Adi Abramovici

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 .).

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.

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.

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

BackgroundStudies 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.MethodsEleven 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.ResultsAnalyses 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.ConclusionsAlthough 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.

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.

Prenatal Vitamin C and e supplementation in smokers is associated with reduced placental abruption and preterm birth: A secondary analysis

Smoking and pre‐eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self‐reported smoking status focusing on outcomes known to be impacted by maternal smoking.

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.

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.

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.