Particulate air pollution, blood mitochondrial DNA copy number, and telomere length in mothers in the first trimester of pregnancy : effects on fetal growth

Growing evidences have shown that particulate matter (PM) exposures during pregnancy are associated with impaired fetal development and adverse birth outcomes, possibly as a result of an exaggerated systemic oxidative stress and inflammation. Telomere length (TL) is strongly linked to biological age and is impacted by oxidative stress. We hypothesized that PM exposure during different time windows in the first trimester of pregnancy influences both mitochondrial DNA copy number (mtDNAcn), an established biomarker for oxidative stress, and TL. Maternal blood TL and mtDNAcn were analysed in 199 healthy pregnant women recruited at the 11th week of pregnancy by quantitative polymerase chain reaction. We also examined whether maternal mtDNAcn and TL were associated with fetal growth outcomes measured at the end of the first trimester of pregnancy (fetal heart rate, FHR; crown-rump length, CRL; and nuchal translucency, NT) and at delivery (birth weight, length, head circumference). The possible modifying effect of prepregnancy maternal body mass index was evaluated. PM10 exposure during the first pregnancy trimester was associated with an increased maternal mtDNAcn and a reduced TL. As regards ultrasound fetal outcomes, both FHR and CRL were positively associated with PM2.5, whereas the association with FHR was confirmed only when examining PM10 exposure. PM10 was also associated with a reduced birth weight. While no association was found between mtDNAcn and CRL, we found a negative relationship between mtDNAcn and fetal CRL only in overweight women, whereas normal-weight women exhibited a positive, albeit nonsignificant, association. As abnormalities of growth in utero have been associated with postnatal childhood and adulthood onset diseases and as PM is a widespread pollutant relevant to the large majority of the human population and obesity a rising risk factor, our results, if confirmed in a larger population, might represent an important contribution towards the development of more targeted public health strategies

A practical approach for the management of obstetric and infertile women during the phase two of the novel coronavirus disease 2019 (COVID \u201019) pandemic

Since December 2019, the outbreak of the novel coronavirus disease 2019 (COVID-19) has rapidly spread from China worldwide until to be declared a pandemic. To date, worldwide, almost 5 million confirmed cases of COVID-19 have been reported. It is urgent to address the impact of this pandemic on the obstetric and reproductive medicine, seeking for reorganization strategies of daily practice [1,2]. Although professional bodies and experts have provided specific guidance [2], based on current limited evidences, data on obstetric, neonatal and reproductive outcomes are still partial [3]. In many countries after national lockdown, a Phase 2 started relaxing restrictions. To manage this phase, we recommend adopting rigorous preventive measures. Global lockdown has significantly impacted on new births, especially on those obtained with assisted reproductive technology (ART)

Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope.

BACKGROUND: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. METHODS: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. RESULTS: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. CONCLUSIONS: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

Circulating Nucleic Acids in Maternal Plasma and Serum in Pregnancy Complications: Are They Really Useful in Clinical Practice? A Systematic Review

Objective: A systematic review was carried out to summarize the available evidence to assess whether circulating nucleic acids in maternal plasma and serum (CNAPS) have the potential to serve as extra and independent markers for the prediction and/or progression monitoring of the most common and severe complications of pregnancy, including preeclampsia, intrauterine growth restriction, preterm delivery, morbidly adherent placenta, gestational diabetes, antiphospholipid syndrome, threatened abortion, intrahepatic cholestasis of pregnancy, and hyperemesis gravidarum. Method: A comprehensive literature search of the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases was conducted to identify relevant studies that included amounts of CNAPS in the abovementioned pregnancy complications. Results: Eighty-three studies met the eligibility criteria. The vast majority of studies were conducted on the quantity of total circulating cell free DNA (cfDNA) and cell free fetal DNA (cffDNA), and some were conducted on messenger RNA (mRNA) species. A few studies have instead evaluated the cell free DNA fetal fraction (cfDNAff), but only in a limited number of pregnancy complications. Despite the growing interest and the abundance of the papers available, little information is available for other new CNAPS, including microRNA (miRNA), long noncoding RNA (lncRNA), mitochondrial DNA (mtDNA), and circular RNA. Conclusion: Due to the heterogeneity of the populations enrolled, the scarcity of the studies that adjusted the CNAPS values for possible confounding factors, and the difficulty in interpreting the published data, no conclusion regarding the statistical robustness and clinical relevance of the data can be made at present. If assayed at the third trimester, the CNAPS have, however, shown better performance, and could be used in populations already at risk of developing complications as suggested by the presence of other clinical features. Other CNAPS, including miRNA, are under investigation, especially for the screening of gestational diabetes mellitus, but no data about their clinical utility are available. Circulating DNA (cfDNA, cffDNA, and cfDNAff) and mRNA have not been properly evaluated yet, especially in patients asymptomatic early in pregnancy but who developed complications later, perhaps because of the high cost of these techniques and the availability of other predictors of pregnancy complications (biochemical, biophysical, and ultrasound markers). Therefore, from the analysis of the data, the positive predictive value is not available. As regards the new CNAPS, including miRNA, there are still no sufficient data to understand if they can be promising markers for pregnancy complications monitoring and screening, since CNAPS are statistically weak and expensive. It is reasonable to currently conclude that the use of the CNAPS in clinical practice is not recommended

Multiparameter Analysis of Heart Rate Variability Signal for the Investigation of High Risk Fetuses

The purpose of this study is to evaluate the information content provided by the fluximetry information and the analysis of fetal heart rate (FHR) signals, obtained from cardiotocographic recordings, during prenatal monitoring, in a high risk population. The parameters assessed on FHR signals are divided in: (i) time domain parameters (ii) frequency domain parameters, and (iii) the complexity parameters: Approximate Entropy (ApEn), Sample Entropy (SampEn), Multiscale Entropy (MSE), the Lempel Ziv Complexity (LZC) and the Detrended Fluctuation Analysis (DFA). The fetuses were classified as fetal growth restricted (FGR). The results have shown that the FGR fetuses preterm delivered have produced a markedly reduced heart rate variability in respect with those fetuses which were characterized by an alteration in the fluximetric indices. The normal range in cord blood sampling analysis excludes the prolonged hypoxia as a causing factor. Finally, it seems that the residual cardiovascular response in FGR fetuses could be correlated to an alteration in the flow of the main vessels

Ultrasound assessment of maternal adipose tissue during 1st trimester screening for aneuploidies and risk of developing gestational diabetes

Introduction: The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). Material and methods: Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) 6592 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG <92 mg/dL underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. Results: The study population included 238 non-diabetic women, 29 women with 1st trimester GDM and 28 women with 2nd trimester GDM. Mean subcutaneous adipose thickness and visceral adipose thickness values in non-diabetic women were 9.8 mm (standard deviation [SD = 4.9) and 7.2 mm (SD = 3.5), respectively. Values in women with 1st trimester GDM were 12.8 mm (SD = 6.5) and 9.9 mm (SD = 4.4). In the 2nd trimester GDM group, the mean subcutaneous adipose thickness was 11.1 mm (SD = 4.6) and the mean visceral adipose thickness 10.5 mm (SD = 5.3). Multiple logistic regression analysis showed that visceral adipose thickness, but not subcutaneous adipose thickness, was significantly and independently associated with both 1st trimester GDM (OR 1.15, 95% CI 1.02-1.29) and 2nd trimester GDM (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05-1.34). Conclusions: Sonographic thickness of maternal visceral adipose tissue was greater in women with GDM than in non-diabetic patients, independently of other known risk factors associated with GDM in the 1st and in the 2nd trimester of pregnancy. Thus, this measurement may be considered of clinical use in 1st trimester screening

Management of gestational diabetes in women with a concurrent Sars-Cov-2 infection, experience of a single center in Northern Italy

Objective: In this study we describe the management of women with gestational diabetes (GD) and an ongoing Sars-Cov-2 infection. The aim of the study is to evaluate whether the COVID-19 infection can further complicate pregnancies and thus if the protocol we usually use for GDM pregnancies is also applicable to patients who have contracted a Sars-Cov-2 infection. Methods: This is a retrospective study analysing all pregnant women with gestational diabetes and a concomitant COVID-19 infection admitted to our Institution for antenatal care between March 1st and April 30th 2020. Results: Among pregnant women with GD and a concomitant COVID-19 infection, the mean age was 32,9 (SD 5,6) years. Two patients (33%) were of Caucasian ethnicity while four (67%) were non-Caucasian. All patients were diagnosed with COVID-19 during the third trimester of pregnancy. Two women were asymptomatic while four were symptomatic. Only two patients (33,3%) received treatment with insulin. None of the patients required intensive care or mechanical ventilation. No complications were found among the newborns. Conclusion: the COVID-19 infection was not found to worsen the prognosis of GD patients or of their offspring. Glycaemic monitoring, diet therapy and insulin, when needed, are sufficient for a good metabolic control and a favourable maternal and fetal outcome