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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)

Elizabeth Asztalos114*, Andrew Willan2, Kellie Murphy3, Stephen Matthews4, Arne Ohlsson5, Saroj Saigal6, Anthony Armson7, Edmond Kelly5, Marie-France Delisle8, Amiram Gafni9, Shoo Lee5, Renee Sananes10, Joanne Rovet11, Patricia Guselle12, Kofi Amankwah13 and for the MACS-5 Collaborative Group

Author Affiliations

1 Department of Newborn & Developmental Paediatrics, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada

2 Program in Child Health Evaluative Sciences, SickKids Research Institute, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

3 Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

4 Departments of Physiology, Obstetrics and Gynecology and Medicine, University of Toronto, Toronto, Ontario, Canada

5 Department of Paediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

6 Department of Pediatrics, McMaster University Medical Centre, Hamilton, Ontario, Canada

7 Department of Obstetrics and Gynecology, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada

8 Department of Obstetrics and Gynecology, BC Women’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada

9 Centre for Health Economics and Policy Analysis, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

10 Department of Psychology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

11 Neuroscience and Mental Health Program, The Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada

12 The Hospital for Sick Children, Toronto, Ontario, Canada

13 Department of Obstetrics & Gynecology, Mackenzie Health, Richmond Hill, Ontario, Canada

14 The Centre for Mother, Infant, and Child Research, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, M4-230, 2075 Bayview Ave.,Toronto M4N 3 M5Ontario, Canada

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BMC Pregnancy and Childbirth 2014, 14:272  doi:10.1186/1471-2393-14-272

Published: 13 August 2014



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.


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.


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.


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.

Trial registration

This study has been registered at (identifier NCT00187382)

Preterm birth; Long-term neurodevelopmental outcomes; Antenatal corticosteroids; Gestational age at birth