Exposure to Maternal Diabetes Could Increase Risk of Psychiatric Disorders in Offspring

An analysis of more than 2.4 million offspring in Denmark suggests children with exposure to maternal diabetes during pregnancy were at a 15% greater risk of developing a psychiatric disorder in the first 40 years of life.

New research from an international team of investigators details the apparent increase in risk of psychiatric disorders, including behavioral and developmental disorders, among children born to women with diabetes.

An analysis including data from more than 2.4 million births within Denmark from 1978-2016, results of the study indicate children born to mothers with any diabetes diagnosis during pregnancy had a 15% greater risk of receiving a diagnosis of a psychiatric disorder during their first 40 years of life compared to offspring born to mothers without a diabetes diagnosis during pregnancy.

“Our study shows a pattern in which prenatal exposure to maternal diabetes diagnosed during pregnancy was associated with increased risks for several psychiatric disorders in the first 4 decades of life,” wrote investigators. “Children born to mothers with any diabetes diagnosis during pregnancy had increased risks of any psychiatric disorder, schizophrenia, anxiety disorders, intellectual disabilities, developmental disorders, and behavioral disorders.”

In the wake of studies suggesting maternal diabetes was associated with increased risk of ADHD in offspring, the current study was conducted by a team of 6 investigators representing institutions in Asia, Europe, and North America to further investigate a potential association with the full-spectrum psychiatric disorders with maternal diabetes. To do so, investigators designed aa population-based cohort study leveraging data from multiple nationwide Danish health registries, which allowed them to identify a population of 2,413,335 live births occurring from 1978-2016 for inclusion in their analyses.

Investigators included 10 types of psychiatric disorders as their outcomes of interest. These were defined as: any psychiatric disorder, substance use disorders, schizophrenia, mood disorders, anxiety disorders, eating disorders, personality disorders, intellectual disorders, developmental disorders, and behavioral disorders. The exposure of interest was defined as any maternal diabetes diagnosis during pregnancy, which was further stratified according to the 3 subtypes of interest: pregestational type 1 diabetes, pregestational type 2 diabetes, and gestational diabetes.

Investigators assessed hazard ratios using Cox proportional hazards regression models with adjustment for multiple covariates, including maternal and paternal history of any psychiatric disorder, offspring sex, calendar period of birth, singleton status, and various maternal characteristics during pregnancy. Of note, sibship design and competing risk analyses were also included as part of the study.

In total, 56,206 individuals were born to mothers with maternal diabetes. This concluded 22,614 exposed to pregestational type 1 diabetes, 6713 exposed to pregestational type 2 diabetes, and 26,879 exposed to gestational diabetes. The 2,413,335-person study cohort included 1,239,148 (51.3%) men, had a median age of 19 (IQR, 5.8-20.8) years, and had an age range of 1-39 years. From the study cohort, investigators obtained a total of 412,662,622 million person-years of follow-up. During the follow-up period, 151,208 offspring received a diagnosis of a psychiatric disorder.

Upon analysis, results suggested offspring born to mothers with any diabetes diagnosis were at an increased risk of any psychiatric disorder (HR, 1.15; 95% CI, 1.10-1.20), schizophrenia (HR, 1.55; 95% CI, 1.15-2.08), anxiety disorders (HR, 1.22; 95% CI, 1.09-1.36), intellectual disabilities (HR, 1.29; 95% CI, 1.11-1.50), developmental disorders (HR, 1.16; 95% CI, 1.03-1.30), and behavioral disorders (HR, 1.17; 95% CI, 1.08-1.27) compared to offspring born to mothers without a diabetes diagnosis.

Investigators pointed out no associations of any maternal diabetes diagnosis were observed for risk of substance use disorders (HR, 0.99; 95% CI, 0.91-1.08), mood disorders (HR, 1.12; 95% CI, 0.90-1.39), eating disorders (HR, 1.21; 95% CI, 0.98-1.50), and personality disorders (HR, 1.09; 95% CI, 0.71-1.65). The sibship analysis indicated the association between maternal diabetes during pregnancy and any psychiatric disorder was attenuated but remained positive for exposure to pregestational type 1 diabetes and type 2 diabetes, with a more robust association of type 2 diabetes than was observed in the primary analysis.

“These findings suggest that careful clinical management of maternal diabetes during pregnancy is needed. Overall, our findings signal the importance of effective strategies for preventing, screening, and treating diabetes among women of fertile age for women’s health and children’s mental health,” investigators added.

This study, “Associations of Maternal Diabetes During Pregnancy With Psychiatric Disorders in Offspring During the First 4 Decades of Life in a Population-Based Danish Birth Cohort,” was published in JAMA Network Open.