LYON, France — Halving the dose of antenatal betamethasone given to prevent severe respiratory distress syndrome (RDS) in infants does not appear to affect later intelligence quotient (IQ) scores or other measures of neurodevelopment, suggests a follow-up study of a randomized trial.
However, it is unclear from the present data, presented at the Congress of the European Paediatric Academic Societies (CEPAS) 2026 on October 31, whether practice could yet be changed to reduce corticosteroid exposure.
Study presenter Olivier Baud, MD, PhD, of the Department of Neonatal Medicine and Neonatal Intensive Care Unit at Hôpital Cochin – Port-Royal, Assistance Publique-Hôpitaux de Paris, explained that the benefits of antenatal corticosteroids have been recognized for more than 50 years.
Yet while “emerging and compelling evidence shows that a reduction in the dosage of these antenatal steroids could provide similar benefits,” he said, “there has been no change in the regimen or the dosage for humans, whatever the maternal conditions.”
In addition, preclinical data have demonstrated “the potential adverse events of exposing the fetus to corticosteroids before birth, especially for brain maturation and brain vulnerability,” he continued, which was “confirmed recently in a population-based registry from Scandinavian countries where children exposed prenatally to antenatal steroids were found to be at risk of mental and behavioral disorders when delivered full-term or late preterm.”
The researchers therefore conducted a randomized, multicenter, double-blind, placebo-controlled noninferiority trial, BETADOSE, which examined whether a 50% reduction in the dose of antenatal betamethasone given to women at risk of very preterm delivery was noninferior to a full dose in preventing severe RDS.
Between January 2, 2017, and October 9, 2019, 3244 women in 37 level 3 referral perinatal centers in France were randomized to the half- or full-dose group, and the results indicated that the half dose was not noninferior to the full dose in terms of the need for surfactant to treat severe RDS, with the half-dose group requiring nonsignificantly more surfactant.
“Nevertheless, when we looked at survival without severe neonatal morbidity among infants born before 32 weeks gestation in prespecified subgroups, we found there was absolutely no difference…between the two treatment groups,” Baud said.
Subsequently, the team conducted the follow-up BETANINO study to assess the effect of that 50% dose reduction in antenatal betamethasone dosing on neurodevelopmental outcomes in children born before 32 weeks’ gestation when they reached 5-6 years of age.
From the original cohort, they were able to include 180 infants born to women in the half-dose group and 202 infants whose mothers were in the full-dose arm. The two groups of children were well balanced in terms of the maternal characteristics.
In terms of neonatal characteristics, there were more children in the half-dose group born before 28 weeks’ gestation, at 30.6% vs 19.8% in the full-dose group, and there were more cases of severe RDS, at 43.9% vs 29.9%.
Full-scale IQ assessment using the “Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition,” showed that half-dose betamethasone was noninferior to the full dose for long-term neurodevelopment, at median scores of 100.9 vs 100.0 on both intention-to-treat and per-protocol analyses, including after adjusting for gestational age at birth, sex, intrauterine growth restriction, bronchopulmonary dysplasia, and parental educational level.
Baud added that the scores were very similar across subindices of the scale, including verbal comprehension, visual spatial, working memory, fluid reasoning, and processing speed.
Scores were also comparable on the NEPSY-II comprehensive neuropsychological assessment, and on the Social Responsiveness Scale-2 T scores to measure autism severity. Baud noted that the median scores were less than 60, indicating that there were “very few patients with evidence of autism spectrum disorders in this cohort.”
He acknowledged that the study is limited by having included less than half of eligible infants (47%), as well as by the lack of assessment of executive function, academic achievement, behavior, and emerging neurodevelopmental difficulties.
In addition, the team examined only infants born before 32 weeks’ gestation, while “the population-based data regarding the potential adverse event of prenatal steroids concern late preterm and full-term infants.”
Baud explained that this was because they did not have funding to study the whole cohort, and so had to restrict their analysis.
He nevertheless concluded that, in terms of full-scale IQ at preschool age in children born before 32 weeks, half-dose antenatal betamethasone is noninferior, and that there was “no statistically significant difference in secondary neurodevelopmental outcomes.”
Baud believed that the study also “provides data to assess the relative impact of socioeconomic status, educational level and other [aspects of] familial environment on neurocognition in infants born very preterm in France.” Tertiary maternal education was associated with +11.7 full-scale IQ points (95% CI, 7.3-16.1; P <.001) and tertiary co-parent education with +6.4 (2.0-10.8; P <.01), the strongest predictors in the model.
Session co-chair Cornelia Hagmann, MD, PhD, professor of neonatology at University Children’s Hospital Zurich in Switzerland, pointed out that sometimes infants need repeat corticosteroid dosing, and wondered whether that was observed in the current cohort.
Baud confirmed that this was the case for 4% of the infants, who received a regimen similar to that used for the first course of treatment, and noted that those infants were included in the analysis, believing that it would have only a marginal impact on the results.
Raju Narasimhan, MD, a senior attending physician in neonatology at Sidra Medicine in Ar-Rayyan, Qatar, asked whether “based on these results, there’s a case for change in practice from two doses to one dose?”
“I think that would be the most important thing which we need to decide,” he added.
Baud replied that the findings “do not imply to change the current regimen, but it is reassuring regarding the potential consequences of the reduction from the full-dose betamethasone treatment.”
He added: “I know that there is a trial ongoing in Canada [SNACS] to assess the ability of a 50% reduction to provide a similar health status in infants born very preterm. But I think that we need to wait for these results before changing the regimen.”
The study was funded by the French Ministry of Health. Baud, Hagmann, and Narasimhan reported no relevant financial relationships.
