Maternal vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years.

BACKGROUND/OBJECTIVE: Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. SUBJECTS/METHODS: We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. RESULTS: Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l-m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (-0.43 units; CI: -0.79, -0.07; P=0.02 for Q1 and -0.56 units; CI: -0.89, -0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. CONCLUSIONS: Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.

Using antifibrinolytics in the peripartum period - concern for a hypercoagulable effect?

INTRODUCTION: Although antifibrinolytic agents are used to prevent and treat hemorrhage, there are concerns about a potential increased risk for peripartum venous thromboembolism. We sought to determine the impact of tranexamic acid and ɛ-aminocaproic acid on in vitro clotting properties in pregnancy. METHODS: Blood samples were obtained from healthy pregnant, obese, and preeclamptic pregnant women (n = 10 in each group) prior to delivery as well as from healthy non-pregnant controls (n = 10). Maximum clot firmness (MCF) and clotting time (CT) were measured using rotation thromboelastometry in the presence of tranexamic acid (3, 30, or 300 µg/mL) or ɛ-aminocaproic acid (30, 300, or 3000 µg/mL). ANOVA and regression analyses were performed. RESULTS: Mean whole blood MCF was significantly higher in healthy pregnant vs. non-pregnant women (66.5 vs. 57.5 mm, p < 0.001). Among healthy pregnant women, there was no significant difference between mean MCF (whole blood alone, and with increasing tranexamic acid doses = 66.5, 66.1, 66.4, 66.3 mm, respectively; p = 0.25) or mean CT (409, 412, 420, 424 sec; p = 0.30) after addition of tranexamic acid. Similar results were found using ɛ-aminocaproic acid. Preeclamptic women had a higher mean MCF after the addition of ɛ-aminocaproic acid and tranexamic acid (p = 0.05 and p = 0.04, respectively) compared to whole blood alone. CONCLUSIONS: Pregnancy is a hypercoagulable state, as reflected by an increased MCF compared to non-pregnant women. Addition of antifibrinolytic therapy in vitro does not appear to increase MCF or CT for non-pregnant, pregnant, and obese women. Whether antifibrinolytics are safe in preeclampsia may require further study.

Obstetric hemorrhage survey: Attitudes and practices of maternal-fetal medicine fellows.

OBJECTIVE: To evaluate experiences related to obstetric hemorrhage and suspected abnormal placentation among first year maternal-fetal medicine fellows. STUDY DESIGN: A cross-sectional anonymous survey was administered at the Society for Maternal-Fetal Medicine fellow retreat in March 2013. Fellows were asked about management strategies that reflected both their individual and institutional practices. RESULTS: There was a 56% response rate (55/98). In cases of postpartum hemorrhage due to uterine atony, there was variable use of the uterine tamponade device. The median incremental time for balloon deflation was every 5 hours (IQR = 2-12). Compared to the east coast, fellows from the west coast performed more hysterectomies (mean±SD; 2.9±2.4 vs. 1.2±1.2, p = 0.004). During a peripartum hysterectomy, 29% of fellows used a handheld cautery device such as Ligasure® or Gyrus®. Fifty-six percent responded that their institution never recommend planned delayed hysterectomies for abnormal placental implantation. CONCLUSION: There is wide variation in practice among first year maternal-fetal medicine fellows in management of peripartum hysterectomy and postpartum hemorrhage.

Midregional pro-adrenomedullin plasma concentrations are blunted in severe preeclampsia.

Levels of the peptide hormone adrenomedullin (AM) are elevated during normal pregnancy, but whether this differs during complications of pregnancy remains unresolved. AM can be quantified by measuring its pre-prohormone byproduct, midregional pro-adrenomedullin (MR-proADM). MR-proADM has shown prognostic value as a biomarker of heart failure, sepsis, and community-acquired pneumonia. Given the relevance of AM to pregnancy, we tested the hypothesis that MR-proADM provides a biomarker for preeclampsia. We find that MR-proADM plasma concentrations are blunted in severe preeclampsia and that MR-proADM is similarly effective as established biomarkers endoglin and placental growth factor at discriminating patients with severe preeclampsia from controls.

Progesterone receptor membrane component 1 (PGRMC1) expression in fetal membranes among women with preterm premature rupture of the membranes (PPROM).

PGRMC1 function is implicated in maintaining fetal membrane (FM) integrity. PGRMC1 was detectable primarily in the cytoplasm of FM cells and was actively regulated in FMs and relevant for PGRMC1-mediated progesterone action. By cell type, PGRMC1 expression was higher in amnion and chorion compared with decidua. By clinical phenotype, PGRMC1 expression was higher among preterm-no-labor and term-no-labor subjects compared to PPROM. PGRMC1 expression appears to be diminished in PPROM subjects.

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.

OBJECTIVES: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. METHODS: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. RESULTS: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (ß-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (ß-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. CONCLUSION: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.

Cervical dilation as a predictor of pregnancy outcome following emergency cerclage.

OBJECTIVE: To determine whether cervical dilation at the time of physical examination indicated cerclage placement can predicts latency and gestational age at delivery. METHODS: A retrospective cohort study of all women who underwent physical examination indicated cerclage placement from 1996 to 2011 at Duke University Hospital (DUH) was performed. Physical examination indicated cerclage was defined as cerclage placement after 16 weeks in women with a cervical length of less than 2.5 cm and/or cervical dilation greater than or equal to 1 cm at time of procedure. Subjects were divided into two groups depending on cervical dilation at time of procedure (2 cm, <2 cm) for comparison. A multivariate linear regression model for the outcome gestational age of delivery was constructed, controlling for confounding variables. RESULTS: A total of 110 women with complete data were available for analysis. Median gestational age at cerclage placement was similar between the two groups (20.3 vs. 20.3 weeks, p = 0.8). Women with cervical dilatation ≥ 2 cm dilation delivered at an earlier median gestational age than women with cervical dilation <2 cm (27.0 vs. 35.6 weeks, p < 0.001). Cervical dilation at the time of cerclage placement independently predicted gestational age at delivery while controlling for use of intracervical Foley balloon catheter for membrane reduction, cerclage suture type, history of prior preterm birth, race, insurance status, and tobacco use. CONCLUSIONS: Women who receive a rescue cerclage are more likely to deliver at an earlier gestational age when cervical dilation is ≥ 2 cm at the time of procedure.

Bleeding per vaginam is associated with funisitis in women with preterm prelabour rupture of the fetal membranes.

OBJECTIVE: To evaluate the risk of funisitis among women with preterm prelabour rupture of the membranes (PPROM) and subsequent bleeding per vaginam. DESIGN: Prospective cohort study. SETTING: A University Hospital in the USA. POPULATION: A total of 157 women with PPROM, divided into those with bleeding per vaginam during the hospital admission (n = 46) and those without bleeding per vaginam (n = 111). METHODS: Pathologist blinded to bleeding status assessed placental pathology for funisitis. MAIN OUTCOME MEASURES: Funisitis. RESULTS: Women with bleeding per vaginam were more likely to have funisitis (67.4% versus 36%, P < 0.001) compared with those without bleeding. Logistic regression demonstrated that bleeding per vaginam predicted funisitis after controlling for gestational age at admission, latency period and gestational age at delivery. CONCLUSIONS: Among women with PPROM, those with bleeding per vaginam are more likely to have funisitis than those without bleeding per vaginam.

Apoptosis in the chorion laeve of term patients with histologic chorioamnionitis.

OBJECTIVE: The balance between cell survival and cell death (apoptosis) is critical during development and may affect organ function. Apoptosis is accelerated in the presence of infection and inflammation in a variety of organ systems. The objective of this investigation was to determine if apoptosis was increased in the chorion laeve of term patients with and without histologic chorioamnionitis. METHODS: Records of placental pathology were reviewed with respect to the presence/absence of histologic chorioamnionitis. Sections from formalin-fixed, paraffin-embedded fetal membrane rolls were stained using the TUNEL method. The proportion of apoptotic nuclei was calculated in seven high-powered fields/section. Those with and without histologic chorioamnionitis were compared. Data were analyzed using the Mann-Whitney U test, with significance defined as p < 0.05. RESULTS: There was no significant difference in demographic or clinical characteristics between the two groups. The chorion laeve from subjects with histologic chorioamnionitis had significantly more apoptotic nuclei when compared to those without chorioamnionitis (11.2% vs. 5%, p = 0.02). CONCLUSION: Apoptosis is more prevalent in the chorion laeve of fetal membranes with histologic chorioamnionitis. This finding suggests that infection/inflammation may impact cell survival within fetal membranes. The implications of these findings warrant further investigation.

Anergy during pregnancy.

OBJECTIVE: This study was undertaken to determine whether the prevalence of anergy is higher among pregnant women than among nonpregnant women. STUDY DESIGN: Sixty human immunodeficiency virus-seronegative women (n = 30 pregnant, n = 30 nonpregnant) from the Duke University Medical Center (Durham, North Carolina) clinic were enrolled. Skin tests were performed with purified protein derivative of tuberculin, Candida antigen, mumps antigen, and tetanus toxoid. A power calculation was done to determine adequate sample size, and data were analyzed with the Fisher exact test and the t test. RESULTS: Three women in each group did not have a response to any of the antigens tested, for an anergy prevalence of 10%. Pregnant women were less likely to have a reaction to skin testing with tetanus toxoid than were nonpregnant women (10% vs 40%; P <.02). CONCLUSION: Human immunodeficiency virus-seronegative pregnant women did not appear to have a higher prevalence of anergy than that seen among comparable nonpregnant women. Human immunodeficiency virus-seronegative pregnant women who are being evaluated with the purified protein derivative of tuberculin skin test are therefore unlikely to need anergy skin testing just because they are pregnant.

Acute fatty liver of pregnancy associated with short-chain acyl-coenzyme A dehydrogenase deficiency.

There is a correlation between pregnancy complications such as acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency. We diagnosed another fatty acid beta-oxidation defect, short-chain acyl-coenzyme A dehydrogenase deficiency, in an infant when evaluating him because his mother had acute fatty liver of pregnancy. Other beta-oxidation defects, in addition to LCHAD deficiency, should be considered in children born after pregnancies complicated by liver disease.

Repeated fetal betamethasone treatment and birth weight and head circumference.

OBJECTIVE: To assess the effect of repeated courses of betamethasone on birth weight and head circumference. METHODS: We conducted a historical cohort study of inpatients receiving betamethasone therapy over 5 years. We compared birth weights and head circumferences of infants whose mothers received one course of betamethasone with those of infants whose mothers received multiple courses. Multiple regression analysis was used to adjust for potential confounding variables. Sufficient power (80%) existed to detect a 20% difference between the groups (alpha = 0.05). RESULTS: Mean birth weights (+/-SD) were 1717 +/- 707 g in the single-course group (n = 107) and 1783 +/- 647 g in the multiple-course group (n = 45) (P =.59, Student t-test). Mean head circumference was 28.2 +/- 3.6 cm in the single-course group and 29.2 +/- 2.9 cm in the multiple-course group (P =.15, Student t-test). In regression analysis, birth weights (1757 g and 1752 g) and head circumferences (28.5 cm and 29.0 cm) did not differ significantly different between the single-course and multiple-course groups. CONCLUSION: Multiple courses of betamethasone do not reduce birth weight or head circumference in neonates compared with single-course therapy.

Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction.

Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. For example, among periodontally healthy mothers the unadjusted prevalence of births of GA < 28 weeks was 1.1%. This was higher among mothers with mild periodontal disease (3.5%) and highest among mothers with moderate-severe periodontal disease (11.1%). The adjusted prevalence rates among GA outcomes were significantly different for mothers with mild periodontal disease (n = 566) and moderate-severe disease (n = 45) by pair-wise comparisons to the periodontally healthy reference group (n = 201) at P = 0.017 and P < 0.0001, respectively. A similar pattern was seen for increased prevalence of low birth weight deliveries among mothers with antepartum periodontal disease. For example, there were no births of BW < 1000 g among periodontally healthy mothers, but the adjusted rate was 6.1% and 11.4% for mild and moderate-severe periodontal disease (P = 0.0006 and P < 0.0001), respectively. Periodontal disease incidence/progression during pregnancy was associated with significantly smaller births for gestational age adjusting for race, parity, and baby gender. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

Maternal periodontitis and prematurity. Part II: Maternal infection and fetal exposure.

Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed "Orange" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and "Red" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

Periodontal medicine: emerging concepts in pregnancy outcomes.

The term periodontal medicine encompasses the study of the contribution of periodontal infections on several systemic conditions such as atherosclerosis, myocardial infarction, stroke, diabetes, and premature delivery. The early reports of a linkage between periodontitis and systemic conditions are gaining further support from additional epidemiological studies. The evidence continues to suggest that maternal periodontitis may bean important risk factor or risk indicator for pregnancies culminating in preterm low birth-weight deliveries. Potential mechanisms by which infectious challenge of periodontal origin and systemic inflammation may serve as a potential modifier of parturition are discussed. Furthermore, preliminary data are presented, supporting a hypothetical model in which periodontal pathogens disseminate systemically within the mother and gain access to the foetal compartment. Several aspects of this hypothetical model remain to be elucidated. Only the clarification of the mechanisms of pathogenesis of both periodontitis and premature deliveries will ultimately allow for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimise the deleterious effects of this chronic infectious and inflammatory condition on systemic conditions represents both an unprecedented challenge and opportunity to our profession.

Umbilical venous D-dimer concentrations with and without labor.

OBJECTIVE: To determine if labor activates the fetal fibrinolytic system. METHODS: A total of 59 umbilical venous blood samples were collecting following vaginal delivery at term (n = 20), cesarean delivery following labor at term (n = 12), vaginal delivery before term (n = 18), and cesarean delivery without labor (n = 9). D-dimer concentrations, a sensitive marker of fibrinolysis, were measured by enzyme-linked immunosorbent assay, and compared between groups by Kruskel-Wallis and Mann Whitney U tests, with significance defined as P < .05. RESULTS: There were no significant differences in median D-dimer concentrations between newborns delivered vaginally or by cesarean after term labor or preterm labor. There were significant differences in median umbilical venous D-dimer concentrations in subjects delivered vaginally or by cesarean after term or preterm labor compared with term subjects without labor delivered by cesarean (427, 773, and 326 versus 87 ng/mL, P = .01). CONCLUSION: Elevation of umbilical plasma D-dimer concentrations in laboring patients suggests activation of fetal fibrinolysis before delivery.

Spontaneous rupture of a primigravid uterus secondary to placenta percreta. A case report.

BACKGROUND: Uterine rupture secondary to placenta percreta has been observed in multiparous patients. These cases are typically associated with a prior history of uterine trauma or infection: hysterotomy, myomectomy, cornual resection, dilatation and curettage, manual removal of the placenta or endometritis. Spontaneous rupture of the primigravid uterus without a history of trauma or infection is an exceedingly rare occurrence. This case represents the second reported in the medical literature and the first to result in a live-born infant. CASE: A 23-year-old, African American primigravida at 26 weeks' gestation presented with acute-onset abdominal pain, severe hypotension, tachycardia and fetal heart rate decelerations. Blood product replacement was initiated, and an emergency laparotomy was performed for a presumptive diagnosis of intraabdominal hemorrhage. A significant hemoperitoneum was encountered, with the fetus floating freely in the peritoneal cavity. The uterus had a fundal rupture with a clinically apparent placenta percreta that necessitated performing a total abdominal hysterectomy. The patient recovered uneventfully, and the infant survived without significant morbidity. CONCLUSION: Spontaneous rupture of the primigravid uterus can occur in the absence of a history of uterine trauma or infection. If a gravid woman presents with hypotension, abdominal pain and fetal distress, the differential diagnosis should include rupture of the uterus, regardless of parity or gynecologic history. Rapid diagnosis, blood product replacement and emergency laparotomy are the key steps in successful management.

Maternal serum interleukin-6 concentration as a marker for impending preterm delivery.

OBJECTIVE: To determine whether serum interleukin-6 concentrations predict impending preterm delivery. METHODS: Blood samples were collected from 130 gravidas at 22-34 weeks' gestation. The study group consisted of 89 women evaluated for preterm contractions or premature rupture of membranes, and these women were compared with 41 outpatient controls without evidence of labor or infection, chosen by clinicians at the time of routine prenatal visits. Serum interleukin-6 concentrations were measured using a specific enzyme-linked immunosorbent assay kit. Analyses were by the Mann-Whitney U and the Kruskal-Wallis tests. RESULTS: All 41 control subjects had serum interleukin-6 concentrations less than 8 pg/mL. Sixteen of the 89 study patients had serum interleukin-6 concentrations greater than or equal to 8 pg/mL and 73 had values less than 8 pg/mL. When the serum interleukin-6 concentration was at least 8 pg/mL, the median interval from collection to delivery was significantly shorter than that among study and control subjects with serum interleukin-6 less than 8 pg/mL (5.5 versus 240 and 1801 hours, respectively; P < .001). The median gestational age at delivery was significantly lower when the serum interleukin-6 concentration was at least 8 pg/mL, compared with study and control subjects with serum interleukin-6 concentrations less than 8 pg/mL (29.6 versus 33.4 and 39.0 weeks, respectively; P < .001). In patients with preterm contractions, the interval from collection to delivery was significantly shorter when the serum interleukin-6 concentration was at least 8 pg/mL than when it was less than 8 pg/mL (3 versus 600 hours, P < .001). Similarly, the median gestational age at delivery was significantly lower when serum interleukin-6 was at least 8 pg/mL (29.0 versus 36.1 weeks, P < .001). CONCLUSION: Maternal serum interleukin-6 concentrations appear to be elevated in women destined to deliver prematurely. Measurement of this cytokine may prove useful in treating patients at high risk for preterm delivery.

Performance of a commercial polymerase chain reaction test for endocervical Chlamydia trachomatis infection in a university hospital population.

OBJECTIVES: To examine the accuracy of a commercial polymerase chain reaction (PCR) test (Amplicor CTR, Roche Diagnostic Systems, Branchburg NJ) for identification of endocervical chlamydial infections through both laboratory evaluation and among a diverse teaching hospital patient population. METHODS: Testing of reliable threshold inocula and reproducibility were carried out using laboratory stock organisms. Paired endocervical samples from patients with a wide range of indications were tested by PCR and an established culture procedure, and discrepant pairs were further analyzed to determine true results. RESULTS: Laboratory evaluation suggested that one copy of target DNA from a viable organism consistently yielded a positive result, and test reproducibility was very good, with an overall coefficient of variation of 15%. Compared to true results in 1,588 paired clinical samples from 1,489 women with a 10% prevalence of infection, the PCR test and culture yielded respective sensitivities of 87.4% and 78.0%, and negative predictive values of 98.6% and 97.6%. Specificity and positive predictive value for both tests were 100%. Cost per specimen was nearly identical at $18.84 and $18.88 respectively. Polymerase inhibitors and organisms lacking target DNA were not found in false-negative PCR samples. CONCLUSION: This commercial PCR test is accurate, cost-competitive, and much faster than culture for diagnosis of endocervical chlamydia infections in our population of intermediate prevalence of chlamydial infection.

Maternal serum interleukin-6 during pregnancy and during term and preterm labor.

OBJECTIVE: To determine the normal concentrations of maternal serum interleukin-6 during the second and third trimesters of pregnancy and the different stages of term and preterm labor, and to examine the clinical usefulness of measuring this cytokine in the serum of women in preterm labor to diagnose asymptomatic intrauterine infections. METHODS: Maternal serum interleukin-6 concentrations were measured cross-sectionally in 315 gravidas in their second and third trimesters and during term and preterm labor. Placentas from women who delivered preterm were examined for histologic chorioamnionitis. RESULTS: At term, women in labor had significantly elevated median maternal serum interleukin-6 concentrations compared with those at term not in labor (4.7 pg/mL versus 2.2 pg/mL, P < .001). Women admitted in preterm labor who delivered had significantly higher median interleukin-6 concentrations than did those in preterm labor who responded to tocolysis (9.3 pg/mL versus 1.9 pg/mL, P < .001). Women in preterm labor who delivered preterm with evidence of chorioamnionitis had significantly higher serum concentrations of interleukin-6 than did those in preterm labor who delivered in the absence of chorioamnionitis (15.9 pg/mL versus 4.6 pg/mL, P = .006). CONCLUSION: Compared with antepartum gravidas, those in term or preterm labor had significantly higher concentrations of maternal serum interleukin-6 concentrations; extremely elevated levels were found in patients whose preterm labor was associated with intrauterine infection.