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Increased frequency of uterine contractions is a component in the cluster of causal conditions that can lead to fetal hypoxia and acidosis and increase the risk for neonatal neurologic injury. For most international obstetrical societies, 5 contractions per 10 min averaged over 30 min is considered as the upper limit of normal uterine activity. We hypothesize that it might be safer to adopt an upper limit of 4 contractions per 10 min.We reviewed our 1970's research database containing 475 patients with closely monitored and well-documented labor and neonatal assessments that included cord blood (CB) pH, base excess (BE), and continuous recording of neonatal heart rate (NHR). Using data segregated by the proportion of the last hour before delivery when uterine contraction frequency (UCF) exceeded 4 and 5 contractions per 10 min respectively, we evaluated outcomes (CB BE, pH, Apgar scores at 1 min, the status of NHR at 16 min after birth, and the proportion of births that did not the result from normal spontaneous vaginal deliveries (NSVDs). ANOVA established relationships between UCF cutoffs and these outcomes. Our sample size is sufficiently large to provide the ability of UCF, per se, to accurately detect an alpha region of .05 88% of the time with an effect size of .15.During the last hour prior to delivery, a UCF cutoff at 4 contractions per 10 min performed better than a UCF cutoff at 5 contractions per 10 min to enable the earlier identification of risks for abnormal outcomes. The longer UCF was increased, the worse were the outcomes that were measured, and the region4 but ≤5 contractions identifies the beginnings of worsening conditions in a variety of measures of poor outcomes.Lowering the recommended threshold for UCF from 5 to 4 contractions per 10-minute period as averaged over 30 min facilitates earlier detection of potentially compromised fetuses and is also an important contributor to a multicomponent contextualized approach to risk assessment.

Background Umbilical artery thrombosis is a rare complication of pregnancy strongly associated with poor fetal and perinatal outcomes, such as intrauterine asphyxia, fetal growth restriction, and stillbirth. Its pathogenesis remains unclear, and there is the added challenge of selecting an appropriate delivery time to achieve excellent neonatal outcomes. Methods Our Hospital is a critical maternal rescue center with approximately 7000 births annually. We present a series of 8 cases of umbilical artery thrombosis diagnosed at the hospital between Apr 1, 2018, and Jan 31, 2020. We identified the cases through a keyword search of the maternity and pathology information management systems. Results Three patients were diagnosed with a transabdominal ultrasound scan and hypoxia on fetal heart monitoring. All three patients had emergency cesarean section delivery. Four patients were observed closely for 5 to 13 weeks from initial detection by an ultrasound scan to delivery. Only one patient was diagnosed after vaginal delivery by Hematoxylin-eosin staining of umbilical cord sections. Seven patients had deliveries by cesarean section, and one patient had a vaginal delivery. All infants were born alive. Conclusions Umbilical artery thrombosis is a challenging and rare condition that can occur at different gestational ages, especially when diagnosed in the third trimester and accompanied by fetal growth restriction. Consequently, these patients require close monitoring of umbilical blood flow and fetal growth and intervention at the appropriate time to achieve an optimal outcome.

Introduction Non-stress test is an important non-invasive tool of antepartum surveillance. The hypoxia, acidemia in the fetus can easily be picked up by a non-stress test. It is important to get a non-stress test done on time to prevent the adverse neonatal outcome. Aim This quality improvement project aims to evaluate the waiting period for a non-stress test (NST) from the point of decision in the antenatal outpatient department and to increase the percentage of pregnant women getting NST done in less than 4 h from the point of decision from a baseline of 41% to 80% in 4 weeks. Method This observational study was conducted in the Department of Obstetrics & Gynecology at All India Institute of Medical Sciences Jodhpur for twelve weeks. This study has three phases—baseline assessment, implementation phase and continued implementation with the assessment phase. The tool used for the analysis of this problem was the Fishbone method. Results The baseline assessment showed that only 41% of pregnant women got the non-stress test done in 4 h. We conducted a plan-do-study-act (PDSA) cycle 3 times, and the target was achieved in the second PDSA cycle. Conclusion This quality improvement project has demonstrated that increasing awareness among all the team members who are dealing with pregnant women requiring NST can significantly increase the percentage of pregnant women getting NST done within 4 h from the point of decision. By detecting the fetal heart rate variation, we can prevent adverse fetal and neonatal outcomes.

Foetal hypoxia–ischaemia is a key trigger of meconium aspiration syndrome (MAS). However, many neonates develop MAS without evidence of hypoxia–ischaemia, suggesting the presence of covert but important risk variables. We evaluated the association of MAS with clinical variables, placental histopathologic findings, and inflammatory biomarkers at birth. Of 1336 symptomatic and asymptomatic term singleton neonates with meconium-stained amniotic fluid, 88 neonates (6.6%) developed MAS. Univariate analysis showed that MAS development was associated with low 1- and 5-min Apgar scores, low cord blood pH, funisitis, higher α1-acid glycoprotein levels, and higher haptoglobin levels (all p 1-acid glycoprotein levels (OR 1.02; 95% Cl 1.01–1.03; p = 0.001). Our data from a large cohort of neonates suggested that intrauterine inflammation is one of the key independent variables of MAS development, together with foetal hypoxia–ischaemia.

To compare Doppler alterations and perinatal outcomes in pregnant women who evolved with early- and late-onset fetal growth restriction (FGR).A retrospective, observational cohort study with pregnant women who evolved with FGR treated between January 2018 and April 2019, in which all live births from singleton pregnancies, over 24 weeks, with FGR ultrasound diagnosis and under 2700 g weight were included in the study.Pregnancies with early-onset FGR were more associated with hypertensive disorders (Early-onset FGR had a lower prevalence but was associated with higher maternal and fetal morbidity and mortality than late-onset FGR.

Background In general, epidural analgesia is considered a safe and efficient way to relieve pain during active labour and is increasingly used in childbirth. It is well documented that epidural analgesia during birth has benefits but also adverse effects. However, evidence is limited on how epidural analgesia influences neonatal outcome in a low-risk population of birthing women. Aim To examine low Apgar score, foetal hypoxia and admission to the neonatal intensive care unit in neonates of low-risk women receiving epidural analgesia during birth. Methods A cohort study using registry data to investigate a population of 23,272 low-risk women giving birth at a university hospital. Results Epidural analgesia was used in 21.6% of low-risk women during birth. Low Apgar score, foetal hypoxia, and admission to the neonatal intensive care unit were found in 0.6%, 0.6%, and 10.0%, respectively in neonates of mothers receiving epidural analgesia during birth compared to 0.3%, 0.6%, and 5.6%, respectively in the non-exposed group. Epidural analgesia was associated with low Apgar score, adjusted odds ratio 1.76 (95% CI 1.07–2.90) and admission to the neonatal intensive care unit, adjusted odds ratio 1.43 (95% CI 1.26–1.62). A mediation analysis indicates the impact of epidural analgesia on adverse neonatal outcomes was mediated by obstetric complications like maternal fever, labour augmentation, and foetal malpresentation. Conclusion This study found use of epidural analgesia during birth in low-risk pregnant women was associated with infant low Apgar score and admission to the neonatal intensive care unit.

BACKGROUND:Most under-five deaths occur within the first month after birth and intrapartum complications are a major contributor to the cause of death. These defects can be easily identified during the ante-natal check-up by use of a non-stress test. Due to the lack of availability of resources and medical experts in remote areas clinical decision support systems powered by machine learning models can provide information to the healthcare provider to make timely and better-informed decisions based on which course of treatment can be planned. AIM:The study aims to develop an accurate and sensitive clinical decision support system model that can identify pathological fetuses based on the fetal heart rate recordings taken during the non-stress test. METHOD: Foetal Heart rate recordings along with 10 other variables were collected from 1800 pregnant women in their third trimester. The data was put through a feature selection algorithm to identify important variables in the set. The data set was randomly divided into 2 independent random samples in the ratio of 70% for training and 30% for testing. After testing various machine learning algorithms based on specificity, sensitivity to accurately classify the fetus into normal, suspected, or pathological Random Forest algorithm was chosen. RESULT:The fetal status determined by Obstetrician 77.85% observations from the normal category, 19.88% from the suspected category, and 8.28% from the pathological category. The Boruta algorithm revealed that all 11 independent variables in the data set were important to predict the outcome in the test set. In the training set the model had an accuracy of 99.04% and in the testing set accuracy was 94.7% (p-value=< 2.2e-16) with the precision of 97.56% to detect the pathological category. CONCLUSION:With the ability of the model to accurately predict the pathological category the CDS can be used by healthcare providers in remote areas to identify high-risk pregnant women and take the decision on the medical care to be provided.

Insulin-like growth factor 1 (IGF-1) plays an important role in the energy balance of the newborn baby's body, is associated with protein stores, which allows us to consider its level as an indicator of nutritional status.Objective: to study the value of insulin-like growth factor 1 and basic nutrients in the blood in premature infants in the process of neonatal adaptation.Materials and methods. Dynamics blood levels of insulin-like growth factor 1 in premature newborns included two trends: decrease (1 group) and increase (2 group). During a pregnancy most mothers of newborns from 1 group had been nonspecific respiratory and urinary-sexual organs’sinfectious diseases, in mothers of newborns from 2 group prevailed disorders which carried high risk of fetal hypoxia. During a neonatal period blood levels of albumen of newborns from 1 group decreased and blood levels of glucose increased; blood levels of nutrients in newborns from 2 group did not change.Conclusions. Dynamics blood levels of insulin-like growth factor 1 in premature newborns are markers of metabolism’s processes which were originated in fetal stage and continue in the neonatal period.

Fetal hypoxic events with unclear predictive value are a common indication for placenta examination. We evaluated whether the use of CD15 immunostaining can improve the assessment of severity and duration of fetal hypoxia.We compared placentas (37-42 gestational weeks) from stillborns/newborns with birth asphyxia (BA) and non-hypoxic newborns. Placental findings were studied in following groups: (1) acute BA (n = 11) due to placental abruption, (2) non-acute BA (n = 121) due to non-acute conditions, (3) non-BA (n = 46) in pregnancies with preeclampsia and gestational diabetes, and (4) controls (n = 30).A high expression of CD15 in feto-placental resistance vessels (FRVs) was present in non-acute BA (95.9%), but absent in acute BA, non-BA and controls (p 0.0001). Furthermore, we found no causal relationship of high expression of CD15 in FRVs to coexisting placental conditions, including severity and mechanisms/patterns of placental injury, fetal erythroblastosis, and maternal conditions. According to a multivariate analysis, only a high expression of CD15 in FRVs was independently associated with severe non-acute fetal hypoxia ([OR] = 15.52; 95% [CI] = 5.92-40.67).We have defined a characteristic pattern of CD15 expression in FRVs that allows to interpret various clinical/placental conditions with respect to fetal hypoxia, with an improved predictability compared to conventional analyses. This approach represents a novel diagnostic strategy for placenta examination, which could indirectly assess severity and duration of intrauterine hypoxia in a heterogeneous population of newborns.

Objective: In order to improve the detection rate of fetal hypoxia in the third trimester and reduce the probability of adverse pregnancy outcome, color doppler ultrasound (CDU), and contractions were used to assess the severity of fetal hypoxia. Methods: The 61 pregnant women diagnosed with intrauterine hypoxia in South District of The Affiliated Hospital of Chengde Medical College from October 2017 to September 2019 were classified as the sick group. Meanwhile, the 61 normal pregnant women were selected as the control group. CDU was used to detect the relevant indexes of umbilical artery (UA) and middle cerebral artery (MCA) in the two groups, including pulse index (PI), resistance index (RI), systolic peak blood flow velocity (S) and diastolic peak blood flow velocity (D). The Apgar scale was used to score neonatal status. According to the score results, newborns were divided into Apgar ≤ 7 group and Apgar > 7 group. The indexes of UA and MCA were compared between the two groups. The amniotic fluid status of pregnant women was assessed using the contractile stimulation test (CST). The rate of amniotic fluid pollution in pregnant women and the incidence of neonatal asphyxia were calculated. Pregnant women were grouped according to the CST score. The correlation between CST score and amniotic fluid pollution and neonatal asphyxia in pregnant women was analyzed. Results: First, the index of fetal UA was obviously higher than that of the control group, while the index of MCA was obviously lower than that of the control group (P < 0.05). Second, the indexes of fetal UA in Apgar ≤ 7 group were obviously higher than those in Apgar > 7 group, while those in MCA were obviously lower than those in Apgar > 7 group (P < 0.05). Third, the incidence of amniotic fluid pollution and neonatal asphyxia in low and middle groups of pregnant women was obviously higher than that in high groups (P < 0.01). Conclusion: This indicates that the CDU technology combined with uterine contraction stimulation experiment can assess the degree of intrauterine hypoxia in the late stage of pregnancy, which provides a feasible scheme for clinical detection of intrauterine hypoxia.

Objetivo. Evaluar la calidad de la atención a neonatos con indicadores de proceso, en patologías seleccionadas. Ma­terial y métodos. Evaluación multicéntrica, transversal de nueve indicadores en 28 hospitales de 11 entidades de México. Se utilizó Lot Quality Assurance Sampling (LQAS) para estándares de calidad y muestra por hospital. Casos seleccio­nados al azar del Subsistema Automatizado de Egresos Hos­pitalarios. Se clasifican hospitales como “cumplimiento con estándar”/“no cumplimiento” por indicador y, cumplimiento con IC95% exacto binomial, regional y nacional, según mues­treo estratificado no proporcional. Resultados. Ningún indicador cumple el estándar de 75% en hospitales, con 0 a 19 hospitales que cumplen, según indicador. Excepto la iden­tificación oportuna de asfixia perinatal e inicio de antibiótico correcto en sospecha de sepsis temprana, el cumplimiento es

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

The healthy development of the fetus depends on the exact course of pregnancy and delivery. Therefore, prenatal hypoxia remains between the greatest threats to the developing fetus. Our study aimed to assess the impact of prenatal hypoxia on postnatal development and behavior of the rats, whose mothers were exposed to hypoxia (10.5 % O2) during a critical period of brain development on GD20 for 12 h. This prenatal insult resulted in a delay of sensorimotor development of hypoxic pups compared to the control group. Hypoxic pups also had lowered postnatal weight which in males persisted up to adulthood. In adulthood, hypoxic males showed anxiety-like behavior in the OF, higher sucrose preference, and lower levels of grimace scale (reflecting the degree of negative emotions) in the immobilization chamber compared to the control group. Moreover, hypoxic animals showed hyperactivity in EPM and LD tests, and hypoxic females had reduced sociability compared to the control group. In conclusion, our results indicate a possible relationship between prenatal hypoxia and changes in sociability, activity, and impaired emotion regulation in ADHD, ASD, or anxiety disorders. The fact that changes in observed parameters are manifested mostly in males confirms that male sex is more sensitive to prenatal insults.

Introduction The aim of the present study was to identify possible associations of fetal heart rate (FHR) patterns during the last 2 hours of labor with fetal asphyxia expressed by umbilical artery acidemia at birth and with neonatal complications in a large obstetric cohort. Material and methods Cardiotocographic recordings from 4988 singleton term childbirths over 1 year were evaluated retrospectively and blinded to the pregnancy and neonatal outcomes in a university teaching hospital in Helsinki, Finland. Umbilical artery pH, base excess and pO(2), low Apgar scores at 5 minutes, need for intubation and resuscitation, early neonatal hypoglycemia, and neonatal encephalopathy were used as outcome variables. According to the severity of the neonatal complications at birth, the cohort was divided into three groups: no complications (Group 1), moderate complications (Group 2) and severe complications (Group 3). Results Of the 4988 deliveries, the ZigZag pattern (FHR baseline amplitude changes of >25 bpm with a duration of 2-30 minutes) occurred in 11.7%, late decelerations in 41.0%, bradycardia episodes in 52.9%, reduced variability in 36.7%, tachycardia episodes in 13.9% and uterine tachysystole in 4.6%. No case of saltatory pattern (baseline amplitude changes of >25 bpm with a duration of >30 minutes) was observed. The presence of the ZigZag pattern or late decelerations, or both, was associated with cord blood acidemia (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.3-4.7) and severe neonatal complications (Group 3) (OR 3.3, 95% CI 2.4-4.9). In contrast, no significant associations existed between the other FHR patterns and severe neonatal complications. ZigZag pattern preceded late decelerations in 88.7% of the cases. A normal FHR preceded the ZigZag pattern in 90.4% of the cases, whereas after ZigZag episodes, a normal FHR pattern was observed in only 0.9%. Conclusions ZigZag pattern and late decelerations during the last 2 hours of labor are significantly associated with cord blood acidemia at birth and neonatal complications. The ZigZag pattern precedes late decelerations, and the fact that normal FHR pattern precedes the ZigZag pattern in the majority of the cases suggests that the ZigZag pattern is an early sign of fetal hypoxia, which emphasizes its clinical importance.

Use of intrapartum fetal heart rate (FHR) monitoring has had limited success in preventing hypoxic injury to neonates. One of the most common limitations of FHR interpretation is the failure to consider chronic and acute clinical factors that may increase the risk of evolving acidemia. This manuscript reviews common clinical factors that may affect the FHR and should be considered when determining the need for early intervention based on changes in the FHR.

Modernization of obstetric care for fetal hypoxia is proposed by hyperventilating the mother’s lungs with oxygen before the first symptoms of oxygen poisoning, General hypothermia of her body, and local hypothermia of the fetal head in the final period of delivery. The review shows the possibility of indirectly estimating the rate of oxygen exchange in the fetal cortex of brain by monitoring the local temperature of the head surface above the crevices and fontanels of the skull. It is shown that progress was achieved by using new data from ultrasound and infrared monitoring of fetal health. Keywords: Fetus, Brain, Hypoxia, Temperature, Hypothermia, Oxygen, Infrared imaging, Diagnostics.

Despite its ubiquitous use, fetal heart rate (FHR) monitoring has not resulted in a significant reduction in hypoxic-ischemic encephalopathy following delivery. This manuscript reviews the reasons for this failure including limitations of FHR to accurately predict hypoxia, low prevalence of hypoxic-ischemic encephalopathy, and lack of standardization of interpretation and intervention. We propose an alternative goal for FHR monitoring during labor to provide optimal care by early identification of truly concerning features, initiation of appropriate interventions, clear documentation of concerns and plans, and clear communication between team members on labor and delivery, including initiation of the chain of command as needed.

Cardiotocography (CTG) is the main method of assessment of the fetus, which due to its informativeness and stability of the information obtained has almost completely replaced the phonoand electrocardiography of the fetus from the clinical practice. A CTG can be used to monitor the fetus during both pregnancy and delivery. Depending on the presence or absence of risk factors, internal or external CTGs are now used. Knowledge of the basic principles, definitions and concepts of CTG, its classification, as well as accumulated clinical experience, helps to interpret the results obtained and improve the outcomes of childbirth. CTG data should be considered in combination with the clinical situation in order to select the correct management of birth tactics and decide on the method of delivery. A recording made during delivery is a medical document that can be used for a comprehensive assessment of the course of delivery, as well as for legal protection of the clinician in complex situations. However, the method has insufficient specificity regarding the diagnosis of acute hypoxia. At present, there are no methods to accurately predict fetal hypoxia, and therefore, to solve this problem, CTG should be routinely performed on all new mothers. Increased experience with CTG helps to interpret the results and improves the outcome of childbirth. However, the method of delivery is always determined by the clinical situation. Despite the wide practical application of CTG, a number of unresolved issues remain, which requires further development of fetal monitoring methods.

Intrauterine fetal hypoxia is one of the leading cause of perinatal mortality and morbidity. This can eventually lead to severe neurological damage like cerebral palsy and in extreme cases to fetal demise. It is thus necessary to monitor the fetus during intrapartum and antepartum period. Cardiotocograph (CTG) as a method of assessing the status of the fetus had been in use for last six decades. Nowadays it is the most widely used non-invasive technique for the continuous monitoring of the fetal heart rate (FHR) and the uterine contraction pressure (UCP). Though its introduction limited the birth related problems, the accuracy of interpretation was hindered by quite a few factors. Different guidelines that are provided for the interpretation are based on crisp logic which fails to capture the inherent uncertainty present in the medical diagnosis. Misinterpretations had led to inaccurate diagnosis which resulted in many medico-legal litigations. The vagueness present in the physician’s evaluation is best modeled using soft-computing based techniques. In this paper authors used the CTG dataset from UCI Irvine Machine Learning Data Repository which contains 2126 data and each data-point is represented by 37 features. Dimensionality of the feature set was reduced using different automated methods as well as manually by the physicians. The resulting data sets were classified using various machine learning algorithms. Aim of this study is to establish which set of features is best suited to give good insight into the status of the fetus and also determine the most effective machine learning technique for this purpose. The accuracy of the outcomes were measured using statistical methods such as sensitivity, specificity, precision, F-Measure, confusion matrix and kappa value. We obtained an accuracy of 99.91% and kappa measure of 0.997 when the feature set was reduced using MRMR.

Sensitive biomarkers are needed to rapidly identify high-risk infants after hypoxia-ischemia for neuroprotective treatment. Hypotension is a key determinant of hypoxic-ischemic neural injury, and a potent stimulus of humoral pressors including angiotensin-II and arginine vasopressin. We therefore aimed to quantify the relationship between vasopressin and angiotensin-II levels in the latent phase after hypoxia-ischemia induced by umbilical cord occlusion (UCO) with both the severity of preceding hypotension and subsequent neuronal injury.Chronically instrumented near-term fetal sheep underwent sham-UCO or UCO for either 15 min or until mean arterial pressure was8 mmHg. Neuronal injury was assessed after 72 h recovery.Umbilical cord occlusion was associated with severe hypotension that recovered after UCO; two fetuses developed profound secondary hypotension within 6 h and died. Vasopressin levels but not angiotensin-II were significantly elevated 1-3 h after UCO and were closely associated with the severity of hypotension during UCO and the subsequent severity of neuronal loss in the parasagittal and lateral cortex, caudate nucleus and putamen. The Youden cut-point for vasopressin at 1 h was 180.0 pmol/L, with sensitivity 100% and specificity 92.3% for severe neuronal injury or death.Vasopressin levels shortly after moderate-severe hypoxia-ischemia may be a useful early biomarker to guide the timely implementation of neuroprotective treatment.It can be difficuIt to rapidly identify infants who might benefit from therapeutic hypothermia. We investigated whether increases in plasma pressor hormones early after hypoxia-ischemia were biomarkers for neonatal hypoxic-ischemic encephalopathy using near-term fetal sheep. Arginine vasopressin levels were elevated at 1-3 h after hypoxia-ischemia and were predictive of the severity of preceding hypotension and subsequent risk of severe neuronal injury or death after hypoxia-ischemia. Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.

The aim of the study was to investigate foetal cardiac function using the modified myocardial performance index (Mod-MPI) in poorly controlled gestational diabetics and its link with intrauterine markers for hypoxia and to an adverse outcome. In a prospective, cross sectional study, 44 consecutive women with severe or poorly controlled gestational diabetic pregnancies in their third trimester on insulin therapy were recruited and matched with 44 women with normal pregnancies which served as the control group. Using Doppler echocardiography the foetal Mod-MPI was calculated. The foetal Mod-MPI was significantly higher in the diabetic group compared to the controls indicating significant myocardial dysfunction. The Mod-MPI served as an excellent marker of adverse outcomes. Foetal myocardial function was significantly impaired in poorly controlled gestational diabetics and there was a significant link of Mod-MPI to intrauterine markers of hypoxia, as well as to an adverse outcome. Mod-MPI has the potential to improve foetal surveillance in gestational diabetes.IMPACT STATEMENT

Background Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD. Methods Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n = 4) and control animals (112 days; n = 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n = 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days. Results Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance. Conclusions Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.

A low fetal cerebroplacental ratio (CPR) in late pregnancy is a marker of a fetus that has failed to reach its growth potential and is associated with a variety of perinatal and pregnancy complications. It is not known if it is also correlated with aberrations in angiogenic, hypoxia-responsive or inflammatory cytokine levels in the maternal circulation. We investigated if there were any differences in levels of biomarkers of angiogenesis, endothelial cell dysfunction, hypoxia and/or inflammation in term pregnancies with a low fetal CPR compared to controls. We hypothesized that as the CPR is a marker of suboptimal growth, this would be reflected in a shift towards upregulation of hypoxia-responsive factors even in non-small for gestational age fetuses.We used Multiplex ELISA to measure a panel of 28 candidate biomarkers of angiogenesis and/or hypoxia in pre-labour maternal plasma from 113 women at term, stratified for CPR10th centile vs. CPR10th centile. Plasma levels of the biomarkers were measured using 2 multiplex Luminex assays - a commercially available human angiogenesis/growth factor panel (RD Systems®), comprising 15 analytes and an in-house custom panel of a further 13 candidate biomarkers.Of the 28 candidate biomarkers investigated, we found significantly elevated levels of Carbonic Anhydrase 9 and soluble Fms-like tyrosine kinase (Vascular Endothelial Growth Factor Receptor 1), and lower levels of Placental Growth Factor in plasma from women with a low fetal CPR. The soluble Fms-like tyrosine kinase-1/Placental Growth Factor ratio was also markedly elevated in this cohort. We also demonstrated significant inverse correlations between the fetal CPR and Carbonic Anydrase 9, soluble Fms-like tyrosine kinase and Hepatocyte Growth Factor.A low fetal CPR is associated with changes in some hypoxia-responsive and angiogenesis factors in the maternal circulation in pregnancies with normally grown fetuses.

Background It is crucial to interpret fetal heart rate patterns with a focus on the pattern evolution during labor to estimate the relationship between cerebral palsy and delivery. However, nationwide data are not available. Objective The aim of our study was to demonstrate the features of fetal heart rate pattern evolution and estimate the timing of fetal brain injury during labor in cerebral palsy cases. Study Design In this longitudinal study, 1069 consecutive intrapartum fetal heart rate strips from infants with severe cerebral palsy at or beyond 34 weeks of gestation, were analyzed. They were categorized as follows: (1) continuous bradycardia (Bradycardia), (2) persistently nonreassuring, (3) reassuring-prolonged deceleration, (4) Hon’s pattern, and (5) persistently reassuring. The clinical factors underlying cerebral palsy in each group were assessed. Results Hypoxic brain injury during labor (those in the reassuring-prolonged deceleration and Hon’s pattern groups) accounted for 31.5% of severe cerebral palsy cases and at least 30% of those developed during the antenatal period. Of the 1069 cases, 7.86% were classified as continuous bradycardia (n=84), 21.7% as persistently nonreassuring (n=232), 15.6% as reassuring-prolonged deceleration (n=167), 15.9% as Hon’s pattern (n=170), 19.8% as persistently reassuring (n=212), and 19.1% were unclassified (n=204). The overall interobserver agreement was moderate (kappa 0.59). Placental abruption was the most common cause (31.9%) of cerebral palsy, accounting for almost 90% of cases in the continuous bradycardia group (64 of 73). Among the cases in the Hon’s pattern group (n=67), umbilical cord abnormalities were the most common clinical factor for cerebral palsy development (29.9%), followed by placental abruption (20.9%), and inappropriate operative vaginal delivery (13.4%). Conclusion Intrapartum hypoxic brain injury accounted for approximately 30% of severe cerebral palsy cases, whereas a substantial proportion of the cases were suspected to have either a prenatal or postnatal onset. Up to 16% of cerebral palsy cases may be preventable by placing a greater focus on the earlier changes seen in the Hon’s fetal heart rate progression.

Supplemental Digital Content is available in the text., Work in preclinical animal models has established that pregnancy complicated by chronic fetal hypoxia and oxidative stress programmes cardiovascular dysfunction in adult offspring. Translating this to the human condition comes with challenges, including the early diagnosis of affected individuals to improve clinical outcomes. We hypothesize that components of programmed cardiovascular dysfunction in offspring can be identified in vivo via analysis of blood pressure variability and heart rate variability and that maternal treatment with the mitochondria-targeted antioxidant MitoQ is protective. Pregnant rats were exposed to normoxia or hypoxia (13% O2) ±MitoQ (500 μM in water), from 6 to 20 days gestation. Offspring were maintained in normoxia postnatally. At 16 weeks of age, 1 male per litter was instrumented with vascular catheters and a femoral blood flow probe under isoflurane anesthesia. After recovery, arterial blood pressure and femoral flow were recorded in conscious, free-moving rats and analyzed. Offspring of hypoxic pregnancy had (1) increased very-low-frequency blood pressure variability (A) and heart rate variability (B), indices consistent with impaired endothelial function and (2) increased heart rate variability low/high-frequency ratio (C) and low-frequency blood pressure variability (D), indices of cardiac and vascular sympathetic hyperreactivity, respectively. MitoQ ameliorated A and B but not C and D. We show that asymptomatic cardiovascular dysfunction in adult offspring programmed by hypoxic pregnancy can be diagnosed in vivo by blood pressure variability and heart rate variability, suggesting that these noninvasive biomarkers could be translated to the clinical setting. MitoQ protected against programmed endothelial dysfunction but not sympathetic hyperreactivity, highlighting the divergent programming mechanisms involved.

During labor, uterine contractions trigger the response of the autonomic nervous system (ANS) of the fetus, producing sawtooth-like decelerations in the fetal heart rate (FHR) series. Under chronic hypoxia, ANS is known to regulate FHR differently with respect to healthy fetuses. In this study, we hypothesized that such different ANS regulation might also lead to a change in the FHR deceleration morphology. The hypothesis was tested in an animal model comprising 7 normoxic and 5 chronically hypoxic fetuses that underwent a protocol of umbilical cord occlusions (UCOs). Deceleration morphologies in the fetal inter-beat time interval (FRR) series were modeled using a trapezoid with four parameters, i.e., baseline b, deceleration depth a, UCO response time τu and recovery time τr. Comparing normoxic and hypoxic sheep, we found a clear difference for τu (24.8 ± 9.4 vs 39.8 ± 9.7 s; p < 0.05), a (268.1 ± 109.5 vs 373.0 ± 46.0 ms; p < 0.1) and Δτ = τu − τr (13.2 ± 6.9 vs 23.9 ± 7.5 s; p < 0.05). Therefore, the animal model supported the hypothesis that hypoxic fetuses have a longer response time τu and larger asymmetry Δτ as a response to UCOs. Assessing these morphological parameters during labor is challenging due to non-stationarity, phase desynchronization and noise. For this reason, in the second part of the study, we quantified whether acceleration capacity (AC), deceleration capacity (DC), and deceleration reserve (DR), computed through Phase-Rectified Signal Averaging (PRSA, known to be robust to noise), were correlated with the morphological parameters. DR and DC correlated with Δτ and τu for a wide range of the PRSA parameter T (max Pearson’s correlation ρ = 0.9, p < 0.05, and ρ = 0.6, p < 0.1, respectively). In conclusion, deceleration morphologies have been found to differ between normoxic and hypoxic sheep fetuses during UCOs. The same difference can be assessed through PRSA based parameters, further motivating future investigations on the translational potential of this methodology on human data.

Background:CTG remains the only non-invasive tool available to the maternity team for continuous monitoring of fetal well-being during labour. Despite widespread use and investment in staff training, difficulty with CTG interpretation continues to be identified as a problem in cases of fetal hypoxia, which often results in permanent brain injury. Given the recent advances in AI, it is hoped that its application to CTG will offer a better, less subjective and more reliable method of CTG interpretation.Objectives:This mini-review examines the literature and discusses the impediments to the success of AI application to CTG thus far. Prior randomised control trials (RCTs) of CTG decision support systems are reviewed from technical and clinical perspectives. A selection of novel engineering approaches, not yet validated in RCTs, are also reviewed. The review presents the key challenges that need to be addressed in order to develop a robust AI tool to identify fetal distress in a timely manner so that appropriate intervention can be made.Results:The decision support systems used in three RCTs were reviewed, summarising the algorithms, the outcomes of the trials and the limitations. Preliminary work suggests that the inclusion of clinical data can improve the performance of AI-assisted CTG. Combined with newer approaches to the classification of traces, this offers promise for rewarding future development.

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO2 and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model., This research was funded by CELLEX FOUNDATION. This work was financially supported by The Cellex Foundation and the Agència de Gestió d’Ajuts Universitaris i de Recerca (Grant 2017 SGR 1531). Additionally, E.E. has received support from the Departament de Salut (Grant SLT008/18/00156). The Nanobioengineering group at the Institute of Bioengineering of Catalonia (IBEC) has received support from the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (No. 2017 SGR 1079) and is part of the CERCA Programme / Generalitat de Catalunya and is supported by the Severo Ochoa programme of the Spanish Ministry of Science and Competitiveness (Grant SEV-2014-0425 (2015–2019)). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. L.R. would also like to acknowledge her support within the BEST Postdoctoral Programme, funded by the European Commission under Horizon 2020’s Marie Skłodowska-Curie Actions COFUND scheme (Grant Agreement No. 712754).

Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic HRV exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n=6) or hypoxia (10% inspired O2, n=9) for the last third of gestation (105-138 dG; term~145 dG) in isobaric chambers. At 138dG, isolated hearts were studied using a Langendorff preparation. We calculated basal iFHRV matrix indices across five signal-analytical domains from the systolic peaks within 15 min segments in each heart. Significance was assumed at p2=0.32 and R2=0.63, respectively). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a lower complexity in iFHRV.Key points summaryWe introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction.Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy.Therefore, the isolated fetal heart carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy.Indices of iFHRV may improve fetal health surveillance by helping to diagnose prediction of fetal hypoxia and acidaemia during antenatal or intra-partum fetal compromise.

We aimed to evaluate maternal serum thiol/disulphide homeostasis in pregnancies complicated by fetal distress (FD). A total of 100 patients beyond the 34th week of pregnancy were included in this study, and they were divided into two groups. The study group included 50 patients who had been diagnosed with FD; the control group was composed of 50 patients who had shown no signs of FD and who had undergone an elective (previous) caesarean section (CS). The native thiol, total thiol and native thiol/total thiol (%) concentrations were lower in Group 1 patients than Group 2 patients (

Objective Prediction of hypoxic acidemia in neonates using cardiotocogram (CTG) features continues to be challenging. The objective of this study was to explore the association between contraction frequency and fetal heart rate characteristics with hypoxic acidemia in low-risk women in labour. Methods Cases were singleton, vertex, in labour with umbilical artery pH ≤7.05. Controls were the next consecutive birth with pH ≥7.15, matched for gestational age, maternal age, and parity. Obstetrical complications and maternal comorbidities were excluded. CTG features were tabulated for the last 2 hours of labour. “Cut-off points” above which acidemia is more likely were calculated for significant variables (Canadian Task Force Classification II-2). Results A total of 190 case-control pairs were included. Among cases we observed greater marked variability, tachycardia, variable and late decelerations, and fewer accelerations and early decelerations. A conditional logistic regression model included tachycardia, accelerations, total decelerations, and contractions. Tachycardia and total decelerations (variable, late) were significant. Tachycardia was most specific in predicting neonatal acidemia, whereas total (variable, late) decelerations were most sensitive. Late decelerations alone and total (variable, late) decelerations were similarly predictive for detecting neonatal acidemia using receiver-operating characteristic analysis; tachycardia was least discriminatory. Acidemic neonates were more likely to have CTGs with ≥11 late decelerations, ≥15 total decelerations (variable, late), and at least 80 minutes of tachycardia in the last 2 hours of labour. Conclusion Tachycardia, late decelerations, and total (variable, late) decelerations were associated with acidosis in our population. Identifying “cut-off” points for the frequency of significant CTG features should be explored as a potential screening tool for neonatal acidemia.

Electronic foetal monitoring using cardiotocography is aimed at the timely recognition and management of foetal hypoxia. The primary objective of this study was to examine whether a relationship exists between the types of foetal hypoxia (acute, subacute, evolving, chronic), as identified on cardiotocography and the nature of hypoxic ischaemic encephalopathy, as observed on MRI scans after birth. We conducted a retrospective study of 16 babies born (out of 52,187 births) at St George's Hospital in London during 2006-2017 with a postnatal diagnosis of HIE. Of the 16 babies, only 11 had both MRI scans and CTG traces available. Of those, 9 showed evidence of intrapartum hypoxia on CTG, but only 6 demonstrated evidence of HIE on MRI. Those with acute hypoxia showed abnormalities in the basal ganglia and thalami. A gradually evolving hypoxia or subacute hypoxia was associated with lesions in myelination and cerebral cortex.Impact Statement

A case of abdominal delivery of the patient with acute intrapartum fetal hypoxia associated with a circumvallate placenta and a furcate cord insertion with the rupture of a chorionic plate vessel is reported.

Background All guidelines regarding electronic fetal heart monitoring (EFM) before 2008 were designed to avoid more hypoxia than acidosis. In addition, the results of the Cochrane meta-analysis of 2013 do not show a significant improvement in neonatal outcomes using EFM or intermittent auscultation (IA). Objectives We retrospectively evaluated the results on delivery outcomes arising from a comparison between EFM and IA during labor of 2 specific and high-quality trials. We hypothesized that revisiting the delivery outcomes through the adoption of the recent National Institute of Child Health and Human Development (NICHHD) guidelines, the reported delivery outcomes would be different. Material and methods The study retrospectively evaluated the results on delivery outcomes arising from the comparison between EFM and IA during labor of the "Dublin trial" and "Vintzileos trial" published, respectively, in 1985 and 1993. A translational model was constructed to recalculate these results, applying a correction factor to estimate the number of pathological patterns using the NICHHD guidelines for EFM. Results After the reevaluation of the 2 trials using the proposed correction factor, the comparison of the recalculated cesarean section and operative delivery rates for fetal distress between EFM and IA group were no longer statistically significant, both in the Dublin trial and Vintzileos trial. Even the comparison of the recalculated incidence of the rate of non-reassuring fetal heart rate (FHR) patterns in the EFM and IA groups has not given any indication of significance for the Vintzileos trial. Conclusions Our results lead to reconsidering the results of the Dublin trial and Vintzileos trial in terms of operational rates of births, hypothesizing that these results would have been significantly lower if FHR traces were interpreted using the current NICHHD guidelines, which aim to identify potential acidotic fetuses rather than hypoxic ones.

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

Fetal concentrations of GFAP and UCH-L1 are elevated in umbilical arterial (UmA) blood of neonates with birth asphyxia plus neonatal encephalopathy (NE), but their source and role of placental clearance/synthesis is unknown. Prospective cohort study of term neonates to (a) determine UmA and venous (UmV) blood concentrations of GFAP and UCH-L1 in term uncomplicated pregnancies and their placental synthesis and/or clearance and (b) compare UmA concentrations in uncomplicated pregnancies with those complicated by fetal hypoxia–asphyxia+NE. Three term groups were studied: uncomplicated cesarean delivery without labor (Group 1, n = 15), uncomplicated vaginal delivery with labor (Group 2, n = 15), and perinatal hypoxia–asphyxia+NE (Group 3, n = 8). UmA GFAP concentrations were lower in Group 1 vs. 2 (P = 0.02) and both demonstrated 100% placental clearance. In contrast, UmA and UmV UCH-L1 concentrations were not unaffected by labor. Group 3 UmA GFAP concentrations were 30- and 8-fold higher than Groups 1 and 2, respectively, P = 0.02, whereas UmA UCH-L1 concentrations were similar in all groups. UmA GFAP is derived from the fetus, and circulating levels, which are modulated by placental clearance, increase during uncomplicated labor and more so in the presence of fetal hypoxia–asphyxia+NE, providing a better biomarker than UCH-L1 for hypoxia–asphyxia+NE.

We tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of congenital heart disease, would lead to abnormal neurodevelopment.Eight mid-gestation fetal sheep were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid-filled environment for 22 ± 2 days under normoxic or hypoxic conditions. Total parenteral nutrition was provided. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were fixed for histopathology. Neurons were quantified in white matter tracts, and the thickness of the external granular layer of the cerebellum was measured to assess neuronal migration. Capillary density and myelination were quantified in white matter. Data were analyzed with unpaired Student t tests or 1-way analysis of variance, as appropriate.Oxygen delivery was reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min, P .01), but umbilical blood flow and caloric delivery were not different between the 2 groups. Compared with normoxic and control animals, hypoxic fetuses had reduced neuronal density and increased external granular layer thickness. Compared with normoxic and control animals, hypoxic fetuses had increased capillary density in white matter. Cortical myelin integrity score was lower in the hypoxic group compared with normoxic and control animals. There was a significant negative correlation between myelin integrity and capillary density.Chronic fetal hypoxia leads to white matter hyper-vascularity, decreased neuronal density, and impaired myelination, similar to the neuropathologic findings observed in children with congenital heart disease. These findings support the hypothesis that fetal hypoxia, even in the setting of normal caloric delivery, impairs neurodevelopment.

Hypoxic-ischemic brain damage (HIBD) occurs due to intrauterine hypoxia ischemia influencing the energy supply for fetal brain cells, which affects the metabolism of the brain to make the brain suffer a severe damage. Erythropoietin (EPO), which regulates hemacytopoiesis, is a kind of cytokine. EPO is sensitive to hypoxia ischemia. In this study, we aimed to investigate the effect of EPO on the expression of Fas/FasL in brain tissues of neonatal rats with HIBD. Neonatal rats were assigned randomly to sham, HIBD, and EPO groups. Five time points for observation were 6, 12, 24, 48, and 72 h after the HIBD rat model had been established, respectively. In the HIBD group, Fas/FasL expression began to rise at 6 h, reached the peak at 12–24 h, and dropped from 24 h. In the EPO group, the expression of Fas/FasL was lower than those in HIBD group at 12, 24, and 48 h (P

To investigate the performance of screening for adverse perinatal outcome by the cerebroplacental ratio (CPR) measured within 24 h prior to induction of labor.This was a prospective observational study of 1902 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) within 24 h before induction of labor. The measured UA-PI and MCA-PI and their ratio were converted to multiples of the median after adjustment for gestational age. Univariable and multivariable logistic regression analysis was used to determine whether CPR improved the prediction of adverse perinatal outcome provided by maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for Cesarean section for presumed fetal distress and adverse neonatal outcome, which included umbilical arterial or venous cord blood pH ≤ 7 and ≤ 7.1, respectively, 5-min Apgar score 7, admission to the neonatal intensive care unit for 24 h or hypoxic ischemic encephalopathy.A combination of maternal and pregnancy characteristics, including age, weight, racial origin, previous obstetric history, pre-eclampsia, gestational age at delivery and amniotic fluid volume, identified 39% of pregnancies requiring Cesarean section for fetal distress at a FPR of 10%; addition of CPR did not improve the performance of screening. In screening for adverse neonatal outcome by a combination of parity and CPR, the DR was 17% at a FPR of 10%.Low CPR, measured within 24 h prior to induction of labor, is associated with increased risk of Cesarean section for fetal distress and adverse neonatal outcome, but the performance of CPR for such surrogate measures of fetal hypoxic morbidity is poor. Copyright © 2018 ISUOG. Published by John WileySons Ltd.

Aim: to identify the risk factors of meconium aspiration and study its impact on neonatal adaptation.Materials and methods. Medical records of 44 women and their infants were studied.Results. In 85 % of cases, the diagnosis of complicated pregnancy was made, in 100 % cases – there was a complicated delivery; 100 % of newborns were put on mechanical ventilation, 95 % of them were diagnosed with cerebral depression syndrome, and 72.5 % – with aspiration pneumonia. Conclusion. A differentiated approach to the management of pregnancy and labor will reduce perinatal morbidity.

Objective: Determination of lactate in fetal scalp blood (FBS) during labour has been recognised since the 1970s. The internationally accepted cutoff of >4.8 mmol/l indicating fetal acidosis is exclusive for the point-of-care device (POC) LactatePro™, which is no longer in production. The aim of this study was to establish a new cutoff for scalp lactate based on neonatal outcomes with the use of the StatstripLactate®/StatstripXpress® Lactate system, the only POC designed for hospital use. Design: Observational study. Setting: January 2016 to March 2020 labouring women with indication for FBS were prospectively included from seven Swedish and one Australian delivery unit. Population: Inclusion criteria: singleton pregnancy, vertex presentation, ≥35+0 weeks of gestation. Method: Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25 minutes from FBS to delivery were included in the final calculations. Main outcome measures: Metabolic acidosis in cord blood defined as pH 10 mmol/l and/or lactate >10 mmol/l. Results: A total of 3334 women were enrolled of whom 799 were delivered within 25 minutes. The areas under the receiver operating characteristics curves (AUC) and corresponding optimal cutoff values were as follows; metabolic acidosis AUC 0.87 (95% CI 0.77–0.97), cutoff 5.7 mmol/l; pH

Coronavirus disease 2019 (COVID-19) pneumonia rarely occurs in pregnant women. Case reports indicate that fibrin and lymphohistiocytic lesions in placentas may be typical. However, a meta-analysis to clarify whether there is a COVID-19-associated pattern of placental lesions has not yet been conducted. Systematic literature search with meta-analysis of publications on 10 or more cases of pregnancy with SARS-CoV-2 infection and placenta examination (30 publications from 2019 to 2021; 1452 placenta cases) was performed. The meta-analysis did not reveal any COVID-19-specific placenta changes. The incidence of both vascular and inflammatory lesions was mainly comparable to that of non-COVID-19 pregnancies. Transplacental viral transmission is very rare and there are no typical placental changes. The most important prognostic factor seems to be maternal-fetal hypoxia in the context of pneumonia.

BACKGROUND Perinatal asphyxia can cause cerebral palsy and hypoxic - ischemic encephalopathy. They are public health problems because they cause permanent disability. METHODS This is a retrospective, analytical, observational study. 162 cases of mothers whose children experienced fetal asphyxia were compare to 361 controls where this condition did not occur. The variables analyzed were classified as: prepartum, intrapartum and organizational. RESULTS Assisted Reproductive Technology obtained pregnancies, smoking, maternal body mass index, lack of one to one assistance during labor, birth on a day of high volume activity increased the risk of fetal asphyxia, as well as other traditionally linked factors like shoulder distocia or age over 35 years. CONCLUSIONS Cerebral palsy cannot always be prevented because it is a syndrome with a multitude of potential causes. But a small number of cases is likely to be linked to acute intrapartum events that could be limited by changing organizational policies such as staff training and implementing team work and discussion. Our paper proposes strategies to try and modify organizational risk factors and therefore limit the incidence of fetal asphyxia.

Late-onset fetal growth restriction (FGR) accounts for approximately 70-80% of all cases of FGR secondary to uteroplacental insufficiency. It is associated with an increased incidence of adverse antepartum and perinatal events, which in most instances result from hypoxic insults either present at the onset of labor or supervening during labor as a result of uterine contractions. Labor represents a stressful event for the fetoplacental unit being uterine contractions associated with an up-to 60% reduction of the uteroplacental perfusion. Intrapartum fetal heart rate monitoring by means of cardiotocography (CTG) currently represents the mainstay for the identification of fetal hypoxia during labor and is recommended for the fetal surveillance during labor in the case of FGR or other conditions associated with an increased risk of intrapartum hypoxia. In this review we discuss the potential implications of an impaired placental function on the intrapartum adaptation to the hypoxic stress and the role of the CTG and alternative techniques for the intrapartum monitoring of the fetal wellbeing in the context of FGR secondary to uteroplacental insufficiency.

Mitochondria-derived oxidative stress during fetal development increases cardiovascular risk in adult offspring of pregnancies complicated by chronic fetal hypoxia. We investigated the efficacy of the mitochondria-targeted antioxidant MitoQ in preventing cardiovascular dysfunction in adult rat offspring exposed to gestational hypoxia, integrating functional experiments in vivo, with those at the isolated organ and molecular levels. Rats were randomized to normoxic or hypoxic (13%-14% O2 ) pregnancy ± MitoQ (500 μM day-1 ) in the maternal drinking water. At 4 months of age, one cohort of male offspring was chronically instrumented with vascular catheters and flow probes to test in vivo cardiovascular function. In a second cohort, the heart was isolated and mounted onto a Langendorff preparation. To establish mechanisms linking gestational hypoxia with cardiovascular dysfunction and protection by MitoQ, we quantified the expression of antioxidant system, β-adrenergic signaling, and calcium handling genes in the fetus and adult, in frozen tissues from a third cohort. Maternal MitoQ in hypoxic pregnancy protected offspring against increased α1 -adrenergic reactivity of the cardiovascular system, enhanced reactive hyperemia in peripheral vascular beds, and sympathetic dominance, hypercontractility and diastolic dysfunction in the heart. Inhibition of Nfe2l2-mediated oxidative stress in the fetal heart and preservation of calcium regulatory responses in the hearts of fetal and adult offspring link molecular mechanisms to the protective actions of MitoQ treatment of hypoxic pregnancy. Therefore, these data show the efficacy of MitoQ in buffering mitochondrial stress through NADPH-induced oxidative damage and the prevention of programmed cardiovascular disease in adult offspring of hypoxic pregnancy.

BackgroundCOVID-19 is the largest outbreak to strike humanity. The wide scale of fatalities and morbidities lead to a concurrent pandemic of uncertainty in scientific evidence. Conflicting evidences are released on daily basis about the neonatal outcomes of COVID-19-positive mothers. The aim of this study was to use the relevant case reports and series to determine the percentage of newborns who test positive for COVID-19 who are born to COVID-19-positive mothers. Secondary outcomes included examining laboratory abnormalities among COVID-19-positive neonates, and any depicted placental abnormalities in COVID-19-positive mothers. For this purpose, systematic review was performed on all studies reporting primary data on fetus-mother pairs with COVID-19. Data bases were searched for studies that met our inclusion and exclusion criteria.ResultsFinal screening revealed 67 studies, from which the primary data of 1787 COVID-19 mothers were identified and had their pregnancy outcome analyzed. Only 2.8% of infants born to COVID-19-positive mothers tested positive, and this finding is identical to percentages reported in former Coronaviridae outbreaks, whereas 20% manifested with intrauterine hypoxia alongside placental abnormalities suggestive of heavy placental vaso-occlusive involvement.ConclusionsThese findings suggest that while vertical transmission is unlikely, there appears to be an underlying risk of placental insufficiency due to the prothrombotic tendency observed in COVID-19 infection. Guidelines for proper prophylactic anticoagulation in COVID-positive mothers need to be established.