Prenatal diagnosis of fetal digestive system malformations and pregnancy outcomes at a tertiary referral center in Fujian, China: A retrospective study.

Fetal digestive system malformations (DSMs) are correlated with chromosomal anomalies. The prenatal diagnosis of DSMs allows for timely treatment and reduces perinatal morbidity and mortality. However, genetic screening for fetal DSMs is rarely reported. This study aimed to investigate genetic etiology and pregnancy outcomes in cases of fetal DSM by analyzing correlations between DSM types and chromosomal anomalies. This retrospective single-center study included 126 fetuses in whom DSMs were detected via prenatal ultrasonography. Genetic etiology was investigated using conventional karyotyping, chromosome microarray analysis (CMA), and whole-exome sequencing (WES). DSMs were categorized as simple DSM (Group A), DSM combined with abnormal ultrasound soft markers (Group B), and DSM combined with comorbidities of other systems (Group C). Abnormal karyotypes were detected in 11/126 (8.7 %) fetuses. Four more pathogenic copy number variants (CNVs) were detected using CMA, increasing the detection rate to 11.9 %. The detection rates significantly differed between the three DSM types (1.78 %, 8.11 %, and 33.33 % in Groups A, B, and C, respectively). The overall adverse pregnancy outcome rate was 33.9 %, and 11.5 %, 23.5 %, and 81.3 %, (P < 0.001), respectively, in Groups A, B, and C. Out of 83 live births, three neonates died, 26 underwent postnatal surgery with 24 favorable outcomes, and 54 did not undergo surgery and were basically normal. Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively. Our findings demonstrate that fetal DSM is closely related to chromosome aneuploidies, CNVs, and point mutations. The prognoses of most fetuses with simple DSM and those with comorbid abnormal ultrasound soft markers were favorable in the absence of chromosomal anomalies and severe structural malformations, provided they underwent timely surgery as neonates. These findings provide guidance for the prenatal diagnosis and clinical management of fetal DSMs and the genetic counseling of parents.

Ultrasonographic characteristics, genetic features, and maternal and fetal outcomes in fetuses with omphalocele in China: a single tertiary center study.

BACKGROUND: Patients with omphalocele, a midline abdominal wall defect at the umbilical cord base, have a low survival rate. However, the long-term outcomes of fetuses with prenatally diagnosed omphalocele have scarcely been studied. Therefore, we investigated the ultrasonographic features, genetic characteristics, and maternal and fetal outcomes of fetuses with omphalocele and provided a reference for the perinatal management of such cases. METHODS: A total of 120 pregnant females with fetal omphalocele were diagnosed using prenatal ultrasonography at the Fujian Provincial Maternity and Child Health Hospital from January 2015 to March 2022. Amniotic fluid or cord blood samples were drawn at different gestational weeks for routine karyotype analysis, chromosomal microarray analysis (CMA) detection, and whole exome sequencing (WES). The maternal and fetal outcomes were followed up. RESULTS: Among the 120 fetuses, 27 were diagnosed with isolated omphalocele and 93 with nonisolated omphalocele using prenatal ultrasonography. Cardiac anomalies were the most observed cause in 17 fetuses. Routine karyotyping and CMA were performed on 35 patients, and chromosomal abnormalities were observed in five patients, trisomy 18 in three, trisomy 13 in one, and chromosome 8-11 translocation in one patient; all were non-isolated omphalocele cases. Six nonisolated cases had normal CMA results and conventional karyotype tests, and further WES examination revealed one pathogenic variant and two suspected pathogenic variants. Of the 120 fetuses, 112 were successfully followed up. Eighty of the 112 patients requested pregnancy termination. Seven of the cases died in utero. A 72% 1-year survival rate was observed from the successful 25 live births. CONCLUSION: The prognosis of fetuses with nonisolated omphalocele varies greatly, and individualized analysis should be performed to determine fetal retention carefully. Routine karyotyping with CMA testing should be provided for fetuses with omphalocele. WES is an option if karyotype and CMA tests are normal. If the fetal karyotype is normal and no associated abnormalities are observed, fetuses with omphalocele could have a high survival rate, and most will have a good prognosis.

Prenatal diagnosis of genetic aberrations in fetuses with pulmonary stenosis in southern China: a retrospective analysis.

BACKGROUND: The genetic etiology of congenital pulmonary stenosis (PS) in fetuses remains inadequately studied. We used karyotype analysis and chromosomal microarray analysis (CMA) to investigate the genetic aberrations associated with PS in human fetuses. METHODS: A retrospective analysis was performed on 84 fetuses with congenital PS in southern China. Fetal amniotic fluid and umbilical cord blood samples were obtained for chromosomal karyotype analysis and CMA. RESULTS: The rate of pathogenic copy number variation (CNV) was 15.5% (13/84) after karyotyping and CMA. An abnormal karyotype was detected in five cases (6.0%, 5/84) via karyotyping, whereas pathogenic CNVs were detected in 13 cases (15.5%, 13/84) via CMA. In addition to the five abnormal karyotypes detected using karyotype analysis, eight additional chromosomal microduplications and microdeletions were detected using CMA, comprising three cases of 22q11.21 microdeletion; two cases of 16p11.2 microdeletion; one case of simultaneous 18q23 microdeletion and 22q13.33 microduplication; one case of 15q24.1q24.2 microdeletion; and one case of 1q21.1q21.2 microduplication. The rate of pathogenic CNV occurrence was 11.5% in fetuses with isolated PS and 17.2% in fetuses with PS combined with other ultrasound abnormalities. This difference between the two experimental groups was statistically significant. Among 84 fetuses with PS, 39 pregnancies were terminated, and five were lost to follow-up. CONCLUSIONS: CMA was not only conducive to detect PS-related pathogenic genomic abnormalities but also to accurately evaluate fetal prognosis in genetic counseling. The early detection of PS and genomic abnormalities will exerta positive impact on fetal intervention and the related prognosis of PS in perinatal infants.