by the CHD. Previously reported smaller HC in CHD should, in our opinion, be attributed to additional pathology. Neurodevelopment studies in infants with CHD should, therefore, always differentiate between isolated and non-isolated cases. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Cardiac ventricular size disproportion is a marker for aortic coarctation (CoA) in fetal life, but approximately 50% of fetuses do not have CoA after birth. The aim of this study was to evaluate the postnatal outcome of cases with fetal ventricular size disproportion in the absence of CoA after birth., Methods: All cases with fetal isolated ventricular size disproportion diagnosed between 2002 and 2015 were extracted from a prenatal congenital heart defects regional registry. Cases were stratified according to presence or absence (non-CoA) of aortic arch anomalies after birth. Postnatal outcome of non-CoA cases was evaluated by assessing the presence of cardiac and other congenital malformations, genetic syndromes and other morbidity after birth. Non-CoA cases were further classified according to whether they had cardiovascular pathology requiring medication or intervention., Results: Seventy-seven cases with fetal ventricular size disproportion were identified, of which 46 (60%) did not have CoA after birth. Of these, 35 did not require cardiovascular intervention or medication, whereas 11 did. Of the 46 non-CoA cases, six presented with clinical pulmonary hypertension requiring treatment after birth, cardiac defects were present in 24 cases and syndromic features were seen in four. Overall, 43% of all non-CoA children were still under surveillance at the end of the study period., Conclusions: The postnatal course of cases with fetal ventricular size disproportion is complicated by prenatally undetected congenital defects (46%) and pulmonary or transition problems (35%) in a significant number of cases that do not develop CoA. Proper monitoring of these cases is therefore warranted and it is advisable to incorporate the risks for additional morbidity and neonatal complications in prenatal counseling. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Background: A disintegrin and metalloprotease 12s (ADAM12s) is a potential first trimester serum marker for fetal trisomy and adverse pregnancy outcome in singletons. In this study, ADAM12s levels in first trimester serum of uncomplicated and complicated twins were evaluated., Methods: ADAM12s was studied in maternal serum of 215 twin pregnancies, collected between 2004 and 2008. ADAM12s was measured 'blind to outcome' using AutoDelfia (PerkinElmer, Turku, Finland). As a reference, data from 2423 singletons were used., Results: The median ADAM12s level was increased in euploid twins [1.61 multiples of the median (MoM); n = 209] compared with singletons. The median ADAM12s MoM was significantly lower in monochorionic (1.36 MoM; n = 41) compared with dichorionic twins (1.67 MoM; n = 168) (Mann-Whitney U test, p = 0.005). Trisomy 21 was identified in two pregnancies. Median ADAM12s MoM in twins complicated by hypertensive disorders (1.77 MoM, n = 35) or small for gestational age fetus (1.54 MoM; n = 24) was not significantly different from uncomplicated twins (1.64 MoM; n = 134)., Conclusion: Median ADAM12s MoM in euploid twins was increased compared with singletons. Monochorionic had significantly lower median ADAM12s MoM than dichorionic twins. Median ADAM12s MoMs were not significantly different in twins complicated by hypertensive disorders or small for gestational age fetus compared with uncomplicated twins., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Objective: To evaluate the potential of maternal serum A Disintegrin And Metalloprotease 12-S (ADAM12s) as an additional marker for the combined test in the Dutch first-trimester national Down syndrome (DS) screening program., Methods: Serum samples were collected between 2004 and 2007 as part of the national program. A total of 218 singleton cases of trisomy 21 (DS), 62 trisomy 18 (Edwards syndrome) and 29 trisomy 13 (Patau syndrome) were identified. All cases were matched with controls for gestation, maternal weight and maternal age. The serum concentration of ADAM12s was determined 'blind' to outcome and expressed in multiples of the gestation-specific median for controls (MoM)., Results: The median ADAM12s was 1.00 MoM in controls and in the DS cases at 8, 9, 10, 11, 12, 13 weeks it was 0.45 (n = 3), 0.73 (22), 0.74 (53), 0.85 (37), 0.92 (71), 1.06 (32) MoM, respectively. The median for trisomy 18 was 0.85 MoM and for trisomy 13 0.63 MoM., Conclusion: The ADAM12s MoM values were clearly reduced in early first-trimester for all trisomies. However, the screening performance for DS did not greatly improve adding ADAM12s. ADAM12s could be an additional biochemical marker for first-trimester screening for trisomies other than DS.

Background: In the Netherlands, prenatal screening for trisomy 21 in the first trimester of pregnancy for singletons is conducted through a combined test based on maternal age, nuchal translucency measurement and maternal serum free beta-hCG and PAPP-A. In our clinic risk calculations in twins are currently based on the NT of both fetuses instead of the combined test. In this study we looked at differences in early first-trimester free beta-hCG and PAPP-A between mono- and dichorionic twins., Methods: A total of 202 twin pregnant women participated in the study and agreed to donate first-trimester serum for research., Results: The data of 200 twins with normal outcome were used for setting up reference values for free beta-hCG and PAPP-A. Trisomy 21 was identified in the two remaining pregnancies. The overall median weight-corrected MoM was 1.99 for free beta-hCG, and 2.14 for PAPP-A in all twins. Monochorionic twins have a significantly lower free beta-hCG weight-corrected MoM (1.53 vs 2.11; Mann-Whitney U, p=0.002) and a significantly lower PAPP-A weight-corrected MoM (1.59 vs 2.40; Mann-Whitney U, p=0.003) compared to dichorionic., Conclusion: This study strengthened the need to make a distinction between mono- and dichorionic twins for the risk calculation in Down syndrome screening as biochemical markers are significantly lower in monochorionic than in dichorionic twins., (Copyright (c) 2009 John Wiley & Sons, Ltd.)