Prenatal Diagnosis最新文献

Objective: To report our recent experience with prenatal detection of significant cardiovascular malformations (CVMs) in Nevada's state-wide maternal population receiving prenatal care.

Methods: We queried our databases for those with significant CVMs diagnosed pre- or postnatally between May 1, 2021, and April 30, 2024. We defined CVMs as those that required, would have required, or will likely require a therapeutic procedure in the first 12 months. Additionally, we included those with atrioventricular and ventriculoarterial discordance and left isomeric situs, both unaccompanied by additional CVMs, and congenital complete heart block. We defined routine prenatal care as obstetric care, which included at least one fetal anatomical survey ultrasound.

Results: We identified 390 cases of significant CVMs. Of the 390 cases, 359 (92%) had prenatal care over the three-year observation period, with prenatal detection rates for the three 12-month intervals: 76% (87/115), 87% (94/108), and 95% (129/136) respectively (p < 0.001 by chi-square). A total of 310 prenatal diagnoses were made from comprehensive fetal echocardiograms performed on 8397 pregnant women at maternal-fetal-medicine centers.

Conclusion: To our knowledge, these results represent the highest prenatal detection rate for significant CVMs, in a state-wide maternal population in the United States.

Objective: To determine outcomes at birth and postnatal sequelae of congenital cytomegalovirus (cCMV) infection following maternal primary infection in the first trimester with normal fetal brain imaging at midgestation.

Methods: A retrospective, single-center cohort study was conducted, including all cases of proven cCMV infection following maternal primary infection in the first trimester from 2014 until 2021 and normal fetal brain imaging before 22 weeks of gestation. All pregnancies were followed according to our protocol, which offers amniocentesis at least 8 weeks after the onset of infection, serial ultrasound scans, and a fetal MRI in the third trimester. No women received treatment with CMV hyperimmune globulin or Valacyclovir during pregnancy. Follow-up of newborns was obtained, and newborns were classified as symptomatic or asymptomatic at birth. Postnatal sequelae were evaluated, and cases with a follow-up period of less than 12 months were excluded.

Results: We found 42 newborns with cCMV, confirmed at birth by PCR for the CMV genome in neonatal urine samples, and normal fetal brain imaging up to 22 weeks of gestation. Extracerebral signs of infection were present in 3/42 fetuses at the second trimester ultrasound (20-22 weeks of gestation). In the third trimester (28-32 weeks of gestation), none showed abnormal brain sonographic findings, but four exhibited extracerebral signs of CMV infection. Among 42 newborns, 29 were classified as asymptomatic (29/42, 69.1%) and 13 as symptomatic at birth (13/42, 30.9%, 95%CI 17.6%-47.1%). Eight newborns had abnormal cranial ultrasound/MRI (8/42, 19%), one presented abnormal postnatal brain imaging associated with hearing loss and four had sensorineural hearing loss (SNHL) at initial assessment. All were treated with oral Valganciclovir. Four newborns with normal hearing at birth had delayed onset SNHL. One case of hearing loss improved after treatment and returned to normal hearing. At a median follow-up of 35 months, 8 infants had hearing loss (8/42, 19%, 95%CI 8.6%-34.1%) and none presented with severe brain abnormalities.

Conclusion: For infants with congenital CMV following untreated first trimester maternal primary infection, the absence of abnormal prenatal brain ultrasound findings at the mid-trimester morphology scan does not rule out the possibility of postnatal neuroimaging anomalies or the need for treatment after birth. However, no severe brain abnormalities were detected after birth in our cohort, and the only observed sequelae were sensorineural hearing loss.

Objective: The purpose of this study was to improve our understanding of severe serine biosynthesis defects through a comprehensive description of prenatal, and postnatal manifestations and the mutational spectrum in a new cohort of 12 unrelated Egyptian Families.

Methods: Detailed fetal ultrasound examination, postnatal assessment, and whole exome sequencing (WES) were performed in a cohort of 12 fetuses with suspected Neu-Laxova syndrome (NLS), the most severe expression of serine biosynthesis defects. Additionally, a comprehensive review of the literature was conducted by merging the data from all the molecularly-confirmed cases with ours to gain a better understanding of the clinical variability of NLS.

Results: Novel clinical manifestations including intrauterine convulsions, hemivertebrae, natal teeth, holoprosencephaly, and rhombencephalosynapsis were observed. Molecular analysis identified 7 and 2 likely disease-causing variants in the PSAT1 and PHGDH genes, respectively. Four of them were novel, including the c.734G>A missense variant in PSAT1, which has been proposed to be a founder variant among Egyptians.

Conclusion: The present cohort expands the spectrum of serine biosynthesis disorders. Moreover, it illuminates the role of prenatal exome sequencing in lethal conditions constituting the most severe end of already-known human diseases.

Objective: We estimated the potential outcomes, costs, and cost-effectiveness of the Vortex shunt, a novel fetal vesicoamniotic shunt (VAS), compared to standard shunts for treating fetal lower urinary tract obstruction (LUTO).

Method: We designed a decision-analytic model comparing the Vortex shunt to current shunts using a theoretical cohort of 1000 pregnancies equivalent to the annual U.S. LUTO cases. Current literature indicates a 50% dislodgement risk and a 36% end-stage renal disease (ESRD) probability for current shunts versus the Vortex shunt's expected 10% dislodgement risk and 18% ESRD rate from pre-clinical studies. Outcomes included preterm delivery, preterm premature rupture of membrane (PPROM), ESRD, neurodevelopmental delay (NDD), neonatal death, costs, and quality-adjusted life years (QALYs). We derived model inputs from the literature and conducted sensitivity analyses.

Results: Of 1000 theoretical LUTO pregnancies, the Vortex shunt resulted in 70 fewer cases of ESRD, 110 fewer preterm deliveries, 50 fewer episodes of PPROM, and 10 fewer children with NDD. The Vortex shunt was the dominant strategy with higher QALYs and estimated lifetime savings of $168,520 for each fetus undergoing VAS. The Vortex shunt was cost-effective 98% of the time.

Conclusion: Our theoretical model suggests that the Vortex shunt is cost-effective compared to current shunts.

Objective: To explore the experiences of people having cfDNA screening to detect unbalanced translocations, and to understand motivations for choosing this option.

Methods: We used a qualitative approach with in-depth semi-structured interviews with reciprocal translocation carriers and their partners. People who underwent cfDNA screening with translocation analysis through Victorian Clinical Genetics Services between 2015 and 2019 were invited to take part. Purposive sampling based on the participant's geographic location, requesting practitioner specialty and cfDNA screening result was used to capture a range of experiences. Interview transcripts were analysed using thematic analysis.

Results: Participants (n = 13) had complex reproductive journeys associated with the translocation and opted for cfDNA screening rather than prenatal diagnosis to avoid risk to their pregnancy. Participants benefited from having a result early in pregnancy and had sufficient confidence in the result to decline a diagnostic testing procedure.

Conclusion: Participants' experiences with cfDNA screening were intertwined with the experience of being a carrier of a reciprocal translocation. cfDNA screening with translocation analysis was perceived as an acceptable alternative to prenatal diagnosis and should be made more accessible to balanced translocation carriers. Access to specialist genetic counselling services is needed to ensure couples are provided with information about all prenatal testing options, including the benefits and limitations associated with cfDNA screening with translocation analysis.

This systematic review aims at presenting the ethical debate on the artificial placenta (AP) by identifying, distinguishing, and organizing the different ethical arguments described in the literature. Articles were selected based on predefined inclusion criteria: discussing ethical arguments, on AP, written in English. QUAGOL methodology was used for analysis. Forty-five articles were included. We identified three themes. First, foundational-ethical issues. There is disagreement on whether the AP subject should be considered an infant or a new moral entity. While physiologically it stays in the fetus, it sits outside the womb. Second, reproductive ethics issues. Few authors believed that the AP would increase reproductive choices. The majority warned that the AP could limit reproductive choices by creating pressure to use it in healthy pregnancies or as an alternative to abortion. Third, research ethics issues. Publications mostly focused on the selection of the in-human trial participants. We concluded that AP ethical literature focuses mostly on the potential use of AP as an alternative to abortion or healthy pregnancies rather than on its intended use as a treatment after extremely premature birth. Therefore, we conclude that the current ethical literature on AP is imbalanced: it leans more toward science fiction than actual clinical and technological reality.

Chromosomal microarray analysis (CMA), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), and trio-whole exome sequencing (WES) were performed in a female fetus with omphalocele. A de novo heterozygous 300-kb deletion in the Xq13.1 region, which includes the MED12 gene, was identified. Follow-up ultrasound at 18⁺⁴ weeks of gestation revealed features consistent with Hardikar syndrome (HS), including a right-sided cleft lip and palate, an omphalocele with intestines, a diaphragmatic hernia with the stomach in the left thoracic cavity, and displacement of the heart to the right. Phenotypic evaluation confirmed the presence of a cleft lip and palate as well as umbilical hernia. These findings suggest that a heterozygous deletion of the entire MED12 gene may contribute to the HS phenotype. This case extends the possible damaging effects of haploinsufficiency of the MED12 gene in the pathogenesis of HS.

Objective: To describe postnatal outcome following the prenatal diagnosis of an abnormal fetal gallbladder.

Methods: We conducted a systematic review of studies from January 1980 to January 2023 that described FGB abnormalities, which included agenesis or non-visualisation, abnormal content presence of sludge, abnormal shape or size and abnormal position, and postnatal outcome to determine the association with pathology.

Results: In 51 studies, 842 fetuses had abnormal FGB. Non-visualisation of the FGB was the most common diagnosis (521 fetuses, mean gestational age 21.6 weeks, range 14-29). The FGB was subsequently visualised prenatally in 128 out of 521 cases (24.6%; 95% CI, 20.9%-28.3%). Of the 393 cases with persistent FGB non-visualisation (75.4%; 95% CI, 71.7-79.1), 48 cases (12.2%; 95% CI, 9.0-15.5) underwent termination of pregnancy (TOP) with FGB agenesis confirmed in 16 out of 26 fetuses that had a postmortem examination (61.5%; 95% CI, 42.8-80.2). After excluding cases with missing outcomes (n = 121), postnatal ultrasound was performed in 82.4% of cases with persistent non-visualised FGB (224/272; 95% CI, 77.8%-86.9%). The gallbladder was not visualised in 63.4% (142/224; 95% CI, 57.1-69.7), confirming GB agenesis. This was an isolated finding in 41.1% of cases (92/224; 95% CI, 34.6-47.5). Of 272 known outcomes, biliary atresia, cystic fibrosis, and structural or chromosomal abnormalities were diagnosed in 8.5% (n = 23), 12.5% (n = 34), 18.0% (n = 49) and 6.3% (n = 17) cases, respectively. The sensitivity (true positive rate) of ultrasound for GB agenesis in fetuses with persistently non-visualised FGB was 58.1% (158/272; 95% CI, 52.2%-64.0%). Fetal gallbladder stones/sludge were described in 100 fetuses mainly in the third trimester of pregnancy (mean gestational age 33.8 weeks). Resolution of postnatally followed up cases occurred in around one-third of the cases (37.3%) within 1 month after birth. There was a low reported association with severe conditions (2%).

Conclusions: This systematic review and meta-analysis found that when the fetal gallbladder was absent in mid-trimester, it was visualised in subsequent fetal ultrasound examinations in around 25% of cases. If persistently absent on prenatal ultrasound, the confirmed rate of GB agenesis was around 50%, with the neonates having biliary atresia, cystic fibrosis, or structural abnormalities. Because of the association with severe conditions, if persistent FGB agenesis is suspected, prenatal diagnosis should be offered. FGB abnormalities such as stones/sludge tended to resolve by 1 year of age with around half of all cases resolving by 1 month postnatal.