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Background: Women are at an increased risk of developing psychiatric conditions such as anxiety and depression during pregnancy. Psychiatric conditions during pregnancy can put mothers and fetuses at risk of worse physical and mental health before, during, and after the completion of a pregnancy. Previous research indicates that women pregnant during COVID-19 were at a greater risk of developing mental health conditions and being exposed to stressors. While most of the research in the field focuses solely on maternal mental health or interactions between stressors and maternal mental health, little research has been done comparing maternal mental health, demographic variables, and socioeconomic variables across pre-, during-, and post-COVID-19 time periods., Methods: We conducted an observational cohort study of 703 mothers divided into pre-, during-, and post-COVID-19 groups based on time of enrollment., Results: Rates of maternal anxiety ( p < 0.001), medication use for anxiety ( p < 0.001), depression ( p < 0.001), medication use for depression ( p < 0.001), history of postpartum depression ( p < 0.001), and medication use for other psychiatric conditions ( p < 0.001) significantly increased during COVID-19 and remained at elevated levels post-COVID-19 compared with pre-COVID-19. Income >150% of the poverty level ( p = 0.003), food security level ( p = 0.010), marital status ( p = 0.001), and private insurance type ( p < 0.001) were significantly increased during COVID-19 compared with pre-COVID-19 levels., Conclusions: Future work should focus on stratifying the effects of the COVID-19 pandemic on maternal mental health by race and ethnicity and establishing guidelines to support maternal mental health during epidemics and pandemics., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Preeclampsia (PE) differentially impairs female and male fetal endothelial cell function, which is associated with an increased risk of adult-onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA-29a-3p and 29c-3p (miR-29a/c-3p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex-dependent manner. RT-qPCR analysis of miR-29a/c-3p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) pregnancies and PE. Bioinformatic analysis of an RNA-seq dataset was performed to identify PE-dysregulated miR-29a/c-3p target genes in female and male P0-HUVECs. Gain- and loss-of-function assays were conducted to determine the effects of miR-29a/c-3p on endothelial monolayer integrity and proliferation in response to transforming growth factor-β1 (TGFβ1) and tumour necrosis factor-α (TNFα) in NT and PE HUVECs at passage 1. We observed that PE downregulated miR-29a/c-3p in male and female P0-HUVECs. PE dysregulated significantly more miR-29a/c-3p target genes in female vs. male P0-HUVECs. Many of these PE-differentially dysregulated miR-29a/c-3p target genes are associated with critical cardiovascular diseases and endothelial function. We further demonstrated that miR-29a/c-3p knockdown specifically recovered the PE-abolished TGFβ1-induced strengthening of endothelial monolayer integrity in female HUVECs, while miR-29a/c-3p overexpression specifically enhanced the TNFα-promoted cell proliferation in male PE HUVECs. In conclusion, PE downregulates miR-29a/c-3p expression and differentially dysregulates miR-29a/c-3p target genes associated with cardiovascular diseases and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex-specific endothelial dysfunction observed in PE. KEY POINTS: Preeclampsia differentially impairs female and male fetal endothelial cell function in responses to cytokines. Pro-inflammatory cytokines are elevated in maternal circulation during pregnancy in preeclampsia. MicroRNAs are critical regulators of endothelial cell function during pregnancy. We have previously reported that preeclampsia downregulated microRNA-29a-3p and 29c-3p (miR-29a/c-3p) in primary fetal endothelial cells. However, it is unknown if PE differentially dysregulates the expression of miR-29a/c-3p in female and male fetal endothelial cells. We show that preeclampsia downregulates miR-29a/c-3p in male and female HUVECs and preeclampsia dysregulates cardiovascular disease- and endothelial function-associated miR-29a/c-3p target genes in HUVECs in a fetal sex-specific manner. MiR-29a/c-3p differentially mediate cell responses to cytokines in female and male fetal endothelial cells from preeclampsia. We have revealed fetal sex-specific dysregulation of miR-29a/c-3p target genes in fetal endothelial cells from preeclampsia. This differential dysregulation may contribute to fetal sex-specific endothelial dysfunction in offspring born to preeclamptic mothers., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

Background: Systemic lupus erythematosus (SLE) can cause placental dysfunctions, which may result in pregnancy complications. Long noncoding RNAs (lncRNAs) are actively involved in the regulation of immune responses during pregnancy. The present study aimed to determine the lncRNA expression profiles in placentas from women with SLE to gain new insights into the underlying molecular mechanisms in SLE pregnancies., Methods: RNA sequencing (RNA-seq) analysis was performed to identify SLE-dysregulated lncRNAs and mRNAs in placentas from women with SLE and normal full-term (NT) pregnancies. Bioinformatics analysis was conducted to predict the biological functions of these SLE-dysregulated lncRNAs and mRNAs., Results: RNA-seq analysis identified 52 dysregulated lncRNAs in SLE placentas, including 37 that were upregulated and 15 downregulated. Additional 130 SLE-dysregulated mRNAs were discovered, including 122 upregulated and 8 downregulated. Bioinformatics analysis revealed that SLE-dysregulated genes were associated with biological functions and gene networks, such as regulation of type I interferon-mediated signaling pathway, response to hypoxia, regulation of MAPK (mitogen-activated protein kinase) cascade, response to steroid hormone, complement and coagulation cascades, and Th1 and Th2 cell differentiation., Conclusions: This is the first report of the lncRNA profiles in placentas from SLE pregnancies. These results suggest that the aberrant expression and the potential regulatory function of lncRNAs in placentas may play comprehensive roles in the pathogenesis of SLE pregnancies. SLE-dysregulated lncRNAs may potentially serve as biomarkers for SLE., (© 2022. The Author(s).)

Background: Systemic lupus erythematosus (SLE) may cause pathogenic changes in the placentas during human pregnancy, such as decreased placental weight, intraplacental hematoma, ischemic hypoxic change, placental infarction, and decidual vasculopathy, which contribute to high maternal and fetal mortality and morbidity. Sex-specific adaptations of the fetus are associated with SLE pregnancies. The present study aimed to determine the transcriptomic profiles of female and male placentas from women with SLE., Methods: RNA sequencing (RNA-seq) was performed to identify differentially expressed protein-coding genes (DEGs) in placentas from women with SLE vs. normal term (NT) pregnancies with female and male fetuses ( n = 3-5/sex/group). Real-time-quantitative PCR was performed ( n = 4 /sex/group) to validate the RNA-seq results. Bioinformatics functional analysis was performed to predict the biological functions and pathways of SLE-dysregulated protein-coding genes., Results: Compared with NT-female (NT-F) placentas, 119 DEGs were identified in SLE-female (SLE-F) placentas. Among these 119 DEGs, five and zero are located on X- and Y-chromosomes, respectively, and four are located on the mitochondrial genome. Compared with NT-male (NT-M) placentas, 458 DEGs were identified in SLE-male (SLE-M) placentas, among which 16 are located on the X-chromosome and zero on the Y-chromosome and mitochondrial genome. Twenty-four DEGs were commonly dysregulated in SLE-F and -M placentas. Functional analysis showed that SLE-dysregulated protein-coding genes were associated with diverse biological functions and pathways, including angiogenesis, cellular response to growth factor stimulus, heparin-binding, HIF (hypoxia-inducible factor)-1 signaling pathway, and Interleukin-17 (IL-17) signaling pathway in both SLE-F and -M placentas. Biological regulations were differentially enriched between SLE-F and -M placentas. Regulation of blood circulation, response to glucocorticoid, and rhythmic process were all enriched in SLE-F, but not SLE-M placentas. In contrast, tumor necrosis factor production, Th17 cell differentiation, and MDA (melanoma differentiation-associated gene)-5 signaling pathway were enriched in SLE-M but not SLE-F placentas., Conclusion: This report investigated the protein-coding gene profiles of placenta tissues from SLE patients using RNA-seq. The results suggest that the SLE-dysregulated protein-coding genes in placentas may contribute to the pathophysiological progress of SLE pregnancies in a fetal sex-specific manner, leading to adverse pregnancy outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Sai, Tian, Liu, Freel, Wang, Zhou, Zheng, Shu and Zhao.)

Objective: Diazoxide is used to treat infants with persistent hypoglycemia, but the prevalence of its use and adverse effects are not well described. We report demographic and clinical characteristics of infants treated with diazoxide in neonatal intensive care units (NICUs)., Study Design: Retrospective cohort study of infants 24-41 weeks' gestation admitted to 392 NICUs from 1997-2016, comparing characteristics between hypoglycemic infants exposed/not exposed to diazoxide. For diazoxide courses > 1 day, we report percentages of infants starting diuretics and/or developing new ventilator/oxygen requirement during therapy., Results: Among 1,249,466 infants, 185,832 had hypoglycemia; 1066/185,832 (0.57%) received diazoxide. Diazoxide use increased over time (P = 0.001). Infants receiving diazoxide varied from 0-14.9% among centers. New diuretic courses were associated with 91/664 (14%), and new oxygen or ventilator requirement during therapy was associated with 64/556 (12%) and 34/647 (5%), respectively., Conclusions: Diazoxide use in NICU settings has increased over time. Infants receiving diazoxide commonly received diuretics.