Umbilical Plasma Research Articles

Evidence of participation of soluble CD14 in the host response to microbial invasion of the amniotic cavity and intra-amniotic inflammation in term and preterm gestations

Objective: Endotoxin has been implicated in the mechanism responsible for the setting of infection in preterm labor. To exert its biological effects, endotoxin binds to a circulating protein knownas lipopolysaccharide binding protein (LBP) and presents endotoxin monomers to CD14, which may be a membrane-bound receptor or a soluble molecule. The endotoxin- LBP-CD14 complex interacts with Toll-likereceptor 4 and other regulatory proteins leading to cellular activation and an inflammatory response. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC)/intra-amnioticinflammation (both preterm and term) and parturition at term are associated with changes in the amniotic fluid and umbilical plasma soluble concentrations of CD14 (sCD14).Study design: Amnioticfluid was retrieved by amniocentesis from 88 patients in the following groups: group 1, preterm labor with intact membranes with MIAC/intra-amniotic inflammation (n = 18) and without these conditions(n = 26); group 2, term gestations not in labor without MIAC/intra-amniotic inflammation (n = 11), in labor without MIAC/intra-amniotic inflammation (n = 12) and in labor with MIAC/intra-amnioticinflammation (n = 13); and group 3, patients who underwent genetic amniocentesis at mid-trimester (n = 8). A sample of cord blood was obtained after delivery in all patients except those ingroup 3. sCD14 was assayed with a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant.Results: sCD14 was detectablein 97% (85/88) of the amniotic fluid samples. Amniotic fluid sCD14 concentrations were lower in patients at term than in the mid-trimester of pregnancy (mid-trimester: median 482 ng/ml, range 258-838 ng/mlvs. term no labor: median 7 ng/ml, range 2-274 ng/ml, p = 0.01). Among patients with preterm labor with intact membranes, the median amniotic fluid sCD14 level of patients with MIAC/intra-amnioticinflammation was higher than in patients without these conditions (median 1568 ng/ml, range 98-5887 ng/ml vs. median 645 ng/ml, range 0-3961 ng/ml, respectively; p = 0.01). Among women at term inlabor, those with MIAC/intra-amniotic inflammation had a higher median amniotic fluid sCD14 concentration than those without these conditions (median 85 ng/ml, range 2-1113 ng/ml vs. median 17 ng/ml, range0-186 ng/ml; p = 0.01). MIAC/ intra-amniotic inflammation in women with preterm labor with intact membranes was associated with a higher median umbilical venous plasma sCD14 concentration (median744 ng/ml, range 0-3620 ng/ml vs. median 0 ng/ml, range 0-2060 ng/ml; p = 0.04). sCD14 was undetectable in plasma from umbilical cords of all neonates born to women at term. An increase in amniotic fluidconcentration of sCD14 was observed in cases of intrauterine infection, not only by Gram-negative bacteria, but also Gram-positive bacteria and Ureaplasma spp.Conclusion: sCD14 is a physiologicalconstituent of amniotic fluid, and its concentrations at term are lower than in the mid-trimester. Intrauterine infection/inflammation is associated with a higher median amniotic fluid sCD14 concentrationin both preterm and term parturition. Neonates born from mothers with preterm labor with intact membranes and MIAC/intra-amniotic inflammation had a higher median concentration of sCD14 in umbilical cordplasma than those without these conditions. sCD14 concentrations are increased in the amniotic fluid and umbilical cord blood even in the absence of a microbiologically proven Gram-negative infection. CD14appears to participate in the host response to intrauterine infection even in cases involving genital mycoplasmas.

S100B protein cord blood levels and development of fetal behavioral states: a study in normal and small-for-dates fetuses

Objective: We aimed to determine whether S100B protein levels in cord blood and the development of fetal behavioral states were altered and interrelated in small-for-dates (SFD) fetuses.Methods:Umbilical cord blood samples were collected from 12 SFD fetuses with normal umbilical artery (UA) Doppler findings, from six SFD fetuses with abnormal Doppler waveform patterns and from 36 controlsmatched for gestational age. S100B protein levels were measured by means of a specific radioimmunoassay. Fetal behavioral state recordings were made before delivery by Cesarean section and data were expressedas percentage of quiet sleep coincidence (C1F), of activity state coincidence (C2-4F) and of no coincidence (NOC). Flow velocimetry waveforms were recorded from the uterine artery, UA and fetal middle cerebralartery (MCA).Results: Mean S100B protein levels in umbilical plasma were significantly higher in the six SFD infants with abnormal prenatal Doppler findings (3.31 ± 0.65 μg/l) thanin SFD infants with normal Doppler findings (1.56 ± 0.35 μg/l) and in controls (1.23 ± 0.43 μg/l). Similarly in these fetuses NOC was higher and C2F significantly lower (p <0.05), but there was no significant difference in C1F. S100B concentrations were correlated with the UA pulsatility index (PI) (r = 0.78, p < 0.01), with the MCA PI (r = -0.78, p< 0.01) and with the UA PI/MCA PI ratio (r = 0.80, p < 0.01). Also, NOC and C2F percentages were correlated with the UA PI (r = 0.61, p < 0.01 and r = -0.61,p < 0.01, respectively), with the MCA PI (r = -0.72, p < 0.001 and r = 0.66, p < 0.01, respectively), and with the UA PI/MCA PI ratio (r = 0.60, p <0.01 and r = -0.54, p < 0.05, respectively). NOC was also correlated with S100B protein (r = 0.48, p < 0.05); the correlation of S100B protein and C2F almost reached significance(r = -0.47, p < 0.05).Conclusions: This study provides evidence of a relationship between a biochemical marker of brain development and/or integrity and the development of fetalbehavioral states, offering additional information on brain maturation in normal and high-risk pregnancies.

Relationship of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Proteins in Umbilical Cord Plasma to Preeclampsia and Infant Birth Weight

In Brief OBJECTIVE To determine whether preeclampsia influences insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor binding protein-3 (IGFBP-3), independent of its effect on birth weight. METHODS Cord blood was collected in 12,804 consecutive deliveries. We identified 258 preeclamptic pregnancies that were subclassified as mild or severe and early or late. For comparison, 609 control pregnancies were selected. Fetal growth was expressed as the ratio between observed and expected birth weight, with adjustment for gestational age at birth. IGF-I, IGFBP-1, and IGFBP-3 were measured in umbilical plasma. The contribution of preeclampsia and birth weight to each measured factor was assessed by multiple linear regression analyses. RESULTS Between mild preeclampsia and controls, there were no differences in IGF-I, IGFBP-1, and IGFBP-3. In severe and early onset preeclampsia, umbilical cord plasma IGF-I was approximately 50% lower, and IGFBP-1 was more than twice as high as in controls (both P < .01). At each birth weight level, IGF-I was lower and IGFBP-1 was higher in severe or early preeclampsia than among controls of similar weight. Birth weight and preeclampsia were, independent of each other, associated with IGF-I, whereas birth weight, but not preeclampsia, was associated with IGFBP-1, after adjustment for gestational age. CONCLUSION Fetal growth restriction caused by severe or early preeclampsia is associated with lower umbilical levels of IGF-I than low birth weight caused by other conditions. Preeclampsia may contribute to the observed IGF-I reduction, either as part of the underlying causes of preeclampsia, or as a consequence of the disease. Insulin-like growth factor-I is decreased and insulin-like growth factor binding protein-1 is increased in severe or early preeclampsia complicated by low birth weight.

Effects of high inspired oxygen fraction during elective Caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation

Oxygen supplementation is given routinely to parturients undergoing Caesarean section under regional anaesthesia. While the aim is to improve fetal oxygenation, inspiring a high oxygen fraction (FIO2) can also increase free radical activity and lipid peroxidation in both the mother and baby. In this prospective, randomized, double-blind study, we investigated the effect of high inspired oxygen fraction (FIO2) on maternal and fetal oxygenation and oxygen free radical activity in parturients having Caesarean section under spinal anaesthesia. Forty-four healthy parturients were randomized to breathe either 21% (air group) or 60% oxygen (oxygen group) intraoperatively via a ventimask. Maternal arterial blood was collected at 5-min intervals from baseline until delivery, and umbilical arterial and venous blood was collected at delivery. We measured blood gases and the products of lipid peroxidation (8-isoprostane, malondialdehyde (MDA), hydroperoxide (OHP)) and purine metabolites. At delivery, the oxygen group had greater maternal arterial PO2 [mean 30.0 (SD 6.3) vs 14.2 (1.9) kPa; mean difference 15.8 kPa, 95% confidence interval 12.9-18.7 kPa, P<0.001] and greater umbilical venous PO2 [4.8 (1.0) vs 4.0 (1.4) kPa; mean difference 0.8 kPa, 95% confidence interval 0.0-1.5 kPa, P=0.04] compared with the air group. Maternal and umbilical plasma concentrations of lipid peroxides (8-isoprostane, MDA, OHP) were greater in the oxygen group than in the air group (P<0.05). We conclude that breathing high FIO2 modestly increased fetal oxygenation but caused a concomitant increase in oxygen free radical activity in both mother and fetus.

Relationship of insulin-like growth factor-I and insulin-like growth factor binding proteins in umbilical cord plasma to preeclampsia and infant birth weight

OBJECTIVE: To determine whether preeclampsia influences insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor binding protein-3 (IGFBP-3), independent of its effect on birth weight. METHODS: Cord blood was collected in 12,804 consecutive deliveries. We identified 258 preeclamptic pregnancies that were subclassified as mild or severe and early or late. For comparison, 609 control pregnancies were selected. Fetal growth was expressed as the ratio between observed and expected birth weight, with adjustment for gestational age at birth. IGF-I, IGFBP-1, and IGFBP-3 were measured in umbilical plasma. The contribution of preeclampsia and birth weight to each measured factor was assessed by multiple linear regression analyses. RESULTS: Between mild preeclampsia and controls, there were no differences in IGF-I, IGFBP-1, and IGFBP-3. In severe and early onset preeclampsia, umbilical cord plasma IGF-I was approximately 50% lower, and IGFBP-1 was more than twice as high as in controls (both P < .01). At each birth weight level, IGF-I was lower and IGFBP-1 was higher in severe or early preeclampsia than among controls of similar weight. Birth weight and preeclampsia were, independent of each other, associated with IGF-I, whereas birth weight, but not preeclampsia, was associated with IGFBP-1, after adjustment for gestational age. CONCLUSION: Fetal growth restriction caused by severe or early preeclampsia is associated with lower umbilical levels of IGF-I than low birth weight caused by other conditions. Preeclampsia may contribute to the observed IGF-I reduction, either as part of the underlying causes of preeclampsia, or as a consequence of the disease.

Umbilical cord plasma interleukin-6 and fetal growth restriction in preeclampsia: a prospective study in Norway

Objective: To study the association between umbilical plasma levels of interleukin-6 (IL-6) in relation to fetal growth in subgroups of preeclampsia, and in control pregnancies. Methods: Umbilical cord plasma was collected from 12,804 consecutive births. A total of 271 singleton cases of preeclampsia were identified, and classified as mild or severe, and as disease with early or late onset. As controls, 611 singleton pregnancies without preeclampsia were selected, and the ratio between observed and expected birth weight was used as a measure of fetal growth. In the analysis, we also included maternal smoking during pregnancy. Umbilical cord plasma IL-6 concentration was measured with an IL-6 bioassay. Comparing controls with subgroups of preeclampsia (severe and early onset), this study had a statistical power of 90% to detect a difference in cord IL-6 of 10 pg/mL. Results: In severe preeclampsia, cord plasma IL-6 concentration was lower than among controls ( P < .001), and there was a sharp decrease in cord plasma IL-6 with decreasing birth weight ratio ( P trend < .001). By further dividing the preeclampsia group into early or late onset, the strong association between low IL-6 levels and low birth weight ratio appeared to be present mainly in early-onset disease. These results were not confounded by maternal smoking. Conclusion: Restricted fetal growth related to preeclampsia is associated with reduced umbilical cord plasma IL-6 concentration in cases with early-onset disease. In these cases, fetal growth restriction could be mediated by impaired trophoblast function.

Inflammatory Mediators in Umbilical Plasma from Neonates Who Develop Early-Onset Sepsis

Objectives: To study whether early-onset neonatal sepsis is associated with a prenatal immune response with elevated umbilical plasma levels of inflammatory mediators, and to study whether mediator levels may be helpful in identifying infected neonates. Setting: Nested case-control study. Methods: Cord blood was sampled from 7,073 consecutively delivered neonates. After review of the medical records, neonates suspected to suffer from infection were classified as infected (n = 52) or noninfected but sick controls (n = 33). We also included a group of healthy controls (n = 99). Umbilical plasma levels of tumour necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, IL-8, soluble TNF receptors (p55 and p75), IL-1 receptor antagonist (IL-1RA) and C-reactive protein were measured by immunoassays. Results: Infected neonates had higher levels of TNFα, IL-1β, IL-6, IL-8, p55, p75 and IL-1RA than healthy controls (all p < 0.01). Among preterm infants (GA <37 weeks), those with infection (n = 11) had higher levels of IL-1β, IL-6, IL-8, p55 and p75 than noninfected sick controls (n = 13) (all p < 0.05), but among term infants, the infected did not differ from the noninfected sick controls. Receiver operator characteristic plots showed that IL-1β, IL-6 and IL-8 identified preterm infected neonates accurately. Conclusions: Early-onset neonatal sepsis is associated with a prenatal immune response with increased TNFα, IL-1β, IL-6, IL-8, p55, p75 and IL-1RA levels in umbilical plasma. Among neonates who present symptoms suggestive of infection, cytokine levels may be helpful in identifying preterm, but not term infected individuals.

Plasma Carnitine Levels of Pregnant Adolescents in Labor

Study Objective: To determine the concentration of plasma carnitine (total, free, and acylcarnitine) during the delivery of uncomplicated pregnancies of adolescent women. To investigate the relationship between maternal and neonatal levels of carnitine and to compare these carnitine levels between pregnant and nonpregnant adolescents. Design: Samples of maternal and umbilical blood were taken at the time of delivery and examined for the determination of the carnitine—total, free, and acylcarnitine—concentration by the use of an enzymatic-radioisotope method. Twenty-two cases of uncomplicated adolescent pregnancies with a normal labor and without perinatal complications were examined. The plasma level of carnitine was also examined in 17 healthy nonpregnant adolescent women, which constituted the control group. Results: The concentrations of plasma carnitine in adolescent pregnancies at the time of delivery were calculated at 19.6 ± 2.15 μMol/L (total), 12.62 ± 1.31 μMol/L (free), and 6.98 ± 1.55 μMol/L (acylcarnitine). The corresponding mean values in umbilical plasma were 30.31 ± 2.06 μMol/L, 22.39 ± 1.64 μMol/L, and 7.92 ± .96 μMol/L. There is a statistically significant difference between the mean values in maternal and umbilical plasma ( P < .0001 for total and free carnitine and P < .012 for acylcarnitine). The correlations between adolescent pregnant women and their infants as regards total, free, and acylcarnitine were 0.137, 0.018, and 0.33, respectively. Neither of these parameters was statistically significant. The corresponding mean values of carnitine in nonpregnant adolescent women were statistically significantly higher than in adolescent pregnant women (total carnitine: 41.61 ± 3.09 μMol/L, free: 31.39 ± 2.81 μMol/L, acylcarnitine: 10.22 ± 1.88 μMol/L, P < .0001). Conclusions: The concentration of plasma carnitine at the end of adolescent pregnancy is low compared to the levels of umbilical carnitine at birth and that found in nonpregnant adolescent women. It may not have an obvious impact on the utilization of fatty acids in an uncomplicated full-term pregnancy; however, it suggests the potential risk for neonatal fatty-acid oxidation in a preterm or complicated pregnancy.

Subject Index Volume 62 (2001)

Hardly any direct information is available on the essential fatty acid (EFA) status of the fetus during intrauterine development. Therefore, we studied 86 umbilical plasma samples obtained by trans-abdominal puncture during ongoing pregnancies (18.3–39.0 weeks of gestational age). These were compared with 51 samples of umbilical cord blood, collected immediately after birth (gestational ages, 28.5–39 weeks). The total amounts of fatty acids in fetal plasma phospholipids (mg/1) did not change during gestation. The relative amounts of linoleic acid (% of total fatty acids) showed a slight increase (P = 0.03) during fetal maturation. Arachidonic acid (20:4n-6) decreased (both absolute (mg/1) and relative (% wt/wt) P ≤ 0.0001), while docosahexaenoic acid (22:6n-3) increased (absolute P < 0.003, relative P < 0.0001) when pregnancy progressed. The EFA profiles of fetal samples were in general comparable with postnatal results of infants born at similar gestational ages. However, the fetal linoleic acid status was lower than the linoleic acid status of the neonates. The same was true for the overall EFA status. The results of this study indicate that the low EFA status observed in preterm infants at birth, is a developmentally related phenomenon.

The composition of saturated fatty acids in plasma phospholipids changes in a way to counteract changes in the mean melting point during pregnancy.

It has been demonstrated that in pathological conditions with an increase in the calculated mean melting point (MMP) of phospholipid (PL) fatty acids (FA) there are changes in the composition of the saturated FA (SFA), which partially counteract this effect: shorter-chain SFA with lower melting points are increased, while longer-chain less fluid SFA are suppressed. The aim of this study was to determine whether there are differences in MMP during pregnancy and in the newborn and, if so, whether similar adaptive changes occur in the composition of the SFA. The FA composition of plasma PL was determined in healthy women (n = 16) twice during pregnancy (15-24 wk and 29-36 wk) and at delivery and in umbilical venous blood obtained at birth. The MMP of maternal PL was significantly higher at delivery compared to mid-gestation, due to a loss of highly unsaturated FA (HUFA) which were replaced by SFA. In addition, changes in the SFA occurred: 16:0 with lower melting point was higher while 18:0 with higher melting point was lower at delivery. MMP of PL FA in umbilical plasma was lower than in maternal plasma at delivery, which was due to higher HUFA content. In contrast to maternal plasma, 16:0 was lower while 18:0, 20:0, and 24:0 were higher in umbilical plasma resulting in a higher MMP of SFA, tending to raise the overall MMP. It can be concluded that, during pregnancy and in the newborn, the FA composition of SFA changes in a way to counteract changes in MMP induced by reduced and increased HUFA, respectively.

Nutritional implications of trans fatty acids during perinatal period, in French pregnant women

Some studies have demonstrated the transfer of trans fatty acids (TFA) across the human placenta. It was suggested that TFA might disturb the metabolism of essential fatty acids (EFA) in fetus and consequently might affect intrauterine human growth more or less according to the TFA intake level of the mother. In this context, the objective of this study was to assess, for French pregnant women, possible impact of their TFA intake on parameters of their term infants: 1/ TFA composition of the umbilical cord (plasma lipids and parietal phospholipids), 2/ birth weight and head circumference. The TFA composition of maternal and umbilical plasma lipids, and parietal phospholipids of umbilical cord were determined by gas chromatography, associated with a thin-layer chromatography for the phospholipids. Because TFA content of adipose tissue is a reliable biochemical indicator of the usual TFA intake level, maternal adipose tissue was also analyzed. Trans fatty acid (TFA) percentage was significantly higher (p = 0.001) in maternal (0.9% of total fatty acids) than in umbilical plasma total lipids (0.6%) thus confirming their placental passage. Moreover, trans isomer pattern of cord plasma lipids was different from the maternal’s one, especially regarding trans isomers of linoleic acid (9c,12c-18:2). Percentage values of 9c,13t + 9t,12t and 9t,12c isomers were respectively, 2 and 3 times higher (p < 0.001) in umbilical than in maternal plasma (Except trans 16:1 acids). All trans isomers observed in umbilical plasma lipids were detected in both parietal and vessel (vein and arteries) phospholipids of umbilical cord. Nevertheless, 9c13t + 9t12t isomer mix level was significantly higher (p < 0.001) in artery than in vein TPL. Moreover, in artery TPL, percentage value of 9c13t+9t12t isomer mix was inversely correlated (r = - 0.703, p = 0.003) with arachidonic acid content. Nevertheless, for this French population, there was no relation between either weight or head circumference of newborn and the TFA levels in both adipose tissue and plasma lipids of their mother.

An in vivo study of ovine placental transport of essential amino acids.

Under normal physiological conditions, essential amino acids (EA) are transported from mother to fetus at different rates. The mechanisms underlying these differences include the expression of several amino acid transport systems in the placenta and the regulation of EA concentrations in maternal and fetal plasma. To study the relation of EA transplacental flux to maternal plasma concentration, isotopes of EA were injected into the circulation of pregnant ewes. Measurements of concentration and molar enrichment in maternal and fetal plasma and of umbilical plasma flow were used to calculate the ratio of transplacental pulse flux to maternal concentration (clearance) for each EA. Five EA (Met, Phe, Leu, Ile, and Val) had relatively high and similar clearances and were followed, in order of decreasing clearance, by Trp, Thr, His, and Lys. The five high-clearance EA showed strong correlation (r(2) = 0.98) between the pulse flux and maternal concentration. The study suggests that five of the nine EA have similar affinity for a rate-limiting placental transport system that mediates rapid flux from mother to fetus, and that differences in transport rates within this group of EA are determined primarily by differences in maternal plasma concentration.

Chronic maternal smoking and cord blood amino acid and enzyme levels at term

Objective: To assess the influence of chronic active maternal smoking on cord blood amino acid and enzyme levels at term. Methods: The concentrations of 24 free amino acids, total protein, and five enzymes were measured in samples of maternal and fetal cord venous plasma from 24 nonsmokers who were not exposed to tobacco smoke and 24 chronic smokers. Cotinine levels were also measured in maternal plasma to evaluate fetal tobacco exposure. The pregnancies were between 37 and 40 weeks’ gestation, were uncomplicated, and were delivered vaginally. Results: Fetal weight was significantly ( P < .01) lower in the smokers than in controls. A positive significant ( P < .001) correlation was found between maternal and umbilical venous cotinine concentrations. Significantly lower concentrations of aspartic acid ( P < .01), hydroxyproline ( P < .05), threonine ( P < .005), alanine ( P < .05), α-aminobutyric acid ( P < .001), methionine ( P < .05), tyrosine ( P < .001), phenylalanine ( P < .01), and lysine ( P < .05) were found in the venous cord plasma of the smokers compared with nonsmokers. The fetomaternal ratios were similar in both groups. The umbilical plasma alkaline phosphatase activity was significantly ( P < .01) lower in the smokers than in the controls. Conclusion: Chronic maternal smoking is associated with alterations of protein metabolism and enzyme activity in fetal cord blood. These may be secondary to irreversible changes in the cellular functions of the trophoblast and may contribute to fetal growth restriction.

Neuroactive steroids, their precursors, and polar conjugates during parturition and postpartum in maternal and umbilical blood: 1. identification and simultaneous determination of pregnanolone isomers

A rapid method for the identification and measurement of four pregnanolone isomers and their polar conjugates in human plasma was developed using a simple quadrupole GC/MS system with electron impact ionization. Steroid levels were measured in the plasma of 13 and three women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma. A good correlation ( r=0.94, P<0.001, n=8) was found between the allopregnanolone in maternal plasma determined by GC/MS and that measured by RIA. Epipregnanolone (3β-hydroxy-5β-pregnan-20-one) was identified and measured for the first time in human plasma; its concentration in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3β-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal plasma, while the differences in 3α-hydroxy-isomers were insignificant. The differences in conjugates were insignificant except in the case of allopregnanolone, the levels of which were lower in umbilical plasma. In all of the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. The possible role of the sulfatation of pregnanolone isomers around parturition is discussed.

Activity and expression of the Na(+)/H(+) exchanger in the microvillous plasma membrane of the syncytiotrophoblast in relation to gestation and small for gestational age birth.

The effect of gestational age, low birth weight, and umbilical plasma pH on the activity and expression of the Na(+)/H(+) exchanger in the microvillous plasma membrane (MVM) of the placental syncytiotrophoblast was investigated. MVM were isolated from placentas of fetuses delivered in the first and second trimesters and from appropriately grown for gestational age (AGA) and small for gestational age (SGA) babies born at term. Na(+)/H(+) exchange activity (amiloride-sensitive Na(+) uptake) was higher (p<0.05) in second trimester and term AGA MVM versus first trimester MVM (median [range]: 1.80 [1.01-3.03], 1.72 [1.16-3.15] versus 1.48 [0.92-1.66] nmol/mg protein/30s, respectively, n = 6, 12, and 9). As regards exchanger isoforms, Western blotting showed that NHE1 expression did not change across gestation, but NHE2 and NHE3 expression were lower (p<0.01) in the first and second trimesters than in term AGA MVM. There were no differences in Na(+)/H(+) exchanger activity or in NHE1-3 expression in term AGA MVM versus SGA (n = 11) MVM. There was no correlation between exchanger activity and umbilical artery or vein plasma pH, although with a relatively small number of samples (n = 12 and 15, respectively). We conclude that there is differential regulation of the activity and expression of Na(+)/H(+) exchanger isoforms in the MVM over the course of gestation in normal pregnancy; this is not affected in pregnancies resulting in SGA babies at term.

P100IUGR fetuses with abnormal umbilical artery Doppler and elevated S100B protein levels

Maternal and umbilical blood samples were collected in IUGR pregnancies with abnormal umbilical artery Doppler findings and in controls. S100B protein levels were measured by means of a specific radioimmunoassay and flow velocimetry waveforms were recorded from uterine, umbilical and fetal middle cerebral arteries. We studied the correlation between S100B protein, an acidic calcium binding protein previously demonstrated as a reliable indicator of brain lesion, and the degree of fetoplacental blood flow impairment to examine whether S100B could be helpful in the detection of brain sufference in intrauterine growth retarded (IUGR) fetuses. Mean S100B protein in umbilical plasma were higher (P &lt; 0.05) in IUGR patients (113.5 ± 65.9 fmol/mL) than in controls (52.7 ± 34.8 fmol/mL), and particularly in those cases in which brain sparing was present (169.6 ± 67.8 fmol/mL). Fetal S100B concentrations were correlated with middle cerebral artery PI (r = −0.50, P &lt; 0.05) and with umbilical artery PI/middle cerebral artery PI ratio (r = 0.51, P &lt; 0.05). This study provides evidence that fetal S100B protein is increased in IUGR and suggests that it may play.

Clinical study on effect of Chinese herbal medicine for supplementing kidney and Qi and activating blood circulation in treating intrauterine growth retardation of fetus

To explore the therapeutic effect and its possible mechanism on using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). Fifty-five cases of IUGR were observed, 30 of them were treated with CHM and 25 treated with amino acid for control. The neonatal birth weight in the CHM group was markedly greater than that in the control group. Not only the maternal fundal height and abdominal circumference, but also the fetal growth parameters, including biparietal diameter, head circumference, abdominal circumference, femur length in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E3) and human placental lactogen (hPL) were close to the normal pregnancy group, but the levels in the control group were significantly different from the normal range. The umbilical venous plasma concentration of essential amino acids was markedly improved after treatment, however, the improvement in the CHM group was more significant than that in the control group. No adverse effect of CHM was found both in mother and fetus. CHM for supplementing Kidney and Qi, and activating blood circulation was more effective in the improvement of placental function and amino acid transportation than those of amino acid.

Nitroglycerin application during cesarean delivery: Plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns

Objective: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. Study Design: At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. Results: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0.5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. Conclusion: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates. (Am J Obstet Gynecol 2000;182:955-61.)

Adrenomedullin is increased in the fetoplacental circulation in intrauterine growth restriction with abnormal umbilical artery waveforms

Objective:To examine whether adrenomedullin, a novel vasoactive peptide produced by the placenta, participates in the uteroplacental hemodynamic alterations in intrauterine growth restriction, we studied the correlation between adrenomedullin levels and fetoplacental blood flow. Study Design:Maternal and umbilical blood samples were collected in pregnancies complicated by intrauterine growth restriction with abnormal umbilical artery Doppler findings and in control pregnancies. Adrenomedullin levels were measured by means of a specific radioimmuncassay, and flow velocimetry wave-forms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Results:Mean adrenomedullin values in umbilical plasma were higher (P < .05) in patients with intrauterine growth restriction (63.7 ± 34.2 pg/mL; n = 16) than in control subjects (38.1 ± 14.8 pg/mL; n = 16). A significant correlation was found between maternal adrenomedullin levels and umbilical artery pulsatility index. Moreover, fetal adrenomedullin concentrations correlated negatively with middle cerebral artery pulsatility index and positively with umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio. Conclusions:This study provides evidence that adrenomedullin is increased in fetuses with intrauterine growth restriction in response to reduced uteroplacental blood flow and suggests that it may participate in the fetal hemodynamic modifications.

Long-chain polyunsaturated fatty acids, pregnancy, and pregnancy outcome

During pregnancy, essential long-chain polyunsaturated fatty acids (LCPUFAs) play important roles as precursors of prostaglandins and as structural elements of cell membranes. Throughout gestation, accretion of maternal, placental, and fetal tissue occurs and consequently the LCPUFA requirements of pregnant women and their developing fetuses are high. This is particularly true for docosahexaenoic acid (DHA; 22:6n-3). The ratio of DHA to its status marker, docosapentaenoic acid (22:5n-6), in maternal plasma phospholipids decreases significantly during pregnancy. This suggests that pregnancy is associated with maternal difficulty in coping with the high demand for DHA. The DHA status of newborn multiplets is significantly lower than that of singletons; the same is true for infants of multigravidas as compared with those of primigravidas and for preterm compared with term neonates. Because the LCPUFA status at birth seems to have a long-term effect, the fetus should receive an adequate supply of LCPUFAs. Data from an international comparative study indicated that, especially for n-3 LCPUFAs, the fetus is dependent on maternal fatty acid intake; maternal supplementation with LCPUFAs, their precursors, or both increased LCPUFA concentrations in maternal and umbilical plasma phospholipids. However, significant competition between the 2 LCPUFA families was observed, which implies that effective supplementation requires a mixture of n-6 and n-3 fatty acids. Further research is needed to determine whether higher LCPUFA concentrations in plasma phospholipid will have functional benefits for mothers and children.