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Psychiatric Disorders in Offspring and the Relation to Maternal Diabetes and BMI

Sep 11, 2021
 
Editor: Steve Freed, R.PH., CDE

Author: Stephanie Anderson, PharmD Candidate 2021, Skaggs School of Pharmacy and Pharmaceutical Sciences

Different types of maternal diabetes and obesity can have many effects on the offspring, including increasing risk for certain psychiatric disorders.

Maternal pregestational obesity is associated with neurodevelopmental and psychiatric disorders in offspring. Obesity in pregnancy can permanently alter metabolic control processes in the fetus, including appetite regulation and pancreatic beta-cell physiology [1]. Type 1 diabetes, type 2 diabetes, and gestational diabetes mellitus (GDM) expose the fetus to an unhealthy environment, including maternal hyperglycemia and oxidative stress. These adverse exposures can have destructive outcomes on organ development and function. For example, a multiethnic study showed that maternal diabetes, requiring medication, is associated with the risk of developing attention-deficit/hyperactivity disorder (ADHD) in offspring.

 

In a paper by Godfrey et al., many bodies of evidence are reviewed to examine maternal obesity and the long-term offspring consequences that are linked. Pre-pregnancy obesity and excessive gestational weight gain are associated with increased risk of obesity in offspring during childhood and into adolescence and adulthood. Additionally, a meta-analysis found an increased risk for autism spectrum disorder (ASD) in children of mothers with obesity during pregnancy. Multiple studies over the last few years also found positive associations between maternal obesity and offspring cerebral palsy. Other consequences examined in this paper include effects on the gut microbiome, asthma development, and the newborn’s immune system.

Focusing on psychiatric disorders, a retrospective cohort study by Xiang and colleagues examined the risk of ASD in offspring associated with maternal type 1 diabetes, type 2 diabetes, and GDM. Among these, all three types of diabetes bring an elevated risk of ASD development. Relative to no diabetes exposure, the adjusted hazard ratios for maternal diabetes were 2.36 for type 1 diabetes, 1.45 for type 2 diabetes, and 1.30 for GDM by 26 weeks gestation. This study, among many other reports, supports the increased risk of ASD among offspring, but a more comprehensive array of psychiatric disorders and the risk of type 2 diabetes across varying degrees of obesity needed to be studied more adequately.

Kong et al. aimed to determine whether exposure to different types of maternal diabetes, either by themselves or in combination with maternal obesity, is associated with an increased risk of the offspring developing a psychiatric disorder. This population-based registry cohort study is valuable because it looks at both maternal diabetes and obesity. Instead of just focusing on one, the study also included many mental disorders (e.g., mood disorders, anxiety disorders, ADHD, ASD, personality disorders, etc.). Cox proportional hazards modeling determined the association of exposure to pre-pregnancy obesity and different types of diabetes with a psychiatric diagnosis.

A higher pre-pregnancy BMI among mothers without diabetes was associated with an increased risk of psychiatric disorders in their children. Significant statistical interactions also showed that maternal diabetes, when paired with obesity, brings additional risk for offspring to develop a psychiatric disorder. Insulin-treated pregestational diabetes (HR 2.71) carries the most added risk, followed by type 2 diabetes (HR 1.97), then gestational diabetes (HR 1.61). The study also reported an original finding that insulin-treated pregestational diabetes in mothers with severe obesity is associated with mood disorders and intellectual disabilities among their offspring (HRs 8.03 and 3.64). Limitations include difficulty properly adjusting for socioeconomic status, genetic factors, and gestational weight gain (BMI only obtained at a single point).

Practice Pearls:

  • Maternal obesity during pregnancy is associated with many consequences in offspring, including increased risk of obesity, atypical development of the immune system, and increased risk of abnormal neurodevelopment.
  • Strong evidence associates type 1 diabetes, type 2 diabetes, and gestational diabetes with the offspring’s development of psychiatric disorders (e.g., ASD, ADHD, mood disorders, anxiety disorders, and personality disorders).
  • The joint association of severe obesity with diabetes carries a superior risk than that of either factor alone for diagnosing a psychiatric disorder in offspring.

 

Godfrey, Keith M, et al. “Influence of maternal obesity on the long-term health of offspring.” The lancet. Diabetes & Endocrinology,

Kong, Linghua, et al. “Associations of Different Types of Maternal Diabetes and Body Mass Index With Offspring Psychiatric Disorders.” JAMA network. February 05, 2020

Xiang, Anny H et al. “Maternal Type 1 Diabetes and Risk of Autism in Offspring.” JAMA vol. 320,1 (2018):

 

Stephanie Anderson, PharmD Candidate 2021, Skaggs School of Pharmacy and Pharmaceutical Sciences