From the Journals

Prenatal betamethasone not linked to later adverse neurocognitive problems



Administering prenatal corticosteroids to women at risk for preterm birth does not appear to contribute to adverse neurocognitive function in children 6-8 years later, regardless of whether they had fetal growth restriction, a new study found.

Pregnant woman in hospital Photodisc/Thinkstock

Women at less than 32 weeks’ gestation are recommended to receive multiple betamethasone doses if they have a high ongoing risk of preterm birth. However, concern existed regarding possible effects of these steroid doses on the infant in later childhood, particularly in cases of fetal growth restriction (FGR) because of “animal studies suggesting long-term adverse effects of treatment on neurosensory function,” Robert D. Cartwright of the University of Auckland (New Zealand), and his associates reported in JAMA Network Open.

Yet no such effects were identified in this preplanned follow-up analysis of the placebo-controlled, randomized Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS). “Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of fetal growth restriction, in view of the associated neonatal benefits and absence of later adverse effects,” the authors concluded.

The original ACTORDS study involved 982 women pregnant with 1,146 fetuses at 23 hospitals throughout Australia and New Zealand, enrolled from April 1998 to July 2004. All enrolled women were less than 32 weeks’ gestation, had received an initial course of corticosteroids, and had an ongoing risk of preterm birth at least 7 days later.

Women were randomly assigned to receive an intramuscular dose of betamethasone or saline placebo weekly until birth or preterm birth risk abated. The current follow-up, when children were 6-8 years old, was planned during the 2-year follow-up. Children underwent a pediatrician’s physical and neurologic exam, vision and hearing screening, and fine and gross motor testing. A psychologist tested children’s IQ, attention, executive function, and academic skills using standardized, validated assessment tools. Caregivers also rated children’s behavioral and emotional problems, executive function abilities, and attention in questionnaires.

Among 988 of 1,059 surviving children assessed, FGR occurred in 28% of children exposed to betamethasone and 25% in the placebo group.

For the primary outcomes, rates of disability-free survival were similar in both the placebo and betamethasone groups for children with (odds ratio, 1.1) and without FGR (OR, 1.0). Rates also were similar for death or survival with moderate to severe disability (FGR: OR, 0.9; and non-FGR: OR, 0.8).

“Some evidence suggested a differential effect for several secondary outcomes, with better scores for selective and divided attention after exposure to repeated antenatal betamethasone in children with FGR, but poorer scores for impulse control in children without FGR,” Dr. Cartwright and his associates reported. “These effects were small and of uncertain clinical significance and may reflect type I error.

“For all other measures of neurocognitive function and learning, exposure to repeated antenatal betamethasone treatment did not alter performance in midchildhood, even in the presence of FGR,” they added.

Children with FGR had an increased risk of death or moderate to severe disability, compared with children without FGR, regardless of treatment group. Those with FGR also had greater risk of motor impairment.

One possible reason for not finding adverse neurocognitive effects in the betamethasone group is “that infants with fetal growth restriction appeared to have greater benefit from repeated antenatal corticosteroid therapy, with a nearly twofold reduction in serious neonatal morbidity,” the authors surmised. “Thus, the decrease in serious postnatal complications may have counteracted any potential adverse effects of corticosteroid exposure.” But they noted a continuing concern about whether “repeated antenatal corticosteroids in FGR could increase the risk of ADHD.”

The research was funded by the National Health Medical Research Council of Australia, the Health Research Council of New Zealand and the Auckland Medical Research Foundation. One coauthor reported receiving grants from National Health and Medical Research Council of Australia, and a second coauthor received grants from the Auckland Medical Research Foundation.

SOURCE: Cartwright RD et al. JAMA Netw Open. 2019 Feb 1. doi:10.1001/jamanetworkopen.2018.7636.

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