Impact of Gestational Weight Gain on Perinatal Outcomes in Obese Women.

Objective This study aims to evaluate perinatal outcomes, according to gestational weight gain (GWG) in obese women. Study Design A retrospective cohort of perinatal outcomes in obese women who gained below, within, or above the 2009 Institute of Medicine guidelines and delivered ≥ 36 weeks. Additionally, outcomes, according to the rate of GWG (kg/week; minimal [< 0.16], moderate [0.16-0.49], or excessive [> 0.49]) were compared among women delivering preterm. Results Overall, 5,651 obese women delivered ≥ 36 weeks. GWG above guidelines was associated with increased cesarean section (adjusted odds ratio [aOR]: 1.44, 95% confidence interval [CI]: 1.21-1.72), gestational hypertension (aOR: 1.58, 95% CI: 1.21-2.06), and macrosomia (birth weight ≥ 4,000 g) (aOR: 2.08, 95% CI: 1.62-2.67). GWG below recommendations was associated with less large for gestational age infants (aOR: 0.60, 95% CI: 0.47-0.75). A total of 6,663 women delivered ≥ 20 weeks. Minimal weekly GWG was associated with increased spontaneous preterm birth (aOR: 1.56, 95% CI: 1.23-1.98) and more small for gestational age (SGA) infants (aOR: 1.55, 95% CI: 1.19-2.01). Excessive weekly GWG was associated with increased indicated preterm birth (aOR: 1.61, 95% CI: 1.29-2.01), cesarean section (aOR: 1.39, 95% CI: 1.20-1.61), preeclampsia (aOR: 1.83, 95% CI: 1.49-2.26), neonatal intensive care unit admission (aOR: 1.33, 95% CI: 1.08-1.63), and macrosomia (aOR: 2.40, 95% CI: 1.94-2.96). Conclusions Obese women with excessive GWG had worse outcomes than women with GWG within recommendations. Limited GWG was associated with increased spontaneous preterm birth and SGA infants.

Vaginal Microbiota in Pregnancy: Evaluation Based on Vaginal Flora, Birth Outcome, and Race.

OBJECTIVE: This study aims to evaluate vaginal microbiota differences by bacterial vaginosis (BV), birth timing, and race, and to estimate parameters to power future vaginal microbiome studies. METHODS: Previously, vaginal swabs were collected at 21 to 25 weeks (stored at -80°C), and vaginal smears evaluated for BV (Nugent criteria). In a blinded fashion, 40 samples were selected, creating 8 equal-sized groups stratified by race (black/white), BV (present/absent), and birth timing (preterm/term). Samples were thawed, DNA extracted, and prepared. Polymerase chain reaction (PCR) with primers targeting the 16S rDNA V4 region was used to prepare an amplicon library. PCR products were sequenced and analyzed using quantitative insight into microbial ecology; taxonomy was assigned using ribosomal database program classifier (threshold 0.8) against the modified Greengenes database. RESULTS: After quality control, 97,720 sequences (mean) per sample, single-end 250 base-reads, were analyzed. BV samples had greater microbiota diversity (p < 0.05)-with BVAB1, Prevotella, and unclassified genus, Bifidobacteriaceae family (all p < 0.001) more abundant; there was minimal content of Gardnerella or Mobiluncus. Microbiota did not differ by race or birth timing, but there was an association between certain microbial clusters and preterm birth (p = 0.07). To evaluate this difference, 159 patients per group are needed. CONCLUSIONS: There are differences in the vaginal microbiota between patients with and without BV. Larger studies should assess the relationship between microbiota composition and preterm birth.

Quantitative Polymerase Chain Reaction to Assess Response to Treatment of Bacterial Vaginosis and Risk of Preterm Birth.

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.

Oral health education and therapy reduces gingivitis during pregnancy.

BACKGROUND: Pregnant women demonstrate increases in gingivitis despite similar plaque levels to non-pregnant counterparts. AIM: To evaluate an intensive protocol aimed at reducing gingivitis in pregnant women and provide pilot data for large-scale randomized controlled trials investigating oral hygiene measures to reduce pregnancy gingivitis and alter maternity outcomes. MATERIALS AND METHODS: One hundred and twenty participants between 16 and 24 weeks gestation with Gingival Index (GI) scores ≥2 at ≥50% of tooth sites were enrolled. Plaque index (PI), gingival inflammation (GI), probing depth (PD), and clinical attachment levels (CAL) were recorded at baseline and 8 weeks. Dental prophylaxis was performed at baseline and oral hygiene instructions at baseline, 4 and 8 weeks. Pregnancy outcomes were recorded at parturition. Mixed-model analysis of variance was used to compare clinical measurements at baseline and 8 weeks. RESULTS: Statistically significant reductions in PI, GI, PD, and CAL occurred over the study period. Mean whole mouth PI and GI scores decreased approximately 50% and the percentage of sites with PI and GI ≥2 decreased from 40% to 17% and 53% to 21.8%, respectively. Mean decreases in whole mouth PD and CAL of 0.45 and 0.24 mm, respectively, were seen. CONCLUSIONS: Intensive oral hygiene regimen decreased gingivitis in pregnant patients.

Effect of corticosteroid interval on markers of inflammation in spontaneous preterm birth.

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.

Gestational age at delivery and perinatal outcomes of twin gestations.

OBJECTIVE: The optimal gestational duration for twin gestations is unknown. Epidemiologic studies show that the lowest perinatal mortality rate for twins is at 37-38 weeks, but these studies lack information on pregnancy complications and neonatal morbidities. This study evaluates pregnancy characteristics and perinatal outcomes of twins in order to assess the optimal gestational age for delivery. STUDY DESIGN: This is a retrospective study of twins delivered at ≥36 weeks at our institution from 1991-2009. The composite rate of perinatal morbidity and mortality (including perinatal death, respiratory distress, suspected sepsis, and need for neonatal intensive care) was determined for weekly intervals from 36-39(+) weeks. RESULTS: There were 377 twin gestations included. Of those 83% were dichorionic. Fifty-three percent had spontaneous labor and 48% were delivered by cesarean section. Perinatal outcomes improved as gestational age advanced to 38 weeks. CONCLUSION: Perinatal morbidity and mortality rates suggest that the optimal time for delivery of twins is at 38 weeks or greater.

Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women.

OBJECTIVE: To estimate the frequency of genital tract colonization by methicillin-resistant Staphylococcus aureus (MRSA) among pregnant women and evaluate the association of such colonization with infant outcome. METHODS: Between July 2003 and July 2006, anovaginal screening cultures for group B Streptococcus (GBS) were prospectively obtained in the third trimester (35 to less than 37 weeks of gestation) and were also processed for identification of Staphylococcus aureus including methicillin-resistant strains. Maternal colonization by MRSA was linked to a computerized database of invasive neonatal infections that occurred at our center during the study period. RESULTS: Among 5,732 mothers (who delivered 5,804 infants) with GBS screening cultures and infant infection data available, 22.9% were GBS-positive and 14.5% were positive for Staphylococcus aureus. A total of 24.3% of the Staphylococcus aureus isolates were MRSA. The overall MRSA colonization rate was 3.5%. Colonization by any Staphylococcus aureus (relative risk 1.6, 95% confidence interval 1.4-1.9) as well as MRSA (relative risk 2.2, 95% confidence interval 1.6-2.8) was significantly more common among GBS-positive than among GBS-negative women. No cases of early-onset invasive neonatal infection by MRSA occurred among infants in the study. CONCLUSION: Genital tract colonization with MRSA affected 3.5% of pregnant women. Such MRSA colonization is associated with colonization by GBS but does not predispose to a high risk of early-onset neonatal MRSA infection. LEVEL OF EVIDENCE: III.

The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants.

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.

Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age.

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.

Impact of interconception antibiotics on the endometrial microbial flora.

OBJECTIVE: The purpose of this study was to evaluate the impact of an interconception antibiotic regimen on endometrial microbial flora and histologic type. STUDY DESIGN: This was a secondary analysis of a double-blind randomized placebo-controlled trial of prophylactic metronidazole plus azithromycin that was given to 241 women (antibiotics, 118 women; placebo, 123 women) with a previous preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histologic types were obtained at randomization and 2 weeks after treatment. The prevalence of either the new acquisition or the resolution of individual microbes, categories of microbes, and plasma cell endometritis were compared by chi-square or Fishers' exact tests. RESULTS: Overall, antibiotics were associated with lower acquisition and higher resolution of microbes. Of women without Gardnerella at baseline, 14% of the women who received antibiotics vs 34% of the women who received placebo had positive endometrial culture for the organism after treatment (P < .05); of those women with G. vaginalis at baseline, 57% of the women who received antibiotics vs 33% of the women who received placebo (P < .05) had a negative follow-up culture. Other gram-negative rods, especially aerobes in general, manifested similar patterns. The impact on anaerobes and plasma cell endometritis was not definitive, but there was a trend toward the increased resolution of the former (77% vs 55%) and reduced acquisition of the latter (28% vs 50%). CONCLUSION: The antibiotic regimen prevented the acquisition and promoted the resolution, but not the eradication, of gram-negative rods such as G. vaginalis and the aerobic subcategory.

Clinical trial of interconceptional antibiotics to prevent preterm birth: subgroup analyses and possible adverse antibiotic-microbial interaction.

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.

The Alabama Preterm Birth Study: diffuse decidual leukocytoclastic necrosis of the decidua basalis, a placental lesion associated with preeclampsia, indicated preterm birth and decreased fetal growth.

OBJECTIVE: Laminar necrosis, a band-like distribution of coagulative necrosis, has been reported at the choriodecidual interface of the free membranes of placentas of women with various adverse neonatal outcomes. Our goal in this study was to evaluate the frequency of an equivalent feature in the decidua basalis, diffuse decidual leukocytoclastic necrosis (DDLN), a diffuse coagulative necrosis admixed with karyorrhectic debris, in preterm births <32 weeks, and to determine its association with various obstetric conditions, markers of placental inflammation, and newborn outcome. STUDY DESIGN: Four hundred and forty-six mother/infant dyads who delivered between 23 and 32 weeks gestational age (GA) had their medical records abstracted, a variety of placental and cord blood cultures performed, cord interleukin-6 (IL-6) levels determined, and the placentas evaluated histologically by a single pathologist (OFP). RESULTS: Women with DDLN (27%) were significantly more likely than other women to have preeclampsia (57.6 vs. 24.8%, p < 0.0001), an indicated preterm birth in this pregnancy (61.9 vs. 26.4%, p < 0.0001), and a prior indicated preterm birth (12.7 vs. 4.1%, p = 0.001), but were not more likely to have an abruption, diabetes, to smoke or be Black. Among DDLN-positive vs. DDLN-negative women, birth weight was significantly lower (1,069 +/- 373 vs. 1,171 +/- 389 g, p = 0.014), despite the GAs being similar (28.6 +/- 2.2 vs. 28.6 +/- 2.3 weeks, p = NS). Women with DDLN were less likely to have a positive placental culture for any organism (50.0 vs. 61.3%p = 0.03), Ureaplasma urealyticum and Mycoplasma hominis in either the placenta or cord blood (29.7 vs. 42.1%, p = 0.02), or an elevated cord blood IL-6 (21.5 vs. 32.9%, p = 0.059). They also were less likely to have acute inflammation of the membranes (27.4 vs. 56.4%, p < 0.0001), chorionic plate (17.0 vs. 48.6%, p < 0.0001) or cord (15.7 vs. 36.6%, p < 0.0001). Decidual necrosis in the free membranes also occurred more frequently in the presence vs. absence of DDLN (25.2 vs. 9.2%, p < 0.0001). Infants whose placentas had DDLN were significantly less likely to have neonatal systemic inflammatory response syndrome (20.7 vs. 35.2%, p = 0.004), but were not significantly different for other neonatal outcomes including respiratory distress syndrome, intraventricular hemorrhage or death. CONCLUSION: DDLN of the decidua basalis is relatively common in placentas of 23-32 week newborns, and, when present, is inversely associated with inflammatory maternal and newborn conditions and positively associated with preeclampsia, indicated preterm birth, and lower birth weight. The positive correlation of DDLN with obstetrical and neonatal conditions associated with underperfusion of the placental bed, suggests that DDLN may be a marker of vascular compromise.

Risk factors for anal sphincter tear in multiparas.

OBJECTIVE: To assess maternal, newborn, and obstetric risk factors associated with anal sphincter tear in multiparous women. METHODS: This case-control study identified 18,779 multiparous vaginal deliveries from 1992 to 2004 from an obstetric automated record database at the University of Alabama at Birmingham. Two hundred eighty-four patients were selected, 145 cases and 139 controls. Variables from the index pregnancy and prior pregnancies were analyzed, and multivariable logistic regression models were constructed to determine significant predictor variables for anal sphincter tear in multiparous women. RESULTS: One hundred forty-five multiparous women with no history of cesarean delivery sustained a sphincter tear. Multivariable logistic regression showed a significant association with episiotomy (odds ratio [OR] 16.3, 95% confidence interval [CI] 7.7-34.4), shoulder dystocia (OR 7.9, CI 1.6-38), forceps delivery (OR 4.7, CI 2.0-11.2), and being married (OR 2.2, CI 1.1-4.6). A second exploratory model that included variables from previous pregnancies, showed that in addition to episiotomy (OR 34.6, CI 8.8-136), shoulder dystocia (OR 11.1, CI 1.3-95.2), forceps delivery (OR 6.1, CI 1.6-23.5), previous sphincter tear (OR 7.7, CI 1.2-48.7), and second stage of labor greater than 1 hour (OR 6.7, CI 1.1-42.5) were associated with tear. CONCLUSION: The strongest clinical risk factors for anal sphincter tear in multiparous women are episiotomy, shoulder dystocia, previous sphincter tear, prolonged second stage of labor, and forceps delivery. LEVEL OF EVIDENCE: II-2.

Interconceptional antibiotics to prevent spontaneous preterm birth: a randomized clinical trial.

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.

The Alabama Preterm Birth Study: intrauterine infection and placental histologic findings in preterm births of males and females less than 32 weeks.

OBJECTIVE: The objective of the study was to determine whether there are differences in the placental histology and various markers of infection/inflammation between preterm male and female fetuses. STUDY DESIGN: The placentas and umbilical cords of 446 infants born at 23 to 32 weeks were examined histologically, cultured for aerobic and anaerobic bacteria and mycoplasmas, and the interleukin-6 levels in cord blood determined. RESULTS: Male infants were significantly more likely to have positive placental cultures than female infants (63.4% versus 51.8%, P = .01, odds ratio 1.5, 1.0 to 2.4). Cord blood Mycoplasma hominis and Ureaplasma urealyticum infections were marginally more common in male than female fetuses (27.6% versus 19.2%, P = .06, odds ratio 1.7, 0.9 to 2.9), but cord blood interleukin-6 levels were not different between male and female fetuses. The only significant histologic difference between male and female placentas was in decidual lymphoplasmacytic cell infiltration (6.3% versus 0.9%, P = .003, odds ratio 8.3, 1.8 to 39.0). Males had a higher percentage of decidual lymphohistiocytic cell infiltration, but the differences were not significant (11.3% versus 7.4%, P = .160, odds ratio 1.6, 0.8 to 3.2). CONCLUSION: Male infants were significantly more likely to have positive placental membrane cultures than female infants. Decidual lymphoplasmacytic cell infiltrations were more common in male versus female placentas, confirming a previous observation and suggesting that a maternal immune reaction to fetal tissue may be more common in male fetuses.

The Alabama preterm birth study: corticosteroids and neonatal outcomes in 23- to 32-week newborns with various markers of intrauterine infection.

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.

Association of asymptomatic bacterial vaginosis with endometrial microbial colonization and plasma cell endometritis in nonpregnant women.

OBJECTIVE: This study was undertaken to determine whether asymptomatic bacterial vaginosis (BV) is associated with an increased risk of endometrial microbial colonization or plasma cell endometritis in nonpregnant women. STUDY DESIGN: In this observational cohort study conducted between August 1995 and August 2001, microbial cultures (n = 769) and histopathology (n = 482) were performed on endometrial specimens obtained from women with a recent preterm or term delivery (83 +/- 16 days). Endometritis was defined as the presence of plasma cells. BV was defined using Amsel and Nugent criteria. RESULTS: The study population was 71% black, 29% white, 69% single, and 31% had 12 years or more of education. Endometrial cultures were positive for at least 1 microorganism in 83% (n = 637/769) of the women and plasma cell endometritis was present in 39% (n = 190/482). BV was present in 26% (n = 191/722) by Amsel and 38% (n = 289/769) by Nugent criteria. Women with Nugent-BV (RR [relative risk] = 1.12, 95% CI 1.05-1.19) but not Amsel-BV (RR = 1.06, 95% CI 1.00-1.13) were significantly more likely to have a positive endometrial culture. A consistent and significant association was observed between BV (by Amsel or Nugent criteria) and an increased frequency of endometrial colonization with BV-associated microorganisms grouped and defined in various ways (RR ranged from 1.96-4.22). No association between BV and plasma cell endometritis was observed. CONCLUSION: Asymptomatic BV is associated with a modest increased likelihood of endometrial microbial colonization and colonization by BV-associated bacteria but is not associated with plasma cell endometritis in nonpregnant women.

Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis.

OBJECTIVE: To determine if extended spectrum prophylactic antibiotic treatment (with efficacy against Ureaplasma urealyticum) reduces post-cesarean delivery clinical endometritis. METHODS: After cord clamping at cesarean delivery, subjects received prophylaxis with cefotetan. Subjects were then simultaneously randomized (double blind) to receive doxycyline plus azithromycin versus placebo. Post-cesarean delivery endometritis was defined clinically as fever of 100.4F or higher with one or more supporting clinical signs or a physician diagnosis of endometritis plus the absence of a nonpelvic source of fever. RESULTS: A total of 597 women were enrolled, 301 in the doxycycline/azithromycin group and 296 in the placebo group. The study population was 56% black, 25.5 +/- 6.2 years of age, and 43% nulliparous. The groups were similar (P >.05) for black race, parity, maternal age, and most risk factors for post-cesarean delivery endometritis. The frequency of post-cesarean delivery endometritis (16.9% versus 24.7%, P =.020), wound infections (0.8% versus 3.6%, P =.030), and a combination of these two outcomes (19.0% versus 27.8%, P =.019) were significantly lower in the doxycycline/azithromycin group compared with the placebo-treated group. The doxycycline/azithromycin versus placebo groups were dissimilar for maternal leukocytosis (24.9% versus 12.5%, P =.042) and frequency of classic uterine incision (7.6% versus 12.5%, P =.048). Adjusting for these factors did not alter the risk ratio for post-cesarean delivery endometritis in the active versus placebo-treated group (relative risk 0.65, 95% confidence interval 0.43, 0.98). Length of stay was longer in the placebo group overall (104 +/- 56 versus 95 +/- 32 hours, P =.016) and among women with endometritis (146 +/- 52 versus 127 +/- 46 hours, P =.047). CONCLUSION: Extended spectrum prophylactic antibiotic treatment (with presumed efficacy against U urealyticum) given to women undergoing cesarean delivery at term shortens hospital stay and reduces the frequency of post-cesarean delivery endometritis and wound infections.

Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth.

OBJECTIVE: To estimate the relationship between maternal periodontal disease and both early spontaneous preterm birth and selected markers of upper genital tract inflammation. METHODS: In this case-control study, periodontal assessment was performed in 59 women who experienced an early spontaneous preterm birth at less than 32 weeks of gestation, in a control population of 36 women who experienced an early indicated preterm birth at less than 32 weeks of gestation, and in 44 women with an uncomplicated birth at term (>or = 37 weeks). Periodontal disease was defined by the degree of attachment loss. Cultures of the placenta and umbilical cord blood, cord interleukin-6 levels, and histopathologic examination of the placenta were performed for all women. RESULTS: Severe periodontal disease was more common in the spontaneous preterm birth group (49%) than in the indicated preterm (25%, P =.02) and term control groups (30%, P =.045). Multivariable analyses, controlling for possible confounders, supported the association between severe periodontal disease and spontaneous preterm birth (odds ratio 3.4, 95% confidence interval 1.5-7.7). Neither histologic chorioamnionitis, a positive placental culture, nor an elevated cord plasma interleukin-6 level was significantly associated with periodontal disease (80% power to detect a 50% difference in rate of histological chorioamnionitis, alpha = 0.05). CONCLUSION: Women with early spontaneous preterm birth were more likely to have severe periodontal disease than women with indicated preterm birth or term birth. Periodontal disease was not associated with selected markers of upper genital tract inflammation. LEVEL OF EVIDENCE: II-2

Periodontal disease and preterm birth: results of a pilot intervention study.

BACKGROUND: Previous case-control and prospective studies have shown an association between the presence of periodontitis and the risk of preterm birth (PTB). The goal of this pilot trial was to determine the feasibility of conducting a trial to determine whether treatment of periodontitis reduces the risk of spontaneous preterm birth (SPTB). METHODS: Three hundred sixty-six (366) women with periodontitis between 21 and 25 weeks' gestation were recruited and randomized to one of three treatment groups with stratification on the following two factors: 1) previous SPTB at <35 weeks and 2) body mass index <19.8 or bacterial vaginosis as assessed by Gram stain. The treatment groups consisted of: 1) dental prophylaxis plus placebo capsule; 2) scaling and root planing (SRP) plus placebo capsule; and 3) SRP plus metronidazole capsule (250 mg t.i.d. for one week). An additional group of 723 pregnant women meeting the same criteria for periodontitis and enrolled in a prospective study served as an untreated reference group. RESULTS: The rate of PTB at <35 weeks was 4.9% in the prophylaxis group, compared to 3.3% in the SRP plus metronidazole group and 0.8% in the SRP plus placebo group (P = 0.75 and 0.12, respectively). The rate of PTB at <35 weeks was 6.3% in the reference group. CONCLUSIONS: This trial indicates that performing SRP in pregnant women with periodontitis may reduce PTB in this population. Adjunctive metronidazole therapy did not improve pregnancy outcome. Larger trials will be needed to achieve statistical significance, especially at less than 35 weeks gestational age.