Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor.

Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/day from 115 to term; CORT), DCA-treated (over 24 h), and DCA + CORT-treated; oxytocin was delivered starting 48 h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine, and glucose/glucose-6-phosphate and increased acetylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation (PCI, PCI + II) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phosphorylcholine after DCA treatment. There were negative correlations of acetylcarnitine/isobutyryl-carnitine to both heart rate (HR) and mean arterial pressure (MAP). These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction.

Correlation of lipid peroxidation and ATP enzyme on erythrocyte membrane with fetal distress in the uterus in patients with intrahepatic cholestasis of pregnancy.

OBJECTIVE: This paper aims to investigate the correlation of lipid peroxide in erythrocytes and ATP (Adenosine Triphosphate) enzyme activity of erythrocyte membrane with fetal distress in patients with intrahepatic cholestasis of pregnancy (ICP). PATIENTS AND METHODS: Forty-three patients with ICP treated at Jining No. 1 People's Hospital were enrolled as a study group, and another forty healthy parturient women in the same period were enrolled as a control group, to extract their elbow venous blood and fetal umbilical cord blood. Thiobarbituric acid (TBA) was used to detect superoxide dismutase (SOD) activity of erythrocytes, malondialdehyde (MDA) activity in plasma, Na+-K+-ATP enzyme activity and Ca2+-Mg2+-ATP enzyme activity of erythrocytes, which were compared between the study and control groups. The correlation of MDA, Na+-K+-ATP enzyme and Ca2+-Mg2+-ATP enzyme activities with fetal distress in the study group was analyzed, and the correlation of MDA with Na+-K+-ATP enzyme activity was investigated. RESULTS: SOD and MDA activities of erythrocytes in maternal blood of the study group were significantly higher than those in the control group (p<0.05, p<0.001, respectively), but MDA activity in umbilical cord blood of the study group was markedly higher than that in the control group (p<0.001). Na+-K+-ATP enzyme and Ca2+-Mg2+-ATP enzyme activities of maternal and fetal erythrocytes of the study group were remarkably lower than those of the control group (p<0.001). MDA in the fetal distress group was significantly higher than that in the no fetal distress group in the study group (p<0.001). Na+-K+-ATP enzyme activity was negatively correlated with MDA concentration in maternal and fetal erythrocytes of patients with ICP (both p<0.001). CONCLUSIONS: Lipid peroxidation in patients with ICP will affect ATP enzyme activity of erythrocyte membrane, and the down-regulation of ATP enzyme activity in umbilical cord blood of patients with ICP may cause fetal distress in the uterus.

The association of second trimester biomarkers in amniotic fluid and fetal outcome.

Objective: To identify the level of amniotic fluid lactate (AFL), placental growth factor (PLGF), and vascular endothelial growth factor (VEGF) at second trimester amniocentesis, and to compare levels in normal pregnancies with pregnancies ending in a miscarriage, an intrauterine growth restricted fetus (IUGR) or decreased fetal movements. Study design: A prospective cohort study. Amniotic fluid was consecutively collected at amniocentesis in 106 pregnancies. Fetal wellbeing at delivery was evaluated from medical files and compared with the levels of AFL, VEGF, and PLGF at the time of amniocentesis. Results: The median level of AFL was 6.9 mmol/l, VEGF 0.088 pg/ml, and PLGF 0.208 pg/ml. The median levels of AFL in pregnancies ended in miscarriage were significantly higher (10.7 mmol/l) compared to those with a live new-born (6.9 mmol/L, p = .02). The levels of VEGF (p = .2) and PLGF (p = .7) were not affected. In pregnancies with an IUGR, the median level of AFL was higher compared to those with normal fetal growth (p = .003). No differences VEGF (p = .5), but significant lower PLGF were found in IUGR pregnancies (p = .03). Conclusions: Pregnancies ending in a miscarriage or with IUGR had significantly higher median values of AFL but lower values of PLGF in the amniotic fluid at the time of second trimester amniocentesis compared to normal pregnancies.

Prenatal CRH: An integrating signal of fetal distress.

Corticotropin-releasing hormone (CRH) is distributed throughout the brain and in peripheral sites but primarily is localized in the paraventricular nucleus of the hypothalamus. It is a "master" stress hormone that is responsible for the synthesis of proopiomelanocortin (POMC) in the anterior pituitary gland. Behaviorally active peptide hormones, including adrenocorticotropin hormone (ACTH) and B-endorphin, are liberated from POMC by enzymes to activate critical processes during stress. CRH is not detectable in the circulation even during extreme stress. However, during human pregnancy, the human placenta expresses the gene for CRH (pCRH) resulting in detectable levels in maternal plasma that increases 20- to 40-fold over the course of gestation. Placental CRH is identical to CRH of hypothalamic origin in size, structure, immunoreactivity, and bioactivity. However, unlike the negative feedback between adrenal cortisol and hypothalamic CRH, cortisol stimulates the synthesis and release of pCRH. The bidirectional release of pCRH into maternal and fetal compartments is associated with regulating the timing of delivery, remodeling the fetal nervous system, and influencing developmental trajectories. Fetal exposure to pCRH during early and late gestation is associated with unique patterns of cortical thinning in school-age children. Placental CRH is elevated in response to physical and behavioral stress and may be an integrative marker of early adversity.

Infant outcome at four years of age after intrapartum sampling of scalp blood lactate for fetal assessment. A cohort study.

OBJECTIVE: To correlate the value of lactate in fetal scalp blood at delivery and the outcomes of the offspring at four years of age. METHODS: Cases where scalp blood lactate was taken within sixty minutes before delivery were identified from the randomized trial "Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress". Data were grouped according to the generally accepted cutoffs for normality, pre-acidemia, acidemia and concentrations above mean +2 SD during the second stage. The outcome measures included gross-/fine motor function, vision, hearing, speaking and cognitive disorders, signs of central motor damage and referral to specialized pediatric services. RESULTS: 307 cases were available for final analyse. With normal scalp lactate concentration, the number of children with a diagnosed disorder was lower compared to the pre-acidemic/acidemic groups, although the findings were only significant for fine motor dysfunction (p = 0.036). Elevated lactate values were significantly associated with increased risk for a poorer capacity of attention and understanding of instructions (OR 1.37, 95% CI 1.07-1.74), and for fine motor dysfunction (OR 1.22, 95% CI 1.00-1.49) at the age of four. CONCLUSION: Higher levels of lactate in fetal scalp blood seems to be associated with increased risk of an aberrant developmental outcome at four years of age in some areas.

Prelabor screening for intrapartum fetal compromise in low-risk pregnancies at term: cerebroplacental ratio and placental growth factor.

OBJECTIVES: To determine the screening performance of low fetal cerebroplacental ratio (CPR), a marker of fetal adaptation to suboptimal growth, and maternal placental growth factor (PlGF) level, both in isolation and in combination, for the prediction of Cesarean section (CS) for intrapartum fetal compromise (IFC) and composite adverse neonatal outcome (CANO). METHODS: This was a prospective cohort study in low-risk women with uncomplicated singleton pregnancy from 36 weeks' gestation to delivery. CPR and PlGF were assessed fortnightly and intrapartum and neonatal outcomes were recorded. CPR and PlGF values from the final assessment for each woman were corrected for gestational age and assessed for screening performance, firstly as continuous variables and then as binary predictors. RESULTS: Of the 264 women who consented to participate in the study, 207 were included in the final analysis. Seven pregnancies required CS for IFC and 38 had CANO. Pregnancies delivered by CS for IFC had lower CPR and PlGF centiles than those in all other pregnancies. Pregnancies with CANO had a lower PlGF centile. The greatest areas under the receiver-operating characteristics curves (AUCs) for the prediction of CS for IFC (0.92; 95% CI, 0.86-0.97) and CANO (0.64; 95% CI, 0.54-0.74) were achieved by a combination of CPR 20th and PlGF 33rd centile thresholds. This produced sensitivities, specificities and positive likelihood ratios for the prediction of CS for IFC of 100%, 86% and 7.14, respectively, and 34.2%, 87.0% and 2.63, respectively, for the prediction of CANO. There was no statistical difference in the AUC for CS for IFC between the combined model and when CPR was used alone, or for CANO between the combined model and CPR or PlGF in isolation. CONCLUSIONS: This pilot proof-of-concept study describes the screening performance of CPR and maternal PlGF level for CS for IFC in low-risk women from 36 weeks' gestation. It was found that CPR and maternal PlGF improved the overall predictive utility for CS for IFC, as well as that for CANO. However, given the lack of significant difference between the combined model and its individual components, it is debatable whether the combined model is a superior screening test. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Correlation between oxidative stress and G6PD activity in neonatal jaundice.

Fetal distress represents a pathophysiological condition in which oxygen is not available to the fetus in sufficient quantities. In cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency, under conditions of oxidative stress, the residual G6PD and complimentary antioxidant mechanisms may become insufficient to neutralize the large amounts of ROS and to prevent severe hemolysis. Alteration in the oxidant-antioxidant profile is also known to occur in neonatal jaundice. The study group included 22 neonates presented with fetal distress during labor and 24 neonates with no evidence of fetal distress (control group). Umbilical cord blood samples were taken immediately after delivery, and the following blood tests were carried out after birth and at discharge from the hospital: erythrocyte count, total bilirubin, G6PD activity, and parameters presenting oxidative status [thiobarbituric acid reactive substances (TBARS), NO, O2 (-), H2O2, SOD, CAT, O2 (-)/SOD, and H2O2/CAT]. There were no significant differences in TBARS and NO values among neonates with or without fetal distress. However, the values of O2 (-), H2O2, SOD, O2 (-)/SOD, and H2O2/CAT among neonates born after fetal distress were significantly higher than in neonates without fetal distress (p < 0.01). In neonates with fetal distress, the total number of RBCs at delivery was significantly lower, accompanied with higher bilirubin content. Also neonates with fetal distress had lower activity of G6PD and lower CAT activity. Higher values of oxidative stress parameters in newborns delivered after fetal distress do not indicate strictly what occurred first-oxidative stress or basic lower G6PD activity.

Hypoxia index in the prediction of abnormal CTG at delivery in uncomplicated pregnancies.

OBJECTIVES: The evaluation of hypoxia index (HI) in the prediction of abnormal fetal heart rate at delivery in uncomplicated pregnancies. MATERIAL AND METHODS: The study group included 148 pregnant patients at term (69 patients with and 79 without brain sparing effect). The value of C/U ratio and HI was determined. Next, its value in predicting abnormal fetal heart rate during labor was evaluated. Then the predictive value of the HI index, C/U and last abnormal values of PI and RI in the MCA and the UA were compared in relation to the analyzed parameters. Evaluation included signs of fetal distress in CTG and abnormal fetal outcome. Then selected parameters, characterizing pregnancy course and fetal outcome with abnormal Doppler indices, were compared. RESULTS: The designated value of hypoxia index characterized by abnormal neonatal outcome was >10 for sHI and >14 for HI. Low prognostic value of MCA PI and RI, and UA PI and RI has been shown. The highest predictive value was marked by C/U and HI. There were no statistically significant differences in prediction of abnormal fetal heart rate during labor between C/U ratio, HI and sHI. CONCLUSIONS: The C/U ratio showed the highest sensitivity in the prediction of fetal abnormal heart rate. The C/U ratio, as a easier test, should be recommended as a first-line test in the prediction of abnormal CTG recordings in uncomplicated pregnancies.

The correlation between fetal bradycardia area in the second stage of labor and acidemia at birth.

OBJECTIVE: To quantify fetal bradycardia in the second stage of labor and to determine the threshold of the area that correlates with neonatal acidemia. METHOD: We analyzed the cardiotocograms of 33 women with single pregnancy and term spontaneous labor who presented fetal bradycardia in the second stage of labor. We retrospectively calculated the fetal bradycardia area in the last 60 min before delivery with an upper limit of 90 bpm and correlated the area with neonatal pH. The study of the regression line determined the cut-off threshold between fetal well-being and distress. Significance was set at p < 0.05. RESULTS: The linear correlation between the bradycardia area and neonatal pH indicate that increasing bradycardia area was correlated with significant pH decrease. The threshold value of the area indicative of severe acidemia was ≥ 12.72 cm(2) (Pearson r = -0.76, p < 0.002). The diagnostic accuracy of the test was 73%. The PPV = 78.5% and the NPV = 68.4%. With such a cut-off, the timing of acidemia can be calculated as 25 min for a fetal heart rate (FHR) of 80 bpm, 13 min for a FHR of 70 bpm, 8 min for a FHR of 60 bpm, 6 min for a FHR of 50 bpm and 5 min for a FHR of 40 bpm. CONCLUSION: The bradycardia area in the second stage of labor significantly correlates with an accurate timing of fetal acidemia. Regardless of the cause of the bradycardia, the time for intervention is often short, meaning that any available intervention may be ineffective in preventing acidemia or even injury.

[Expression of erythropoietin and its receptor in the brain of newborn rats suffering from fetal distress].

OBJECTIVE: To study the expression of erythropoietin (EPO) and its receptor (EPOR) in the brain of newborn rats suffering fetal distress. METHODS: A model of fetal distress was prepared by ligating bilateral uterine arteries of the rats with full-term pregnancy for 10 minutes before cesarean sections. The expression levels of EPO and EPOR in the brain of newborn rats were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot at 0, 2, 6, 12, 24, 48, 72 hrs and 7 days after birth. Serum EPO levels were measured using ELISA simultaneously. The newborn rats born by cesarean sections which were not subjected to uterine artery ligation were used as the control group. RESULTS: The expression of EPO protein and mRNA in brain tissues in the fetal distress group increased significantly compared with the control group 2, 6 and 12 hrs after birth (P<0.05). The expression of EPOR protein and mRNA in brain tissues in the fetal distress group increased significantly compared with the control group 2, 6, 12, 24 and 48 hrs, and 3 days after birth (P<0.05). Serum EPO levels in the fetal distress group were significantly higher than in the control group 2 hrs after birth. CONCLUSIONS: The EPO and EPOR levels in the brain increase quickly after birth in newborn rats suffering from fetal distress. The EPOR is high expressed for a longer time than EPO. This can provide a basis for the treatment of neonatal brain damage induced by fetal distress by exogenous EPO.

Conditions associated with placental dysfunction.

Placental dysfunction is a term to describe suboptimal placental function leading to variations in the fetal supply of all its necessary required nutrients as well as the disruption in the cleansing of fetal catabolic products. The dysfunctional placenta may interrupt the manufacturing of other essential factors involved in pregnancy conservation, can compromise the fetal appropriate, atraumatic and sterile medium to grow, the immunologic shield from maternal antibodies and the normal amniotic fluid levels. Placental dysfunction can lead to a group of disorders representing a diverse and important category of pathological processes conducting to fetal and neonatal morbidity and mortality. The mechanisms by which these inflammatory processes cause death and disability are diverse and can be separated into four distinct classes: first, placental damage with loss of function; second, induction of premature labor; third, release of inflammatory mediators; fourth, transplacental infection. Several conditions have been associated with placental dysfunction: IUGR, hypertension, hypoxic-ischemic injury, preterm labor, and fetal death.

Oxidative stress in fetal distress: potential prospects for diagnosis.

Our aim was to investigate the relation between fetal distress and oxidative stress. Fetal distress was associated with increased concentration of superoxide in the fetal blood and with significant increase of the level of H2O2 in both maternal and fetal blood. The activity of superoxide dismutase was increased roughly sixfold (p<0.01) in the maternal (7330 +/- 2240 U/g of hemoglobin in controls (C) and 36811 +/- 16862 U/g in fetal distress (FD)) and fetal blood (C: 5930 +/- 2641 U/g; FD: 41912 +/- 17133 U/g). In contrast, fetal distress was related to a considerable decrease of catalase activity in both maternal (C: 26011 +/- 8811 U/g; FD: 7212 +/- 1270 U/g) and fetal blood (C: 37194 +/- 9191 U/g; FD: 6173 +/- 1965 U/g). From this we concluded that in fetal distress, the maternal and fetal bloods are exposed to superoxide- and H2O2-mediated oxidative stress, which could be initiated by hypoxic conditions in the fetal blood and placenta. A tremendous increase/decrease of the activities of superoxide dismutase/catalase in the blood of women bearing a distressed fetus in comparison to healthy subjects implies that the assessment of superoxide dismutase/catalase activity could be of use for establishing a timely and accurate ante- or intrapartum diagnosis of fetal distress.

[Up-regulation of glucose regulated protein 78 induced by 2-deoxyglucose plays a protective role for fetal rat cerebral neuron following intrauterine distress].

OBJECTIVE: To evaluate the influence of up-regulation of glucose regulated protein 78 (GRP 78) induced by 2-deoxyglucose (2DG) on fetal rat cerebral neuron apoptosis following intrauterine distress and the unification of endoplasmic reticulum and mitochondrium. METHODS: (1) Fetal rat intrauterine distress model was established and rats were divided into normal group (N = 10), ischemia- reperfusion(IR) group (n = 40) and treatment group (n = 40, injection of 2DG into pregnant rats' abdomen after operation ). (2) Neuron apoptosis and the influence of 2DG on apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The expression of GRP78, caspase-9, -12, and cytoron C protein were detected by western blot technique. RESULTS: (1) The number of TUNEL positive neuron in normal group was 4.3 +/- 1.8/mm2. The expression of GRP78, caspase-9, -12, cytoron C in cytoplasm were 0.012 +/- 0.003, 0.004 +/- 0.003, 0.006 +/- 0.002, 0.012 +/- 0.005, respectively. (2) The number of TUNEL positive neuron in the IR group were 43.6 +/- 11.4/mm2 (reperfusion 3 h), 64.4 +/- 9.3/mm2 (reperfusion 6 h), 74.2 +/- 12.1/mm2 (reperfusion 12 h), 97.3 +/- 8.9/ mm2 (reperfusion 24 h), respectively. They were significantly more than that in normal group (P < 0.05). The expression of GRP78 at corresponding times in IR group were 0.092 +/- 0.008 (reperfusion 3 h), 0.078 +/- 0.006 (reperfusion 6 h), 0.054 +/- 0.009 (reperfusion 12 h), 0.038 +/- 0.007 (reperfusion 24 h), respectively. The expression of cytoron C in cytoplasm at corresponding times in IR group were 0.040 +/- 0.006 (reperfusion 3 h), 0.076 +/- 0.009 (reperfusion 6 h), 0.108 +/- 0.005 (reperfusion 12 h), 0.089 +/- 0.008 (reperfusion 24 h), respectively. The expression of caspase-9 at corresponding times in IR group were 0.042 +/- 0.003 ( reperfusion 3 h), 0.086 +/- 0.007 (reperfusion 6 h), 0.142 +/- 0.006 (reperfusion 12 h), 0.112 +/- 0.009 (reperfusion 24 h), respectively. The expression of caspase-12 at corresponding times in IR group were 0.076 +/- 0.006 (reperfusion 3 h), 0.113 +/- 0.010 (reperfusion 6 h), 0.125 +/- 0.005 (reperfusion 12 h), 0.057 +/- 0.008 (reperfusion 24 h), respectively. They were significantly higher than that in normal group (P < 0.05). (3) The number of TUNEL positive neuron in the treatment group were 19.4 +/- 10.6/mm2 (reperfusion 3 h), 26.4 +/- 12.3 /mm2 (reperfusion 6 h), 39.3 +/- 13.3/mm2 (reperfusion 12 h), 49.3 +/- 13.6/mm2 (reperfusion 24 h), respectively. They were significantly lower than that in IR group, but more than that in normal group (P < 0.05). The expression of GRP78 at corresponding times in the treatment group were 0.158 +/- 0.012 (reperfusion 3 h), 0.175 +/- 0.005 (reperfusion 6 h), 0.125 +/- 0.013 (reperfusion 12 h), 0.079 +/- 0.004 (reperfusion 24 h), respectively. They were significantly higher than that in IR group and normal group (P < 0.05) . The expression of cytoron C in cytoplasm at corresponding times in IR group were 0.026 +/- 0.002 (reperfusion 3 h), 0.042 +/- 0.008 (reperfusion 6 h), 0.062 +/- 0.007 (reperfusion 12 h), 0.045 +/- 0.004 (reperfusion 24 h), respectively. The expression of caspase-9 at corresponding times in IR group were 0.033 +/- 0.002 (reperfusion 3 h), 0.063 +/- 0.005 (reperfusion 6 h), 0.092 +/- 0.005 (reperfusion 12 h), 0.068 +/- 0.008 (reperfusion 24 h), respectively. The expression of caspase-12 at corresponding times in IR group were 0.061 +/- 0.004 (reperfusion 3 h), 0.068 +/- 0.009 (reperfusion 6 h), 0.072 +/- 0.007 (reperfusion 12 h), 0.054 +/- 0.005 (reperfusion 24 h), respectively. They were significantly lower than that in IR group, but higher than that in normal group (P < 0.05). CONCLUSIONS: Fetal rat cerebral neuron apoptosis following intrauterine distress is associated with the action of endoplasmic reticulum and mitochondrium. Up-regulation of GRP78 induced by 2DG counteracts primary cellular damage caused by endoplasmic reticulum stress. 2DG plays a protective role for fetal rat cerebral neuron following intrauterine distress.

Predictors of umbilical artery acidosis in preterm delivery.

OBJECTIVE: The purpose of this study was to investigate the significance of preterm acidosis and its risk factors. STUDY DESIGN: From a cohort of 786 consecutive singleton neonates who were born after spontaneous or iatrogenic preterm delivery at 24.0-33.6 weeks of gestation from January 1993 to December 2005 with an evaluation of umbilical artery pH at delivery, we extracted demographic, obstetric, neonatal, and placental histologic variables and related them to umbilical artery evidence of fetal acidemia, which was defined as pH <7.10. Excluded were stillbirths and neonates with major congenital anomalies. Fetal distress was defined as nonreassuring fetal hearth rate tracing or biophysical profile or appearance of thick meconium at delivery. Statistical analysis included 1-way analysis of variance and logistic regression with a probability value of <.05 considered significant. RESULTS: Neonates with umbilical cord evidence of acidosis (n = 34) were born more frequently after abruption (P < .001), fetal distress (P < .001), and by cesarean delivery (P < .04) and were born less frequently after a complete course of corticosteroids (P = .03) and labor (P = .05) than nonacidotic babies (n = 752). Acute inflammatory lesions at placental histologic evaluation were less frequent (P = .049), and placental vascular lesions were more common in acidotic than in nonacidotic preterm neonates (P = .039). Logistic regression analysis demonstrated that cord acidosis was associated independently with the occurrence of abruptio placentae (odds ratio, 7.3; 95% CI, 2.9, 18.8), fetal distress (odds ratio, 12.0; 95% CI, 4.9, 18.3), and vascular placental lesions (odds ratio, 2.8; 95% CI, 1.2, 6.8) CONCLUSION: In preterm infants, umbilical artery acidosis is significantly more common in the presence of placental abruption, fetal distress, and histologic evidence of placental vascular disease.

Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome.

The many physiologic roles of human alpha-fetoprotein (HAFP) and its correlation with perinatal distress/pregnancy outcome are rarely addressed together in the biomedical literature, even though HAFP has long been used as a biomarker for fetal birth defects. Although the well being of the fetus can be monitored by the measurement of gestational age-dependent HAFP in biologic fluid levels (serum, amniotic fluid, urine, and vaginal fluids) throughout pregnancy, the majority of clinical reports reflect largely second trimester and (less likely) first trimester testing due to regulatory clinical restrictions. However, reports of third-trimester and pregnancy term measurement of HAFP levels performed in clinical research and/or investigational settings have gradually increased over the years and have expanded our base knowledge of AFP-associated pregnancy disorders during these stages. The different structural forms of HAFP (isoforms, epitopes, molecular variants, etc.) detected in the various biologic fluid compartments have been limited by antibody recognition of specific epitopic sites developed by the kit manufacturers based on antibody specificity, sensitivity, and precision. Concomitantly, the advances in elucidating the various biologic actions of AFP are opening new vistas toward understanding the physiologic roles of AFP during pregnancy. The present review surveys HAFP as a biomarker for fetal distress during the perinatal period in view of its structural and functional properties. An attempt is then made to relate the AFP fluid levels to adverse pregnancy complications and outcomes. Hence, the present review was divided into two major sections: (I) AFP structure and function considerations and (II) the relationship of AFP levels to the distressed fetus during the third trimester and at term.

Tocolysis and delayed delivery versus emergency delivery in cases of non-reassuring fetal status during labor.

AIM: To determine whether fetal intrauterine resuscitation using tocolysis and delayed delivery is better for the fetus than emergency delivery when fetal hypoxia is suspected because of a non-reassuring fetal heart-rate (FHR) pattern using conventional heart rate monitoring. METHODS: This was a prospective and randomized study, conducted between 2001 and 2004 at Pereira Rossell Hospital, Montevideo, Uruguay. The population consisted of 390 fetuses, in which intrauterine distress was diagnosed using electronic FHR monitoring. Of these, 197 were randomly assigned to the emergency delivery group and 193 to the fetal intrauterine resuscitation group. The inclusion criteria were: term singleton pregnancy, in labor, cephalic presentation, and no placental accidents. RESULTS: The time between randomization and birth was 16.9 +/- 7.6 min (mean +/- SD) for the emergency delivery group, and 34.5 +/- 11.7 min (mean +/- SD) for the resuscitation group. The relative risk (RR) of acidosis in the umbilical artery (pH < 7.1) in the emergency delivery group was 1.47 (0.95-2.27). The RR of base deficit < or =12 mEq/L in the emergency delivery group was higher than in the resuscitation group (RR = 1.48 [1.0-2.2], P = 0.04). When considering the need for admission to the neonatal care unit, the relative risk was higher in the emergency delivery group than in the resuscitation group (RR = 2.14 [1.23.3.74], P = 0.005). No maternal adverse effects were reported. CONCLUSION: Tocolysis and delayed delivery renders better immediate neonatal results than emergency delivery when fetal distress is suspected because of a non-reassuring fetal heart pattern. In addition, it may decrease the need for emergency delivery without increasing maternal and fetal adverse side-effects.

Different degrees of fetal oxidative stress in elective and emergent cesarean section.

BACKGROUND: Several studies have addressed the influence of labor and mode of delivery on oxidative stress. Still it is unclear whether oxidative stress is related to delivery itself or whether it reflects a pre-existing fetal oxidative status. OBJECTIVE: To investigate whether the degree of fetal oxidative stress is different between distressed fetuses that were delivered by emergent cesarean section and non-distressed fetuses that were delivered by elective cesarean section. METHODS: The protocol of this prospective study was approved by the Institutional Review Board Committee. Amniotic fluid and umbilical artery blood were prospectively collected from 21 parturients who were delivered by an emergent cesarean section for non-reassuring fetal heart rate pattern and from 21 parturients who were delivered by an elective cesarean section in a tertiary care center. Oxidative stress was evaluated in amniotic fluid, umbilical cord plasma and erythrocytes by determining malondialdehyde concentration and glutathione peroxidase (GPX) activity. RESULTS: Malondialdehyde concentration was higher in amniotic fluid (mean +/- SEM) (2.2 +/- 0.7 nmol/l vs. 0.6 +/- 0.02 nmol/l, p < 0.05), in umbilical cord plasma (1.2 +/- 0.2 nmol/l vs. 0.7 +/- 0.3 nmol/l, p < 0.05) and in umbilical cord erythrocytes (159.6 +/- 48.6 nmol/g Hb vs. 85.8 +/- 5.2 nmol/g Hb, p < 0.05) in women delivering by emergent cesarean compared to those delivering by elective cesarean. GPX activity was enhanced in amniotic fluid (12.4 +/- 2.2 U/l vs. 5.1 +/- 0.6 U/l, p < 0.05) and GPX activity/hemoglobin ratio was higher in cord blood (22.0 +/- 0.8 U/g Hb vs. 18.7 +/- 0.9 U/g Hb, p < 0.05) in women delivering by emergent cesarean compared to those delivering by elective cesarean. CONCLUSION: Distressed fetuses delivered by emergency cesarean exhibited increased malondialdehyde concentrations, an indicative parameter for oxidative damage, and enhanced GPX activity an antioxidant enzyme, in amniotic fluid and umbilical cord blood compared to non-distressed fetuses delivered by elective cesarean section. This is probably an indication of higher fetal oxidative stress.

Meconium-stained liquor during labor is associated with raised neonatal cord blood 8-iso-prostaglandin F2alpha concentration.

OBJECTIVE: The purpose of this study was to compare the umbilical arterial 8-iso-prostaglandin F2alpha, concentrations between pregnancies that were complicated by moderate or thick meconium-stained liquor and those with clear liquor. STUDY DESIGN: Umbilical cord arterial blood samples were collected from 247 singleton pregnancies with either moderate or thick meconium-stained liquor at any stage of labor or clear liquor at all stages of labor for the determination of the total 8-iso-prostaglandins F2alpha concentration. RESULTS: The median total 8-iso-prostaglandins F2alpha concentration of the meconium-stained liquor group was significantly higher than that of the control group (719.2 vs 115.8 pg/mL). Among the meconium-stained liquor group, those who had a change from "clear liquor" at early labor to "moderate/ thick meconium-stained liquor" at late first stage or at delivery (late meconium-stained liquor group) had higher 8-iso-prostaglandins F2alpha concentration, compared with those who had moderate/ thick meconium-stained liquor since early labor (early meconium-stained liquor group; 959.8 vs 499.9 pg/mL). With the use of multiple regression analysis, meconium-stained liquor, duration of second stage of labor, and abnormal fetal heart tracings were independent determinants of cord blood 8-iso-prostaglandins F2alpha concentration. CONCLUSION: Moderate or thick meconium-stained liquor is an independent factor for increased oxidative stress in pregnancy.

[Effects of fetal anoxia and acidosis on superoxide dismutase].

OBJECTIVE: To analyze the effects of fetal anoxia, respiratory and metabolic acidosis on the activity of antioxidation in fetal distress. METHODS: Blood samples were taken from umbilical artery in 386 neonates for blood gas analysis and detection of the concentration of superoxide dismutase (SOD). Normal situation, anoxia, acidosis, respiratory acidosis, metabolic acidosis and mixed acidosis were diagnosed in all neonates according to the results of blood gas values, and the neonate asphyxia was diagnosed according to the Apgar scores (one minute). The effect of anoxia and acidosis to SOD were analyzed with multiple factor analysis of variation. RESULTS: (1) Among the all 386 cases, 317 were normal, 31 with anoxia, 17 with acidosis, and 21 with both anoxia and acidosis. Among the total cases of acidosis, 8 respiratory, 21 metabolic, and 9 mixed acidosis. (2) The plasma levels of SOD of umbilical artery blood in anoxia, acidosis, both anoxia and acidosis, and normal sitution were (118.5 +/- 7.1) mmol/L, (122.0 +/- 11.4) mmol/L, (140.0 +/- 7.0) mmol/L, and (98.5 +/- 2.6) mmol/L, respectively. The results of unvariate analysis of variance showed that anoxia: F = 4.999 (P < 0.05), acidosis: F = 7.025 (P < 0.01), and both anoxia and acidosis: F = 0.013 (P > 0.05). (3) The plasma levels of SOD with respiratory acidosis, metabolic acidosis and mixed acidosis were (127.3 +/- 18.4) mmol/L, (126.0 +/- 8.1) mmol/L, (150.0 +/- 10.4) mmol/L. The results of univariate analysis of variance showed that respiratory acidosis: F = 4.404 (P < 0.05), metabolic acidosis: F = 3.965 (P < 0.05), and mixed acidosis: F = 0.015 (P > 0.05). CONCLUSION: The superoxidation and antioxidation can be effected by factors like anoxia and acidosis, respiratory acidosis and metabolic acidosis. However, the mechanisms of these effects are different. There is additive, but not synergistic effects among them.

[Acute fetal distress]. / La souffrance foetale aiguë.

Three different clinical patterns of acute fetal distress may be observed during labor: an ante-partum hypoxia with a persistent nonreactive and "fixed" fetal heart rate (FHR) on admission to the hospital, a progressive intra-partum asphyxia manifested, as the labor continues, by a substantial rise in baseline heart rate, a loss of variability and repetitive severe variable or late decelerations, and finally, as a result of a catastrophic event, a sudden prolonged FHR deceleration to approximately 60 beats per minute lasting until delivery. However the majority of fetuses with nonreassuring tracings of FHR are neurologically intact, as evidenced by the high false-positive rate of electronic fetal monitoring (EFM). Therefore the diagnosis of fetal distress must be corroborated by complementary methods, such as continuous recording of the fetal electrocardiogram or computed-assisted EFM, fetal pulse oximetry or fetal scalp sampling with immediate determination of blood gases or lactates. Defavorable outcome of an acute fetal distress leading to neonatal encephalopathy or death is best predicted by a persisting low Apgar score (<3) for more than 5 minutes and by a severe metabolic acidosis (umbilical artery pH<7,00 and base-excess>-12mmol/l).