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. 2021 Oct 1;4(10):e2128005.
doi: 10.1001/jamanetworkopen.2021.28005.

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

Raquel Nogueira Avelar E Silva  1   2   3 , Yongfu Yu  2   4 , Zeyan Liew  5   6 , Anne Vested  1 , Henrik Toft Sørensen  1   2 , Jiong Li  1   2
Affiliations

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

Raquel Nogueira Avelar E Silva et al. JAMA Netw Open. .

Abstract

Importance: Maternal diabetes has been suggested as a risk factor for attention-deficit/hyperactivity disorder and autism in offspring, but evidence on its association with the full spectrum of psychiatric disorders remains lacking.

Objective: To investigate the associations between maternal diabetes diagnosed before or during pregnancy and 10 types of psychiatric disorders in offspring during the first 4 decades of life.

Design, setting, and participants: This population-based cohort study used data from several Danish nationwide medical and administrative registries in Denmark on all 2 413 335 live births from 1978 to 2016. Data were analyzed between October 1, 2019, and July 15, 2021.

Exposures: Any maternal diabetes diagnosis during pregnancy (56 206 offspring [2.3%]) and 3 diabetes subtypes (pregestational type 1 diabetes, 22 614 offspring [1.0%]; pregestational type 2 diabetes, 6713 offspring [0.3%]; and gestational diabetes, 26 879 offspring [1.1%]).

Main outcomes and measures: Outcomes included 10 types of psychiatric disorders: any psychiatric disorder, substance use disorders, schizophrenia, mood disorders, anxiety disorders, eating disorders, personality disorders, intellectual disorders, developmental disorders, and behavioral disorders. Hazard ratios (HRs) and 95% CIs were computed using Cox proportional hazards regression models. Covariates included maternal and paternal history of any psychiatric disorder, offspring sex, calendar period of birth, singleton status, and several maternal characteristics during pregnancy (ie, age, parity, educational level, smoking, cohabitation, residence, and body mass index). Sibship design and competing risk analyses were also conducted.

Results: A total of 2 413 335 individuals (1 239 148 male participants [51%]; age range, 1-39 years; median age, 19.0 years [IQR, 5.8-20.8 years]) were included in this study. During the 39-year follow-up time, 151 208 offspring (6.4%) received a diagnosis of a psychiatric disorder. Offspring born to mothers with any diabetes diagnosis during pregnancy were at increased risk of developing 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 with offspring born to mothers without a diabetes diagnosis during pregnancy. No association was observed for substance use disorders, mood disorders, eating disorders, and personality disorders.

Conclusions and relevance: This study shows a pattern that suggests that prenatal exposure to maternal diabetes during pregnancy was associated with increased risk of psychiatric disorders overall and most specific psychiatric disorders in offspring in their first 4 decades of life.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Yu reported receiving grants from Lundbeckfonden during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Risks of Psychiatric Disorders in Offspring Exposed to Any Maternal Diabetes Diagnosis During Pregnancy Compared With the Unexposed
A, Any psychiatric disorder. B, Substance use disorders. C, Schizophrenia. D, Mood disorders. E, Anxiety disorders.
Figure 2.
Figure 2.. Risks of Psychiatric Disorders in Offspring Exposed to Any Maternal Diabetes Diagnosis During Pregnancy Compared With the Unexposed
A, Eating disorders. B, Personality disorders. C, Intellectual disabilities. D, Developmental disorders. E, Behavioral disorders.
Figure 3.
Figure 3.. Associations Between Maternal Diabetes During Pregnancy and Psychiatric Disorders in Offspring During the First 4 Decades of Life
Model 1 indicates unadjusted; model 2, adjusted for maternal and paternal history of psychiatric disorder, and calendar year of birth; and model 3, adjusted for sex, singleton status, maternal characteristics (parity, educational level, smoking, cohabitation, residence, age). GDM indicates gestational diabetes; HR, hazard ratio; and PGDM, pregestational diabetes.
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References

    1. McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P. Gestational diabetes mellitus. Nat Rev Dis Primers. 2019;5(1):47. doi:10.1038/s41572-019-0098-8 - DOI - PubMed
    1. Wan H, Zhang C, Li H, Luan S, Liu C. Association of maternal diabetes with autism spectrum disorders in offspring: a systemic review and meta-analysis. Medicine (Baltimore). 2018;97(2):e9438. doi:10.1097/MD.0000000000009438 - DOI - PMC - PubMed
    1. Ornoy A, Reece EA, Pavlinkova G, Kappen C, Miller RK. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Res C Embryo Today. 2015;105(1):53-72. doi:10.1002/bdrc.21090 - DOI - PubMed
    1. Rivera HM, Christiansen KJ, Sullivan EL. The role of maternal obesity in the risk of neuropsychiatric disorders. Front Neurosci. 2015;9:194-194. doi:10.3389/fnins.2015.00194 - DOI - PMC - PubMed
    1. Wang X, Lu J, Xie W, et al. . Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2. Proc Natl Acad Sci U S A. 2019;116(47):23743-23752. doi:10.1073/pnas.1912625116 - DOI - PMC - PubMed

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