title: The clinical use of corticosteroids in pregnancy.
abstract: BACKGROUND
  The use of antenatal steroid therapy is common in pregnancy. In early pregnancy, steroids may be used in women for the treatment of recurrent miscarriage or fetal abnormalities such as congenital adrenal hyperplasia. In mid-late pregnancy, the antenatal administration of corticosteroids to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; antenatal corticosteroids are now standard care for pregnancies at risk of premature delivery in high- and middle-income countries. The widespread uptake of this therapy is due to a compelling body of evidence demonstrating improved neonatal outcomes following antenatal corticosteroid exposure, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function. As we approach the 50th anniversary of landmark work in this area by Liggins and Howie, it is apparent that much remains to be understood with regards to how we might best apply antenatal corticosteroid therapy to improve pregnancy outcomes at both early and mid to late gestation.
  
  
  METHODS
  Drawing on advances in laboratory science, pre-clinical and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the benefits, risks and uncertainties regarding antenatal corticosteroid use in pregnancy. Three, well-established therapeutic uses of antenatal steroids, namely recurrent miscarriage, congenital adrenal hyperplasia and preterm birth, were selected to frame the review.
  
  
  RESULTS
  Even the most well-established antenatal steroid therapies lack the comprehensive pharmacokinetic and dose-response data necessary to optimize dosing regimens. New insights into complex, tissue-specific corticosteroid signalling by genomic-dependent and independent mechanisms have not been used to inform corticosteroid treatment strategies. There is growing evidence that some fetal corticosteroid treatments are either ineffective, or may result in adverse outcomes, in addition to lasting epigenetic changes in a variety of homeostatic mechanisms. Nowhere is the need to better understand the intricacies of corticosteroid therapy better conveyed than in the findings of Althabe and colleagues who recently reported an increase in overall neonatal mortality and maternal morbidity in association with antenatal corticosteroid administration in low-resource settings.
  
  
  CONCLUSIONS
  New research to clarify the benefits and potential risks of antenatal corticosteroid therapy is urgently needed, especially with regard to corticosteroid use in low-resource environments. We conclude that there is both significant scope and an urgent need for further research-informed refinement to the use of antenatal corticosteroids in pregnancy.
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia matthew.kemp@uwa.edu.au.
authors.forename: M W
authors.initials: MW
authors.lastname: Kemp
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: J P
authors.initials: JP
authors.lastname: Newnham
authors.affiliation: Office of the Pro Vice-Chancellor (Health and Medical Research), The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: J G
authors.initials: JG
authors.lastname: Challis
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Tommy's Centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Stock
mesh_terms: D000026:Abortion, Habitual / Q000517:prevention & control; D000305:Adrenal Cortex Hormones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000312:Adrenal Hyperplasia, Congenital / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000453:epidemiology; D011256:Pregnancy Outcome / Q000453:epidemiology; D047928:Premature Birth / Q000517:prevention & control; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D011987:Receptors, Steroid / Q000819:agonists / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D011987:Receptors, Steroid
keywords: congenital adrenal hyperplasia; corticosteroids; low-resource settings; pregnancy; preterm birth; quality control; recurrent miscarriage