Chronic Fetal Hypoxia Research Articles

Chronic fetal hypoxia and antenatal Vitamin C exposure differentially regulate molecular signalling in the lung of female lambs in early adulthood.

Chronic fetal hypoxia is commonly associated with fetal growth restriction and can predispose to respiratory disease at birth and in later life. Antenatal antioxidant treatment has been investigated to overcome the effects of oxidative stress in utero to improve respiratory outcomes. We aimed to determine if the effects of chronic fetal hypoxia and antenatal antioxidant administration persist in the lung in early adulthood. Chronically catheterised pregnant sheep were exposed to normoxia (N; n = 20) or hypoxia (H; n = 18; 10% O2) ± maternal daily i. v. saline (N = 11; H = 8) or Vitamin C (VC; NVC = 9; HVC = 10) from 105 to 138days (term, ∼145days). Lungs were collected from female lambs 9months after birth (early adulthood). Lung tissue expression of genes and proteins regulating oxidative stress, mitochondrial function, hypoxia signalling, glucocorticoid signalling, surfactant maturation, inflammation and airway remodelling were measured. Chronic fetal hypoxia upregulated lung expression of markers of prooxidant, surfactant lipid transport and airway remodelling pathways in early adulthood. Antenatal Vitamin C normalized prooxidant and airway remodelling markers, increased endogenous antioxidant, vasodilator and inflammatory markers, and altered regulation of hypoxia signalling and glucocorticoid availability. There are differential effects of antenatal Vitamin C on molecular markers in the lungs of female lambs from normoxic and hypoxic pregnancy in early adulthood.

Maladaptive cardiomyocyte calcium handling in adult offspring of hypoxic pregnancy: protection by antenatal maternal melatonin.

Chronic fetal hypoxia is one of the most common complications of pregnancy and can programme cardiac abnormalities in adult offspring including ventricular remodelling, diastolic dysfunction and sympathetic dominance. However, the underlying mechanisms at the level of the cardiomyocyte are unknown, preventing the identification of targets for therapeutic intervention. Therefore, we aimed to link echocardiographic data with cardiomyocyte function to reveal cellular mechanism for cardiac dysfunction in rat offspring from hypoxic pregnancy. Further, we investigated the potential of maternal treatment with melatonin as antenatal antioxidant therapy. Wistar rats were randomly allocated into normoxic (21% O2) or hypoxic (13% O2) pregnancy with or without melatonin treatment (5µg/ml; normoxic melatonin in the maternal drinking water from gestational day 6 to 20 (term=22days). After delivery, male and female offspring were maintained to adulthood (16weeks). Cardiomyocytes were isolated from the left and right ventricles, and calcium (Ca2+) handling was investigated in field-stimulated myocytes. Systolic and diastolic function was negatively impacted in male and female offspring of hypoxic pregnancy demonstrating biventricular systolic and diastolic dysfunction and compensatory increases in cardiac output. Ca2+ transients from isolated cardiomyocytes in offspring of both sexes in hypoxic pregnancy displayed diastolic dysfunction with a reduced rate of [Ca2+]i recovery. Cardiac and cardiomyocyte dysfunction in male and female adult offspring was ameliorated by maternal antenatal treatment with melatonin in hypoxic pregnancy. Therefore, cardiomyocyte Ca2+ mishandling provides a cellular mechanism explaining functional deficits in hearts of male and female offspring in pregnancies complicated by chronic fetal hypoxia. KEY POINTS: This study identified significant changes in Ca2+ handling within cardiomyocytes isolated from offspring of hypoxic pregnancy including reduced systolic Ca2+ transients, impaired diastolic recovery of [Ca2+]i and a greater increase in systolic [Ca2+]i amplitude to β-adrenergic stimulation. These changes in cardiomyocyte Ca2+ handling help to explain dysregulation of biventricular systolic and diastolic dysfunction determined by echocardiography. The data show protection against maladaptive cardiomyocyte calcium handling and thereby improvement in cardiac function in adult offspring of hypoxic pregnancy treated with melatonin with doses lower than those recommended for overcoming jet lag in humans. Melatonin treatment alone in healthy pregnancy did cause some alterations in cardiac structure. Therefore, maternal treatment with melatonin should only be given to pregnancies affected by chronic fetal hypoxia.

CLASSİFİCATİON OF CLİNİCAL SYMPTOMS DEPENDİNG ON THE SEVERİTY OF ANEMİA İN PREGNANT WOMEN

The article provides information on the results of research conducted to study the changes in clinical signs during pregnancy in women with different degrees of iron deficiency anemia (IDA). Hemogram parameters were studied using the “ Mythic 18” (Switzerland) hematological analyzer. For this purpose, the mutual relationships between the main indicators of iron metabolism and the main symptoms of anemia were analyzed using clinical-biochemical methods in the blood of 110 women of reproductive age at various stages of pregnancy. The main contingent of the study consisted of 80 pregnant women with IDA (main group). 30 pregnant women without anemia were included in the comparison group, and 21 healthy women without pregnancy were included in the control group. It has been determined that in multiparous pregnant women, the hemoglobin level in mild anemia is Me = 10.4 (10.0-10.5), in moderate anemia Me = 8.9 (8.3-9.5), in severe anemia Me = 6.9 (6.3-6.9) p<0.001; the level of iron in mild anemia is Me = 9.0 (8.0-9.4), in moderate anemia Me = 6.7 (6.1-7.7), in severe anemia Me = 5.3 (3.5-5.8) p<0.001; the level of ferritin in mild anemia is Me = 19.3 (12.0-28.0), in moderate anemia Me = 9.9 (9.1-12.0), in severe anemia Me = 3.0 (2.0-8.0) p<0.001. During pregnancy, significant changes occur in iron metabolism in iron deficiency anemia. Pregnancy anemia is a significant risk factor for fetal and maternal morbidity. Thus, depending on the severity of anemia, complications such as intrauterine growth retardation, chronic fetal hypoxia, preeclampsia, preterm birth, and primary birth weakness during delivery have been predominant. This allows us to carry out corrective treatment.

Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

Analysis Of Risk Factors For Hypoxic Damages Of Newborn`S Central Nervous System

Currently, perinatal damage to the central nervous system of newborns occupies an important place in the structure of pathology of young children, which is associated with high prevalence, severity of clinical manifestations and the risk of disability formation. The purpose of our study was to determine the significance of risk factors for the development and to develop criteria for the severity of hypoxic-ischemic CNS damage in newborns. We examined 120 newborns with moderate to severe perinatal CNS damage. The examination consisted of the collection of maternal history, which included information on somatic and gynecological diseases, the course of this pregnancy, childbirth, general clinical examination methods, examination of a newborn with an assessment of somatic and neurological status. The results of the study showed that modifying risk factors for the development of moderate perinatal encephalopathy are the threat of miscarriage, toxicosis, the age of the mother over 35 years old, moderate anemia, acute upper respiratory tract infections, gynecological pathology, taking antifungal drugs, rapid and protracted childbirth, weak birth activity. We also found that the modifying risk factors for the development of severe perinatal encephalopathy are stillbirth, bad habits in the father, closely related marriage, obesity, chronic foci of infection, acute bacterial infectious diseases, urogenital infection, NSAIDs, rapid and protracted childbirth, chronic fetal hypoxia.

Placental Chorangiosis: Clinical Risk Factors and Pregnancy Outcomes

Background: Placental chorangiosis is a response to fetal hypoxia, linked to be associated with maternal/fetal disorders and higher mortality rates. Therefore, this study aimed to explore the association of placental chorangiosis with specific maternal clinical risk factors, as well as its impact on pregnancy outcomes compared to pregnancies with normal placental conditions. Methods: This retrospective case-control study was conducted at King Saud University Medical City (KSUMC) between September 2018 and December 2021. A total of 78 pregnant women were included, and 26 cases of placental chorangiosis were identified and included in the study, which were randomly matched to 52 controls. The demographic data of maternal factors (age, body mass index (BMI), type of gestation, gravidity, and parity) and pregnancy outcomes (abortion, gestation age at delivery, mode of delivery, born alive or not, Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score at 1 and 5 minutes, birth weight, and mean placental weight) were retrieved from the patient’s medical records, all placental histopathological examination were reviewed. Simple and multiple logistic regression analysis were used, and crude and adjusted odds ratios (ORs) and relative risk (RR) were reported with a 95% confidence interval (95% CI). Results: None of the potential maternal risk factors (age, BMI, type of gestation, gravidity, and parity) were statistically associated with chorangiosis. Chorangiosis, however, exhibit statistically significant associations with an increased number of abortions (RR: 21.59, 95% CI: 1.24–376.20, p = 0.003), intrauterine fetal death (IUFD; RR: 4.50, 95% CI: 1.53–13.25, p = 0.004), and low neonatal APGAR scores at 5 minutes (RR: 3.31, 95% CI: 1.22–9.01, p = 0.029). Conclusion: Placental chorangiosis is a rare pathological change in the placenta resulting from the interaction of several maternal and fetal disorders. When present, it can serve as an important indicator of chronic fetal hypoxia and predict poor obstetrical outcomes.

Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth.

Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.

The Investigation of Cerebroplacental Ratio and Some Cranial Biometric Measurements in Fetuses with Isolated Congenital Heart Disease

Objective: In this study, we aimed to compare the measurements of some fetal cranial structures and Doppler parameters between the groups with congenital heart disease and healthy pregnant women. Materials and Methods: The study included 30 patients with intrauterine congenital heart disease and 30 healthy pregnant women. Fetuses with additional structural and genetic abnormalities were excluded from the study. In both groups, biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), umbilical artery resistance index (UA-RI), and umbilical artery systole/diastole ratio (UA S/D), as well as superior-inferior diameter of the cavum septum pellucidum (CSP) were measured by ultrasound. The cerebroplacental ratio (CPR), which is an indicator of the protective effect on the brain, was calculated. Data were statistically compared between the two groups, and P < 0.05 was considered statistically significant. Results: A statistically significant difference was found between the groups in UA-RI and UA S/D values. The UA-RI and UA S/D values were significantly higher in the patient group than in the control group (P=0.048; P < 0.001). HC values were lower in the congenital heart disease group, and this result was statistically significant (P=0.047). There was no statistically significant difference between groups in BPD, HC, and TCD Z-scores. There was no statistically significant difference between groups in MCA-PI < 5th percentile, UA-PI > 95th percentile, and CPR < 1 scores. Conclusion: Congenital heart disease may cause chronic fetal hypoxia during the intrauterine process and lead to changes in the fetomaternal circulation. This study suggests that there may be relationships between fetal cranial biometric retardation and cerebral perfusion changes.

Ductus venosus opens in high-risk pregnancies without signs of increased central venous pressure.

It has been belived that changes in diastolic blood velocities in the fetal ductus venosus were due to increased central venous pressure secondary to increased fetal heart strain during hypoxia or heart failure. There have been recent reports of changes in ductus venosus blood velocity without signs of increased fetal heart strain. The aim of this evaluation was to compare blood velocity in the right hepatic vein as a marker of increased central venous pressure in relationship to changes in ductus venosus blood velocity. Fifty pregnancies suspected of fetal growth resitriction were evaluated by Doppler ultrasound. Blood velocity was recorded in the right hepatic vein, ducus venosus and in the umbilical vein. Placental blood flow was also recorded in the uterine and umbilical arteries as well as the fetal middle cerebral artery. Increased umbilical artery pulsatility index was recorded in 19 fetuses and 20 has signes of brain sparing according to recordings in the middle cerebral artery. Abnormal blood velocity in the ductus venosus was recorded in 5 fetuses, none of these fetuses had an abnormal pulsatility in the right hepatic vein. Opening of the ductus venosus is not only related to fetal cardiac strain. This might indicate that the ductus venosus does not primarily open due to increased central venous pressure in moderate fetal hypoxia. Increased fetal cardiac strain might be a late event in the process of chronic fetal hypoxia.

FETOPLACENTAL INSUFFICIENCY AND OZONE THERAPY

Placental insufficiency, as well as its complication intrauterine chronic fetal hypoxia, is one of the important problems of modern perinatology. At the same time, its numbers have been increasing in recent years. Purpose - Evaluation of the effect of ozone therapy on the blood circulation of the mother and fetus, fetoplacental blood flow and the degree of adaptation of the fetus to hypoxia according to the results of cardiotocography, ultrasound and dopplerometry. Material and methods: 38 pregnant women who applied to the Department of Obstetrics and Gynecology of Clinic No. 1 of the Samara State Medical University with fetoplacental insufficiency were divided into two groups according to the type of treatment: patients who received complex treatment with ozone therapy, and patients who received standard medical procedures. Results: about a third of women in each group had a combined extragenital pathology. Women in both groups were statistically comparable when compared in terms of general clinical characteristics, basic anthropometric data, extragenital diseases and reproductive history. The most common complications of childbirth were premature rupture of amniotic fluid (4 in the 1st group - 22.2% and 5-25% in the 2nd group) and acute fetal hypoxia (3-16.7% and 3-15%). Conclusion: Thus, the indicators of maternal-fetal circulation, fetoplacental circulation in women in the ozone therapy group were more positive than in the 2nd group, and the level of fetal adaptability to hypoxia was higher.

Asphyxia of newborns: new ideas about risk factors and pathogenetic mechanisms of the condition

Intrauterine hypoxia and asphyxia during childbirth are among the leading causes of neonatal deaths in the structure of «Separate conditions arising in the perinatal period» according to the Ministry of Health of the Russian Federation. The main causes of asphyxia are chronic intrauterine hypoxia and acute fetal hypoxia (most often in the intrapartum period). The article observes current data on antenatal and intrapartum risk factors for the development of asphyxia in newborns. Risk factors (modifiable and non-modifiable) triggering intrauterine hypoxia are discussed, as well as methods of management and prevention of asphyxia to prevent the subsequent development of hypoxic-ischemic encephalopathy. The importance of the problem under consideration is due to the need to find promising «tools» for managing neonatal and infant mortality, as well as preventing the long-term consequences of hypoxic brain damage.

Differentially diagnostic criteria for intratual and early neonatal pneumonia

Aim. To differentiate clinical signs in intrauterine and early neonatal pneumonia.Materials and methods. The studies were carried out in the Maternity ward and the “Mother and Child” ward of the second stage of nursing of the State Institution “Istiklol” in Dushanbe. In total, a retrospective analysis of 260 newborn development records and medical records was carried out. Two groups were formed, group 1 consisted of 110 (42.3%) newborns with a confirmed diagnosis of intrauterine pneumonia, the second group - of 150 (57.6%) with early neonatal pneumonia. Statistical analysis of the material was performed using the Statistica 10.0 software package (StatSoft, USA).Results. According to the anamnesis, 45.7% of 1st group mothers had premature childbirth, while in the second group 37.3% of mothers. Among the mothers of group 1, real pregnancy was characterized (p> 0.05) by colpitis (76.9%), anemia (71.3%), threatened abortion (48.6%), chronic fetal hypoxia (57.4%), high frequency of premature rupture of amniotic fluid (34.6%), discoordination of labor (25.0%). Statistically significant (p <0.001) (40.6%) in children of the second group observed an increase in temperature (above 38°C). The majority of newborns with intrauterine pneumonia did not have the act of sucking - 74.8%, 32.2% of newborns (p <0.01) noted the absence of the act of swallowing. Dyspnea was observed in 97.7.5% of children with intrauterine pneumonia and 74.7% of children with early neonatal pneumonia, auxiliary muscles were involved in the breathing, and therefore 69.6% of newborns with intrauterine pneumonia and 76.3% with early neonatal pneumonia (p<0.05) needed respiratory support.Conclusion. The course and the type of complications of pregnancy in mothers with infected children were different. Differential diagnostic signs between intrauterine and early neonatal pneumonia were established.

Disturbance of utero-placental-fetus blood flow in pregnant women with community-acquired pneumonia of bacterial and viral (COVID-19) etiology

Introduction. Placental insufficiency is one of the most frequently developing complications in pregnant women with acute respiratory failure, which is a consequence of community-acquired pneumonia (CAP), including viral etiology. The impact of COVID-19 infection on the course of pregnancy, the condition of the fetus and newborns has not been studied enough. Aim. To study the state of uteroplacental-fetal circulation, placenta and fetus in women with bacterial and COVID-19-associated CAP in the second and third trimesters of pregnancy. Materials and methods. The history of childbirth and the results of examinations of 120 women in the second and third trimesters of pregnancy were analyzed, including 37 women with moderate CAP of bacterial etiology, 48 women with COVID-19 infection. The comparison group consisted of 35 women with uncomplicated pregnancy. The state of the placenta and fetus was assessed according to the data of ultrasound and utero-placental-fetal blood flow – Doppler study. Pulsation indices (PI) and cerebro-placental ratio (CPR) were analyzed. Results. According to our data, the risk of developing chronic placental insufficiency in pregnant women with COVID-19-associated CAP of moderate severity was higher than in groups of women with CAP of bacterial etiology and in the comparison group. In groups with CAP, significant differences were found in the indices of CPR, PI of the uterine arteries, umbilical cord arteries and middle cerebral artery, corresponding to I (A, B) or II degree of disturbance of the uteroplacental and/or placental-fetal blood flow. Chronic intrauterine fetal hypoxia and fetal growth retardation were more frequently detected in the group with COVID-19-associated CAP. Newborns born to mothers with COVID-19 infection have an increased risk of neonatal damage to the central nervous system (CNS). Conclusion. COVID-19-associated CAP, compared with CAP of bacterial etiology, increases the risk of chronic placental insufficiency, intrauterine fetal hypoxia and fetal growth retardation, and the development of neonatal CNS damage.

The role of hypoxia in the pathogenesis of congenital hyperplasia of blood vessels in the head and neck in children (literature review)

To date, scientists have found that stress plays an important role in the formation of congenital malformations. It can be caused by the influence of negative environmental factors on the pregnant woman or by her own diseases. One of the consequences of stress is hypoxia. It can be acute and chronic, and can have a negative impact both during pregnancy and during childbirth. They also distinguish local and general hypoxia. The consequences of the negative impact of oxygen deficiency on the embryo and fetus can manifest itself both in utero and after birth, leading to various kinds of congenital malformations, diseases, and sometimes fetal death, or increase the risk of sudden infant death syndrome. Hyperplasia of blood vessels, the so-called children’s hemangiomas, develops both in utero, especially with chronic fetal hypoxia, and during childbirth. It develops due to insufficient blood supply and oxygen deficiency in various parts of the body, most often in the head and neck. In an embryo under conditions of hypoxia, tachycardia develops – with an increase in heart rate and, if it is ineffective, local vasodilation occurs. Only then, under the condition of continuing hypoxia, does an increase in the number of blood vessels develop. This often leads to the formation of hyperplasia of the blood vessels, the so-called children’s hemangiomas.This pathology is quite common, especially among fair-skinned children, which makes its study, in particular the factors that cause this pathology, relevant today.

The main risk factors for the development of cerebral palsy in children

Introduction. Currently, worldwide the formation of cerebral palsy (CP) makes a great contribution to the gain in childhood disability prevalence. The goal is to conduct a comparative analysis of risk factors and the main causes of the development of CP in children living in the Belgorod region for the period from 2020 to 2021. Materials and methods. There were analyzed histories of two hundred two CP children aged from four months to seven years. Results. Spastic forms of the disease predominated in the structure of infantile CP. Significantly more often this pathology occurred in premature babies at an early age and children residing in urban areas. The most frequent risk factors for the onset of the disease were such pathology of pregnancy as chronic fetoplacental insufficiency and chronic intrauterine fetal hypoxia. Delayed psycho-speech development had a leading place among all manifestations of the central nervous system in CP patients is beyond doubt. An analysis of the causes leading to the onset of the disease showed that in most cases it is not possible to discriminate one of them, since a combination of several unfavourable factors is often noted during pregnancy and parturition. CP children require constant care from relatives, long courses of complex drug and rehabilitation treatment.

Impact of the intrauterine environment on future reproductive and metabolic health

Key content As survival of babies born following high‐risk pregnancies continues to increase globally, understanding the long‐term impacts of suboptimal intrauterine environments on future health becomes increasingly important. The intrauterine environment is a key influence on later metabolic health, particularly the tendency to later‐life obesity and dyslipidaemia. Recent evidence shows that female reproductive function is also highly sensitive to the influence of the early life environment. Various suboptimal intrauterine environments are linked to adverse reproductive and metabolic outcomes, including maternal obesity, low‐protein diets and chronic fetal hypoxia. Learning objectives To know that the prevalence of high‐risk intrauterine environments is increasing in maternity populations because of, for example, increasing rates of maternal obesity. To be aware of the later‐life health implications for the fetus when caring for women with high‐risk pregnancies. To understand that children who are survivors of high‐risk pregnancies are at increased risk of adverse metabolic health outcomes and more work is required to determine optimal follow‐up.

Serum S100B Protein Concentrations in SGA/FGR newborns.

Fetal growth restriction is associated with chronic fetal hypoxia, poor perinatal outcome and increased perinatal mortality. There are no reliable methods to detect cell damage in the central nervous system (CNS) in these patients. The findings of increased an acidic calcium-binding protein (S100B) concentration in biological fluids of infants after brain injury have supported the use of S100B as a biochemical marker of CNS damage. The purpose of the study was to assess blood S100B concentrations in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns and to evaluate the usefulness of S100B for early detection of hypoxia. The investigation was carried out between November 2011 and April 2014. Serum S100B protein level was assessed in cord blood collected from newborns after birth. Medical records of mothers of neonates studied were reviewed for pregnancy induced hypertension (PIH), preeclampsia, maternal smoking during pregnancy and abnormalities in umbilical artery (UA) Doppler ultrasound examination. The study was carried out in 88 SGA neonates and 80 AGA neonates. The median value of S100B protein concentration in the SGA study group was significantly higher than in AGA controls (p < 0.001). Cord blood serum S100B concentration in SGA neonates with prenatal normal UA Doppler ultrasound findings (n = 32) did not differ from that SGA neonates with abnormal prenatal UA Doppler findings (n = 25) (p = 0.74), but was significantly higher than in AGA newborns (p < 0.001). Elevated S100B protein levels in cord blood collected from SGA newborns may be helpful in detecting infants at higher risk of postnatal neurologic disturbances at an early stage.

Correlation between placental histopathology and perinatal outcome in COVID-19.

ABSTRACTObjectives:An alarming rate of adverse perinatal outcomes as well as maternal deaths has been reported worldwide during this pandemic. It would be prudent to start thinking on the lines of acute or chronic intrauterine fetal hypoxia due to placental microvascular pathology or villitis caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Autopsy studies of deceased patients with severe COVID-19 have revealed the presence of diffuse pulmonary alveolar damage, thrombosis, and microvascular injuries. It is expected that similar pathological features such as microvascular injuries could be found in the placenta of infected pregnant women.Materials and Methods:Placentas of singleton pregnancies from 42 SARS-CoV-2 positive mothers delivered at term were submitted for histopathological examination. Those with multifetal gestation, hypertensive disorder, fetal growth restriction, structural or chromosomal anomalies in the fetus, thrombophilia, prolonged prelabor rupture of membranes, and placenta accreta spectrum were excluded from the study. Histopathological examination was done by two pathologists independently and only those results concurred by both were reported. Histopathological features and corresponding neonatal outcome were analyzed.Results:Reports of 42 placentas from patients with SARS-CoV-2, delivered at term (37–40 weeks) were analyzed in our study. Features of maternal vascular malperfusions (MVM) were present in 45% (n = 19) cases. Features of fetal vascular malperfusions (FVM) were present in 23.8% (n = 10) cases. There were 47.6% (n = 20) cases showing at least one feature of acute inflammatory pathology (AIP) and 42.8% (n = 18) showing features of chronic inflammatory pathology (CIP). Neonatal respiratory distress syndrome was found in 19% (n = 8) of the neonates. Correspondingly, nearly all placentas (n = 7) of these neonates showed features of MVM, FVM, AIP and CIP. There was no maternal or neonatal mortality in our study group.Conclusion:The main findings of our study include maternal as well as fetal vascular malperfusions and placental inflammatory pathology. These findings provide an outline for better understanding of etiological factors and pathogenesis of adverse perinatal outcomes in SARS-CoV-2 infection.

Dichotomous Responses to Chronic Fetal Hypoxia Lead to a Predetermined Aging Phenotype

Hypoxia-induced intrauterine growth restriction increases the risk for cardiovascular, renal, and other chronic diseases in adults, representing thus a major public health problem. Still, not much is known about the fetal mechanisms that predispose these individuals to disease. Using a previously validated mouse model of fetal hypoxia and bottom-up proteomics, we characterize the response of the fetal kidney to chronic hypoxic stress. Fetal kidneys exhibit a dichotomous response to chronic hypoxia, comprising on the one hand cellular adaptations that promote survival (glycolysis, autophagy, and reduced DNA and protein synthesis), but on the other processes that induce a senescence-like phenotype (infiltration of inflammatory cells, DNA damage, and reduced proliferation). Importantly, chronic hypoxia also reduces the expression of the antiaging proteins klotho and Sirt6, a mechanism that is evolutionary conserved between mice and humans. Taken together, we uncover that predetermined aging during fetal development is a key event in chronic hypoxia, establishing a solid foundation for Barker’s hypothesis of fetal programming of adult diseases. This phenotype is associated with a characteristic biomarker profile in tissue and serum samples, exploitable for detecting and targeting accelerated aging in chronic hypoxic human diseases.

Clinical significance of predictive and diagnostic indices of fetal pathology associated with placental insufficiency in women with endometriosis

BACKGROUND: Modern achievements of pharmacology, surgery and reproductive medicine have determined an increase in the implementation of reproductive function in endometriosis of various localization. The onset of pregnancy in presence of impaired endometrial receptivity and progesterone resistance, pro-inflammatory and pro-thrombotic status, abnormal functioning of the immune system, structural changes in the reproductive organs leads to impaired formation of the embryo (feto) placental system, early reproductive losses, complicated pregnancy and adverse perinatal outcomes. In this regard, the endometriosis and pregnancy issue requires close study and specific proposals to optimize pregnancy management.&#x0D; AIM: The aim of this study was to develop predictive (PIs) and diagnostic (DIs) indices of placenta-associated fetal pathology in pregnant women with endometriosis, to determine their prognostically and diagnostically significant parameters.&#x0D; MATERIALS AND METHODS: This prospective study in the dynamics of gestation included a comprehensive clinical and laboratory examination of 175 pregnant women with endometriosis (100 subjects with adenomyosis and 75 subjects with ovarian endometriosis). To develop PIs and DIs, two comparison groups with fetal pathology due to placental insufficiency were retrospectively identified, depending on the location of endometriosis. Group I consisted of 49 pregnant women with adenomyosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia; Group II comprised 29 pregnant women with ovarian endometriosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia. The control group (Group III) included 30 healthy pregnant women with a normal course of gestation. The examination was performed at 10-14 weeks, 20-24 weeks, and 28-34 weeks of gestation and included an assessment of placental insufficiency markers such as placental growth factor (PlGF), placental -1-microglobulin (PAMG-1), tumor necrosis factor (TNF), lymphocytes with membrane receptor FasR (L CD95+), C-reactive protein, placental alkaline phosphatase (PAPh), and fetal hemoglobin (HbF). The information value of individual parameters and indices was determined by ROC analysis, odds ratio, and clinical epidemiology tests.&#x0D; RESULTS: Pregnancy in presence of endometriosis in 100% of cases was complicated by placental insufficiency of varying severity (with fetal pathology in 81.5% of cases), the frequency of which had statistically significant differences between the groups of pregnant women with adenomyosis and ovarian endometriosis (2 = 4.06, p = 0.04). To predict growth retardation and / or chronic fetal hypoxia, we have developed PI I (PlGF / TNF 100) and PI II (PAMG-1 / PlGF 100), which characterize the state of placental angio-and vasculogenesis depending on systemic inflammatory response level. For early diagnosis of fetal pathology, we have proposed DI I (CRP / PAPh 100), DI II (HbF / PlGF 100) and DI III (L CD95+ / PAPh 100), which allow for diagnosing placental alterations with impaired placental energy supply due to an increase in inflammatory status. Evaluation of prognostic and diagnostic significance of PIs and DIs showed that the most informative tools are PI I (Se = 86.1%, Sp = 80.5%) and DI I (Se = 88.3%, Sp = 83.7%).&#x0D; CONCLUSIONS: The use of PIs allows for risk stratification of pregnant women from the 1st trimester of gestation to address the issue of the prevention method. The clinical capabilities of DIs optimize obstetric tactics for the timely prescription of therapy for placental insufficiency and targeted diagnosis of fetal pathology. Pregnant women with endometriosis should be classified as a high perinatal risk group, and therefore the proposed PIs and DIs should be included in the dynamic examination complex.