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Maternal Hyperglycemia in Pregnancy and Offspring Internalizing and Externalizing Behaviors

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Abstract

Objective

To examine the associations between exposure to gestational diabetes mellitus (GDM) and maternal glycemic markers during pregnancy and offspring behaviors at 3 and 5 years. We hypothesized that exposure to maternal hyperglycemia would be associated with more behavioral problems in offspring.

Methods

We included 548 mother–child pairs from the prospective pre-birth Gen3G cohort (Canada). Glycemic markers were measured during a 75 g oral glucose tolerance test (OGTT) in the second trimester of pregnancy. Based on OGTT, we classified 59 women (10.8%) as having GDM according to international diagnostic criteria. Mothers reported offspring behavior using the Strengths and Difficulties Questionnaire (SDQ) at 3 and 5 years, and the Child Behavior Checklist (CBCL) at 5 years. We used linear mixed models and multivariate regression to assess the associations between GDM or glycemic markers and children's behavior, adjusted for child sex and age, and maternal demographic factors, body mass index and family history of diabetes.

Results

Exposure to GDM was associated with higher SDQ externalizing scores at 3 and 5 years [B = 1.12, 95% CI (0.14, 2.10)] in fully adjusted linear mixed models. These results were supported by the CBCL at 5 years. Higher levels of maternal glucose at 1 h and 2 h during OGTT were associated with greater SDQ externalizing scores. Fasting glucose levels were not associated with child behavior scores. We did not observe associations between glycemic markers and internalizing behaviors.

Conclusions

Exposure to higher levels of maternal glycemia during pregnancy was associated with more externalizing behaviors in children at 3 and 5 years.

Significance

What is already known on this subject? Prenatal exposure to gestational diabetes mellitus (GDM) has been linked to a higher risk of long-term consequences in offspring including metabolic problems and cognitive difficulties. However, prior studies examining associations between GDM and behavior in children reported mixed results.

What this study adds? We reported associations between exposure to maternal GDM and post-OGTT hyperglycemia during pregnancy and greater levels of externalizing behaviors in children at 3 and 5 years of age. Our results underscore the importance of early detection of behavioral problems in children.

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Data Availability

Data can be made available on request.

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References

  • Achenbach, T. M., & Rescorla, L. A. (2000). Manual for the ASEBA preschool forms and profiles. University of Vermont, Research Center for Children, Youth, & Families.

  • Adane, A. A., Mishra, G. D., & Tooth, L. R. (2016). Diabetes in pregnancy and childhood cognitive development: A systematic review. Pediatrics, 137(5), e20154234. https://doi.org/10.1542/peds.2015-4234

    Article  PubMed  Google Scholar 

  • Barbour, L. (2003). New concepts in insulin resistance of pregnancy and gestational diabetes: Long-term implications for mother and offspring. Journal of Obstetrics and Gynaecology, 23(5), 545–549. https://doi.org/10.1080/0144361031000156500

    Article  CAS  PubMed  Google Scholar 

  • Barker, D. J. P. (2007). The origins of the developmental origins theory. Journal of Internal Medicine, 261(5), 412–417. https://doi.org/10.1111/j.1365-2796.2007.01809.x

    Article  CAS  PubMed  Google Scholar 

  • Bellanti, C. J., & Bierman, K. L. (2000). Disentangling the impact of low cognitive ability and inattention on social behavior and peer relationships. Journal of Clinical Child Psychology, 29(1), 66–75. https://doi.org/10.1207/S15374424jccp2901_7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boney, C. M., Verma, A., Tucker, R., & Vohr, B. R. (2005). Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics, 115(3), e290. https://doi.org/10.1542/peds.2004-1808

    Article  PubMed  Google Scholar 

  • Bongers, I. L., Koot, H. M., van der Ende, J., & Verhulst, F. C. (2004). Developmental trajectories of externalizing behaviors in childhood and adolescence. Child Development, 75(5), 1523–1537.

    Article  PubMed  Google Scholar 

  • Bonora, E., Targher, G., Alberiche, M., Bonadonna, R. C., Saggiani, F., Zenere, M. B., Monauni, T., & Muggeo, M. (2000). Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: Studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care, 23(1), 57–63.

    Article  CAS  PubMed  Google Scholar 

  • Breton, E., Gagné-Ouellet, V., Thibeault, K., Guérin, R., Van Lieshout, R., Perron, P., Hivert, M., & Bouchard, L. (2020). Placental NEGR1 DNA methylation is associated with BMI and neurodevelopment in preschool-age children. Epigenetics, 15(3), 323–335. https://doi.org/10.1080/15592294.2019.1666653

    Article  CAS  PubMed  Google Scholar 

  • Capron, C., Thérond, C., & Duyme, M. (2007). Psychometric properties of the French version of the self-report and teacher Strengths and Difficulties Questionnaire (SDQ). European Journal of Psychological Assessment, 23(2), 79–88. https://doi.org/10.1027/1015-5759.23.2.79

    Article  Google Scholar 

  • Chiu, Y. N., Gau, S. S. F., Tsai, W. C., Soong, W. T., & Shang, C. Y. (2009). Demographic and perinatal factors for behavioral problems among children aged 4–9 in Taiwan. Psychiatry and Clinical Neurosciences, 63(4), 569–576. https://doi.org/10.1111/j.1440-1819.2009.01979.x

    Article  PubMed  Google Scholar 

  • Daley, D., & Birchwood, J. (2010). ADHD and academic performance: Why does ADHD impact on academic performance and what can be done to support ADHD children in the classroom? Child: Care Health and Development, 36(4), 455–464. https://doi.org/10.1111/j.1365-2214.2009.01046.x

    Article  CAS  PubMed  Google Scholar 

  • Daraki, V., Roumeliotaki, T., Koutra, K., Georgiou, V., Kampouri, M., Kyriklaki, A., Vafeiadi, M., Papavasiliou, S., Kogevinas, M., & Chatzi, L. (2017). Effect of parental obesity and gestational diabetes on child neuropsychological and behavioral development at 4 years of age: The Rhea mother–child cohort, Crete, Greece. European Child and Adolescent Psychiatry, 26(6), 703–714. https://doi.org/10.1007/s00787-016-0934-2

    Article  PubMed  Google Scholar 

  • Gao, Q., & Gao, Y. M. (2007). Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord. International Journal of Developmental Neuroscience, 25(6), 349–357. https://doi.org/10.1016/j.ijdevneu.2007.08.002

    Article  CAS  PubMed  Google Scholar 

  • Ghandour, R. M., Sherman, L. J., Vladutiu, C. J., Ali, M. M., Lynch, S. E., Bitsko, R. H., & Blumberg, S. J. (2019). Prevalence and treatment of depression, anxiety, and conduct problems in US children. Journal of Pediatrics, 206, 256–267. https://doi.org/10.1016/j.jpeds.2018.09.021

    Article  PubMed  Google Scholar 

  • Goodman, R. (2001). Psychometric properties of the strengths and difficulties questionnaire. Journal of the American Academy of Child & Adolescent Psychiatry, 40(11), 1337–1345. https://doi.org/10.1097/00004583-200111000-00015

    Article  CAS  Google Scholar 

  • Guillemette, L., Allard, C., Lacroix, M., Patenaude, J., Battista, M. C., Doyon, M., Moreau, J., Ménard, J., Bouchard, L., Ardilouze, J. L., Perron, P., & Hivert, M. F. (2016). Genetics of Glucose regulation in Gestation and Growth (Gen3G): A prospective prebirth cohort of mother-child pairs in Sherbrooke, Canada. British Medical Journal Open, 6(2), e010031. https://doi.org/10.1136/bmjopen-2015-010031

    Article  Google Scholar 

  • Guo, D., Ju, R., Zhou, Q., Mao, J., Tao, H., Jing, H., Zhu, C., & Dai, J. (2020). Association of maternal diabetes with attention deficit/hyperactivity disorder (ADHD) in offspring: A meta-analysis and review. Diabetes Research and Clinical Practice, 165, 108269. https://doi.org/10.1016/j.diabres.2020.108269

    Article  PubMed  Google Scholar 

  • Howe, C. G., Cox, B., Fore, R., Jungius, J., Kvist, T., Lent, S., Miles, H. E., Salas, L. A., Rifas-Shiman, S., Starling, A. P., Yousefi, P., Ladd-Acosta, C., Baccarelli, A., Binder, E. B., Chatzi, V. L., Czamara, D., Dabelea, D., DeMeo, D. L., Ghantous, A., … v. (2020). Maternal gestational diabetes mellitus and newborn DNA methylation: Findings from the pregnancy and childhood epigenetics consortium. Diabetes Care, 43(1), 98–105. https://doi.org/10.2337/dc19-0524

    Article  CAS  PubMed  Google Scholar 

  • International Association of Diabetes. (2010). International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care, 33(3), 676–682.

    Article  Google Scholar 

  • Ivanova, M. Y., Achenbach, T. M., Rescorla, L. A., Harder, V. S., Ang, R. P., Bilenberg, N., Bjarnadottir, G., Capron, C., De Pauw, S. S. W., Dias, P., Dobrean, A., Doepfner, M., Duyme, M., Eapen, V., Erol, N., Esmaeili, E. M., Ezpeleta, L., Frigerio, A., Gonçalves, M. M., … Verhulst, F. C. (2010). Preschool psychopathology reported by parents in 23 societies: Testing the seven-syndrome model of the child behavior checklist for ages 1.5–5. Journal of the American Academy of Child & Adolescent Psychiatry, 49(12), 1215–1224.

    Google Scholar 

  • Kanney, N., Patki, A., Chandler-Laney, P., Garvey, W. T., & Hidalgo, B. A. (2022). Epigenetic age acceleration in mothers and offspring 4–10 years after a pregnancy complicated by gestational diabetes and obesity. Metabolites. https://doi.org/10.3390/metabo12121226

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim, C., Harrall, K. K., Glueck, D. H., Needham, B. L., & Dabelea, D. (2022). Gestational diabetes mellitus, epigenetic age and offspring metabolism. Diabetic Medicine. https://doi.org/10.1111/dme.14925

    Article  PubMed  PubMed Central  Google Scholar 

  • Kirwan, J. P., Huston-Presley, L., Kalhan, S. C., & Catalano, P. M. (2001). Clinically useful estimates of insulin sensitivity during pregnancy: Validation studies in women with normal glucose tolerance and gestational diabetes mellitus. Diabetes Care, 24(9), 1602–1607. https://doi.org/10.2337/diacare.24.9.1602

    Article  CAS  PubMed  Google Scholar 

  • Kong, L., Chen, X., Gissler, M., & Lavebratt, C. (2020). Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: A narrative review. International Journal of Obesity, 44(10), 1981–2000. https://doi.org/10.1038/s41366-020-0609-4

    Article  PubMed  Google Scholar 

  • Krzeczkowski, J. E., Lau, A., Fitzpatrick, J., Tamana, S., Smithson, L., de Souza, R., Kozyrskyj, A. L., Lefebvre, D., Becker, A. B., Subbarao, P., Turvey, S. E., Pei, J., Schmidt, L. A., Sears, M. R., van Lieshout, R. J., Mandhane, P. J., CHILD Study Investigators. (2019). Maternal metabolic complications in pregnancy and offspring behavior problems at 2 years of age. Maternal and Child Health Journal, 23(6), 746–755. https://doi.org/10.1007/s10995-018-2691-y

    Article  PubMed  Google Scholar 

  • Lippert, R. N., & Brüning, J. C. (2021). Maternal metabolic programming of the developing central nervous system: Unified pathways to metabolic and psychiatric disorders. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2021.06.002

    Article  PubMed  Google Scholar 

  • Mack, L. R., & Tomich, P. G. (2017). Gestational diabetes: Diagnosis, classification, and clinical Care. Obstetrics and Gynecology Clinics of North America, 44(2), 207–217. https://doi.org/10.1016/j.ogc.2017.02.002

    Article  PubMed  Google Scholar 

  • Matsuda, M., & DeFronzo, R. A. (1999). Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care, 22(9), 1462–1470. https://doi.org/10.2337/diacare.22.9.1462

    Article  CAS  PubMed  Google Scholar 

  • McQuade, J. D., & Hoza, B. (2008). Peer problems in attention deficit hyperactivity disorder: Current status and future directions. Developmental Disabilities Research Reviews, 14(4), 320–324. https://doi.org/10.1002/ddrr.35

    Article  PubMed  Google Scholar 

  • Metzger, B. E., Lowe, L. P., Dyer, A. R., Trimble, E. R., Sheridan, B., Hod, M., Chen, R., Yogev, Y., Coustan, D. R., Catalano, P. M., et al. (2008). Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics. Diabetes. https://doi.org/10.2337/db08-1112

    Article  Google Scholar 

  • Moyer, V. A. (2014). Screening for gestational diabetes mellitus: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine, 160(6), 414–420. https://doi.org/10.7326/M13-2905

    Article  PubMed  Google Scholar 

  • Nomura, Y., Marks, D. J., Grossman, B., Yoon, M., Loudon, H., Stone, J., & Halperin, J. M. (2012). Exposure to gestational diabetes mellitus and low socioeconomic status: Effects on neurocognitive development and risk of attention-deficit/ hyperactivity disorder in offspring. Archives of Pediatrics and Adolescent Medicine, 166(4), 337–343. https://doi.org/10.1001/archpediatrics.2011.784

    Article  PubMed  Google Scholar 

  • Polanczyk, G. V., Salum, G. A., Sugaya, L. S., Caye, A., & Rohde, L. A. (2015). Annual research review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents. Journal of Child Psychology and Psychiatry and Allied Disciplines, 56(3), 345–365. https://doi.org/10.1111/jcpp.12381

    Article  PubMed  Google Scholar 

  • Riglin, L., Petrides, K. V., Frederickson, N., & Rice, F. (2014). The relationship between emotional problems and subsequent school attainment: A meta-analysis. Journal of Adolescence, 37(4), 335–346. https://doi.org/10.1016/j.adolescence.2014.02.010

    Article  PubMed  Google Scholar 

  • Scholtens, D. M., & Metzger, B. E. (2019). Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal glycemia and childhood glucose metabolism. Diabetes Care, 42(7), E128–E129. https://doi.org/10.2337/dci19-0024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willoughby, M. T. (2003). Developmental course of ADHD symptomatology during the transition from childhood to adolescence: A review with recommendations. Journal of Child Psychology and Psychiatry, 1, 88–106.

    Article  Google Scholar 

  • Xu, T., Faleschini, S., Rifas-Shiman, S. L., Monthé-Drèze, C., Oken, E., Hivert, M.-F., & Tiemeier, H. (2021). Maternal glucose tolerance in pregnancy and child cognitive and behavioural problems in early and mid-childhood. Paediatric and Perinatal Epidemiology, 35(1), 109–119. https://doi.org/10.1111/ppe.12710

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank the participants of the Gen3G cohort and Chamaine Washington for the English language revision.

Funding

This work was supported by a Fonds de recherche du Québec—Santé (FRQS) operating grant (to M-FH, grant #20697); a Canadian Institute of Health Research (CIHR) operating grant (to M-FH grant #MOP 115071 and to LB #PJT-152989); a Diabète Québec grant (to PP) and a Fonds de Recherche du Québec—Société et culture (FRQSC) postdoctoral fellowship award (to SF). LB is a senior research scholar from the FRQS. JFL is a junior II scholar from the FRQS.

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Authors and Affiliations

  1. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA

    Sabrina Faleschini & Marie-France Hivert

  2. Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada

    Myriam Doyon, Mélina Arguin, Patrice Perron, Luigi Bouchard & Marie-France Hivert

  3. Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada

    Jean-François Lepage

  4. Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, MA, USA

    Henning Tiemeier

  5. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, L8S 4L8, Canada

    Ryan J. Van Lieshout

  6. Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada

    Patrice Perron

  7. Clinical Department of Laboratory Medicine, CIUSSS du Saguenay-Lac-St-Jean – Hôpital de Chicoutimi, Chicoutimi, QC, G7H 7K9, Canada

    Luigi Bouchard

  8. Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada

    Luigi Bouchard

  9. Diabetes Unit, Massachusetts General Hospital, Boston, MA, 02114, USA

    Marie-France Hivert

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  1. Sabrina Faleschini
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  2. Myriam Doyon
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  3. Mélina Arguin
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  4. Jean-François Lepage
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  5. Henning Tiemeier
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  6. Ryan J. Van Lieshout
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  7. Patrice Perron
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  8. Luigi Bouchard
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  9. Marie-France Hivert
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Contributions

M-FH, HT, LB and PP conceptualized and designed the study, and critically reviewed the manuscript for important intellectual content. SF drafted the initial manuscript, carried out statistical analysis, and revised the manuscript with inputs of all other co-authors. MD and MA coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. J-FL and RJVL critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Marie-France Hivert.

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Authors declare that they have no conflict of interest.

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All study protocols were approved by the institutional review board from the Centre Hospitalier Universitaire de Sherbrooke.

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Faleschini, S., Doyon, M., Arguin, M. et al. Maternal Hyperglycemia in Pregnancy and Offspring Internalizing and Externalizing Behaviors. Matern Child Health J 27, 1765–1773 (2023). https://doi.org/10.1007/s10995-023-03706-4

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