Prenatal systemic glucocorticoids exposure linked to higher risk of some mental disorders

Prenatal systemic glucocorticoids exposure linked to higher risk of some mental disorders | Image Credit: © WavebreakMediaMicro - © WavebreakMediaMicro - stock.adobe.com.

The prenatal exposure to glucocorticoids was associated with a higher risk of some mental disorders among offspring, according to a newly-published study in JAMA Network Open.

Authors of the study noted that current evidence of this association is lacking and has limitations. As a result, the authors' objective was "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)," they wrote in the publication.

Among pregnant people, systemic glucocorticoids are used for those at risk of preterm birth and in those with autoimmune or inflammatory disorders to decrease neonatal morbidity and mortality and decrease inflammation and symptoms, respectively.

"Cortisol, an endogenous glucocorticoid, plays a critical role in normal fetal development, including development of the central nervous system (CNS)," the authors wrote. "However, prenatal exposure to excess glucocorticoid levels (maternal stress or treatment) may increase the risk of mental disorders in offspring via multiple mechanisms."

Previous studies have been limited by general population comparator cohorts, which could introduce confounding by indication, shared risk factors, and genetics.

Using a Denmark population-based cohort study, the investigators examined the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring. Disorders included autism spectrum disorders, intellectual disabilities, anxiety, stress-related disorders, and attention-deficit hyperactivity disorder (ADHD) and mood disorders.

The study design consisted of data from registries in Denmark with follow-up until December 31, 2018, and included all Danish infants born alive from 1996 to 2016. Data analyses were performed from January to December 2023.

In all, a total of 1,061,548 infants (52% male) were included in the final study cohort. Of these, 31,518 were born to mothers at risk of preterm delivery while 288,747 were born to mothers with autoimmune or inflammatory disorders.

For offspring of 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 ADHD
• 7.2% vs 4.6% (RR, 1.5 [95% CI, 1.1-2.0]) for mood, anxiety, and stress-related disorders

For offspring of mothers with autoimmune or inflammatory disorders, 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
• 6.6% vs 4.6% (RR, 1.4 [95% CI, 1.2-1.8]) for mood, anxiety, and stress-related disorders

The investigative team noted that findings were confirmed via an active comparator and sibling design, though confounding by disease severity could not be ruled out.

"In this cohort study, prenatal exposure to glucocorticoids was associated with higher risk of some mental disorders," concluded the authors. "These data support continued caution in the use of glucocorticoids in pregnant people."

Reference:

Laugesen K, Skajaa N, Petersen I, et al. Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids. JAMA Netw Open. 2025;8(1):e2453245. doi:10.1001/jamanetworkopen.2024.53245