Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes

ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, Australia, 5006.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2011; 7(6):CD003935. DOI: 10.1002/14651858.CD003935.pub3
Source: PubMed

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.

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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). "
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