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.
Objective To report normative data on uterine volume and endometrial thickness in girls, according to pubertal stages; to evaluate factors that affect uterine volume; and to compare transabdominal ...ultrasound (TAUS) and magnetic resonance imaging (MRI). Design Cross-sectional study of a nested cohort of girls participating in The Copenhagen Mother-Child Cohort. Setting General community. Patient(s) One hundred twenty-one healthy girls, aged 9.8–14.7 years. Intervention(s) None. Main Outcome Measure(s) Clinical examination, including pubertal breast stage (Tanner classification: B1–B5). Uterine volume: ellipsoid TAUS (n = 112) and 3-dimensional TAUS (n = 111); ellipsoid MRI (n = 61). Endometrial thickness: TAUS (n = 110) and MRI (n = 60). Result(s) Uterine volume and endometrial thickness were positively correlated with pubertal stages; e.g., ellipsoid TAUS: r = 0.753, and endometrium TAUS: 0.648. In multiple regression analyses, uterine volume was associated with the number of large follicles (TAUS >5 mm) (Beta 0.270); estradiol (E2 ) (Beta 0.504); and height (Beta 0.341). Volumes from ellipsoid vs. 3-dimensional TAUS were strongly correlated ( r = 0.931), as were TAUS and MRI: ellipsoid volume ( r = 0.891) and endometrial thickness ( r = 0.540). Uterine volume was larger in TAUS compared with MRI; mean difference across the measured range: 7.7 (5.2–10.2) cm3 . Agreement was best for small uteri. Conclusion(s) Uterine volume and endometrial thickness increased as puberty progressed. Circulating E2 from large follicles was the main contributor to uterine and endometrial growth. The TAUS and MRI assessments of uterus and endometrium were strongly correlated.
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.
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).
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.
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.
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.
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.
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.
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.
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 (β = −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 (β = 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.
Objective To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. Design A multinational, ...randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Setting Not applicable. Patient(s) A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). Intervention(s) One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Main Outcome Measure(s) Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Result(s) Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. Conclusion(s) GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. Clinical Trial Registration Number EudraCT 2005-001507-19.
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 β-hCG in relation to birth weight discordance (BWD) ≥25% in monochorionic diamniotic (MCDA) twin pregnancies.
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.
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 β-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%.
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.
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.
We present longitudinal ...measurements of fetal- and infant AGD. We evaluate the impact of testosterone and dihydrotestosterone at minipuberty on AGD and penile size.
Secondary analyses of an observational, prospective pregnancy and birth cohort, COPANA (2020-2022).
Copenhagen University Hospital - Rigshospitalet.
685 healthy, singleton pregnant women enrolled, 657 women attended 3rd trimester ultrasound, 589 infants completed follow-up.
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).
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.
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.
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.
Is artificial intelligence (AI) ready to replace clinicians in clinical skills assessment? In this paper, Johnsson et al. use Kane's framework to compare validity evidence between the two.
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