Prenatal Diagnosis最新文献

Objectives: Umbilical artery Doppler intermittent absent and reversed end-diastolic flow (iAREDF) is associated with increased perinatal morbidity and mortality in monochorionic twins with selective fetal growth restriction. The clinical significance of umbilical artery iAREDF in appropriately grown monochorionic twins is not well described.

Methods: This is a single-institution retrospective cohort study describing characteristics and outcomes of monochorionic diamniotic twins with appropriate for gestational age growth and umbilical artery iAREDF in comparison to monochorionic diamniotic twins with selective fetal growth restriction and iAREDF, or sFGR type III. The cohorts were compared for antenatal resolution of iAREDF, estimated gestational age at delivery, fetal and maternal complications, delivery characteristics, and survival outcomes.

Results: Ten appropriately grown monochorionic diamniotic twin pairs with umbilical artery iAREDF and 23 with sFGR Type III delivered at a mean gestational age of 30.4 (± 5) weeks and 30.7 (± 4) weeks, respectively (p = 0.93). No significant differences were observed in the Doppler course (deterioration or improvement) prior to delivery, fetal or maternal complications, delivery characteristics (with the exception of the persistence of the growth differences), or survival outcomes between groups.

Conclusions: Monochorionic diamniotic twins with intermittent absent and reversed end-diastolic umbilical artery velocity may be at increased risk for adverse perinatal outcomes even if criteria for selective fetal growth restriction are not met.

Objective: Congenital diaphragmatic hernia (CDH) is a rare abnormality with highly heterogeneous genetic causes. This study investigated chromosomal and monogenic abnormalities in fetal CDH patients and evaluated the efficacy of chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) for genetic diagnosis. The clinical features of the patients were also evaluated.

Methods: We evaluated the genetic and clinical data of 51 prenatally diagnosed fetuses with CDH. CMA was performed for every patient. If CMA did not yield diagnostic results, the samples were subjected to WES.

Results: Compared with fetuses with isolated CDH (n = 42), those with non-isolated CDH (n = 9) presented a higher genetic diagnostic rate (22.2% vs. 2.4%). The overall diagnostic yield was 5.9%, comprising 3.9% from chromosomal microarray analysis (CMA) and an additional 2.0% from whole exome sequencing (WES). CMA identified (1) mosaic trisomy 18 in a patient with isolated CDH; and (2) 4q terminal deletion syndrome in a patient with non-isolated CDH. WES identified a novel missense mutation, PLS3 c.1763A > G, associated with X-linked CDH in a patient with non-isolated CDH and a family history of recurrent CDH.

Conclusion: Genetic testing should be offered for all fetuses with CDH, regardless of whether the cases are isolated or non-isolated. WES should be considered if CMA fails to provide a diagnostic result, particularly in patients with non-isolated CDH and a family history of recurrent CDH.

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.

Objectives: Prenatal genetic diagnosis can impact care across the perinatal continuum; however, prenatal suspicion for genetic disorders may be complicated by incomplete knowledge of fetal rare-disease phenotypes. Here, we describe the prenatal presentations of a cohort of infants with rare genetic conditions who were diagnosed postnatally in a neonatal intensive care unit (NICU), to characterize prenatal presenting features and evaluate why the diagnosis was not identified prenatally.

Methods: Retrospective cohort study of infants born over a 7 year period (2017-2023) who were admitted to a Level IV NICU and received a postnatal genetic diagnosis prior to 1 year of age. We identified which of these infants had been imaged prenatally at our Maternal Fetal Care Center (MFCC) as an opportunity for prenatal genetic diagnosis. Clinical data were abstracted from the medical records.

Results: 51 cases met the inclusion criteria. Nine of the 51 infants were not strongly suspected to have a genetic syndrome prenatally when seen at the MFCC, as evidenced by lack of prenatal genetic consultation and lack of documented suspicion for a genetic etiology. These cases largely had absent or uncertain prenatal phenotypes. In most cases (42/51, 82.4%), prenatal diagnostic testing was not pursued even if offered. Overall, postnatal diagnoses, of which there was one dual diagnosis, were made by karyotype/FISH (11/52, 21.1%), microarray (8/52, 15.4%), gene panel/targeted testing (17/52, 32.7%), or exome sequencing (16/52, 30.8%).

Conclusions: Our data illustrate the challenges in fetal phenotyping and support a broad approach to prenatal testing to facilitate early genetic diagnosis, which may meaningfully impact postnatal care.

Objective: Neonatal airway compromise requiring intubation, due to micrognathia or a mass lesion obstructing the fetal airway, remains difficult but important to predict prenatally. We aimed to validate MR predictors of difficult neonatal airway (DNA) in a multicentre retrospective cohort of fetuses with micrognathia and oropharyngeal/neck masses.

Method: The radiology databases of two large Australian maternal-fetal medicine centers were searched for subjects meeting inclusion criteria: Pregnancies of > 18 weeks' gestation evaluated with prenatal ultrasound and MRI between 2007 and 2022 where either fetal micrognathia or a fetal cervical, oral or oropharyngeal mass was identified on prenatal ultrasound and MRI, and details of delivery/postnatal course were available including: nature of delivery, need for the fetal airway to be secured at delivery, degree of difficulty in airway securement, survival > 24 h postnatally. Imaging predictors of a difficult neonatal airway (DNA) were assessed blinded to these neonatal outcomes.

Results: Twenty-six fetuses met the inclusion criteria. Oropharyngeal and neck mass location with polyhydramnios was 100% sensitive and 82% specific for DNA. JI < 5th centile with polyhydramnios was 83% sensitive and 70% specific. JI < 5th centile with polyhydramnios was associated with DNA in 80% of cases delivered by ex utero intrapartum (EXIT) delivery and none with non-EXIT delivery mode.

Conclusion: A cervical or oropharyngeal mass with polyhydramnios predicted a difficult neonatal airway. Polyhydramnios with jaw index < 5th centile was less sensitive and less specific for a difficult neonatal airway.

Objective: To determine the prevalence of genetic and endocrine abnormalities and to assess fetal, neonatal and surgical outcomes in cases of hypospadias associated with fetal growth restriction.

Method: A multicentric retrospective study was conducted across five prenatal diagnosis centers in Paris. The cohort encompassed all fetuses diagnosed with the combination of fetal growth restriction < 10th percentile (FGR) and hypospadias from 2013 to 2021. Maternal data, fetal outcome and results of prenatal investigations were collected, along with postnatal data, encompassing endocrinological and genetic assessments, functional aspects and surgical outcomes.

Results: Among the 82 patients included in the cohort, there were 14 (17%) terminations of pregnancy and four (5%) in utero deaths, leaving 64 (78%) live neonates, including five (6%) with early neonatal death. Among the 52 (63%) cases where hypospadias and FGR were considered as ultrasound-isolated anomalies, six (12%, [3.2%-20.8%]) exhibited chromosomic, genetic, or endocrinological abnormalities diagnosed half prenatally and half postnatally. Fifty percent of the overall hypospadias were proximal. Most children underwent surgical intervention before reaching 2 years of age, with 50% encountering complications and often required reintervention.

Conclusion: The association of FGR and hypospadias should not be underestimated as genetic or endocrinological abnormalities were identified even when hypospadias and FGR initially appear isolated. Additionally, the overall prognosis may be worsened using complex and iterative surgical procedures.

Objective: The severity of spina bifida aperta can be assessed prenatally by ultrasound. Morphological findings assist parents in choosing between management options. We aimed to document those management choices since the introduction of fetal surgery, and compare initial ultrasound findings prior to referral to findings in a fetal surgery center.

Method: Single center cohort study of 245 consecutive fetuses with a second-trimester diagnosis of SBA. Data included nature of referral (for assessment or for surgery), condition-specific findings on ultrasound, and further management. We compared the reported findings on the initial ultrasound to ours for the presence of hindbrain herniation, lesion level, ventricular width, kyphosis, leg movement, and club feet.

Results: Seventy-two percent (n = 177) of fetuses met the eligibility criteria for surgery; in 60% (n = 106) parents opted for fetal surgery. Of 136 patients specifically referred for surgery, 27 were ineligible (20%). Of the others, 93 proceeded with surgery. In up to 28% (n = 30) of surgery referrals, eligibility criteria such as lesion level (n = 30, 28%) or leg movement (72%, n = 78) as severity indicators were not reported.

Conclusion: Fetal surgery uptake was high in patients referred for surgery. Second assessment in a fetal surgery center often reveals additional relevant information.

Objective: To investigate the association of agenesis of the ductus venosus (ADV) with genetic abnormalities using genetic studies-Chromosomal Microarray Analysis (CMA) and Exome Sequencing (ES).

Design: Retrospective study of all fetuses diagnosed with ADV between January 2013 and December 2022 in a tertiary center.

Results: ADV was diagnosed in 33 fetuses. The diagnosis was made at a mean gestational age of 21.2 ± 8.4 weeks. Conventional karyotype was applied in a single fetus (3.0%), CMA was applied in 21 fetuses (66.7%), and five fetuses (22.8%) were additionally tested with ES. ADV was isolated in eight fetuses (24%), whereas in 25 (76%) it was associated with abnormal ultrasound findings, including increased nuchal translucency (NT), intrauterine growth restriction (IUGR) and variable structural malformations, mostly cardiac (42%) followed by central nervous system (CNS) and skeletal malformations (24%). Genetic abnormalities were found in six fetuses out of 22 investigated (27%), of which 3 were detected by ES, 3 by CMA and 1 by conventional karyotype. A higher incidence of genetic aberrations was evident among ADVs associated with abnormal ultrasound findings. Genetic abnormalities were indicative of Prader Willi/Angelman syndrome, Noonan syndrome, CASK related disorder, 16q24.3 microdeletion syndrome and Trisomy 21.

Conclusion: ADV associated with abnormal ultrasound findings is commonly correlated with genetic abnormalities and consequently unfavorable pregnancy outcomes. Our study emphasizes the value of genetic studies chiefly among cases associated with abnormal ultrasound findings, enabling early diagnosis of fetal pathologies associated with ADV, and providing better parental counseling.