Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes
ABSTRACT It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial.
To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data.
Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth.
We assessed trial quality and extracted data independently.
We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79).Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments.
The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.
- SourceAvailable from: Tamara Yawno
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- "However, a number of potentially adverse nonpulmonary effects of antenatal glucocorticoids have been described (Miller and Wallace, 2013), including reduction of fetal growth (Miller et al., 2007, Miller et al., 2012, Sutherland et al., 2012), reduced fetal brain weight (Huang et al., 1999), and reduced myelination within the fetal brain (Dunlop et al., 1997, Huang et al., 2001, Antonow-Schlorke et al., 2009). In human pregnancies, for example, birth weight is reduced for babies born more than 7 days after single (Murphy et al., 2012) or multiple (Wapner et al., 2007, Crowther et al., 2011) courses of maternal glucocorticoid treatment. In mice, a single prenatal dose of betamethasone (BM) impaired performance of the offspring in behavioral tests (Rayburn et al., 1998). "
ABSTRACT: The risk of preterm delivery often means that the fetus will be exposed to exogenous synthetic glucocorticoids to accelerate fetal lung maturation, but effects on other organs, particularly the brain, are not understood. The neurosteroid allopregnanolone (AP) is a GABAA receptor agonist that influences fetal brain development, suppresses CNS activity, and has neuroprotective properties. In this study we determined the impact of maternal glucocorticoid (betamethasone) administration on brain development and AP synthesis in preterm fetal sheep.Neuropharmacology 05/2014; 85. DOI:10.1016/j.neuropharm.2014.05.031 · 4.82 Impact Factor
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ABSTRACT: Corticosteroids administered to women in preterm labor are the standard of care for reducing neonatal morbidity and mortality associated with prematurity. These agents promote lung development and reduce the incidence of neonatal intraventricular hemorrhage. Several studies have investigated the method by which fetal lung fluid is cleared after birth. This exploration resulted in the elucidation of the Starling equation or the hypothesis that fluid filtration through capillary membranes is dependent on the balance between the pressure blood places on the capillary membranes and the osmotic pressure of the membranes. The clinical observation that a neonate experiences a vaginal squeeze during a vaginal birth may be important, but it can account for only a small percentage of the lung fluid absorbed. Perhaps more importantly, amiloride-sensitive sodium transport channels (ENaCs) have emerged as key factors in the movement of alveolar fluid from the lung into the vascular system. Several potential clinical applications have been developed from this new knowledge about the physiology of lung fluid clearance at birth. Neonates born late preterm or at term by elective cesarean before the onset of labor are more likely to develop respiratory distress than those born vaginally. Based on the mechanism of action of antenatal corticosteroids, these drugs may be beneficial in the clearance of fetal lung fluid in this population. This article reviews how fetal lung fluid is cleared; the pharmacologic effects of corticosteroids on the fetus; and the risks, benefits, and controversies associated with corticosteroid use.Journal of midwifery & women's health 11/2011; 56(6):591-7. DOI:10.1111/j.1542-2011.2011.00119.x · 1.04 Impact Factor
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ABSTRACT: This study was conducted to examine the frequency and clinical significance of a positive Amnisure test in patients with preterm labor and intact membranes by sterile speculum exam. A retrospective cohort study was performed including 90 patients with preterm labor and intact membranes who underwent Amnisure tests prior to amniocentesis (< 72 h); most patients (n=64) also underwent fetal fibronectin (fFN) tests. Amniotic fluid (AF) was cultured for aerobic/anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8. (1) the prevalence of a positive Amnisure test was 19% (17/90); (2) patients with a positive Amnisure test had significantly higher rates of adverse pregnancy and neonatal outcomes (e.g., impending preterm delivery, intra-amniotic infection/inflammation, and neonatal morbidity) than those with a negative Amnisure test; (3) a positive test was associated with significantly increased risk of intra-amniotic infection and/or inflammation, delivery within 7, 14, or 28 days and spontaneous preterm birth (< 35 weeks) among patients with a negative fFN test. A positive Amnisure test in patients with preterm labor and intact membranes is a risk factor for adverse pregnancy outcome, particularly in patients with a negative fFN test. A positive Amnisure test in patients without symptoms or signs of ROM should not be taken as an indicator that membranes have ruptured.The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 01/2012; 25(9):1690-8. DOI:10.3109/14767058.2012.657279 · 1.21 Impact Factor