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Biomedical subjects

M Stangenberg

Publications and source records attributed to M Stangenberg.

At least 19 recordsLinked to original sources

Cytokines in fetal blood and amniotic fluid in Rh-immunized pregnancies.

OBJECTIVE: To determine fetal serum and amniotic fluid (AF) levels of interleukin (IL)-3, IL-6, granulocyte-macrophage colony-stimulating factor, stem cell factor, and erythropoietin, and to explore the relationship between cytokines and hemoglobin concentration, white blood cell count (WBC), and platelet count in fetuses affected by Rh immunization. METHODS: Thirty-four consecutive Rh-immunized patients in gestational weeks 19-33 were included. All patients were investigated by funipuncture and 13 by amniocentesis. The levels of IL-3, IL-6, granulocyte-macrophage colony-stimulating factor, stem cell factor, and erythropoietin were estimated using commercially available immunoassays. RESULTS: There was a significant correlation between erythropoietin concentrations in fetal serum and AF (r = 0.54, P < .05), whereas none of the other cytokines showed a positive correlation between these two compartments. Fetal serum contained higher concentrations of IL-3, granulocyte-macrophage colony-stimulating factor, stem cell factor, and erythropoietin compared with AF. In contrast, the IL-6 level was significantly higher in AF compared with fetal serum (P = .002). Erythropoietin and IL-3 levels were both negatively correlated with fetal hemoglobin concentrations (r = -0.75, P = .02, and r = -0.67, P = .045). The fetal WBC correlated significantly with the fetal serum concentration of granulocyte-macrophage colony-stimulating factor (r = 0.38, P = .04). CONCLUSION: Human fetuses with anemia due to erythrocyte immunization exhibit an increased production of erythropoietin and IL-3. Other studied cytokines (such as stem cell factor, granulocyte-macrophage colony-stimulating factor, and IL-6) did not correlate with the degree of fetal anemia. Among the studied cytokines, only erythropoietin showed a positive correlation between fetal serum and AF.

Amniotic Fluid↗

Cordocentesis.

During the last decade cordocentesis has become common procedure in perinatal medicine. Although the method represents potential possibilities, it is also afflicted with several limitations. The present review focuses on technique, indications, and complications.

Bradycardia↗

Umbilical artery Doppler flow-velocity waveforms and fetal acid-base balance in Rhesus-isoimmunized pregnancies.

Pulsed Doppler blood-flow velocity waveforms in the umbilical arteries, as well as blood gases, hematocrit, and lactate concentration in umbilical venous blood, were examined in 21 patients undergoing 49 cordocentesis, 34 of which were followed by fetal blood transfusion into the umbilical vein. The aim of the study was to evaluate the correlations, if any, between the Doppler indices from the umbilical artery (pulsatility index, resistance index, systolic/diastolic ratio) and the blood gas values (pO2, pCO2, O2 content, pH) and lactate content in the umbilical vein. The only correlation confirmed in this study was in the subgroup of anemic fetuses undergoing fetal blood transfusion, where correlation existed between A/B and the initial O2 content (r = -0.41, p < 0.02). We conclude that, in Rhesus-isoimmunized pregnancies, in contrast to other pregnancies, a close correlation does not exist between the Doppler indices in the umbilical artery and the fetal blood gas values.

Acid-Base Equilibrium↗

Umbilical artery Doppler flow-velocity waveforms in Rhesus-isoimmunized fetuses before and after fetal blood sampling or transfusion.

Pulsed-Doppler examinations of blood-flow velocities in the umbilical artery were carried out before and after 15 diagnostic cordocenteses and 34 fetal blood transfusions into the umbilical vein. There were decreases in the systolic/diastolic ratio (A/B) (p < 0.01), the pulsatility index (PI) (p < 0.05), and the resistance index (RI) (p < 0.01) after cordocentesis but not after fetal blood transfusion. There were no correlations between the initial hematocrit and the umbilical artery Doppler indices in the sample nor in the fetal blood sampling group. In the fetal blood transfusion group, on the other hand, there was a negative correlation between the initial hematocrit and A/B (r = -0.44; p < 0.01) and the RI (r = -0.35; p < 0.05). The umbilical artery Doppler flow-velocity indices did not predict the fetal hematocrit.

Blood Flow Velocity↗

Oxygenation of the human fetus as a function of hemoglobulin concentration.

We studied the relationships between fetal hemoglobin concentration, acid base status, and lactate concentration in umbilical venous and fetal heart blood in 157 fetuses affected by blood group incompatibility who had been exposed for 214 fetal blood sampling procedures (cordocentesis in 153 and intracardiac puncture in 61 cases). All blood samplings were obtained before fetal blood transfusions were administered. The results indicate that the human fetus can maintain a normal acid-base status until a 50% reduction of the hemoglobin concentration. A further reduction of hemoglobulin is associated with an accumulation of lactate both in umbilical venous and fetal heart blood. The partial oxygen tension and the oxygen saturation in umbilical venous blood remained virtually unchanged with decreasing hemoglobin concentration (r = -0.11, P = 0.21; r = 0.09, P = 0.31, respectively), whereas these parameters decreased significantly (r = 0.33, P = 0.02; r = 34, P = 0.02) in blood obtained from the fetal heart. The partial carbon dioxide tension of umbilical vein blood decreases significantly with a reduced hemoglobin concentration (r = 0.25 P = 0.008). We speculate that these alterations in acid-base status in umbilical vein and fetal heart blood reflect a circulatory transition from a high to a low cardiac output as the hemoglobin concentration decreases.

Acid-Base Equilibrium↗

Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: quantitative measurements by radioimmunoassay in human fetal serum.

There is evidence for a role for IGF-I in the endocrine control of human fetal growth despite the low serum IGF-I concentrations. The formation in serum of binary complexes between IGF-I or -II and either of six IGF binding proteins (IGFBP-1 to -6) and, in particular, of long-lived ternary complexes between IGF-I or -II, IGFBP-3, and acid-labile subunit is thought to regulate IGF-I bioavailability by increasing its serum half-life. The present study assesses the bioavailability of circulating IGF-I in 19- to 35-wk gestation human fetuses in utero 1) by quantitative RIA measurements of IGF and IGFBP in serum and 2) by examining whether serum proteolysis of IGFBP-3 may further increase IGF-I bioavailability. Fetal serum concentrations of IGFBP-3, IGF-I, and IGF-II were low with marked or only modest increases with gestational age (p < 0.001, p < 0.005, and p < 0.05, respectively). The mean molar ratio between IGF-I plus -II and IGFBP-3 demonstrated a molar excess of IGF (50%) similar to that in adolescents but in contrast to the 1:1 molar ratio in adults. The median IGFBP-2 concentration was 3-fold elevated to a molar concentration similar to that of IGFBP-3 (adult serum displays 10-fold higher IGFBP-3 concentrations). The median serum IGFBP-1 concentration was not elevated as previously reported in newborns. IGFBP-3 protease activity was not increased in fetal serum, in contrast to pregnancy serum and amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗

Decreased ternary complex formation and predominance of a 29 kDa IGFBP-3 fragment in human fetal serum.

Insulin-like growth factor-I (IGF-I) has been proposed to be important in the endocrine control of fetal growth in humans, although serum IGF-I concentrations are 10-fold lower than during rapid pubertal growth. However, the bioavailability of IGF-I in fetal serum may be increased by changes in the specific IGF binding proteins (IGFBPs). We have recently suggested that the bioavailability of circulating IGF-I is increased in the human fetus due to the molar excess of IGF-I plus IGF-II relative to IGFBP-3 as well as the increased concentrations of IGFBP-2, which does not form a long-lived ternary complex. We have presently studied ternary complex formation between IGF, IGFBP-3, and acid labile subunit (ALS) to further assess if IGF-I bioavailability is increased in human fetal serum. In 19-35 week gestation fetal sera, a markedly decreased formation of the ternary complex was demonstrated by the general absence of IGFBP-3 (detected by Western immunoblotting) in the approximately 130-150 kDa ternary complex after neutral size chromatography. The predominant form of IGFBP-3 in fetal serum was a 29 kDa fragment, which, following deglycosylation by Endoglycosidase-F, was demonstrated to consist of a approximately 20 kDa protein core. Despite the predominance of the 29 kDa IGFBP-3 fragment, we have previously demonstrated that the IGFBP-3 protease activity is not increased in fetal serum, in contrast to pregnancy or non-insulin dependent diabetes mellitus (NIDDM) sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hypoxanthine in fetal umbilical venous blood and amniotic fluid from pregnancies complicated by rhesus isoimmunization.

Concentrations of hypoxanthine (HX) was determined in umbilical venous blood and amniotic fluid obtained at 74 instances in 36 rhesus immunized patients before the onset of labor. HX concentrations were related to gestational age, concentrations of hemoglobin and lactate, pH, and partial oxygen pressure in umbilical venous blood. Multiple regression analysis revealed hemoglobin concentration to be the only variable that had any explanatory power to HX in amniotic fluid. No one of the studied variables gave any significant contribution to a regression model to explain HX in umbilical venous blood. We conclude that HX levels in umbilical venous blood and in amniotic fluid from rhesus immunized patients were not associated with fetal blood gases before the onset of labor.

Amniocentesis↗

Erythropoietin concentrations in amniotic fluid and umbilical venous blood from Rh-immunized pregnancies.

We set out to investigate prospectively the levels of erythropoietin in amniotic fluid and umbilical venous blood, and to attempt to relate these to fetal haemoglobin and lactate concentrations and to pCO2 and PO2 in Rh immunised patients studied before the onset of labor. Fetal blood was obtained by cordocentesis, and amniotic fluid by amniocentesis from a consecutive series of 36 Rh immunized patients at the time of fetal blood sampling. There was a close correlation (tau = 0.357, P = 0.0001) between the concentrations of erythropoietin in umbilical venous blood and those in amniotic fluid. Erythropoietin in umbilical venous blood correlated inversely with hemoglobin (tau = 0.453, P = 0.0001), and directly with lactate concentrations (tau = 0.450, P = 0.0005). When all other variables were considered, multiple regression analysis demonstrated hemoglobin concentration to be the only variable to be related to the level of erythropoietin in umbilical venous blood taken before transfusion. When the same analysis was performed on the same variables, adding erythropoietin concentration in amniotic fluid as the dependent variable, only erythropoietin in umbilical venous blood was found to be related to the level of erythropoietin in amniotic fluid. We conclude that the erythropoietin concentration in umbilical venous blood from Rh-immunized patients before the onset of labor, is related to fetal anemia. We also conclude that erythropoietin concentration in amniotic fluid is related to that in fetal blood, thereby indicating that the fetus is an important source of amniotic fluid erythropoietin in non laboring patients.

Amniotic Fluid↗

Intrauterine intravascular transfusions in fetal erythroblastosis: the influence of net transfusion volume on fetal survival.

The intravascular volume load that an anemic fetus can tolerate was studied retrospectively in 124 consecutive intravascular transfusions in 35 erythroblastic fetuses. The tolerated volume load correlated well to the estimated fetal weight. Transfusion volume loads above 20 ml/kg of the estimated fetal weight resulted in a lower fetal survival. We recommend an upper transfusion limit at 20 ml/kg corresponding to approximately 20% of the feto-placental blood volume.

Blood Transfusion, Intrauterine↗

Mucopolysaccharidosis VII as cause of fetal hydrops in early pregnancy.

We report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as beta-glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. beta-Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal.

Adult↗

Lack of relation between fetal blood gases and fetal blood flow velocity waveform indices found in rhesus isoimmunised pregnancies.

OBJECTIVE: To investigate the relation between umbilical vein blood gas components and the vascular resistance in four fetal arteries in Rh-immunised pregnancies. DESIGN: A prospective observational study over a 4-month period. SETTING: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. SUBJECTS: Fifteen Rh-isoimmunised pregnant women. INTERVENTIONS: Pulsed Doppler examinations of the umbilical artery, fetal internal carotid artery, thoracic aorta and abdominal aorta before transabdominal fetal blood sampling from the umbilical vein on 38 occasions. MAIN OUTCOME MEASURES: Doppler flow velocity pulsatility index (PI), systolic/diastolic ratio (A/B) and resistance index (RI) in the four fetal arteries investigated were related to the umbilical vein blood gases and acid-base status (PO2, PCO2, O2-content, CO2-content, HCO3, base excess and lactate concentration). RESULTS: There were no correlations between the Doppler indices in any of the vessels studied and the blood gases components in the umbilical vein. The ratios between the corresponding Doppler indices in the different vessels were also independent of the blood gases and acid-base status and there were no significant differences in the Doppler indices in the same vessel between fetuses with blood gas values over the 75th centile and those with values below the 25th centile. CONCLUSION: This study does not support a reduction in peripheral vascular resistance in the fetal cerebrum in relation to fetal hypoxia in Rh-immunized pregnancies.

Blood Flow Velocity↗

Nonimmune hydrops fetalis: case reports and brief review.

We report two cases of nonimmune hydrops fetalis diagnosed prenatally. One fetus died in utero, and the second fetus survived and the infant was discharged from the intensive care nursery at 4 weeks of age. A brief review of the literature and the difficulties in arriving at a diagnosis and the management are described, along with certain prognostic factors determining the outcome.

Adult↗

Is fetal insulin secretion affected by fetal hypoxia?

Fifty-five pregnant Rhesus isoimmunized women were subjected to fetal blood sampling or fetal blood transfusion on 135 occasions. Glucose and C-peptide concentrations were measured in fetal blood, in addition to the routine investigations for complete blood count, blood gases and lactate concentration, in order to investigate whether fetal insulin secretion was affected by hypoxia from fetal anemia. We found a strong relation between the concentration of C-peptide and gestational age at sampling (r = 0.53, P less than or equal to 0.000001). Multiple regression analysis also demonstrated that glucose (P less than or equal to 0.0051) and lactate (P less than or equal to 0.0003) also affected the concentration of C-peptide. We were unable to find any relation between C-peptide concentrations and blood gas variables. We conclude that fetal insulin secretion, measured as C-peptide concentration in fetal blood, is not affected by hypoxia from anemia as long as hemoglobin concentration remains within the range 2.1-14.8 g/dl).

Age Factors↗

Fetal heart rate responses to anemia in Rh isoimmunization.

On 52 occasions 24 Rh immunized women were monitored with a nonstress test (NST) prior to fetal blood sampling. Cardiotocographic characteristics were recorded for each NST. Fetal blood was analysed for hemoglobin and hematocrit. Fetal hemoglobin and hematocrit were positively correlated to long-term variability, acceleration amplitude and negatively correlated to deceleration amplitude (linear regression analysis; p less than 0.05). Decelerations were almost without exception associated with low concentrations of hemoglobin and hematocrit. In fetuses of 32 weeks' gestation or more, a loss of variability (less than or equal to 5 bpm) was associated with severe anemia. Hemoglobin and hematocrit were significantly lower in the group with a pathological NST (n = 15) compared with the group with a normal NST (n = 37) (Mann-Whitney U test; p less than 0.05). The predictive value of a pathological test was 13/15 concerning hemoglobin and hematocrit; whereas, the predictive value of a normal test was poor. A pathological NST, especially when decelerative, is a good predictor of fetal anemia, but a normal NST is no guarantee for a normal blood status.

Anemia↗