Scientists from Denmark who analysed data from more than 1m births have suggested that children exposed to glucocorticoids prenatally may have an increased risk of developing autism, attention-deficit/hyperactivity disorder (ADHD), and other mood-related conditions.
The Aarhus University team said previous studies linking the drugs to mental disorders are limited, which had prompted them to fill evidence gaps.
For their study – looking at births from 1996 to 2016 – they compared children who were exposed to glucocorticoids in utero with those who were not.
Medpage Today reports that some mothers had taken glucocorticoids to reduce the risk for preterm delivery, while others took them to help manage autoimmune or inflammatory disorders.
The findings highlight the importance of balancing the benefits of taking glucocorticoids during pregnancy with potential risks, said Kristina Laugesen, MD, PhD, a physician and researcher in the Department of Clinical Epidemiology at Aarhus University and Aarhus University Hospital, and lead author of the study, published in JAMA Network Open.
“Adverse effects of glucocorticoids and how to minimise use is an ongoing debate among clinicians,” Laugesen said. “The drug has many beneficial effects… but we need to focus on reducing prescribing by increasing awareness.”
Children exposed to steroids because their mothers were at risk for preterm delivery had a 50% higher risk for autism spectrum disorders and a 30% higher risk for ADHD than children who were not exposed but whose mothers were also at risk for preterm delivery.
Researchers also observed a 50% higher risk for mood, anxiety, and stress-related disorders (risk ratio, 1.5; 95% CI, 1.1-2.0).
Those whose mothers had an autoimmune or inflammatory disorder and were exposed to steroids had from 30% to 40% higher risk of developing the mental disorders than children born to similar mothers but who were not exposed to the drugs.
Laugesen said clinicians should take note that the differences were modest in risk for disorders between children exposed to steroids and those who were not.
Mark Clapp, MD, MPH, a maternal-foetal medicine specialist at Massachusetts General Hospital in Boston, said prescribing glucocorticoids is commonplace for pregnant women at risk for preterm labour, especially when administered before 34 weeks of pregnancy. Steroids increase blood sugar, putting the neonate at risk of developing hypoglycaemia.
“Some hypothesise there may be long-term effects for the neonate for being hypoglycaemic, though this association is not well understood, and the data are mixed.”
Clapp said most clinicians make the call to administer steroids to mothers at risk for preterm delivery using shared decision-making.
“This means we should counsel the patients on all of the information that we have, acknowledge places of ambiguity or lack of clarity about the best way forward, and then work with the patient to make the best decision,” he said.
Both Clapp and Laugesen said further research is needed to help physicians decide the best treatment option for their patients.
“The findings are important to encourage more research on the topic,” Laugesen said. “For instance, increased surveillance and continued re-evaluation of the risk of preterm birth may decrease use of glucocorticoids.
Concerning women with autoimmune disorders, alternative medication may be an option, but more research is needed on the safety of these other medications.”
Study details
Mental disorders among offspring prenatally exposed to systemic glucocorticoids
Kristina Laugesen, Nils Skajaa, Henrik Toft Sørensen et al.
Published in JAMA Network Open on 3 January 2025
Abstract
Importance
Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.
Objective
To investigate the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring at the age of 15 years, comparing exposed vs unexposed offspring born to mothers with the same underlying disease (risk of preterm delivery and autoimmune or inflammatory disorders).
Design, Setting, and Participants
This nationwide population-based cohort study used data from registries in Denmark with follow-up until December 31, 2018. Participants included all Danish infants born alive from 1996 to 2016. Analyses were performed from January to December 2023.
Exposures
Prenatal exposure to systemic glucocorticoids.
Main Outcomes and Measures
Fifteen-year crude and adjusted risks, risk differences, and risk ratios (RR) for mental disorders using Kaplan-Meier estimator comparing exposed vs unexposed offspring born to mothers with the same underlying disease.
Results
A total of 1 061 548 infants (52% male) were included in the final study cohort, including 31 518 born to mothers at risk of preterm delivery and 288 747 born to mothers with autoimmune or inflammatory disorders. Among offspring born to mothers at risk of preterm delivery, the adjusted risks for exposed vs unexposed were 6.6% vs 4.3% (RR, 1.5 [95% CI, 1.2-1.9]) for autism spectrum disorders; 1.6% vs 1.3% (RR, 1.3 [95% CI, 0.8-1.8]) for intellectual disabilities; 5.8% vs 4.3% (RR, 1.3 [95% CI, 1.0-1.7]) for attention-deficit hyperactivity disorder (ADHD); and 7.2% vs 4.6% (RR, 1.5 [95% CI, 1.1-2.0]) for mood, anxiety, and stress-related disorders. Among offspring born to mothers with autoimmune or inflammatory disorders, the adjusted risks for exposed vs unexposed were 4.8% vs 3.8% (RR, 1.3 [95% CI, 1.1-1.5]) for autism spectrum disorders; 1.1% vs 0.8% (RR 1.4, [95% CI, 0.9-2.0]) for intellectual disabilities; 5.5% vs 4.4% (RR, 1.3 [95% CI, 1.0-1.5]) for ADHD; and 6.6% vs 4.6% (RR, 1.4 [95% CI, 1.2-1.8]) for mood, anxiety, and stress-related disorders. Findings were confirmed through an active comparator and sibling design. However, confounding by disease severity could not be ruled out.
Conclusions and Relevance
In this cohort study, prenatal exposure to glucocorticoids was associated with higher risk of some mental disorders. These data support continued caution in the use of glucocorticoids in pregnant women.
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