Maternal diabetes (pregestational or gestational diabetes) and severe obesity are linked to increased risk of several mental disorders in children.
The offspring of mothers with obesity and different types of diabetes could be at an increased risk of developing psychiatric and neurodevelopmental disorders. Researchers performed this study to assess the risks associated explicitly with mothers with obesity exposed to insulin-treated pregestational diabetes, non-insulin-treated type 2 diabetes, and gestational diabetes, all stratified for maternal BMI.
Epidemiological studies have shown that pregestational obesity is associated with neurodevelopmental and psychiatric disorders in offspring. There is a cascade of functions that are impacted by obesity, beginning with the metabolic and endocrine functions of the adipose tissue. The risk of insulin resistance increases due to the excessive amounts of secreted pro-inflammatory cytokines, glycerol, nonesterified fatty acids, and hormones. Now, if insulin resistance is combined with deficient pancreatic insulin secretion, it results in a lack of glucose control, which in turn, increases the risk of type 2 diabetes. Furthermore, this diabetes has the potential to influence placental metabolic functions, which will expose the fetus to maternal hyperglycemia, oxidative stress, lipotoxicity, inflammation, and insulin resistance, all of which are believed to not only affect organ development and function but have a long-lasting outcome.
In this population-based cohort study, different types of maternal diabetes were examined, both separately and together with maternal obesity, to seek the incidence of psychiatric disorders in the mother’s offspring.
Using the Cox proportional hazard model, researchers were able to estimate the correlation of exposure to maternal prepregnancy obesity and various types of diabetes. Maternal prepregnancy obesity was stratified by body mass index categories in conjunction with the outcome of the offspring, detailing psychiatric diagnosis and the purchase of psychotropic drugs. The purchase of psychotropic drugs was considered to be sensitivity analyses. To assess the maternal body mass index, the average weight was compared to the strata overweight, moderately obese, and severely obese. Measures of effect size were quantified with hazard ratios and confidence intervals. Statistical significance was determined with a two-sided p-value <0.5.
Following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline, this study was inclusive of 649,043 pregnancies ending in live births in Finland between January 1, 2004, and December 31, 2014. The study and data analysis were conducted from January 1, 2019, to July 5, 2019. For this type of study in Finland, consent is not required because no participants were contacted. Thus, the Drugs and Pregnancy database steering committee and the data protection authority in Finland approved this study.
Several different databases were used to gather the necessary information pertinent to this research. The data from the Drugs and Pregnancy database encompassed the following: Medical Birth Register, the Register of Congenital Malformations, and the Register of Induced Abortions. The Finnish Register of Reimbursement Drugs possessed data on maternal and offspring drug purchases. The only medications taken into consideration were those prescribed by a dentist or physician and dispensed from a pharmacy. The Finnish Care Registers for Health Care (HILMO) was used to extract data on medical diagnoses of mothers and offspring.
Compared to normal-weight mothers without diabetes, non–insulin-treated type 2 diabetes in mothers with severe obesity was associated with psychiatric disorders in the offspring (hazard ratio, 1.97; 95% CI, 1.64-2.37). However, there was a smaller effect size for mothers with severe obesity and insulin-treated pregestational diabetes (hazard ratio, 2.71; 95% CI, 2.03-3.61). Lastly, in women with severe obesity and gestational diabetes, the overall effect size was the lowest (hazard ratio, 1.61; 95% CI, 1.50-1.72).
Fetal exposure to pregestational, type 1 & 2, gestational, and non-specified pregestational diabetes has been associated with a multitude of psychiatric disorders including autism, ADHD, mood, and conduct disorders. Of which, insulin-treated pregestational diabetes is associated with being the highest risk, followed by type 2 diabetes and then gestational diabetes. This study did possess quite a few limitations, however. Some limitations included were that the adjustment for the socioeconomic position was not as favorable, the maternal body mass index was only obtained once, and offspring follow-up time was short.
- Pregestational and gestational diabetes in mothers, combined with severe obesity, is linked to psychiatric disorders in their offspring.
- Insulin-treated pregestational diabetes has the highest risk associated with the risk of offspring developing psychiatric disorders.
- This study did not include an adequate follow-up time of the offspring.
Linghua Kong, MS. “Associations of Different Types of Maternal Diabetes and Body Mass Index With Offspring Psychiatric Disorders.” JAMA Network Open, American Medical Association, 7 Feb. 2020, jamanetwork.com/journals/jamanetworkopen/fullarticle/2760442.
Kong, Linghua, et al. “The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity and Diabetes.” Pediatrics, U.S. National Library of Medicine, Sept. 2018, www.ncbi.nlm.nih.gov/pubmed/30093539.
Deonna Andrews, PharmD Candidate 2020 of Florida Agricultural & Mechanical University College of Pharmacy and Pharmaceutical Sciences