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Objective: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10 th percentile)., Methods: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB., Results: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively)., Conclusions: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: S100B is produced by glia of the central and peripheral nervous systems and is considered a marker of neurologic injury in the perinatal period. Indeed, increased neonatal urine S100B concentration is associated with adverse neurological outcomes including intraventricular hemorrhage and hypoxic-ischemic encephalopathy, while elevated adult serum concentrations are associated with infectious diseases/sepsis. The objective of this study was to determine whether amniotic fluid (AF) S100B concentrations change with advancing gestational age and intra-amniotic infection (IAI)., Study Design: S100B concentration was measured in the AF of women in midtrimester, at term, and in pregnancies with preterm labor and intact membranes (PTL) or preterm premature rupture of membranes (PPROM), with and without IAI. Placental pathology was performed and neonatal outcomes were analyzed., Results: (1) AF S100B concentration did not change during gestation; (2) patients with IAI had significantly higher AF S100B concentration than those without IAI following an episode of PTL or PPROM and; (3) neonates who had morbidity/mortality had had an elevated AF S100B concentration; however, this could be explained by the association with intra-amniotic infection/inflammation. Thus, AF S100B concentration was not an independent predictor of neonatal morbidity or fetal/neonatal death., Conclusions: An elevated concentration of AF S100B may reflect intra-amniotic infection/inflammation and not necessarily fetal neurologic damage.

Objective: Pregnancy loss after mid-trimester amniocentesis occurs in 0.5-1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinically silent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide variety of cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/or fetal death., Method: A retrospective case-control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancy loss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay (sensitivity, 18.3 pg/ml). The Kolmogorov-Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis was performed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1., Results: MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those with a normal pregnancy outcome (pregnancy loss, mean 2.95 +/- 0.19 pg/ml vs. normal outcome, mean 2.78 +/- 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis (area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7-31.1), a sensitivity of 70%, and a specificity of 76%., Conclusion: A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 than those who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinical implications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of the procedure.

Objective: The objective of this study was to determine whether concentrations of activin A and corticotropin-releasing factor in amniotic fluid can identify patients at risk of fetal death., Study Design: A retrospective case-control study of women who have had a midtrimester amniocentesis was designed. Case subjects consisted of patients who had a spontaneous fetal death after the procedure, whereas the control group consisted of patients who had a normal pregnancy outcome after midtrimester amniocentesis. Dimeric activin A was measured by a specific 2-site enzyme immunoassay, and corticotropin-releasing factor was measured by a specific and sensitive radioimmunoassay after acidic extraction. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and chi2 tests and regression analysis., Results: First, activin A was detectable in all amniotic fluid samples. Second, the concentration of activin A in amniotic fluid increased with advancing gestational age. Third, patients who subsequently had a fetal death had a higher median concentration of activin A than those with a normal pregnancy outcome (P <.01). Fourth, an amniotic fluid concentration of activin A greater than the 95th confidence interval for gestational age was found in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P <.005). Finally, the median concentration of corticotropin-releasing factor in amniotic fluid was not different in case subjects and control subjects., Conclusions: An elevated concentration of activin A in amniotic fluid identifies women at risk of fetal death.

The traditional paradigm that prostaglandins (PGS) are of central importance in the initiation of labor has been challenged. A group of investigators has recently reported that the amniotic fluid concentrations of PGE(2) and PGF(2 alpha) increase only late in the course of labor implying that "the accumulation of prostaglandins in amniotic fluid is an after-effect of labor and not indicative of a role of these compounds in the initiation of human parturition." The present study was conducted to determine whether amniotic fluid prostaglandin concentrations increase prior to the onset of human labor, the central question in this controversy. Three amniocenteses were performed in 17 women with intrahepatic cholestasis of pregnancy -- the first two prior to the onset of labor and the third during early spontaneous labor. PGE(2) and PGF(2 alpha) were measured with sensitive and specific radioimmunoassays. Amniotic fluid concentrations of PGE(2) and PGF(2 alpha) increased prior to the onset of spontaneous labor. An additional increase in the concentrations of PGE(2) and PGF(2 alpha) was found in samples obtained in early labor. We conclude that an increase in prostaglandin bioavailability precedes the onset of spontaneous human parturition.

The purpose of this study was to determine whether preterm parturition is associated with changes in maternal plasma and amniotic fluid dehydroepian-drosterone-sulfate concentrations. A cross sectional study was constructed according to the gestational age at admission and response to tocolysis. Group 1 consisted of women admitted with preterm labor and intact membranes between 28 and 31 weeks and 6 days gestational age (n = 40). Group 2 included 40 patients with preterm labor between 32 and 36 weeks gestational age. Both groups were classified into two subgroups: preterm delivery within seven days of admission and term delivery. Commercially available immunoassay kits validated for amniotic fluid analysis of DHEA-S, were used to measure maternal plasma and amniotic fluid DHEA-S concentrations. Maternal plasma DHEA-S concentrations were significantly higher in women with preterm labor who delivered preterm than in those who delivered at term. (Group 1: median 800 ng/ml [range 100-1100] vs. median 200 ng/ml [70-800], P < 0.001; Group 2: median 850 ng/ml [300-1700] vs. median 300 ng/ml [90-1100], P < 0.001). In contrast, no significant differences were detected in amniotic fluid DHEA-S concentrations. Our data suggest that the rise in maternal plasma DHEA-S concentrations observed in patients with preterm labor may be related to the effects of stress during labor.

Problem: GRO alpha/MGSA is a new member of the chemokine superfamily CXC(alpha) and is produced by a variety of cells including macrophages, fibroblasts, epithelial, and endothelial cells, and keratinocytes. This chemokine has chemoattractant activity and may participate in neutrophil recruitment and activation during the course of intrauterine infection. This study was conducted to investigate the effect of labor and microbial invasion of the amniotic cavity (MIAC) on amniotic fluid, fetal, and maternal plasma GRO alpha concentrations., Method: A cross-sectional study was designed using parameters that included gestational age, results of amniotic fluid (AF) cultures, and labor status at the time of amniocentesis. Fluid was retrieved by transabdominal amniocentesis. MIAC was defined as a positive amniotic fluid culture for bacteria. Umbilical cord blood was retrieved at the time of delivery. Amniotic fluid, maternal and fetal plasma GRO alpha concentrations were measured with a sensitive and specific ELISA (Quantikine, R&D Systems, Minneapolis, MN)., Results: 1) GRO alpha was detectable in amniotic fluid, umbilical cord, and maternal plasma samples; 2) GRO alpha concentrations in amniotic fluid increased with advancing gestational age; 3) Both term and preterm gestations with MIAC were associated with higher amniotic fluid GRO alpha concentrations than those with sterile amniotic fluid, independent of the labor status (term, MIAC, labor: median 2.7 ng/ml, range 1.4-12.7 vs. term, no MIAC, labor: median 2.1 ng/ml, range 0.7-3.4, vs term, no MIAC, no labor: median 1.9 ng/ml, range 1.8-4.2; P < 0.005; preterm: MIAC median 5 ng/ml, range 0.6-47.9 vs. no MIAC: median 2.3 ng/ml, range 0.5-10; P < 0.008); 4) A strong correlation was found between umbilical cord plasma GRO alpha concentrations and neonatal neutrophil count, and between GRO alpha concentrations and white blood cell count in the amniotic fluid (r = 0.67, P < 0.0005 and r = 0.38, P < 0.001, respectively)., Conclusion: GRO alpha is a physiologic constituent of amniotic fluid and cord blood. Amniotic fluid GRO alpha concentrations increase with gestational age. Intrauterine infection both preterm and at term is associated with an increase in GRO alpha concentrations of amniotic fluid, suggesting that GRO alpha may play an important role in recruitment of neutrophils into the amniotic cavity.