Performance of comprehensive first trimester fetal anatomy assessment

Objective

Ultrasound assessment of the fetal anatomy and fetal echocardiography are feasible in the first trimester of pregnancy. This study was designed to assess the performance of a comprehensive fetal anatomy assessment in a high-risk population at a tertiary fetal medicine unit.

Methods

A retrospective review of high-risk patients undergoing comprehensive fetal anatomy ultrasound assessment between 11 weeks and 13 + 6 weeks of gestation was conducted. Findings of the early anatomy ultrasound scan were compared with those of the second trimester anatomy scan, and birth outcomes or post-mortem results.

Results

Early anatomy ultrasounds were performed in 765 patients. The sensitivity of the scan for detecting fetal anomalies compared to the birth outcome was 80.5% (95% CI 73.5–86.3) and specificity was 93.1% (95%CI 90.6–95.2). Positive and negative predictive values were 78.5% (95% CI 71.4–84.6) and 93.9% (95% CI 91.4–95.8), respectively. The most missed and overdiagnosed abnormalities were ventricular septal defects. The second trimester ultrasound had sensitivity of 69.0% (95% CI 55.5–80.5) and specificity of 87.5% (95% CI 84.3–90.2).

Conclusions

In a high-risk population, early assessments had similar performance metrics as the second trimester anatomy ultrasound. We advocate for a comprehensive fetal assessment in the care of high-risk pregnancies.     

Prenatal exposure to environmental pro-oxidants induces mitochondria-mediated epigenetic changes: a cross-sectional pilot study

Mitochondria play a central role in maintaining cellular and metabolic homeostasis during vital development cycles of foetal growth. Optimal mitochondrial functions are important not only to sustain adequate energy production but also for regulated epigenetic programming. However, these organelles are subtle targets of environmental exposures, and any perturbance in the defined mitochondrial machinery during the developmental stage can lead to the re-programming of the foetal epigenetic landscape. As these modifications can be transferred to subsequent generations, we herein performed a cross-sectional study to have an in-depth understanding of this intricate phenomenon. The study was conducted with two arms: whereas the first group consisted of in utero pro-oxidant exposed individuals and the second group included controls. Our results showed higher levels of oxidative mtDNA damage and associated integrated stress response among the exposed individuals. These disturbances were found to be closely related to the observed discrepancies in mitochondrial biogenesis. The exposed group showed mtDNA hypermethylation and changes in allied mitochondrial functioning. Altered expression of mitomiRs and their respective target genes in the exposed group indicated the possibilities of a disturbed mitochondrial-nuclear cross talk. This was further confirmed by the modified activity of the mitochondrial stress regulators and pro-inflammatory mediators among the exposed group. Importantly, the disturbed DNMT functioning, hypermethylation of nuclear DNA, and higher degree of post-translational histone modifications established the existence of aberrant epigenetic modifications in the exposed individuals. Overall, our results demonstrate the first molecular insights of in utero pro-oxidant exposure associated changes in the mitochondrial-epigenetic axis. Although, our study might not cement an exposure-response relationship for any particular environmental pro-oxidant, but suffice to establish a dogma of mito-epigenetic reprogramming at intrauterine milieu with chronic illness, a hitherto unreported interaction.

Graphical abstract

     

Environmental issues for sustainable development

Environmental Science and Pollution Research -