Gestational Diabetes and Neurodevelopment: Unraveling the Link to Autism and ADHD

Introduction

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide, characterized by glucose intolerance that first appears during pregnancy. Its prevalence is rising globally due to increasing maternal age, obesity, and sedentary lifestyle patterns (American Diabetes Association, 2023). Traditionally, the focus has been on maternal outcomes and risks such as preeclampsia, cesarean delivery, and progression to type 2 diabetes postpartum. However, an emerging body of research highlights that GDM may also have long-term consequences for offspring neurodevelopment, particularly an increased risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).

A large meta-analysis presented at the European Association for the Study of Diabetes (EASD) 2025 annual meeting and summarized in Nature reviewed data from 48 studies covering more than nine million pregnancies and found a significant association between maternal GDM and risk of ASD and ADHD in offspring (Nature, 2025a). These findings bring renewed attention to the complex interplay between maternal metabolic health and fetal brain development.

The Evidence: A Closer Look

The meta-analysis by S. Lai and colleagues (2025) reported that children born to mothers with GDM were:

• 56% more likely to be diagnosed with ASD (pooled risk ratio: ~1.56, 95% CI varies by study)

• 36% more likely to be diagnosed with ADHD

• More likely to have lower IQ scores compared with children born to mothers without GDM

These results align with another major systematic review published in The Lancet Diabetes & Endocrinology earlier this year, which included data from over 56 million mother-child pairs and similarly concluded that maternal diabetes of any type (type 1, type 2, or GDM) increases the risk of neurodevelopmental disorders (Xu et al., 2025).

It is worth noting that these associations were observed across multiple populations and remained significant even after adjusting for common confounders such as maternal age, socioeconomic status, and pre-pregnancy BMI.

Biological Plausibility: How Could GDM Affect the Fetal Brain?

Several mechanisms have been proposed to explain the observed associations between GDM and neurodevelopmental disorders:

1. Hyperglycemia-Induced Oxidative Stress:
   Elevated maternal blood glucose levels can lead to oxidative stress and inflammatory responses in the placenta, which may disrupt the fetal brain’s microenvironment (Catalano & Shankar, 2017).

2. Altered Placental Function:
   GDM is associated with changes in placental nutrient transport and hormonal signaling, potentially affecting fetal insulin levels and neuronal growth (Desoye & Nolan, 2016).

3. Epigenetic Modifications:
   Maternal hyperglycemia has been shown to induce DNA methylation and histone modifications in key neurodevelopmental genes, leading to long-lasting changes in gene expression (Ruchat et al., 2013).

4. Maternal-Fetal Immune Crosstalk:
   Low-grade chronic inflammation seen in GDM may influence neuroimmune development, a pathway increasingly implicated in ASD pathophysiology (Estes & McAllister, 2016).

These mechanisms are not mutually exclusive and likely interact, making GDM a complex, multifactorial risk factor for neurodevelopmental outcomes.

Limitations of the Evidence

While the findings are compelling, several limitations must be considered before inferring causality:

• Observational Nature: Most studies are cohort or case-control designs; therefore, they cannot establish direct cause-effect relationships (Nature, 2025a).

• Residual Confounding: Despite statistical adjustments, confounders such as parental genetics, environmental exposures, and maternal nutrition may still influence outcomes.

• Heterogeneity in GDM Definitions: Diagnostic criteria for GDM differ across countries, which can lead to variability in reported associations.

• Publication Bias: Studies with null findings may be underrepresented in the literature.

Therefore, while the evidence supports an association, it stops short of proving that controlling GDM will directly reduce ASD/ADHD incidence — randomized controlled trials or well-designed interventional studies would be needed to confirm this.

Clinical and Public Health Implications

The implications of these findings are significant given that GDM affects 6–15% of pregnancies worldwide (International Diabetes Federation, 2024). The take-home messages for clinicians and expectant mothers include:

• Early Screening: Universal or risk-based screening for GDM (usually at 24–28 weeks gestation) remains crucial.

• Optimal Management: Lifestyle modifications (balanced diet, moderate exercise) and pharmacotherapy when necessary (e.g., insulin or metformin) can improve maternal glycemic control and possibly mitigate downstream risks.

• Postpartum Follow-Up: Women with GDM should receive follow-up testing for type 2 diabetes and counseling on lifestyle measures.

• Child Developmental Surveillance: Offspring of GDM pregnancies may benefit from early developmental screening to enable timely intervention if neurodevelopmental delays are detected.

Future Directions

More research is needed to:

• Determine whether tight glycemic control during pregnancy can reduce neurodevelopmental risk.

• Identify critical windows of vulnerability during fetal development (e.g., early vs. late pregnancy hyperglycemia).

• Explore genetic susceptibilities that may interact with maternal hyperglycemia.

• Conduct studies in low- and middle-income countries where data are limited but GDM prevalence is rising rapidly.

Such research could guide the development of targeted interventions, including nutritional strategies, pharmacological therapies, and public health policies.

Conclusion

The latest large-scale analyses reinforce the idea that gestational diabetes is not just a maternal health concern but also a determinant of the child’s long-term neurodevelopmental health. While these associations should not cause undue alarm, they highlight the importance of preventing, diagnosing, and managing GDM as part of comprehensive maternal-fetal care. Addressing maternal metabolic health could be a powerful way to promote healthy brain development for the next generation.

References

• American Diabetes Association (2023). Standards of Medical Care in Diabetes—2023. Diabetes Care, 46(Suppl 1): S1–S291.

• Catalano PM, Shankar K. (2017). Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ, 356:j1.

• Desoye G, Nolan CJ. (2016). The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy. Diabetologia, 59(6):1089–1094.

• Estes ML, McAllister AK. (2016). Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci, 16(8):469–486.

• Ruchat SM et al. (2013). Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics, 8(9):935–943.

• Xu L et al. (2025). Maternal diabetes and risk of neurodevelopmental disorders in offspring: a systematic review and meta-analysis. Lancet Diabetes Endocrinol.

• Nature. (2025a). Gestational diabetes linked to autism in study: what scientists say. Nature News (September 2025).

Author Details

Dr. Mainak Mukhopadhyay

Associate Professor

Department of Biosciences

JIS University, Kolkata

(Ph.D. from Indian Institute of Technology Kharagpur, 2014)

Google Scholar Profile: https://scholar.google.com/citations?user=7mKAs4UAAAAJ&hl=en