Umbilical Blood Concentrations Research Articles

Maternal SARS-CoV-2 Infection at Delivery Increases IL-6 Concentration in Umbilical Cord Blood.

SARS-CoV-2 infection in pregnant women may induce inflammation within the amniotic cavity and/or an increase in proinflammatory cytokines in fetal circulation. The aim was to investigate levels of IL-6 in maternal blood, umbilical cord blood, and amniotic fluid in pregnant women infected with SARS-CoV-2 at delivery. A single-center prospective observational case-control study of pregnant women diagnosed with SARS-CoV-2 infection at delivery was conducted. A total of 48 infected and 42 healthy women had IL-6 concentrations measured in their blood, amniotic fluid, and umbilical cord blood. The concentrations of IL-6 in maternal blood and amniotic fluid were similar in the study and control groups, while umbilical cord blood concentrations were significantly higher in SARS-CoV-2-positive women. The umbilical cord blood IL-6 concentration was related to composite neonatal morbidity. Maternal SARS-CoV-2 infection in pregnant women at delivery increases umbilical cord blood IL-6 concentration. The correlation between maternal and umbilical blood concentrations indicates a possibility of passage of IL-6 through the placenta. Perinatal alterations resulting from maternal SARS-CoV-2 infection at delivery carry a risk of impacting the health of infants even in asymptomatic course of infection.

Oxytocin Dosing and Maternal-Fetal Effects Using a Pharmacokinetic Model

Objective- Although oxytocin is widely used in labor and childbirth, questions remain regarding the pharmacokinetics (PK), pharmacodynamics (PD) and dose of oxytocin in pregnant people as well as the potential effects on the fetus and newborn. The objective of the current study was to use published studies to investigate the PK/PD and dose of oxytocin in pregnancy, examine the placental transfer of oxytocin through the development of a physiologically-based PK (PBPK) model, and postulate whether the model predicts the effect(s) of oxytocin on fetuses and newborn infants. Methods- A literature review of articles related to oxytocin in the areas of PK/PD, placental transfer and its influence on newborns were reviewed and summarized. A PBPK model for oxytocin was developed to predict maternal-fetal transfer. Results- Previous studies have demonstrated a positive relationship between the plasma oxytocin concentration and uterine contractions during labor. An ex vivo study demonstrated maternal to fetal and fetal to maternal oxytocin transfer, but a clinical study investigating oxytocin concentrations in umbilical blood could not confirm these results. Previous studies have suggested that a high concentration of oxytocin is related to fetal bradycardia and possibly autism in the child. Conclusion- The current study developed a PBPK model to measure the placental transfer of oxytocin and its potential for adverse effects on the fetus and developing child. Further research is needed to determine oxytocin’s efficacy and safety in the maternal population and in their fetuses and developing children, and modeling techniques such as PBPK will contribute to that understanding.

Evaluation of Creatine Kinase, Lactate Dehydrogenase, and Amylase Concentrations in Umbilical Blood of Preterm Infants after Long-Term Tocolysis

Creatine kinase (CK), lactate dehydrogenase (LDH), and amylase levels of preterm infants following long-term tocolysis in pregnant women are limited. The objective of this study was to determine if the tocolytic therapy affects CK, LDH, and amylase levels in the umbilical blood. This study included 215 preterm infants born to women treated with and without ritodrine hydrochloride. CK, LDH, and amylase levels in the umbilical blood at delivery were determined. Infants were divided according to the ritodrine tocolysis, as follows: Group A (n = 91), not exposed to ritodrine; Group B (n = 44), IV ritodrine for <1 week; Group C (n = 80), IV ritodrine for ≥1 week. The CK concentration in cord blood of Group C (198.8 ± 14.2 IU/L) was significantly higher in comparison with Group A (155.0 ± 7.3 IU/L, P < 0.05). There was no significant difference in LDH and amylase levels in the three groups. The CK significantly correlated with gestational age (r = 0.42, P < 0.01) and birth weight (r = 0.38, P < 0.01). LDH and amylase levels did not change with gestational age nor birth weight. In conclusion, long-term ritodrine tocolysis leads to increased umbilical blood CK level.

Effects of different modes of delivery on arterial oxygen saturation in the fetus

Objective To compare the effects of different modes of delivery on arterial oxygen saturation in the fetus.Methods One hundred and twenty ASA Ⅰ or Ⅱ parturients aged 22-32 yr with a single fetus at full term lying in normal headdown position were divided into 3 groups according to the modes of delivery (n =40 each):group cesarean section (group CS) ; group labor analgesia (group LA) and group spontaneous labor (group SL).In group CS cesarean section was performed under epidural anesthesia with 0.5％ ropivacaine.Epidural catheter was placed at L2,3 interspace in groups CS and LA.In group LA labor analgesia was started from the first stage and maintained until complete cervical dilatation.The patients received epidural PCA (PCEA) with O.125 ％ropivacaine plus fentanyl 2 μg/ml.PCEA setting was as follows:a loading dose of 8-10 ml; demand bolus 5 ml;20 min lockout; background infusion 6-10 ml/h.Blood samples were taken from umbilical artery at delivery for blood gas analysis and determination of serum concentrations of lactate,β-endorphin (β-EP) and neuropeptide Y (NP-Y).Apgar score and neurological and adaptive capacity score (NACS) were recorded.Results There was no significant difference in Apgar score,NACS and NP-Y and β-EP concentrations in umbilical arterial blood among the 3 groups.The lactate concentration and the absolute value of BE were significantly higher while pH was lower in group SL than in groups CS and LA.PO2 was significantly higher while PCO2 was lower in group LA than in groups SL and CS,and the lactate concentration and absolute value of BE were significantly lower while pH was higher in group LA than in group SL.Conclusion The 3 modes of delivery have significant effects on arterial oxygenation in fetus but have no clinical significance. Key words: Analgesia, obstetrical; Analgesia, epidural; Labor; Oxygen consumption ; Fetus

Effects of combined spinal-epidural analgesia and patient controlled epidural labor analgesia in latent and active phase

Objective To compare the effects,stress reaction and concentration of ropivacaine in umbilical cord blood of patients who accepted combined spinal epidural analgesia or patient controlled epidural labor analgesia in latent and active phase.Methods After approved by the ethics committee and informed consents from 80 nulliparous parturients who were admitted to Beijing Friendship Hospital,Capital University of Medical Sciences between January to June 2009,and who were term,single,cephalic presentation delivery and ASA Ⅰ-Ⅱ,were divided into two groups randomly:latent phase group (Group L,cervical dilation 0.5-2.5 cm,n=40) and active phase group (Group A,cervical dilation ≥3.0 cm,n =40).Ropivacaine 2 mg and fentanyl 10 μg was administered in subarachnoid space of all patients.Then,patient controlled epidural infusion of 0.1 ％ ropivacaine plus fentanyl 2 μg/ml were administered.Pain scores (visual analogue score,VAS),lower extremity muscle strength,duration of labor,delivery mode,total dosage used,maternal satisfaction,Apgar score (1 min and 5 min) were evaluated; concentration of ropivacaine (high performance liquid chromategraphy) in cord blood,and concentration of cortisol (radioimmunoassay) in maternal venous blood and cord blood were detected.Forty nulliparous parturients without labor analgesia were taken as control group (Group C).Chi-square test and one way analysis of variance was applied for statistical analysis.Results (1) VAS in Group L and Group A were lower than that of Group C when cervix dilated at 7.0-8.0 cm (2.9± 1.4,2.6± 1.5 vs 9.2±0.7,F=201.50,P＜0.01) and fully dilated (4.7±2.2,3.6±2.0 vs 9.1±0.7,F =-62.07,P＜0.01,respectively).(2) Tbe concentration of cortisol in maternal venous blood right after delivery was higher than that before analgesia in all groups,and the change in group C was significantly greater than that in group L and group A [(902±172) μg/L vs (761±125) μg/L and (731±184) μg/L,t =-3.491 and-3.483,all P＜0.01],moreover there was no significant difference between group L and group A (P＞0.05).There were no difference in cortisol concentration of umbilical blood among the three groups [(168±46) μg/L,(159±49) μg/L and (170±86) μg/L,F=0.23,P＞0.05].(3) There was no difference between ropivacaine concentration in umbilical blood of group L and group A [(0.21±0.10) mg/L vs (0.20±0.03) mg/L,t=0.557,P＞0.05].(4) No significant differences was shown among the three groups in the duration of first and second stage of labor,rate of augmentation,neonatal birth weight,Apgar score at 1 min and 5 min (all P＞0.05).Compared with group C,group L and group A had higher rate of vaginal delivery (52.5％ vs 75.0％ and 85.0％,P＜0.05) and lower rate of cesarean section (45.0％ vs 20.0％ and 15.0％,P＜0.05).The duration of analgesia in group L was longer than that in group A [(215±143) min vs (118±50) min,t =3.722,P＜0.01] and the dosage of fentanyl was also higher [(28± 11) μg vs (17±6) μg,t =5.084,P＜0.01].Conclusions Labor analgesia with combined spinal epidural could decrease cesarean section rate and maternal stress reaction without prolonging the duration of labor and inhibiting neonatal stress reaction.Labor analgesia start from latent phase would not increase the concentration of ropivacaine in cord blood. Key words: Lobor, obstetric; Analgesia, obstetrical; Analgesia, patient-controlled; Anesthesia, epidural; Anesthesia, spinal

Increased Umbilical Cord Plasma Interleukin-1 Levels was Correlated with Adverse Outcomes of Neonatal Hypoxic-ischemic Encephalopathy

To explore whether or not the umbilical blood levels of cytokines can be used to indicate the adverse outcomes of hypoxic-ischemic encephalopathy (HIE) patients. Umbilical artery blood and peripheral venous blood samples were collected on the 1st, 3rd and 7th days after birth to detect the levels of IL-1 beta, IL-8 and TNF-alpha. Neurological examination and Denver developmental screening test (DDST-II) were performed at the 6 and 12 months evaluations to detect any neurodevelopmental abnormalities. The results showed: (i) the serum concentrations of IL-1 beta, IL-8 and TNF-alpha in umbilical and peripheral blood were significantly higher in HIE patients than control groups; (ii) the umbilical blood concentrations of IL-1 beta exhibited the best positive correlation with HIE grades, when compared with IL-8 and TNF-alpha; and (iii) abnormal neurological outcomes at 6 and 12 months of age were best predicted by umbilical levels of IL-1 beta. Thus, umbilical concentrations of IL-1 beta were associated with the grades and adverse outcomes of HIE.

Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood

Endothelial cells produce nitric oxide (NO), a potent vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Little is known about the potential physiological roles of ADMA in a perinatal setting. This study measures concentrations of ADMA in umbilical blood using enzyme-linked immunosorbent assay and those of NO as nitrite/nitrate (NOx −) using the Griess assay. Their relationship to the degree of prematurity and maternal clinical condition is examined. Results show that ADMA concentrations in umbilical blood from control newborns were about twice as high as those of lactating women, healthy children, and healthy adults. Umbilical blood NOx − concentrations from control newborns were about half of those of lactating women, healthy children, and healthy adults. Consequently, the levels of ADMA relative to NOx − were about 4-fold higher in umbilical blood from control newborns than in blood from lactating women, healthy children, and healthy adults. Furthermore, the umbilical blood ADMA concentrations and the ratios of ADMA to NOx − in newborns were higher according to their birth prematurity and lower birth weight. The umbilical ADMA concentrations were independent of the delivery mode and maternal preeclampsia. We infer that the high ADMA levels play physiological roles in maintaining vascular tone and blood redistribution to vital organs during birth, thereby favoring the circulatory transition from fetal to neonatal life.

Impact of the mother's zinc deficiency on the woman's and newborn's health status

The results of studying the prevalence of zinc deficiency in pregnant women and children at birth are presented. About 77% of the mothers and, in average, every third–fifth child depending on gestational age at birth have decreased serum zinc concentration (below 13 μmol/L). Malnutrition regarding macro- and micronutrients increases the risk of zinc deficiency in examined women (AP=28%; RR=1.4; CI=0.9–3.5). Zinc deficiency increases the risk of pregnancy complications, exacerbations of chronic diseases with gestation as background, labor activities disorders, with hypogalactia and decreasing zinc concentration in the breast milk as concomitant conditions. A relationship between the mothers’ serum zinc concentration and trace element concentration in umbilical blood, body height and body mass, adaptive possibilities and child morbidity at birth has been established. Children in their first year of life with a zinc concentration in umbilical blood below 13 μmol/L are characterized by reduced rate of linear growth, delay of psycho-motor development and increased morbidity.

Concentrations of Pentosidine, an Advanced Glycation End-product, in Umbilical Cord Blood

Advanced glycation end-products (AGEs) are formed over several weeks to months by non-enzymatic glycation and oxidation (“glycoxidation”) reactions between carbohydrate-derived carbonyl groups and protein amino groups, known as the Maillard reaction. Pentosidine is one of the best-characterized AGEs and is accepted as a satisfactory marker for glycoxidation in vivo. The present study was intended to measure pentosidine concentrations in umbilical cord blood from newborns with various gestational ages using our recently established high-performance liquid chromatography method [Tsukahara, H. et al. (2003) Pediatr. Res. 54, 419–424]. Our study demonstrates, for the first time, that pentosidine is detected in most of the umbilical blood samples. This study also shows that the umbilical blood concentrations of pentosidine are considerably lower than normal adult values, but that they increase with gestation progression and fetal growth. Umbilical pentosidine concentrations were significantly elevated in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. We conclude that accumulation of AGEs and oxidative stress occurs in fetal tissues and organs in utero at the early stage of human life and that their accumulation is augmented in the maternal preeclampsic condition.

Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy.

Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre-eclampsia. To provide a basis for elucidation of the relationship between pre-eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood. Fifty-nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8-20 weeks' gestation (early), 11 at 28-34 weeks (middle) and 24 at 35-40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method. The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood. This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.

Effects of High-Inspired Oxygen Fraction During Elective Caesarean Section Under Spinal Anaesthesia on Maternal and Fetal Oxygenation and Lipid Peroxidation

Women undergoing cesarean section under regional anesthesia commonly receive supplemental oxygen. A high oxygen fraction may be administered to enhance fetal oxygenation, but this measure also may increase free radical formation and promote lipid peroxidation in both mother and infant. This prospective randomized double-blinded study was intended to clarify the effects of a high-inspired oxygen fraction on these parameters. Forty-four parturients in good general health (ASA I-II) were randomly assigned to breathe either air (containing 21% oxygen) or 60% oxygen during elective cesarean section using the ventimask, a high-flow Venturi-type facemask. Spinal anesthesia was performed using 0.5% hyperbaric bupivacaine and fentanyl. Maternal arterial blood was sampled every 5 minutes, and umbilical cord blood at delivery. Blood gases were measured as well as products of lipid peroxidation including 8-isoprostane, malondialdehyde (MDA), and hydroperoxide (OHP). Maternal and fetal characteristics and operative variables were similar in the air and high-oxygen groups. Oxygen-treated women had higher arterial PO 2 levels at the time of delivery, the mean difference being 16 kPa (P <.001). They also had higher umbilical cord blood venous PO 2 levels than women breathing room air, with a mean difference of 0.8 kPa (P <.04). Both maternal and umbilical blood concentrations of 8-isoprostane, DA, and OHP were greater in women given supplemental oxygen. In both groups, maternal arterial PO 2 correlated positively with umbilical venous levels of 8-isoprostane, OHP, and MDA. Plasma MDA levels increased significantly within 10 minutes of beginning oxygen supplementation. All Apgar scores that exceeded 7 and 9 at 1 and 5 minutes, respectively. Healthy women undergoing cesarean delivery experience a modest increase in fetal oxygenation when breathing a high-inspired oxygen fraction during surgery, but levels of oxygen free radicals increase in both the mother and fetus. The clinical import of the latter observation remains uncertain. In view of the limited benefit, patient discomfort from wearing an oxygen facemask might be taken into account.

Third trimester fetal growth and umbilical venous blood concentrations of IGF-1, IGFBP-1, and growth hormone at term.

Insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1) and growth hormone (GH) concentrations were measured in umbilical venous blood after delivery of 78 term newborn infants. Three groups of pregnancies were prospectively identified during the third trimester, according to fetal size and subsequent fetal growth, assessed by repeated ultrasound scans. Fetal size was considered either appropriate for gestational age (AGA) or small for gestational age (SGA), according to whether the first ultrasound measurement of abdominal circumference was equal to or above, or below the tenth centile for gestational age, respectively. Subsequent fetal growth was quantified by the change in the standard deviation score of abdominal circumference measurements between the first and last scans before delivery. Fetal growth retardation (FGR) was defined as a (negative) change in SD score of greater than -1.5. Eighteen SGA fetuses with evidence of FGR had significantly lower IGF-1 (median 0.05 (range 0.0-0.24) U/ml) at delivery than 35 SGA fetuses with normal growth (median 0.13 (range 0.0-0.94) U/ml; P < 0.05) and 25 AGA fetuses with normal growth (median 0.31 (range 0.0-0.84) U/ml; P < 0.05). The median concentration in the SGA group with normal growth was also significantly lower than that of the AGA group with normal growth. There were no significant differences in IGFBP-1 or GH concentrations between the three groups. These observations indicate that umbilical blood concentrations at birth of IGF-1, but not IGFBP-1 or GH, relate to both fetal size and fetal growth during the third trimester of pregnancies reaching term.

Maternal and cord serum levels of tissue polypeptide antigen (TPA) in normal pregnancies.

The tumor antigen and cytoskeleton protein tissue polypeptide antigen (TPA) have been determined in maternal serum throughout pregnancy. TPA levels in serum from pregnant women (n = 70) were not different from those in nonpregnant women (n = 61) until pregnancy week 28, from which time levels increased until parturition. Duplex pregnancies (n = 7) had higher serum TPA concentrations than simplex pregnancies, which was significant in pregnancy weeks 28 (p less than 0.014) and 32 (p = 0.05). Maternal serum TPA concentrations did not change during abortion or parturition and the mixed umbilical blood concentration of TPA equaled that in the mother's serum just after parturition. The correlation between placenta weight and maternal serum TPA levels was significant (p = 0.025). The decline of TPA after labor indicated a t1/2 for serum TPA of 7.5 days.

Fetal Neuroendocrine Mechanisms in Development and Parturition

This chapter presents the evidence for fetal neuroendocrine mechanisms in intrauterine growth and birth in humans and rats. The fetal hypothalamus is active in stimulating intrauterine growth. In humans, this appears from the low birth weight found in congenital anomalies in which the fetal hypothalamus was absent—that is, acephaly, anencephaly, and certain cases of microcephaly. In rats, fetal growth is impaired after removal of the fetal pituitary and/or brain or destruction of the hypothalamus. The intermediate lobe hormone—α-melanocyte-stimulating hormone (MSH)—is found to stimulate fetal growth in rats. Although this hormone is also found to be present in the human fetus during the intrauterine growth spurt, while absent in human anencephalics, its relation to intrauterine growth has still to be confirmed. The fetal brain in humans is not involved in the initiation of labor in the same way as found in the sheep but rather plays a role in the exact timing of the moment of birth around the species mean pregnancy length. Neurohypophysial hormones are present in very high concentrations in umbilical blood, and these fetal hormones are thought to accelerate the course of labor. This hypothesis is supported by the protracted course of labor found in human anencephalics and brainless rat fetuses. The fetus itself plays an active role in its own intrauterine growth and parturition by means of neuroendocrine mechanisms.

Increased Serum Gastrin Concentrations and Gastric Acid Hyposecretion in the Immediate Newborn Period

Thirty-two infants and their mothers were studied to determine the source of elevated serum gastrin concentrations in umbilical blood and to learn whether neonates hypersecreted acid in response to hypergastrinemia. Gastrin concentrations in the umbilical artery and vein were similar. Both were significantly higher than maternal gastrin concentrations. No significant amount of gastrin could be measured in placental extracts. These results suggest that the increased neonatal gastrin concentrations were fetal in origin. Continuous basal acid secretory studies done for 4 hr in 32 infants and for 8 hr in 9 infants demonstrated hyposecretion of gastric acid for the first 5 hr of life. Acid secretion from hour 6 to 8 was similar to that in older children. Increased gastrin levels were still present at hour 8 and were associated with normal gastric acid secretion.