Micro-computed tomography (CT) is a non-invasive alternative to conventional macroscopic dissection for the evaluation of human fetal cardiac anatomy. This paper aims to systematically review the literature regarding the use of micro-CT to examine human fetal hearts, to illustrate its educational and research implications and to explain its possible directions for the future. A systematic literature review was conducted following the PRISMA statement to identify publications concerning micro-CT applications for the isolated human fetal heart. The search strategy identified nine eligible studies. Micro-CT is technically feasible for postmortem examination of the human fetal heart coming from early and late termination of pregnancy. It reaches high diagnostic accuracy, and it seems to perform better than autopsy in small samples or in the case of early termination of pregnancy. Applications derived from micro-CT allow multiple off-time evaluations and interdisciplinary comparisons for educational purposes and research perspectives in biological and bioengineering domains.

The possible link between SARS-CoV-2 infection and adverse pregnancy outcomes has so far demonstrated heterogeneous results in terms of maternal, fetal, and neonatal complications. We aim to investigate the correlation between SARS-CoV-2 seroconversion and/or neutralization titer and pregnancy outcomes. We analyzed a population of 528 pregnant women followed up from the first trimester of gestation until delivery. For each woman, we collected a first blood sample between 11 and 13 weeks of gestation and a second sample in the perinatal period (between peripartum and puerperium) to assess the presence of SARS-CoV-2 antibodies and/or microneutralization titer (MN titer). Data on pregnancy outcomes (gestational age at delivery, preterm birth before 34 weeks, hypertensive disorders, gestational diabetes, and abnormal fetal growth) were collected. We observed that serologic status per se is not associated with major pregnancy complications. On the contrary, the MN titer was associated with increased odds of gestational diabetes. Although we mainly reported asymptomatic SARS-CoV-2 infections and the absence of severe maternal and neonatal adverse outcomes, SARS-CoV-2 infection might challenge the maternal immune system and explain the moderate increase in adverse outcome odds.

Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11–13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay.

Sonographic findings of cerebral arteriovenous malformations in the fetus are uncommon and usually regard aneurysm of the Galen vein. Outcome of arteriovenous malformations is usually severe. We report a case of a fetus at 21 weeks’ gestation with a rarer arteriovenous malformation, referred to us for echocardiography on account of a suspicious cardiomegaly at obstetrical scan. Upon examination, we found cardiomegaly, together with an associated moderate tricuspid regurgitation, however, there were no clear features of tricuspid dysplasia. Considering an unusually dilated superior vena cava, we found via color Doppler imaging a systodiastolic flow at Color Doppler progressing. Subsequent MRI of the central nervous system determined the localization in the sinus dura mater. Due to an already evident hemodynamic impact, the parents opted for the termination of the pregnancy. Autopsy confirmed a voluminous arteriovenous malformation of the transverse sinus of the dura mater, severe cardiomegaly, mainly of the ventricles, and hypoplasia of the lungs.

Background/Objectives: Prenatal Exome Sequencing (pES) has revolutionized prenatal diagnosis in fetuses with congenital anomalies. Although its performance is very promising, previous pES studies have mainly focused on diagnostic yield, often without considering the actual impact on ongoing pregnancies. In this study, we aim to (1) assess whether a prenatal molecular diagnosis can reliably predict the clinical features of the unborn child and (2) determine the gestational age (gw) at which ultrasound (US) findings are sufficient to support the pathogenicity of genetic variants detected by pES. Methods: We retrospectively selected 47 cases complicated by US anomalies that underwent Exome Sequencing (ES) and for which complete clinical assessment was available. A blinded reanalysis of ES data was performed, considering only prenatal features. Results: In our cohort, standard ES led to a molecular diagnosis in 43% of cases. The blinded reanalysis revealed that a complete or partial retrospective prenatal diagnosis was achievable in 95% of diagnosed cases. The mean gestational week at which US data would have supported molecular diagnosis was 22 + 5 weeks. The clinical follow-up confirmed a syndromic presentation in 21 out of 23 newborns and in all terminated pregnancies. Conclusions: Our study further confirms that pES is a valuable diagnostic tool for detecting genetic etiology in fetuses with congenital malformations. In most cases, pES results accurately predict the postnatal phenotype. However, the prenatal setting requires specific adjustments and precautions, and a negative pES result cannot be considered reassuring.