Impact of Azithromycin-Based Extended-Spectrum Antibiotic Prophylaxis on Noninfectious Cesarean Wound Complications.

OBJECTIVE: Adding azithromycin to standard antibiotic prophylaxis for unscheduled cesarean delivery has been shown to reduce postcesarean infections. Because wound infection with ureaplasmas may not be overtly purulent, we assessed the hypothesis that azithromycin-based extended-spectrum antibiotic prophylaxis also reduces wound complications that are identified as noninfectious. STUDY DESIGN: This is a secondary analysis of the C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) randomized controlled trial, which enrolled women with singleton pregnancies ≥24 weeks who were undergoing nonelective cesarean. Women were randomized to adjunctive azithromycin or identical placebo up to 1 hour preincision. All wound complications occurring within 6 weeks were adjudicated into infection and noninfectious wound complications (seroma, hematoma, local cellulitis, and other noninfectious wound breakdown). The primary outcome for this analysis is the composite of noninfectious wound complications. RESULTS: At a total of 14 sites, 2,013 women were randomized to adjunctive azithromycin (n = 1,019) or placebo (n = 994). Groups were similar at baseline. Although there was a lower rate of noninfectious wound complications in the azithromycin group compared with placebo (2.9 vs. 3.8%), this was not statistically significant (p = 0.22). CONCLUSION: While adding azithromycin to usual antibiotic prophylaxis for nonelective cesarean delivery does reduce the risk of postcesarean infections, it did not significantly reduce the risk of postcesarean noninfectious wound complications.

Family Physicians' Perceived Prevalence, Safety, and Screening for Cigarettes, Marijuana, and Electronic-Nicotine Delivery Systems (ENDS) Use during Pregnancy.

OBJECTIVE: Assess perceptions of prevalence, safety, and screening practices for cigarettes and secondhand smoke exposure (SHSe), marijuana (and synthetic marijuana), electronic nicotine delivery systems (ENDS; eg, e-cigarettes), nicotine-replacement therapy (NRT), and smoking-cessation medications during pregnancy, among primary care physicians (PCPs) providing obstetric care. METHODS: A web-based, cross-sectional survey was e-mailed to 3750 US physicians (belonging to organizations within the Council of Academic Family Medicine Educational Research Alliance). Several research groups' questions were included in the survey. Only physicians who reported providing "labor and delivery" obstetric care responded to questions related to the study objectives. RESULTS: A total of 1248 physicians (of 3750) responded (33.3%) and 417 reported providing labor and delivery obstetric care. Obstetric providers (N = 417) reported cigarette (54%), marijuana (49%), and ENDS use (24%) by "Some (6% to 25%)" pregnant women, with 37% endorsing that "Very Few (1% to 5%)" pregnant women used ENDS. Providers most often selected that very few pregnant women used NRT (45%), cessation medications (ie, bupropion or varenicline; 37%), and synthetic marijuana (23%). Significant proportions chose "Do not Know" for synthetic marijuana (58%) and ENDS (27%). Over 90% of the sample perceived that use of or exposure to cigarettes (99%), synthetic marijuana (99%), SHS (97%), marijuana (92%), or ENDS (91%) were unsafe during pregnancy, with the exception of NRT (44%). Providers most consistently screened for cigarette (85%) and marijuana use (63%), followed by SHSe in the home (48%), and ENDS (33%) and synthetic marijuana use (28%). Fewer than a quarter (18%) screened consistently for all substances and SHSe. One third (32%) reported laboratory testing for marijuana and 3% reported laboratory testing for smoking status. CONCLUSION: This sample of PCPs providing obstetric care within academic settings perceived cigarettes, marijuana, and ENDS use to be prevalent and unsafe during pregnancy. Opportunities for increased screening during pregnancy across these substances were apparent.

The effect of omega-3 supplementation on pregnancy outcomes by smoking status.

BACKGROUND: Smoking during pregnancy is associated with adverse maternal and neonatal outcomes such as preterm delivery, intrauterine growth restriction, stillbirth, and low birth weight. Because smoking causes oxidative stress, some have suggested using antioxidants to counteract the effects of oxidative stress. Smokers have lower serum levels of omega-3 fatty acids, an important antioxidant, and thus, investigating whether omega-3 supplementation in smokers reduces adverse maternal and neonatal outcomes represents an important area of research. OBJECTIVE: To investigate whether the antioxidant effect of omega-3 fatty acid supplementation on the incidence of adverse pregnancy outcomes differs between smokers and nonsmokers. STUDY DESIGN: Secondary analysis of a multicenter randomized controlled trial of omega-3 supplementation for preterm delivery prevention in women with a singleton pregnancy and a history of a previous singleton spontaneous preterm delivery. Subjects were randomized to begin omega-3 or placebo before 22 weeks, which was continued until delivery. All women received 17 alpha-hydroxyprogesterone caproate intramuscularly weekly beginning between 16 and 20 weeks of gestation and continued until 36 weeks of gestation or delivery, whichever occurred first. The primary outcome was spontaneous preterm delivery. Secondary outcomes were indicated preterm delivery, any preterm delivery (spontaneous and indicated), pregnancy-associated hypertension (gestational hypertension and preeclampsia), a neonatal composite (retinopathy of prematurity, intraventricular hemorrhage grade III or IV, patent ductus arteriosus, necrotizing enterocolitis, sepsis, respiratory morbidity, or perinatal death), low birth weight (<2500 g), small for gestational age (less than the 10th percentile), and neonatal intensive care unit or intermediate nursery admission. The study population was stratified into smokers and nonsmokers, and the incidence of each outcome was compared by omega-3 supplementation versus placebo in each subgroup. Zelen tests were performed to test for homogeneity of effect in smokers and nonsmokers. RESULTS: Of 851 subjects included in the analysis, 136 (16%) smoked. Baseline characteristics between omega-3 and placebo groups did not differ in smokers or nonsmokers. Omega-3 supplementation was associated with a lower risk of spontaneous preterm delivery in smokers (relative risk, 0.56, 95% confidence interval, 0.36-0.87) but not in nonsmokers (relative risk 1.04, 95% confidence interval 0.84-1.29); P value for interaction = 0.013. Low birth weight was also less frequent in smokers receiving omega-3 supplementation (relative risk 0.57, 95% confidence interval 0.36-0.90) compared with nonsmokers (relative risk 0.93, 95% confidence interval 0.71-1.24); P value for interaction = 0.047. The effect on other secondary outcomes did not differ significantly between smokers and nonsmokers. CONCLUSION: Omega-3 supplementation in smokers may have a protective effect against recurrent spontaneous preterm delivery and low birth weight.

Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.

BACKGROUND: The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. METHODS: In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. RESULTS: The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63). CONCLUSIONS: Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

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.

A qualitative assessment of the perceived risks of electronic cigarette and hookah use in pregnancy.

BACKGROUND: Studies reveal that electronic cigarette (e-cigarette) and hookah use are increasing among adolescents and young adults. However, the long-term health effects are unknown, especially with regards to pregnancy. Because of the increased use in women of reproductive age, and the unknown long-term health risks, our primary objectives were to determine the perceived risks of e-cigarette and hookah use in pregnancy, and learn common colloquial terms associated with e-cigarettes. Furthermore, we sought to determine if there is a stigma associated with e-cigarette use in pregnancy. METHODS: Eleven focus groups including 87 participants were conducted immediately following regularly scheduled CenteringPregnancy® prenatal care with women at three different clinics in the greater Houston area. A minimum of two facilitators led the groups, using ten lead-in prompts, with Spanish translation as necessary. Facilitators took notes which were compared immediately following each group discussion and each group was audio recorded and transcribed. Three facilitators utilized NVivo 9.0 software to organize the transcribed data into nodes to identify major themes. To increase rigor, transcripts were further analyzed by two obstetricians who were instructed to find the major themes. RESULTS: Analyses revealed contradicting themes concerning e-cigarette use. In general, e-cigarettes were perceived as safer alternatives to regular tobacco cigarettes, especially if used as smoking cessation devices. A major theme is that use in pregnancy is harmful to the fetus. However, it was perceived that use for smoking cessation in pregnancy may have fewer side effects. We found that a common term for e-cigarettes is "Blu." In our discussion of hookah use, participants perceived use as popular among teenagers and that use in pregnancy is dangerous for the fetus. CONCLUSIONS: Although a strong theme emerged against hookah use, we found contradicting themes in our discussions on e-cigarette use in pregnancy. It is possible that e-cigarette use will not carry the same stigma as regular cigarette smoking in pregnancy. In addition, the impression of e-cigarettes as a healthier alternative to smoking may influence use in pregnancy. Clinicians need to be prepared for questions of e-cigarette safety and efficacy as smoking cessation devices from their pregnant patients who smoke, and women who smoke and are planning to become pregnant.

In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model.

BACKGROUND: Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure METHODS: Sprague-Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N = 3/ group). RESULTS: We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold; p = 0.03) while acetylation is increased (1.79-fold; p = 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold; p < 0.001; 0.12-fold; p < 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold; p = 0.038). CONCLUSION: We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.

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.

Review of multicenter studies by multiple institutional review boards: characteristics and outcomes for perinatal studies implemented by a multicenter network.

OBJECTIVE: The objective of the study was to describe characteristics and outcomes of a review of multisite perinatal studies by individual institutional review boards (IRBs) and identify barriers and opportunities for streamlined IRB review. STUDY DESIGN: We compared the review of 5 collaborative protocols by individual IRBs at National Perinatal Research Consortium centers from 2007 through 2012. Three randomized trials, 1 observational study, and 1 follow-up study of a trial were selected. IRB logs and communications were reviewed and abstracted by trained team members. RESULTS: Seven or 8 IRBs reviewed each protocol. Monthly IRB meeting frequency varied from 1 to 6. Full board review was required by all IRBs for the primary trials but not by all for the observational protocols. The overall duration from submission to approval (P = .024) and number of stipulations (P = .007) differed across protocols but not across IRBs. However, times from submission-to-IRB review (P = .011) and IRB review-to-initial letter (P < .007) differed across sites. Both overall submission-to-approval and initial review-to-approval times increased with the increasing number of IRB review stipulations (both values P < .001). Significant delays (>60 days) were few and not consistent across IRBs or protocols. Most stipulations were stylistic or editorial modifications rather than regulatory requests. All protocols were approved without changes, and no more than 1 IRB meeting was needed at each site. CONCLUSION: Findings confirm unnecessary duplication and variability and some similarities in IRB review processes and outcomes for multisite perinatal studies. This may help guide initiatives to streamline IRB review and reduce research delays and burdens.

Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

OBJECTIVE: Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women. METHODS: Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (< 16 or ≥ 16 weeks gestation) and (b) body mass index (BMI) class (non-obese and obese). The Breslow-Day test for homogeneity was used to assess for variations in effect of LDA across gestational age and BMI groups. RESULTS: Of 2503 women, 461 (18.4%) initiated LDA < 16 weeks. LDA effect was not better when initiated < 16 weeks (RR: 0.93, 95% CI: 0.67-1.31) versus ≥ 16 weeks (RR: 0.90, 95% CI: 0.75-1.08), (p value for interaction = 0.87). Similarly, LDA effect was not better in non-obese (RR: 0.91, 95% CI: 0.7-1.13) versus obese women (RR: 0.89, 95% CI: 0.7-1.13), (p value for interaction = 0.85). CONCLUSION: LDA for preeclampsia prevention was not more effective when initiated < 16 weeks or used in non-obese women at risk for preeclampsia. No particular subgroup of women was more or less likely to benefit from LDA therapy.

Low-dose aspirin, smoking status, and the risk of spontaneous preterm birth.

OBJECTIVE: We evaluated the relationship between aspirin supplementation and perinatal outcomes for potential effect modification by smoking status. STUDY DESIGN: A secondary analysis of two multicenter trials for which prophylactic aspirin supplementation was given to either low- or high-risk women for prevention of preeclampsia (PE). We examined the effect of aspirin by smoking status using the Breslow-Day test. Primary outcomes for this analysis were PE and preterm birth (PTB) < 37 weeks. We also examined PTB subtypes, small for gestational age (SGA), and neonatal intensive care unit (NICU) admission. RESULTS: The effect of prenatal aspirin on the risk of PE did not differ by smoking status (relative risk [RR] 95% confidence interval [CI] for smokers; RR 95% CI for nonsmokers) in low-risk (Breslow-Day p = 0.32) or high-risk (RR 95% CI for smokers; RR 95% CI for nonsmokers) (Breslow-Day p = 0.58) women. Among women at low risk for PE, the effect of aspirin supplementation on PTB was not different for nonsmokers (RR 1.00 [95% CI 0.8-1.3]) or smokers (RR 0.80 [95% CI 0.4-1.7]), (Breslow-Day p = 0.54). Aspirin was protective for PTB in nonsmokers (RR 0.80 [95% CI 0.7-0.9]), but not in smokers (RR 1.1 [95% CI 0.9-1.4]) in the high-risk group (Breslow-Day p = 0.03). Aspirin was also associated with increased spontaneous and early PTB and NICU admission in smokers and not nonsmokers in the high-risk group only. CONCLUSION: Aspirin supplementation was associated with worse outcomes related to preterm birth in smokers in a high-risk but not low-risk cohort.

Epidural use and clinical chorioamnionitis among women who delivered vaginally.

OBJECTIVE: Chorioamnionitis, an important cause of maternal and neonatal morbidity, is influenced by epidural use and the occurrence of epidural fever. We evaluated the association between chorioamnionitis, histologic placental findings, and intrapartum factors focusing on epidural use. MATERIALS AND METHODS: We conducted a secondary analysis of a randomized controlled trial of different doses of oxytocin to prevent postpartum hemorrhage among women who delivered vaginally. The primary outcome was clinical diagnosis of chorioamnionitis leading to antibiotic therapy. Intrapartum factors examined included epidural use, parity, labor induction, gestational age, maternal age, ethnicity, body mass index, cervical dilatation at admission, preeclampsia/eclampsia, preterm labor, and duration of labor. RESULTS: Of the 1,798 women randomized, we excluded 13 multifetal births leaving 1,785 for analysis: 1,491 had an epidural and 294 did not. Of those with epidural, 8.0% had clinically diagnosed chorioamnionitis compared with only 1.0% without epidural: unadjusted odds ratio (OR) = 8.3 (95% confidence interval [CI]: 2.63-26.40); p < 0.0001. After multivariable logistic regression, epidural use (adjusted OR: 5.80; 95% CI: 1.77-19.11), increasing parity (0.42; 0.32-0.55), and preeclampsia (0.31; 0.14-0.66) were significantly associated with chorioamnionitis. CONCLUSION: Epidural use is statistically associated with an increase in clinical diagnosis of chorioamnionitis. A cause and effect relationship cannot be confirmed from this study. Independently of labor duration and increasing parity, preeclampsia appeared protective.

Higher-dose oxytocin to prevent obstetric hemorrhage at vaginal delivery-does duration of infusion matter?

OBJECTIVE: Postpartum higher-dose oxytocin (80 U) compared with lower dose (10 U) given in 500 mL over 1 hour does not decrease postpartum hemorrhage (PPH) requiring treatment, but reduces the risk of hematocrit decline ≥ 6% among women delivering vaginally. Our objective was to evaluate whether the duration of administration of oxytocin influences outcomes. STUDY DESIGN: We compared a cohort receiving a postpartum oxytocin infusion of 80 U/500 mL over 1 hour to a concurrent cohort of women receiving 80 U/500 mL over 8 hours. The primary outcome was any treatment of PPH (uterotonics, blood transfusion, tamponade, and surgery). Secondary outcomes included pre- to postdelivery median hematocrit change and hematocrit decline ≥ 6%. RESULTS: There were 653 and 676 women identified in the 1- and 8-hour cohorts, respectively. There was no difference in PPH requiring any treatment between the 1- and 8-hour cohorts (6 vs. 6%, p = 0.70). There were no differences in individual treatment components including blood transfusion (p = 0.75). Median hematocrit decline (p = 0.02) was lower in the 8-hour cohort, but there was no difference in frequency of hematocrit decline ≥ 6% (p = 0.15). Results were unchanged by multivariable adjustments. CONCLUSIONS: Postpartum higher-dose oxytocin administered over 1 hour compared with 8 hours was not associated with an increased treatment of PPH or frequency of hematocrit decline ≥ 6%.

Is midtrimester vitamin D status associated with spontaneous preterm birth and preeclampsia?

OBJECTIVE: The objective of this study is to evaluate whether midtrimester maternal vitamin D is associated with preeclampsia < 37 weeks or spontaneous preterm birth (SPTB) < 35 weeks. STUDY DESIGN: Nested case-control comprising two case subsets: (1) 100 women with preeclampsia < 37 weeks and (2) 100 women with SPB < 35 weeks. Controls consisted of 200 women delivered between 39 and 40 weeks. Stored maternal serum obtained between 15 and 21 weeks was tested for total 25-hydroxy vitamin D (25-OH D) levels using liquid chromatography-tandem mass spectrometry. Mean 25-OH D levels and prevalence of vitamin D insufficiency (25-OH D < 30 ng/mL) and deficiency (25-OH D < 15 ng/mL) were compared. RESULTS: In this study, 89 preeclampsia, 90 SPTB cases, and 177 controls had valid measurements. Mean midtrimester vitamin D was not significantly different between women with preeclampsia (27.4 ng/mL ± 14.4) and controls (28.6 ± 12.6) (p = 0.46), or SPTB (28.8 ± 13.2) and controls (p = 0.92). After adjusting for potential cofounders, neither vitamin D insufficiency (adjusted odds ratio [OR], 1.1; 95% confidence interval [CI], 0.6-2.0) nor deficiency (adjusted OR, 1.4; 95% CI, 0.7-3.0) was significantly associated with preeclampsia. Likewise, SPTB was not significantly associated with either vitamin D insufficiency or deficiency (adjusted OR, 0.8; 95% CI, 0.4-1.4, adjusted OR, 1.3 or 95% CI, 0.6-3.0, respectively). CONCLUSION: Midtrimester maternal vitamin D was not significantly associated with preeclampsia < 37 weeks or SPTB < 35 weeks.

Dose and duration of oxytocin to prevent postpartum hemorrhage: a review.

OBJECTIVE: Oxytocin, the most commonly used uterotonic agent in the United States to prevent postpartum hemorrhage, has no established standard dose. The aim of this review is to present data on oxytocin dosing for the prevention of postpartum hemorrhage. STUDY DESIGN: We conducted a PubMed search for clinical trials that utilized oxytocin for hemorrhage prophylaxis following either vaginal or cesarean delivery. We further narrowed the results to studies that compared alternative dosing and duration of oxytocin administration. RESULTS: Seven of 46 eligible reports were selected for detailed review. We compared the dose and duration of oxytocin used, study population, and outcomes (estimated blood loss, need for additional uterotonics, and change in hematocrit after delivery). Dose of oxytocin used ranged from 5 to 100 IU and duration of administration ranged from 5 to 30 seconds (intravenous bolus) to 8 hours diluted in crystalloid. CONCLUSION: Overall, higher infusion doses (up to 80 IU/500 mL) and bolus doses of oxytocin appear to be more effective than lower doses or protracted administration of a fixed dose at reducing outcome measures of postpartum hemorrhage, particularly among cesarean deliveries.

Antimicrobials for preterm birth prevention: an overview.

OBJECTIVE: Preterm birth (PTB) remains a major cause of neonatal morbidity and mortality. The association between PTB and infection is clear. The purpose of this report is to present a focused review of information on the use of antibiotics to prevent PTB. METHODS: We performed a search of the PubMed database restricted to clinical trials or meta-analyses published in English from 1990 through May 2011 using keywords "antibiotics or antimicrobials" and "preterm." RESULTS: The search yielded 67 abstracts for review. We selected 31 clinical trials (n = 26) or meta-analysis (n = 5) for further full-text review. Discussion of each eligible clinical trial, its specific inclusion criteria, antibiotic regimen used, and study results are presented. Overall, trials evaluating antibiotic treatment to prevent preterm birth have yielded mixed results regarding any benefit. CONCLUSION: Routine antibiotic prophylaxis is not recommended for prevention of preterm birth.

Tocolytic therapy for acute preterm labor.

The pathophysiology leading to preterm labor is not well understood and often multifactorial; initiating factors include intrauterine infection, inflammation, ischemia, overdistension, and hemorrhage. Given these different potential causes, directing therapy for preterm labor has been difficult and suboptimal. To date, no single drug has been identified as successful in treating all of the underlying mechanisms leading to preterm labor. In addition, the methodology of many of the tocolytic studies is limited by lack of sufficient patient numbers, lack of comparison with a placebo, and inconsistent use of glucocorticoids. The limitations in these individual studies make it difficult to evaluate the efficacy of a single tocolytic by meta-analysis. Despite these limitations, the goals for tocolysis for preterm labor are clear: To complete a course of glucocorticoids and secure the appropriate level of neonatal care for the fetus in the event of preterm delivery. The literature demonstrates that many tocolytic agents inhibit uterine contractility. The decision as to which tocolytic agent should be used as first-line therapy for a patient is based on multiple factors, including gestational age, the patient's medical history, common and severe side effects, and a patient's response to therapy. In a patient at less than 32 weeks gestation, indomethacin may be a reasonable first choice based on its efficacy, ease of administration, and minimal side effects. Concurrent administration of magnesium for neuroprotection may be given. At 32 to 34 weeks, nifedipine may be a reasonable first choice because it does not carry the fetal risks of indomethacin at these later gestational ages, is easy to administer, and has limited side effects relative to beta-mimetics. In an effort to review a commonly faced obstetrical complication, this article has provided a summary of the most commonly used tocolytics, their mechanisms of action, side effects, and clinical data regarding their efficacy.

Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression.

Several studies linking alterations in differential placental methylation with pregnancy disorders have implicated (de)regulation of the placental epigenome with fetal programming and later-in-life disease. We have previously demonstrated that maternal tobacco use is associated with alterations in promoter methylation of placental CYP1A1 and that these changes are correlated with CYP1A1 gene expression and fetal growth restriction. In this study we sought to expand our analysis of promoter methylation by correlating it to gene expression on a genome-wide scale. Employing side-by-side IlluminaHG-12 gene transcription with Infinium27K methylation arrays, we interrogated correlative changes in placental gene expression and DNA methylation associated with maternal tobacco smoke exposure at an epigenome-wide level and in consideration of signature gene pathways. We observed that the expression of 623 genes and the methylation of 1024 CpG dinucleotides are significantly altered among smokers, with only 38 CpGs showing significant differential methylation (differing by a methylation level of ≥10%). We identified a significant Pearson correlation (≥0.7 or ≤-0.7) between placental transcriptional regulation and differential CpG methylation in only 25 genes among non-smokers but in 438 genes among smokers (18-fold increase, p < 0.0001), with a dominant effect among oxidative stress pathways. Differential methylation at as few as 6 sites was attributed to maternal smoking-mediated birth weight reduction in linear regression models with Bonferroni correction (p < 1.8 × 10(-6)). These studies suggest that a common perinatal exposure (such as maternal smoking) deregulates placental methylation in a CpG site-specific manner that correlates with meaningful alterations in gene expression along signature pathways.

Maternal tobacco use is associated with increased markers of oxidative stress in the placenta.

OBJECTIVE: We sought to extend our prior observations and histopathologically characterize key metabolic enzymes (CYP1A1) with markers of oxidative damage in the placental sections from smokers. STUDY DESIGN: Placental specimens were collected from term singleton deliveries from smokers (n = 10) and nonsmokers (n = 10) and subjected to a detailed histopathological examination. To quantify the extent of oxidative damage, masked score-graded (0-6) histopathology against 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxydeoxyguanisine (8-OHdG) was performed. Minimal significance (P < .05) was determined with a Fisher's exact and a 2-tailed Student t test as appropriate. RESULTS: We observed a significant increase in the presence of syncytial knots in placentas from smokers (70% vs 10%, P = .02). These gross observations were accompanied by a significant aberrant placental aromatic hydrocarbon metabolism (increased CYP1A1, 4.4 vs 2.1, P = .002) in addition to evidence of oxidative damage (4-HNE 3.4 vs 1.1, P = .00005; 8-OHdG 4.9 vs 3.1, P = .0038). CONCLUSION: We observed a strong association between maternal tobacco use and aberrant placental metabolism, syncytial knot formation, and multiple markers of oxidative damage.