Maternal and fetal circulation of unusual bile acids: A pilot study

Background: Large amounts of unusual bile acids are synthesized by the fetal liver in late gestation. These compounds are mostly transferred from fetus to mother, although some are excreted into the amniotic fluid. We investigated the role of placental transfer of bile acids in fetal bile acid metabolism, particularly with respect to the unusual bile acids (1β‐hydroxylated and ketonic bile acids). Methods: We measured concentrations of bile acids in umbilical cord blood and urine of newborn infants, and in perinatal maternal serum and urine, using gas chromatography‐mass spectrometry. Serum and urine specimens from healthy non‐pregnant women were used as controls. Results: In newborn infants at delivery, cord blood and urine contained mostly primary and 1β‐hydroxylated bile acids, respectively. We also detected large amounts of ketonic bile acids in their urine, and the urinary concentration of total bile acids was elevated. Main maternal bile acids at 30 and 35 weeks of gestation and at delivery were 1β‐hydroxylated bile acids. After delivery, main bile acids changed from 1β‐hydroxylated bile acids to primary bile acids (P < 0.03), which also predominated in healthy non‐pregnant women. Conclusion: Fetally synthesized unusual bile acids were transported from fetus to mother. Pregnant women appear to excrete these bile acids into the urine, lowering both fetal and maternal serum bile acid concentrations.     

Non-Enzymatic Glycation of Fetal Tissue in Diabetic Pregnancy

ABSTRACT. Non-enzymatic glycation of fetal tissue was studied by determining the glucitollysine content of umbilical cord extracts from twelve infants of diabetic mothers and fourteen infants of healthy, non-diabetic women (controls). The single, glycated amino-acid glycitollysine, which reflects the extent of glycation processes in biological samples, was measured by a standard amino acid ion exchange chromatography followed by reverse phase high pressure liquid chromatography. Infants of diabetic mothers had significantly higher cord glucitollysine levels than infants of control mothers (14.3+4.6 vs. 5.5+2.1 ng/mg dry tissue; M+SD, p <0.001). Moreover, five infants of diabetic mothers with congenital anomalies had strikingly high glucitollysine levels, higher than the mean +4 SD of the controls. We conclude, that non-enzymatic glycation of fetal tissue does occur as a result of an in utero exposure to cumulative glycemia. Major congenital anomalies in diabetic pregnancies are associated with a greater extent of non-enzymatic glycation of umbilical cord tissue.     

Non-enzymatic glycation of fetal tissue in diabetic pregnancy. Estimation of the glucitollysine content of umbilical cord extracts

Non-enzymatic glycation of fetal tissue was studied by determining the glucitollysine content of umbilical cord extracts from twelve infants of diabetic mothers and fourteen infants of healthy, non-diabetic women (controls). The single, glycated amino-acid glycitollysine, which reflects the extent of glycation processes in biological samples, was measured by a standard amino acid ion exchange chromatography followed by reverse phase high pressure liquid chromatography. Infants of diabetic mothers had significantly higher cord glucitollysine levels than infants of control mothers (14.3 + 4.6 vs. 5.5 + 2.1 ng/mg dry tissue; M + SD, p less than 0.001). Moreover, five infants of diabetic mothers with congenital anomalies had strikingly high glucitollysine levels, higher than the mean +4 SD of the controls. We conclude, that non-enzymatic glycation of fetal tissue does occur as a result of an in utero exposure to cumulative glycemia. Major congenital anomalies in diabetic pregnancies are associated with a greater extent of non-enzymatic glycation of umbilical cord tissue.     

Abnormal umbilical artery Doppler waveforms and cord blood inhibin a and inhibin B levels

Inhibin A and inhibin B are glycoprotein hormones produced by human placenta and by several fetal organs during pregnancy. They are secreted in maternal circulation in increasing amounts from early until term pregnancy, and in umbilical cord blood levels are significantly lower than in maternal serum and do not differ from mid-pregnancy to term gestation. In the present study, we aimed to determine whether secretion of inhibin A and inhibin B into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. A group of women (n = 13) with abnormal Doppler umbilical artery flow velocimetry and a group of control women (n = 11) with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms were studied. In each woman, inhibin A and inhibin B concentrations were estimated in umbilical cord artery and vein. In the two groups of women, mean inhibin A levels did not differ between umbilical cord artery and vein. In addition, no difference was retrieved both in umbilical cord artery and vein values between healthy controls and patients with abnormal Doppler umbilical artery flow velocimetry. On the contrary, inhibin B levels were significantly higher in samples from umbilical cord vein than artery, in both groups of pregnant women (both p < 0.001). However, women with abnormal Doppler umbilical artery flow velocimetry had inhibin B levels significantly higher than healthy controls (p = 0.005) only in the umbilical cord artery, but not in the vein. In the presence of abnormal Doppler umbilical artery flow velocity, the concentrations of inhibin B are increased in the arterial umbilical circulation, suggesting that inhibin B is released from multiple fetal sources as a response to hypoxemic stress. As inhibins may affect the hypothalamus-pituitary-adrenal axis which plays an important role in the mechanisms of adaptations to the post-natal life, inhibin B in fetal circulation might then be beneficial to a fetus whose intrauterine survival is threatened by impaired umbilical-placental blood flow.     

Role of the fetus in perinatal infection and neonatal brain damage

Increasing evidence supports the view that infants exposed to perinatal infection are at increased risk for brain injury. We suggest that elevated cytokines in the amniotic fluid or in the fetal circulation be viewed as a humoral expression and that inflammatory cells in chorionic plate or umbilical cord blood vessel walls be viewed as a morphologic expression of the fetal inflammatory response. We discuss the evidence supporting the hypothesis that the fetal inflammatory response contributes to neonatal brain injury and later developmental disability. Little support has been found for a maternal contribution. Intervention should be designed with the fetus in mind.     

Relationship between newborn and maternal iron status and haematological indices.

The haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, haematocrit, serum iron and total iron binding capacity, and serum ferritin concentrations in umbilical cord blood samples taken from 96 appropriate-for-gestational age infants delivered at term were measured and compared to the respective maternal values measured at 36 weeks' gestation. All the values were higher in cord blood. Only maternal mean corpuscular volume and mean corpuscular haemoglobin were correlated with cord serum iron. Cord blood haematological indices were not correlated with either gestation at delivery or birth weight. However, newborn serum ferritin was positively correlated with gestation at delivery, while the maternal:newborn ferritin ratio was inversely correlated with gestation and birth weight. The results suggest that maternal haematological and iron indices are not predictive of the haemoglobin or iron status of the newborn, and that the fetus continues to take up iron from the mother until delivery.     

Evaluation of umbilical cord pH and its relationship with Apgar score in term newborn infants

The value of the Apgar score as an index of birth asphyxia has been recently questioned. The purpose of the present study is to evaluate the relationship between cord blood pH and Apgar score in term newborn infants.A cross-sectional study involving 76 term newborn infants was performed from March through September 1995 at the Obstetric Unit of Hospital de Clínicas de Porto Alegre. The blood samples were obtained from umbilical cord artery and vein at the moment of delivery. Infants were divided in three different groups according to the Apgar score: Group A (n=60): >or=7 at one and five minutes; Group B (n=13): < 7 at one minute and >or=7 at five minutes; Group C (n=3): < 7 at one and five minutes. The frequency of acidemia in Group A was 18.3% (11 newborn infants) considering arterial pH < 7.20 and 5% considering arterial pH or= 7.20 and nine (56.2%) had arterial pH > 7.10. None of the newborn infants in Group C had arterial pH > 7.10. The sensitivity and specificity values for Apgar score less than 7 at one minute for detection of fetal acidemia were, respectively, 54.1% and 94.1%. This study confirms a poor correlation between Apgar score and umbilical blood cord pH, even in a term newborn, and emphasizes the importance of obtaining umbilical cord pH to consider the diagnosis of perinatal asphyxia.     

Immunoreactive human epidermal growth factor concentrations in amniotic fluid, umbilical artery and vein serum, and placenta in full-term and preterm infants

Immunoreactive human epidermal growth factor (IR-hEGF) was measured in samples taken from 27 full-term and 14 preterm infants. The samples included amniotic fluid, amniotic membranes, fetal and maternal sides of the placenta, and matched umbilical artery and umbilical vein serum. Our results demonstrated the presence of IR-hEGF in the human placenta, amniotic fluid and cord blood during the second half of gestation. The increase in placental tissue, amniotic fluid, and cord blood concentration with progressive gestation suggests a possible functional role for EGF during perinatal development.     

Plasma methionine enkephalin levels in the human newborn at birth

Plasma met-enkephalin immunoreactivity (MET-ENKi) and catecholamine levels were measured in umbilibal cord blood from 46 healthy newborn infants. Clinical data including Apgar scores, birth weight, gestational age, route of delivery, fetal heart tracings and arterial blood gas values were also obtained. Thirty-nine infants were delivered by the vaginal route. All but 1 infant delivered by cesarian section had undergone a trial of labor. Plasma MET-ENKi in the newborn infants was markedly greater than levels found in healthy adult volunteers: 360 +/- 25 versus 25 +/- 2 pg/ml, respectively. MET-ENKi levels were similar in umbilical arterial and umbilical venous blood, and in infants delivered vaginally or by cesarian section.     

Fructose in fetal cord blood and its relationship with maternal and 48-hour-newborn blood concentrations

Background

Studies have suggested that different non-glucose sugars and sugar alcohols play a role in placental and fetal metabolism. However, the role of fructose in the fetal and newborn metabolism is unclear and studies are scarce.

Aim

Our objective was to investigate the presence of fructose in umbilical cord blood in full-term gestation and its relationship with maternal and 48-hour-old- newborn blood concentrations, to evaluate fructose production by the fetus and newborn infant.

Methods

Blood fructose and glucose concentrations were determined by HPLC in 26 paired samples of maternal blood, umbilical cord vein, and peripheral newborn blood at 48 h after birth. ANOVA, the Friedman Analysis of Variance on Ranks and the Pearson correlation with p < 0.05 were used.

Results

Fructose concentration in umbilical cord blood was higher than maternal blood (p = 0.024), suggesting endogenous fructose production by the fetal-placental unit via the sorbitol pathway. Fructose concentrations were higher in newborns at 48 h after birth than in the fetal umbilical cord blood (p = 0.004), suggesting that fructose production is a continuous process from fetus to newborn.

Conclusions

Fructose production by the sorbitol pathway, present in the fetus and newborn, is an alternative pathway in glucose metabolism probably used to maintain redox balance in the fetus. We suggest that endogenous fructose, similar to dietary ingested fructose, under physiological conditions produces the backbone for triacylglycerol and lipid synthesis in the fetus and newborn. Therefore the route for metabolizing fructose is already present in the early steps of human development.     

Morbidity, Mortality, and Placental Pathology in Excessively Long Umbilical Cords: Retrospective Study

The purpose of this study was to compare specific fetal, maternal, and placental factors, including neonatal morbidity and mortality, in infants with umbilical cords (UCs) of normal length to the same factors in infants with excessively long umbilical cords (ELUCs). We performed an 18-year retrospective chart review of the medical records of mothers and infants with ELUCs (926 cases) and normal-length UCs (200 cases) and recorded maternal factors, fetal factors, and neonatal outcomes. Corresponding placental pathologic reports and slides were reviewed. Statistical analysis comparing the two groups included univariate and multivariate analyses. ELUCs were significantly associated with certain maternal factors (systemic diseases, delivery complications, increased maternal age), fetal factors (non-reassuring fetal status, respiratory distress, vertex presentation, cord entanglement, fetal anomalies, male sex, increased birth weight), gross placental features (increased placental weight, right-twisted cords, markedly twisted cords, true knots, congestion), and microscopic placental features (nucleated red blood cells, chorangiosis, vascular thrombi, vascular cushions, meconium, increased syncytial knots, single umbilical artery). Some of these histopathologic features have previously been associated with fetal hypoxia and/or altered blood flow in the placenta. Infants with ELUCs were found to be at a significantly increased risk of brain imaging abnormalities and/or abnormal neurological follow-up. In addition, mothers with a history of an ELUC are at increased risk of a second long cord. Received February 4, 2000; accepted April 24, 2000.     

The water content of the human umbilical cord

105 umbilical cords from 53 term and 52 preterm newborn infants were freeze-dried after removal of the blood vessels, to determine the water content. The mean umbilical cord water content (i.e. mean of water content of fetal and placental ends of the cord), was 88.9% (SD 2.73) for term cords and 91.9% (SD 1.99) for preterm cords. The mean water content fell with increasing gestation. The fetal end of the cord had a significantly higher water content than the placental end. Similarly, the volume of a 4-cm length segment of cord was significantly greater at the fetal than placental end. There was no correlation between cord water content or volume and several other variables including birthweight, size for gestational age and placental weight. These observations suggest a metabolically active role for the umbilical cord.     

Anemia in the newborn

In neonatal period anemia is a complex problem owing to the unique blood picture. The erythrocytic system undergoes serial adaptation to meet progressively changing demands of oxygen in the embryo, the fetus and neonate. This leads to rapid change in normal hematological change in post-birth period. Definition of anemia is difficult because as described earlier, several important factors influence normal blood in the newborn infants. The etiology of neonatal anemia can be classified into i) hemorrhage (ii) hemolysis (iii) failure of red cell production. Severe fetal hemorrhage may accompany various placental anomalies like placenta praevia, abruptio placenta and accidental incision of placenta during the caesarian section. It is reported that 10% of all infants born following placenta praevia and 4% of infants born following abruptio placenta present with severe anemia. The passage of fetal erythrocytes in maternal circulation occurs commonly during pregnancy. In 50% of pregnancies some fetal cells are passed in maternal circulation sometimes during gestation or during birth process. Treatment of a neonate with anemia due to blood depends on the degree of hypovolemia or anemia and whether the blood loss has been acute or chronic. Newborn with pale skin should be differentiated from an asphyxiated baby.     

The effects of acute and chronic perinatal stress on plasma vasopressin concentration and renin activity at birth

The effects of acute and chronic intrauterine stress on plasma vasopressin (AVP) concentration and renin activity (PRA) in the cord blood of 36 newborn infants were studied. AVP concentrations in the umbilical artery were significantly higher than those in the umbilical vein in all infants, except in those delivered by elective cesarean section after normal pregnancy. AVP concentrations in the umbilical arterial blood after normal term pregnancy and vaginal delivery (779 pg/ml, log mean) were higher than those in the cord blood of infants delivered vaginally after maternal hypertensive disease (198 pg/ml). Compared to the values of the latter group, the AVP values were significantly lower (39 pg/ml) in infants delivered by cesarean section without labor because of severe growth retardation and decreased heart rate variability. The group of normal term infants delivered by elective cesarean section after normal pregnancy had the lowest AVP concentrations (13 pg/ml). PRA in the umbilical arterial blood was not different from that in the umbilical venous blood. The highest mean level of PRA (14.5 ng/ml/h) was observed in premature infants delivered by cesarean section because of fetal growth retardation and pathological heart rate variability, and the lowest mean level in term infants delivered by elective cesarean section (3.4 ng/ml/h). PRA was significantly increased in term infants delivered vaginally after normal pregnancy (7.8 ng/ml/h) or after hypertensive pregnancy (11.7 ng/ml/h) in comparison to that of term infants delivered by elective cesarean section.(ABSTRACT TRUNCATED AT 250 WORDS)     

CoQ10 plasmatic levels in breast-fed infants compared to formula-fed infants

BACKGROUND: Coenzyme Q10 has been recognized as an important antioxidant factor besides its main role in bioenergetic metabolism. CoQ10 tissue levels depend both on exogenous dietetic intake and on endogenous biosynthesis, as this compound can be partly synthesized in human cells. Q10 plasma levels reflect the tissue content of the coenzyme and can be used to evaluate the presence of this compound in the human organism. DESIGN/METHODS: Aim of the study was to measure CoQ10 plasmatic levels in a newborn breast-fed population and to compare them to CoQ10 levels in a newborn formula-fed population in order to verify whether changes in CoQ10 plasmatic contents could be related to a different dietetic intakes. We measured CoQ10 plasmatic levels in 25 healthy term neonates with different dietetic intakes: 15 breast-fed and 10 bottle-fed with a common infant formula. These infants were evaluated prospectively during the first month of life. The analyses were performed on the mothers' blood samples and cord blood samples at the time of delivery, then on infants at 4 and 28 days of age. RESULTS: Our results showed markedly reduced Q10 levels in cord blood samples compared to maternal Q10 plasmatic levels at the time of delivery, suggesting placental impermeability towards this molecule or increased fetal utilization during labor and delivery. At 4 days of age Q10 levels had increased in both groups of neonates, but significantly more in breast-fed infants compared to formula-fed babies (p <0.05). At 4 weeks of age no significant changes occurred in breast-fed infants, while values increased significantly in formula-fed infants (p <0.05). The content of Q10 in breast milk samples was lower than in infant formula. CONCLUSIONS: The results of this study show that CoQ10 plasmatic levels are at least partly influenced by the exogenous dietetic supply.     

Surfactant protein D in newborn infants: factors influencing surfactant protein D levels in umbilical cord blood and capillary blood

Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system. The role of SP-D in the metabolism of surfactant is as yet quite unclear. The aims of this study were to establish normal values of SP-D in the umbilical cord blood and capillary blood of mature newborn infants and to assess the influence of perinatal conditions on these levels. A total of 458 infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at age 4 to 10 d. The concentration of SP-D in umbilical cord blood and capillary blood was measured by enzyme-linked immunosorbent assay. The median concentration of SP-D in umbilical cord blood was 392.1 ng/mL and was found to be influenced by maternal smoking and labor. The median concentration of SP-D in capillary blood was 777.5 ng/mL and was found to be influenced by the mode of delivery, the highest levels being observed in infants born by cesarean section. It was concluded that SP-D concentrations in umbilical cord blood and capillary blood are highly variable and depend on several perinatal conditions. Further studies are needed to elucidate the effect of respiratory distress and infection on SP-D concentrations.     

Congenital oral mucosal abnormalities in true umbilical cord knots

OBJECTIVE: The pathogenesis and clinical significance of true umbilical cord knots remain controversial. Here, we tested the hypothesis of the presence of congenital oral mucosal changes in newborns with true umbilical cord knots. STUDY DESIGN: Seven consecutive infants with true umbilical cord knots and 50 gestational age- and sex-matched controls were enrolled. The proportion of oral frenulum abnormalities and the two-dimensional vascular network geometry [fractal dimension, D, at two scales: D(1-46), and D(1-15), with the relative Lempel-Ziv complexity, (L-Z)], were analyzed. RESULTS: Infants with true umbilical cord knots showed significantly higher proportions of mandibular frenulum agenesis compared to controls (p = 0.000006). The oral vascular networks of these infants exhibited a significantly higher D(1-46) and D(1-15) (p < 0.0001, respectively), and higher L-Z values (p < 0.0001) than control networks. CONCLUSION: These findings indicate the presence of significant congenital oral mucosal changes in newborn infants with true umbilical cord knots, thus suggesting a previously unrecognized association between true umbilical cord knots and a subclinical extracellular matrix disorder.     

Transplacental passage of islet cell antibody in infants of diabetic mothers.

The incidence of pancreatic islet cell antibody (ICAb) was assessed in the cord blood and sera of infants of diabetic mothers (IDM). ICAb activity was detected in the cord blood of 10 of 36 (27.8%) consecutive IDM studied and in 0 of 111 (0%) cord bloods of normal control infants. In all instances, ICAb activity in the cord sera was of the immunoglobulin (IgG) class and was associated with ICAb in maternal sera at the time of delivery. No correlation was observed between the incidence of ICAb in IDM and alterations in fetal growth parameters, congenital malformation rates, cord blood insulin levels, or the incidence of neonatal complications. The evidence would support transplacental passage of ICAb from diabetic mothers to their offspring, but would not support a primary pathogenetic role for ICAb in the clinical or metabolic alterations observed in these infants.     

The effect of asphyxia on gut blood flow in term neonates

Transcutaneous Doppler ultrasound measurements were made of the superior mesenteric artery of 25 term infants to correlate the intestinal blood flow with neonatal acid-base status as measured in umbilical artery blood and newborn condition as reflected by Apgar score. Compared with the babies whose umbilical artery pH was higher than 7.20 (peak systolic velocity: 84.1 cn/sn, mean velocity 48.6 cm/sn), the blood flow of superior mesenteric artery was significantly decreased in the newborn babies whose umbilical artery pH was less than 7.20 (peak systolic velocity 48.8 cm/sn, mean velocity=32.6 cm/sn). Although no such relationship existed between Apgar scores and superior mesenteric artery blood flow indices, a significant linear correlation between superior mesenteric artery blood flow and umbilical artery pH was noted. A reduction of intestinal circulation was observed during umbilical cord blood acidemia and hypoxemia.     

Clinical manifestations in term newborn infants with different degrees of acidemia in umbilical cord blood

OBJECTIVE: To verify if Apgar score plus umbilical cord pH are adequate to predict which newborn infant will develop multiorgan system disfunction. METHODS: A study including all term newborn infants with Apgar scores in the first and fifth minutes of life < 7 and umbilical cord blood pH < 7.20 born in Hospital de Clínicas de Porto Alegre from March 1995 through March 1998 was performed. Venous umbilical cord blood was collected for blood gas analysis. Newborn infants were divided in two groups: Group A with pH < 7.0, and Group B with pH >/= 7.0 and < 7.20. Patients were evaluated for the presence of pulmonary hypertension, renal failure, inappropriate secretion of antidiuretic hormone, ischemic cardiopathy, early seizures, neurologic injury at hospital discharge and death. RESULTS: Twenty five newborn infants were included in the study.Twelve formed Group A, and 13, Group B. There were no differences between both groups in respect to mode of delivery, gender, color and birth weight. Group B had a lower gestational age than Group A. There were significant differences between both groups in mean cord blood pH, pCO(2) and BE (p<0.05). There was a positive association between umbilical cord blood pH and Apgar score. Higher occurrence of neurologic injury at hospital discharge in Group A was the only statistically significant clinical manifestation (p<0.05). CONCLUSION: Apgar score and umbilical cord pH are not adequate criteria to predict multiorgan system dysfunction.