title: Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5).
abstract: BACKGROUND
  The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age.
  
  
  METHODS
  A total of 1719 children, with the breakdown into groupings of <30, 30-36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis.
  
  
  RESULTS
  Gestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037.
  
  
  CONCLUSIONS
  Preterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research.
  
  
  BACKGROUND
  This study has been registered at (identifier NCT00187382).
authors.affiliation: Department of Newborn & Developmental Paediatrics, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada. elizabeth.asztalos@sunnybrook.ca.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Asztalos
authors.forename: Andrew
authors.initials: A
authors.lastname: Willan
authors.forename: Kellie
authors.initials: K
authors.lastname: Murphy
authors.forename: Stephen
authors.initials: S
authors.lastname: Matthews
authors.forename: Arne
authors.initials: A
authors.lastname: Ohlsson
authors.forename: Saroj
authors.initials: S
authors.lastname: Saigal
authors.forename: Anthony
authors.initials: A
authors.lastname: Armson
authors.forename: Edmond
authors.initials: E
authors.lastname: Kelly
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Delisle
authors.forename: Amiram
authors.initials: A
authors.lastname: Gafni
authors.forename: Shoo
authors.initials: S
authors.lastname: Lee
authors.forename: Renee
authors.initials: R
authors.lastname: Sananes
authors.forename: Joanne
authors.initials: J
authors.lastname: Rovet
authors.forename: Patricia
authors.initials: P
authors.lastname: Guselle
authors.forename: Kofi
authors.initials: K
authors.lastname: Amankwah
mesh_terms: D000328:Adult; D001623:Betamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000401:mortality* / Q000517:prevention & control; D018743:Perinatal Care; D047928:Premature Birth / Q000188:drug therapy*; D012678:Sensation Disorders / Q000209:etiology*; D015996:Survival Rate; D047929:Term Birth; D013997:Time Factors; D055815:Young Adult
chemical_list: D003907:Dexamethasone; D001623:Betamethasone