Placental dysfunction is the primary cause of selective fetal growth restriction (sFGR), and the specific role of mitochondria remains unclear. This study aims to elucidate mitochondrial functional defects in sFGR placentas and explore the roles of mitochondrial genomic and epigenetic alterations in its pathogenesis. The placental villi of MCDA twins with sFGR were collected and the morphology and number of mitochondria were observed by transmission electron microscopy. Meanwhile, the levels of reactive oxygen species (ROS), ATP and oxidative damage markers were assessed. Mitochondrial DNA (mtDNA) copy number detection, targeted sequencing and methylation sequencing were performed. The expression of placental cytochrome c oxidase subunit I (COX I) and mitochondrial long non-coding RNAs (lncRNAs) were evaluated by Western blotting and qPCR. Compared with placentae from normal fetuses, pronounced mitochondrial damage within cytotrophoblast was revealed in sFGR placentae, alongside augmented mitochondrial number in syncytiotrophoblast. Enhanced oxidative stress in these placentae was evidenced by elevated markers of oxidative damage, accompanied by increased ROS production and diminished ATP generation. In sFGR placentae, a notable rise in mitochondrial copy number and one heterozygous mutation in the MT-RNR2 gene were observed, along with decreased COX Ⅰ levels, increased lncND5, lncND6, lncCyt b, and MDL1 synthesis, and decreased RMRP synthesis. Findings collectively confirmed an exacerbation of oxidative stress within sFGR placentae, coinciding with mitochondrial dysfunction, compromised energy production, and ultimately the failure of compensatory mechanisms to restore energy balance, which may result from mutations in the mitochondrial genome and abnormal expression of epigenetic regulatory genes.

Background: Evidences regarding the associations between maternal upper respiratory tract infection/influenza during pregnancy and the risk of congenital heart disease (CHD) is still controversial. This study was specifically designed to examine the associations by a case-control study and a meta-analysis of the published evidences and our finding.Methods: A hospital-based case-control study involving 262 children with simple CHD and 262 children with complex CHD, along with 262 control children, was conducted through June, 2016 to December, 2017. All children were aged 0–2 years old. Furthermore, a meta-analysis based on both previously published studies and our case-control study was performed.Results: In the case-control study, after adjusting for possible confounders, maternal upper respiratory tract infection/influenza during early pregnancy was found to be related to an increased risk of CHD (OR = 3.40 and 95% CI: 2.05–5.62 for simple CHD; OR = 2.39 and 95% CI: 1.47–3.88 for complex CHD). After a meta-analysis, the adverse impact was still kept significant (OR = 1.47 and 95% CI: 1.28–1.67 for simple CHD; OR = 1.44 and 95% CI: 1.14–1.75 for complex CHD). The very similar associations were also observed among single type of CHD, herein, ventricular septal defects (VSD) and tetralogy of fallot (TOF) in the case-control study. In the subsequent meta-analysis, however, the significant association only existed in VSD.Conclusions: Although there is still conflicting in TOF, the results are overall consistent, which provide new enforced evidence that maternal upper respiratory tract infection/influenza during early pregnancy, in general, play an important role in the occurrence of CHD.

Objective: To evaluate submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency (NT) and normal karyotype. Methods: A total of 319 fetuses with increased NT (≥3.0 mm) were tested using conventional karyotyping. When cytogenetic analysis showed normal chromosomes, the parents then received a consultation for chromosomal microarray (CMA) analysis, and a subsequent morphology scan was performed between 20 and 24 weeks gestation. Submicroscopic chromosomal abnormalities were assessed and compared between the fetuses with and without structural defects. Likewise, the prevalence of pathologic copy number variants (CNVs) among cases with increased NT was compared with the 926 low-risk cases consisted of patients whose sole indication for testing was advanced maternal age. Results: Chromosomal abnormality was identified in 32.29 (103/319) of fetuses, and 137 samples were tested using CMA. Additional pathogenic copy number variants (CNVs) were also detected in 5.12% (7/137) of the fetuses. There was no significant difference in the abnormal detection rate between fetuses showing an abnormal morphology scan and those with a normal morphology scan (11.11% [2/18] versus 4.20% [5/119], respectively; p > .05). The prevalence of pathological CMA results in cases with increased NT was significantly higher when compared with the low-risk patients (5.12% [7/137] versus 1.19% [11/926], respectively; p = .0009). Conclusions: Nuchal translucency (NT) ≥3.0 mm are associated with the highest risk for a CMA abnormality. Submicroscopic chromosomal abnormalities should be accessed when the fetus was found to be with increased NT and normal karyotype. It is, therefore, important to inform parents in a professional prenatal counseling setting regarding the potential advantages of CMA.

Next-generation sequencing (NGS) has been applied for carrier screening, effectively reducing the incidence of severe diseases. However, some severe, high-prevalent and complex diseases, including spinal muscular atrophy (SMA), α-/β-thalassemia, 21-hydroxylase deficiency (21-OHD), and fragile-X syndrome (FXS), cannot be fully addressed by NGS, resulting in a high residual risk ratio. This study aims to evaluate the clinical utility of a long-read sequencing (LRS) panel for carrier screening of these five complex diseases. A total of 2926 participants were retrospectively enrolled from International Peace Maternity and Child Health Hospital from Jan 2019 to Dec 2022. All the participants were previously screened for 149 genes correlated to 147 diseases by NGS. The samples were collected and analyzed with the LRS panel targeting the five complex diseases. LRS identified 236 carrier variants, including 54 for SMA, 113 for α-thalassemia, 19 for β-thalassemia, 47 for 21-OHD, and three for FXS. NGS identified only 56.4% (133/236) of the variants detected by LRS. NGS failed to detect three SMA carriers with SMN1 intragenic variants, while reported 10 false-positive carriers for α-thalassemia (HKαα miscalled as -α3.7). Both 21-OHD and FXS were beyond its detection scope. NGS identified only three of the seven at-risk couples determined by LRS. The total estimated at-risk couple rate for 151 genes in NGS and LRS panels was 1.0996%. SMA, α-/β-thalassemia, 21-OHD, and FXS were among the top 30 high-prevalent diseases and had a combined at-risk couple rate of 0.2433%, accounting for 22.1% of the total ratio. NGS could only identify 22.7% of the at-risk couples for the five diseases in the LRS panel. Comprehensive carrier screening for high-prevalent diseases had higher clinical utility than expanding the list of low-prevalent diseases. Incorporating LRS into the NGS carrier screening strategy would facilitate more effective carrier screening.

Background: Chromosomal mosaicism (CM) is a common biological phenomenon observed in humans. It is one of the main challenges in prenatal diagnosis due to uncertain outcomes, especially when fetal ultrasonographic features appear normal. This study aimed to assess the phenotypic features of CM detected during prenatal diagnosis and the risk factors affecting parents’ pregnancy decisions.Materials and methods: A retrospective cohort study involving 18,374 consecutive pregnancies that underwent prenatal diagnosis by karyotyping, fluorescence in situ hybridization (FISH), or chromosome microarray analysis (CMA) was conducted. The association of risk factors with malformations detected by ultrasound and pregnancy outcomes was assessed using the chi-square test and binary logistic regression. Discordant results between the different methods were identified and further analyzed.Results: During this five-year period, 118 (0.6%) patients were diagnosed with CM. The incidences of CM in the chorionic villus, amniotic fluid, and umbilical cord blood were 3.2, 0.5, and 0.7%, respectively. The frequency of ultrasound malformations in individuals with a high fraction of autosomal CM was significantly higher than that in other groups (62.5% vs. 21.4–33.3%, all p <0.05). Inconsistent results between karyotyping and CMA/FISH were observed in 23 cases (19.5%). The risk of pregnancy termination in cases with ultrasound malformations, consistent results, autosomal CM, or a high CM fraction increased with an odds ratio of 3.09, 8.35, 2.30, and 7.62 (all p <0.05). Multiple regression analysis revealed that all four factors were independent risk factors for the termination of pregnancy.Conclusion: Patients with a high fraction of autosomal CM are more likely to have ultrasound malformations. Inconsistent results between different methods in CM are not rare. Ultrasound malformations, consistent results between different methods, autosomal CM, and a high CM fraction were independent risk factors for the choice to terminate pregnancies.