Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation: A Systematic Review and Meta-analysis.

Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. Data Sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. Study Selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded. Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. Main Outcomes and Measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission. Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and Relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.

Altered Cardiovascular Defense to Hypotensive Stress in the Chronically Hypoxic Fetus.

The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by the inability to study the human fetus non-invasively for long period of gestation. Using experimental animals, there has also been an inability to induce gestational hypoxia while recording fetal cardiovascular function as the hypoxic pregnancy is occurring. We use novel technology in sheep pregnancy that combines induction of controlled chronic hypoxia with simultaneous, wireless recording of blood pressure and blood flow signals from the fetus. Here, we investigated the cardiovascular defense of the hypoxic fetus to superimposed acute hypotension. Pregnant ewes carrying singleton fetuses surgically prepared with catheters and flow probes were randomly exposed to normoxia or chronic hypoxia from 121±1 days of gestation (term ≈145 days). After 10 days of exposure, fetuses were subjected to acute hypotension via fetal nitroprusside intravenous infusion. Underlying in vivo mechanisms were explored by (1) analyzing fetal cardiac and peripheral vasomotor baroreflex function; (2) measuring the fetal plasma catecholamines; and (3) establishing fetal femoral vasoconstrictor responses to the α1-adrenergic agonist phenylephrine. Relative to controls, chronically hypoxic fetal sheep had reversed cardiac and impaired vasomotor baroreflex function, despite similar noradrenaline and greater adrenaline increments in plasma during hypotension. Chronic hypoxia markedly diminished the fetal vasopressor responses to phenylephrine. Therefore, we show that the chronically hypoxic fetus displays markedly different cardiovascular responses to acute hypotension, providing in vivo evidence of mechanisms linking its greater susceptibility to superimposed stress.

Effectiveness of fetal scalp stimulation test in assessing fetal wellbeing during labor, a retrospective cohort study.

BACKGROUND: It is discussed whether fetal scalp stimulation (FSS) test is a reliable complimentary tool to cardiotocography (CTG) to assess fetal wellbeing during labor. The test is based on the assumption that a well-oxygenated fetus, in contrast to the depressed fetus, will respond to a certain stimulus. The aim of this study was to investigate the effectiveness of the FSS-test. METHODS: A retrospective observational study carried out Copenhagen University Hospital, Herlev, Denmark. Laboring women with singleton pregnancies in cephalic presentation after gestation week 33 and indication for fetal blood sampling (FBS) were eligible for inclusion. The FSS-test was classified as positive when an acceleration was absent at the time of FBS and negative when an acceleration was present. Lactate in scalp blood was measured by the point-of-care device LactatePro™ and pH in artery umbilical cord blood by the stationary blood gas analyzer ABL800. Lactate level < 4.2 mmol/L in scalp blood and arterial cord pH > 7.1 were cut-offs for normality. RESULTS: Three hundred eighty-five women were included. The cohort was divided by the FBS-to-delivery time: Group 1 (n = 128) ≤ 20 min, Group 2 (n = 117) 21-59 min and Group 3 (n = 140) ≥ 60 min. The proportion of FSS-positive tests differed significantly between the groups (p < 0.000). In Group 1 the sensitivity, specificity and likelihoods for scalp lactate ≥4.2 mmol/L were 81.5 (95% CI 67-90.1), 13.3 18.5 (95% CI 5.9-24.6), LHR+ 0.94 (95% CI 0.8-1.1) and LHR - 1.4 (95% CI 0.6-3.2) and for umbilical artery pH ≤ 7.10 the values were 82.6% (95% CI 61.2-95.1), 16% (95% CI 9.4-24.7), 1.0 (95% CI 0.8-1.2) and 1.1 (95% CI 0.4-3) respectively. Regardless of the FBS-to-delivery time the LHR+ for lactate ≥4.2 mmol/L increased to 1.38 (95% CI 1.2-1.6). CONCLUSION: The effectiveness of scalp stimulation test was poor for both ruling in and out fetal hypoxia during labor. Absence of a provoked acceleration seems to be a normal phenomenon in the second stage of labor.

Is obesity in pregnancy associated with signs of chronic fetal hypoxia?

INTRODUCTION: The prevalence of obesity in pregnancy is increasing worldwide. Maternal obesity increases risks of severe fetal and neonatal complications. The underlying pathophysiological mechanisms are unclear. One possible contributing factor could be chronic fetal hypoxia. The aim of this study was to compare placentas from women with and without obesity with respect to placental lesions, which could reflect compensatory mechanisms in response to chronic fetal hypoxia as well as lesions possibly leading to chronic fetal hypoxia. In addition, levels of erythropoietin in cord blood were compared between offspring of lean and obese women. MATERIAL AND METHODS: This cohort study included 180 women with uneventful, full-term, singleton pregnancies, out of which 91 lean women had a body mass index (BMI) of 18.5-24.9 kg/m2 and 89 women had obesity (BMI ≥30 kg/m2 ). Women were recruited at Södersjukhuset between 16 October 2018 and 2 December 2019. Placentas were investigated by two senior perinatal pathologists, who were blinded for maternal BMI. Cord blood was analyzed for levels of erythropoietin. RESULTS: Levels of erythropoietin in cord blood increased with maternal BMI (P = .01, ß = 0.97, 95% CI 0.27-1.68). There was no difference between placentas of obese and lean women in number of placental lesions reflecting chronic fetal hypoxia or in lesions that could possibly lead to chronic fetal hypoxia. CONCLUSIONS: This study of term and uneventful pregnancies demonstrated a positive association between maternal obesity and concentrations of erythropoietin in cord blood at birth. This finding supports the hypothesis of chronic fetal hypoxia as a risk factor for complications in the pregnancies of obese women. There were no differences in lesions associated with hypoxia between placentas of obese and lean women.

Placental delayed villous maturation is associated with evidence of chronic fetal hypoxia.

Background Normal development of the human placenta, referred to as villous tree maturation, entails formation of the vasculosyncytial membranes. These structures develop by the approximation of syncytiotrophoblasts with the villous capillary endothelium and constitute the most efficient sites of gaseous exchange in the placenta. Defective maturation of the villous tree can lead to deficient vasculosyncytial membranes, implicated in the high incidence of hypoxic complications. Hypoxia, in turn, can stimulate production of erythropoietin, whereby increased fetal plasma or amniotic fluid concentrations of this hormone reflect fetal hypoxemia. The current study was undertaken to determine whether delayed villous maturation is associated with changes in amniotic fluid erythropoietin concentrations. Methods Placental histologic examination was performed using hematoxylin and eosin. Subsequent to histologic assessment of delayed villous maturation, the diagnosis was confirmed with CD-15 immunohistochemistry. The controls (n = 61) were pregnancies without villous maturation abnormalities, and cases (n = 5) were pregnancies with delayed villous maturation. Amniotic fluid erythropoietin concentrations were measured using a specific immunoassay. Results Concentrations of erythropoietin in the amniotic fluid (1) of controls were less than the limit of detection and (2) of cases with delayed villous maturation were significantly higher than those of controls (P-value = 0.048). Conclusion Delayed villous maturation is associated with higher concentrations of amniotic fluid erythropoietin.

Ex Utero Extracorporeal Support as a Model for Fetal Hypoxia and Brain Dysmaturity.

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.

Maternal serum thiol/disulfide homeostasis in pregnancies complicated by fetal hypoxia.

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 (p < .001). The disulphide, disulphide/native thiol (%) and disulphide/total thiol (%) concentrations were higher in Group 1 patients than Group 2 patients (p < .001). This study suggests that maternal thiol/disulphide homeostasis is impaired in pregnancies complicated by FD.IMPACT STATEMENTWhat is already known about this subject? Oxidative stress (OS) has previously been investigated in FD. This study reports for the first time a new novel and automatic measurement method.What do the results of this study add? This study shows that the thiol balance shifts in the direction of disulphide in the cases of FD.What are the implications of these findings for clinical practice and further research? Thiol balance can be used for the timely diagnosis of FD.

Effects of Vasoactive Medications and Maternal Positioning During Cesarean Delivery on Maternal Hemodynamics and Neonatal Acid-Base Status.

Maternal hemodynamics, positioning, and anesthesia technique for cesarean delivery influence neonatal acid-base balance; direct effects from drugs that cross the placenta also have an influence. Spinal anesthesia limits fetal exposure to depressant drugs and avoids maternal airway instrumentation, but is associated with hypotension. Hypotension may be prevented/treated with vasopressors and intravenous fluids. Current evidence supports phenylephrine as the first-line vasopressor. Fifteen degrees of lateral tilt during cesarean delivery has been advocated to relieve vena caval obstruction, but routine use may be unnecessary in healthy nonobese women having elective cesarean delivery if maternal blood pressure is maintained near baseline.

Neuroapoptosis in newborns with respiratory acidosis at birth.

BACKGROUND: S100B protein is one of the most accurate biomarkers for diagnosis of neuroapoptosis and brain damage. The aim was to evaluate the lactate concentration and acid-base balance (pH, pCO2, pO2, HCO3c and BEb) in umbilical cord blood to predict high risk of neuroapoptosis and analyze the relationship between the levels of these biomarkers and umbilical cord blood S100B protein concentration at birth. METHODS: Apparently healthy newborns were included. S100B protein and blood gas test (lactate and acid-base balance) were determined in umbilical cord blood at birth. Newborns were classified into two groups: with and without high risk of neuroapoptosis. Newborns with high umbilical cord blood S100B protein concentration were considered newborns at high risk of neuroapoptosis. RESULTS: Sixty-one newborns were included, 12 had high risk of neuroapoptosis and 49 did not. S100B protein concentration correlate directly with pCO2 levels (Rho: 0.286, p = .0321) and lactate concentration (Rho: 0.278, p = .0315); and indirectly with pH (Rho: -0.332, p = .01). The analysis of the ROC curves yielded significant curves for pH and pCO2 to predict high risk of neuroapoptosis, pH optimal cutoff value was 7.19 (sensitivity: 50%, specificity: 83.7%, AUC: 0.708); and pCO2 optimal cutoff value was 60 mmHg (sensitivity: 30%, specificity: 85.4%, AUC: 0.705). CONCLUSIONS: Respiratory acidosis is associated to high concentrations of S100B protein in umbilical cord blood at birth. Umbilical cord blood pH and pCO2 may be useful in differentiating newborns at high risk of neuroapoptosis. Umbilical cord blood gas test may be valuable as risk indicator for neuroapoptosis at birth.

Placental clearance/synthesis of neurobiomarkers GFAP and UCH-L1 in healthy term neonates and those with moderate-severe neonatal encephalopathy.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Prediction of Hypoxic Acidemia in Last 2 Hours of Labour in Low-Risk Women.

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.

Chronic intrauterine hypoxia alters neurodevelopment in fetal sheep.

OBJECTIVE: We tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of congenital heart disease, would lead to abnormal neurodevelopment. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Amniotic fluid and umbilical cord serum erythropoietin in term and prolonged pregnancies.

OBJECTIVE: Erythropoietin - a hormone regulating erythropoiesis - is a biomarker of chronic fetal hypoxia. High erythropoietin levels in fetal plasma and amniotic fluid are associated with increased risk of adverse neonatal outcome. Since the risk of perinatal morbidity and mortality is increased in pregnancies beyond 41 gestational weeks, we evaluated erythropoietin levels in amniotic fluid and umbilical cord serum in apparently low-risk term (≥ 37 gestational weeks) and prolonged pregnancies (≥ 41 gestational weeks) with labor induction. STUDY DESIGN: This prospective cohort study comprised 93 singleton pregnancies at 37+0-42+1 gestational weeks, of which prolonged pregnancies numbered 63 (67.7%). Amniotic fluid samples were collected at time of labor induction by amniotomy. Umbilical cord blood samples for evaluation of pH, base excess, and umbilical cord serum erythropoietin were collected at birth. Erythropoietin levels were measured by immunochemiluminometric assay. Normal value of amniotic fluid erythropoietin level was defined as ≤ 3 IU/L, and abnormal value as ≥ 27 IU/L. Normal umbilical cord serum erythropoietin was defined as < 40 IU/L. Data on maternal pregnancy and delivery characteristics and short-term neonatal outcomes such as Apgar score were obtained from the hospital charts. Associations were calculated using Spearman's rank correlation coefficient. The Chi-square test, Fisher's exact test and the Mann-Whitney U test were utilized to determine differences in the study groups. RESULTS: Amniotic fluid erythropoietin levels correlated with gestational age (r = 0.261, p = 0.012) and were higher among prolonged pregnancies as compared to term pregnancies (p = 0.005). There were 78 (83.9%) vaginal deliveries, and among these erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum (r = 0.513, p < 0.000). Umbilical cord serum erythropoietin levels correlated with gestational age among vaginal deliveries (r = 0.250, p = 0.027). Erythropoietin levels in amniotic fluid and umbilical cord serum did not correlate with umbilical artery pH or base excess, or other adverse pregnancy outcome. CONCLUSIONS: In vaginal deliveries erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum. Erythropoietin levels correlated with gestational age, probably due to weakening placental function and relative hypoxemia occurring in advanced gestation. However, in this relatively low-risk study population erythropoietin was not related to adverse delivery outcome.

Arterio-venous blood gas Δvalues for validation of umbilical cord blood samples at birth are not only biased by sample mix ups but also affected by clinical factors.

INTRODUCTION: Traditional validation of umbilical cord blood samples with positive veno-arterial ΔpH and arterio-venous ΔpCO2 values confirms the source of samples, whereas negative Δvalues represent mix-up of samples. To investigate whether this is true, the distributions of V-A ΔpO2 and A-V Δlactate were also explored and related to clinical characteristics. In addition, different cord blood sampling techniques were evaluated. MATERIAL AND METHODS: Register study with cord blood acid-base and clinical data from 27 233 newborns. Clinical characteristics were related to positive, zero and negative Δvalues. Blood samplings from unclamped and double-clamped cords were compared. A two-sided P < 0.05 was considered significant. RESULTS: ΔpH and ΔpCO2 values distributed into positive, around zero, and negative sub-populations, with significant differences in pH and clinical characteristics between sub-populations. No such sub-populations were distinguished for ΔpO2 and Δlactate. The 2.5th and 5th ΔpH percentiles were 0.013 and 0.022, respectively, and for ΔpCO2 0.30 and 0.53 kPa. Applying 5th percentile criteria resulted in 3.5% of "approved" cases showing a ΔpO2  ≤ 0. Puncture and sampling of the unclamped cord resulted in significantly better sample quality. CONCLUSIONS: Unphysiological negative ΔpO2 values occurred despite correct validation with traditional criteria. Δlactate cannot be used for validation because both positive and negative values are physiological. Positive/around zero/negative ΔpH and ΔpCO2 sub-populations were associated with significant differences in pH and clinical characteristics, indicating that defective sampling and sample handling are not the sole explanations for negative Δvalues. Prompt puncture and sampling of the unclamped cord resulted in best sample quality.

Significance of assay of nucleated RBCs in umbilical cord blood in neonates with meconium-stained amniotic fluid.

BACKGROUND: Approximately 8-15% of all infants are born with evidence of meconium-stained amniotic fluid (MSAF). MSAF is a potentially serious sign of fetal compromise and may indicate fetal hypoxia Objectives and aim of the work: The present study was designed to evaluate the relationship between meconium stained amniotic fluid and fetal nucleated red blood cell counts. As well, we aim to evaluate the relationship between the presence of meconium in amniotic fluid and Apgar scores in neonates. SUBJECTS AND METHODS: A prospectively case-controlled study was performed on 40 women with clear amniotic fluid as control and 40 women with meconium-stained amniotic fluid as the study group. At delivery, 2 ml of umbilical cord blood was collected and analyzed for nucleated red blood cell (NRBC). RESULTS: The mean NRBC counts in meconium-stained amniotic fluid was significantly higher than the control group (18.35 ± 7.7 and 9.6 ± 4.96), respectively (p < .001). There were statistically significant differences concerning 1- and 5-min Apgar scores with lower values in the MSAF group (p < .001 and .001, respectively). CONCLUSION: Our results support previous studies which indicate the presence of meconium can be associated with chronic fetal hypoxia as demonstrated by elevated fetal NRBC levels.

Chronically Hypoxic Fetal Lambs Supported by an Extra-Uterine Device Exhibit Mitochondrial Dysfunction and Elevations of Hypoxia Inducible Factor 1-Alpha.

INTRODUCTION: We have recently developed an extra-uterine environment for neonatal development (EXTEND) capable of supporting premature fetal lambs and have been able to replicate hypoxic in utero conditions by controlling fetal oxygen delivery. In this study, we investigated the fetal mitochondrial response to hypoxia. METHODS: Eight premature fetal lambs were delivered via hysterotomy and transitioned to extra-uterine support for 3 weeks. The lambs were divided into 2 groups: normoxic fetuses which maintained physiologic oxygen delivery and hypoxic fetuses in which oxygen delivery was significantly reduced. Control fetuses were delivered via hysterotomy but not cannulated. Measurements of mitochondrial membrane potential (MMP) were performed in peripheral blood mononuclear cells. RESULTS: There were no significant differences in MMP between normoxic EXTEND fetuses and controls. Hypoxic fetuses had significantly more depolarized mitochondria compared to normoxic fetuses overall, and these changes were specifically appreciated in weeks 1 and 2, but not by week 3. Hypoxic fetuses had significantly elevated levels of HIF-1α compared to normoxic fetuses in the first 2 weeks. DISCUSSION: Normoxic fetal lambs supported by EXTEND demonstrate normal mitochondrial function as evidenced by equivalent membrane potentials compared to control fetuses. Hypoxic fetuses exhibit mitochondrial dysfunction, though they do show evidence of adaptation after 3 weeks of hypoxic exposure.

Assessment of lactate production as a response to sustained intrapartum hypoxia in large-for-gestational-age newborns.

INTRODUCTION: Lactate concentration in umbilical cord blood is an important measure of intrapartum anaerobic metabolism. The aim of the study was to compare lactate production of large-for-gestational-age (LGA) fetuses against appropriate-for-gestational-age (AGA) fetuses during hypoxia, in diabetic and non-diabetic mothers. MATERIAL AND METHODS: A total of 17 358 validated paired arterial and venous umbilical cord blood samples taken at birth with a full panel of pH, glucose, and lactate were analyzed relative to LGA (n = 2789) and AGA (n = 14 569). Umbilical cord blood acidemia (pH < mean minus 2 SD) was identified in 518 cases. RESULTS: Diabetes, but not acidemia, was more common among LGA (5.4%) than AGA cases (2.9%) (respectively P < .0001 and P < .69). At normal pH, glucose was lower in non-diabetes LGA cases, but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .067). Glucose levels were higher in all groups during acidemia (P ≤ .0005), with lower values in non-diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P = .005 and P < .58). At normal pH, lactate was lower in non-diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .98); during acidemia, lactate levels were higher in all groups (P < .0001), resulting in no significant difference between LGA and AGA in diabetes as well as in non-diabetes cases (respectively P = .29 and P < .084). CONCLUSIONS: Considering cord acidemia a proxy for intrapartum hypoxia, LGA fetuses showed no impaired ability to produce lactate during hypoxia. Maternal diabetes did not hamper the ability of LGA fetuses to produce lactate during hypoxia.

Effects of inter-twin vascular anastomoses of monochorionic twins with selective intrauterine growth restriction on the contents of placental mitochondria DNA.

BACKGROUND: Placental mitochondrial DNA (mtDNA) has been proposed to be an indicator for placental hypoxia. This study was designed to evaluate the effect of vascular anastomoses between monochorionic (MC) twins on placental mtDNA. METHODS: In this study, twin-twin transfusion syndrome (TTTS) treated with laser therapy and MC twins without TTTS (without laser therapy) resulting in two live babies were included in this study. The placental mtDNA fold changes (FC) between the small and large twins were analyzed using real-time quantitative PCR. TTTS twins with selective intrauterine growth restriction (sIUGR) are categorized as group 1, TTTS without sIUGR as group 2, MC twins without TTTS but with sIUGR as group 3, and MC twins without both TTTS and sIUGR as group 4. RESULTS: There were seven cases in group 1, eight in group 2, 26 in group 3, and 24 in group 4 cases. The placental mtDNA FC were significantly higher in group 1 (1.57 ± 0.9) compared to that of the group 3 (0.86 ± 0.6). CONCLUSION: In MC twin pregnancies with sIUGR, the placental mtDNA FC between the small and large twins are different between cases with and without inter-twin anastomoses. These findings suggest that the inter-twin anastomoses in the MC twins with sIUGR may provide rescue perfusion from the appropriate-for-gestational-age twin to the sIUGR one.

Increase of neuronal injury markers Tau and neurofilament light proteins in umbilical blood after intrapartum asphyxia.

AIM: Compare the levels of the brain injury biomarkers Tau and neurofilament light protein (NFL) in cases of asphyxia with those in controls. MATERIALS AND METHODS: We analyzed the neuronal proteins Tau and NFL in umbilical blood of 10 cases of severe-moderate intrapartum asphyxia and in 18 control cases. RESULTS: The levels of both Tau and neurofilament were significantly higher after asphyxia and it appeared to be a correlation between the levels of the biomarkers and the severity of the insult. DISCUSSION: Future studies are warranted to support or refute the value of Tau/NFLin clinical practice. CONCLUSION: Fetal asphyxia remains a clinical problem resulting in life-long neurological disabilities. We urgently need more accurate early predictive markers to direct the clinician when to provide neuroprotective therapy.

The introduction of umbilical cord lactate measurement and associated neonatal outcomes in a South African tertiary hospital labor ward.

PURPOSE: To investigate the utility of umbilical artery (UA) lactate measurements in a South African hospital for assessing intrapartum care and predicting neonatal outcomes. MATERIALS AND METHODS: From 3 March-12 November 2014, we conducted a prospective cohort study of UA lactate levels at Kalafong Hospital, Pretoria, South Africa. Following birth, a UA blood sample (<0.5uL) was taken from a double-clamped segment of cord and the lactate measured. Maternal and neonatal characteristics and outcomes were recorded. RESULTS: During the study, there were 4668 deliveries; including 1091 emergency cesarean and 154 instrumental deliveries. A lactate was recorded for 946 deliveries (20.3%). 190 babies required neonatal resuscitation, with an optimal cutoff for lactate of 5.45 mmol/L (sensitivity 68%, specificity 72%). 124 babies required nursery admission with the optimal cutoff for lactate 4.95 mmol/L (sensitivity 61%, specificity 59%). 55 babies had an Apgar score <7 at 5 min and the optimal lactate for this outcome was 5.65 mmol/L (sensitivity 64%, specificity of 69%). CONCLUSIONS: Umbilical lactate can be used in a middle-low resource setting as a measurement of intrapartum hypoxia, with reasonable sensitivity and specificity for the prediction of, or need for, resuscitation, admission to the nursery, and low Apgar scores.