Antenatal Betamethasone Does Not Impair Neurocognitive Function in Fetal Growth Restriction

By Will Boggs MD

February 10, 2019

NEW YORK (Reuters Health) - Repeated antenatal doses of betamethasone does not impair neurocognitive function in elementary-school-aged children born with fetal growth restriction, according to a secondary analysis from the ACTORDS clinical trial.

"We were a little surprised by the results, as animal studies have repeatedly raised concerns about exposing fetuses with growth restriction to increasing amounts of corticosteroids," said Dr. Christopher J. D. McKinlay of the University of Auckland, New Zealand.

"But our study clearly shows that treatment with repeated doses of betamethasone for preterm birth is safe in the long term, even in the presence of fetal growth restriction. This is an important finding, as growth restriction is common in cases where repeat doses are indicated (27% in our study)," he told Reuters Health by email.

The Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS) showed that repeated antenatal doses of corticosteroids are not associated with adverse effects on neurocognitive function, learning, behavior, growth, lung function and cardiometabolic function in offspring at mid-childhood.

In their secondary analysis of ACTORDS data, Dr. McKinlay's team investigated whether the presence of fetal growth restriction influenced the effects of repeated antenatal doses of betamethasone on neurocognitive function and behavior in 988 children (mean age at follow-up, 7.5 years).

About a quarter of the children (28.2% of the betamethasone group and 24.6% of the placebo group) had been born with fetal growth restriction.

At corrected ages of 6 to 8 years, the rates of survival free of any disability and of death or moderate to severe disability, the primary outcomes, were similar between treatment groups in the subgroups with and without fetal growth restriction, respectvely, with no evidence of an interaction effect, the team reports in JAMA Network Open, online February 1.

Regardless of the presence or absence of fetal growth restriction, repeated betamethasone treatment was associated with significantly greater survival free of any disability and significantly reduced death or moderate to severe disability.

Among children born with fetal growth restriction, repeated-dose betamethasone therapy reduced the incidence of respiratory distress syndrome, the severity of neonatal lung disease and serious neonatal morbidity, as well as the need for mechanical ventilation, oxygen and surfactant therapy.

Regardless of treatment exposure, however, children with fetal growth restriction fared worse than those without fetal growth restriction, with an increased risks of death or moderate to severe disability and motor impairment, lower IQs and lower scores for measures of attention, executive function and reading.

"It is sometimes mistakenly assumed that growth-restricted fetuses don't need repeat dose treatment due to higher endogenous corticosteroid levels," Dr. McKinlay said. "However, our study has shown that growth-restricted fetuses not only have higher rates of respiratory and other morbidities but also are more likely to benefit from repeated doses therapy."

"The safety of antenatal corticosteroids in fetal growth restriction has been a specific concern with repeat doses," he said. "Our study has provided reassurance that adverse effects on long-term brain development are very unlikely. I would not hesitate to use repeat doses of antenatal betamethasone if there is risk of very preterm birth in the next 7 days, regardless of the reason a woman is considered at risk. My only caution would be that these results may not necessarily apply in low-resource settings."


JAMA Netw Open 2019.