Prenatal Diagnosis最新文献

Objective: To present the imaging features of Caroli's disease (CD) on prenatal ultrasound and magnetic resonance imaging (MRI).

Methods: This was a retrospective case series of prenatally diagnosed CD between 2017 and 2024. Clinical data from these cases were collected and reviewed.

Results: Five fetuses with CD were included, three of which had a definite combination of ARPKD and suspected in the other 2. Prenatal ultrasonography revealed multiple intrahepatic bile duct dilatations in four fetuses, each of which displayed the "horn comb" sign in a cross-section of the liver. All five fetuses had abnormal kidney ultrasounds: three showed enlarged and hyperechogenic kidneys and two showed hyperechogenic kidneys. The MRI scans of all fetuses showed a "central dot" (C-DOT) sign in the liver. By MRI, three fetuses had enlarged kidneys, one slightly had hyperintensity kidneys, and one had no significant kidney abnormalities. Pregnancy termination was chosen in all cases.

Conclusions: CD may be identified by fetal ultrasound through the characteristic arrangement of intrahepatic dilated bile ducts ("horn comb" sign). Fetal MRI is advantageous for detecting the C-DOT sign, which confirms the diagnosis of CD. In our experience, these findings tend to become apparent in the late second to early third trimester of pregnancy.

Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake. We included 184 sources, including white and gray literature and non-English sources. We identified 17 considerations that were documented to have influenced the decision whether to introduce NIPT across five domains: clinical considerations, ethical considerations and societal values, financial considerations, demand and capacity and applicable oversight. Fewer factors seem to have been considered in the US as compared to Japan or the Netherlands. Countries subsequently made choices on how to implement NIPT-we identified 35 such choices. While most of the identified choices were eventually considered by all three countries, they made different decisions (e.g., on out-of-pocket costs). In 2022, the estimated proportion of pregnant persons who used NIPT was 58% in the Netherlands, 49% in the US, and 9% in Japan. While differences in cultural values, population characteristics, and healthcare systems explain some variation, we identified other more adaptable aspects of the decision-making process (e.g., oversight) that may be useful for countries introducing NIPT or similar technologies to consider.

Objective: To describe the outcome of a case of severe drug-resistant fetal tachyarrhythmia with progressive hydrops treated with fetoscopic transesophageal pacing (FTEP).

Method: A case of fetal tachyarrhythmia complicated by progressive hydrops is presented. The fetus, diagnosed at 26⁺² weeks of gestation, had supraventricular tachycardia with a mechanism suggestive of atrial reentry. Maternal treatment included digoxin, sotalol and amiodarone, which were ineffective in controlling the arrhythmia. After failure of pharmacological therapy, FTEP was performed.

Results: A male baby was delivered by cesarean section, with the Apgar scores of 10 at 1 min, 5 and 10 min at 35⁺² weeks of gestation. An initial neonatal electrocardiogram demonstrated normal sinus rhythm. Follow-up is now up to 1 year, without tachyarrhythmia or cardiac dysfunction.

Conclusion: FTEP offers a potential rescue therapy for cases of severe drug-resistant fetal tachyarrhythmia associated with progressive fetal hydrops and cardiac dysfunction.

Prenatal exome sequencing (ES) can establish rare genetic diagnoses in a fetus but may also lead to occult genetic diagnosis in a biological parent. We present a case of dual fetal and maternal diagnosis by prenatal ES, in a fetus with unexplained anemia and in a pregnant patient with sickle cell disease (SCD) and recurrent unexplained hypoxia. ES identified a novel, likely pathogenic gamma globin variant, HbF Mission Bay HBG2 (c.86T > A, p.Leu29Gln), in both the fetus and mother. Deleterious variants in HBG2 have been associated with cyanosis, hypoxia, methemoglobinemia, and hemolytic anemia that are typically confined to infancy. In the pregnant patient who herself had a separate diagnosis of SCD, the HBG2 variant manifested with hypoxia as an infant herself, recurrent hypoxia in adulthood, and methemoglobinemia during pregnancy due to persistence of HbF. This same variant manifested in the fetus as anemia requiring multiple in utero transfusions as well as neonatal methemoglobinemia after birth.

Objective: To evaluate phenotype and genotype characteristics of fetuses and children with upper limb anomalies.

Method: Retrospective cohort study of a prenatal and postnatal cohort with upper limb anomalies from January 2007 to December 2021 in a Fetal Medicine Unit. Prenatally on ultrasound suspected upper limb anomalies, such as transverse and longitudinal reduction defects, polydactyly, and syndactyly, and postnatally identified children referred to the Congenital Hand Team were evaluated separately.

Results: The prenatal group included 199 pregnancies: 64 transverse and 19 longitudinal reduction defects, 103 polydactylies, and 13 cases with syndactyly. The majority of cases with longitudinal reduction defects (n = 10, 52.6%), polydactyly (n = 62, 60.2%), and syndactyly (n = 10, 76.9%) were non-isolated, as opposed to transverse reduction defects, which were generally isolated (n = 41, 64.1%). The postnatal cohort included 362 children with upper limb anomalies with 49 transverse and 22 longitudinal reduction defects, 226 polydactylies, and 65 syndactylies. Chromosomal or monogenic abnormalities were identified in 76/199 (38.2%) cases of the prenatal cohort and in 31/362 (8.6%) cases of the postnatal cohort.

Conclusion: Prenatal identification of minor defects of the digits is a challenge, with more postnatal than prenatal cases. The majority of cases with isolated anomalies in both groups had no underlying chromosomal or monogenic cause, nor were they associated with a syndrome, as compared to the non-isolated cases. Conducting structural anomaly scans and genetic counseling are crucial to assess the risk of genetic abnormalities.

Objective: To explore the personal experiences of women faced with the decision to continue a triplet pregnancy or undergo multifetal pregnancy reduction.

Methods: A qualitative study with semi-structured interviews was conducted between October 2021 and April 2023. Participants included women who continued a triplet pregnancy, and those who underwent multifetal pregnancy reduction from triplet to twins or singletons, 1-6 years post-decision. Interviews focused on: (1) the decision-making process, and (2) the emotional aspects and psychological impact of the decision. Thematic analysis was used to identify patterns, involving familiarization, defining themes, and producing the final report.

Results: Data saturation was achieved after 16 interviews, revealing two main themes: (1) maternal intuition as a guiding force, and (2) navigating the crossroads: coping and reflection on the decision. These themes illustrate an interplay between maternal intuition and intrinsic feelings in the decision whether to perform multifetal pregnancy reduction, seemingly less influenced by external factors. Mothers who adhere to their intuition (15/16) have a low likelihood of experiencing regret. Despite the inclination to share and seek support, a persistent taboo surrounds the topic of multifetal pregnancy reduction. The findings also emphasize a considerable gap in aftercare for women, regardless of their decision.

Conclusion: There is a need for improved care and support for parents facing the decision of continuing a triplet pregnancy or deciding on multifetal pregnancy reduction. Efforts should focus on fostering open societal dialog about this taboo subject, and addressing the gap in aftercare to provide comprehensive support to women post-decision and post-birth, thereby establishing a more supportive and compassionate framework.

Fetal lower urinary tract obstruction (LUTO) encompasses a spectrum of rare congenital anomalies affecting the fetal urinary system, leading to significant morbidity and mortality. This condition, arising from various anatomical anomalies such as posterior urethral valves (PUV), urethral atresia, and cloacal malformations, disrupts normal urine flow, resulting in secondary complications such as pulmonary hypoplasia and renal impairment. Current management strategies, including fetal vesicoamniotic shunting (VAS) and fetal cystoscopy, aim to alleviate obstruction and mitigate associated risks. While VAS has been a longstanding intervention, fetal cystoscopy presents a promising alternative by enabling direct visualization and targeted treatment of urinary tract obstructions. However, fetal cystoscopy is not without challenges, including technical complexities and risks associated with invasive procedures. This review explores the rationale, indications, technical considerations, outcomes, and future innovations of fetal cystoscopy in managing LUTO. It highlights the critical role of accurate diagnosis, patient selection, and procedural expertise in optimizing fetal and maternal outcomes. Despite existing challenges, ongoing advancements in technology and clinical practice hold the potential for further enhancing the safety and efficacy of fetal cystoscopy, underscoring its evolving role in prenatal care.

Objective: This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT.

Method: We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked.

Results: A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p < 0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5 Mb in size, and nine (13.85%) were between 5 and 10 Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p < 0.05).

Conclusions: Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

Variants of the ACTG2 gene cause autosomal dominant ACTG2 visceral myopathy, a disorder of smooth muscle dysfunction of the bladder and gastrointestinal system. Bladder involvement can behave as fetal megacystis (FM). We report four prenatal cases of ACTG2 visceral myopathy. All four cases presented with FM identified by ultrasound in the second trimester. All had invasive genetic investigations during pregnancy, and trio exome sequencing revealed likely pathogenic or pathogenic ACTG2 variants in the fetuses. Three of the four variants were de novo, and one was inherited form mother who had symptoms of smooth muscle dysfunction since childhood. ACTG2 visceral myopathy is the most concern in fetuses with isolated second-trimester megacystis. Genetic diagnosis of single gene disorders associated with FM is useful in parental counseling, pregnancy management and risk assessment of recurrence in future pregnancy.

Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities (NDDRSB) is an extremely rare but severe disorder. Here, we describe the case of a 24-week-old fetus from a Chinese family with healthy parents. The fetus presented with hydrops fetalis and abnormal limb posturing. Chromosomal microarray analysis revealed that the fetus had a heterozygous 17p12 deletion, which is associated with hereditary neuropathy with liability to pressure palsies. Trio-based exome sequencing (ES) analysis revealed that the deletion was inherited from the father, who has a normal phenotype. Trio-based ES identified a novel nonsense variant (c.229C>T, p.Q77*) and a rare nonsense variant (c.325C>T, p.R109*) in the mediator complex subunit 11 (MED11) gene. Both parents were heterozygous carriers for one of the variants in MED11. This is the first study to report the presence of hydrops fetalis and abnormal limb posturing phenotypes in fetuses with MED11 variants. These results expand the prenatal phenotypic spectrum of NDDRSB, which is helpful for genetic counseling and early prenatal diagnosis of fetuses with ultrasound abnormalities. In addition, the novel c.229C>T variant expands the spectrum of MED11 variants.