School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo

Lex W. Doyle*, Peter J. Anderson, Ross Haslam, Katherine J. Lee, Caroline Crowther, Brian Darlow, Nicola Austin, Noel French, Catherine Campbell, Elizabeth Carse, Marie Hayes, Jane Harding, Chris McKinlay, Coila Bevan, Antonio De Paoli, Lee Sutton, Ingrid Rieger, Crista Wocadlo, Paul Colditz, Margo PritchardPeter H. Gray, Andrew Watkins, Gillian Opie, Elaine Kelly, Heather Woods, Catherine Callanan, Noni Davis, Julianne Duff, Phil Weston, Pat Ashwood

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

IMPORTANCE: Antenatal magnesium sulfate given to pregnant women at imminent risk of very preterm delivery reduces the risk of cerebral palsy in early childhood, although its effects into school age have not been reported from randomized trials.

OBJECTIVE: To determine the association between exposure to antenatal magnesium sulfate and neurological, cognitive, academic, and behavioral outcomes at school age.

DESIGN, SETTING, AND PARTICIPANTS: The ACTOMgSO4 was a randomized clinical trial conducted in 16 centers in Australia and New Zealand, comparing magnesium sulfate with placebo given to pregnant women (n = 535 magnesium; n = 527 placebo) for whom imminent birth was planned or expected before 30 weeks' gestation. Children who survived from the 14 centers who participated in the school-age follow-up (n = 443 magnesium; n = 424 placebo) were invited for an assessment at 6 to 11 years of age between 2005 and 2011.

MAIN OUTCOMES AND MEASURES: Mortality, cerebral palsy, motor function, IQ, basic academic skills, attention and executive function, behavior, growth, and functional outcomes. Main analyses were imputed for missing data.

RESULTS: Of the 1255 fetuses known to be alive at randomization, the mortality rate to school age was 14% (88/629) in the magnesium sulfate group and 18% (110/626) in the placebo group (risk ratio [RR], 0.80; 95% CI, 0.62-1.03, P = .08). Of 867 survivors available for follow-up, outcomes at school age (corrected age 6-11 years) were determined for 669 (77%). Comparing the magnesium sulfate and placebo groups revealed no statistically significant difference in proportions with cerebral palsy (23/295 [8%] and 21/314 [7%], respectively; odds ratio [OR], 1.26; 95% CI, 0.84-1.91; P = .27) or abnormal motor function (80/297 [27%] and 80/300 [27%], respectively; OR, 1.16; 95% CI, 0.88-1.52; P = .28). There was also little difference between groups on any of the cognitive, behavioral, growth, or functional outcomes.

CONCLUSIONS AND RELEVANCE: Magnesium sulfate given to pregnant women at imminent risk of birth before 30 weeks' gestation was not associated with neurological, cognitive, behavioral, growth, or functional outcomes in their children at school age, although a mortality advantage cannot be excluded. The lack of long-term benefit requires confirmation in additional studies.

TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12606000252516.

Original languageEnglish
Pages (from-to)1105-1113
Number of pages9
JournalJAMA: Journal of the American Medical Association
Volume312
Issue number11
DOIs
Publication statusPublished - 17 Sept 2014
Externally publishedYes

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