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 Asztalos, Andrew Willan, Kellie Murphy, Stephen Matthews, Arne Ohlsson, Saroj Saigal, Anthony Armson, Edmond Kelly, Marie-France Delisle, Amiram Gafni, Shoo Lee, Renee Sananes, Joanne Rovet, Patricia Guselle, Kofi Amankwah, MACS-5 Collaborative Group, Elizabeth Asztalos, Andrew Willan, Kellie Murphy, Stephen Matthews, Arne Ohlsson, Saroj Saigal, Anthony Armson, Edmond Kelly, Marie-France Delisle, Amiram Gafni, Shoo Lee, Renee Sananes, Joanne Rovet, Patricia Guselle, Kofi Amankwah, MACS-5 Collaborative Group

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.

Method: 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.

Conclusion: 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).

Figures

Figure 1
Figure 1
Study profile. This study profile outlines the recruitment of the children born preterm and term.

References

    1. Murphy KE, Hannah ME, Willan AR, Hewson SA, Ohlsson A, Kelly EN, Matthews SG, Saigal S, Asztalos E, Ross S, Delisle MF, Amankwah K, Guselle P, Gafni A, Lee SK, Armson BA, MACS Collaborative Group Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial. Lancet. 2008;372(9656):2143–51. doi: 10.1016/S0140-6736(08)61929-7.
    1. Asztalos EV, Murphy K, Hannah M, Willan A, Ohlsson A, Kelly E, Saigal S, Ross S, Delisle M-F, Amankwah K, Guselle P, Gafni A, Lee S, Armson BA, Sananes R, Tomat L, Matthews S. Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS): 2-year outcomes. Pediatrics. 2010;126(5):e1045–55. doi: 10.1542/peds.2010-0857.
    1. Asztalos EV, Murphy KE, Willan AR, Matthews SG, Ohlsson A, Saigal S, Armson BA, Kelly EN, Delisle MF, Gafni A, Lee SK, Sananes R, Rovet J, Guselle P, Amankwah K, Saleem M, Sanchez J, MACS-5 Collaborative Group Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: Outcomes in Children at 5 years of age (MACS-5) JAMA Pediatr. 2013;167(12):1102–10.
    1. Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997;39(4):214–23. doi: 10.1111/j.1469-8749.1997.tb07414.x.
    1. Gioia GA, Isquith PK, Guy PK, Kenworthy L. Behavior Rating Inventory of Executive Function (BRIEF) Odessa, FL: Psychological Assessment Resources; 2000.
    1. Achenbach TM. Manual for the Child Behavior Checklist- 1½-5 years. Burlington, Vermont: University of Vermont; 2002.
    1. Schmidt B, Whyte RK, Asztalos E, Moddeman D, Poets C, Rabi Y, Solimano A, Roberts RS, for the Canadian Oxygen Trial (COT) Group Effects of targeting higher vs. lowerarterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA. 2013;309(20):2111–20. doi: 10.1001/jama.2013.5555.
    1. Schmidt B, Davis P, Moddeman D, Ohlsson A, Roberts RS, Saigal S, Solimano A, Vincer M, Wright LL. Trial Of Indomethacin Prophylaxis in Preterms Investigators. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weightinfants. N Engl J Med. 2001;344(26):1966–72. doi: 10.1056/NEJM200106283442602.
    1. Whyte RK, Kirpalani H, Asztalos EV, Andersen C, Blajchman M, Heddle N, LaCorte M, Robertson CMT, Clarke MC, Vincer MJ, Doyle LW, Roberts RS, and for the PINTOS Study Group Neurodevelopmental outcome of extremely low birth weight infants assigned to restrictive or liberal haemoglobin thresholds for blood transfusion. Pediatrics. 2009;123(1):207–13. doi: 10.1542/peds.2008-0338.
    1. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Tin W, Caffeine for Apnea of Prematurity Trial Group Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112–21. doi: 10.1056/NEJMoa054065.
    1. Steer P, Flint C. ABC of Labour care: preterm labour and premature rupture of membranes. Br Med J. 1999;318:1059–62. doi: 10.1136/bmj.318.7190.1059.
    1. Davis EP, Waffarn F, Uy C, Hobel CJ, Glynn LM, Sandman CA. Effect of prenatal glucocorticoid treatment on size at birth among infants born at term gestation. J Perinatol. 2009;29:731–37. doi: 10.1038/jp.2009.85.
    1. Waffarn F, Davis EP. Effects of antenatal corticosteroids on the hypothalamic-pituitary-adrenocortical axis of the fetus and newborn: experimental findings and clinical considerations. Amer J Obstet Gynecol. 2012;207:446–54. doi: 10.1016/j.ajog.2012.06.012.
    1. Alexander N, Rosenlöcher F, Stalder T, Linke J, Distler W, Morgner J, Kirschbaum C. Impact of antenatal synthetic glucocorticoid exposure on endocrine stress reactivity in term-born children. J Clin Endocrin Metab. 2012;97(10):3538–44. doi: 10.1210/jc.2012-1970.
    1. Dunlop SA, Archer MA, Quinlivan JA, Beazley LD, Newnham JP. Repeated prenatal corticosteroids delay myelination in the ovine central nervous system. J Matern Fetal Med. 1997;6(6):309–13. doi: 10.1002/(SICI)1520-6661(199711/12)6:6<309::AID-MFM1>;2-S.
    1. Quinlivan JA, Beazley LD, Evans SF, Newnham JP, Dunlop SA. Retinal maturation is delayed by repeated, but not single, maternal injections of betamethasone in sheep eye. Eye. 2000;14(Pt 1):93–98. doi: 10.1038/eye.2000.20.
    1. Church MW, Adams BR, Anumba JI, Jackson DA, Kruger ML, Jen KLC. Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats. Neurotxicology and Teratology. 2012;34(1):196–205. doi: 10.1016/j.ntt.2011.09.004.
Pre-publication history
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