Clinical implementation of first trimester screening for congenital heart defects.

OBJECTIVE: To examine the feasibility and performance of implementing a standardized fetal cardiac scan at the time of a routine first-trimester ultrasound scan. METHOD: A retrospective, single-center study in an unselected population between March 2021 and July 2022. A standardized cardiac scan protocol consisting of a four-chamber and 3-vessel trachea view with color Doppler was implemented as part of the routine first-trimester scan. Sonographers were asked to categorize the fetal heart anatomy. Data were stratified into two groups based on the possibility of evaluating the fetal heart. The influence of maternal and fetal characteristics and the detection of major congenital heart disease were investigated. RESULTS: A total of 5083 fetuses were included. The fetal heart evaluation was completed in 84.9%. The proportion of successful scans increased throughout the study period from 76% in the first month to 92% in the last month. High maternal body mass index and early gestational age at scan significantly decreased the feasibility. The first-trimester detection of major congenital heart defects was 7/16, of which four cases were identified by the cardiac scan protocol with no false-positive cases. CONCLUSION: First-trimester evaluation of the fetal heart by a standardized scan protocol is feasible to implement in daily practice. It can contribute to the earlier detection of congenital heart defects at a very low false positive rate.

Longitudinal evaluation of fetal and infant AGD in healthy children: association with penile size, testosterone and DHT.

CONTEXT: The anogenital distance (AGD) is considered a postnatal readout of early fetal androgen action. Little is known of prenatal AGD and how it correlates with AGD postnatally. OBJECTIVES: We present longitudinal measurements of fetal- and infant AGD. We evaluate the impact of testosterone and dihydrotestosterone at minipuberty on AGD and penile size. DESIGN: Secondary analyses of an observational, prospective pregnancy and birth cohort, COPANA (2020-2022). SETTING: Copenhagen University Hospital - Rigshospitalet. PARTICIPANTS: 685 healthy, singleton pregnant women enrolled, 657 women attended 3rd trimester ultrasound, 589 infants completed follow-up. MAIN OUTCOME MEASURES: 3rd trimester ultrasound (GW29-34): Fetal AGD. Minipuberty clinical examination (app. 3.5 months postpartum): infant AGD, penile width and stretched length (SPL), circulating testosterone and dihydrotestosterone (LC-MS/MS). RESULTS: AGD was available in 650/657 fetuses (310 boys) and 588/589 infants (287 boys). Boys had longer fetal and infant AGD compared to girls; fetal AGDas: mean (SD) 21.4 mm (±3.5), fetal AGDaf: 12.8 mm (±2.3), p < 0.001, infant AGDas: 32.0 mm (±5.6) and infant AGDaf: 15.8 (±3.3), p < 0.001. Fetal AGD correlated with infant AGD in boys and girls (Spearman's r = 0.275, p < 0.001 and r = 0.189, p = 0.001 respectively), but not with circulating testosterone or dihydrotestosterone at minipuberty. Penile size correlated positively with circulating androgen levels at minipuberty, i.e.: SPL vs testosterone: r = 0.235, p < 0.001. CONCLUSIONS: AGD is sexual dimorphic already in the 3rd trimester. Fetal and infant AGD correlates. AGD is associated with body size but not circulating androgen levels at minipuberty. These findings suggest that fetal and infant AGD, reflect androgen action during early fetal development.

Cohort profile: The Copenhagen Analgesic Study-The COPANA cohort.

BACKGROUND: Development of the gonads during fetal life is complex and vital for adult reproductive health. Cell and animal studies have shown an alarming effect of mild analgesics on germ cells in both males and females. More than 50% of pregnant women use mild analgesics during pregnancy, which potentially could compromise the reproductive health of the next generation. OBJECTIVES: We present a research protocol designed to evaluate the effect of prenatal exposure to mild analgesics and endocrine-disrupting chemicals on gonadal function in the offspring. POPULATION: Healthy, singleton pregnant women and their partners. DESIGN: The COPANA cohort is a prospective, observational pregnancy and birth cohort. METHODS: Participants were enrolled during the first trimester of pregnancy. Information on the use of mild analgesics was collected retrospectively 3 months prior to pregnancy and prospectively every 2 weeks throughout the study. We collected extensive data on lifestyle and reproductive health. Biospecimens were collected in the first trimester (maternal and paternal urine- and blood samples), in the third trimester in conjunction with a study-specific ultrasound scan (maternal urine sample), and approximately 3 months post-partum during the infant minipuberty period (maternal and infant urine- and blood samples). A comprehensive evaluation of reproductive function in the infants during the minipuberty phase was performed, including an ultrasound scan of the testis or ovaries and uterus. PRELIMINARY RESULTS: In total, 685 pregnant women and their partners were included between March 2020 and January 2022. A total of 589 infants (287 males) and their parents completed the follow-up during the minipuberty phase (December 2020-November 2022). CONCLUSIONS: The Copenhagen Analgesic Study holds the potential to provide novel and comprehensive insights into the impact of early and late prenatal exposure to mild analgesics and other endocrine-disrupting chemicals on future reproductive function in the offspring.

AI supported fetal echocardiography with quality assessment.

This study aimed to develop a deep learning model to assess the quality of fetal echocardiography and to perform prospective clinical validation. The model was trained on data from the 18-22-week anomaly scan conducted in seven hospitals from 2008 to 2018. Prospective validation involved 100 patients from two hospitals. A total of 5363 images from 2551 pregnancies were used for training and validation. The model's segmentation accuracy depended on image quality measured by a quality score (QS). It achieved an overall average accuracy of 0.91 (SD 0.09) across the test set, with images having above-average QS scoring 0.97 (SD 0.03). During prospective validation of 192 images, clinicians rated 44.8% (SD 9.8) of images as equal in quality, 18.69% (SD 5.7) favoring auto-captured images and 36.51% (SD 9.0) preferring manually captured ones. Images with above average QS showed better agreement on segmentations (p < 0.001) and QS (p < 0.001) with fetal medicine experts. Auto-capture saved additional planes beyond protocol requirements, resulting in more comprehensive echocardiographies. Low QS had adverse effect on both model performance and clinician's agreement with model feedback. The findings highlight the importance of developing and evaluating AI models based on 'noisy' real-life data rather than pursuing the highest accuracy possible with retrospective academic-grade data.

Validity evidence supporting clinical skills assessment by artificial intelligence compared with trained clinician raters.

BACKGROUND: Artificial intelligence (AI) is becoming increasingly used in medical education, but our understanding of the validity of AI-based assessments (AIBA) as compared with traditional clinical expert-based assessments (EBA) is limited. In this study, the authors aimed to compare and contrast the validity evidence for the assessment of a complex clinical skill based on scores generated from an AI and trained clinical experts, respectively. METHODS: The study was conducted between September 2020 to October 2022. The authors used Kane's validity framework to prioritise and organise their evidence according to the four inferences: scoring, generalisation, extrapolation and implications. The context of the study was chorionic villus sampling performed within the simulated setting. AIBA and EBA were used to evaluate performances of experts, intermediates and novice based on video recordings. The clinical experts used a scoring instrument developed in a previous international consensus study. The AI used convolutional neural networks for capturing features on video recordings, motion tracking and eye movements to arrive at a final composite score. RESULTS: A total of 45 individuals participated in the study (22 novices, 12 intermediates and 11 experts). The authors demonstrated validity evidence for scoring, generalisation, extrapolation and implications for both EBA and AIBA. The plausibility of assumptions related to scoring, evidence of reproducibility and relation to different training levels was examined. Issues relating to construct underrepresentation, lack of explainability, and threats to robustness were identified as potential weak links in the AIBA validity argument compared with the EBA validity argument. CONCLUSION: There were weak links in the use of AIBA compared with EBA, mainly in their representation of the underlying construct but also regarding their explainability and ability to transfer to other datasets. However, combining AI and clinical expert-based assessments may offer complementary benefits, which is a promising subject for future research.

The significance of mitochondrial haplogroups in preeclampsia risk.

OBJECTIVE: To determine whether mitochondrial haplogroups function as disease-modifiers or as susceptibility factors in preeclampsia using a traditional haplogroup association model. METHODS: This retrospective study haplotyped 235 control and 78 preeclamptic pregnancies from Denmark using either real-time PCR or Sanger sequencing depending on the rarity of the haplogroup. RESULTS: No significant association between haplogroups and the risk of preeclampsia was found, nor was any role for haplogroups in disease severity uncovered. CONCLUSION: Mitochondrial haplogroups are not associated with preeclampsia or the severity of preeclampsia in the Danish population. However, this study cannot exclude a role for less common mtDNA variation. Models that can examine these should be applied in preeclamptic patients.

Triple trouble: uncovering the risks and benefits of early fetal reduction in trichorionic triplets in a large national Danish cohort study.

BACKGROUND: Triplet pregnancies are high risk for both the mother and the infants. The risks for infants include premature birth, low birthweight, and neonatal complications. Therefore, the management of triplet pregnancies involves close monitoring and may include interventions, such as fetal reduction, to prolong the pregnancy and improve outcomes. However, the evidence of benefits and risks associated with fetal reduction is inconsistent. OBJECTIVE: This study aimed to compare the outcomes of trichorionic triplet pregnancies with and without fetal reduction and with nonreduced dichorionic twin pregnancies and primary singleton pregnancies. STUDY DESIGN: All trichorionic triplet pregnancies in Denmark, including those with fetal reduction, were identified between 2008 and 2018. In Denmark, all couples expecting triplets are informed about and offered fetal reduction. Pregnancies with viable fetuses at the first-trimester ultrasound scan and pregnancies not terminated were included. Adverse pregnancy outcome was defined as a composite of miscarriage before 24 weeks of gestation, stillbirth at 24 weeks of gestation, or intrauterine fetal death of 1 or 2 fetuses. RESULTS: The study cohort was composed of 317 trichorionic triplet pregnancies, of which 70.0% of pregnancies underwent fetal reduction to a twin pregnancy, 2.2% of pregnancies were reduced to singleton pregnancies, and 27.8% of pregnancies were not reduced. Nonreduced triplet pregnancies had high risks of adverse pregnancy outcomes (28.4%), which was significantly lower in triplets reduced to twins (9.0%; difference, 19.4%, 95% confidence interval, 8.5%-30.3%). Severe preterm deliveries were significantly higher in nonreduced triplet pregnancies (27.9%) than triplet pregnancies reduced to twin pregnancies (13.1%; difference, 14.9%, 95% confidence interval, 7.9%-21.9%). However, triplet pregnancies reduced to twin pregnancies had an insignificantly higher risk of miscarriage (6.8%) than nonreduced twin pregnancies (1.1%; difference, 5.6%; 95% confidence interval, 0.9%-10.4%). CONCLUSION: Triplet pregnancies reduced to twin pregnancies had significantly lower risks of adverse pregnancy outcomes, severe preterm deliveries, and low birthweight than nonreduced triplet pregnancies. However, triplet pregnancies reduced to twin pregnancies were potentially associated with a 5.6% increased risk of miscarriage.

First-trimester biomarkers and ultrasound biometries in relation to growth discordance in monochorionic diamniotic twins.

Objective: The aim of this study was to investigate the association and predictive value between intertwin discordance in first trimester biometries crown-rump length (CRL) and nuchal translucency (NT), and the first trimester biochemical markers PAPP-A and free ß-hCG in relation to birth weight discordance (BWD) ≥25% in monochorionic diamniotic (MCDA) twin pregnancies.Methods: First trimester screening information and pregnancy outcome data on MCDA twin pregnancies with delivery from July 2008 to July 2017 were retrieved from the Danish Fetal Medicine Database. CRL discordance was divided into: <10% (reference group) and ≥10%. NT discordance was divided into: <20% (reference group) and ≥20%. The twin pregnancies were classified according to BWD into the following groups: <10% (reference group), 10-24.9%, and ≥25% including cases undergoing umbilical cord occlusion due to selective fetal growth restriction (sFGR). The twin pregnancies with the most severe BWD (BWD ≥25%) were subdivided into three groups including cases with only one growth-restricted (<10th centile) infant defined as sFGR, and cases where both twins were <10th centile. Median multiples of the median (MoM) values of PAPP-A and free ß-hCG were compared with the group with BWD <10% using the Wilcoxon two-sample test. The ability of CRL discordance and NT discordance to predict BWD ≥25% was examined by the area under the receiver operator characteristic (ROC) curve.Results: A total of 762 MCDA pregnancies were included. The proportion of pregnancies with CRL discordance ≥10% and NT discordance ≥20% was significantly higher in the group with severe BWD discordance (27.0% vs. 4.7% (p < 0.001) and 40.9% vs. 23.9% (p = 0.001), respectively). When examining the three subgroups of severe BWD, we found a significantly higher percentage of pregnancies with CRL discordance ≥10% in the group where umbilical cord occlusion was performed (52.6% vs. 4.7% in the group with BWD <10% (p < 0.001)) and in the group of BWD ≥25% with sFGR (21.7% vs. 4.7% (p < 0.001)). Additionally, a significantly higher percentage of pregnancies with NT discordance ≥20% was found in the group where umbilical cord occlusion was performed (52.6% vs. 23.9% (p = 0.005)) and in the group with both twins <10th centile (66.7% vs. 23.9% (p = 0.003)). No statistically significant differences were found when comparing levels of PAPP-A and free ß-hCG MoMs with the group with BWD <10%. In ROC curves, CRL discordance yielded an AUC for prediction of BWD ≥25% of 0.70 (95% CI 0.63-0.76), and for NT discordance AUC was 0.59 (95% CI 0.52-0.66)). OR for any BWD ≥ 25% was 6.7 (95% CI 3.8-12.0) for pregnancies with a CRL discordance ≥10% compared to pregnancies with a CRL discordance <10%.Conclusions: This study shows that a discordance in CRL and NT in MCDA twins are both significantly associated with development of BWD. The most important predictor remains CRL discordance ≥10%, thereby suggesting the unequal growth pattern in many cases with BWD is evident already in the first trimester of the pregnancy. No association was found between first trimester biochemical markers and severe BWD.

First-Trimester Maternal Serum Adiponectin/Leptin Ratio in Pre-Eclampsia and Fetal Growth.

The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3−13+6) from 126 women who later developed PE with proteinuria (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12−0.27) compared with controls, median 0.32 (IQR: 0.19−0.62) (p < 0.001). A multiple logistic regression showed that PE was negatively associated with log A/L ratio independent of maternal BMI (odds ratio = 0.315, 95% CI = 0.191 to 0.519). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively associated with PE, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737), albeit not clinically relevant as a single marker. No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with a significantly lower relative birth weight (p < 0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls (ß = −0.165, p < 0.05) but not in PE pregnancies), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight (ß = 2.98, p < 0.05), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in the first trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity, but rather on leptin-associated pathways.

Risks and pregnancy outcome after fetal reduction in dichorionic twin pregnancies: a Danish national retrospective cohort study.

BACKGROUND: Twin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a national cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications. OBJECTIVE: This study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins-reduced, nonreduced, and primary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery. STUDY DESIGN: This was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in nonreduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons. RESULTS: In total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%-8.2%) of reduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%-6.1%) were delivered before 28 weeks, and 4.2% (95% confidence interval, 1.7%-8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%-7.4%), and delivery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%-5.0%) and 2.8% (95% confidence interval, 0.3%-9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%-3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%-2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%-7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%-1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%-0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%-0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (P<.01). The overall risk of pregnancy complications was significantly lower among reduced twin pregnancies than among nonreduced dichorionic twin pregnancies (P=.02). CONCLUSION: In a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks.

Variant in ACTG2 Causing Megacystis Microcolon Hypoperistalsis Syndrome and Severe Familial Postpartum Bleeding.

INTRODUCTION: Megacystis microcolon hypoperistalsis syndrome (MMIHS) is a rare condition with high morbidity and mortality. It is characterized by megacystis, microcolon, and intestinal hypoperistalsis leading to various grades of bladder and bowel obstruction. CASE PRESENTATION: This report describes a pregnant woman with a history of bowel obstruction, urine retention, and heavy postpartum bleeding where ultrasound findings of fetal megacystis during pregnancy led to genetic testing in the family. The fetus, the pregnant woman, and four female family members were heterozygous for a pathogenic variant detected in the ACTG2 gene. The fetus was treated successfully for hydronephrosis using vesicoamniotic shunting. DISCUSSION: Early diagnosis of a fetus with MMIHS is important to secure multidisciplinary prenatal and neonatal treatment. Furthermore, gene testing must be considered when a woman presents a history of pseudo-obstruction and urine retention to prevent complications during pregnancy and labor. Finally, recurrent familial postpartum bleeding should lead to referral to genetic evaluation.

A Rare Dichorionic Triamniotic Triplet Pregnancy with Spontaneous Twin Anemia-Polycythemia Sequence between Two Dichorionic Fetuses.

INTRODUCTION: This report presents a rare case of spontaneous twin anemia-polycythemia sequence (TAPS) between two dichorionic fetuses in a spontaneous, homozygotic, dichorionic, triamniotic, triplet pregnancy treated with multiple intrauterine blood transfusions (IUTs) and partial exchange transfusions (PETs). CASE PRESENTATION: The pregnancy was diagnosed with stage IV TAPS at gestational week 25+1. The patient was treated with laser surgery combined with multiple IUTs and PETs. The triplets were delivered at a planned caesarean section at gestational week 28+1 with postnatal hemoglobin values of 18.21, 26.43, and 11.92 g/dL in triplet 1, 2, and 3, respectively. At 4 years of age, triplet 1 is considered healthy, triplet 2 is diagnosed with mild mental retardation, and triplet 3 with profound mental retardation and dystonic cerebral palsy. DISCUSSION: This is an extremely rare case of TAPS between dichorionic fetuses in a triplet pregnancy, and routine surveillance with measurement of middle cerebral artery peak systolic velocity in dichorionic pregnancies may contribute to the detection of similar cases in the future. Furthermore, this case contributes with rare long-term follow-up data of children treated for high-stage TAPS with multiple IUTs and PETs.

Second-trimester cardiovascular biometry in growth-restricted fetuses; a multicenter cohort study.

BACKGROUND: Intrauterine growth restriction is associated with an increased risk of cardiovascular changes neonatally. However, the underlying pathways are poorly understood, and it is not clear whether the dysfunction is already present in the fetus. OBJECTIVE: This study aimed to investigate fetal cardiac dimensions assessed from images at the second trimester anatomy scan from fetuses classified postnatally as small for gestational age and intrauterine growth restricted and compare them with appropriate for gestational age fetuses. STUDY DESIGN: This was a substudy from The Copenhagen Baby Heart Study, a prospective, multicenter cohort study including fetuses from the second trimester of pregnancy in Copenhagen from April 2016 to October 2018. The mothers were recruited at the second trimester anatomy scan that included extended cardiovascular image documentation followed by consecutively measured heart biometry by 2 investigators blinded for the pregnancy outcome. The fetuses were classified postnatally as small for gestational age and intrauterine growth restricted according to the International Society of Ultrasound in Obstetrics and Gynecology 2020 guidelines using birthweight and with a retrospective assessment of Doppler flow. The mean differences in the cardiovascular biometry were adjusted for gestational age at the time of the second trimester scan and the abdominal circumference. The z-scores were calculated, and the comparisons were Bonferroni corrected (significance level of P<.005). Receiver operating characteristic curves were computed after performing backward regression on several maternal characteristics and biomarkers. RESULTS: We included 8278 fetuses, with 625 (7.6%) of them being small for gestational age and 289 (3.5%) being intrauterine growth restricted. Both small for gestational age and intrauterine growth restricted fetuses had smaller heart biometry, including the diameter at the location of the aortic valve (P<.005), the ascending aorta in the 3-vessel view (P<.005), and at the location of the pulmonary valve (P<.005). The intrauterine growth restricted group had significantly smaller hearts with respect to length and width (P<.005) and smaller right and left ventricles (P<.005). After adjusting for the abdominal circumference, the differences in the aortic valve and the pulmonary valve remained significant in the intrauterine growth restricted group. Achievement of an optimal receiver operating characteristic curve included the following parameters: head circumference, abdominal circumference, femur length, gestational age, pregnancy associated plasma protein-A multiples of median, nullipara, spontaneous conception, smoking, body mass index <18.5, heart width, and pulmonary valve with an area under the curve of 0.91 (0.88-0.93) for intrauterine growth restricted cases. CONCLUSION: Intrauterine growth restricted fetuses had smaller prenatal cardiovascular biometry, even when adjusting for abdominal circumference. Our findings support that growth restriction is already associated with altered cardiac growth at an early stage of pregnancy. The heart biometry alone did perform well as a screening test, but combined with other factors, it increased the sensitivity and specificity for intrauterine growth restriction.

Consensus on Training and Assessment of Competence in Performing Chorionic Villus Sampling and Amniocentesis: An International Delphi Survey.

INTRODUCTION: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. METHODS: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. RESULTS: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. CONCLUSION: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

Prevalence of Bicuspid Aortic Valve and Associated Aortopathy in Newborns in Copenhagen, Denmark.

Importance: The prevalence and characteristics of bicuspid aortic valve (BAV) are mainly reported from selected cohorts. BAV is associated with aortopathy, but it is unclear if it represents a fetal developmental defect or is secondary to abnormal valve dynamics. Objective: To determine the prevalence of BAV and BAV subtypes and to describe the associated aortopathy in a large, population-based cohort of newborns. Design, Setting, and Participants: The Copenhagen Baby Heart Study was a cross-sectional, population-based study open to all newborns born in Copenhagen between April 1, 2016, and October 31, 2018. Newborns with BAV were matched 1:2 to newborns with a tricuspid aortic valve (non-BAV group) on sex, singleton/twin pregnancy, gestational age, weight, and age at time of examination. Exposures: Transthoracic echocardiography within 60 days after birth. Main Outcomes and Measures: Primary outcome was BAV prevalence and types, ie, number of raphes and spatial orientation of raphes or cusps (no raphes), according to the classification system of Sievers and Schmidtke (classified as type 0, 1, or 2, with numbers indicating the number of raphes). Secondary outcome was valve function and BAV-associated aortopathy, defined as aortic diameter z score of 3 or greater or coarctation. Results: In total, 25 556 newborns (51.7% male; mean age, 12 [SD, 8] days) underwent echocardiography. BAV was diagnosed in 196 newborns (prevalence, 0.77% [95% CI, 0.67%-0.88%]), with male-female ratio 2.1:1. BAV was classified as type 0 in 17 newborns (8.7% [95% CI, 5.5%-13.5%]), type 1 in 178 (90.8% [95% CI, 86.0%-94.1%]) (147 [75.0% {95% CI, 68.5%-80.5%}] right-left coronary raphe, 27 [13.8% {95% CI, 9.6%-19.3%}] right coronary-noncoronary raphe, 4 [2.0% {95% CI, 0.8%-5.1%}] left coronary-noncoronary raphe), and type 2 in 1 (0.5% [95% CI, 0.1%-2.8%]). Aortic regurgitation was more prevalent in newborns with BAV (n = 29 [14.7%]) than in those without BAV (1.3%) (absolute % difference, 13.4% [95% CI, 7.8%-18.9%]; P < .001). Newborns with BAV had higher flow velocities across the valve (0.67 [95% CI, 0.65-0.69] m/s vs 0.61 [95% CI, 0.60-0.62] m/s; mean difference, 0.06 m/s [95% CI, 0-0.1]) and larger aortic root and tubular ascending aortic diameters than those without BAV (10.7 [95% CI, 10.7-10.9] mm vs 10.3 [95% CI, 10.2-10.4] mm; mean difference, 0.43 mm [95% CI, 0.2-0.6 mm] and 9.8 [95% CI, 9.6-10.0] mm vs 9.4 [95% CI, 9.3-9.5] mm; mean difference, 0.46 mm [95% CI, 0.30-0.70], respectively) (P < .001 for all). Aortopathy was seen in 65 newborns (33.2%) with BAV (62 with aortic z score ≥3; 3 with coarctation). Conclusions and Relevance: Among newborns in Copenhagen, the prevalence of BAV was 0.77%. Aortopathy was common in newborns with BAV, suggesting that it also represents a fetal malformation.

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations-A nationwide register-based study from Denmark.

OBJECTIVE: To evaluate the association between prenatally detected isolated ventricular septum defects (VSDs) and chromosomal aberrations in a nationwide study in Denmark. METHOD: Nationwide, register-based study with prospectively collected data including all singleton pregnancies from 2014-2018. From the Danish Fetal Medicine Database, we retrieved data on maternal characteristics, first-trimester biomarkers, pre- and postnatal diagnoses, genetic test results, and pregnancy outcomes. VSDs were considered isolated in the absence of other malformations or soft markers, and with a low first-trimester risk assessment for trisomies 21, 18 and 13. All cases of an isolated VSD with a chromosomal anomaly were audited. The genetic tests included karyotyping and chromosomal microarray. RESULTS: We retrieved data on 292 108 singleton pregnancies; 323 registered with a prenatally detected VSD and 697 with a VSD detected postnatally (incidence of 0.35%). Only 1/153 (0.7%, 95% CI 0.02;3.6%) of the isolated prenatally detected VSDs had an abnormal genetic test result (del (8)(q23.1)). Moreover, they had a lower free ß-hCG MoM (0.9 MoM vs 0.99 MoM, P = 0.02), and were more likely born small for gestational age (SGA), defined as birthweight 2 or more SD below the mean, compared with the control population (5.2% vs 2.5%, P = 0.03). CONCLUSION: We found a prevalence of chromosomal aberrations of 0.7% in fetuses with a prenatally detected isolated VSD. Moreover, we found an association between isolated VSDs and a larger proportion being born SGA.

Refractory Fetal Supraventricular Tachycardia with Hydrops Successfully Converted by Intraperitoneal Flecainide in the Fetus: A Case Report.

INTRODUCTION: Supraventricular tachycardia is the most common fetal tachyarrhythmia and if persistent often associated with fetal hydrops which can cause intrauterine and neonatal death. CASE PRESENTATION: We present a case of early second trimester supraventricular tachycardia in a hydropic fetus, initially refractory to transplacental treatment. CONCLUSION: The supraventricular tachycardia was successfully treated when supplemented with intraperitoneal flecainide in the fetus.

Menstrual Pattern, Reproductive Hormones, and Transabdominal 3D Ultrasound in 317 Adolescent Girls.

CONTEXT: The knowledge of normal variation of reproductive hormones, internal genitalia imaging, and the prevalence of gynecological disorders in adolescent girls is limited. OBJECTIVE: The study aimed to describe reproductive parameters in postmenarchal girls from the general population including the frequency of oligomenorrhea, polycystic ovary syndrome, and use of hormonal contraception. DESIGN: The Copenhagen Mother-Child Cohort is a population-based longitudinal birth cohort of 1210 girls born between 1997 and 2002. SETTING: University hospital. PARTICIPANTS: A total of 317 girls were included, with a median age of 16.1 years and time since menarche of 2.9 years. MAIN OUTCOME MEASURE(S): Tanner stage, height, weight, age at menarche, menstrual cycle length and regularity, ovarian/uterine volume, and number of follicles were recorded. Serum concentrations of FSH, LH, anti-Müllerian hormone (AMH), inhibin B, estradiol, testosterone, SHBG, androstenedione, dehydroepiandrosterone sulfate, 17-OH-progesterone, and IGF-1 were measured. RESULTS: Twenty girls (6.3%) had oligomenorrhea and differed significantly in serum androgens and AMH, age at and time since menarche from girls with regular cycles. Twenty-seven girls were classified with PCOS (8.5%) and had significantly higher 17-OH-progesterone, estradiol, AMH, LH, and age at menarche than the reference group. Girls on oral contraception had significantly higher serum SHBG concentrations and lower serum concentrations of all hormones except AMH and IGF-1. Ovarian follicles 2 to 29.9 mm correlated positively with serum AMH (P < 0.0001). CONCLUSIONS: Most 16-year-old girls had regular menstrual cycles, normal reproductive hormones, and uterine and ovarian ultrasound. Serum AMH reflected ovarian follicle count and may be a useful biomarker of ovarian reserve.

Short-Term Flow Changes in Monochorionic Survivor Twins after Ultrasound-Guided Umbilical Cord Occlusion.

OBJECTIVE: To determine hemodynamic changes by Doppler ultrasound of the living fetus during 24 h after umbilical cord occlusion (UCO) in monochorionic diamniotic (MCDA) twin pregnancies. METHOD: We conducted a prospective observational study on fetuses undergoing UCO from 2015 to 2017. Doppler parameters peak systolic velocity (PSV) and umbilical pulsatility index (PI) were obtained in the middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus (DV) before and right after UCO, and at 1, 3, 6, 12, and 24 h after. We used multiple of the median (MoM) to adjust for gestational age. Spaghetti plots visualized flow changes over time. Mixed model adjusting for paired longitudinal data compared the values at different time points. RESULTS: A total of 16 women were included. MCA-PSV dropped within the first hour after surgery from 0.91 to 0.82 MoM (p = 0.08). MCA-PI and UA-PI increased in the first hour from 0.75 to 0.91 MoM (p = 0.02) and 0.94 to 0.98 MoM (p = 0.22), respectively. The DV-PIV increased to 1.14 MoM 3 h after surgery (p = 0.07). The spaghetti plots illustrated the small changes within the first hours and showed a stabilization of flow measurements near initial values 24 h after UCO. CONCLUSION: Within the first hours after UCO the circulation of the survivor twin undergoes small hemodynamic changes.

Magnetic Resonance Imaging: A New Tool to Optimize the Prediction of Fetal Anemia?

INTRODUCTION: The false-positive rate in the prediction of fetal anemia is 10-15%. We investigated if a new, noninvasive MRI method used as a supplement to ultrasound could improve the prediction. METHODS: Fetuses suspected of anemia and controls were scanned in a 1.5-tesla MRI scanner 1-4 times during pregnancy. Cases were scanned before and after intrauterine blood transfusion with a T1-mapping MRI sequence in a cross-section of the umbilical vein. RESULTS: Inclusion of 8 cases and 11 controls resulted in 10 case scans (2 cases were included twice) and 33 control scans. In controls, the T1 relaxation time was 1,005-1,391 ms; in cases with severe anemia, 1,505-1,595 ms, moderate anemia 1,503-1,525 ms, and no/mild anemia 1,245-1,410 ms. After blood transfusions, values dropped to 1,123-1,288 ms. The mean value in moderate and severe anemic cases was 275 ms higher than in controls (95% CI 210-341 ms, p < 0.0001), and after blood transfusion it was comparable to controls (3 ms, 95% CI -62 to 68 ms, p = 0.934). A 1,450-ms cut-off would have identified all cases in need of blood transfusion with no false-positive cases. CONCLUSIONS: Our findings indicate a potential for this new MRI method to improve the prediction of fetal anemia as a supplement to ultrasound.