Offspring of severely obese mothers with insulin-treated pregestational diabetes are at an estimated 128% increased risk of being diagnosed with a psychiatric disorder.
Ida A. K. Nilsson, PhD
If a mother had severe obesity and insulin-treated pregestational diabetes, type 2 diabetes, or gestational diabetes, their offspring was at an estimated 128%, 54%, or 18% increased risk to be diagnosed with an ICD-10 F code.
Ida A. K. Nilsson, PhD, and a team of investigators examined more than 647,000 births to learn the associations of different types of maternal diabetes—with and without obesity—with psychiatric disorders in their offspring. The investigators found that the risk was highest for women exposed to insulin-treated pregestational diabetes.
Nilsson, from the molecular medicine and surgery department at Karolinska Institutet in Sweden, and colleagues included all pregnancies which ended in live births in Finland between January 2004-December 2014. Data were collected from the Drugs and Pregnancy database. Primary and secondary diagnoses of psychiatric disorders for offspring and mothers were obtained from the Finnish Care Registers for Health Care (HILMO).
The investigators categorized maternal body mass index (BMI) as severely obese (>35); moderately obese (>30 to <35); overweight (>25 to <30); and normal weight (>18.5 to <25). Pregestational BMI for mothers was severely obese for 3.7%; moderately obese for 7.7%; overweight for 20.7%; and normal weight for 59.2% of births.
Among the 647,099 births studied, 105,966 fetuses (16.3%) were exposed in utero to maternal diabetes, 4000 (.62%) to insulin-treated pregestational diabetes—3880 with insulin purchase also during pregnancy— 3724 (.57%) to type 2 diabetes without insulin, and 98,242 to gestational diabetes not treated with insulin.
There were statistically significant interactions between maternal prepregnancy BMI and maternal diabetes with offspring have any psychiatric diagnosis (insulin-treated pregestational diabetes, P <.001; type 2 diabetes, P <.001; gestational diabetes, P = .007). Maternal diabetes, in addition to obesity, added an increased risk for offspring to receive a psychiatric diagnosis—effect size larger in the insulin-treated pregestational diabetes first, then type 2, and then gestational diabetes.
Insulin-treated pregestational diabetes (HR, 2.71; 95% CI, 2.03-3.61), type 2 diabetes (HR, 1.97; 95% CI, 1.61-2.37), and gestational diabetes (HR, 1.61; 95% CI, 1.50-1.72) were associated with an estimated 128%, 54%, and 18% increased risk for their offspring to receive any ICD-10 F code diagnosis for mothers with severe obesity compared to mothers with only severe obesity (HR, 1.43; 95% CI, 1.33-1.54).
If a mother had severe obesity and insulin-treated pregestational diabetes it was associated with offspring mood disorders (HR, 8.03; 95% CI, 3.32-19.43) and intellectual disability (HR, 3.64; 95% CI, 1.63-8.14). There was no association with offspring anxiety disorders.
The children of severely obese mothers with type 2 diabetes had higher risks of mood disorders (HR, 3.61; 95% CI, 2.09-6.25), anxiety disorders (HR, 2.15; 95% CI, 1.35-3.42) and intellectual disabilities (HR, 2.00; 95% CI, 1.03-3.85) than the offspring of normal-weight mothers without diabetes. Those born to mothers with severe obesity and type 2 diabetes were also at increased risk of specific developmental disorders (HR, 2.29; 95% CI, 1.81-2.91), ASD (HR, 2.28; 95% CI, 1.18-4.41), ADHD or conduct disorders (HR, 3.21; 95% CI, 2.20-4.70), and other behavioral and emotional disorders (HR, 1.65; 95% CI, 1.10-2.46) compared to children born to healthy mothers.
Overall, 34,892 offspring (5.39%) had a psychiatric disorder diagnosed during the study period (before the age of 11 years old). Psychiatric disorders included mood disorders (.31%); anxiety disorders (.73%); specific development disorders (2.77%); ADHD or conduct disorders (.81%); or other behavioral and emotional disorders.
Of the mothers without diabetes, higher prepregnancy BMI (moderate and severe obesity) was linked to an increased risk of any ICD-10 F code diagnosis among their offspring (moderate obesity, HR, 1.3 [95% CI, 1.24-1.36]; severe obesity, HR, 1.43 [95% CI, 1.33-1.54]), compared to those with BMI < 25. Specifically, the offspring had an increased risk of anxiety disorders (moderate obesity, HR, 1.31 [95% CI, 1.16-1.49]; severe obesity, HR, 1.41 [95% CI, 1.15-1.72]), intellectual disabilities (moderate obesity, HR, 1.56 [95% CI, 1.32-1.84]; severe obesity, HR, 1.40 [95% CI, 1.06-1.86], and ADHD or conduct disorders (moderate obesity, HR, 1.43 [95% CI, 1.26-1.61]; severe obesity, HR, 1.87 [95% CI, 1.58-2.23]).
Those offspring were also at an increased risk to being diagnosed with specific developmental disorders (moderate obesity, HR, 1.46 [95% CI, 1.37-1.55]; severe obesity, HR, 1.67 [95% CI, 1.26-1.61]).
Nearly 13,500 children (2.07%) purchased psychotropic medication, including antipsychotics and hypnotics or anxiolytics, antidepressants, and stimulants.
Additional research with longer follow-up on offspring and exploration of biological mechanisms are needed, the investigators concluded.
The study, “Associations of Different Types of Maternal Diabetes and Body Mass Index With Offspring Psychiatric Disorders,” was published online in JAMA Network Open.