Fetal hypoxic

Gestational exposures have enduring impacts on brain and neuroimmune development and function. Perturbations of pregnancy leading to placental structure/function deficits, cell stress, immune activation, and endocrine changes (metabolic, growth factors, etc.) all increase neuropsychiatric risk in offspring. The existing literature links obstetric diseases with placental involvement to offspring neuroimmune outcomes and neurodevelopmental risk. Psychoneuroimmune outcomes in offspring brain include changes to microglia, cytokine/chemokine production, cell stress, and long-term immunoreactivity...

Gestational hypoxia adversely affects uterine artery function, increasing complications. However, an effective therapy remains unidentified. Here, we show in rodent uterine arteries that hypoxic pregnancy promotes hypertrophic remodelling, increases constrictor reactivity via protein kinase C signalling, and triggers compensatory dilatation via nitric oxide-dependent mechanisms and stimulation of large conductance Ca2+ -activated K+ -channels. Maternal in vivo oral treatment with the mitochondria-targeted antioxidant MitoQ in hypoxic pregnancy normalises uterine artery reactivity and prevents vascular remodelling...

OBJECTIVE:  Ocular hemorrhages (OHs) may cause visual disturbances and incidence vary from 18 to 39% in newborns. Precipitated/instrumental delivery and perinatal asphyxia were predefined risk factors. Acidosis can interfere with coagulation and disrupt the pressure of ocular capillaries and put infants with moderate acidosis with or without hypoxic-ischemic encephalopathy at risk for OH. We aimed to evaluate the OH in neonates with fetal acidosis. STUDY DESIGN: Neonates >34 weeks are included if pH < 7...

Successful implantation requires coordinated migration and invasion of trophoblast cells into a receptive endometrium. Reduced forkhead box M1 (FOXM1) expression limits trophoblast migration and angiogenesis in choriocarcinoma cell lines, and in a rat model, placental FOXM1 protein expression was significantly upregulated in the early stages of pregnancy compared to term pregnancy. However, the precise role of FOXM1 in implantation events remains unknown. By analyzing mice blastocysts at embryonic day (E3.5), we have demonstrated that FOXM1 is expressed as early as the blastocyst stage, and it is expressed in the trophectoderm of the blastocyst...

Long-term outcomes of persistent pulmonary hypertension of newborn (PPHN) depend on disease severity, duration of ventilation, and associated anomalies. Congenital diaphragmatic hernia survivors may have respiratory morbidities and developmental delay. The presence of PPHN is associated with increased mortality in hypoxic-ischemic encephalopathy, though the effects on neurodevelopment are less clear. Preterm infants can develop pulmonary hypertension (PH) early in the postnatal course or later in the setting of bronchopulmonary dysplasia (BPD)...

Persistent Pulmonary Hypertension of the Newborn (PPHN) is more common in Low and middle income countries (LMICs) due to high incidence of sepsis, perinatal asphyxia and meconium aspiration syndrome. Presence of hypoxic respiratory faillure and greater than 5% difference in preductal and post ductal saturation increases clinical sucipision for PPHN. The availability of Inhaled nitric oxide and extracorporaeal membrane oxygenation is limited but pulmonary vasodilators such as sildenafil are readily available in most LMICs...

Diverse genetic developmental lung diseases can present in the neonatal period with hypoxemic respiratory failure, often associated with with pulmonary hypertension. Intractable hypoxemia and lack of sustained response to medical management should increase the suspicion of a developmental lung disorder. Genetic diagnosis and lung biopsy are helpful in establishing the diagnosis. Early diagnosis can result in optimizing management and redirecting care if needed. This article reviews normal lung development, various developmental lung disorders that can result from genetic abnormalities at each stage of lung development, their clinical presentation, management, prognosis, and differential diagnoses...

Preterm infants with bronchopulmonary dysplasia (BPD) are prone to develop pulmonary hypertension (PH). Strong laboratory and clinical data suggest that antenatal factors, such as preeclampsia, chorioamnionitis, oligohydramnios, and placental dysfunction leading to fetal growth restriction, increase susceptibility for BPD-PH after premature birth. Echocardiogram metrics and serial assessments of NT-proBNP provide useful tools to diagnose and monitor clinical course during the management of BPD-PH, as well as monitoring for such complicating conditions as left ventricular diastolic dysfunction, shunt lesions, and pulmonary vein stenosis...

Neonates with a perinatal hypoxic insult and subsequent neonatal encephalopathy are at risk of acute pulmonary hypertension (aPH) in the transitional period. The phenotypic contributors to aPH following perinatal asphyxia include a combination of hypoxic vasoconstriction of the pulmonary vascular bed, right heart dysfunction, and left heart dysfunction. Therapeutic hypothermia is the standard of care for neonates with moderate-to-severe hypoxic ischemic encephalopathy. This review summarizes the underlying risk factors, causes of aPH in neonates with perinatal asphyxia, discusses the unique phenotypical contributors to disease, and explores the impact of the initial insult and subsequent therapeutic hypothermia on aPH...

BACKGROUND: The evidence-based management of human labor includes the antepartum identification of patients at risk for intrapartum hypoxia. However, available evidence has shown that most of the hypoxic-related complications occur among pregnancies classified at low-risk for intrapartum hypoxia, thus suggesting that the current strategy to identify the pregnancies at risk for intrapartum fetal hypoxia has limited accuracy. OBJECTIVE: To evaluate the role of the combined assessment of the cerebroplacental ratio (CPR) and uterine arteries (UtA) Doppler in the prediction of obstetric intervention (OI) for suspected intrapartum fetal compromise (IFC) within a cohort of low-risk singleton term pregnancies in early labor...

BACKGROUND: Abnormal placental development is a significant factor contributing to perinatal morbidity and mortality, affecting approximately 5-7% of pregnant women. Trophoblast syncytialization plays a pivotal role in the establishment and maturation of the placenta, and its dysregulation is closely associated with several pregnancy-related disorders, including preeclampsia and intrauterine growth restriction. However, the underlying mechanisms and genetic determinants of syncytialization are largely unknown...

OBJECTIVE: To compare the effect of peripheral oxygen saturation (SpO2 ) target range (TR) (either 91%-95% and 92%-96%) on the frequency and duration of hypoxic and hyperoxic episodes while on automated oxygen control using the OxyGenie controller. DESIGN: Randomised cross-over study. SETTING: Tertiary-level neonatal unit in the Netherlands. PATIENTS: Infants (n=27) with a median (IQR) gestational age of 27+0 (25+5-27+3) weeks and postnatal age of 16 (10-22) days, receiving invasive or non-invasive respiratory support...

Background: Fetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown. Methods: Pregnant mice were subjected to acute or chronic hypoxia (12.5% O2 ) resulting in reduced fetal weight. Placenta oxygen transport was assessed by blood oxygenation level dependent (BOLD) contrast magnetic resonance imaging (MRI)...

The Developmental Origins of Health and Disease hypothesis sustains that exposure to different stressors during prenatal development prepares the offspring for the challenges to be encountered after birth. We studied the gestational period as a particularly vulnerable window where different stressors can have strong implications for fetal programming of the offspring's life-long metabolic status via alterations of specific placentally expressed nutrient transporters. To study this mechanism, we used a murine prenatal stress model, human preeclampsia, early miscarriage, and healthy placental tissue samples, in addition to in vitro models of placental cells...

Preeclampsia (PE) poses a considerable risk to the long-term cardiovascular health of both mothers and their offspring due to a hypoxic environment in the placenta leading to reduced fetal oxygen supply. Cholesterol is vital for fetal development by influencing placental function. Recent findings suggest an association between hypoxia, disturbed cholesterol homeostasis, and PE. This study investigates the influence of hypoxia on placental cholesterol homeostasis. Using primary human trophoblast cells and placentae from women with PE, various aspects of cholesterol homeostasis were examined under hypoxic and hypoxia/reoxygenation (H/R) conditions...

OBJECTIVE: An emergency cesarean section (CS), which is extremely life-threatening to the mother or fetus, seems to be performed within an adequate time horizon to avoid negative fetal-maternal denouement. An effective and vigilant technique for anesthesia remains vital for emergency cesarean delivery. Therefore, this study aimed to validate the impact of various anesthesia tactics on maternal and neonatal outcomes. METHOD: This was a retrospective cohort study of parturient patients who were selected for emergency CS with the assistance of general or neuraxial anesthesia between January 2015 and July 2021 at our institution...

BACKGROUND: Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid-late pregnancy, it is urgent to further explore whether it affects the long-term synthesis of NO in offspring vascular endothelial cells...

In high-resource countries, adverse perinatal outcomes are currently rare in term, non-malformed fetuses, undergoing labor, but they remain a leading cause of medico-legal dispute. Precise terminology is important to describe situations related to inadequate fetal oxygenation in labor, to ensure appropriate communication between healthcare professionals and adequate transmission of information to parents. This position statement provides consensus definitions from European perinatologists and midwives regarding the most appropriate terminology to describe situations related to inadequate fetal oxygenation in labor: suspected fetal hypoxia, severe newborn acidemia, newborn metabolic acidosis, and hypoxic-ischemic encephalopathy...

OBJECTIVE: To determine the difference in time to attainment of full enteral feeds between fetal growth restricted (FGR) preterm neonates with and without absent/reversed end-diastolic flow (AREDF). Secondary objectives were to compare the short-term outcomes including the incidence of necrotizing enterocolitis (NEC) and feed intolerance between the two groups and to determine the factors affecting the time to attainment of full enteral feeds (FEF) among preterm FGR neonates. METHODS: A prospective cohort study was conducted among consecutive preterm FGR neonates delivered at 28-36 weeks gestation admitted in level III NICU...

INTRODUCTION: Previous studies have shown that fetal hypoxia predisposes individuals to develop addictive disorders in adulthood. However, the specific impact of maternal stress, mediated through glucocorticoids and often coexisting with fetal hypoxia, is not yet fully comprehended. METHODS: To delineate the potential effects of these pathological factors, we designed models of prenatal severe hypoxia (PSH) in conjunction with maternal stress and prenatal intrauterine ischemia (PII)...