title: Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes.
abstract: BACKGROUND
  It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial.
  
  
  OBJECTIVE
  To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids.
  
  
  METHODS
  We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 January 2015), searched reference lists of retrieved studies and contacted authors for further data.
  
  
  METHODS
  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.
  
  
  METHODS
  We assessed trial quality and extracted data independently.
  
  
  RESULTS
  We included 10 trials (a total of 4733 women and 5700 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, number needed to treat to benefit (NNTB) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNTB 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. In women, for the two primary outcomes, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liggins Institute, The University of Auckland, Private Bag 92019, 85 Park Road, Auckland, New Zealand.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Crowther
authors.forename: Christopher J D
authors.initials: CJ
authors.lastname: McKinlay
authors.forename: Philippa
authors.initials: P
authors.lastname: Middleton
authors.forename: Jane E
authors.initials: JE
authors.lastname: Harding
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D001623:Betamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000187:drug effects; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012127:Respiratory Distress Syndrome, Newborn / Q000517:prevention & control*; D019233:Retreatment / Q000009:adverse effects
chemical_list: D000305:Adrenal Cortex Hormones; D001623:Betamethasone