Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Considering comorbidities: neurodevelopmental implications for children of diabetic mothers

Pediatric Research volume 97, pages 1439–1440 (2025)Cite this article

Access through your institution
Buy or subscribe

It is increasingly recognized that the intrauterine milieu profoundly influences lifelong health, particularly for the developing brain.1 In this issue of Pediatric Research, Nivins et al. investigated neurodevelopmental outcomes in otherwise healthy infants exposed to prenatal maternal diabetes.2 With a robust cohort size of 4863 mother-infant dyads, they were able to assess both the independent and combined effects of maternal diabetes with and without maternal overweight, obesity, or hypertensive disorders of pregnancy (HDP) on neurodevelopmental outcomes at 12–24 months of age. Using the Ages and Stages Questionnaire (ASQ) to assess early child development, prenatal exposure to maternal diabetes alone was not associated with increased risk for adverse outcomes. However, the combination of diabetes with one or more additional maternal comorbid conditions was associated with impaired offspring personal-social skills, communication, and fine motor skills at two years of age. Moreover, this work revealed that diabetic mothers experienced significantly higher rates of comorbid obesity and HDP, as well as depression and anxiety, and reported lower household incomes, highlighting the complexity of prenatal maternal factors that influence early developmental outcomes.

The authors suggest these impairments may reflect abnormal brain development resulting from noxious exposures within the intrauterine environment, including oxidative stress and chronic inflammation, which are significant mechanisms of altered neurodevelopment. Animal studies have shown that prenatal diabetes exposure leads to pathological hormonal and cytokine activation, resulting in sustained neuroinflammation with reactive gliosis and decreased synaptic integrity.3 Human studies have reported mixed results, but many are limited by relatively small sample size and lack of adjustment for confounding from comorbid maternal medical conditions and important sociodemographic factors.4 The study by Nivins et al. addresses many of these limitations by carefully accounting for highly relevant, and potentially more impactful, confounders such as maternal mental health, education, and household income.2 However, studies on prenatal exposures and fetal programming remain vexing because of the paucity of tools to safely measure and assess their specific influences on later neurodevelopment. The largest human studies to date found negative associations between maternal prenatal diabetes and neurodevelopmental outcomes through school age, but were also limited by long intervals between exposures and emerging neuropsychological behaviors and also a lack of adjustment for relevant confounders.4 Recent innovations in quantitative brain magnetic resonance imaging (qMRI) now provide the opportunity for non-invasive, real-time assessment of fetal and neonatal brain development that serve as more proximate markers of prenatal exposure and important predictors for later neurodevelopment.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Amgalan, A., Andescavage, N. & Limperopoulos, C. Prenatal origins of neuropsychiatric diseases. Acta Paediatr. 110, 1741–1749 (2021).

    Article  PubMed  Google Scholar 

  2. Nivins, S., Tomfohr-Madsen, L., Lebel, C. Prenatal maternal diabetes, comorbidities, and risk for neurodevelopmental impairment in the first two years. Pediatr Res. 2024, online ahead of print.

  3. Vuong, B. et al. Exposure to gestational diabetes mellitus induces neuroinflammation, derangement of hippocampal neurons, and cognitive changes in rat offspring. J. Neuroinflammation. 14, 80–89 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Adane, A. A., Mishra, G. D. & Tooth, L. R. Diabetes in pregnancy and childhood cognitive development: A systematic review. Pediatrics 137, e20154234 (2106).

    Article  Google Scholar 

  5. Xuan, D. et al. Brain development in infants of mothers with gestational diabetes mellitus: A diffusion tensor imaging study. J. Comput. Assist Tomogr. 44, 947–952 (2020).

    Article  PubMed  Google Scholar 

  6. Na, X. et al. Maternal obesity during pregnancy is associated with lower cortical thickness in the neonate brain. AJNR Am. J. Neuroradiol. 42, 2238–2244 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ou, X., Thakali, K. M., Shankar, K., Andres, A. & Badger, T. M. Maternal adiposity negatively influences infant brain white matter development. Obesity 23, 1047–1054 (2015).

    Article  CAS  PubMed  Google Scholar 

  8. Figueiró-Filho, E. A. et al. Neurological function in children born to preeclamptic and hypertensive mothers - A systematic review. Pregnancy Hypertens. 10, 1–6 (2017).

    Article  PubMed  Google Scholar 

  9. Wu, Y. et al. Association of prenatal maternal psychological distress with fetal brain growth, metabolism, and cortical maturation. JAMA Netw. Open. 3, e1919940 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cook, K. M. et al. Greater neighborhood disadvantage is associated with alterations in fetal functional brain network structure. J. Pediatr. 274, 114201 (2024).

    Article  PubMed  Google Scholar 

  11. Leonard, S. A., Main, E. K., Scott, K. A., Profit, J. & Carmichael, S. L. Racial and ethnic disparities in severe maternal morbidity prevalence and trends. Ann. Epidemiol. 33, 30–36 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Field C. et al. Social determinants of health and diabetes in pregnancy. Am. J. Perinatol. 2024, online ahead of print.

  13. Demétrio, F., Teles, C. A. S., Santos, D. B. D. & Pereira, M. Food insecurity in pregnant women is associated with social determinants and nutritional outcomes: a systematic review and meta-analysis. Cien Saude Colet. 25, 2663–2676 (2020).

    Article  PubMed  Google Scholar 

  14. Muthusamy, S., Wagh, D., Tan, J., Bulsara, M. & Rao, S. Utility of the ages and stages questionnaire to identify developmental delay in children aged 12 to 60 months: A systematic review and meta-analysis. JAMA Pediatr. 176, 980–989 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Developing Brain Institute, Washington, DC, USA

    Katherine M. Ottolini & Nickie Andescavage

  2. Division of Neonatology, Children’s National Hospital, Washington, DC, USA

    Katherine M. Ottolini & Nickie Andescavage

Authors
  1. Katherine M. Ottolini
    View author publications

    Search author on:PubMed Google Scholar

  2. Nickie Andescavage
    View author publications

    Search author on:PubMed Google Scholar

Contributions

K.M.O. and N.A. both conceptualized, wrote, and critically reviewed this manuscript.

Corresponding author

Correspondence to Katherine M. Ottolini.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ottolini, K.M., Andescavage, N. Considering comorbidities: neurodevelopmental implications for children of diabetic mothers. Pediatr Res 97, 1439–1440 (2025). https://doi.org/10.1038/s41390-024-03764-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41390-024-03764-6

Search

Advanced search

Quick links