# Twenty-year outcomes after repeat doses of antenatal corticosteroids prior to 32 weeks’ gestation: Follow-up of a randomised clinical trial

## TL;DR

A study found no major health benefits or harms in adulthood from repeat antenatal corticosteroid use in pregnant women at risk of preterm birth.

## Contribution

This is the first long-term follow-up showing no significant adult health effects from repeated antenatal corticosteroids.

## Key findings

- No significant difference in asthma diagnosis rates at 20 years between groups exposed to repeat corticosteroids and placebo.
- No major benefits or harms observed in respiratory or general health outcomes in adulthood.
- Follow-up limitations include a 61% participation rate and reliance on questionnaires and administrative data.

## Abstract

For women who have received a course of antenatal corticosteroids ≥7 days prior and have ongoing risk of preterm birth within the next 7 days, repeat dose(s) of corticosteroids up to 32 weeks’ gestation have been shown to reduce neonatal respiratory distress syndrome and serious health problems in the neonatal period but not other neonatal morbidities such as chronic lung disease, death, severe intraventricular haemorrhage or necrotising enterocolitis. Repeat antenatal corticosteroids were not associated with either benefit or harms in mid-childhood. However, this may have been too early to evaluate potential adverse effects on respiratory and other long-term outcomes. We aimed to assess if exposure to repeat dose(s) of antenatal corticosteroids administered to pregnant women up to 32 weeks’ gestation has beneficial or harmful effects on respiratory and general health of the offspring in adulthood.

We assessed the adult offspring of New Zealand participants in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids for the Prevention of Neonatal Respiratory Disease (ACTORDS), a multicentre, placebo-controlled trial where women at risk of preterm birth within the next week, 7 or more days after having received a single course of corticosteroids were randomised to a repeat dose of intramuscular betamethasone or placebo, that could be repeated weekly if at ongoing preterm birth risk. Follow-up at 20 years included a health questionnaire and consent to access administrative data sources. The primary outcome was any asthma diagnosis. Secondary outcomes included neurodevelopmental, cardiovascular, mental and general health, functional difficulties and social outcomes. Of 352 infants born to 290 maternal trial participants, we assessed 214 (61%; 96 (45%) female) at mean (standard deviation) age 20.5 (1.5) years. The rate of any asthma diagnosis was similar in both groups (58/107 (54%) repeat bethamethasone versus 50/107 (47%) placebo; risk ratio adjusted for gestational age at trial entry, multiplicity and birth centre 1.13, 95% confidence interval, 0.87, 1.46). Differences between the groups for the secondary outcomes were generally small and confidence intervals included the possibility of no difference between groups.

In this follow-up of a randomised clinical trial, our data suggest neither major harm nor benefit for the offspring in early adulthood following exposure to repeat dose(s) of antenatal corticosteroids compared with a single course prior to 32 weeks’ gestation. Smaller effects cannot be excluded and follow-up of adult offspring from other trials of repeat antenatal corticosteroids is recommended.

International Standard Randomized Controlled Trial, number ISRCTN48656428.

Antenatal corticosteroids given to women at risk of preterm birth reduce the baby’s risk of difficulty breathing after birth.

For women who don’t give birth preterm but remain at risk, weekly repeat dose(s) of corticosteroids up to 32 weeks of pregnancy have also been shown to reduce the baby’s risk of difficulty breathing or having serious complications after birth and are not associated with any harms up to 8 years of age.

However, there is concern that follow-up to 8 years may not have been long enough to evaluate potential harmful consequences for breathing and other health conditions.

We aimed to assess if exposure to repeat dose(s) of antenatal corticosteroids given to pregnant women up to 32 weeks’ gestation has beneficial or harmful effects on lung conditions and general health of their children as adults.

We assessed participants at 20 years of age who had been exposed to repeat dose(s) of antenatal corticosteroids or only one course followed by placebo during a randomised clinical trial.

We used a health questionnaire and routinely collected administrative data to compare the rates of any asthma diagnosis, any other lung conditions, or any other general health conditions.

We found no differences in any asthma diagnosis or any other conditions between those exposed to repeat antenatal corticosteroids and those who were not.

Our data suggest neither benefit nor harm following exposure to repeat dose(s) of antenatal corticosteroids for the offspring 20 years later.

The main limitations were the follow-up rate of only 61% and the use of health questionnaires and routinely collected data rather than in-person assessments.