Diabetes Metab J.  2022 Nov;46(6):912-922. 10.4093/dmj.2021.0340.

Influence of Maternal Diabetes on the Risk of Neurodevelopmental Disorders in Offspring in the Prenatal and Postnatal Periods

• Perea V
• Urquizu X
• Valverde M
• Macias M
• Carmona A
• Esteve E
• Escribano G
• Pons N
• Giménez O
• Gironés T
• Simó-Servat A
• Domenech A
• Alonso-Carril N
• Quirós C
• Amor AJ
• López E
• Barahona MJ

• KMID: 2536149
• DOI: http://doi.org/10.4093/dmj.2021.0340

Abstract

Background
This study aimed to evaluate the influence of maternal diabetes in the risk of neurodevelopmental disorders in offspring in the prenatal and postnatal periods.
Methods
This cohort study included singleton gestational diabetes mellitus (GDM) pregnancies >22 weeks’ gestation with live newborns between 1991 and 2008. The control group was randomly selected and matched (1:2) for maternal age, weeks of gestation and birth year. Cox regression models estimated the effect of GDM on the risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and maternal type 2 diabetes mellitus (T2DM). Moreover, interaction between maternal T2DM and GDM-ADHD relationship was evaluated.
Results
Children (n=3,123) were included (1,073 GDM; 2,050 control group). The median follow-up was 18.2 years (interquartile range, 14.2 to 22.3) (n=323 with ADHD, n=36 with ASD, and n=275 from women who developed T2DM). GDM exposure was associated with ADHD (hazard ratio [HR]_crude, 1.67; 95% confidence interval [CI], 1.33 to 2.07) (HR_adjusted, 1.64; 95% CI, 1.31 to 2.05). This association remained significant regardless of the treatment (diet or insulin) and diagnosis after 26 weeks of gestation. Children of mothers who developed T2DM presented higher rates of ADHD (14.2 vs. 10%, P=0.029). However, no interaction was found when T2DM was included in the GDM and ADHD models (P>0.05). GDM was not associated with an increased risk of ASD (HR_adjusted, 1.46; 95% CI, 0.74 to 2.84).
Conclusion
Prenatal exposure to GDM increases the risk of ADHD in offspring, regardless of GDM treatment complexity. However, postnatal exposure to maternal T2DM was not related to the development of ADHD.

Keyword

Diabetes, gestational; Diabetes mellitus, type 2; Neurodevelopmental disorders

Figure

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  Fig. 1. Flowchart of the cohort of gestational diabetes mellitus (GDM) pregnancies and matched pregnancies including detailed information on the pregnancies excluded. T1DM, type 1 diabetes mellitus.

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  Fig. 2. Crude cumulative incidence of attention-deficit/hyperactivity disorder (ADHD) by diabetes exposure in utero and diagnosis of type 2 diabetes mellitus (T2DM) later in life in their mothers. +/− indicates presence or absence of gestational diabetes mellitus (GDM) or/and T2DM.

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