Fetal echogenic bowel: what is real echogenicity? A quantitative method based on histogram analysis of the grayscale.

INTRODUCTION: The aim of this study was to use computerized analysis of the grayscale spectrum (histogram) to provide an objective assessment of the echogenicity of the fetal bowel. Moreover, we investigated the role of histogram analysis in the prenatal prediction of postnatal outcomes in fetuses with echogenic bowel (FEB). METHODS: This is a single-center retrospective study including all fetuses with a diagnosis of echogenic bowel (FEB) in the mid-second trimester between 2015 and 2021. Ultrasound images were analyzed using ImageJ software. The mean of the grayscale histograms of bowel, liver, and iliac/femur bone was obtained for each patient and the ratio between these structures was used to overcome gain variations. We compared these values with those of a matched control group of singleton uncomplicated pregnancies and with a group of patients referred for FEB, where the FEB was not confirmed by the expert operator (FEB false positive, FEBfp). RESULTS: There was a statistically significant difference between Bowel/Liver and Bowel/Bone histogram ratios between the FEB group and the control groups (p<0.05). Mean ratio cut-offs were provided for the diagnosis of FEB. Among the patients with confirmed FEB, both ratios were not able to discriminate the cases with adverse outcomes. In contrast, the presence of dilated bowel or other markers was associated with an adverse outcome. CONCLUSIONS: Histogram analysis may refine the diagnosis of FEB and reduce the number of false positive diagnoses. For the prediction of fetal outcome, the presence of additional features is clinically more significant than the degree of bowel echogenicity.

Informed choice and routinization of the second-trimester anomaly scan: a national cohort study in the Netherlands.

BACKGROUND: Since 2007 all pregnant women in the Netherlands are offered the second-trimester anomaly scan (SAS) in a nationwide prenatal screening program. This study aims to assess the level of informed choice of women opting for the SAS and to evaluate the presence of routinization 16 years after its implementation. It further explores decisional conflict and women's decision making. METHODS: This prospective national survey study consisted of an online questionnaire which was completed after prenatal counseling and before undergoing the SAS. Informed choice was measured by the adapted multidimensional measure of informed choice (MMIC) and was defined in case women were classified as value-consistent, if their decision for the SAS was deliberated and made with sufficient knowledge. RESULTS: A total of 894/1167 (76.6%) women completed the questionnaire. Overall, 54.8% made an informed choice, 89.6% had good knowledge, 59.8% had deliberated their choice and 92.7% held a positive attitude towards the SAS. Women with low educational attainment (p=0.004) or respondents of non-Western descent (p=0.038) were less likely to make an informed choice. Decisional conflict was low, with a significantly lower decisional conflict score in women that made an informed choice (p<0.001). Most respondents (97.9%) did not perceive pressure to undergo the SAS. CONCLUSIONS: Our study showed a relatively low rate of informed choice for the SAS, due to absence of deliberation. Therefore, some routinization seem to be present in the Netherlands. However, most women had sufficient knowledge, did not perceive pressure and experienced low decisional conflict.

Current practice of first-trimester ultrasound screening for structural fetal anomalies in developed countries.

OBJECTIVES: First-trimester ultrasound screening is increasingly performed to detect fetal anomalies early in pregnancy, aiming to enhance reproductive autonomy for future parents. This study aims to display the current practice of first-trimester ultrasound screening in developed countries. METHOD: An online survey among 47 prenatal screening experts in developed countries. RESULTS: First-trimester structural anomaly screening is available in 30 of the 33 countries and is mostly offered to all women with generally high uptakes. National protocols are available in 23/30 (76.7%) countries, but the extent of anatomy assessment varies. Monitoring of scan quality occurs in 43.3% of the countries. 23/43 (53.5%) of the respondents considered the quality of first-trimester ultrasound screening unequal in different regions of their country. CONCLUSIONS: First-trimester screening for structural fetal anomalies is widely offered in developed countries, but large differences are reported in availability and use of screening protocols, the extent of anatomy assessment, training and experience of sonographers and quality monitoring systems. Consequently, this results in an unequal offer to parents in developed countries, sometimes even within the same country. Furthermore, as offer and execution differ widely, this has to be taken into account when results of screening policies are scientifically published or compared.

Organ-specific learning curves of sonographers performing first-trimester anatomical screening and impact of score-based evaluation on ultrasound image quality.

INTRODUCTION: First-trimester anatomical screening (FTAS) by ultrasound has been introduced in many countries as screening for aneuploidies, but also as early screening for fetal structural abnormalities. While a lot of emphasis has been put on the detection rates of FTAS, little is known about the performance of quality control programs and the sonographers' learning curve for FTAS. The aims of the study were to evaluate the performance of a score-based quality control system for the FTAS and to assess the learning curves of sonographers by evaluating the images of the anatomical planes that were part of the FTAS protocol. METHODS: Between 2012-2015, pregnant women opting for the combined test in the North-Netherlands were also invited to participate in a prospective cohort study extending the ultrasound investigation to include a first-trimester ultrasound performed according to a protocol. All anatomical planes included in the protocol were documented by pictures stored for each examination in logbooks. The logbooks of six sonographers were independently assessed by two fetal medicine experts. For each sonographer, logbooks of examination 25-50-75 and 100 plus four additional randomly selected logbooks were scored for correct visualization of 12 organ-system planes. A plane specific score of at least 70% was considered sufficient. The intra-class correlation coefficient (ICC), was used to measure inter-assessor agreement for the cut-off scores. Organ-specific learning curves were defined by single-cumulative sum (CUSUM) analysis. RESULTS: Sixty-four logbooks were assessed. Mean duration of the scan was 22 ± 6 minutes and mean gestational age was 12+6 weeks. In total 57% of the logbooks graded as sufficient. Most sufficient scores were obtained for the fetal skull (88%) and brain (70%), while the lowest scores were for the face (29%) and spine (38%). Five sonographers showed a learning curve for the skull and the stomach, four for the brain and limbs, three for the bladder and kidneys, two for the diaphragm and abdominal wall and one for the heart and spine and none for the face and neck. CONCLUSION: Learning curves for FTAS differ per organ system and per sonographer. Although score-based evaluation can validly assess image quality, more dynamic approaches may better reflect clinical performance.

Patient experience with non-invasive prenatal testing (NIPT) as a primary screen for aneuploidy in the Netherlands.

BACKGROUND: Non-invasive prenatal testing (NIPT) as a screening method for trisomy 21 and other chromosomal abnormalities has been adopted widely across the globe. However, while many clinical validation studies have been performed, less is known regarding the patient experience with NIPT. This study explored how individuals experience NIPT in a pre- and post-test setting, where NIPT is broadly available as a primary screening method with the option of reporting beyond common trisomies. METHODS: Participants were recruited using social media with a strategy designed to select individuals who had the option to have NIPT as part of the TRIDENT-2 study (In the Netherlands, NIPT is only available within the TRIDENT studies executed by the NIPT consortium. This research was done independently from the NIPT consortium.) in the Netherlands. The study used online questionnaires and semi-structured interviews. Both were developed around a patient experience framework consisting of seven themes: information, patient as active participant, responsiveness of services, lived experience, continuity of care and relationships, communication, and support. RESULTS: Overall, 4539 questionnaire responses were analyzed and 60% of the respondents had experienced NIPT. Of those, 1.7% received a high-risk result for trisomy or another chromosomal copy number variant (referred to as an "additional finding"). Overall, participants felt they had received sufficient information and had control over their decision regarding whether or not to choose NIPT. The vast majority of respondents who had NIPT were positive about their experience and would use it again. Those with results showing an increased probability for trisomy or additional findings were more likely to report negative feelings such as tension and anxiety, and less likely to feel that they had been sufficiently prepared for the implications of their results. CONCLUSIONS: The patient experience with first-tier NIPT in the Netherlands was largely positive. Areas for improvement included counseling on the implications of screening and the different possible outcomes of NIPT, including additional findings that may be uncovered by expanding NIPT beyond the common trisomies. The experiences reported in this study may be useful for other countries intending to implement NIPT.

Additional value of advanced ultrasonography in pregnancies with two inconclusive cell-free DNA draws.

OBJECTIVE: We aimed to evaluate the additional value of advanced fetal anatomical assessment by ultrasound in pregnancies with twice inconclusive noninvasive testing (NIPT) due to low fetal fraction (FF). METHODS: We performed a multicenter-retrospective study between 2017 and 2020 including 311 pregnancies with twice inconclusive NIPT due to low FF ≤ 1%. Women were offered invasive testing and advanced fetal anatomical assessment at ≤18 weeks' gestation. Ultrasound findings, genetic testing, and pregnancy/postnatal outcomes were evaluated. RESULTS: Ninety-two/311 (29.6%) women underwent invasive testing. Structural anomalies were diagnosed in 13/311 (4.2%) pregnancies (nine at the first scan and four at follow-up). In 6/13 (46.2%) cases, genetic aberrations were confirmed (one case of Trisomy 13 (detectable by NIPT), two of Triploidy, one of 16q12-deletion, HCN4-mutation and UPD(16) (nondetectable by NIPT). Genetic aberrations were found in 4/298 (1.3%) structurallynormal pregnancies (one 47XYY, two microscopic aberrations, one monogenic disorder found postpartum). Structural anomalies in genetically normal fetuses (2.0%) were not more prevalent compared to the general pregnant population (OR 1.0 [0.4-2.2]). CONCLUSION: In pregnancies with twice inconclusive NIPT due to low FF, fetal structural anomalies are not more prevalent than in the general obstetric population. The detailed anatomical assessment has the added value to detect phenotypical features suggestive of chromosomal/genetic aberrations and identify pregnancies where advanced genetic testing may be indicated.

Timing of diagnosis of fetal structural abnormalities after the introduction of universal cell-free DNA in the absence of first-trimester anatomical screening.

INTRODUCTION: Since 2021, first-trimester anatomical screening (FTAS) is offered in the Netherlands alongside genome-wide cell-free DNA (cfDNA). Previously, only second-trimester anatomical screening (STAS) was offered. This study identifies structural abnormalities amenable to first-trimester diagnosis detected at/after STAS in the period following cfDNA implementation and preceding FTAS introduction. METHODS: This retrospective cohort includes 547 fetuses referred between 2017 and 2020 because of suspected structural abnormalities before/at/after STAS. Additional prenatal investigations and postnatal follow-up were searched. Abnormalities were classified into "always", "sometimes", and "never" detectable in the first-trimester based on a previously suggested classification. RESULTS: Of the 547 pregnancies, 13 (2.6%) received FTAS and 534 (97.6%) received a dating ultrasound and STAS. In 492/534 (92.1%) anomalies were confirmed; 66 (13.4%) belonged to the "always detectable" group in the first trimester, 303 (61.6%) to the "sometimes detectable", and 123 (25.0%) to the never detectable. Of the "always detectable" anomalies 29/66 (44%) were diagnosed during dating ultrasounds and 37 (56%) during STAS. The rate of termination of pregnancy for anomalies detected during FTAS and at/after STAS was 84.6% (n = 11/13) and 29.3% (n = 144/492) (p < 0.01). CONCLUSION: When FTAS is not part of screening paradigms, most fetal anomalies remain undetected until the second trimester or later in pregnancy, including 56% of anomalies "always detectable" in the first trimester.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Cardiovascular determinants of impaired placental function in women with cardiac dysfunction.

Female heart disease has for a long time been an underrecognized problem in the field of cardiology. With an ever-growing number of these patients getting pregnant, cardiac dysfunction during pregnancy is an increasingly large medical problem. Previous work has shown that maternal heart disease may have an adverse effect on pregnancy outcome in both mother and child. The placenta forms the connection and it is postulated that cardiac dysfunction negatively affects the placenta, and consequently, neonatal outcome. Given the paucity of data in this field, more research on the influence of cardiac (mal)function on placental (mal)function is needed. The present review describes placental function in women with various types of cardiac dysfunction, thereby aiming to provide more insight into possible underlying mechanisms of placental malfunction. Organ dysfunction in patients with heart failure is for an important part based on reduced perfusion and venous congestion. This has been shown in other organs such as kidneys, liver and brain. In pregnant women with cardiac dysfunction, placental dysfunction may follow similar patterns. Moreover, other factors, such as pre-existing hypertension and chronic hypoxia may lead to further impairment of placental function, through abnormal vascular remodeling of the uterine spiral arteries. The pathophysiology of placental dysfunction in pregnant women with cardiac dysfunction may thus be multifactorial. It is therefore important to monitor closely cardiac and placental function in such high-risk pregnancies. Gaining a better understanding of the underlying pathophysiological mechanisms may have important clinical implications in terms of pregnancy counseling, monitoring and outcome.

Altered neurodevelopmental DNA methylation status after fetal growth restriction with brain-sparing.

It is under debate how preferential perfusion of the brain (brain-sparing) in fetal growth restriction (FGR) relates to long-term neurodevelopmental outcome. Epigenetic modification of neurotrophic genes by altered fetal oxygenation may be involved. To explore this theory, we performed a follow-up study of 21 FGR children, in whom we prospectively measured the prenatal cerebroplacental ratio (CPR) with Doppler sonography. At 4 years of age, we tested their neurodevelopmental outcome using the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and the Behavior Rating Inventory of Executive Function. In addition, we collected their buccal DNA to determine the methylation status at predefined genetic regions within the genes hypoxia-inducible factor-1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), erythropoietin (EPO), EPO-receptor (EPOR), brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor, type 2 (NTRK2) by pyrosequencing. We found that FGR children with fetal brain-sparing (CPR <1, n = 8) demonstrated a trend (0.05 < p < 0.1) toward hypermethylation of HIF1A and VEGFA at their hypoxia-response element (HRE) compared with FGR children without fetal brain-sparing. Moreover, in cases with fetal brain-sparing, we observed statistically significant hypermethylation at a binding site for cyclic adenosine monophophate response element binding protein (CREB) of BDNF promoter exon 4 and hypomethylation at an HRE located within the NTRK2 promoter (both p <0.05). Hypermethylation of VEGFA was associated with a poorer Performance Intelligence Quotient, while hypermethylation of BDNF was associated with better inhibitory self-control (both p <0.05). These results led us to formulate the hypothesis that early oxygen-dependent epigenetic alterations due to hemodynamic alterations in FGR may be associated with altered neurodevelopmental outcome in later life. We recommend further studies to test this hypothesis.

The implementation of non-invasive prenatal testing (NIPT) in the Netherlands.

In the Netherlands prenatal screening is offered as a mean to increase reproductive choices of couples. All women are counseled on the existing options by trained midwives. The government puts a great emphasis on informed choice and on womens' opinions and reactions to screenings options. Since 2017 non-invasive prenatal testing (NIPT, cf-DNA) is offered as first tier screening for aneuploidies in the genome-wide (GW) variant at the cost of 175 Euro's. Uptake is around 50%. This screenings offer is perceived as unconventional for the traditionally cautious Dutch system.

Psychological outcomes, knowledge and preferences of pregnant women on first-trimester screening for fetal structural abnormalities: A prospective cohort study.

INTRODUCTION: The primary aim of this study is to investigate the impact of a 13-week anomaly scan on the experienced levels of maternal anxiety and well-being. Secondly, to explore women's knowledge on the possibilities and limitations of the scan and the preferred timing of screening for structural abnormalities. MATERIAL AND METHODS: In a prospective-cohort study conducted between 2013-2015, pregnant women in the North-Netherlands underwent a 13-week anomaly scan. Four online-questionnaires (Q1, Q2, Q3 and Q4) were completed before and after the 13- and the 20-week anomaly scans. In total, 1512 women consented to participate in the study and 1118 (74%) completed the questionnaires at Q1, 941 (64%) at Q2, 807 (55%) at Q3 and 535 (37%) at Q4. Psychological outcomes were measured by the state-trait inventory-scale (STAI), the patient's positive-negative affect (PANAS) and ad-hoc designed questionnaires. RESULTS: Nine-nine percent of women wished to be informed as early as possible in pregnancy about the absence/presence of structural abnormalities. In 87% of women levels of knowledge on the goals and limitations of the 13-week anomaly scan were moderate-to-high. In women with a normal 13-week scan result, anxiety levels decreased (P < .001) and well-being increased over time (P < .001). In women with false-positive results (n = 26), anxiety levels initially increased (STAI-Q1: 39.8 vs. STAI-Q2: 48.6, P = 0.025), but later decreased around the 20-week anomaly scan (STAI-Q3: 36.4 vs. STAI-Q4: 34.2, P = 0.36). CONCLUSIONS: The 13-week scan did not negatively impact the psychological well-being of pregnant women. The small number of women with screen-positive results temporarily experienced higher anxiety after the scan but, in false-positive cases, anxiety levels normalized again when the abnormality was not confirmed at follow-up scans. Finally, most pregnant women have moderate-to-high levels of knowledge and strongly prefer early screening for fetal structural abnormalities.

Performance of the FMF First-Trimester Preeclampsia-Screening Algorithm in a High-Risk Population in The Netherlands.

OBJECTIVE: The aim of the study was to evaluate the performance of the first-trimester Fetal Medicine Foundation (FMF) screening algorithm, including maternal characteristics and medical history, blood pressure, pregnancy-associated plasma protein A and placenta growth factor, crown rump length, and uterine artery pulsatility index, for the prediction of preeclampsia in a high-risk population in the Netherlands. METHODS: This is a prospective cohort including nulliparous women and women with preeclampsia or intrauterine growth restriction in previous pregnancy. We screened patients at 11-14 weeks of gestation to calculate the risk for preeclampsia. The primary outcome was preeclampsia and gestational age at delivery. Performance of the model was evaluated by area under the receiver operating characteristic (ROC) curves (AUCs) and calibration graphs; based on the ROC curves, optimal predicted risk cutoff values for our study population were defined. RESULTS: We analyzed 362 women, of whom 22 (6%) developed preeclampsia. The algorithm showed fair discriminative performance for preeclampsia <34 weeks (AUC 0.81; 95% CI 0.65-0.96) and moderate discriminative performance for both preeclampsia <37 weeks (AUC 0.71; 95% CI 0.51-0.90) and <42 weeks (AUC 0.71; 95% CI 0.61-0.81). Optimal cutoffs based on our study population for preeclampsia <34, <37, and <42 weeks were 1:250, 1:64, and 1:22, respectively. Calibration was poor. CONCLUSIONS: Performance of the FMF preeclampsia algorithm was satisfactory to predict early and preterm preeclampsia and less satisfactory for term preeclampsia in a high-risk population. However, by addressing some of the limitations of the present study, the performance can potentially improve. This is essential before implementation is considered.

Reduced right ventricular function on cardiovascular magnetic resonance imaging is associated with uteroplacental impairment in tetralogy of Fallot.

BACKGROUND: Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). METHODS: Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. RESULTS: We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF; P = 0.037 and P = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 and P = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%, p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. CONCLUSIONS: Reduced RV function before pregnancy is associated with abnormal uteroplacental Doppler flow parameters. It could be postulated that reduced RV function on pre-pregnancy CMR (≤2 years) is a predisposing factor for impaired placental function in women with repaired ToF.

Fetal Brain-Sparing, Postnatal Cerebral Oxygenation, and Neurodevelopment at 4 Years of Age Following Fetal Growth Restriction.

Objectives: To assess the role of fetal brain-sparing and postnatal cerebral oxygen saturation (rcSO2) as determinants of long-term neurodevelopmental outcome following fetal growth restriction (FGR). Methods: This was a prospective follow-up study of an FGR cohort of 41 children. Prenatally, the presence of fetal brain-sparing (cerebroplacental ratio < 1) was assessed by Doppler ultrasound. During the first two days after birth, rcSO2 was measured with near-infrared spectroscopy. At 4 years of age, intelligence (IQ points), behavior (T-scores), and executive function (T-scores) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Child Behavior Checklist, and Behavior Rating Inventory of Executive Function-Preschool Version, respectively. Using linear regression analyses, we tested the association (p < 0.05) between brain-sparing/rcSO2 and normed neurodevelopmental scores. Results: Twenty-six children (gestational age ranging from 28.0 to 39.9 weeks) participated in the follow-up at a median age of 4.3 (range: 3.6 to 4.4) years. Autism spectrum disorder was reported in three children (11.5%). Fetal brain-sparing was associated with better total and externalizing behavior (betas: -0.519 and -0.494, respectively). RcSO2 levels above the lowest quartile, particularly on postnatal day 2 (≥ 77%), were associated with better total and internalizing behavior and executive functioning (betas: -0.582, -0.489, and -0.467, respectively), but also lower performance IQ (beta: -0.530). Brain-sparing mediated some but not all of these associations. Conclusions: In this FGR cohort, fetal brain-sparing and high postnatal rcSO2 were-independently, but also as a reflection of the same mechanism-associated with better behavior and executive function. Postnatal cerebral hyperoxia, however, was negatively associated with brain functions responsible for performance IQ.

Nuchal translucency of 3.0-3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review.

INTRODUCTION: Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results. MATERIAL AND METHODS: A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period July 2012 to June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0 and 3.4 mm) tested between September 2015 and December 2018. RESULTS: A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies-1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464). CONCLUSIONS: Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21 to 1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be raised. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinically significant conditions then the genome-wide >10-Mb resolution NIPT test, which detects most aberrations, could be proposed.

Intra- and Interobserver Reproducibility of Third Trimester Middle Cerebral Artery Pulsatility Index Measurement: A Prospective Cross-Sectional Study.

BACKGROUND: Middle cerebral artery (MCA) pulsatility index (PI) Doppler in the third trimester of pregnancy is increasingly used. OBJECTIVES: The aim of the study was to investigate intra- and interobserver reproducibility of MCA PI in the third trimester. METHOD: Singleton pregnancies between 30+0 and 40+0 weeks were recruited. MCA Doppler velocimetry measurements were performed prospectively, independently, and blindly. Intra- and interobserver reproducibility was assessed by concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC); Bland-Altman plots were built, and limits of agreement (LoA) were calculated. Results were interpreted according to the cutoff set by the True Reproducibility of Ultrasound Techniques Review. RESULTS: We enrolled 101 patients. ICCs for intraobserver reproducibility were 0.84 and 0.78 for raw values and percentiles, respectively; CCCs were 0.72 and 0.64. For interobserver reproducibility ICCs were 0.84 and 0.78, CCCs 0.72 and 0.63. According to the chosen criteria, these values show a poor-moderate reproducibility of third trimester MCA PI. Cohen's Kappa coefficients were 0.59 and 0.42, indicating a moderate agreement in discriminating normal and abnormal values. CONCLUSIONS: Intra- and interobserver reproducibility of third trimester MCA PI, as assessed by ICC, CCC, and LoA, is far from satisfactory. This should be taken into account before taking clinical decisions.