HLA-G antigen and parturition: maternal serum, fetal serum and amniotic fluid levels during pregnancy

OBJECTIVE: To determine whether soluble HLA-G1 (sHLA-G1) concentrations in maternal serum and in amniotic fluid are lower at term than in the second trimester. METHODS: In this prospective study amniotic fluid and maternal serum samples were aspirated from 21 pregnant women during genetic amniocentesis at 16-20 weeks' gestation, and from 19 women undergoing a cesarean section at term. In the latter group arterial umbilical cord blood was aspirated as well. sHLA-G1 levels were determined using ELISA assay. This assay included the anti-HLA-G monoclonal antibodies 87G and 16G1, both as capture antibodies and horseradish-peroxidase-labeled rabbit anti-human beta(2)-microglobulin antibodies, as the detection antibody. The relative concentrations of sHLA-G1 were measured from the absorbancy of the blue product at 650 nm. Student's t test was used for statistical analysis. RESULTS: sHLA-G1 levels in amniotic fluid were significantly lower at term than in the second trimester (0.160 +/- 0.05 vs. 0.272 +/- 0.150 OD units; p < 0.05). Levels of sHLA-G1 in maternal serum declined toward term, but the difference from the second trimester was not statistically significant (0.266 +/- 0.157 vs. 0.205 +/- 0.120 OD units; p = 0.193). There was a strong correlation of sHLA-G1 concentrations between cord serum and maternal serum (R(2) = 0.79; p < 0.001), but not between cord serum and amniotic fluid (R(2) = 0.00004) or amniotic fluid and maternal serum (R(2) = 0.02). CONCLUSIONS: sHLA-G1 antigen expression is higher in amniotic fluid than in maternal-fetal compartments and significantly decreases toward term. We speculate that the declining amniotic fluid sHLA-G1 levels may stimulate a maternal immunological response against the fetus and contribute to the initiation of parturition.     

Epidermal growth factor in urine of pregnant women and in amniotic fluid throughout pregnancy

To investigate the role of epidermal growth factor (EGF) in feto-placental development, we measured the urinary and amniotic fluid EGF levels throughout pregnancy. Thirty urinary samples of non-pregnant women, 85 of normal pregnant women, 21 of women with toxemic pregnancy, 17 of postpartum women and 30 of newborns, and 55 amniotic fluid samples of pregnant women with a variety of conditions necessitating amniotomy and amniocentesis at 25-39 weeks of gestation were collected. EGF concentrations were measured by double-antibody radioimmunoassay. Urinary EGF levels of pregnant women reached their peak (24.6 +/- 6.7 ng/mg creatinine) at 19-22 gestational weeks; after that, they slightly decreased. Although there is no significant difference between the urinary EGF levels of non-pregnant women (19.0 +/- 5.1) and those of pregnant women (18.1 +/- 3.2), the EGF levels of toxemic women (12.2 +/- 1.5) were lower than those of normal pregnant women. The levels in puerperium women were similar to those found during pregnancy. However, the neonates had higher urinary EGF concentrations than those in pregnant women. On the other hand, EGF levels in amniotic fluid were higher according to gestational weeks and the levels of intrauterine growth retardation (IUGR) cases lower compared with normal pregnancy. Furthermore, EGF concentrations in amniotic fluid have a significant correlation with the creatinine levels in amniotic fluid. These data suggest that EGF plays an important role in fetoplacental development and it is possible that the measurement of amniotic fluid EGF might become available for the clinical assessment of fetal maturation.     

Influence of postdatism and meconium on fetal erythropoietin.

OBJECTIVE: To determine whether fetal erythropoietin (Epo) concentrations are increased in pregnancies extending beyond 41 weeks' gestation and whether this is influenced by the presence of meconium-stained amniotic fluid. METHODS: Epo concentrations were measured in 116 fetal umbilical cord blood samples from otherwise uncomplicated pregnancies between 37 to 43 weeks' gestation during the period of October 1996 to October 1997. An enzyme-linked immunosorbent assay kit was used to measure Epo. Maternal demographics and birth outcomes including Apgar score, cord blood pH, and base deficit were obtained. Fetuses born between 41 and 43 weeks' gestation (post-term) were compared with matched controls born between 37 and 40 weeks' gestation (term). In addition, both post-term and term fetuses with meconium-stained amniotic fluid were compared with matched controls without meconium. RESULTS: Post-term fetuses without meconium had significantly higher Epo levels compared with term fetuses (mean +/- SEM: 50.6 +/- 6.5 versus 29.5 +/- 3.3 mIU/ml, p = 0.002). When matched for gestational age, fetuses with meconium-stained amniotic fluid had significantly greater Epo concentrations compared with controls without meconium (post-term, 80.7 versus 50.6 mIU/ml; term, 61.4 versus 29.5 mIU/ml; p < 0.05). However, no significant difference in Epo levels was found between post-term fetuses with meconium and term fetuses with meconium (80.7 +/- 15.7 mIU/ml versus 61.4 +/- 12.8 mIU/ml, respectively). Mean cord blood pH and base deficit values for all groups were within normal clinical range. CONCLUSION: Cord blood Epo concentrations were significantly increased in pregnancies extending beyond 41 weeks. Irrespective of gestational age, meconium-stained amniotic fluid was associated with a significant rise in Epo. High Epo levels in these pregnancies imply subacute or chronic fetal hypoxia. Close clinical monitoring of post-term fetuses and those with meconium-stained amniotic fluid is warranted.     

Granulocyte colony-stimulating factor in preterm and term pregnancy, parturition, and intra-amniotic infection

OJBECTIVE: To determine the sources of granulocyte colony-stimulating factor (G-CSF) in amniotic fluid and to examine its relation to labor and clinically diagnosed intra-amniotic infection. METHODS: We assessed G-CSF and G-CSF receptor expression in placentas (n = 50) from 5-40 weeks' gestation, and G-CSF concentrations were measured in amniotic fluid (n = 146), bronchoalveolar lavage fluid (n = 8), and paired maternal serum, cord blood, neonatal serum, and neonatal urine samples (n = 16). RESULTS: Immunohistochemical staining and messenger RNA analysis showed placental expression of G-CSF and G-CSF receptor throughout gestation. The number of decidual stromal cells expressing G-CSF receptor was significantly higher in women with intra-amniotic infection compared with women without infection (27 +/- 2 versus 18 +/- 3 cells per high power field, P =.02). Amniotic fluid concentrations of G-CSF were not significantly different in noninfected preterm compared with term samples (1708 +/- 1673 versus 1612 +/- 2100 pg/mL, P =.9). Labor was not associated with a significant increase in amniotic fluid G-CSF concentrations (1864 +/- 3151 versus 1612 +/- 2100 pg/mL, P =.77, term labor versus no labor; 3335 +/- 5364 versus 1708 +/- 1673 pg/mL, P =.09, preterm). Concentrations of G-CSF in maternal serum, amniotic fluid, bronchoalveolar lavage fluid, and neonatal urine were increased during intra-amniotic infection (all P <.05). CONCLUSION: Amniotic fluid G-CSF concentrations were similar in preterm and term pregnancies and were not significantly influenced by labor. Intra-amniotic infection was associated with an increased number of placental cells expressing the G-CSF receptor and higher concentrations of G-CSF in amniotic fluid, maternal serum, neonatal urine, and neonatal bronchoalveolar lavage samples.     

Increased inorganic sulfate concentrations in amniotic fluid.

We assayed inorganic sulfate by ion chromatography in 49 amniotic fluid samples from pregnancies of 14 to 38 weeks gestation. In second trimester samples (14 to 26 weeks gestation), amniotic fluid sulfate concentrations (317 +/- 22 mumol/L, mean +/- SE; n = 32) were not different from previously reported maternal serum values but were significantly lower (p < 0.001) than in the third trimester (693 +/- 42 mumol/L; n = 16). In third trimester samples, sulfate concentrations were significantly correlated with creatinine and uric acid but not chloride, suggesting that renal excretion may be the major source of the amniotic fluid sulfate in the late stages of gestation.     

Amniotic fluid beta-endorphin and beta-lipotropin concentrations during the second and third trimesters

Amniotic fluid beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were measured by radioimmunoassay after silicic acid extraction and gel chromatographic separation of the two peptides in uncomplicated second-trimester and term pregnancies, in diabetic patients at term, and in pregnancies complicated by Rh-isoimmunization, premature labor, and intrauterine growth retardation. Furthermore, the lecithin/sphingomyelin (L/S) ratios as well as the dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels were determined in most of the amniotic fluid specimens. Both the mean (+/- SE) beta-EP (65.3 +/- 9.1 fmol/ml) and beta-LPH (150 +/- 15.8 fmol/ml) concentrations were significantly higher in the 20 patients with normal pregnancies of 16 to 21 weeks' duration than those found in 21 patients with uncomplicated term pregnancies of 38 weeks' gestation, averaging 42.6 +/- 6.0 and 80.1 +/- 10.7 fmol/ml, respectively. The mean amniotic fluid beta-EP and beta-LPH concentrations measured in the latter subjects were similar to those observed in 23 diabetic patients with otherwise uncomplicated term pregnancies. The mean amniotic fluid beta-EP and beta-LPH levels found in the limited number of patients with Rh-isoimmunization (N = 9), premature labor (n = 8), and intrauterine growth retardation (n = 5) with pregnancies of 24 to 36, 24 to 36, and 34 to 38 weeks' gestation, respectively, were not significantly different from the mean amniotic fluid beta-EP and beta-LPH concentrations of uncomplicated term pregnancies. In all patients but those with Rh-isoimmunization, beta-EP concentrations exhibited a positive correlation with beta-LPH levels. However, the molar beta-LPH:beta-EP ratio was significantly lower at term than during the early second trimester. Neither beta-EP nor beta-LPH correlated with the amniotic fluid L/S ratio and only beta-LPH exhibited a significant inverse correlation with amniotic fluid DHEA-S. The latter was significantly higher in uncomplicated term than second-trimester pregnancies. These results confirm that immunoassayable beta-EP is present in amniotic fluid and declines toward term. These data demonstrate that immunoassayable beta-LPH is present in amniotic fluid and show a more pronounced decrease toward the end of pregnancy than beta-EP. Neither peptide, at least on account of the amniotic fluid levels, appears to be associated with fetal maturation. The physiologic significance of amniotic fluid beta-EP and beta-LPH and their possible role as markers of fetal response to stress remain to be elucidated.     

The effect of labor on maternal and fetal vitamins C and E

OBJECTIVE: This study was conducted to compare maternal and fetal plasma, amniotic fluid, and chorioamnion levels of vitamins C and E in term (>38 weeks' gestation) subjects undergoing elective repeat cesarean section (CS) without labor with values of subjects of similar gestational age and dietary intake undergoing labor and vaginal delivery (VD). STUDY DESIGN: Healthy women undergoing elective repeat CS (n = 5) or uncomplicated VD (n = 5) at term (>38 weeks' gestation) were studied. For CS patients, maternal and fetal (cord) blood, amniotic fluid, and chorioamnion samples were collected at time of surgery. For VD patients, maternal blood and amniotic fluid were obtained at 5 cm cervical dilation and fetal cord blood and chorioamnion were collected at delivery. Each patient completed a nutritional questionnaire. Plasma and membrane vitamin E concentrations were determined by reversed-phase high-performance liquid chromatography and standardized to cholesterol or membrane protein, respectively. Vitamin C was determined with the use of the 2,4-DNPH method. RESULTS: Dietary intakes for vitamins C and E as well as maternal and fetal vitamin E plasma concentrations were similar for CS and VD patients. In both groups, maternal levels were higher than fetal levels(P <.05). Chorioamnion membrane vitamin E measurements in both groups were similar. Vitamin C concentrations in CS and VD patients were highest in amniotic fluid, lower in fetal plasma, and lowest in maternal plasma. However, mean vitamin C concentrations in maternal plasma, amniotic fluid, and fetal plasma of VD patients were significantly lower, being only 20% +/- 6%, 29% +/- 11%, and 22% +/- 2% of values obtained from CS patients. CONCLUSION: During labor in healthy women at term, uterine contractile activity may generate reactive oxygen species (ROS) through the process of repetitive ischemia and reperfusion. With the significant depletion of vitamin C during labor, we speculate that water-soluble vitamin C scavenges ROS in the aqueous phase and recycles lipid-soluble vitamin E to combat ROS-induced tissue damage.     

孕妇血清表皮生长因子在判断胎儿成熟度中的价值

目的了解正常孕妇在妊娠各期血清中表皮生长因子（ＥＧＦ）及孕激素（Ｐ）,与羊水中ＥＧＦ、Ｐ、淀粉酶（Ａｍｓ）、肌酐（Ｃｒ）、间接胆红素（ＴＢ）的浓度变化在判断胎儿成熟度中的价值。方法用放射免疫法测定正常孕妇１８１例（早孕３５例,中孕６９例,晚孕７７例）血清及其中８７例孕妇（中孕４４例,晚孕４３例）羊水中的ＥＧＦ、Ｐ浓度变化;用生化分析仪测定此８７例孕妇羊水中Ａｍｓ、Ｃｒ、ＴＢ浓度变化。同时还对其中２３例足月分娩的新生儿的脐静脉、脐动脉血清中ＥＧＦ及Ｐ的浓度进行测定。结果孕妇血清中ＥＧＦ和Ｐ的浓度均随孕周增长而增加。羊水中ＥＧＦ浓度与羊水中Ａｍｓ、Ｃｒ浓度呈正相关。孕３２周以后,当ＥＧＦ≥４．５μｇ／Ｌ时,胎儿成熟率为７０．５９％。结论妊娠期孕妇血清中ＥＧＦ的浓度变化可用于判断胎儿成熟度     

The relationship between maternal serum and amniotic fluid alpha-fetoprotein in women undergoing early amniocentesis.

alpha-Fetoprotein levels were measured on 148 paired samples from the maternal serum and amniotic fluid in women greater than or equal to age 35, who were undergoing early amniocentesis (12 to 14 weeks) for chromosomal analysis. These 148 women were white, weighed less than 200 pounds, had no serious medical problems, and did not have a fetal abnormality detected by ultrasonography or karyotype analysis. There was a significant rise in the maternal serum alpha-fetoprotein concentration from 12 to 14 weeks' gestation. Amniotic fluid alpha-fetoprotein peaked at 13 weeks and then significantly declined by 14 weeks' gestation. Similar to reports from normal pregnancies at 16 and 17 weeks, we found no correlation between the maternal serum and amniotic fluid alpha-fetoprotein levels between 12 and 14 weeks. Amniotic fluid alpha-fetoprotein levels cannot be predicted by levels in the maternal serum in pregnancies between 12 and 14 weeks' gestation.     

The neuropeptide histidyl proline diketopiperazine throughout human pregnancy: an inverse correlation with amniotic fluid prolactin

Histidyl proline diketopiperazine values have been established in human amniotic fluid (n = 81) and maternal serum (n = 36) throughout gestation (10 to 42 weeks). Newborn cord serum (n = 10) and first-voided fetal urine (n = 10) levels were also documented. These measurements reveal increasing amniotic fluid levels with term gestation values (15,551 pg/ml) nearly thirteen-fold higher than maternal serum concentrations (1150 pg/ml). Corresponding fetal urine and cord serum concentrations were 16,781 and 2160 pg/ml, respectively. The amniotic fluid values are not influenced by fetal sex or maternal labor, nor do they correlate with amniotic fluid alpha-fetoprotein levels. However, there is a significant inverse correlation (r = -0.628; p less than 0.0001) between amniotic fluid prolactin and histidyl proline diketopiperazine after midgestation. The hypothesis that histidyl proline diketopiperazine may be a regulatory peptide for decidual prolactin production was tested by culturing term decidua in the presence of varying concentrations of histidyl proline diketopiperazine, but no inhibitory effect was observed. Decidual cultures did not produce measurable amounts of histidyl proline diketopiperazine. It is suggested that amniotic fluid histidyl proline diketopiperazine is derived from fetal urine.     

Renal function in the newborn. Newborn creatinine related to birth weight, maturity and maternal creatinine

The maternal and newborn renal function in 84 normal pregnant women delivering at term was investigated. There was no difference between maternal and newborn plasma concentrations of urea (3.9 +/- 1.0 vs. 3.9 +/- 1.2 mmol/l) and creatinine (65.8 +/- 13.3 vs. 65.3 +/- 11.6 mumols/l). The plasma sodium and potassium concentrations were significantly higher in the newborn (139.6 +/- 4.1 vs. 136.8 +/- 5.1 mmol/l, p less than 0.001, and 5.1 +/- 1.3 vs. 4.2 +/- 0.9 mmol/l, p less than 0.001, respectively). Significant correlations were found between newborn sodium (p less than 0.02) and potassium (p = 0.0001) with maternal potassium concentrations, newborn urea with maternal urea concentrations (p = 0.0001), and newborn creatinine with maternal creatinine concentrations (p = 0.0001), gestation of delivery (p less than 0.05) and birth weight (p = 0.025).     

Folate and vitamin B12 concentrations in maternal and fetal blood, and amniotic fluid in second trimester pregnancies complicated by neural tube defects.

OBJECTIVE: To investigate maternal and fetal folate and vitamin B12 concentrations in pregnancies affected by neural tube defects (NTD). DESIGN: Measurement of folate and vitamin B12 concentrations in amniotic fluid, fetal blood and maternal blood samples in midgestation. SUBJECTS: 32 women undergoing termination of pregnancy at 14-21 weeks gestation for social reasons (n = 24) or for fetuses with neural tube defects (n = 8). INTERVENTIONS: Fetoscopy before intra-amniotic injection of prostaglandins. RESULTS: In normal pregnancies there was a positive correlation between maternal and fetal serum folate, and the fetal serum and red blood cell folate concentrations were higher than the maternal. There were no differences in amniotic fluid, maternal blood or fetal blood folate concentrations between pregnancies with NTD and normal pregnancies. Although amniotic fluid vitamin B12 was lower in pregnancies with NTD, maternal serum vitamin B12 concentration was not reduced. CONCLUSION: In this small group of pregnancies with NTD at mid-gestation there is no evidence to suggest folate or vitamin B12 deficiency.     

Galanin concentrations in maternal circulation, amniotic fluid and umbilical cord blood during term labor: relationship with maternal body mass and neonatal birth weight.

BACKGROUND: Galanin is a hypothalamic regulatory peptide involved in the regulation of appetite. It is synthesized by the nervous system, anterior pituitary gland, adrenal medulla, pancreas, intestine and placenta. Placental secretion of galanin has until now only been investigated in animals. Additionally, galanin concentration has not been assessed in umbilical cord blood and amniotic fluid. PATIENTS AND METHODS: Galanin concentrations were measured in maternal circulation before term delivery, in cord blood and in amniotic fluid of 45 healthy pregnant women (gestational age 38 - 40 gestational weeks). The control group consisted of 26 normally menstruating healthy women. RESULTS: Plasma galanin concentrations were found to be similar in pregnant healthy women before term delivery (20.8 +/- 1.9 pg/ml) and non-pregnant women (19.0 +/- 1.7 pg/ml). Galanin concentration in umbilical cord blood (26.5 +/- 2.2 pg/ml) was significantly higher (p < 0.05) than in maternal circulation. Galanin concentration in amniotic fluid (20.4 +/- 1.0 pg/ml) was similar to that observed in maternal plasma, but significantly (p < 0.01) lower than in umbilical cord blood. A significant correlation was found between maternal body mass index and plasma galanin concentration (tau = 0.246; p < 0.05) and between birth weight and cord blood galanin concentration (tau = 0.345; p = 0.01). There was no significant correlation between placental mass and cord blood galanin concentration (tau = 0.124; p = 0.26). CONCLUSIONS: Plasma galanin concentration in pregnant women before term delivery is similar to that in non-pregnant women. The fetus rather than the placenta is the source of the high galanin concentration in umbilical cord blood. The role of galanin in the regulation of newborn weight is uncertain.     

Fluoride concentration in amniotic fluid and fetal cord and maternal plasma

Fluoride concentrations were determined in plasma of 50 pregnant women, 44 samples of amniotic fluid and fetal cord blood of 29 fetuses at various stages of normal pregnancies, from an area with a relatively low water fluoride (less than 0.5 ppm) content. The mean concentrations of fluoride from maternal plasma, cord plasma and amniotic fluid (+/- S.D.) were 0.033 +/- 0.003, 0.028 +/- 0.005 and 0.017 +/- 0.003 ppm, respectively. Maternal and fetal plasma fluoride concentrations did not differ significantly. In the older age group fetal cord plasma fluoride concentration was significantly lower than maternal plasma levels (0.012 +/- 0.08 ppm vs. 0.023 +/- 0.001, respectively; p less than 0.05). Amniotic fluid fluoride levels were significantly higher at term than in midtrimester pregnancy, 0.017 +/- 0.0018 vs. 0.010 +/- 0.009 ppm (P less than 0.05), respectively. This higher concentration may imply higher fetal urinary excretion of fluoride at term due to the lower sequestration of fluoride as the process of bone calcification is more complete.     

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.     

Amniotic fluid in baboon pregnancies with normal versus growth-retarded fetuses

Amniotic fluid samples from 12 pregnant baboons at 173 to 176 days of gestation were studied. Five fetuses were growth retarded and seven were normally developed. Mean amniotic fluid volumes and composition (osmolality, protein concentration, delta optical density at 450 nm, and amniotic fluid/maternal plasma creatinine ratio) were similar in the two groups. Growth-retarded fetuses had amniotic fluids with a lower mean (+/- SE) pH than their normally developed peers (7.50 +/- 0.083 versus 7.85 +/- 0.084, p = 0.023). Intrauterine growth-retarded fetuses appeared to ingest amniotic fluid at a slower mean rate than normally developed fetuses (609 +/- 50.9 versus 769 +/- 48.6 ml/day, p = 0.05), but the difference disappeared when the estimates were corrected for fetal weight. Whether these data may be extrapolated to human pregnancies is speculative but appears likely in view of the similarities between amniotic fluid volume and composition in normal baboon and human pregnancies.     

C-reactive protein in vaginal fluid of patients with preterm premature rupture of membranes

OBJECTIVE: To assess whether C-reactive protein (CRP) concentrations in cervical amniotic fluid reflect the condition of the intrauterine environment in patients with preterm premature rupture of membranes (PROM) before 35 weeks of gestation. METHODS: Amniotic fluid was obtained in 29 consecutive patients admitted with the diagnosis of preterm PROM earlier than 35 weeks of gestation either by amniocentesis or by collecting cervical fluid. CRP was measured in maternal blood, amniotic fluid, vaginal fluid and in cord blood obtained at delivery. Intraamniotic infection was defined as a positive amniotic fluid for aerobic or anaerobic bacteria, or Mycoplasma. The placentas and umbilical cords were examined for the presence of chorioamnionitis and funisitis. RESULTS: A significant correlation was found between vaginal fluid CRP concentrations and both amniotic fluid (r = 0.95, p < 0.001) and umbilical cord levels (r = 0.47, p < 0.05). No correlation was found between maternal blood and vaginal fluid CRP concentrations. The proportion of patients with intraamniotic infection was 37.9% (11/29). The median (range) vaginal fluid CRP concentration was higher in patients with intraamniotic infection than in those with sterile amniotic fluid [901 (0-1354) vs. 507 (0-798) ng/mL, p < 0.001]. The median (range) vaginal fluid CRP concentration was higher in fetuses with (n = 12) than in those without funisitis (n = 17) [901 (598-1354) vs. 487 (0-1115) ng/mL, p < 0.01]. After adjustment for gestational age, vaginal fluid CRP concentration > 800 ng/mL remained a predictor of intraamniotic infection and funisitis. CONCLUSIONS: Increased vaginal fluid CRP concentration is associated with intraamniotic infection and funisitis. As CRP is produced by hepatocytes and does not cross the placenta, its measurement in vaginal fluid might be an additional parameter for the assessment of fetal well-being in patients with premature PROM.     

Increasing amniotic fluid magnesium concentrations with stable maternal serum levels: a prospective clinical trial

OBJECTIVE: To compare the effect of prolonged maternal intravenous MgSO4 administration on amniotic fluid and serum concentrations of magnesium over time in preterm labor patients. STUDY DESIGN: Patients at 24-34 weeks of singleton gestation who presented with contractions (> 8 in 60 minutes) underwent amniocentesis to rule out intrauterine infection after signing an informed consent form. Some of these women who were clinically judged to have preterm labor received intravenous MgSO4: a 4-g loading dose followed by a 2 g/h maintenance dose. For technical reasons some patients had amniocentesis performed before initiation of MgSO4 (controls), while others had the procedure during tocolytic therapy (study subjects). Duration of treatment until amniocentesis was recorded, and blood samples were drawn at the time of amniocentesis. Maternal serum and amniotic fluid magnesium levels were measured using a colorimetric end point method. Data were evaluated using the Student t test and linear regression analysis. RESULTS: Mean magnesium levels in maternal serum rose from 1.74 +/- 0.2 mg/dL in controls to 4.01 +/- 0.4 mg/dL in the study group. Mean magnesium levels in Mean magnesium levels in amniotic fluid were 1.41 +/- 0.18 mg/dL in the controls versus 2.28 +/- 0.53 mg/dL in the treatment group. Duration of MgSO4 treatment ranged from 3 to 22 hours. Amniotic fluid magnesium concentrations increased significantly during therapy (correlation coefficient = 0.89; p < 0.001), while maternal serum levels remained stable over time (correlation coefficient between maternal serum levels and time = -0.39; p=0.34). CONCLUSION: Although maternal serum magnesium levels remained stable with intravenous MgSO4 therapy, concentrations continued to rise in amniotic fluid over time. However, amniotic fluid magnesium levels never exceeded maternal serum concentrations during the study period.     

Biologically active corticotropin-releasing hormone in maternal and fetal plasma during pregnancy

Corticotropin-releasing hormone was measured in the plasma of 110 pregnant women and in the umbilical cord plasma of 25 premature infants and 43 infants born at term. Mean maternal plasma corticotropin-releasing hormone was undetectable (less than 41 pg/ml) until mid-second trimester, rose to a mean of 204 +/- 24 pg/ml by 30 weeks' gestation, to 326 +/- 41 by 35 weeks, and then rose sharply near term, with a mean of 2930 pg/ml at 38 to 40 weeks' gestation. Sequential measurements in seven pregnant women confirmed that plasma corticotropin-releasing hormone rose in a predictable pattern, with a dramatic increase in the final weeks of pregnancy. There was little hour-to-hour variability in maternal plasma concentrations. Corticotropin-releasing hormone was also detectable in umbilical cord plasma; mean corticotropin-releasing hormone was 194 +/- 44 in the preterm infants and 150 +/- 19 in the term infants. The corticotropin-releasing hormone extracted from both the maternal and fetal circulation was biologically active in vitro and caused the dose-dependent release of adrenocorticotropic hormone and beta-endorphin from cultured rat anterior pituitary cells. A significant correlation was found between maternal plasma corticotropin-releasing hormone and cortisol levels the morning after betamethasone administration, a finding that supports a physiologic role for maternal plasma corticotropin-releasing hormone. We conclude that the placenta secretes large amounts of biologically active corticotropin-releasing hormone into both the maternal and fetal circulation during pregnancy. We demonstrate that this corticotropin-releasing hormone is secreted into the maternal plasma in a reproducible pattern during normal term pregnancy and suggest that sequential corticotropin-releasing hormone measurements may prove to be of clinical utility. In addition, placental corticotropin-releasing hormone may be an important modulator of the hypothalamic-pituitary-adrenal axis during pregnancy.     

Increased maternal plasma concentration of endothelin-1 during labor pain or on delivery and the existence of a large amount of endothelin-1 in amniotic fluid

The concentration of endothelin-1 (ET-1) in plasma and amniotic fluid from normal pregnant women was determined by a sensitive sandwich-enzyme immunoassay system, established recently. The plasma ET-1 level increased gradually during normal pregnancy as the pregnancy advanced, the levels (0.40 +/- 0.02 pmol/l, n = 45) being significantly (p less than 0.05) higher after 29 weeks of gestation than those (0.32 +/- 0.01 pmol/l, n = 30) before 28 weeks of gestation. The plasma ET-1 level during labor pain was significantly higher (0.59 +/- 0.06 pmol/l, n = 10) than that (0.40 +/- 0.02 pmol/l, n = 45) in the 3rd trimester of pregnancy without labor pain (p less than 0.02). Moreover, a high level of ET-1 (17.38 +/- 0.25 pmol/l, n = 18) was detected in amniotic fluid on term delivery. The ET-1 level in amniotic fluid was significantly higher than the levels in maternal and umbilical cord plasma (p less than 0.001 and p less than 0.001, respectively). After delivery the maternal ET-1 level decreased gradually and 2 day postpartum ET-1 levels reached the normal non-pregnant level.