Determinants of fetal and maternal atrial natriuretic peptide concentrations at delivery in man

Matched maternal venous (MV), umbilical artery (UA) and umbilical vein (UV) concentrations of atrial natriuretic peptide [ANP] were measured in 36 normotensive women at term delivery (23 vaginal, 13 caesarean) and 17 non-pregnant women in the first half of the menstrual cycle. MV [ANP] at caesarean section was similar to that in non-pregnant women, but UA and UV [ANP] were higher (P less than 0.01 for both). UA, but not UV, [ANP] was markedly raised after vaginal delivery. Plasma concentrations of aldosterone [ALD] were measured in 16 of the matched sets of samples. No statistically significant association was found between [ANP] and [ALD] in either maternal or fetal samples. Neither maternal nor fetal [ANP] correlated with serum Na+ or osmolality, haematocrit, blood pressure or heart rate.     

Glucagon, insulin and glucose levels in maternal and imbilical cord plasma with studies of placental transfer.

Plasma immunoreactive glucagon, as well as insulin and glucose levels, was measured in 62 women and their infants following a term gestation vaginal delivery. Simultaneously obtained samples were drawn from the maternal antecubital vein (MV), umbilical vein (UV), and umbilical artery (UA). Forty-seven of these subjects were untreated (control) and 15 had received a maternal intravenous injection of 1 mg of glucagon within 40 minutes of delivery. It was shown that the umbilical cord glucagon levels were not different from the maternal levels in the control subjects (mean MU, 181.0; UU, 191.9; UA, 161.0 pg/ml). There was no correlation between the maternal and umbilical glucagon levels or the UV glucagon levels and the insulin or glucose concentrations. Neither the fetal sex, placental weight, or infant weight were correlated with the MV or UV glucagon concentration. Following the glucagon injection, the maternal plasma glucagon levels rose significantly, whereas the umbilical blood values did not change. These results suggest that glucagon does not significantly pass through the human term placenta.     

Determinants of fetal and maternal atrial natriuretic peptide concentrations at delivery in man

Summary. Matched maternal venous (MV), umbilical artery (UA) and umbilical vein (UV) concentrations of atrial natriuretic peptide [ANP] were measured in 36 normotensive women at term delivery (23 vaginal, 13 caesarean) and 17 non-pregnant women in the first half of the menstrual cycle. MV [ANP] at caesarean section was similar to that in nonpregnant women, but UA and UV [ANP] were higher ( P <0.01 for both). UA, but not UV, [ANP] was markedly raised after vaginal delivery. Plasma concentrations of aldosteronce[ALD] were measured in 16 of the matched sets of samples. No statistically significant association was found between [ANP] and [ALD] in either maternal or fetal samples. Neither maternal nor fetal [ANP] correlated with serum Na⁺ or osmolality, haematoerit, blood pressure or heart rate.     

Studies on the cortisol levels in maternal vein, umbilical artery, and umbilical vein classified according to the mode of delivery

We measured maternal venous(MV), umbilical arterial(UA), and umbilical venous(UV) cortisol levels of 180 pregnancies at term. In vacuum extraction cases, the cortisol levels of three individual samples were significantly higher than in other modes of delivery. In cesarean section delivery the cortisol levels of three individual samples were the lowest of all modes of delivery. The cortisol level of MV was higher than that of UA and UV in all deliveries. The cortisol levels of three samples showed no difference between the induced labor group and the spontaneous onset of labor group regardless of the delivery mode. In spontaneous vaginal delivery the cortisol levels of three individual samples were significantly higher in primipara than in multipara. Positive correlation was observed in all modes of delivery between the cortisol levels of MV & UA, MV & UV, and UA & UV. There was a negative correlation between the cortisol levels of MV and umbilical arteriovenous cortisol difference in multipara spontaneous vaginal deliveries. There was also a negative correlation between cortisol levels of MV and the umbilical arterial/venous ratio. These data suggest that the fetus may produce cortisol by itself and maternal cortisol may inflow to the fetus.     

Serum cortisol levels of maternal vein, umbilical artery, and umbilical vein classified by mode of delivery

We measured maternal venous (MV), umbilical arterial (UA), and umbilical venous (UV) cortisol levels of 180 pregnancies at term. The cortisol level of MV was higher than that of UA and UV in all deliveries. The cortisol levels of three samples had no difference between the induced labor group and the spontaneous onset of labor group regardless of delivery mode. In spontaneous vaginal delivery the cortisol levels of three individual samples were significantly higher in primipara than in multipara. The positive correlations were observed in any modes of deliveries between the cortisol levels of MV and UA, and MV and UA and UV. These data suggest that the fetus may produce cortisol by itself and maternal cortisol may inflow to the fetus.     

Leptin concentrations in the umbilical vein and artery. Relationship to maternal and neonatal anthropometry

OBJECTIVE: To determine the relationships between serum leptin levels in the umbilical vein (UV) and artery (UA) and the anthropometry of mothers and neonates. STUDY DESIGN: Blood was taken from 61 pregnant women who were admitted for delivery and from the umbilical vein and artery just before delivery of the placenta. Leptin level was measured by immunoradiometric assay. Comparisons between serum leptin concentrations in UVs and both maternal and neonatal anthropometry were made according to neonatal sex. RESULTS: Mean leptin UA and UV concentrations in female infants were significantly higher than those in male infants (both, P = .002). Leptin concentrations in UVs of the total infants were related to maternal body weight and body mass index preconceptionally as well as at birth, to neonatal birth weight, to gestational age, to Kaup index and to body fat content of the infants. CONCLUSION: A sex difference was observed not only in serum leptin concentrations UA and UV but also in the degree of significance between the relationship of cord leptin and both maternal and neonatal anthropometry. Also, the UA leptin level had a closer relationship to neonatal anthropometry, but the UV leptin level was more closely related to maternal anthropometry.     

Umbilical Cord Plasma Glutathione S-Transferase Alpha 1-1 Levels as a Marker of Neonatal Hepatocellular Integrity

Objective: To investigate possible delivery-related impaired neonatal hepatocellular integrity by assessment of arterial and venous umbilical cord plasma levels of glutathione S-transferase Alpha 1-1.Methods: Glutathione S-transferase Alpha 1-1 levels were assessed in arterial and venous umbilical cord, and maternal venous plasma samples. The influence of maternal, delivery, and neonatal characteristics on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels was studied, using linear regression analysis after log-transformation.Results: Median (range) arterial umbilical cord glutathione S-transferase Alpha 1-1 plasma levels were higher than venous umbilical cord levels (9.68 [0.64–1125] μg/L and 7.66 [0.78–987.5] μg/L, respectively, P < .005). Median (range) arterial and venous umbilical cord glutathione S-transferase Alpha 1-1 levels were higher than, and did not correlate with, maternal venous plasma levels (8.79 [1.79–183] μg/L and 6.47 [1.58–164.5] μg/L versus 1.47 [0.46–10.4] μg/L, P < .001). Neonates born vaginally demonstrated higher median (range) levels than those delivered by cesarean (13.41 [1.02–1125] μg/L and 5.73 [0.64–172.90] μg/L, respectively, P < .001). Neonates with unfavorable pH (arterial pH under 7.20) demonstrated higher median (range) levels than those with normal pH (arterial pH at least 7.20) (15.15 [0.77–1125] μg/L and 8.82 [0.64–120.90] μg/L, respectively, P < .001). Stepwise multiple linear regression analysis showed that birth weight had the largest influence on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels, followed by arterial base deficit, and route of delivery.Conclusion: Arterial umbilical cord glutathione S-transferase Alpha 1-1 plasma levels, being unrelated to maternal venous levels, might give a reliable impression of early neonatal hepatocellular integrity and may become an additional indicator of neonatal condition immediately after birth.     

Prolactin levels in blood from the intervillous space of the human placenta

The secretory products of the human placenta are released in the intervillous space (IS), which also represents the main site of maternal-fetal exchange. This compartment, however, has not been studied in terms of prolactin (PRL) metabolism during gestation. In the present study we determined PRL levels in maternal peripheral (MP) blood, in blood from the IS and in blood from the umbilical artery (UA) and vein (UV) of 24 clinically normal parturients and their concepti. PRL levels in MP plasma (means = 111.7 +/- 5.5 ng/ml) did not differ significantly (p greater than 0.05) from those in IS plasma (means = 131.6 +/- 64.3 ng/ml). PRL levels in UA plasma (means = 206.2 +/- 67.5 ng/ml) also showed no significant difference (p greater than 0.05) from those in UV plasma (means = 243.8 +/- 86.1 ng/ml) but both were significantly higher than MP and IS plasma levels (p less than 0.01). These data permit us to conclude that the placenta may not be the source of PRL circulating in maternal peripheral blood.     

Lumbar epidural analgesia with bupivacaine in labor. Drug concentration in maternal and neonatal blood at birth and during the first day of life.

Lumbar epidural analgesia with bupivacaine was administered to 33 women for relief of pain during labor. At delivery blood samples were drawn from the umbilical cord vessels and from a maternal peripheral vein. Blood samples were also collected from the noenate and its mother, 1, 4, and 20 hours after delivery. Analyses of bupivaccaine concentrations were carried out in all samples with a gas-chromatographic technique. The drug concentration in the umbilical vein (UV) was usually higher than the corresponding umbilical artery value (UA), but with increasing time interval between the last bupivaccaine infection and delivery the UA/UV drug concentration ratio rose. After delivery the rate of drug decline in blood was similar in mother and newborn infant. The clinical condition of the infant was unrelated to the drug concentration in the umbilical cord vessels.     

Cyclic adenosine 3',5'-monophosphate (cAMP) in pregnancy body fluids during normal and abnormal pregnancy.

cAMP levels in maternal urine (MU), maternal plasma (MP), and amniotic fluid (AF) were measured by competitive protein-binding assay in medically uncomplicated pregnancies (Group A) and some abnormal pregnancies (Group B). In Group A, MU values increased from 3.43 +/- 0.3 mu/Moles per gram of creatinine (mean +/- S.E.M.) at 12 to 29 weeks to its peak value, 5.72 +/- 1.03 at 33 to 35 weeks (p less than 0.025). Thereafter, the values decreased until term. In AF, cAMP levels increased from 9.4 +/- 1.02 at 10 to 19 weeks to 32.6 +/- 2.7 picomoles per milliliter between 35 and 42 weeks (p less than 0.005). Mean +/- S.E.M. MP levels between 4 to 20 and 21 to 42 weeks showed no significant difference (14.97 +/- 15.89 +/- 0.57 picomoles per milliliter, respectively). Umbilical cord plasma contained higher concentrations than in MP and AF. In Group B, abnormal MU patterns were observed in hypertensive disorders, chronic renal disease, and postmaturity. In a single patient with hyperthyroidism, abnormal MU and AF (but not MP) levels were observed. Abnormalities in MU and AF concentrations of the nucleotide are thus not specific for one disease entity.     

Feto-maternal plasma oxytocin levels in normal and anencephalic pregnancies

In 4 women with anencephalic fetuses, the oxytocin level was measured in the maternal plasma in the second stage of labor and in the umbilical artery (UA) and umbilical vein (UV) by radioimmunoassay (RIA). In these cases, the mean maternal OT level was 13.4 +/- 8.0 microU/ml (mean +/- S.E.), which was not significantly different from the OT levels in cases of normal spontaneous birth and elective cesarean section. The UA and UV plasma OT levels in these cases were below the detectable level (less than 2 microU/ml), whereas in normal spontaneous births, they were 18.2 +/- 4.9 microU/ml and 12.2 +/- 2.3 microU/ml, respectively. The OT level in the UA was higher than that in the UV. There was no difference between the mean OT levels in patients with, versus those without contractions, but the plasma OT levels in the second stage of labor were higher than those in the first stage. In normal pregnancies the plasma OT concentration increased during parturition. These results suggest that placental transfer of maternal plasma OT to the fetal circulation is limited, and that in cases of anencephalic fetuses, maternal labor does not necessarily require fetal OT as a trigger or for its maintenance.     

The effect of diazepam on neonatal neurobehavioral response

Diazepam was administered I.V. in 10mg doses to 26 normal women in labor, and its blood concentration in the mother and newborn, Apgar score and acid-base status in umbilical cord blood were determined immediately after delivery. The effect of diazepam on the neurobehavioral response of the newborn was evaluated by using the early neonatal neurobehavioral scale (ENNS) by Scanlon et al. Diazepam was swiftly transported into fetal blood through the placenta, to attain a higher blood concentration in the umbilical vein (UV) than in the maternal vein (MV) at 1-2 min after administration. The UV blood concentration of diazepam was always higher than the MV blood concentration, irrespective of the time between administration and delivery. A comparison of the blood concentration in the umbilical vein and the umbilical artery (UA), showed that the UV blood concentration was higher until 30 min after administration, but roughly eqalled the UA blood concentration thereafter. In terms of mean values in all the patients, the blood concentration in the UV (506 +/- 245 ng/ml) was significantly higher than that in the MV (350 +/- 204 ng/ml) or the UA (394 +/- 142 ng/ml). No significant difference was detected between the diazepam-treated group and the control in respect to the Apgar score, acid-base status in cord blood, neonatal serum bilirubin or time required for restration of the newborn to body weight at birth. The ENNS test showed suppression of nearly all the response immediately after birth, with suppression of response to pinprick, rooting response and sucking response persisting until 8 hr after birth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Perinatal glucose metabolism as an indicator for stress and hypoxia during different forms of delivery

In 82 term newborns divided into three groups (spontaneous delivery, caesarean section and vacuum extraction) we investigated umbilical artery pH, artery and vein glucose levels and calculated the veno-arterial difference of glucose. The three groups showed significant differences of artery and vein glucose levels. The highest umbilical artery (UA) and umbilical vein (UV) glucose levels were found after vacuum extractions (n = 13, UA: 98 mg/dl, UV: 104 mg/dl), the lowest levels were present in the group of caesarean section (n = 16, UA: 52 mg/dl, UV: 65 mg/dl). After spontaneous deliveries the intermediate levels were observed (n = 55, UA: 70 mg/dl, UV: 84 mg/dl). The mean of UA-UV-glucose difference was low after vacuum extractions and statistically different from the values after caesarean section and spontaneous deliveries. The mean of UA-pH did not show statistically significant differences in the three groups. The regression analysis between UA-pH and UA-UV-glucose difference revealed a highly significant dependency in the group of caesarean section (p less than 0.01) but no dependency after vacuum extraction. Significant dependency was also found in the group of spontaneous delivery (p less than 0.05).     

Maternal and fetal circulating sKL and ET-1 levels as function of normal labor at term

Objectives.?To determine whether labor is associated with alterations of the levels of soluble c-kit ligand (sKL) and endothelin-1 (ET-1) in maternal plasma and umbilical cord blood.

Methods.?The sKL and ET-1 levels were investigated in umbilical cord and maternal plasma on the day of delivery in 18 pregnant women with vaginal delivery during labor, 18 non-pregnant women and 9 pregnant women before cesarean delivery, using an ELISA assay.

Results.?Umbilical cord plasma sKL levels were significantly higher than the maternal plasma in both types of delivery (p?=?0.0001, p?<?0.0001, respectively). However, maternal plasma ET-1 levels in the presence of labor were significantly higher than the cesarean delivery group (p?<?0.0001). No difference was noted for sKL and ET-1 in umbilical cord vessels of both groups. Furthermore, a highly significant inverse correlation was documented between the individual levels of cord plasma ET-1 and the levels of cord plasma sKL (r?=??0.6269, p?=?0.0054).

Conclusions.?The sKL levels found in umbilical cord plasma are consistent with the pleiotropic effects of sKL in facilitating the transition of the fetus to the neonatal stage. The reduced ET-1 maternal plasma levels, compared to non-pregnant women, probably are indicative of a putative mechanism for embryo protection from vasoconstriction sequelae. This assumption is strengthened by the corresponding ET-1 levels in umbilical cord plasma.     

Studies on catecholamine and its metabolites in the evaluation of fetal distress]

To determine the usefulness of catecholamine (CA) levels in the evaluation of fetal distress during delivery, norepinephrine (NE), its intermediate metabolite 3,4-dihydroxyphenylethyleneglycol (DOPEG), and 3,4-dihydroxyphenylacetic acid (DOPAC), which is the main intermediate metabolite of dopamine (DA), were simultaneously measured in umbilical arterial and venous blood (UA, UV) and in maternal venous blood (MV). The correlations of these concentrations with blood pH and the 1-min. Apgar score were examined. Of the 124 subjects studied, 24 had elective cesarean section (CS), and 100 had vaginal delivery (VD), which was uncomplicated in 84 (ND) and complicated by fetal distress in 16 (FD). The results were as follows: 1. In the ND, FD and CS groups, UA-NE and UA-DOPEG levels were high, as follows: FD group greater than ND group greater than CS group and FD group greater than ND, CS group, respectively. 2. There were no significant differences between DOPAC levels in UA, UV and MV plasma and in FD, ND and CS groups. 3. In the ND group, higher UA-NE values were found in the group at UA-pH less than 7.20 than in those at UA-pH greater than or equal to 7.20, but UA-DOPEG values did not vary significantly with UA-pH. 4. In the ND group, higher UA-DOPEG values were found with Apgar score less than or equal to 7 than with Apgar score greater than or equal to 8, but UA-NE values did not vary significantly with the Apgar score.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placental transfer of intravenous nicardipine and disposition into breast milk during the control of hypertension in women with pre-eclampsia

Objective: To assess nicardipine safety for fetuses and neonates. Methods: Nicardipine was measured in maternal plasma (MP), umbilical cord arterial (UaP) and venous (UvP) plasma and breast milk (BrM) of 18 women with severe preeclampsia. Results: Nicardipine was infused for a mean 11.9?±?10.5 days before and 4.6?±?1.6 days after delivery. Nicardipine dose and MP concentration were linearly correlated, as were MP with UaP, UvP, and BrM concentrations. The BrM/MP ratio was 0.06 to 0.30. The mean relative infant dose was 0.082%. Conclusion: Nicardipine is safe for fetuses and neonates due to its low levels of placental transfer and disposition in BrM.     

Endothelin in maternal and umbilical cord blood in spontaneous labor and at elective cesarean delivery.

We measured endothelin-1, a potent vasoconstrictor peptide released by the vascular endothelium, in maternal, umbilical cord, and retroplacental blood plasma in cases of spontaneous and elective cesarean delivery. Mean (+/- standard error) endothelin-1 in the maternal plasma increased with advancing pregnancy, from 1.2 +/- 0.13 pmol/L at 32-34 weeks to 2.4 +/- 0.2 pmol/L at 38-41 weeks (P less than .01) and 3.4 +/- 0.3 pmol/L (P less than .02) during labor. Concentrations were significantly higher in umbilical cord plasma than in maternal venous plasma, and higher in the cord venous plasma after vaginal delivery (52.9 +/- 11.4 pmol/L) than after cesarean performed before the onset of labor (9.0 +/- 1.1 pmol/L) (P less than .001). In spontaneous labor, concentrations in the retroplacental blood plasma (23.3 +/- 4.5 pmol/L) were approximately ten times higher than those in the maternal peripheral blood. Levels in the umbilical cord and retroplacental blood plasma were the highest found so far in any physiologic condition, suggesting that an increased intrauterine release of endothelin-1 at delivery may promote constriction of the blood vessels in the umbilical cord and placental bed.     

The impact of chorionicity on umbilical cord acid-base values in twin gestations.

OBJECTIVE: To evaluate the impact of chorionicity on inter-twin differences in acid-base status at birth. METHODS: Records for twin pregnancies delivered at > or = 24 weeks' gestation from 1 January 1990 to 31 June 2000 were reviewed. Collected data included maternal demographics, gestational age, fetal presentation, anesthesia, delivery mode, inter-twin interval, umbilical artery (UA) and venous (UV) acid-base values, Apgar scores and birth weights. The influence of chorionicity on umbilical cord biochemistry was evaluated. (p < 0.05 was considered significant.) RESULTS: Analysis was carried out in 87 twin pairs (29 monochorionic, MC; and 58 dichorionic, DC). MC and DC twins were similar in maternal age (25.5 vs. 28.2 years), estimated gestational age (33.7 vs. 33.6 weeks), Cesarean delivery (55.2 vs. 52.6%), delivery interval (10 vs. 5 min) and respective birth weights (twin A, 1882 vs. 1981; and twin B, 1828 vs. 1872 g). MC first twins had a higher UA pH (7.31 +/- 0.05 vs. 7.26 +/- 0.08; p = 0.0005) than DC first twins. MC first and second twins had higher UA and UV bicarbonate levels than their DC counterparts (DeltapH = 21.7 +/- 5.1 vs. 18.5 +/- 3.1 mmol/l and 22.0 +/- 3.5 vs. 19.6 +/- 2.5 mmol/l, respectively; p = 0.003). MC twins were more discordant in UA pH than DC twins (DeltapH = 0.043 +/- 0.09 vs. 0.003 +/- 0.07; p = 0.009). MC and DC twins had a similar venous pH (DeltapH = 0.01 +/- 0.06 vs. 0.02 +/- 0.06; p = 0.5). CONCLUSIONS: There is a significant association between placental chorionicity and umbilical cord biochemistry in twins. Although it is possible that the mechanism of this finding is related to placental angioarchitecture, it is unlikely to be a result of simple mixing of blood volumes between twins. The physiology of underlying processes requires further study.     

High levels of human chromogranin A in umbilical cord plasma and amniotic fluid at parturition

OBJECTIVE: The human placenta is a neuroendocrine organ that produces several hypothalamic and pituitary hormones that are secreted during pregnancy and parturition into maternal and fetal circulation and amniotic fluid. Human chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla and released in response to several stressful events. During pregnancy, intrauterine tissues express and synthesize CgA mRNA and peptide and secret it into the biologic fluids of pregnancy, so we investigated whether maternal, umbilical, and amniotic human CgA levels are affected by the stress of parturition. METHODS: We measured pregnancy CgA levels in maternal and umbilical cord plasma and in amniotic fluid at term (39-40 weeks), by enzyme-linked immunosorbent assay at elective cesarean (n = 16), after spontaneous vaginal delivery (n = 12), and longitudinally throughout labor and 2 hours postpartum. RESULTS: CgA levels were highest in umbilical cord blood (P <.001). Umbilical cord plasma and amniotic fluid CgA levels were significantly higher at spontaneous vaginal delivery than at cesarean (P <.001), and the levels were not changed in maternal plasma according to cervical dilatation and postpartum. CONCLUSIONS: The present findings showed that the stress of parturition increased CgA levels in umbilical cord plasma and amniotic fluid and was probably of fetal origin. Whatever the mode of delivery, CgA levels in infants were much more elevated than in mothers, providing evidence for an unusual and sustained high level of sympathoadrenal stimulation in full-term neonates.     

Plasma oxytocin in human pregnancy and parturition

Oxytocin concentrations were determined in serial peripheral plasma samples collected from clinically normal women during pregnancy and labor. Measurable concentrations of this hormone were detected in all maternal plasma samples during pregnancy, but there were wide differences in values between patients. Serial samples from individual patients revealed a pattern of gradual rise of oxytocin levels with advancing gestation and the increase in concentration was statistically significant. There were no significant differences in oxytocin levels at any stage of labor, with or without epidural analgesia. Oxytocin levels at the onset of the second stage did not differ statistically from those at crowning. Comparison of cross-sectional data showed no significant difference between the mean oxytocin concentration in early labor and in late pregnancy. Oxytocin surges occurred, but not in a regular pattern. Plasma oxytocin concentration did not increase after pelvic examination, sweeping of the membranes, low amniotomy or after cervical vibration. After spontaneous vaginal delivery, umbilical arterial plasma levels of oxytocin were consistently higher than plasma concentrations from the umbilical vein. The fetal arterio-venous difference was less pronounced at elective cesarean section. At spontaneous vaginal delivery, with and without epidural anesthesia, plasma levels from the umbilical artery were significantly higher than the maternal levels. After vaginal delivery, oxytocin levels in cord plasma were significantly higher than at elective abdominal delivery. Some methodological aspects with regard to blood sampling and to plasma oxytocin radioimmunoassay procedures are discussed. From the results presented it is concluded that the human fetus can be an important source of oxytocin and that neurohumoral birth reflexes described in animals do not occur systematically in man.