Fetal Stress Research Articles

Amniotic fluid biomarkers of fetal stress response to cardiac dysfunction in twin-twin transfusion syndrome

Recipient twin (RT) cardiovascular changes in twin-twin transfusion syndrome (TTTS) are associated with increased mortality. This relationship is likely related to a cascade of pathophysiologic changes in the RT progressing to multisystem organ failure. We sought to evaluate biomarkers of inflammation, stress, and tissue injury within amniotic fluid (AF) of RTs undergoing selective fetoscopic laser photocoagulation (SFLP) for TTTS and examine their relationship with fetal echocardiographic findings. AF samples from RTs were obtained from 39 monochorionic-diamniotic pregnancies complicated by TTTS. Those without preoperative fetal echocardiograms or evidence of selective intrauterine growth restriction were excluded from analysis with 24 remaining samples. 15 commonly utilized clinical biomarkers for inflammation, stress, and tissue injury were assessed using a flow-cytometry based multiplex immunoassay. Fetal echocardiograms were performed prior to SFLP with myocardial performance index (MPI) utilized as a measure of cardiac dysfunction. Pearson’s correlation was used for data analysis. RT Left ventricular MPI (LV-MPI) ranged from 0.28-0.74, with 11/24 RTs demonstrating abnormal MPI for GA (Z-score > 2). RT AF cortisol (r = 0.4527, p = 0.020), IL-6 (r = 0.44, p = 0.025), CRP (r = 0.431, p = 0.028), and myoglobin (r = 0.401, p = 0.042) levels correlated with recipient left ventricular MPI (LV-MPI). AF cortisol strongly correlated with AF myoglobin (r = 0.576, p < 0.001). RT with abnormal LV-MPI exhibited significantly higher AF cortisol levels compared to those with normal LV-MPI (p = 0.029). RT amniotic fluid demonstrates markers of inflammation, stress and cardiac injury in recipient twins with cardiac dysfunction. These markers may be indicators of disease progression in TTTS secondary to cardiac dysfunction. The presence of these markers implicate stress and the immune response in the pathophysiologic response to cardiac dysfunction in TTTS.

Perinatal Oxidative Stress and Kidney Health: Bridging the Gap between Animal Models and Clinical Reality.

Oxidative stress arises when the generation of reactive oxygen species or reactive nitrogen species overwhelms antioxidant systems. Developing kidneys are vulnerable to oxidative stress, resulting in adult kidney disease. Oxidative stress in fetuses and neonates can be evaluated by assessing various biomarkers. Using animal models, our knowledge of oxidative-stress-related renal programming, the molecular mechanisms underlying renal programming, and preventive interventions to avert kidney disease has grown enormously. This comprehensive review provides an overview of the impact of perinatal oxidative stress on renal programming, the implications of antioxidant strategies on the prevention of kidney disease, and the gap between animal models and clinical reality.

Predelivery placenta-associated biomarkers and computerized intrapartum fetal heart rate patterns

BackgroundIncreasing syncytiotrophoblast stress in term and postdate placentas is reflected by increasing antiangiogenic dysregulation in the maternal circulation, with low “proangiogenic” placental growth factor concentrations and increased “antiangiogenic” soluble fms-like tyrosine kinase-1 concentrations. Imbalances in these placenta-associated proteins are associated with intrapartum fetal compromise and adverse pregnancy and delivery outcome. Cardiotocography is widely used to assess fetal well-being during labor, but it is insufficient on its own for predicting adverse neonatal outcome. Development of improved surveillance tools to detect intrapartum fetal stress are needed to prevent neonatal adverse outcome. ObjectiveThis study aimed to assess whether predelivery circulating maternal angiogenic protein concentrations are associated with intrapartum computerized fetal heart rate patterns, as calculated by the Oxford System for computerized intrapartum monitoring (OxSys) 1.7 prototype. We hypothesized that in pregnancies with low “proangiogenic” placental growth factor levels, increased “antiangiogenic” soluble fms-like tyrosine kinase-1 levels, and increased soluble fms-like tyrosine kinase-1–placental growth factor ratio, the OxSys 1.7 prototype will generate more automated alerts, indicating fetal compromise. Our secondary objective was to investigate the relationship between maternal circulating placenta-associated biomarkers and rates of automated alerts in pregnancies with and without adverse neonatal outcome. Study DesignThis was an observational prospective cohort study conducted at a single tertiary center from September 2016 to March 2020. Of 1107 singleton pregnancies (gestational week ≥37+0), 956 had available prelabor and predelivery placental growth factor and soluble fms-like tyrosine kinase-1 concentrations and intrapartum cardiotocography recordings. All neonatal and delivery outcomes were externally reviewed and categorized into 2 groups—the “complicated” group (n=32) and the “uncomplicated” group (n=924)—according to predefined adverse neonatal outcome. Eight different cardiotocography features were calculated by OxSys 1.7: baseline at start of cardiotocography, baseline at end of cardiotocography, short-term variation at start, short-term variation at end, nonreactive initial trace, and throughout the entire cardiotocography, maximum decelerative capacity, total number of prolonged decelerations, and OxSys 1.7 alert. OxSys 1.7 triggered an alert if the initial trace was nonreactive or if decelerative capacity and/or the number of prolonged decelerations exceeded a predefined threshold. Included women and attending clinicians were blinded to both biomarker and OxSys 1.7 results. ResultsMean maternal placental growth factor concentration was lower in the group with OxSys 1.7 alert compared with the group without the alert (151 vs 169 pg/mL; P=.04). There was a weak negative correlation between predelivery high soluble fms-like tyrosine kinase-1 and low short-term variation start (rs=−0.068; 95% confidence interval, −0.131 to −0.004; P=.036), predelivery high soluble fms-like tyrosine kinase-1 and low short-term variation end (rs=−0.068; 95% confidence interval, −0.131 to −0.005; P=.036), and high soluble fms-like tyrosine kinase-1–placental growth factor ratio and low short-term variation end (rs=−0.071; 95% confidence interval, −0.134 to −0.008; P=.027). The rate of decelerative capacity alerts increased more rapidly as placental growth factor decreased in the “complicated” compared with the “uncomplicated” group (0% to 17% vs 4% to 8%). ConclusionMore automated alerts indicative of fetal distress were generated by OxSys 1.7 in pregnancies with low maternal predelivery placental growth factor level, in line with likely increasing placental stress toward the end of the pregnancy. An antiangiogenic predelivery profile (lower placental growth factor) increased the rates of alerts more rapidly in pregnancies with adverse neonatal outcome compared with those without. We suggest that future studies developing and testing prediction tools for intrapartum fetal compromise include predelivery maternal placental growth factor measurements.

Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex

The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio-temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples (n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ.

Cyclophosphamide Induces Lipid and Metabolite Perturbation in Amniotic Fluid during Rat Embryonic Development.

Cyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of CP on the lipid and metabolic profiles of amniotic fluid was evaluated using a UHPLC-Q-Exactive Orbitrap MS-based method. Metabolome analysis was performed using the MS-DIAL software with LipidBlast and NIST. Initially, we identified 636 and 154 lipid compounds in the positive and negative ion modes and 118 metabolites for differential analysis. Mainly 4 types of oxidized lipids in the amniotic fluid were found to accumulate most significantly after CP treatment, including very-long-chain unsaturated fatty acids (VLCUFAs), polyunsaturated fatty acid (PUFA)-containing triglycerides (TGs), oxidized phosphatidylcholine (PC), and sphingomyelin (SM). Tryptophan and some long-chain saturated fatty acids were lowered pronouncedly after CP treatment. These findings suggest that CP may exert teratogenic toxicity on pregnant rats through maternal and fetal oxidative stress. The UHPLC-Q-Exactive Orbitrap MS-based lipidomics approach is worthy of wider application for evaluating the potential toxicity of other agents (toxicants) during embryonic development.

Influence of Fetal Attachment and Pregnancy Stress on Health Promotion Behavior in Primigravida

Purpose: This study aimed to identify the effect of fetal attachment and pregnancy on health promoting behavior in primigravida.Methods: The subjects were 149 primigravidas who enrolled in nationwide online cafe for pregnant and childcare women. The data were collected from February, 2008 to February, 28 in 2022. The collected data were analyzed by IBM SPSS Statistics ver. 24.0.Results: The primigravidas’ health promoting behavior was significantly affected by the fetal attachment (β=0.37, p&lt;0.001), spouse stress (β=0.32, p&lt;0.001), subjective health condition (β=0.28, p&lt;0.001), academic background (β=0.25, p&lt;0.001), primigravidas themselves stress (β=-0.24, p=0.001), and monthly income (β=0.18, p=0.005). These variables explained 41.5% of the variance in health promoting behavior.Conclusion: It is necessary to seek out how to improve the fetal attachment through interactions with fetus, for enhancing primigravidas’ health promoting behavior and to develop a program by educational levels, for forming positive mind about health. Moreover, various efforts and strategies are required to reduce the pregnancy stress and enhance the health of both primigravidas and fetus, by early detecting and alleviating the pregnancy stress.

Resveratrol Supplementation in Obese Pregnant Rats Improves Maternal Metabolism and Prevents Increased Placental Oxidative Stress.

Maternal obesity (MO) causes maternal and fetal oxidative stress (OS) and metabolic dysfunction. We investigated whether supplementing obese mothers with resveratrol improves maternal metabolic alterations and reduces OS in the placenta and maternal and fetal liver. From weaning through pregnancy female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating until 19 days’ gestation (dG), half the rats received 20 mg resveratrol/kg/d orally (Cres and MOres). At 19dG, maternal body weight, retroperitoneal fat adipocyte size, metabolic parameters, and OS biomarkers in the placenta and liver were determined. MO mothers showed higher body weight, triglycerides and leptin serum concentrations, insulin resistance (IR), decreased small and increased large adipocytes, liver fat accumulation, and hepatic upregulation of genes related to IR and inflammatory processes. Placenta, maternal and fetal liver OS biomarkers were augmented in MO. MOres mothers showed more small and fewer large adipocytes, lower triglycerides serum concentrations, IR and liver fat accumulation, downregulation of genes related to IR and inflammatory processes, and lowered OS in mothers, placentas, and female fetal liver. Maternal resveratrol supplementation in obese rats improves maternal metabolism and reduces placental and liver OS of mothers and fetuses in a sex-dependent manner.

Association of Umbilical Cord Serum Oxidative Stress Markers, ADMA and Adiponectin with Adverse Fetal Outcomes in Hypertensive Disorders of Pregnancy

Background: Limited studies are available on fetal oxidative stress and endothelial dysfunction and their association with adverse fetal outcomes in hypertensive disorders of pregnancy (HDP). Method: Umbilical cord blood samples were collected at delivery from 134 pregnant women with HDP and 59 controls. Markers of oxidative stress, endothelial dysfunction and inflammation and adipokines were analyzed. Results were correlated with adverse fetal outcomes. Results: Malondialdehyde, total antioxidant status(TAS), ADMA and hsCRP levels were increased in late and early onset preeclampsia. Adiponectin levels were decreased in early onset preeclampsia. High ADMA levels were positively associated with preterm births and fetal mortality and high TAS, protein carbonyl content(PC), ADMA and low adiponectin levels were positively associated with low birth weight babies. Conclusion: Fetal systemic oxidative stress, endothelial dysfunction and inflammation were altered in early and late onset preeclampsia. High TAS, PC and ADMA levels and low adiponectin levels were positively associated with adverse fetal outcomes in HDP.

Maternal–fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study

BackgroundMaternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant’s neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA.ResultsA total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a ‘Fetal Stress Index’ (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn’s saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D.ConclusionsGenes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

Neonatal testicular torsion after severe perinatal asphyxia treated with therapeutic hypothermia

Neonatal testicular torsion (NTT) has been postulated to occur as a result of hyperactive cremasteric reflex, which can be caused by fetal stress; however, no study has reported severe perinatal asphyxia causing NTT. We report about a male neonate with severe perinatal asphyxia treated with therapeutic hypothermia who showed left testicular torsion on the 16th day of life. We could not determine when the torsion occurred; however, we hypothesized that it occurred during the perinatal period because both perinatal asphyxia and therapeutic hypothermia could be risk factors for testicular torsion. NTT has been considered to occur as a result of a hyperactive cremasteric reflex on the loose fixation of the tunica vaginalis to the scrotal wall, and both fetal stress and low temperature have been considered to cause cremasteric reflex. NTT lacks noticeable signs and symptoms; thus, it can be overlooked in severe cases, as in our patient. Therefore, physicians treating male neonates with severe perinatal asphyxia with or without therapeutic hypothermia should examine their scrotum considering NTT. • Both perinatal asphyxia and therapeutic hypothermia could be risk factors of NTT. • The scrotum of male neonates with severe perinatal asphyxia must be examined daily. • Physicians should consider the possible occurrence of NTT.

Heart rate markers for prediction of fetal acidosis in an experimental study on fetal sheep

To overcome the difficulties in interpreting fetal heart rate (FHR), several tools based on the autonomic nervous system and heart rate variability (HRV) have been developed. The objective of this study was to use FHR and HRV parameters for the prediction of fetal hypoxia. It was an experimental study in the instrumented fetal sheep. Repeated umbilical cord occlusions were performed to achieve severe acidosis. Hemodynamic parameters, ECG, and blood gases were analyzed. The variables used were heart rate baseline, HRV analysis (RMSSD, SDNN, LF, HF, HFnu, Fetal Stress Index (FSI), …), and morphological analysis of decelerations. The gold standard used to classify hypoxia was the fetal arterial pH (pH < 7.10). Different multivariable statistical methods (logistic regression and decision trees) were applied for the detection of acidosis. 21 lambs were instrumented. A total of 130 pairs of FHR/fetal pH analysis were obtained of which 29 in the acidosis group and 101 in the non-acidosis group. After logistic regression model with bootstrap resampling and stepwise backward selection, only one variable was selected, FSI. The AUC of FSI alone in this model was 0.81 with a sensitivity of 0.66, specificity of 0.88, PPV of 0.61, and NPV of 0.90 considering a threshold of 68. Decision trees with CHAID and CART algorithms showed a sensitivity of 0.48 and 0.59, respectively, and a specificity of 0.94 for both. All employed methods identified HRV variables as the most predictive of acidosis. The primary variables selected automatically were those from the HRV. Supporting the use of FHRV measures for the screening of fetal acidosis during labour is interesting.

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner

The adverse effects of maternal prenatal stress (PS) on child’s neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

Evaluating the Impact of Perinatal Depression on Fetal and Childhood Development

Perinatal maternal depression leads to a variety of biochemical and behavioral changes in utero. These alterations are linked to impaired fetal development and may also be detrimental to future neonatal, pediatric, and adolescent health. There is a marked rise in the incidence of atopic triad conditions, such as dermatitis and asthmatic wheezing, in children of pregnant mothers with antepartum depression, possibly due to an aberrant TH2 immunologic response and increased fetal oxidative stress. Maternal antepartum depression may also contribute to small-for-gestational age birth status, anomalous fetal neurotransmitter levels, and depression throughout infancy and adolescence. Cortisol has been implicated as a common causative factor responsible for many of these negative offspring outcomes. Minimal research on untreated major depression in pregnancy has been conducted. However, current studies emphasize the importance of holistically evaluating the risks associated with untreated major depression in pregnancy in order to minimize harmful effects on children.

Selenium Supplementation in Pregnancy-Maternal and Newborn Outcomes.

Background Several studies have suggested that increased oxidative stress during pregnancy may be associated with adverse maternal and foetal outcomes. As selenium is an essential mineral with an antioxidant role, our aim was to perform a systematic review of the existing literature reporting the effects of selenium supplementation during pregnancy on maternal and neonatal outcomes. Materials and Methods Six electronic databases (Medline, Embase, Cochrane Library, Web of Science, Scopus, and PubMed) were searched for studies reporting the effects of selenium supplementation during pregnancy and the postpartum period on maternal and neonatal outcomes. Only randomised controlled trials on human subjects reported in English and published up to October 2021 were included. Quality assessments were conducted using the modified Downs and Black quality assessment tool. Data were extracted using a narrative synthesis. Results Twenty-two articles were included in our systematic review (seventeen reported on maternal outcomes, two on newborn outcomes, and three on both). Maternal studies reported the effects of selenium supplementation in the prevention of thyroid dysfunction, gestational diabetes, pregnancy-induced hypertension/preeclampsia, oxidative stress, postpartum depression, premature rupture of membranes, intrauterine growth retardation, breastmilk composition, and HIV-positive women. Newborn studies reported the effects of maternal selenium supplementation on foetal oxidation stress, foetal lipid profile, neonatal hyperbilirubinemia, and newborn outcomes in HIV-positive mothers. The majority of studies were inappropriately designed to establish clinical or scientific utility. Of interest, four studies reported that selenium supplementation reduced the incidence of thyroid dysfunction and permanent hypothyroidism during the postpartum period by reducing thyroid peroxidase and thyroglobulin antibody titres. Conclusion The evidence supporting selenium supplementation during pregnancy is poor and there is a need for appropriately designed randomised controlled trials before routine use can be recommended.

Associations between fetal heart rate variability and umbilical cord occlusions-induced neural injury: An experimental study in a fetal sheep model.

This study evaluated the association between fetal heart rate variability (HRV) and the occurrence of hypoxic-ischemic encephalopathy in a fetal sheep model. The experimental protocol created a hypoxic condition with repeated cord occlusions in three phases (A, B, C) to achieve acidosis to pH <7.00. Hemodynamic, gasometric and HRV parameters were analyzed during the protocol, and the fetal brain, brainstem and spinal cord were assessed histopathologically 48h later. Associations between the various parameters and neural injury were compared between phases A, B and C using Spearman's rho test. Acute anoxic-ischemic brain lesions in all regions was present in 7/9 fetuses, and specific neural injury was observed in 3/9 fetuses. The number of brainstem lesions correlated significantly and inversely with the HRV fetal stress index (r=-0.784; p=0.021) in phase C and with HRV long-term variability (r=-0.677; p=0.045) and short-term variability (r=-0.837; p=0.005) in phase B. The number of neurological lesions did not correlate significantly with other markers of HRV. Neural injury caused by severe hypoxia was associated with HRV changes; in particular, brainstem damage was associated with changes in fetal-specific HRV markers.

Prediction of Neonatal Acidosis Based on the Type of Fetal Hypoxia Observed on the Cardiotocograph (CTG)

Cardiotocograph (CTG) was introduced into clinical practice to promptly recognize the features of intrapartum fetal hypoxic stress, so that timely action could be taken to avoid hypoxic-ischaemic encephalopathy (HIE) and perinatal deaths. However, the current systematic evidence suggests that the introduction of CTG into clinical practice over 50 years has not resulted in improvement in the rates of cerebral palsy or perinatal deaths. This is because most fetuses are able to withstand intrapartum hypoxic stresses without sustaining damage, and if the features of fetal compensatory responses are erroneously considered as “pathological”, “Abnormal” or “Category III” CTG tracing, it would lead to an exponential increase in unnecessary operative interventions without any improvement in perinatal outcomes. Neonatal acidosis at birth, determined by the estimation of pH in the umbilical artery has been considered as a surrogate marker of poor perinatal outcome. This is because significant intrapartum fetal hypoxic stress which leads to fetal decompensation, would lead to the onset of anaerobic metabolism and production of lactic acid in fetal tissues and organs. Entry of lactic acid into the fetal systemic circulation may cause damage to fetal central organs resulting in organ damage and death, and this lactate may lower the pH in the umbilical artery. Understanding the different types of fetal hypoxia on the CTG trace may help practicing clinicians to predict the rate of fall in fetal pH, and therefore, predict the umbilical cord pH at birth. It is important to appreciate that non-hypoxic pathways of fetal compromise such as chorioamnionitis may not be associated with low umbilical arterial pH at birth. Fetal pathophysiological approach to CTG interpretation based on deeper understanding of types of intrapartum hypoxia and features of non-hypoxic pathways of injury may help avoid the onset of neonatal metabolic acidosis and improve perinatal outcomes.

Fetal exposure to maternal stress and male reproductive function in a cohort of young adults

To study associations between maternal stress during pregnancy and reproductive function in young men. A cohort study nested in a population-based birth cohort. Not applicable. Young men (n = 1,052; response rate, 19%) participated in the Fetal Programming of Semen Quality cohort from 2017 to 2019. They were recruited from pregnancies in the Danish National Birth Cohort (1996-2001). The men completed an online questionnaire, clinical examination, and collection of blood and semen samples. Information on maternal life and emotional stresses was available from a telephone interview covering the interval from the beginning of pregnancy to approximately gestational week30. We applied negative binomial, linear, and logistic regression to examine associations between life and emotional stress scores (range, 0-18) and reproductive function. The primary outcomes were measures of semen quality, and the secondary outcomes included reproductive hormone levels and testicular volume. Overall, we observed no negative associations between maternal life or emotional stress and male reproductive function. Maternal emotional stress was associated with higher total sperm count (16% difference; 95% confidence interval [CI], 1-33), serum estradiol (11% difference; 95% CI, 2-21), and calculated free testosterone (β = 17.8; 95% CI, 1.26-34.3). The results were robust to inverse probability weighting introduced to account for selection. Although our findings may appear reassuring, further efforts to validate the measures of stress during pregnancy and improve our understanding of the full spectrum of fetal stress exposures and consequences for health later in life are needed.

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling.

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT1 receptors and NADPH oxidase, and lower expression of AT2, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.

Environmental Risk Factors and Cognitive Outcomes in Psychosis: Pre-, Perinatal, and Early Life Adversity.

Risk for psychosis begins to accumulate as early as the fetal period through exposure to obstetric complications like fetal hypoxia, maternal stress, and prenatal infection. Stressors in the postnatal period, such as childhood trauma, peer victimization, and neighborhood-level adversity, further increase susceptibility for psychosis. Cognitive difficulties are among the first symptoms to emerge in individuals who go on to develop a psychotic disorder. We review the relationship between pre-, perinatal, and early childhood adversities and cognitive outcomes in individuals with psychosis. Current evidence shows that the aforementioned environmental risk factors may be linked to lower overall intelligence and executive dysfunction, beginning in the premorbid period and persisting into adulthood in individuals with psychosis. It is likely that early life stress contributes to cognitive difficulties in psychosis through dysregulation of the body's response to stress, causing changes such as increased cortisol levels and chronic immune activation, which can negatively impact neurodevelopment. Intersectional aspects of identity (e.g., sex/gender, race/ethnicity), as well as gene-environment interactions, likely inform the developmental cascade to cognitive difficulties throughout the course of psychotic disorders and are reviewed below. Prospective studies of birth cohorts will serve to further clarify the relationship between early-life environmental risk factors and cognitive outcomes in the developmental course of psychotic disorders. Specific methodological recommendations are provided for future research.

Effect of low-dose ketamine on fetal oxidative stress: A randomized trial

Effect of low-dose ketamine on fetal oxidative stress: A randomized trial