Neurocognitive and behavioural outcomes in offspring exposed to maternal pre-existing diabetes: a systematic review and meta-analysis
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.
KeywordsADHD 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
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.
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.
- 2.Murphy HR, Bell R, Cartwright C et al (2017) Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study. Diabetologia 60(9):1668–1677. https://doi.org/10.1007/s00125-017-4314-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Macintosh MC, Fleming KM, Bailey JA et al (2006) Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ 333(7560):177. https://doi.org/10.1136/bmj.38856.692986.AE CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Camprubi Robles M, Campoy C, Garcia Fernandez L, Lopez-Pedrosa JM, Rueda R, Martin MJ (2015) Maternal diabetes and cognitive performance in the offspring: a systematic review and meta-analysis. PLoS One 10(11):e0142583. https://doi.org/10.1371/journal.pone.0142583 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012. https://doi.org/10.1001/jama.283.15.2008 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Wells G, Shae B, O’Connell D et al. (2013) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 22 Aug 2018
- 28.Persson B, Gentz J (1984) Follow-up of children of insulin-dependent and gestational diabetic mothers. Neuropsychological outcome. Acta Paediatr Scand 73(3):349–358. https://doi.org/10.1111/j.1651-2227.1994.tb17747.x CrossRefPubMedGoogle Scholar
- 31.Potharst ES, Houtzager BA, van Sonderen L et al (2012) Prediction of cognitive abilities at the age of 5 years using developmental follow-up assessments at the age of 2 and 3 years in very preterm children. Dev Med Child Neurol 54(3):240–246. https://doi.org/10.1111/j.1469-8749.2011.04181.x CrossRefPubMedGoogle Scholar