Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis.

BACKGROUND: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors. METHODS AND FINDINGS: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes. CONCLUSIONS: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg.

Repeat prenatal corticosteroid prior to preterm birth: a systematic review and individual participant data meta-analysis for the PRECISE study group (prenatal repeat corticosteroid international IPD study group: assessing the effects using the best level of evidence) - study protocol.

BACKGROUND: The aim of this individual participant data (IPD) meta-analysis is to assess whether the effects of repeat prenatal corticosteroid treatment given to women at risk of preterm birth to benefit their babies are modified in a clinically meaningful way by factors related to the women or the trial protocol. METHODS/DESIGN: The Prenatal Repeat Corticosteroid International IPD Study Group: assessing the effects using the best level of Evidence (PRECISE) Group will conduct an IPD meta-analysis. The PRECISE International Collaborative Group was formed in 2010 and data collection commenced in 2011. Eleven trials with up to 5,000 women and 6,000 infants are eligible for the PRECISE IPD meta-analysis. The primary study outcomes for the infants will be serious neonatal outcome (defined by the PRECISE International IPD Study Group as one of death (foetal, neonatal or infant); severe respiratory disease; severe intraventricular haemorrhage (grade 3 and 4); chronic lung disease; necrotising enterocolitis; serious retinopathy of prematurity; and cystic periventricular leukomalacia); use of respiratory support (defined as mechanical ventilation or continuous positive airways pressure or other respiratory support); and birth weight (Z-scores). For the children, the primary study outcomes will be death or any neurological disability (however defined by trialists at childhood follow up and may include developmental delay or intellectual impairment (developmental quotient or intelligence quotient more than one standard deviation below the mean), cerebral palsy (abnormality of tone with motor dysfunction), blindness (for example, corrected visual acuity worse than 6/60 in the better eye) or deafness (for example, hearing loss requiring amplification or worse)). For the women, the primary outcome will be maternal sepsis (defined as chorioamnionitis; pyrexia after trial entry requiring the use of antibiotics; puerperal sepsis; intrapartum fever requiring the use of antibiotics; or postnatal pyrexia). DISCUSSION: Data analyses are expected to commence in 2011 with results publicly available in 2012.

Early goal directed therapy for sepsis during pregnancy.

Sepsis is a leading cause of death in pregnancy and results in significant perinatal mortality. These deaths occur despite the younger age of pregnant patients, the low rate of comorbid conditions and the potential for effective interventions that should result in rapid resolution of illness. To date, no "evidence-based" recommendations are specific to the pregnant patient who is critically ill or septic. Optimal care for the septic patient requires a multidisciplinary team with expertise in obstetrics, maternal-fetal medicine, critical care, infectious disease, anesthesia, and pharmacy. Coordination of care and good communication amongst team members is essential. Incorporation of early goal directed therapy for suspected sepsis into obstetric practice is needed to optimize maternal and neonatal outcomes.

Subcutaneous tissue reapproximation, alone or in combination with drain, in obese women undergoing cesarean delivery.

OBJECTIVE: To compare the efficacy of subcutaneous suture reapproximation alone with suture plus subcutaneous drain for the prevention of wound complications in obese women undergoing cesarean delivery. METHODS: We conducted a multicenter randomized trial of women undergoing cesarean delivery. Consenting women with 4 cm or more of subcutaneous thickness were randomized to either subcutaneous suture closure alone (n = 149) or suture plus drain (n = 131). The drain was attached to bulb suction and removed at 72 hours or earlier if output was less than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate (defined by any of the following: subcutaneous tissue dehiscence, seroma, hematoma, abscess, or fascial dehiscence). RESULTS: From April 2001 to July 2004, a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a follow-up wound assessment. Both groups were similar with respect to age, race, parity, weight, cesarean indication, diabetes, steroid/antibiotic use, chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus drain group (relative risk 1.3, 95% confidence interval 0.8-2.1). Individual wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%), seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus 3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound complications (3.5% versus 6.6%), were similar (P > .05) between women treated with suture alone and those treated with suture plus drain, respectively. CONCLUSION: The additional use of a subcutaneous drain along with a standard subcutaneous suture reapproximation technique is not effective for the prevention of wound complications in obese women undergoing cesarean delivery.

Labor induction in women with an unfavorable Bishop score: randomized controlled trial of intrauterine Foley catheter with concurrent oxytocin infusion versus Foley catheter with extra-amniotic saline infusion with concurrent oxytocin infusion.

OBJECTIVES: This study was undertaken to determine whether the addition of extra-amniotic saline infusion improves the efficacy of the Foley catheter in women undergoing cervical ripening and induction of labor with an unfavorable cervical examination. STUDY DESIGN: One hundred consenting women with a Bishop score less than 5 with singleton gestation, intact membranes, vertex presentation, who required induction of labor were randomly assigned to 2 groups: Foley alone (Foley, n=49) or to the Foley catheter with extra-amniotic saline infusion (EASI, 30 mL of NS per hour infused through the distal port of the Foley, n=51). All women received concurrent dilute oxytocin infusion per protocol. The primary analysis was intent to treat. Nonparametric tests were used as indicated. RESULTS: At randomization, the groups were well balanced for potential confounders including: parity, gestational age, prior cesarean delivery, preeclampsia, mean dilation, effacement, and Bishop score. There were no differences between the groups for time to delivery (Foley 17.7 +/- 10.5 hours vs EASI 17.4 +/- 11.7 hours, P=.9), the proportion of women delivered before 24 hours (Foley 41/49 [84%] vs EASI 39/51 [77%], P=.37) or cesarean rates (Foley 9/49 [17.7%] vs EASI 9/51 [18.4%], P=.92). There were also no differences in complications, including chorioamnionitis, endometritis, and neonatal morbidity. CONCLUSION: EASI does not increase the efficacy of cervical ripening and induction of labor with a Foley catheter and concurrent oxytocin infusion.