Repeated antenatal corticosteroids: Effects on cerebral palsy and childhood behavior

https://doi.org/10.1016/j.ajog.2003.12.016Get rights and content

Abstract

Objective

This study was undertaken to determine the effects of repeated courses of antenatal corticosteroids on childhood behavior and disabilities, including cognitive delay and cerebral palsy.

Study design

Nonrandomized regional cohort of 541 very preterm infants born in Western Australia from singleton pregnancies and alive at 3 years were included in the study.

Main outcome measures

Physical, cognitive, and psychological assessments up to 6 years.

Results

Increasing numbers of antenatal corticosteroid courses were associated with a reduction in the rate of cerebral palsy. Three or more courses were also associated with increased rates of aggressive/destructive, distractible, and hyperkinetic behavior and these effects were present at both ages 3 and 6 years. Measures of internalizing behavior and intelligence quotient were unaffected by antenatal corticosteroid use.

Conclusion

Repeated antenatal courses of corticosteroids may protect against cerebral palsy but are associated with hyperactivity later in childhood.

Section snippets

Methods

The cohort has been described previously in detail.11 Briefly, the cohort comprised all 880 live-born very preterm infants (20-32 completed weeks' gestation) born in Western Australia between January 1, 1990, and June 30, 1992. All infants from singleton pregnancies and alive at 3 years were included in the study, resulting in a cohort of 541 subjects. Eighty-eight percent of the infants had been born at King Edward Memorial Hospital for Women, which is the sole tertiary level perinatal center

Statistical analyses

Analyses of categorical data were by χ2 test or Mantel-Haenszel test for linear association of ordinal variables. Univariate analyses of numeric variables were calculated by F test or Kruskal-Wallis χ2 for parametric and nonparametric variables respectively as appropriate. Analysis of variance was used to describe the continuous dependent variables of IQ and behavioral outcomes with covariates which included aboriginality, maternal parity, smoking practice, socioeconomic score, pregnancy

Results

Seventeen percent of singleton infants did not survive until 3 years, and survival was significantly associated with antenatal corticosteroid use. Most deaths occurred within the neonatal period. Maternal and infant characteristics of the 541 surviving infants are shown in Table I according to antenatal corticosteroid treatment group. Forty-eight percent of the infants had been treated with at least 1 course of antenatal corticosteroids. There were no differences between the groups in rates of

Disability outcomes

The results of disability and cognitive tests are shown in Table II. Cerebral palsy was present in 22 children (4%) and was half as common in infants who had received 1 or more courses of antenatal corticosteroids. On univariate analysis, there was a statistical trend toward protection from cerebral palsy with increasing numbers of antenatal corticosteroid courses (P = .051). This effect became statistically significant when controlled for other confounding variables (gestational age group, place

Behavioral outcomes at 3 years

Behavioral outcomes at 3 years are shown in Table III. The proportion overall who completed their questionnaires was 77% and this percentage varied with parental socioeconomic score and between corticosteroid treatment groups. Percentages varied from 96% for the highest socioeconomic score to 60% for the lowest. There was no significant effect of the number of antenatal corticosteroid courses on the total CBCL score or on the internalizing subscale, either in univariate or multiple analyses,

Behavioral outcomes at 6 years

There was no significant effect of antenatal corticosteroid treatment group on the total CBCL score at 6 years (Table III). There was, however, a persisting effect of antenatal corticosteroid group on the aggressive/ destructive behavioral subscales, with 26% of those receiving 3 or more courses of antenatal corticosteroids scoring above the 90th percentile level and this effect remained statistically significant when controlled for other significant covariates (P = .049). These children were 3.8

Comment

This study provides information on neurologic, cognitive, and behavioral outcomes at 3 and 6 years after corticosteroid administration in the antenatal period. There previously have been studies of outcomes up to age 20 years after single-course treatment given in the context of randomized controlled trials,2., 3. but no published outcomes relating to the consequences of repeated courses. The results of our analyses indicated that repeated courses of corticosteroids before birth were associated

Acknowledgements

We are grateful to Professor Fiona Stanley and Dr Garth Kendall for providing us with access to interview a sample of children in the Western Australian Pregnancy (Raine) Cohort Study to serve as a comparison group, and to Dr Jonathan Rampono and Professor Karen Simmer for their advice on preparation of the manuscript.

References (25)

  • M Ikegami et al.

    Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs

    Am J Respir Crit Care Med

    (1997)
  • J.P Newnham et al.

    Maternal, but not fetal, administration of corticosteroids restricts fetal growth

    J Matern Fetal Neonatal Med

    (1999)
  • Cited by (232)

    View all citing articles on Scopus

    Supported by grants from the Western Australian Health Promotion Foundation (Healthway) and the Women and Infants Research Foundation, Western Australia.

    View full text