Prenatal Diagnosis最新文献

We report the first prenatal diagnosis of a de novo WBP11 variant in a fetus with growth restriction and structural brain anomalies. The case highlights the challenges of counselling with a new and evolving gene-disease association.

Objective: To evaluate the diagnostic accuracy of sonographic estimated fetal weight discordance (EFWD) ≥ 20% in predicting birthweight discordance (BWD) ≥ 20% (i.e., selective fetal growth restriction [sFGR]) in monochorionic (MC) twin pregnancies.

Method: Retrospective cohort study including uncomplicated MC twin pairs (n = 213) and MC twins with sFGR (n = 134), with available ultrasound within 14 days of birth approximately 2002 and 2023 in our center. Within 14 and 7 days of birth, we calculated sensitivity and specificity. In a subgroup of twins with available ultrasound within 3 days of birth, the absolute error of BWD was calculated (BWD-EFWD).

Results: The sensitivity and specificity of EFWD ≥ 20% within 14 days of birth in predicting BWD ≥ 20% were 84% (95% CI 76-89) and 85% (95% CI 79-89), respectively. Ultrasounds available within 7 days of birth (n = 192/347) showed comparable diagnostic accuracies (sensitivity 85% [95% CI 75-92], and specificity 81% [95% CI 73-88]). Among twins with available ultrasound within 3 days of birth (n = 90/347), the absolute error of BWD was -2.0% (SD 8.0), indicating a mean overestimation of BWD.

Conclusion: In MC twins with sFGR, the accuracy of sonographic EFWD ≥ 20% in predicting BWD ≥ 20%, is relatively high. BWD is overestimated by an average of two percentage points within 3 days of birth.

Objective: To analyze the legal consent requirements and customary procedures in clinical trials of fetal therapy with continuing neonatal interventions across four European countries using the BOOSTB4 trial as a case study.

Methods: The study of country-specific legal consent requirements and the actual consent procedures in the BOOSTB4 trial, incorporating surveys with the trial's principal investigators.

Results: Prenatal consent was obtained solely from the pregnant women in all participating countries, in line with legal requirements. However, in all countries both prospective parents were engaged in prenatal counseling. In Sweden, the Netherlands and Germany obtaining consent from both parents for continuing neonatal interventions is mandatory. In the United Kingdom, officially only the consent of one parent is required. Nevertheless, researchers there are cautious of including pregnant women or neonates if parents disagree to trial participation, a concern echoed by Dutch, German and Swedish researchers.

Conclusion: While the pregnant woman's autonomy is paramount for prenatal trial participation, trials involving continuing neonatal interventions should adopt a two-step prenatal counseling approach. This approach allows a distinction between consent for fetal and neonatal procedures and allows researchers to comprehend parental perspectives without undermining the pregnant woman's individual rights.

Objective: A core set of generic Patient Reported Outcome Measures (PROMs) was recently developed to collect information from patients about their health status and quality of life. This study aims to: (1) identify relevant Patient Reported Outcome Measures (PROMs) from this core set for parents facing a fetal anomaly diagnosis and determine their optimal use and (2) assess the usability and feasibility of the adapted setting-specific PROMs in a Dutch Fetal Medicine Department.

Method: A diverse expert panel of parents and healthcare professionals selected relevant PROMs along with their optimal timing and application. In a subsequent pilot feasibility study, parents completed the PROMs and discussed results with professionals. Responses were converted to T-scores using the PROMIS short forms. Usability and feasibility were assessed via questionnaires.

Results: Twenty-eight participants (19 parents, 9 professionals) agreed on two key PROMs: "ability to participate in social roles" and 'emotional distress (anxiety and depression)'. In the pilot study (n = 32; 21 parents, 11 professionals), PROMs were completed in 5.9 min on average, with participants opting to complete PROMs digitally from home. Parents found PROMs useful for enhancing communication with their partners and healthcare providers. The study identified the need for case managers, training on interpreting PROM results, a user-friendly Information Technology (IT) platform, and customized PROMs.

Conclusion: This study shows potential benefits of PROMs in Fetal Medicine but encountered challenges regarding complexity, professional engagement, and time constraints in practice.

Objective: To investigate genetic defects in fetuses diagnosed with isolated unilateral multicystic dysplastic kidney (MCDK).

Methods: This retrospective study analyzed 138 cases of unilateral fetal MCDK identified through second-trimester anatomical ultrasound examinations. Fourteen cases were excluded because of their association with extrarenal anomalies. All participants underwent invasive prenatal diagnostic procedures for copy number variant (CNV) detection via chromosomal microarray analysis (CMA). For those with negative CNV results, exome sequencing (ES) was offered as an add-on diagnostic approach. Clinical and laboratory data were systematically collected and reviewed, encompassing maternal demographics, prenatal sonographic findings, molecular testing outcomes, and pregnancy results.

Results: Of the 124 cases with isolated unilateral MCDK, CMA identified two instances of sex chromosomal aneuploidy, five cases of pathogenic CNVs, and one case demonstrating a pathogenic region of homozygosity associated with Silver-Russell Syndrome. The diagnostic yield for CNVs using CMA was found to be 4.8%. Among the patients who received negative CMA results, 73 proceeded to second-trimester trio ES; no disease-causing variants were detected. One case without prenatal ES developed bilateral ventriculomegaly in the third trimester; postnatal trio ES revealed a de novo likely pathogenic variant c.5138 G > A (p.Ser1713Asn) in the SCN1A gene.

Conclusion: The observed diagnostic yield of 4.8% for CNVs underscores the importance of utilizing CMA in pregnancies complicated by fetal isolated unilateral MCDK. Further research involving larger sample sizes is essential to enhance our understanding of the contribution of monogenic disorders to this condition.

This report describes a novel prenatal presentation of PRKAG2 syndrome in a female. Delivered at 37 weeks, she had severe pulmonary valve stenosis, successfully treated with balloon dilation at one month. Early childhood featured persistent, asymptomatic sinus bradycardia and sinus node dysfunction, followed by childhood-onset epilepsy. By age 8, she developed symptomatic bradycardia. Echocardiography revealed ventricular hypertrophy, and whole exome sequencing identified a heterozygous PRKAG2 variant (c.1642T >C). This case expands the phenotype of PRKAG2 syndrome, uniquely combining congenital pulmonary stenosis with progressive conduction disease and epilepsy, distinct from severe fetal cardiomyopathy or Noonan syndrome.

Objectives: To estimate the residual risk of fetal chromosomal aberrations in pregnant women with normal cell-free DNA (cfDNA) screening results to refine prenatal counseling.

Methods: A retrospective single-center study was conducted between April-2017 and March-2021. In total, 46,007 women received a normal cfDNA screening result. The cohort was subdivided into women receiving normal results for only chromosomes 13/18/21 (targeted cfDNA) and all autosomes (genome-wide cfDNA with a test resolution ∼10-20 Mb). Cytogenomic follow-up included prenatal or postnatal chromosomal microarray (CMA) data.

Results: Out of 46,007 women with normal cfDNA results, 806 (1.8%) were referred for CMA testing; the majority (511/806) were referred due to ultrasound anomalies. The residual risk for a pathogenic chromosomal aberration in the entire targeted cfDNA cohort was 1:641 (0.15%); in the genome-wide cfDNA group, it was 1:699 (0.14%). For fetuses with ultrasound anomalies, the residual risk for a pathogenic chromosomal aberration in the targeted-cfDNA group was 1:8 (13.3%), and 1:12 (8.1%) in the genome-wide cfDNA group.

Conclusions: The residual risk of a pathogenic CNV after a normal cfDNA result is low in women who opt for screening. However, when ultrasound anomalies are detected, this risk is severely increased, justifying the use of invasive testing even with normal cfDNA results. These figures can be used for pre-and-post-test counseling.

Objective: To compare placental volumes between pregnancies with and without fetal CHD, including fetuses with CHD and genetic abnormalities, and to investigate the association between placental volume and regional fetal brain volumes.

Method: Pregnant women carrying a fetus with critical CHD with or without a genetic abnormality (CHD Genetic or CHD Isolated) or a fetus without CHD (Control) had placental and fetal brain volumes measured from MRI. Mixed effects linear regression models examined the associations between study group and placental and fetal brain volumes.

Results: Seventy-one pregnant women/fetuses underwent 124 MRIs. In multivariate analysis, placental volume was 33% smaller among CHD Genetic males, 15% smaller among CHD Isolated males, and 7% smaller among CHD Genetic females compared to Control males. Adjusting for placental volume and confounders, CHD Genetic had smaller total and regional brain volumes compared to Controls. Fetal cortex was not smaller at baseline, but the difference grew over gestation. Reduced brain volumes were present, but less pronounced, for CHD Isolated. Placental volume was independently associated with subcortical gray matter, total brain, and intracranial volumes.

Conclusion: Impaired placental and fetal brain development are most prominent for CHD fetuses with genetic abnormalities.

Objective: This study aimed to investigate the association between fetal fraction (FF) on non-invasive prenatal testing (NIPT) and pregnancy-related complications using a large sample to support improved prenatal management.

Methods: This retrospective cohort study included women with singleton pregnancies and negative NIPT results between January 2015 and March 2022 as part of the Japan Multicenter Study. Chi-square tests and binary logistic regression analyses were used to assess the association between FF and pregnancy-related complications.

Results: A total of 40,716 responses were analyzed. No significant association was found between FF and placental abruption (χ² (1) = 2.84, p = 0.09). Women in the low FF group (FF < 10.27%, < 25th percentile) had higher risks of fetal demise, adjusted OR = 1.79, 95% CI [1.31, 2.43]), preterm birth (adjusted OR = 1.63, 95% CI [1.30, 2.06]), fetal growth restriction (FGR) (adjusted OR = 1.50, 95% CI [1.10, 2.05]), and hypertensive disorders of pregnancy (HDP) (adjusted OR = 1.44, 95% CI [1.24, 1.66]). No significant differences were observed for gestational diabetes mellitus (GDM) (adjusted OR = 1.13, 95% CI [0.99, 1.30], p = 0.081).

Conclusion: Low FF on NIPT is associated with an increased risk of several pregnancy complications, highlighting the need for careful management.