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Objective: The aim of this study was to determine whether quantitative polymerase chain reaction (qPCR) bacterial load measurement is a valid method to assess response to treatment of bacterial vaginosis and risk of preterm birth in pregnant women., Study Design: Secondary analysis by utilizing stored vaginal samples obtained during a previous randomized controlled trial studying the effect of antibiotics on preterm birth (PTB). All women had risk factors for PTB: (1) positive fetal fibronectin (n=146), (2) bacterial vaginosis (BV) and a prior PTB (n=43), or (3) BV and a prepregnancy weight<50 kg (n=54). Total and several individual BV-related bacteria loads were measured using qPCR for 16S rRNA. Loads were correlated with Nugent scores (Spearman correlation coefficients). Loads were compared pre- and posttreatment with Wilcoxon rank-sum test. Individual patient differences were examined with Wilcoxon signed-rank test., Results: A total of 243 paired vaginal samples were available for analysis: 123 antibiotics and 120 placebo. Groups did not differ by risk factors for PTB. For all samples, bacterial loads were correlated with Nugent score and each of its specific bacterial components (all p<0.01). Baseline total bacterial load did not differ by treatment group (p=0.87). Posttreatment total bacterial load was significantly lower in the antibiotics group than the placebo group (p<0.01). Individual patient total bacterial load decreased significantly posttreatment in the antibiotics group (p<0.01), but not in the placebo group (p=0.12). The rate of PTB did not differ between groups (p=0.24). PTB relative risks calculated for BV positive versus BV negative women and women with the highest quartile total and individual bacterial loads were not statistically significant., Conclusion: qPCR correlates with Nugent score and demonstrates decreased bacterial load after antibiotic treatment. Therefore, it is a valid method of vaginal flora assessment in pregnant women who are at high risk for PTB., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The objective of the study was to evaluate whether the time interval from corticosteroid administration to delivery is associated with variations in inflammatory/infectious markers in women with spontaneous preterm birth (SPTB)., Study Design: We conducted a secondary analysis of a prospectively collected cohort of women experiencing SPTB from 23(0/7) to 31(6/7) weeks. Patients were categorized by corticosteroid receipt and time interval until delivery. Prevalence of markers of inflammation and colonization/infection (cord blood interleukin [IL]-6 levels; Ureaplasma urealyticum [UU], Mycoplasma hominis [MH], and other anaerobic/aerobic cultures; histology of the placental disc, membranes and cord) were compared between groups using χ(2) and Mantel-Haenszel tests., Results: Two hundred seventy-three patients had SPTB. Prevalence of elevated IL-6 (P = .028) and positive UU/MH cultures (P = .019) were highest in women not receiving corticosteroids and those delivering more than 7 days from receipt. The prevalence of both decreased in groups with delivery delayed at least 12 hours but increased as the interval lengthened to more than 48 hours. Overall positive placental cultures also nadired among those delivering at 12-24 hours after corticosteroids (P = .049). As the interval increased, prevalence of acute inflammation at the rupture site increased (P = .017). There were similar, but nonsignificant, increases in chorionic plate inflammation and funisitis., Conclusion: The relationship between time interval from corticosteroids and evidence of inflammation in women experiencing SPTB is U shaped, suggesting earlier stages of inflammation in women with delayed delivery or transient decreases of inflammation in response to corticosteroids. This warrants further investigation to elucidate the natural history of SPTB and its modulation by corticosteroids., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Determine whether elevated second trimester maternal serum α-fetoprotein (AFP) is associated with clinical and histopathologic markers of inflammation at preterm delivery., Methods: 105 women <32 weeks' gestation were included. AFP levels were dichotomized at 2.0 multiples of the median (MoM). Rates of neonatal morbidities, clinical chorioamnionitis, cord blood IL-6 level, and placental inflammatory findings were compared., Results: Thirteen (12.4%) had elevated AFP. Fewer women with AFP ≥ 2 MoM had histologic placental or membrane rupture site inflammation, funisitis, or placental culture positive for Mycoplasma and Ureaplasma species, compared to those with normal AFP. Neonatal death was increased in the elevated AFP group (23.1% vs. 2.27%, RR 10.6). Elevated AFP was associated with a nonsignificant increase in indicated birth (54% vs. 35%; p = 0.225). Virtually all inflammatory findings were confined to the spontaneous delivery group., Conclusion: Elevated midtrimester AFP conveyed significant risk of neonatal death, but was negatively associated with clinical or histopathologic inflammation in preterm infants.

Objective: The purpose of this study was to determine the association between in utero exposure to acute inflammation and long-term major neurodevelopmental disability at age 6 years among children born prior to 32 weeks' gestation., Study Design: This was a follow-up investigation of a cohort of maternal-infant dyads delivered between 23 and < 32 weeks' gestation. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests between 5 and 8 years of age. Pregnancy and neonatal data were analyzed among children with versus those without major neurodevelopmental disability (including IQ < 70 [n = 41], cerebral palsy [CP, n = 11], and a composite major disability [n = 52])., Results: A total of 261 (70%) of the 375 maternal-infant dyads with surviving children were successfully recruited and evaluated at 6.8 +/- 0.7 years. Mean delivery gestational age (GA) and birthweight were 28.8 +/- 2.2 weeks and 1163 +/- 382 g, respectively. Neither surrogate indicators for nor direct markers of in utero exposure to acute inflammation were significantly associated with severe adverse outcomes. Delivery GA was significantly associated with outcome. Logistic regression indicated that each increasing gestational week was associated with a significantly decreased risk of an IQ < 70 (OR 0.75, 95% CI 0.6-0.9). An average 1.9 point increase in IQ at 6 years of age was observed per gestational week gained (23 to 32 weeks). Periventricular leukomalacia was associated with a 9.6 point mean deficit in IQ. The perceptive vocabulary scores (IQ proxy) of primary caregivers were significantly lower among children with an IQ < 70 vs > or = 70 (87.5 +/- 11.5 vs 92.1 +/- 11.2, P = .016)., Conclusion: Among children born between 23 and 32 weeks' gestation, neonatal complications, GA at delivery, and caregiver IQ, but not in utero exposure to acute inflammation, were associated with increased risk of severe adverse neurodevelopmental outcomes at age 6 years.

Objective: This study was undertaken to evaluate the frequency of umbilical cord blood infections with Ureaplasma urealyticum and Mycoplasma hominis in preterm 23- to 32-week births and to determine their association with various obstetric conditions, markers of placental inflammation, and newborn outcomes., Study Design: 351 mother/infant dyads with deliveries between 23 and 32 weeks' gestational age who had cord blood cultures for U. urealyticum and M. hominis had their medical records abstracted, other placental cultures performed, cord interleukin-6 levels determined, placentas evaluated histologically, and infant outcomes determined., Results: U. urealyticum and/or M. hominis were present in 23% of cord blood cultures. Positive cultures were more common in infants of nonwhite women (27.9% vs 16.8%; P = .016), in women less than 20 years of age, in those undergoing a spontaneous compared to an indicated preterm delivery (34.7% vs 3.2%; P = .0001), and in those delivering at earlier gestational ages. Intrauterine infection and inflammation were more common among infants with a positive U. urealyticum and M. hominis culture as evidenced by placental cultures for these and other bacteria, elevated cord blood interleukin-6 levels, and placental histology. Infants with positive cord blood U. urealyticum and M. hominis cultures were more likely to have neonatal systemic inflammatory response syndrome (41.3% vs 25.7%; P = .007; adjusted odds ratio, 1.86; 1.08-3.21) and probably bronchopulmonary dysplasia (26.8% vs 10.1%; P = .0001; adjusted odds ratio 1.99; 0.91-4.37), but were not significantly different for other neonatal outcomes, including respiratory distress syndrome, intraventricular hemorrhage, or death., Conclusion: U. urealyticum and M. hominis cord blood infections are far more common in spontaneous vs indicated preterm deliveries and are strongly associated with markers of acute placental inflammation. Positive cultures are associated with neonatal systemic inflammatory response syndrome and probably bronchopulmonary dysplasia.

Objective: The purpose of this study was to explore whether endometrial microbial colonization and plasma cell endometritis are risk factors for adverse pregnancy outcomes, and whether these outcomes are influenced by interactions between interconceptional antibiotics and the micro-flora., Study Design: Subgroup analyses of data from a double-blind, randomized, placebo-controlled trial of a course of metronidazole plus azithromycin given every 4 months to women with a prior preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histology were obtained at randomization and repeated 2 weeks after the first treatment. Fifty-nine on antibiotics versus 65 on placebo had pregnancy outcomes. Prevalence of adverse pregnancy outcomes (pregnancy loss or preterm birth < 37 weeks) was stratified by treatment group and endometrial characteristics. Subgroups were assessed and screened for potential interaction (P values for significance set a priori at < .01), prior to formal statistical testing for interaction (P values < .05)., Results: The prevalence of adverse pregnancy outcome was 62.7% in the presence of endometrial microbial colonization at baseline (any microbe) and 50% in the absence of colonization (RR = 1.25; 99% CI 0.42-3.7). Prevalence of adverse pregnancy outcomes was 61.9% with plasma cell endometritis, and 70.8% without; RR = 0.87 (0.50-1.5). There was a nonsignificant reduction in adverse pregnancy outcome in the absence of Gardnerella vaginalis or gram-negative rods with RR (95% CI) = 0.60 (0.3-1.2) and 0.66 (0.4-1.2), respectively. In the presence of these microbes, antibiotics appeared to increase adverse outcomes: RR = 1.5 (1.1-2.0) and 1.5 (1.1-2.1), respectively. This reversal of impact represents a crossover interaction., Conclusion: Neither baseline endometrial microbial colonization nor plasma cell endometritis were risk factors for adverse pregnancy outcome. However, colonization with specific microbes interacted with antibiotics to increase adverse outcomes.

Objective: Intrauterine inflammation/infection is cited as a contraindication to the use of corticosteroids (CS). Our goal was to determine if CS given prenatally to enhance fetal maturity were harmful to infants with various indications of intrauterine infection., Study Design: This was a retrospective analysis of data obtained from 457 consecutively enrolled infants delivered between 23 and 32 weeks. Cultures and a histologic examination of the placenta, and cord blood interleukin (IL)-6 levels were obtained. Neonatal outcomes included periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), respiratory distress syndrome (RDS), chronic lung disease (CLD), necrotizing enterocolitis (NEC), systemic inflammatory response syndrome (SIRS), and infant death., Results: Of the 457 pregnancies, 57.6% had a positive placental culture, 49.8% had histologic chorioamnionitis/funisitis, 28.8% had elevated cord IL-6 levels, and 12.5% had clinical chorioamnionitis. With intrauterine infection/inflammation, none of the neonatal outcomes were significantly worse if mothers were treated with CS. For those with histologic chorioamnionitis/funisitis, of the outcomes historically improved with CS, RDS (59.9 vs 72.2% P = .16), IVH (9.7 vs 14.7% P = .38), and neonatal death (9.9 vs 11.1% P = .82) all occurred less frequently with CS treatment, but differences were not significant. Similar results were seen for women with a positive placental culture. For women with an elevated IL-6, RDS was significantly reduced (59.4 vs 84.2 %, P = .045). Neonatal SIRS was significantly reduced with CS in women with histologic chorioamnionitis/funisitis (39.7 vs 65.7%, P = .005), positive placental cultures (32.7 vs 56.3%, P = .01), and elevated IL-6 levels (42.7 vs 73.7%, P = .02)., Conclusion: In women with intrauterine infection/inflammation, CS use was not associated with significant worsening in any neonatal outcome, and was associated with significant reductions in RDS and SIRS. These data suggest that CS use may not be contraindicated in the presence of intrauterine inflammation/infection.

Objective: We hypothesized that upper genital tract microbial infection associated with spontaneous preterm birth may precede conception. Our objective was to estimate if antibiotic administration during the interpregnancy interval in nonpregnant women with a previous preterm birth before 34 weeks' gestational age would reduce the rate of spontaneous preterm birth in the subsequent pregnancy., Study Design: Women with a spontaneous preterm birth < 34 weeks' gestational age were randomized at 4 months' postpartum to receive oral azithromycin 1 g twice (4 days apart) plus sustained-release metronidazole 750 mg daily for 7 days, or identical-appearing placebos. This regimen was repeated every 4 months until the subsequent pregnancy., Results: A total of 241 women were randomized; 124 conceived a subsequent pregnancy and were available for study, including 59 in the antibiotic group and 65 in the placebo group. In the antibiotic versus placebo group, neither subsequent spontaneous preterm birth (< 37 weeks: 52% vs 46%, P = .568; < 35 weeks: 40% vs 30%, P = .276; < 32 weeks: 31% vs 23%, P = .376) nor miscarriage (< 15 weeks: 12% vs 14%, P = .742) was significantly different. Although not statistically significant, mean delivery gestational age in the subsequent pregnancy was 2.4 weeks earlier in the antibiotic versus placebo group (32.0 +/- 7.9 vs 34.4 +/- 6.3 weeks, P = .082), and mean birth weight was lower in the antibiotic group (2046 +/- 1209 vs 2464 +/- 1067 g, P =.060)., Conclusion: Intermittent treatment with metronidazole plus azithromycin of nonpregnant women with a recent early spontaneous preterm birth does not significantly reduce subsequent preterm birth, and may be associated with a lower delivery gestational age and lower birth weight.

Objective: This study was undertaken to determine whether endometrial microbial colonization or plasma cell endometritis is increased after spontaneous versus indicated preterm delivery or a spontaneous term delivery., Study Design: Postpartum, endometrial specimens were obtained after a spontaneous (mean 83, +/- 17.6 days) or indicated (mean 83, +/- 16.7 days) preterm delivery before 34 weeks' gestation and after a spontaneous term delivery (mean 82, +/- 15.7 days; P=.980). Cultures for aerobic and anaerobic bacteria, Trichomonas vaginalis, and genital mycoplasmas were performed. Histologic endometritis was defined as the presence of plasma cells., Results: The study population (n=820) was 71% black, 29% white, 69% unmarried, and 31% had less than 12 years of education. Endometrial cultures were positive for at least 1 microorganism in 82% of the women. No significant difference in positive endometrial cultures were observed among women after a spontaneous versus an indicated preterm delivery (85% vs 79%, P=.102), or a spontaneous preterm versus a spontaneous term delivery (85% vs 81%, P=.123). Plasma cell endometritis was present in 39% of 506 specimens sufficient for histologic examination and was also similar in the three groups (P=.160)., Conclusion: Microbial colonization of the endometrium and plasma cell endometritis are similar 3 months after spontaneous or indicated preterm or term births. Therefore, chronic infection and inflammation of the endometrium (documented at 3 months postpartum) do not appear to be risk factors for subsequent delivery in women with a prior spontaneous delivery less than 34 weeks' gestation.