Amniotic fluid concentrations of adrenomedullin in preterm labor.

OBJECTIVE: To determine whether adrenomedullin levels in amniotic fluid were associated with preterm labor. METHODS: We measured immunoreactive adrenomedullin in amniotic fluid collected by amniocentesis from 36 women with clinical diagnosis of preterm labor or preterm premature rupture of membranes (PROM) and from 18 normal pregnant women. RESULTS: Amniotic fluid from cases of PROM and failure to respond to tocolysis were associated significantly with higher amniotic fluid adrenomedullin concentrations (177.0 +/- 22.5 pg/mL and 182.7 +/- 22.0 pg/mL, respectively, P < .01) than that from uncomplicated pregnancies (101.2 +/- 28.1 pg/mL) or preterm labor responsive to tocolysis (102.3 +/- 26.8 pg/mL). CONCLUSION: Amniotic fluid adrenomedullin is higher than normal in cases of PROM and preterm labor unresponsive to tocolysis, perhaps indicating enhanced synthesis from placenta or fetal membranes being stimulated by bacterial products.     

Elevated amniotic fluid leptin levels in early second trimester are associated with earlier delivery and lower birthweight in twin pregnancy

OBJECTIVE: To explore the possibility of using early second trimester amniotic fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. STUDY DESIGN: Amniotic fluid leptin levels from 18 twin-pregnant women in early second trimester were analyzed for their correlation with gestational age at delivery and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from small for gestational age (SGA) twin pregnancies were compared with those in 20 amniotic fluid samples collected from non-SGA twin pregnancies. RESULTS: A significant correlation was observed between amniotic fluid leptin levels and gestational age at delivery (r = 0.71, p < 0.001) as well as fetal birthweight (r = 0.72, p < 0.001). There was also a significant correlation between gestational age at delivery and fetal birthweight (r = 0.92, p < 0.001). The average gestational age at delivery was 30.4 +/- 1.4 weeks in the SGA group, with a mean birthweight of 1552 +/- 200 g at delivery. For the non-SGA group, the values were 37.3 +/- 0.5 weeks and 2759 +/- 115 g ( p < 0.001), respectively. Amniotic fluid leptin levels were found to be significantly higher ( p < 0.001) for women in the SGA group (11.4 +/- 1.5 ng/mL) than for those in the non-SGA group (5.4 +/- 0.5 ng/mL). CONCLUSION: Higher amniotic fluid leptin levels in early second trimester were associated with both lower gestational age at delivery and lower birthweight. Our results suggest that amniotic fluid leptin levels in early second trimester may be a good marker for the prediction of perinatal complications in twin pregnancy.     

Gender differences in amniotic fluid cytokine levels.

OBJECTIVE: Placental trophoblast invasion and amniotic fluid cytokine receptor levels have been reported to vary with fetal gender. We investigated whether fetal gender affects amniotic fluid levels of the inflammatory cytokines interleukin (IL)-6 and IL-10 and the pro-angiogenesis cytokine angiogenin. METHODS: Specimens from singleton gestations undergoing mid-trimester amniocentesis for genetic indications were used. Inclusion criteria were (1) outcome information available, (2) no structural or chromosomal anomaly and (3) no conditions associated with preterm delivery. Amniotic fluid IL-6, IL-10 and angiogenin levels were measured by immunoassay. Statistical analysis included the Mann-Whitney U test and Fisher's exact test with p < 0.05 indicating significance. RESULTS: A total of 74 samples were analyzed. Angiogenin levels were significantly lower in amniotic fluid samples from pregnancies with a male than with a female fetus (median (range): 22.2 (5.9-66.4) vs. 32.0 (11.4-159.2) ng/ml, p=0.007), in contrast to no differences in amniotic fluid IL-6 and IL-10 levels (p=0.4 and p=0.1, respectively). In pregnancies with male fetuses delivering preterm (< 37 weeks), angiogenin was also detected at lower levels (p=0.02). There were no gender differences with respect to race, nulliparity or maternal age. CONCLUSION: Angiogenin levels, but not IL-6 or IL-10 levels, are significantly lower in second-trimester amniotic fluid of women with male compared with female fetuses, including those women delivering preterm.     

A role for the 72 kDa gelatinase (MMP-2) and its inhibitor (TIMP-2) in human parturition, premature rupture of membranes and intraamniotic infection

OBJECTIVE: Degradation of the extracellular matrix in fetal membranes has been implicated in the process of parturition and rupture of membranes. Matrix metalloproteinases (MMPs) are enzymes capable of degrading extracellular matrix including collagen. Tissue inhibitors of matrix metalloproteinases (TIMPs) inhibit the activity of MMPs by covalently binding to the enzymes. MMP-2 degrades Type IV collagen and TIMP-2 is its specific inhibitor. The objective of this study was to determine if human parturition, rupture of membranes (term and preterm) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in the concentrations of MMP-2 and TIMP-2 in amniotic fluid. STUDY DESIGN: A cross-sectional study was conducted with women in the following categories: 1) term with intact membranes, in labor and not in labor; 2) preterm labor and intact membranes who delivered at term, who delivered preterm and preterm labor with MIAC; 3) preterm premature rupture of membranes (PROM) with and without infection; 4) term and preterm PROM not in labor; and 5) midtrimester. MMP-2 and TIMP-2 concentrations in amniotic fluid were determined using sensitive and specific immunoassays. RESULTS: The concentration of TIMP-2 increased with advancing gestational age (r = 0.6, p < 0.001). No correlation was found between MMP-2 concentrations and gestational age. Human parturition and rupture of membranes (term and preterm) and in patients with intact membranes were not associated with changes in the amniotic fluid MMP-2 concentrations. In contrast, 1) patients with spontaneous labor (term and preterm) had significantly lower median concentrations of TIMP-2 compared to those not in labor (p < 0.05 for both); 2) MIAC in women with preterm labor and preterm PROM was associated with a significant decrease in amniotic fluid TIMP-2 concentrations (p < 0.04 for both comparisons); 3) Rupture of the membranes (term and preterm) was also associated with a significant decrease in the amniotic fluid TIMP-2 concentrations (p < 0.05 and p < 0.03, respectively). CONCLUSIONS: Human parturition (preterm and term), rupture of fetal membranes (term and preterm) and intraamniotic infection are associated with a significant decrease in amniotic fluid TIMP-2 concentrations.     

Meconium in the amniotic fluid of pregnancies complicated by preterm premature rupture of membranes is associated with early onset neonatal sepsis

Objective: This study was to determine the significance of meconium in the amniotic fluid of pregnancies complicated by preterm premature rupture of membranes (PPROM) without labor.Methods: A case-control study of 31 pregnancies complicated by PPROM at 27-36 weeks gestation with meconium present (study group) and 93 pregnancies complicated by PPROM but without meconium was performed. The patients were matched for year of delivery, gestational age, race, and parity. Pregnancy and neonatal outcome variables of the 2 groups were compared.Results: The incidence of early onset neonatal sepsis was significantly increased in the study group (16.1% vs. 1.1%; P < 0.001). Similarly, chorioamnionitis (48.3% vs. 22.5%; P < 0.01), cesarean delivery for a nonreassuring fetal heart rate pattern (19.4% vs. 3.2%; P < 0.01), a 5-min Apgar score < 7 (22.5% vs. 8.6%; P < 0.05), and fetal growth retardation (FGR) (12.9% vs. 2.2%; P < 0.05) were also more common in pregnancies complicated by PPROM with meconium. The mean umbilical cord arterial pH was significantly lower in these pregnancies (7.18 +/- 0.07 vs. 7.28 +/- 0.08; P < 0.001). After controlling for confounding variables with multiple logistic regression analysis, we found that meconium in the amniotic fluid remained associated with early onset neonatal sepsis.Conclusions: The presence of meconium in the amniotic fluid of pregnancies complicated by PPROM is associated with an increased incidence of early onset neonatal group B beta-hemolytic streptococcus (GBBS) sepsis.     

Dye-determined amniotic fluid volume and intrapartum/neonatal outcome.

OBJECTIVE: To ascertain if a dye-determined amniotic fluid volume was predictive of intrapartum and perinatal outcome. MATERIALS AND METHODS: The low and normal amniotic fluid volumes (< 5th percentile and > or =5th percentile for gestational age) and the raw dye-determined amniotic fluid distributions were correlated with 10 clinical outcome measures in 74 pregnancies. RESULTS: In this observational study, median gestational age at delivery was 36 weeks (range 26 to 41) and 16 deliveries were for fetal distress (14 Cesarean and two forceps). There were no differences between the outcomes of pregnancies with low and normal amniotic fluid volumes for any of the clinical outcomes (variable decelerations influencing delivery, p=0.381; late decelerations, p=0.875; Cesarean births for fetal intolerance of labor, p=0.259; intrauterine growth restriction, p=0.998; or umbilical cord arterial pH< 7.2, p=0.259). Analogous results were obtained when the gestational age-adjusted amniotic fluid volumes were compared directly between the pregnancies with normal and abnormal outcomes. There was no difference between the mean amniotic fluid volumes in those pregnancies with variable decelerations influencing delivery (p=0.287), late decelerations (p=0.555), Cesarean births for fetal intolerance of labor (p=0.310), intrauterine growth restriction (p=0.267) or umbilical cord arterial pH< 7.2, and the pregnancies without these intrapartum events. Reduced variability was more commonly observed in pregnancies with higher amniotic fluid volumes (p=0.038, 771 ml, 95% CI 468 to 1269, compared to those without normal variability 444 ml, 95% CI 374 to 526). CONCLUSIONS: Dye-determined amniotic fluid volume does not appear to be predictive of adverse intrapartum and neonatal outcome.     

Complete chorioamniotic membrane separation. Case report and review of the literature

We present a patient who developed complete chorioamniotic membrane separation (CMS) in two consecutive pregnancies. The first pregnancy ended with an intrauterine fetal death at 25 weeks of gestation. The entire separated amniotic sac had twisted around the umbilical cord. In the subsequent pregnancy, a complete CMS was diagnosed at 34 weeks of gestation. In both pregnancies, the patient underwent an early 2nd-trimester genetic amniocentesis. A review of the literature shows that extensive CMS is associated with miscarriage, in utero fetal death, umbilical cord complications, and preterm delivery. Most reported cases occurred after invasive intrauterine procedures.     

Influence of labor on fetoplacental adrenomedullin concentrations

OBJECTIVE: Circulating adrenomedullin is increased in pregnancy, and placental and fetal membranes participate significantly in its secretion. Recent studies have suggested a potential role for this peptide in the regulation of fetoplacental circulation and placental hormonal secretion. Because adrenomedullin acts also as a uterorelaxant in rats, this study was designed to investigate whether fetoplacental adrenomedullin production changes with human labor, either at term or preterm. STUDY DESIGN: Eighty pregnant women grouped according to gestational age and presence of labor were studied. Adrenomedullin concentrations in plasma, amniotic fluid, and placental tissue extracts were measured by means of radioimmunoassay and immunohistochemistry. In addition, the ability of amnion and chorion-decidua to secrete adrenomedullin was investigated in vitro. RESULTS: Adrenomedullin concentrations in amniotic fluid were higher in preterm labor, whereas no differences were found in adrenomedullin expression or concentrations in tissues or in maternal and fetal plasma between vaginal delivery or elective cesarean section, both at term and preterm. During term labor (8 patients), maternal plasma adrenomedullin concentration decreased with advancing cervical dilatation, being 173 pg/mL at the beginning of the active stage of labor and 57 pg/mL at the time of delivery. Adrenomedullin concentration in the medium of amnion- and chorion-decidua-cultured cells was higher after vaginal delivery. CONCLUSION: These results suggest that a decrease in adrenomedullin production is not involved in the onset of labor in human subjects but rather that it may play a role other than that of a myometrial relaxant in human parturition.     

Elevated amniotic fluid C-reactive protein at the time of genetic amniocentesis is a marker for preterm delivery

OBJECTIVE: A pre-existing intrauterine inflammation in the first half of gestation has been proposed as a possible condition that leads to preterm delivery. Indeed, elevated levels of inflammatory mediators (eg, interleukin-6, tumor necrosis factor) in midtrimester amniotic fluid have been found in cases of preterm delivery and/or spontaneous abortion. The objective of this study was to investigate whether the amniotic fluid C-reactive protein level at the time of genetic amniocentesis is a marker for spontaneous preterm delivery before 34 and 37 weeks of gestation. STUDY DESIGN: Women who underwent genetic amniocentesis between 15 and 18 weeks of gestation with (1) singleton gestation, (2) uneventful pregnancy course before the amniocentesis, and (3) absence of fetal abnormalities were included in the study. Patients with abnormal karyotype were excluded. C-reactive protein concentration was measured in amniotic fluid and in maternal blood immediately after genetic amniocentesis. All patients were followed until delivery for the occurrence of pregnancy complications. Nonparametric tests and receiver-operating characteristic curve analysis were used for statistical purposes. RESULTS: The prevalence of spontaneous preterm delivery before 34 and 37 weeks was 3.3% (10 of 306 pregnancies) and 8.5% (26 of 306 pregnancies), respectively. Women with preterm delivery at <37 weeks had a higher median (range) of amniotic fluid C-reactive protein concentration than those women who delivered at term (median, 113.3 ng/mL [range, 16-623 ng/mL] vs median, 57.8 ng/mL [range, 0-808.9 ng/mL]; P <.005). Women with preterm delivery at <34 weeks had a higher median (range) amniotic fluid C-reactive protein concentration than those women who delivered at term (median, 183.8 ng/mL [range, 46.5-447 ng/mL] vs median, 57.8 ng/mL [range, 0-808.9 ng/mL]; P <.005]. No correlation was found between amniotic fluid C-reactive protein and maternal blood C-reactive protein concentrations. No relationship was found between maternal blood C-reactive protein concentration and preterm delivery before either 34 or 37 weeks. Amniotic fluid C-reactive protein concentration of >110 ng/mL had a sensitivity of 80.8% and a specificity of 69.5% in the prediction of spontaneous preterm delivery at <34 weeks. CONCLUSION: This study supports the theory that a subclinical intrauterine/fetal inflammatory process early in gestation may be important for the occurrence of preterm delivery in the second half of gestation.     

Clara cell protein 16 concentration in mid-trimester amniotic fluid: association with fetal gender, fetal G>A +38 CC16 gene polymorphism and pregnancy outcome

Clara cell protein 16 (CC16) is a major immunomodulatory protein produced in the fetal lung. We hypothesized that the mid-trimester amniotic fluid concentration of CC16 would vary according to a +38 CC16 polymorphism in the fetal genome and that increased levels would be an early indicator of subsequent adverse pregnancy outcome. Mid-trimester singleton amniotic fluids from 244 women were assayed for CC16 by ELISA. DNA from fetal cells in 179 amniotic fluids were tested for the A>G polymorphism at position +38 in exon 1 by PCR. Outcome data were obtained from 233 women after completion of laboratory testing. Median CC16 levels were higher in amniotic fluids containing male fetuses than in those with females (p=0.0005). Median amniotic fluid CC16 levels were higher in Hispanics than in Whites and Asians (p<0.05). CC16*G homozygosity was associated with elevated amniotic fluid CC16 concentrations compared to CC16*A homozygotes (p=0.02). Intraamniotic CC16 levels were highest in pregnancies that subsequently resulted in preterm premature rupture of membranes (PPROM) (p=0.01). We conclude that mid-trimester intraamniotic CC16 concentrations vary by gender, ethnicity and fetal CC16 gene polymorphism. Elevated CC16 levels are predictive of subsequent development of PPROM.     

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.     

Amniotic fluid insulin,C peptide concentrations,and fetal morbidity in infants of diabetic mothers

Glucose, insulin, C peptide, and insulin antibody concentrations were measured in amniotic fluid collected under basal conditions and 2 hours after an arginine challenge from 61 insulin-treated diabetic women (12 basal and 49 after arginine challenge) and 31 nondiabetic pregnant women in late gestation (23 basal and eight after arginine challenge). The insulin, C peptide, and glucose concentrations were significantly higher in diabetic pregnant women than in nondiabetic pregnant women in each case. In the amniotic fluid obtained after arginine challenge in diabetic pregnant women, C peptide concentration was correlated with both insulin concentration (r = 0.61) and birth weight (r = 0.53). The insulin and C peptide concentrations were significantly higher (p < 0.025) in samples from diabetic pregnancies associated with fetal morbidity than from diabetic pregnancies without fetal morbidity. Basal amniotic fluid insulin and C peptide concentrations were slightly greater in overweight infants of diabetic mothers compared to those of normal weight, whereas the differences for insulin and C peptide concentrations in the amniotic fluid obtained after arginine challenge were highly significant (p < 0.0125 and p < 0.0005, respectively). Finally insulin and C peptide concentrations in the amniotic fluid obtained after arginine challenge in diabetic pregnant women showed a correlation with maternal metabolic control but not with the degree (White classification) of maternal diabetes. No or negligible interference of insulin antibody in the radioimmunoassay of insulin in amniotic fluid was observed.     

Ultrasound evaluation of polyhydramnios and twin pregnancy

We analyzed the ultrasound examinations and medical records of 75 pairs of twins who were delivered between January, 1983, and December, 1984, to study the relationship between increased amniotic fluid volume, fetal abnormalities, and preterm labor. Ten of these 75 twin pregnancies demonstrated elevated amniotic fluid volume that persisted throughout pregnancy. Total intrauterine volumes were elevated in these cases, and nine of the ten pregnancies were abnormal. In addition, it was noted that elevation of the amniotic fluid volume alone did not explain the high rate of preterm labor and delivery in twin gestations.     

Relationship between meconium staining and amniotic fluid volume in term pregnancies

OBJECTIVE: Our purpose was to evaluate the relationship between meconium-stained amniotic fluid (MEC-AF) and amniotic fluid volume (AFV) and their impact on the risk of cesarean delivery for fetal indications in term pregnancies. METHODS: 1,655 live-born singleton gestations delivering at > or = 37 weeks within 7 days of sonographic assessment of the amniotic fluid index (AFI) were studied. AFI was categorized as: oligohydramnios (< or = 5.0 cm); decreased (5.1-8.0 cm); normal (8.1-18.0 cm); increased (18.1-23.9 cm), and polyhydramnios (> or = 24.0 cm). Frequencies of MEC-AF for each AFV category were stratified by gestational age (GA) and rates of cesarean delivery for fetal indications compared between patients with clear amniotic fluid and those with MEC-AF. Stepwise logistic regression analyses were performed for determinants of MEC-AF and the need for cesarean delivery for fetal indications. RESULTS: The frequency of MEC-AF at birth in term pregnancies was not related to AFV: oligohydramnios (16.7%); decreased (16.7%); normal (20.1%); increased (24.4%), and polyhydramnios (22.1%). The only factor associated with the occurrence of MEC-AF was increasing GA at delivery (p < 0.01). Both MEC-AF (p < 0.02) and decreasing neonatal ponderal index (p < 0.02) were independently associated with cesarean delivery for fetal distress. CONCLUSIONS: MEC-AF does not appear to be related to AFV in term pregnancies, and its presence increases the risk of cesarean delivery for fetal distress independent of AFV and neonatal ponderal index.     

Amniotic fluid prolactin and fetal lung maturation

Concentrations of prolactin in amniotic fluid, fetal plasma, and maternal plasma were determined in 34 rhesus monkeys delivered by hysterotomy under general anesthesia at gestational ages of 110 to 160 days (term, 165 days). Included were 15 cases (gestational ages 110 to 143 days) in which the mothers received 2 mg of betamethasone intramuscularly daily for 3 days prior to delivery. Fetal lung maximum volumes were determined in addition to the following indices of fetal lung surfactant: lung alveolar stability, lung phosphatidylcholine concentrations, lung extract surface tensions, and amniotic fluid lecithin to sphingomyelin ratios. Amniotic fluid prolactin was found to correlate significantly with lung alveolar stability (r = 0.51; p less than 0.01), lung phosphatidylcholine (r = 0.51; p less than 0.01), lung extract surface tension (r = -0.39, p less than 0.05) and amniotic fluid lecithin/sphingomyelin ratio (r = 0.50; p less than 0.01). These correlations remained statistically significant even when the effects of gestational age were taken into account. These findings suggest that amniotic fluid may modulate fetal production of surfactant via its prolactin content.     

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.     

Matrix metalloproteinase 3 in parturition,premature rupture of the membranes,and microbial invasion of the amniotic cavity

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. STUDY DESIGN: A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value < 0.05 was considered statistically significant. RESULTS: (1) MMP-3 was detected in 99.5% (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. CONCLUSIONS: (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.     

Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery

OBJECTIVE: The purpose of this study was to evaluate the role of monocyte chemotactic protein-1 in cervical and amniotic fluid in women in preterm labor and with preterm premature rupture of membranes. STUDY DESIGN: Women with singleton pregnancies (相似文献   

A role for the novel cytokine RANTES in pregnancy and parturition.

OBJECTIVE: RANTES (regulated on activation, normal T cell expressed and secreted), a potent and versatile chemokine, is capable of attracting monocytes, lymphocytes, basophils, and eosinophils. This cytokine has been implicated in the regulation of the inflammatory response and in the recruitment of macrophages to the implantation site in early pregnancy. RANTES messenger ribonucleic acid and protein have been detected in fetal tissue and first-trimester trophoblast in response to bacterial endotoxin. The purpose of this study was to determine whether intrauterine infection, parturition (preterm and term), and gestational age affect the amniotic fluid concentrations of RANTES in human pregnancy. STUDY DESIGN: A cross-sectional study was designed to examine the relationship between labor, microbial invasion of the amniotic cavity, gestational age, and RANTES expression in amniotic fluid. Amniotic fluid was obtained from 214 women in the following groups: (1) midtrimester (n = 22), (2) preterm labor with intact membranes in the presence (n = 20) or absence (n = 74) of microbial invasion of the amniotic cavity, (3) term, not in labor (n = 44) and term, in labor in the presence (n = 27) and absence (n = 27) of microbial invasion of the amniotic cavity. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. RANTES concentrations were determined by use of a sensitive and specific immunoassay. RESULTS: (1) Amniotic fluid RANTES concentrations decrease with advancing gestational age (r = 0. 43; P <.01). (2) Labor at term was associated with an increase in median concentrations of RANTES (labor-median, 8.4 pg/mL; range, <1.3-94.4 vs no labor-median, <1.3 pg/mL; range, <1.3-230.3; P <.01). (3) Women with preterm labor who delivered preterm (no microbial invasion of the amniotic cavity) had a higher median concentration of amniotic fluid RANTES than those who delivered at term (median, 12.7 pg/mL; range, <1.3-928 vs median, <1.3 pg/mL; range, <1.3-127. 5; P <.001). (4) Microbial invasion of the amniotic cavity was associated with a significant increase in median amniotic fluid RANTES in both preterm and term labor (preterm labor with microbial invasion of the amniotic cavity-median, 51.6 pg/mL; range, <1.3-2290 vs preterm labor without microbial invasion of the amniotic cavity-median, 12.7 pg/mL; range, <1.3-928 and vs preterm labor with delivery at term-median, <1.3 pg/mL; range, <1.3-127.5; P <.001 for each; term labor with microbial invasion of the amniotic cavity-median, 16.8 pg/mL; range, <1.3-171.4 vs term labor without microbial invasion of the amniotic cavity-median, 8.4 pg/mL; range, <1.3-94.4; P <.05 and vs no labor and no microbial invasion of the amniotic cavity-median, 1.4 pg/mL; range, <1.3-230.3; P <.001 and P <.05, respectively). CONCLUSION: These results support a role for RANTES in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.     

Sexual dimorphism in the levels of amniotic fluid leptin in pregnancies at 16 weeks of gestation: relation to fetal growth

OBJECTIVE: To investigate whether in the first half of pregnancy levels of leptin in amniotic fluid are sexually dimorphic, and are related to fetal growth. STUDY DESIGN: Samples of amniotic fluid were collected during amniocentesis from 211 pregnancies with a single fetus with a normal karyotype (107 from male fetuses). Fetal growth was evaluated at 16 and 32 weeks of gestation, by sonography, and in a subset of 137 women at delivery. RESULTS: Amniotic fluid leptin was significantly lower in male than female fetuses (7.91+/-0.36 ng/ml versus 10.45+/-0.38 ng/ml; p = 0.0001). In females, levels of leptin were inversely related to BPD measured at 16 weeks (r = -0.241; p = 0.013) to biparietal diameter (BPD) (r = -0.281; p = 0.0076) and abdominal circumference (r = 0.268; p = 0.0107) measured at 32 weeks of gestation and to neonatal weight (r = -0.236; p = 0.051), neonatal weight/height (r = -0.271; p = 0.026) or neonatal Kaup index (r = 0.255; p = 0.045). Leptin was not related to any fetal parameter in males. CONCLUSIONS: Levels of leptin in amniotic fluid at 16 weeks of gestation are sexually dimorphic and are inversely related to fetal growth, particularly of females.