Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes.

OBJECTIVE: The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. STUDY DESIGN: Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS: The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). CONCLUSION: We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Vaginal vs. cesarean delivery for preterm breech presentation of singleton infants in California: a population-based study.

OBJECTIVE: To examine the morbidity and mortality associated with vaginal breech delivery (VBD) of premature, low-birth-weight (LBW) (< 2.5 kg) newborns as compared to delivery by cesarean section. STUDY DESIGN: A retrospective cohort study of singleton, preterm (< 37 weeks), LBW, nonanomalous newborns in California (January 1, 1991-December 31, 1999) was performed. Neonatal morbidity and mortality by route of delivery were compared. RESULTS: Overall, 14,417 LBW, preterm, breech newborns were delivered (14% vaginally and 86% by cesarean). There were 150,570 LBW, preterm, cephalic newborns, of whom 82% were delivered vaginally. VBD of LBW newborns in nulliparous women was associated with increased neonatal mortality in newborns weighing 500-1,000 g (OR 11.7; 95% CI 7.9, 17.2), 1,001-1,500 g (OR 17.0; 95% CI 6.8, 42.7), 1,501-2,000 g (OR 7.2; 95% CI 2.4, 21.4), and 2,001-2,500 g (OR 6.6; 95% CI 2.1, 21.2) as compared with breech delivery by cesarean in nulliparous women. Birth trauma was increased in VBD of newborns weighing 1,500-2,000 g (OR 3.8; 95% CI 1.4, 10.1) and 2,001-2,500 g (OR 4.5; 95% CI 2.6, 7.9) as compared to breech delivery by cesarean in nulliparous women. Birth asphyxia was increased in breech newborns weighing 2,001-2,500 g (OR 3.5; 95% CI 2.2, 5.6) delivered vaginally in nulliparous women as compared to cephalic vaginal deliveries. CONCLUSION: VBD of the preterm, LBW newborn is associated with significantly increased neonatal mortality as compared to cesarean section at similar birth weights. Birth trauma (> 1,500 g) was greater with VBD as compared to breech delivery by cesarean, and asphyxia (> 2,000 g) was greater with VBD as compared to cephalic vaginal delivery, suggesting that cesarean delivery may be a safer route of delivery for preterm breech fetuses.