Prenatal Systemic Glucocorticoid Exposure and an Increased Risk of Future Mental Disorders
1. In this cohort study of offspring born to mothers at risk for preterm delivery or diagnosed with an autoimmune or inflammatory disorder, there was an association between systemic glucocorticoid exposure prenatally and future development of a mental disorder.
Evidence Rating Level: 2 (Good)
Systemic glucocorticoids have been prescribed for use in preterm labour as a way to decrease fetal morbidity and mortality, and for individuals with autoimmune or inflammatory disorders. Cortisol, a hormone, and endogenous glucocorticoid is involved in key development processes in utero, including development of the central nervous system (CNS). However, there may be an increased risk of the infant developing mental disorders if exposed to excess glucocorticoids prenatally. The goal of this cohort study was to understand the association between glucocorticoid exposure prenatally and the development of mental disorders in offspring. Data was excluded for stillbirths, infants born to mothers who used systemic glucocorticoids up to 3 months before conception, and infants with missing gestational age data. Among the offspring born to mothers at risk of delivering preterm, they were divided into exposed and unexposed. Similarly, offspring born to mothers with autoimmune or inflammatory diseases were divided into exposed and unexposed. When the offspring reached the follow-up stage, they were assessed for mental disorders commonly occurring in this age group including intellectual disability, autism spectrum disorders, ADHD, and mood-related disorders. A total of 1 061 548 infants were included in the analysis, of whom, 31 518 were born to mothers at risk of preterm birth (3659 [11.6%] exposed) and 288 747 born to mothers with autoimmune or inflammatory conditions (6453 [2.2%] exposed). Exposed offspring had mothers with a higher prevalence of pregnancy complications compared with unexposed offspring born to mothers at risk of preterm delivery. For offspring born to mothers at risk of preterm delivery, the adjusted risk for various conditions were as follows: autism spectrum disorder were 6.6% vs 4.3% (RR, 1.5 [95% CI, 1.2-1.9]); intellectual disabilities were 1.6% and 1.3% (RR, 1.3 [95% CI, 0.8-1.8]); ADHD were 5.8% vs 4.3% (RR, 1.3 [95% CI, 1.0-1.7]); and mood, anxiety and stress-related disorders, were 7.2% vs 4.6% (RR, 1.5 [95% CI, 1.1-2.0]) comparing exposed vs unexposed respectively. The same comparison was looked at in offspring born to mothers with autoimmune or inflammatory disorders. For the exposed vs unexposed in that cohort respectively, the adjusted risks 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. As evidenced by the results, there was an association between prenatal exposure to systemic glucocorticoids and the development of mental disorders later in life.
