Integrated 2D Doppler indices of uteroplacental and fetal blood flow in diagnosis of intrauterine hypoxia

Relevance . Intrauterine hypoxia associated with placental disorders is a significant factor of ante-, intra- and postnatal fetal and newborn death. Despite clinical examination of pregnant women using ultrasound and cardiotocography, cases of intrauterine hypoxia often remain undetected prenatally. Clinical manifestation of placental disorders and intrauterine hypoxia are associated with pathological changes of blood flow resistance in the uterine, placental and fetal vessels. A combined Doppler assessment of blood flow in the uterine, placental and fetal vessels could improve detection of intrauterine hypoxia. The aim of the study was to assess the prognostic significance of integrated 2D Doppler indices of uteroplacental and fetal blood flow for the detection of fetal hypoxia in the 3rd trimester and to predict unfavorable perinatal outcomes. Materials and Methods. The outcomes of pregnancy of 48 women with fetal hypoxia delivered at 29 - 40 gestational weeks (study group), and 21 women who gave birth to healthy full-term infants (control group) were retrospectively analyzed. On the eve of delivery all women had 2D Doppler assessment of the uterine arteries, umbilical arteries, and fetal middle cerebral artery with an assessment of the cerebro-placental ratio, umbilical-cerebral ratio and cerebro-placental-uterine ratio. Results and Discussion . Analysis of the obtained values of cerebro-placental-uterine ratio, cerebro-placental ratio and umbilical-cerebral ratio showed the benefit from use of integrated 2D Doppler indices in the diagnosis of fetal hypoxia at 29 - 40 gestations weeks and in predicting complications in newborns. The high sensitivity of the cerebro-placental-uterine ratio (90.5%) makes it possible to effectively use this index for the diagnosis of intrauterine hypoxia. Conclusion. Pathological cerebro-placental-uterine ratio 2.44 is a clinically significant 2D Doppler criterion that predicts a high risk of asphyxia, respiratory distress syndrome, hypotrophy, and perinatal hypoxic-ischemic encephalopathy. Lower values of the cerebro-placental ratio and umbilical-cerebral ratio sensitivity (77.1% and 81.3%, respectively) limit their use for the diagnosis of fetal hypoxia as compared with cerebro-placental-uterine ratio.

Prenatal Chronic Hypoxia in Rats Leads to Insulin Resistance and Hypertension in Adult Offspring

Background To investigate the effects of chronic intrauterine hypoxia on insulin resistance, hypertension, and the correlation between them in adult offspring rats. Methods A total of 25 pregnant Sprague Dawley rats were randomly assigned into 4 prenatal chronic hypoxia (H) groups (10% ± 1% oxygen) and a control group (21% oxygen). The H groups were divided into whole (1–21 day), early (1–7 day), mid (8–14 day), and late (15–21 day) gestational hypoxia groups (H1, H2, H3, and H4, respectively) with pregnant rats being housed in a hypoxia box for 3 hours per day. Five male and 5 female offspring in each group were studied at 1 day, 3 months, and 6 months old. Blood pressure, fasting blood glucose, fasting serum insulin, and insulin resistance index were determined. Results The mean blood pressure of offspring rats in H groups was higher at 3 months, and further increased at 6 months old compared to the control group (P < 0.05). The fasting blood glucose and homeostasis model insulin resistance index (HOMA-IR) of male and female offspring in the whole pregnancy (H1) and early pregnancy (H2) hypoxia groups were significantly higher than those in the control group at 6 months (P < 0.05). Fasting blood glucose and HOMA-IR were positively correlated with mean blood pressure (P < 0.05). The renal mass index in H2 group was lower at 3 months, and further decreased at 6 months compared to controls (P < 0.05). The mRNA and protein levels of insulin receptor, insulin receptor substrate (IRS-1 and IRS-2) in the kidneys in hypoxia groups were significantly decreased at 6 months in H1 and H2 hypoxia groups when compared with controls (P < 0.05). Conclusions Chronic intrauterine hypoxia causes insulin resistance and hypertension in adult offspring rats through poor intrauterine growth environment, and insulin resistance is positively associated with hypertension.

Prenatal Sonographic Diagnosis and Clinical Management of Fetal Small Bowel Volvulus

Background The purpose of this research is to explore prenatal ultrasound features and clinical managements of fetal small bowel volvulus. At present, researchers mainly focus on the prenatal ultrasound features of fetal small bowel volvulus, and rarely summarize them in combination with the principles of clinical treatment. Methods 11 cases of fetal small bowel volvulus identified by prenatal ultrasound or neonatal surgery in our institution between January 2019 and January 2021 were included. General characteristics of pregnant women, features of prenatal ultrasound, clinical managements and prognosis of neonates were collected. Finally, prenatal ultrasound features and obstetric managements of fetal volvulus was summarized. Results At the first diagnosis, the whirlpool sign and intestinal dilatation were visualized in 11 cases. 3 cases underwent emergency caesarean because of the disappearance of dilated bowel peristalsis, massive ascites and fetal intrauterine hypoxia. The rest 8 cases were followed up by ultrasound, pregnancy outcomes were four regressed intrauterine spontaneously and delivered at term, two underwent emergency caesarean, one premature and one induced labor. 6 cases underwent neonatal surgery immediately after birth and received favorable outcomes.Conclusions Intestinal distention and the whirlpool sign are important ultrasonic features in the diagnosis of fetal small bowel volvulus. The disappearance of intestinal peristalsis of the volvulus segment, massive ascites and intrauterine hypoxia are the main basis for emergency prenatal clinical intervention.

Effect of Hypoxia in Uterus on the Expression of MBP and NF-H+L in the White Matter of Old Rats

Hypoxia in utero is a common problem in embryonic development. Early fetal and neonatal periods are periods of rapid brain growth and development, and their development depends on adequate oxygenation. The growth and development of the fetus in the mother’s uterus require an adequate supply of oxygen. Conversely, lack of oxygen can adversely affect fetal development. The purpose of this article is to study the effect of intrauterine hypoxia on the expression of MBP and NF-H+L in the white matter of the offspring of aged rats and establish a hypoxia model of SD rats through controlled experiments. Detect fetal rat blood gas and blood ion indexes and use immunohistochemistry to detect the expression of MBP and NF-H+L in the paraventricular white matter of the offspring of the offspring of rats. Parallel image analysis, and then observe the myelin sheath and axis in the offspring of the offspring under electron microscope ultrastructure of protrusions and microvessels. The results show that the main effect of intrauterine hypoxia can reduce the expression of MBP (1666.93, 2179.85, 432.72) and NF-H+L (721.266,1785.832, 246.512) in the offspring of the white matter in the elderly rats (all P<0.05)), MBP was highly positively correlated with NF-H+L (R=0.64, P<0.01). Observation by electron microscopy showed that compared with the blank control group, the offspring of the intrauterine hypoxia group showed more myelination, axon damage, and microvascular disease in the brain of the elder generation of rats. Therefore, intrauterine hypoxia can affect the expression of MBP and NF-H+L in the white matter of offspring in the offspring of the offspring, resulting in demyelination and damaged axons.

Gestational Hypoxia and Blood-Brain Barrier Permeability: Early Origins of Cerebrovascular Dysfunction Induced by Epigenetic Mechanisms

Fetal chronic hypoxia leads to intrauterine growth restriction (IUGR), which is likely to reduce oxygen delivery to the brain and induce long-term neurological impairments. These indicate a modulatory role for oxygen in cerebrovascular development. During intrauterine hypoxia, the fetal circulation suffers marked adaptations in the fetal cardiac output to maintain oxygen and nutrient delivery to vital organs, known as the “brain-sparing phenotype.” This is a well-characterized response; however, little is known about the postnatal course and outcomes of this fetal cerebrovascular adaptation. In addition, several neurodevelopmental disorders have their origins during gestation. Still, few studies have focused on how intrauterine fetal hypoxia modulates the normal brain development of the blood-brain barrier (BBB) in the IUGR neonate. The BBB is a cellular structure formed by the neurovascular unit (NVU) and is organized by a monolayer of endothelial and mural cells. The BBB regulates the entry of plasma cells and molecules from the systemic circulation to the brain. A highly selective permeability system achieves this through integral membrane proteins in brain endothelial cells. BBB breakdown and dysfunction in cerebrovascular diseases lead to leakage of blood components into the brain parenchyma, contributing to neurological deficits. The fetal brain circulation is particularly susceptible in IUGR and is proposed to be one of the main pathological processes deriving BBB disruption. In the last decade, several epigenetic mechanisms activated by IU hypoxia have been proposed to regulate the postnatal BBB permeability. However, few mechanistic studies about this topic are available, and little evidence shows controversy. Therefore, in this mini-review, we analyze the BBB permeability-associated epigenetic mechanisms in the brain exposed to chronic intrauterine hypoxia.

Transient late gestation prenatal hypoxic insult results in functional deficits but not gross neuroanatomic deficits in mice

Intrauterine hypoxia is a common cause of brain injury in children with a wide spectrum of long-term neurodevelopmental sequela even after milder injury that does not result in significant neuroanatomical injury. Published prenatal hypoxia models generally require many days of modest hypoxia or are invasive, difficult to replicate surgery to ligate the uterine artery. Postnatal models of neonatal hypoxic brain injury are not able to study the effects of antenatal risk factors that contribute to outcomes of hypoxia to the developing brain. In addition, the most common postnatal hypoxia models induce significant cell death and large focal neuroanatomic injury through unilateral ischemia, which is not a common pattern of injury in children. Large animal models suggest that brief transient prenatal hypoxia alone is sufficient to lead to significant functional impairment to the developing brain. Thus, to further understand the mechanisms underlying hypoxic injury to the developing brain, it is vital to develop murine models that are simple to reproduce and phenocopy the lack of neuroanatomic injury but significant functional injury seen in children affected by mild intrauterine hypoxia. Here we characterized the effect of late gestation (embryonic day 17.5) transient prenatal hypoxia on long-term anatomical and neurodevelopmental outcomes. Prenatal hypoxia induced hypoxia inducible factor 1 alpha in the fetal brain. There was no difference in gestational age at birth, litter size at birth, survival, fetal brain cell death, or long-term changes in gray or white matter between offspring after normoxia and hypoxia. However, there were several long-term functional consequences from prenatal hypoxia, including sex-dichotomous changes. Both males and females have abnormalities in repetitive behaviors, hindlimb strength, and decreased seizure threshold. Males demonstrated increased anxiety. Females have deficit in social interaction. Hypoxia did not result in motor or visual learning deficits. This work demonstrates that transient late gestation prenatal hypoxia is a simple, clinically-relevant paradigm for studying putative environmental and genetic modulators of the long-term effects of transient hypoxia on the developing brain.

Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

Clinically, intrauterine hypoxia is the foremost cause of perinatal morbidity and developmental plasticity in the fetus and newborn infant. Under hypoxia, deviations occur in the lung cell epigenome. Epigenetic mechanisms (e.g., DNA methylation, histone modification, and miRNA expression) control phenotypic programming and are associated with physiological responses and the risk of developmental disorders, such as bronchopulmonary dysplasia. This developmental disorder is the most frequent chronic pulmonary complication in preterm labor. The pathogenesis of this disease involves many factors, including aberrant oxygen conditions and mechanical ventilation-mediated lung injury, infection/inflammation, and epigenetic/genetic risk factors. This review is focused on various aspects related to intrauterine hypoxia and epigenetic programming in lung development and disease, summarizes our current knowledge of hypoxia-induced epigenetic programming and discusses potential therapeutic interventions for lung disease.

FETAL QRS-COMPLEXES DETECTECTIONS IN ABDOMINAL SIGNAL BY USING WAVELET-BISPECTRUM

Fetal hypoxia or distress is a physical stress experienced by a fetus due to a lack of oxygen. Intrauterine hypoxia and the resultant perinatal brain damages may lead to extraordinary effects, including continuous lifelong treatments. One of the ways for detecting symptoms of hypoxia is monitoring of the fetus heart activity. At present, the basic method of monitoring the condition of unborn baby is the ultrasound cardiotocography (CTG). Considerably more information for early detection of the fetal hypoxia may be obtained by analyzing fetal electrocardiogram (FECG).

Ultrasound Parameters of Umbilical Artery Blood Flow Are Associated with Amniotic Fluid and Umbilical Artery Concentrations of Erythropoietin and Oxidative Stress Injury

Intrauterine hypoxia is the most frequent adverse intrauterine condition that occurs under a variety of circumstances including preeclampsia, placental insufficiency, high-altitude pregnancy, and any inflammatory condition during pregnancy resulting from gestational diabetes or even maternal obesity. However, early diagnosis of intrauterine hypoxia is still a challenge. In this study, we comparatively analyzed the systolic to diastolic ratio (S/D), resistant index (RI), and pulse index (PI) of the umbilical artery (UmA) and middle cerebral artery (MCA) blood flows obtained from 46 pregnant women with intrauterine hypoxia and 80 normal pregnant women at 28-31, 32-36, and 37-41 gestational weeks. Results found that the S/D, RI, and PI of UmA and MCA blood flows at 28-31, 32-36, and 37-41 gestational weeks were all increased in hypoxic fetuses than in normal fetuses ( P < 0.05 ). The malondialdehyde (MDA) level was elevated but superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities were reduced in the UmA blood of pregnant women with intrauterine hypoxia compared with normal pregnant women ( P < 0.05 ). It was found that the NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4) activities were increased in the UmA blood of pregnant women with intrauterine hypoxia compared with normal pregnant women ( P < 0.05 ). Results of ELISA methods showed that the expression level of survivin was lower but the expression levels of caspase-3, caspase-6, and caspase-9 were higher in the placental tissues of pregnant women with intrauterine hypoxia than those in normal pregnant women ( P < 0.05 ). The concentrations of erythropoietin in the amniotic fluid and UmA blood were increased in pregnant women with intrauterine hypoxia compared with normal pregnant women ( P < 0.05 ). The Spearman correlation analysis showed that the S/D, RI, and PI of UmA blood flow at 37-41 gestational weeks were positively correlated with the levels of Nox2, Nox4, and MAD and the UmA concentration of erythropoietin but negatively correlated with the activities of SOD, GSH-Px, and CAT ( P < 0.05 ). In summary, the study indicates that ultrasound parameters of the UmA blood flow including S/D, RI, and PI could serve as predictors of intrauterine hypoxia.