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The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29‐year‐old Japanese primipara with treatment‐resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N‐desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) are transcripts originating from the genome that do not serve as templates for protein synthesis. They function as epigenetic and translational regulators in various pathophysiological mechanisms, including cell proliferation and apoptosis. The ferroptosis signaling pathway, a novel mode of cell death, participates in numerous pathophysiological processes. Its signaling transmission is both complex and precise, featuring interconnected and interdependent pathways. Recent studies suggest that ncRNAs can finely regulate key genes in the ferroptosis pathway, thus modulating cellular functions, reducing oxidative stress, and maintaining maternal-fetal interface homeostasis. Future strategies targeting the ncRNA/ferroptosis axis may provide new perspectives and potential intervention points for treating preeclampsia. This article clarifies how the ncRNA/ferroptosis axis impacts preeclampsia, revealing how ncRNAs interact with ferroptosis, and pinpointing new molecular targets for the treatment of preeclampsia, thereby providing theoretical support for clinical strategies. [ABSTRACT FROM AUTHOR]

Introduction: An optimal fetal supply of docosahexaenoic acid (DHA) is critical for normal brain development. The relationship between maternal DHA intake and DHA delivery to the fetus is complex and is dependent on placental handling of DHA. Little data exist on placental DHA levels in pregnancies supplemented with the recommended dose of 200 mg/d. Our objective was to determine how prenatal DHA at the recommended 200 mg/d impacts maternal, placental, and fetal DHA status in both normal-weight and high-BMI women compared to women taking no supplements. Methods: Maternal blood, placenta, and cord blood were collected from 30 healthy pregnant women (BMI 18.9–43.26 kg/m2) giving birth at term. Red blood cells (RBCs) and villous tissue were isolated, and lipids were extracted to determine DHA content by LC-MS/MS. Data were analyzed by supplement group (0 vs. 200 mg/d) and maternal BMI (normal weight or high BMI) using two-way ANOVA. We measured maternal choline levels in maternal and cord plasma samples. Results: Supplementation with 200 mg/d DHA significantly increased (p < 0.05) maternal and cord RBC DHA content only in pregnancies complicated by high BMI. We did not find any impact of choline levels on maternal or cord RBC phospholipids. There were no significant differences in total placental DHA content by supplementation or maternal BMI (p > 0.05). Placental levels of phosphatidylinositol (PI) and phosphatidic acid containing DHA species were higher (p < 0.05) in high-BMI women without DHA supplementation compared to both normal-BMI and high-BMI women taking DHA supplements. Conclusion: Maternal DHA supplementation at recommended doses cord increased RBC DHA content only in pregnancies complicated by higher BMI. Surprisingly, we found that obesity was related to an increase in placental PI and phosphatidic acid species, which was ameliorated by DHA supplementation. Phosphatidic acid activates placental mTOR, which regulates amino acid transport and may explain previous findings of the impact of DHA on placental function. Current recommendations for DHA supplementation may not be achieving the goal of improving fetal DHA levels in normal-weight women. [ABSTRACT FROM AUTHOR]

Background: Respiratory functions may be impaired in cesarean section (C/S) delivery performed under spinal anesthesia (SA) and oxygen supplementation may be required. Therefore, we conducted a randomized controlled study aimed to evaluate the effects of different oxygen administrations in pregnant women on the lungs during C/S under SA using ultrasound and oxygen reserve index (ORI). Methods: We conducted a randomized, controlled, single-center study from May 1, 2021, to March 31, 2022. A total of 90 patients scheduled for C/S under SA were randomly divided into 3 groups. Following the SA, patients in group 0 were treated with room air, in Group 3 were administered 3 L/min O₂ with a nasal cannula (NC), in Group 6 were administered 6 L/min O₂ with a simple face mask. In addition to routine monitoring, ORI values were measured. Lung aeration was evaluated through the modified lung ultrasound score (LUS) before the procedure (T0), at minute 0 (T1), 20 (T2), and hour 6 (T3) after the procedure, and ∆LUS values were recorded. Results: After SA, the ORI values of Group 3 were higher than Group 0 at all times (p < 0.05), while the intraoperative 1st minute and the 10th, 25th and 40th minutes after delivery (p = 0.001, p = 0.027, p = 0.001, p = 0.019) was higher than Group 6. When the LUS values of each group were compared with the T0 values a decrease was observed in Group 3 and Group 6 (p < 0.001, p = 0.016). While ∆LUS values were always higher in Group 3 than in Group 0, they were higher only in T1 and T2 in Group 6. Conclusion: We determined that it would be appropriate to prefer 3 L/min supplemental oxygen therapy with NC in C/S to be performed under SA. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) outbreak in 2019 has necessitated investigating its potential adverse effects on pregnancy outcomes and fetal development. Objective: This study aimed to review the evidence on the impact of SARS‐CoV‐2 infection during pregnancy on fetal outcomes. Method of Study: Literatures since the outbreak of COVID‐19 from PubMed and Web of Science were summarized in this narrative review, to show the effects of maternal SARS‐CoV‐2 infection during pregnancy on fetal development. Results: SARS‐CoV‐2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal–fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS‐CoV‐2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth. However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes. Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes. Conclusion: SARS‐CoV‐2 infection during pregnancy activates the maternal–fetal immune interface through vertical transmission, and has short‐ and long‐term effects on fetal development, including the central nervous system. Future long‐term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF‐1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast‐specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short‐ and long‐term consequences of abnormal fetal growth in the future. [ABSTRACT FROM AUTHOR]

Purpose: To obtain evidence of the clinical validity of the nursing diagnosis (ND) risk for disturbed maternal–fetal dyad in high‐risk pregnancy. Method: Causal validation of the ND through a case–control study performed in a university hospital with 155 high‐risk pregnant women: 31 cases and 124 controls. A causal association was found between the ND etiological factors and the occurrence of disruption of the symbiotic maternal–fetal dyad; an association was verified when the etiological factor presented a p‐value <0.05 and odds ratio >1. Findings: The risk factor absent–inadequate prenatal care; populations at risk, such as young‐advanced maternal age and economically disadvantaged pregnant women; and association conditions, such as maternal conditions and compromised fetal oxygen transport, increased the outcome likelihood. The associated condition maternal illnesses appeared as a protective factor. Conclusions: Evidence of clinical validity of the ND risk for disturbed maternal–fetal dyad was obtained, and an association between etiological factors and disruption of the symbiotic maternal–fetal dyad was found. Implications for nursing practice: The results contribute to advance scientific knowledge in nursing teaching, research, and practice and support the nursing process in high‐risk pregnancies. [ABSTRACT FROM AUTHOR]

Endocytosis represents a category of regulated active transport mechanisms. These encompass clathrin-dependent and -independent mechanisms, as well as fluid phase micropinocytosis and macropinocytosis, each demonstrating varying degrees of specificity and capacity. Collectively, these mechanisms facilitate the internalization of cargo into cellular vesicles. Pregnancy is one such physiological state during which endocytosis may play critical roles. A successful pregnancy necessitates ongoing communication between maternal and fetal cells at the maternal-fetal interface to ensure immunologic tolerance for the semi-allogenic fetus whilst providing adequate protection against infection from pathogens, such as viruses and bacteria. It also requires transport of nutrients across the maternal-fetal interface, but restriction of potentially harmful chemicals and drugs to allow fetal development. In this context, trogocytosis, a specific form of endocytosis, plays a crucial role in immunological tolerance and infection prevention. Endocytosis is also thought to play a significant role in nutrient and toxin handling at the maternal-fetal interface, though its mechanisms remain less understood. A comprehensive understanding of endocytosis and its mechanisms not only enhances our knowledge of maternal-fetal interactions but is also essential for identifying the pathogenesis of pregnancy pathologies and providing new avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Advanced maternal age may affect the intrauterine environment and increase the risk of neurodevelopmental disorders in offspring. Thyroid hormones are critical for fetal neurological development but whether maternal age influences fetal thyroid hormone levels in euthyroid mothers is unknown. Objective: This study evaluated the association between cord blood thyroid hormones and maternal age, fetal sex, maternal thyroid function, and other perinatal factors. Methods: The study population consisted of 203 healthy women with term singleton pregnancies who underwent elective cesarean section. Maternal levels of free T3 (fT3), free T4 (fT4) and TSH before delivery, and cord levels of fT3, fT4 and TSH were measured. Spearman's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between cord thyroid hormone parameters and maternal characteristics. Results: There were no significant differences in maternal serum or cord blood thyroid hormone levels between male and female births. In multivariate linear regression analysis, maternal age and maternal TSH values were negatively associated with the cord blood levels of fT3 in all births, after adjusting for confounding factors. Maternal age was more closely associated with the cord blood levels of fT3 in female than in male births. Conclusion: The inverse association between maternal age and cord blood levels of fT3 in euthyroid pregnant women suggested an impact of maternal aging on offspring thyroid function. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 virus activates maternal and placental immune responses. Such activation in the setting of other infections during pregnancy is known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. Methods and results: We assessed the impact of maternal SARS-CoV-2 on HBCs isolated from 24 term placentas (N = 10 SARS-CoV-2 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells (HBC-iMGs), with impaired synaptic pruning behavior compared to HBC models from negative controls. Conclusion: These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming. [ABSTRACT FROM AUTHOR]

Maternal-fetal microchimerism is a fascinating phenomenon in which maternal cells migrate to the tissues of the offspring during both pregnancy and breastfeeding. These cells primarily consist of leukocytes and stem cells. Remarkably, these maternal cells possess functional potential in the offspring and play a significant role in shaping their immune system development. T lymphocytes, a cell population mainly found in various tissues of the offspring, have been identified as the major cell type derived from maternal microchimerism. These T lymphocytes not only exert effector functions but also influence the development of the offspring's T lymphocytes in the thymus and the maturation of B lymphocytes in the lymph nodes. Furthermore, the migration of maternal leukocytes also facilitates the transfer of immune memory across generations. Maternal microchimerism has also been observed to address immunodeficiencies in the offspring. This review article focuses on investigating the impact of maternal cells transported within maternal microchimerism on the immune system development of the offspring, as well as elucidating the effector functions of maternal cells that migrate through the placenta and breast milk to reach the offspring. [ABSTRACT FROM AUTHOR]

Background: Maternal‐fetal immunology is intricate, and the effects of mRNA‐S maternal vaccination on immune regulation at the maternal‐fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA‐S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology. Objectives: This investigation sought to examine the prospective influence of mRNA‐S‐based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal‐fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM‐CTCs). Methods: We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA‐S vaccine exposure. We assessed the expression of angiotensin‐converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs). Results: Our findings revealed that cells and EVs subjected to mRNA‐S‐based vaccination exhibited altered protein expression levels of S proteins. At the feto‐maternal interface, both placental and fetal membrane tissues demonstrated similar ACE‐2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE‐2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL‐10 and CXCL‐11, as well as proinflammatory cytokines such as IL‐6 in response to eSPs. However, the levels of Ccl‐2 and IL‐1β remained unchanged in decidual cells under the same conditions. Conversely, hFM‐CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs. Conclusion: In conclusion, our study indicates that mRNA‐S‐based maternal vaccination during pregnancy may influence the maternal‐fetal interface's COVID‐19 interaction and immune regulation. Further investigation is warranted to assess safety and implications. [ABSTRACT FROM AUTHOR]

The article calls for universal lead testing in pregnancy. It outlines reason to consider a universal lead testing approach that include inadequate prediction of blood lead levels (BLL) during pregnancy by risk-factor-based screening paradigms, universal blood testing for other conditions, opportunity for health promotion, BLL assay as an inexpensive test, and early intervention upon identification of lead in the blood of a pregnant individual.

Throughout the literature, many pathologic lung lesions and complications following coronavirus disease 2019 (COVID-19) infection have been reported including pneumatocele formation which could potentially lead to pneumothorax development. This case report discusses the clinical course of a 45-day-old male with respiratory distress, whose condition worsened over time. Investigations revealed elevated COVID-19 immunoglobulin G (IgG) antibodies with negative COVID polymerase chain reaction (PCR) accompanied by radiologic evidence of pneumatocele formation, which was further complicated by pneumothorax. The clinical presentation of the patient was consistent with post-COVID infection but he had no history of contact with a sick individual which prompted further investigation of the source of the infection. Upon reviewing the history of the mother, symptoms consistent with COVID-19 around 32 weeks of pregnancy were revealed, which raises the possibility of maternal-fetal exchange of COVID-19 infection. This article presents the youngest reported patient with COVID-19 pneumonia that led to pneumatocele formation.

The introduction of noninvasive prenatal testing has resulted in substantial reductions to previously accepted false-positive rates of prenatal screening. Despite this, the possibility of false-positive results remains a challenging consideration in clinical practice, particularly considering the increasing uptake of genome-wide noninvasive prenatal testing, and the subsequent increased proportion of high-risk results attributable to various biological events besides fetal aneuploidy. Confined placental mosaicism, whereby chromosome anomalies exclusively affect the placenta, is perhaps the most widely accepted cause of false-positive noninvasive prenatal testing. There remains, however, a substantial degree of ambiguity in the literature pertaining to the clinical ramifications of confined placental mosaicism and its potential association with placental insufficiency, and consequentially adverse pregnancy outcomes including fetal growth restriction. Other causes of false-positive noninvasive prenatal testing include vanishing twin syndrome, in which the cell-free DNA from a demised aneuploidy-affected twin triggers a high-risk result, technical failures, and maternal origins of abnormal cell-free DNA such as uterine fibroids or unrecognized mosaicisms. Most concerningly, maternal malignancies are also a documented cause of false-positive screening results. In this review, we compile what is currently known about the various causes of false-positive noninvasive prenatal testing. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective The perinatal period and in utero environment are important for fetal growth, development, and fetal programming. This study aimed to determine the effect of parental anthropometry and the maternal metabolic milieu on offspring adiposity at 2 years of age. Study Design This longitudinal birth cohort includes analysis of maternal (n = 337) and paternal (n = 219) anthropometry and maternal and fetal metabolic markers (n = 337), including glucose, homeostatic model of assessment (HOMA), C-peptide, and leptin from participants of the ROLO (the Randomized Control Trial of Low) pregnancy study, and their partners, to determine an association with offspring anthropometry at two years of age. Results Linear regression, when adjusted for confounders, indicated maternal and paternal anthropometry and was associated with offspring weight and length at 2 years of age. Maternal height was negatively associated with general adiposity in the total cohort of children (p = 0.002) and in female children (p = 0.006) and central adiposity in the total child cohort (p < 0.001). Paternal height was also negatively associated with general adiposity in all children (p = 0.002) and central adiposity in total (p = 0.023) and female children (p = 0.008). Maternal glucose, insulin resistance, and fetal C-peptide positively correlated with anthropometry in total, male, and female children. Conclusion Parental anthropometry in the perinatal period has a long-lasting effect on offspring anthropometry beyond the neonatal period. Maternal and fetal metabolic factors influence adiposity, and this extends beyond the perinatal period. Parental adiposity may play a significant role in early childhood adiposity and may be a target for interventions to decrease the risk of early childhood obesity. Key Points Parental height and weight were associated with offspring anthropometry and measures of offspring adiposity at 2 years of age. Maternal glucose, insulin resistance, and fetal C-peptide correlated with offspring anthropometry. Parental anthropometry has long-term effect on offspring adiposity and is seen at 2 years of age. [ABSTRACT FROM AUTHOR]

Placental phospholipid synthesis is critical for the expansion of the placental exchange surface area and for production of signaling molecules. Despite their importance, it is not yet established which enzymes involved in the de novo synthesis and remodeling of placental phospholipids are expressed and active in the human placenta. We identified phospholipid synthesis enzymes by immunoblotting in placental homogenates and immunofluorescence in placenta tissue sections. Primary human trophoblast (PHT) cells from term healthy placentas (n = 10) were cultured and exposed to 13C labeled fatty acids (16:0, 18:1 and 18:2 n-6, 22:6 n-3) for 2 and 24 h. Three phospholipid classes; phosphatidic acid, phosphatidylcholine, and lysophosphatidylcholine containing 13C fatty acids were quantified by Liquid Chromatography with tandem mass spectrometry (LC/MS–MS). Acyl transferase and phospholipase enzymes were detected in human placenta homogenate and primarily expressed in the syncytiotrophoblast. Three representative 13C fatty acids (16:0, 18:1 and 18:2 n-6) were incorporated rapidly into phosphatidic acid in trophoblasts, but 13C labeled docosahexaenoic acid (DHA; 22:6 n-3) incorporation was not detected. 13C DHA was incorporated into phosphatidylcholine. Lysophosphatidylcholine containing all four 13C labeled fatty acids were found in high abundance. Phospholipid synthesis and remodeling enzymes are present in the syncytiotrophoblast. 13C labeled fatty acids were rapidly incorporated into cellular phospholipids. 13C DHA was incorporated into phospholipids through the remodeling pathway rather than by de novo synthesis. These understudied pathways are highly active and critical for structure and function of the placenta. • Human placenta trophoblasts express de novo phospholipid synthesis and phospholipid remodeling enzymes. • Uniformly labeled 13C fatty acids are rapidly incorporated into cellular phospholipid lipids. • Docosahexaenoic acid is incorporated into trophoblast phospholipids through the remodeling pathway as evidenced by a lack of 13C DHA in the phosphatidic acid form. [ABSTRACT FROM AUTHOR]

Embryo implantation induces the adaptive reprogramming of metabolism at the maternal-fetal interface, resulting in a hypoxic, mildly inflammatory, and slight acidic microenvironment. This type of microenvironment is conductive to establish endometrial receptivity, decidualization, trophoblast invasion and maternal-fetal immune tolerance by regulating the recruitment, activation, metabolism and polarization of immune cell. Successful embryo implantation necessitates the well -timed and suitable initiation and termination of the immune-inflammatory response and the glycolysis -dominated metabolic reprogramming. The dysregulation of immunometabolism caused by pathologic factors can result in adverse pregnancy outcomes, such as embryo implantation failure or post-implantation miscarriage. Macrophage as the most abundant antigen-presenting cell in the endometrium during the implantation window plays a crucial role in regulating immunometabolism at the maternal -fetal interface due to the remarkable immune plasticity and metabolic flexibility. We review the immunometabolic microenvironment and regulatory mechanisms at the maternal -fetal interface, to provide a reference for the advancement of clinical intervention approaches so as to improve the pregnancy outcomes in both natural conception and assisted reproduction. [ABSTRACT FROM AUTHOR]

• Maternal response to COVID-19 messenger RNA vaccine does not impair trophoblast development. • SARS-CoV-2 antibodies in maternal blood do not impair trophoblast development. • This study supports the safety of COVID-19 messenger RNA vaccination during pregnancy. The safety of COVID-19 messenger RNA (mRNA) vaccination during pregnancy remains a topic of concern. Its effect on placenta development has been poorly studied, even though this is essential for healthy pregnancy outcomes. We investigated the effect of the maternal immune response to COVID-19 mRNA vaccination on the development of syncytiotrophoblast (STB), a functional cell layer of the placenta where the maternal-fetal exchange takes place. We collected sera from pregnant women before vaccination and after the second vaccination with the Pfizer-BioNTech mRNA vaccine (n=12 paired samples). Human trophoblast stem cells were subjected to in vitro STB differentiation in the presence of the serum samples. Cell morphology, proliferation, and marker gene expression were assessed to determine STB differentiation. All cells obtained an STB-like morphology, upregulated STB markers, and downregulated trophoblast stem cell markers. We did not find any significant differences in the extent of differentiation between STBs treated with pre- and post-vaccination serum samples. This in vitro study suggests that the maternal inflammatory response and the presence of SARS-CoV-2 antibodies in the maternal blood are not harmful to STB development of the placenta. These findings support the growing body of evidence that COVID-19 mRNA vaccination during pregnancy is safe. [ABSTRACT FROM AUTHOR]

The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed. [ABSTRACT FROM AUTHOR]

The placenta establishes a maternal-fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors, and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of transcription factors GATA2 and GATA3 in labyrinth trophoblast progenitors (LaTPs) have underdeveloped placenta and die by ~embryonic day 9.5. Single-cell RNA sequencing analysis revealed excessive accumulation of multipotent LaTPs upon conditional deletion of GATA factors. The GATA factor-deleted multipotent progenitors were unable to differentiate into matured SynTs. We also show that the GATA factor-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promotes trophoblast progenitor-to-SynT commitment, ensuring establishment of the maternal-fetal exchange interface. [ABSTRACT FROM AUTHOR]

Background Tularemia is caused by the gram-negative bacterium Francisella tularensis. Although rare, tularemia during pregnancy has been associated with pregnancy complications; data on efficacy of recommended antimicrobials for treatment are limited. We performed a systematic literature review to characterize clinical manifestations of tularemia during pregnancy and examine maternal, fetal, and neonatal outcomes with and without antimicrobial treatment. Methods We searched 9 databases, including Medline, Embase, Global Health, and PubMed Central, using terms related to tularemia and pregnancy. Articles reporting cases of tularemia with ≥1 maternal or fetal outcome were included. Results Of 5891 articles identified, 30 articles describing 52 cases of tularemia in pregnant patients met inclusion criteria. Cases were reported from 9 countries, and oropharyngeal and ulceroglandular tularemia were the most common presenting forms. A plurality (46%) of infections occurred in the second trimester. Six complications were observed: lymph node aspiration, lymph node excision, maternal bleeding, spontaneous abortion, intrauterine fetal demise, and preterm birth. No deaths among mothers were reported. Of 28 patients who received antimicrobial treatment, 1 pregnancy loss and 1 fetal death were reported. Among 24 untreated patients, 1 pregnancy loss and 3 fetal deaths were reported, including one where F. tularensis was detected in placental and fetal tissues. Conclusions Pregnancy loss and other complications have been reported among cases of tularemia during pregnancy. However, risk of adverse outcomes may be lower when antimicrobials known to be effective are used. Without treatment, transplacental transmission appears possible. These data underscore the importance of prompt recognition and treatment of tularemia during pregnancy. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is a rare autoimmune disease. Transient neonatal myasthenia gravis (TNMG) is caused by pathogenic maternal autoantibodies that cross the placenta and disrupt signaling at the neuromuscular junction. This is a systematic review of this transient immunoglobulin G (IgG)-mediated disease. TNMG affects 10–20% of children born to mothers with MG. The severity of symptoms ranges from minor feeding difficulties to life-threatening respiratory weakness. Minor symptoms might go unnoticed but can still interfere with breastfeeding. Acetylcholine-esterase inhibitors and antibody-clearing therapies such as immunoglobulins can be used to treat TNMG, but most children do well with observation only. TNMG is self-limiting within weeks as circulating antibodies are naturally cleared from the blood. In rare cases, TNMG is associated with permanent skeletal malformations or permanent myopathy. The mother's antibodies can also lead to spontaneous abortions. All healthcare professionals meeting pregnant or birthing women with MG or their neonates should be aware of TNMG. TNMG is hard to predict. Reoccurrence is common among siblings. Pre-pregnancy thymectomy and intravenous immunoglobulins during pregnancy reduce the risk. Neonatal fragment crystallizable receptor (FcRn) blocking drugs for MG might reduce TNMG risk. [ABSTRACT FROM AUTHOR]

Introduction: The epidemiological investigation of congenital anomalies (CA) represents a challenge due to the multiplicity of associated risk factors, notably environmental ones. The monitoring of genotoxic effects in different populations is a useful tool in human biomonitoring and has great biological importance in estimating the exposure risks to complex mixtures of chemical substances. Objective: This study aimed to determine the presence of environmental xenobiotics and evaluate their genotoxic effect, in mothers of newborns with and without CA, and the possible association/correlation between those biomarkers and CA. Materials and methods: A descriptive case and control cross‐sectional study was developed on 290 postpartum women from Santa Fe, Argentina. Results: Significant differences were observed between both groups, for places of residence and gynecological variables. Metabolites of organochlorine (OC), organophosphate (OP), and pyrethroid (PYR) pesticides were detected. The most frequently detected compounds were atrazine (ATZ) (57.14%), carbendazim (CBZ) (46.42%), and methylparaben (46.42%), among others. A positive correlation was found between the number of pesticides in blood and genotoxic variables. On the other hand, mothers of children with genitourinary anomalies were the ones with the highest concentrations of ATZ and OP. Discussion and conclusion: These results showed a deep background in the health reality of Santa Fe, which could greatly impact the health of future adults, who have been born preterm. On the other hand, the mixture of pesticides detected confirms the environmental living conditions of women and the transplacental exposure to these compounds in each pregnancy. The potential effects on long‐term descendent health are unknown and unpredictable. [ABSTRACT FROM AUTHOR]

Current studies have indicated that insufficient trophoblast epithelial‐mesenchymal transition (EMT), migration and invasion are crucial for spontaneous abortion (SA) occurrence and development. Exosomal miRNAs play significant roles in embryonic development and cellular communication. Hereon, we explored the roles of serum exosomes derived from SA patients on trophoblast EMT, migration and invasion. Exosomes were isolated from normal control (NC) patients with abortion for unplanned pregnancy and SA patients, then characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. Exosomal miRNA profiles were identified by miRNA sequencing. The effects of serum exosomes on trophoblast migration and invasion were detected by scratch wound healing and transwell assays, and other potential mechanisms were revealed by quantitative real‐time PCR (RT‐PCR), western blotting and dual‐luciferase reporter assay. Finally, animal experiments were used to explore the effects of exosomal miR‐410‐3p on embryo absorption in mice. The serum exosomes from SA patients inhibited trophoblast EMT and reduced their migration and invasion ability in vitro. The miRNA sequencing showed that miR‐410‐3p was upregulated in SA serum exosomes. The functional experiments showed that SA serum exosomes restrained trophoblast EMT, migration and invasion by releasing miR‐410‐3p. Mechanistically, SA serum exosomal miR‐410‐3p inhibited trophoblast cell EMT, migration and invasion by targeting TNF receptor‐associated factor 6 (TRAF6) at the post‐transcriptional level. Besides, SA serum exosomal miR‐410‐3p inhibited the p38 MAPK signalling pathway by targeting TRAF6 in trophoblasts. Moreover, milk exosomes loaded with miR‐410‐3p mimic reached the maternal‐fetal interface and aggravated embryo absorption in female mice. Clinically, miR‐410‐3p and TRAF6 expression were abnormal and negatively correlated in the placental villi of SA patients. Our findings indicated that exosome‐derived miR‐410‐3p plays an important role between SA serum and trophoblasts in intercellular communication, suggesting a novel mechanism by which serum exosomal miRNA regulates trophoblasts in SA patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are developmental disabilities that are estimated to occur in 2-5% of elementary school children and that negatively impact a childs ability to function without support. Timely diagnosis-informed interventions are crucial to optimizing the developmental trajectory of children with FASD. The true prevalence of FASD among children receiving services for developmental disabilities is unknown. METHODS: An FASD prevalence study was carried out between 2011 and 2014 among a sample of 5- to 7-year-old children who were receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Children whose parent or caregiver consented were evaluated using the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study assessment protocol and classification criteria. RESULTS: Among 216 eligible caregiver-child dyads, 44 completed assessments that were sufficient to obtain a classification for FASD, including fetal alcohol syndrome (FAS), partial FAS, alcohol-related neurodevelopmental disorder, or no fetal alcohol spectrum disorder. Fifteen children were classified as meeting the criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1000 (6.9%) among all eligible children was estimated. None of the children classified as FASD were receiving services because of an FASD diagnosis, and none had previously been diagnosed with FASD. Autism was the most common qualifying diagnosis for which children classified as FASD were receiving services. CONCLUSIONS: The 6.9% prevalence estimate among Regional Center clients was higher than the prevalence estimate of 2.3% in the same community among 5- to 7-year-old children in the general population, though the estimate was based on only 20% of eligible dyads. All children in the sample were receiving Regional Center services for another diagnosis. Barriers to eligibility for services for children with FASD may lead to less than optimum care for these children. Study findings support the facilitation of access to developmental services for children with FASD.

Objective: Drug exposure during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. We used available electronic health records (EHRs) to describe the use of medications during the first trimester in pregnant women and to compare drug exposure between those women who had an abortion (either elective or spontaneous) compared to those who had live births. Materials and Methods: Case-control study of abortions, either elective or spontaneous (cases), and live birth pregnancies (controls) in Sistema d'Informaci? per al Desenvolupament de la Investigaci? en Atenci? Prim?ria (Catalan Primary Health electronic health records) from 2012 to 2020. Exposure to drugs during first trimester of pregnancy was considered to estimate the association with abortion by conditional logistic regression and adjusted by health conditions and other drugs exposure. Results: Sixty thousand three hundred fifty episodes of abortions were matched to 118,085 live birth pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs. 7.2%, p?0.001), smoking (4.5% vs. 3.6%, p?

Abstract Normal fetal development is critically dependent on optimal nutrient supply by the placenta, and placental amino acid transport has been demonstrated to be positively associated with fetal growth. Mechanistic target of rapamycin (mTOR) is a positive regulator of placental amino acid transporters, such as System A. Oleic acid (OA) has been previously shown to have a stimulatory role on placental mTOR signaling and System A amino acid uptake in primary human trophoblast (PHT) cells. We investigated the mechanistic link between OA and System A activity in PHT. We found that inhibition of mTOR complex 1 or 2, using small interfering RNA to knock down raptor or rictor, prevented OA‐stimulated System A amino acid transport indicating the interaction of OA with mTOR. Phosphatidic acid (PA) is a key intermediary for phospholipid biosynthesis and a known regulator of the mTOR pathway; however, phospholipid biosynthetic pathways have not been extensively studied in placenta. We identified placental isoforms of acyl transferase enzymes involved in de novo phospholipid synthesis. Silencing of 1‐acylglycerol‐3‐phosphate‐O‐acyltransferase‐4, an enzyme in this pathway, prevented OA mediated stimulation of mTOR and System A amino acid transport. These data indicate that OA stimulates mTOR and amino acid transport in PHT cells mediated through de novo synthesis of PA. We speculate that fatty acids in the maternal circulation, such as OA, regulate placental functions critical for fetal growth by interaction with mTOR and that late pregnancy hyperlipidemia may be critical for increasing nutrient transfer to the fetus.

Introduction: An optimal fetal supply of docosahexaenoic acid (DHA) is critical for normal brain development. The relationship between maternal DHA intake and DHA delivery to the fetus is complex and is dependent on placental handling of DHA. Little data exist on placental DHA levels in pregnancies supplemented with the recommended dose of 200 mg/d. Our objective was to determine how prenatal DHA at the recommended 200 mg/d impacts maternal, placental, and fetal DHA status in both normal-weight and high-BMI women compared to women taking no supplements. Methods: Maternal blood, placenta, and cord blood were collected from 30 healthy pregnant women (BMI 18.9–43.26 kg/m2) giving birth at term. Red blood cells (RBCs) and villous tissue were isolated, and lipids were extracted to determine DHA content by LC-MS/MS. Data were analyzed by supplement group (0 vs. 200 mg/d) and maternal BMI (normal weight or high BMI) using two-way ANOVA. We measured maternal choline levels in maternal and cord plasma samples. Results: Supplementation with 200 mg/d DHA significantly increased (p < 0.05) maternal and cord RBC DHA content only in pregnancies complicated by high BMI. We did not find any impact of choline levels on maternal or cord RBC phospholipids. There were no significant differences in total placental DHA content by supplementation or maternal BMI (p > 0.05). Placental levels of phosphatidylinositol (PI) and phosphatidic acid containing DHA species were higher (p < 0.05) in high-BMI women without DHA supplementation compared to both normal-BMI and high-BMI women taking DHA supplements. Conclusion: Maternal DHA supplementation at recommended doses cord increased RBC DHA content only in pregnancies complicated by higher BMI. Surprisingly, we found that obesity was related to an increase in placental PI and phosphatidic acid species, which was ameliorated by DHA supplementation. Phosphatidic acid activates placental mTOR, which regulates amino acid transport and may explain previous findings of the impact of DHA on placental function. Current recommendations for DHA supplementation may not be achieving the goal of improving fetal DHA levels in normal-weight women.

Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in better placentation and fetus-growth, hence termed pregnancy trained dNKs (PTdNKs). Here we show that PTdNKs provide increased protection of the fetus from Fusobacterium nucleatum (FN) infection. We demonstrate that PTdNKs secrete elevated amounts of the bacteriocidal protein granulysin (GNLY) upon incubation with FN compared to dNKs derived from first pregnancies, which leads to increased killing of FN. Furthermore, we showed mechanistically that the GNLY secretion is mediated through the interaction of the FN's Fap2 protein with Gal-GalNAc present on PTdNKs. Finally, we show in vivo, using GNLY-tg mice that enhanced protection of the fetuses from FN infection is observed, as compared to wild type and that this enhance protection is NK cell dependent. Altogether, we show a new function for PTdNKs as protectors of the fetus from bacterial infection. Author summary: During this project, we aimed to elucidate the influence of natural killer (NK) cells in the protection of fetuses during pregnancy. At the maternal-fetal interface a special subset of NK cells can be found, the decidual NK (dNK) cells, which have been shown to be rather nurturing, in contrast to the cytotoxic peripheral blood NK cells. These cells are thought to be essential for the healthy development of placenta and fetus in the uterus. Bacterial and viral infections are quite common during pregnancy and pose a significant risk for the fetus and its development. In this manuscript, we describe how the dNK cells primed through first pregnancy show specific antibacterial properties against the bacterium Fusobacterium nucleatum via the lytic protein granulysin in contrast to the peripheral blood NK cells. Additionally, we showed that NK cells expressing granulysin in mice protect the developing fetuses from the effects of a maternal infection with the bacterium. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a pregnancy-specific disorder with complex pathogenesis. Cuproptosis is a novel identified form of programmed cell death, however, the link between cuproptosis and clinical outcomes in PE is still not fully understood. In this study, we searched for cuproptosis-related genes (CRGs) in the placental tissues of normal and PE patients to clarify the importance of cuproptosis in the development of PE and provide potential predictive indicators for the occurrence of PE. Methods: Using RNA sequencing data in the GEO database, we conducted functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), supported by linear regression model and operating characteristic curve (ROC) curve analysis, and summarized the role of CRGs in preeclampsia. Results: A total of 2831 differentially expressed genes related to PE were screened through multiple database analyses. After further intersection with 19 reported CRGs, 5 CRGs have been closely associated with the pathogenesis of PE, including NFE2L2, PDHA1, PDHB, DLD and GLS. NFE2L2 was identified as a key central gene. Pearson correlation analysis showed that CRGs could be related to several maternal and fetal outcome factors, including the highest pregnancy blood pressure, placenta weight, umbilical blood flow pulsatility index (PI), and neonatal weight. Linear regression equation revealed that the expression of NFE2L2 is negatively correlated with the highest pregnancy blood pressure and umbilical blood flow PI but positively correlated with placental weight and neonatal weight. QRT-PCR showed that the expression of these CRGs was significantly lower in placental tissues. Conclusions: This cuproptosis pattern may be a potential prognostic factor in patients with PE and could provide new insights into disease progression. [ABSTRACT FROM AUTHOR]

Normal fetal development is critically dependent on optimal nutrient supply by the placenta, and placental amino acid transport has been demonstrated to be positively associated with fetal growth. Mechanistic target of rapamycin (mTOR) is a positive regulator of placental amino acid transporters, such as System A. Oleic acid (OA) has been previously shown to have a stimulatory role on placental mTOR signaling and System A amino acid uptake in primary human trophoblast (PHT) cells. We investigated the mechanistic link between OA and System A activity in PHT. We found that inhibition of mTOR complex 1 or 2, using small interfering RNA to knock down raptor or rictor, prevented OA‐stimulated System A amino acid transport indicating the interaction of OA with mTOR. Phosphatidic acid (PA) is a key intermediary for phospholipid biosynthesis and a known regulator of the mTOR pathway; however, phospholipid biosynthetic pathways have not been extensively studied in placenta. We identified placental isoforms of acyl transferase enzymes involved in de novo phospholipid synthesis. Silencing of 1‐acylglycerol‐3‐phosphate‐O‐acyltransferase‐4, an enzyme in this pathway, prevented OA mediated stimulation of mTOR and System A amino acid transport. These data indicate that OA stimulates mTOR and amino acid transport in PHT cells mediated through de novo synthesis of PA. We speculate that fatty acids in the maternal circulation, such as OA, regulate placental functions critical for fetal growth by interaction with mTOR and that late pregnancy hyperlipidemia may be critical for increasing nutrient transfer to the fetus. [ABSTRACT FROM AUTHOR]

A case–control study was conducted to examine the association of particulate matter exposure during the pre-natal (the first, second, and third trimesters. and the whole pregnancy) and post-natal periods (the first year after birth) with childhood asthma in Beijing, China. Multivariable logistic regressions showed that childhood asthma was significantly associated with exposures to PM2.5 and PM10 during the entire pregnancy, with ORs of 1.28(95%CI:1.06–1.56) and 1.21(95%CI:1.02–1.42), respectively. The highest association with a 10 μg/m3 increase in PM2.5 and PM10 were both seen for the second trimester, with ORs of 1.17(95% CI: 1.05–1.30) and 1.14(95% CI: 1.04–1.24). Subgroup analyses suggested that significant and positive effects were subject to be observed in children with a family history of atopy. This study added evidence that exposures to PM2.5 and PM10 during pregnancy might increase the risk of childhood asthma in seriously polluted area, highlighting stronger associations in the second trimester. [ABSTRACT FROM AUTHOR]

Background: Twin pregnancies are complex and have often been associated with various complications affecting both mother and baby. Understanding the different maternal and foetal outcomes can provide crucial insights for healthcare practitioners. The aim was to determine the maternal and foetal outcomes of twin pregnancies and understand the factors influencing these outcomes. Methods: A prospective observational study was conducted with women experiencing twin pregnancies of more than 28 weeks gestation. Patients were followed up until 7 days postnatally and the outcomes were analyzed against various parameters such as age, foetal presentation, and mode of delivery. Statistical software SPSS V 26 was utilized for data analysis and ethical considerations were duly met. Results: A total of 22,922 deliveries were recorded, with 195 being twin pregnancies. Most twin deliveries were among women aged 20-29 years, with nearly half being first pregnancies. Major findings include a prevalence of preterm deliveries (59.6%), a high incidence of maternal anaemia (54%), and a significant number of neonatal intensive care unit (NICU) admissions (45.45%). No statistically significant difference was observed in the fetomaternal outcomes about the mode of delivery or booking status. Conclusion: Twin pregnancies are associated with a higher likelihood of preterm deliveries, maternal anaemia, and newborn NICU admissions. Importantly, the mode of delivery and booking status did not significantly affect the feto-maternal outcomes. This study underscores the need for individualized patient care in managing twin pregnancies. [ABSTRACT FROM AUTHOR]

Background: Extensive production and usage of commercially available products containing TiO2 NPs have led to accumulation in the human body. The deposition of TiO2 NPs has even been detected in the human placenta, which raises concerns regarding fetal health. Previous studies regarding developmental toxicity have frequently focused on TiO2 NPs < 50 nm, whereas the potential adverse effects of large-sized TiO2 NPs received less attention. Placental vasculature is essential for maternal–fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO2 NPs (100 nm in size) on the placenta and fetal development and elucidates the underlying mechanism from the perspective of placental vasculature. Pregnant C57BL/6 mice were exposed to TiO2 NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5–16.5. Results: TiO2 NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO2 NP-exposed groups exhibited a dose-dependent decrease in body weight and length, as well as in placental weight and diameter. In vivo imaging showed an impaired placental barrier, and pathological examinations revealed a disrupted vascular network of the labyrinth upon TiO2 NP exposure. We also found an increase in gene expression related to the transforming growth factor-β (TGF-β) -SNAIL pathway and the upregulation of mesenchymal markers, accompanied by a reduction in endothelial markers. In addition, TiO2 NPs enhanced the gene expression responsible for the endothelial-to-mesenchymal transition (EndMT) in cultured human umbilical vein endothelial cells, whereas SNAIL knockdown attenuated the induction of EndMT phenotypes. Conclusion: Our study revealed that maternal exposure to 100 nm TiO2 NPs disrupts placental vascular development and fetal mice growth through aberrant activation of EndMT in the placental labyrinth. These data provide novel insight into the mechanisms of developmental toxicity posed by NPs. [ABSTRACT FROM AUTHOR]

Pre -eclampsia is a pregnancy complication with multiple organs and system injuries, seriously impairing maternal and fetal health. Nevertheless, the etiopathogenesis of pre -eclampsia has not been fully elucidated yet. In normal pregnancy, Toll-like receptor 4 (TLR4) at the maternal-fetal interface regulates the homeostasis of the inflammatory-immune microenvironment. In pre -eclampsia, abnormal TLR4 signaling at the maternal -fetal interface not only mediates deviated inflammatory-immune reaction, but also interacts with other novel pathological phenomena, including ferroptosis, pyroptosis, metabolism reprogramming, and cellular senescence. Furthermore, TLR4 at the maternal -fetal interface may mediate the abnormal development of the nervous system in the offspring. In addition, targeting TLR4 at the maternal-fetal interface may be one of the potential pharmacological mechanisms for new therapeutic research in pre -eclampsia. Based on recent relevant literature, this article explores the multiple possible roles of TLR4 at the maternal-fetal interface in pre-eclampsia and provides reference for the study of the pathogenesis and therapies of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid critical for fetal brain development that is transported to the fetus from the mother by the placenta. The lysophosphatidylcholine (LPC) transporter, Major Facilitator Superfamily Domain Containing 2a (MFSD2a), is localized in the basal plasma membrane of the syncytiotrophoblast of the human placenta, and MFSD2a expression correlates with umbilical cord blood LPC-DHA levels in human pregnancy. We hypothesized that placenta-specific knockdown of MFSD2a in pregnant mice reduces phospholipid DHA accumulation in the fetal brain. Methods: Mouse blastocysts (E3.5) were transduced with an EGFP-expressing lentivirus containing either an shRNA targeting MFSD2a or a non-coding sequence (SCR), then transferred to pseudopregnant females. At E18.5, fetuses were weighed and their placenta, brain, liver and plasma were collected. MFSD2a mRNA expression was determined by qPCR in the brain, liver and placenta and phospholipid DHA was quantified by LC-MS/MS. Results: MFSD2a-targeting shRNA reduced placental mRNA MFSD2a expression by 38% at E18.5 (n = 45, p < 0.008) compared with SCR controls. MFSD2a expression in the fetal brain and liver were unchanged. Fetal brain weight was reduced by 13% (p = 0.006). Body weight, placenta and liver weights were unaffected. Fetal brain phosphatidyl choline and phosphatidyl ethanolamine DHA content was lower in fetuses with placenta-specific MFSD2a knockdown. Conclusions: Placenta-specific reduction in expression of the LPC-DHA transporter MFSD2a resulted in reduced fetal brain weight and lower phospholipid DHA content in the fetal brain. These data provide mechanistic evidence that placental MFSD2a mediates maternal–fetal transfer of LPC-DHA, which is critical for brain growth. [ABSTRACT FROM AUTHOR]

Deficiency of essential trace element, Se, has been implicated in adverse birth outcomes and in child linear growth because of its important role in redox biology and associated antioxidant effects. We used data from a randomised controlled trial conducted among a cohort of pregnant and lactating women in Dhaka, Bangladesh to examine associations between Se biomarkers in whole blood (WBSe), serum and selenoprotein P (SEPP1) in maternal delivery and venous cord (VC) blood. Associations between Se biomarkers, birth weight and infant growth outcomes (age-adjusted length, weight, head circumference and weight-for-length z-scores) at birth, 1 and 2 years of age were examined using regression analyses. WB and serum Se were negatively associated with birth weight (adjusted β , 95 % CI, WBSe delivery: −26·6 (–44·3, −8·9); WBSe VC: −19·6 (–33·0, −6·1)); however, delivery SEPP1 levels (adjusted β : −37·5 (–73·0, −2·0)) and VC blood (adjusted β : 82·3 (30·0, 134·7)) showed inconsistent and opposite associations with birth weight. Positive associations for SEPP1 VC suggest preferential transfer from mother to fetus. We found small associations between infant growth and WBSe VC (length-for-age z-score β , 95 % CI, at birth: −0·05 (–0·1, −0·01)); 12 months (β : −0·05 (–0·08, −0·007)). Weight-for-age z-score also showed weak negative associations with delivery WBSe (at birth: −0·07 (–0·1, −0·02); 12 -months: −0·05 (–0·1, −0·005)) and in WBSe VC (at birth: −0·05 (–0·08, −0·02); 12 months: −0·05 (–0·09, −0·004)). Given the fine balance between essential nutritional and toxic properties of Se, it is possible that WB and serum Se may negatively impact growth outcomes, both in utero and postpartum. [ABSTRACT FROM AUTHOR]

BackgroundExposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis.MethodsPregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p'-DDT and o,p'-DDT) or DDE (p,p'-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated.ResultsWe observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p'-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p'-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p'-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p'-DDE, respectively, compared to control.ConclusionsThese data demonstrate that perinatal exposure to DDTs or p,p'-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

BackgroundPer- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures.MethodsStudy participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes.ResultsT/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal-fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples.ConclusionsOur findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.

Ustekinumab (USK) was used in the treatment of two pregnant patients with Crohn's disease. It was given in the third trimester and restarted postnatally for both women. One woman remained on USK and in remission throughout pregnancy. The second woman, took a treatment break, flared, and then had remission induced with reintroduction of USK. Both women delivered healthy term infants. The interval from last dose to birth was 11 and 8 weeks respectively. Interestingly, USK levels in cord blood was observed in higher concentrations than in the maternal serum taken in third trimester. While no adverse effect in infants has been observed, clinicians should remain aware of fetal transfer when using USK in pregnancy. An evaluation of risk and benefit may favour continuing USK in pregnancy in patients with refractory disease. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a complex disorder that is defined by glucose intolerance with onset during pregnancy. The incidence of GDM is increasing worldwide. Pregnancies complicated with GDM have higher rates of maternal and fetal morbidity with short- and long-term consequences, including increased rates of cardiovascular disease and type II diabetes for both the mother and offspring. The pathophysiology of GDM still remains unclear and there has been interest in the role of small extracellular vesicles (sEVs) in the maternal metabolic adaptations that occur in pregnancy and GDM. Small EVs are nanosized particles that contain bioactive content, including miRNAs and proteins, which are released by cells to provide cell-to-cell communication. Pregnancy induces an increase in total and placental-secreted sEVs across gestation, with a further increase in sEV number and changes in the protein and miRNA composition of these sEVs in GDM. Research has suggested that these sEVs have an impact on maternal adaptations during pregnancy, including targeting the pancreas, skeletal muscle and adipose tissue. Consequently, this review will focus on the differences in total and placental sEVs in GDM compared to normal pregnancy, the role of sEVs in the pathophysiology of GDM and their clinical application as potential GDM biomarkers.

Abstract Background Massive fetomaternal hemorrhage (FMH) is a rare event during pregnancy that may cause severe fetal anemia or death. Case presentation This paper reports two cases of fetomaternal hemorrhage with unexplained reasons. Both cases required emergency caesarean sections for non-reassuring fetal status and were treated with neonatal blood transfusion. Fetomaternal hemorrhage was confirmed via maternal Kleihauer-Betke test. Conclusion We found parenchymal pallor, increased nucleated red blood cells (nRBCs), and syncytial knots (SKs) in the placentas, which are compatible with fetal anemia. Immunohistochemical staining indicated VEGF, CD34, and CD31 expression in the endothelial cells of the capillaries, characteristic of massive FMH placenta. This article also reviews the particular histopathological changes in FHM placenta according to the placental lesion classification system.

Compelling epidemiological and animal experimental data demonstrate that cardiometabolic and neuropsychiatric diseases originate in a suboptimal intrauterine environment. Here, we review evidence suggesting that altered placental function may, at least in part, mediate the link between the maternal environment and changes in fetal growth and development. Emerging evidence indicates that the placenta controls the development and function of several fetal tissues through nutrient sensing, modulation of trophoblast nutrient transporters and by altering the number and cargo of released extracellular vesicles. In this Review, we discuss the development and functions of the maternal-placental-fetal interface (in humans and mice) and how cross-talk between these compartments may be a mechanism for in utero programming, focusing on mechanistic target of rapamycin (mTOR), adiponectin and O-GlcNac transferase (OGT) signaling. We also discuss how maternal diet and stress influences fetal development and metabolism and how fetal growth restriction can result in susceptibility to developing chronic disease later in life. Finally, we speculate how interventions targeting placental function may offer unprecedented opportunities to prevent cardiometabolic disease in future generations. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the presence of Pregnancy-associated glycoprotein −1 (PAG-1) mRNA expression in the maternal circulation of pregnant buffaloes during the early stage of pregnancy. Contemporaneously, the mRNA expression levels of Interferon-tau (IFNt) and some Interferon stimulated genes (ISGs) (interferon stimulated gene 15 ubiquitin-like modifier interferon , ISG15; Mixoviruses resistance 1 and 2 , MX1 and MX2; 2′,5′-oligoadenylate synthase 1 ,OAS1) were evaluated in order to expand our knowledge of the molecular processes involved in the early stages of pregnancy and to identify potential biomarkers of maternal-fetal cellular interaction in buffalo. The study was conducted on 38 synchronized and artificially inseminated buffalo cows (d 0), divided ex post into 3 groups: Pregnant (n = 17), Non-pregnant (n = 15) and Embryo mortality (n = 6). Blood samples were collected on d 14, 19, 28 and 40 after artificial insemination (AI) for peripheral blood mononuclear cells (PBMCs) isolation. Expression levels of mRNA of PAG-1, IFNt, ISG15. MX1, MX2 and OAS1 were measured using RT-qPCR. No significant changes were observed in IFNt and PAG gene expressions between groups, while significant differences (p < 0.001) were found for ISG15, MX1, MX2, and OAS1. Pairwise comparisons revealed that the differences between groups occurred on days 19 and 28 post-AI. ISG15 proved to have the best diagnostic performance for distinguishing between pregnant animals and animals that experienced embryo mortality with the ROC analysis. According to the results of the univariate analyses, day 19 was identified as the most indicative to discriminate between groups while the most reliable genes for this differentiation were ISG15, MX1 and MX2. MX2 proved to be the best gene for discriminating pregnant buffaloes using the discriminant analysis, while MX1 was the gene that best predicted embryo mortality. Our results showed that among PAG-1, IFNt and ISGs expression as diagnostic and prognostic markers of maternal-fetal cellular interaction in buffalo cows, ISGs proved to be the best peripheral biomarkers for predicting pregnancy and embryonic mortality during the peri-implantation period. These insights into the mechanisms behind maternal-fetal interaction and the development of a method for the early detection of embryo distress may enable us to implement effective strategies to support embryo survival. • Diagnostic and prognostic markers of pregnancy in buffalo. • Identification of genes that better discriminate pregnant buffaloes and predict embryo mortality. • Evaluation of mRNA expression of genes involved in the establishing and maintaining of pregnany. PBMC represent a less invasive and alternative to caruncular tissue for the evaluation of gene expression. [ABSTRACT FROM AUTHOR]

Background: Patients with omphalocele, a midline abdominal wall defect at the umbilical cord base, have a low survival rate. However, the long-term outcomes of fetuses with prenatally diagnosed omphalocele have scarcely been studied. Therefore, we investigated the ultrasonographic features, genetic characteristics, and maternal and fetal outcomes of fetuses with omphalocele and provided a reference for the perinatal management of such cases. Methods: A total of 120 pregnant females with fetal omphalocele were diagnosed using prenatal ultrasonography at the Fujian Provincial Maternity and Child Health Hospital from January 2015 to March 2022. Amniotic fluid or cord blood samples were drawn at different gestational weeks for routine karyotype analysis, chromosomal microarray analysis (CMA) detection, and whole exome sequencing (WES). The maternal and fetal outcomes were followed up. Results: Among the 120 fetuses, 27 were diagnosed with isolated omphalocele and 93 with nonisolated omphalocele using prenatal ultrasonography. Cardiac anomalies were the most observed cause in 17 fetuses. Routine karyotyping and CMA were performed on 35 patients, and chromosomal abnormalities were observed in five patients, trisomy 18 in three, trisomy 13 in one, and chromosome 8–11 translocation in one patient; all were non-isolated omphalocele cases. Six nonisolated cases had normal CMA results and conventional karyotype tests, and further WES examination revealed one pathogenic variant and two suspected pathogenic variants. Of the 120 fetuses, 112 were successfully followed up. Eighty of the 112 patients requested pregnancy termination. Seven of the cases died in utero. A 72% 1-year survival rate was observed from the successful 25 live births. Conclusion: The prognosis of fetuses with nonisolated omphalocele varies greatly, and individualized analysis should be performed to determine fetal retention carefully. Routine karyotyping with CMA testing should be provided for fetuses with omphalocele. WES is an option if karyotype and CMA tests are normal. If the fetal karyotype is normal and no associated abnormalities are observed, fetuses with omphalocele could have a high survival rate, and most will have a good prognosis. [ABSTRACT FROM AUTHOR]