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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 10th 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. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes.Study Design: Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation.Results: One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2).Conclusions: Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the success rate of cytogenetic analysis from specimens obtained at the time of second-trimester termination of pregnancy by dilation and evacuation.Study Design: All second-trimester dilation and evacuations performed by a single practitioner at a single institution from 1993 through 1995 were evaluated to pick out those patients in whom biopsy specimens were submitted for cytogenetic analysis. The main outcome studied was the ability to obtain karyotype results for these specimens.Results: Cytogenetic studies were performed on 258 dilation and evacuation specimens with a median gestational age of 18 weeks (range 13-25 weeks). The indications for termination were fetal aneuploidy (n = 88, 34%), sonographically diagnosed fetal malformations (n = 82, 32%), intrauterine fetal death (n = 67, 26%), oligohydramnios or premature rupture of membranes (n = 16, 6%), and others (hematologic and metabolic disorders, n = 5, 2%). Successful karyotyping was achieved for 99% of specimens obtained at second-trimester dilation and evacuation, with 3 failures of growth (1% failure rate). The failures included a 14-week molar pregnancy, an 18-week fetus with Dandy-Walker malformation, and a 19-week intrauterine fetal death. Of the samples obtained in cases of intrauterine fetal death, 99% (66/67) provided adequate cytogenetic information.Conclusions: Karyotyping for abnormal second-trimester pregnancies and intrauterine fetal deaths at the time of a dilation and evacuation procedure has a success rate nearing 100%. In contrast to previous reports, our data indicate that it is unnecessary to perform pretermination invasive karyotyping in patients with abnormal second-trimester pregnancies or intrauterine fetal death who elect to undergo dilation and evacuation. Chromosome analysis at the time of termination of pregnancy by dilation and evacuation reduces patient discomfort, risk of infection, and cost while still providing reliable and vital cytogenetic information for future genetic counseling. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery.Study Design: One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospectively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix. The primary outcome studied was preterm (< 35 weeks) delivery.Results: Excluding six induced preterm deliveries, 96 pregnancies were analyzed. The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm (n = 17) and 31.3 mm in pregnancies delivered at term (n = 79) (p = 0.003); the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies, respectively (not significant). The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately (p < 0.0005). The 25th percentiles of ultrasonographic (25 mm) and manual (16 mm) cervical lengths showed relative risks for preterm delivery of 4.8 (95% confidence interval 2.1 to 11.1, p = 0.0004) and 2.0 (95% confidence interval 0.5 to 4.7, p = 0.1), respectively; sensitivity, specificity, and positive and negative predictive values were 59%, 85%, 45%, 91%, and 41%, 77%, 28%, and 86%, respectively.Conclusion: Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination. Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks' gestation. [ABSTRACT FROM AUTHOR]

This article reviews the current trends in the evaluation and management of bacterial infection involving the uterus, placenta, membranes, amniotic fluid, and fetus occurring near the time of birth. The discussion includes information regarding risk, incidence, pathophysiology, bedside diagnosis, interventional options including antibiotics, corticosteroids, fetal monitoring, and delivery, and possible preventive measures which affect the outcome. The adequate evaluation and management of perinatal infection requires a team approach with obstetricians and pediatricians. Clinical screening is useful in developing the diagnosis, but amniotic fluid evaluation remains the proposed gold standard. The role of cytokines is becoming increasingly important, as is seen in the association of IL-6 with positive amniotic fluid cultures and periventricular leukomalacia. Prompt recognition and management of the pregnancy affected by infection can improve perinatal outcomes. A management protocol is presented to help structure the approach to suspected infection. Premature delivery due to perinatal infection may be preventable. [ABSTRACT FROM AUTHOR]

Background: Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities.Methods: We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.Results: The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001).Conclusions: Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.). [ABSTRACT FROM AUTHOR]

Objective: To determine whether β2 -adrenoceptor (β2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester., Design: A case-control ancillary study to a multicentre randomised controlled trial., Setting: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development., Population: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length., Methods: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27., Main Outcome Measures: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks., Results: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited., Conclusions: β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objective: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women., Design: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls., Setting: A multicentre study in 16 academic medical centres in the USA., Population: Low-risk nulliparous women., Methods: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics., Main Outcome Measures: Change in PlGF, sFlt-1 and sEng., Results: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester., Conclusion: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia., (© Published 2013 This article is a U.S. Government work and is in the public domain in the USA © 2013 RCOG.)

Background: Each year at least one million children worldwide die of pneumococcal infections. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but does not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection., Objectives: To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to June 2004), EMBASE (January 1985 to June 2004), and reference lists of articles., Selection Criteria: Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing or with another vaccine to prevent infant infections., Data Collection and Analysis: Two authors independently assessed methodological quality and extracted data using a data collection form. Study authors were contacted for additional information., Main Results: Three trials (280 participants) were included. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (one trial, 149 pregnancies, relative risk (RR) 0.51; 95% confidence interval (CI) 0.18 to 1.41). Although the data suggest an effect in reducing pneumococcal colonisation in infants by 16 months of age (one trial, 56 pregnancies, RR 0.33; 95% CI 0.11 to 0.98), there was no evidence of this effect in infants at two months of age (RR 0.28; 95% CI 0.02 to 5.11) or by seven months of age (RR 0.32; 95% CI 0.08 to 1.29)., Authors' Conclusions: There is insufficient evidence to support whether pneumococcal vaccination during pregnancy could reduce infant infections.

Background: Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven., Objectives: To assess the effects of prophylactic oral betamimetics administered to women with twin pregnancies., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (May 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to May 2004), EMBASE (January 1985 to May 2004), and reference lists., Selection Criteria: Randomized controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth., Data Collection and Analysis: Standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Trials were independently assessed for methodological quality by at least two authors, who extracted data using a data collection form., Main Results: Five trials (344 twin pregnancies) were included. All trials compared oral betamimetics to placebo. Betamimetics reduced the incidence of preterm labour (one trial, 50 twin pregnancies, relative risk (RR) 0.40; 95% confidence interval (CI) 0.19 to 0.86). However, betamimetics did not reduce preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10) or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, weighted mean difference 111.2 grams; 95% CI 22.2 to 200.2). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, RR 1.19; 95% CI 0.77 to 1.85) or small-for-gestational age neonates (two trials, 178 neonates, RR 0.92; 95% CI 0.52 to 1.65). Two trials (388 neonates) showed that betamimetics significantly reduced the incidence of respiratory distress syndrome but the difference was not significant when the analysis was adjusted for correlation of babies from twins. Three trials (452 neonates) showed no evidence of an effect of betamimetics in reducing neonatal mortality (RR 0.80; 95% CI 0.35 to 1.82)., Authors' Conclusions: There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.

Background: The incidence of chlorioamnionitis occurs in between 8 to 12 women for every 1000 live births and 96% of the cases of chlorioamnionitis are due to ascending infection. Following spontaneous vaginal delivery, 1% to 4% of women develop postpartum endometritis. The incidence of neonatal sepsis is 0.5% to 1% of all infants born. Maternal vaginal bacteria are the main agents for these infections. It is reasonable to speculate that prevention of maternal and neonatal infections might be possible by washing the vagina and cervix with an antibacterial agent for all women during labour. Chlorhexidine belongs to the class of compounds known as the bis-biguanides. Chlorhexidine has antibacterial action against a wide range of aerobic and anaerobic bacteria, including those implicated in peripartal infections., Objectives: To evaluate the effectiveness and side-effects of chlorhexidine vaginal douching during labour in reducing maternal and neonatal infections (excluding Group B Streptococcal and HIV)., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (from 1966 to 2002), EMBASE (from 1980 to 2002), CINAHL (from 1982 to 2002) and LILACS (from 1982 to 2002)., Selection Criteria: Randomized or quasi-randomized trials comparing chlorhexidine vaginal douching during labour with placebo or other vaginal disinfectant to prevent (reduce) maternal and neonatal infections (excluding Group B Streptococcal and HIV)., Data Collection and Analysis: Two reviewers independently assessed trial eligibility and quality, extracted and entered the data into the RevMan software and interpreted the data. A third reviewer analysed and interpreted the data. The fourth reviewer also interpreted the data., Main Results: Three studies (3012 participants) were included. There was no evidence of an effect of vaginal chlorhexidine during labour in preventing maternal and neonatal infections. Although the data suggest a trend in reducing postpartum endometritis, the difference was not statistically significant (relative risk 0.83; 95% confidence interval 0.61 to 1.13)., Reviewers' Conclusions: There is no evidence to support the use of vaginal chlorhexidine during labour in preventing maternal and neonatal infections. There is a need for a well-designed randomized controlled trial using appropriate concentration and volume of vaginal chlorhexidine irrigation solution and with adequate sample size.

Background: Heavy colonization with group B streptococcus (GBS) has been associated with increased risk of preterm birth and neonatal sepsis; the burden of neonatal GBS disease varies geographically. To determine whether variation in heavy colonization and GBS serotypes could contribute to geographic differences in disease burden, we assessed the prevalence of heavy colonization and the distribution of serotypes in asymptomatic pregnant women in multiple countries., Methods: Cervical, lower vaginal and urine samples were collected from women attending seven prenatal clinics in six countries. Light colonization was defined as GBS isolation from Lim broth only; heavy colonization was isolation from urine or sheep blood agar plates. Isolates were serotyped using capillary precipitation., Results: GBS was present in 11.3% of 1308 participants (range 7.1-21.7%); 5.0% were heavily colonized (0.4-18.8%) and 6.4% were lightly colonized (2.9-8.0%). Serotypes III and V were most common (both 17.2%). Serotypes VII and VIII were found in one study center., Conclusions: The prevalence of heavy colonization and GBS serotypes varied significantly among our study centers. Whether this variation could in part explain geographic differences in neonatal morbidity and mortality is a hypothesis that needs further study.

Objectives: To evaluate birthweight-specific neonatal mortality and perinatal interventions in major medical centers in developed and developing countries., Methods: A survey was developed and electronically mailed to 13 medical centers participating in the Global Network for Perinatal and Reproductive Health (GNPRH). The ability of a center to provide requested data was assessed. The mortality rates and use of specific perinatal interventions in centers in developing countries were compared with developed countries., Results: Nine centers in developing countries responded to the survey, and three centers in developed countries were used for comparison. Data collection was highly variable. Most developing country centers were able to provide data by birthweight but not by gestational age. The differences in mortality rates between developing and developed countries were more pronounced at lower gestational ages and birthweights. A difference was found in perinatal interventions between developing and developed countries. In the former, viability was generally considered 28 weeks, and the gestational age at which cesarean sections were usually performed for the sake of the fetus at preterm gestations varied from 26 to 37 weeks. Most centers did not routinely induce for pPROM; only five out of nine centers used antibiotics to prolong latency. Most centers used tocolysis beginning at 26-28 weeks through 32-37 weeks, and a variety of tocolytic agents were used. Most centers routinely used corticosteroids for preterm infants, and all centers employed repeat weekly steroid dosing if undelivered., Conclusions: Despite the fact that the GNPRH centers included in this study represent some of the best health care available in these countries, they lag far behind centers in developed countries in neonatal mortality rates and their use of various obstetric practices. Furthermore, incomplete and inconsistent data collection complicates the evaluation of the factors contributing to high neonatal mortality rates.

Objective: To examine the use of antibiotic prophylaxis in cesarean section in different countries and in relation to a reference regimen., Method: Fifty consecutive cesarean sections performed in eight centers in five countries were surveyed. Data from each center were compared to a regimen recommended by the Cochrane Collaboration (one dose of ampicillin or cefazolin administered to all women shortly before the procedure or immediately after cord clamping) using logistic regression with adjustment for procedure type., Result: Prophylaxis was used widely, but only four centers administered prophylaxis to all women. Ampicillin and cefazolin were the principal antibiotics used, but broad-spectrum agents and multidrug regimens were also used commonly. Only two centers reliably administered the antibiotic at the appropriate time. The majority of women received only one dose of antibiotic in only three centers., Conclusion: The use of antibiotic prophylaxis in cesarean section was variable and often at odds with published recommendations.

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.

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.

The role of infection in the pathogenesis of preterm labor and delivery, and the specific mechanisms through which this association is demonstrated are presented. Cellular and biochemical changes that initiate parturition in the setting of infection are discussed, particularly prostaglandins and cytokines.