, Volume 62, Issue 9, pp 1561–1574 | Cite as

Neurocognitive and behavioural outcomes in offspring exposed to maternal pre-existing diabetes: a systematic review and meta-analysis

  • Jennifer M. YamamotoEmail author
  • Jamie L. Benham
  • Deborah Dewey
  • J. Johanna Sanchez
  • Helen R. Murphy
  • Denice S. Feig
  • Lois E. Donovan



We performed a systematic review and meta-analysis to determine whether exposure to maternal pre-existing diabetes in pregnancy is associated with neurocognitive or behavioural outcomes in offspring.


We searched MEDLINE, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews and Scopus for studies that examined any neurocognitive or behavioural outcomes in offspring of mothers with pre-existing diabetes in pregnancy in accordance with a published protocol (PROSPERO CRD42018109038). Title and abstract review, full-text review and data extraction were performed independently and in duplicate. Risk of bias was assessed using the Newcastle–Ottawa scale. Meta-analyses of summary measures were performed using random-effects models.


Nineteen articles including at least 18,681 exposed and 2,856,688 control participants were identified for inclusion. Exposure to maternal pre-existing diabetes in pregnancy was associated with a lower pooled intelligence quotient in the offspring (pooled weighted mean difference −3.07 [95% CI −4.59, −1.55]; I2 = 0%) and an increased risk of autism spectrum disorders (effect estimate 1.98 [95% CI 1.46, 2.68]; I2 = 0%). There was also an increased risk of attention deficit/hyperactivity disorder (pooled HR 1.36 [95% CI 1.19, 1.55]; I2 = 0%), though this was based on only two studies. Although most studies were found to be high quality in terms of participant selection, in many studies, comparability of cohorts and adequacy of follow-up were sources of bias.


There is evidence to suggest that in utero exposure to maternal pre-existing diabetes is associated with some adverse neurocognitive and behavioural outcomes. It remains unclear what the role of perinatal factors is and the degree to which other environmental factors contribute to these findings.


ADHD ASD Autism Behaviour Childhood Diabetes IQ Meta-analysis Neurocognitive Offspring Pregnancy Systematic review 



Attention deficit/hyperactivity disorder


Autism spectrum disorder


General Certificate of Secondary Education


Intelligence quotient


Risk ratio



The authors would like to thank H. L. Robertson (University of Calgary, Calgary, Canada) for her expert advice in developing our search strategy. We also thank L. Lau (University of Calgary, Calgary, Canada) for her contribution to data extraction.

Contribution statement

JMY, JLB, LED, DSF, HRM, JJS and DD conceived and designed the study. JMY and JLB performed the search, data extraction and data analysis. JMY wrote the initial manuscript draft. JMY, JLB, LED, DSF, HRM, JJS and DD all participated in the critical revision of the manuscript for important intellectual content and approved the final version. JMY is the guarantor of this work, had full access to all of the study data and takes responsibility for the integrity of the data.


This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2019_4923_MOESM1_ESM.pdf (170 kb)
ESM (PDF 170 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicine, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  2. 2.Department of Obstetrics and Gynecology, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  3. 3.Alberta Children’s Hospital Research Institute, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  4. 4.Department of Community Health Sciences, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  5. 5.Department of Paediatrics, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  6. 6.Owerko Centre at the Alberta Children’s Hospital Research Institute, Cumming School of MedicineUniversity of CalgaryCalgaryCanada
  7. 7.Sunnybrook Research InstituteTorontoCanada
  8. 8.Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation TrustCambridgeUK
  9. 9.Women’s Health Academic Centre, Division of Women’s and Children’s HealthKing’s College LondonLondonUK
  10. 10.Norwich Medical SchoolUniversity of East AngliaNorwichUK
  11. 11.Mount Sinai HospitalTorontoCanada
  12. 12.Lunenfeld-Tanenbaum Research InstituteTorontoCanada
  13. 13.Department of MedicineUniversity of TorontoTorontoCanada

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