Population Study Article | Published:

Neonatal regulatory behavior problems are predicted by maternal early pregnancy overweight and obesity: findings from the prospective PREDO Study

Pediatric Researchvolume 84pages875881 (2018) | Download Citation




Maternal overweight/obesity and comorbid hypertensive disorders and gestational diabetes associate with neurodevelopmental delay in the offspring in childhood. We hypothesize that these maternal conditions associate also with the offspring regulatory behavior problems and impact on neurodevelopment via the offspring regulatory behavior.


A number of 3117 women of the PREDO Study filled in a questionnaire on regulatory behavior problems at the child’s mean age of 16.9 days and 2116 of them a questionnaire on developmental milestones at the child’s mean age of 42.2 months. Data on maternal BMI and comorbid disorders come from the Finnish Medical Birth Register.


Offspring of overweight/obese mothers in comparison to normal weight mothers had higher levels of regulatory behavior problems and 22% (95% confidence interval 5–42%) higher odds of having problems on multiple domains of behavioral regulation at the mean age of 16.9 days. Offspring regulatory behavior problems partially mediated the association between maternal overweight/obesity and developmental milestones comprising communication, gross motor, fine motor, problem solving, and personal/social domains of development. Comorbid disorders did not associate with offspring regulatory behavior problems.


Regulatory behavior problems of the offspring have prenatal origins and partially mediate the effects of maternal overweight/obesity on offspring neurodevelopment.

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  1. 1.

    Hemmi, M. H., Wolke, D. & Schneider, S. Associations between problems with crying, sleeping and/or feeding in infancy and long-term behavioural outcomes in childhood: a meta-analysis. Arch. Dis. Child 96, 622–629 (2011).

  2. 2.

    Becker, K. et al. Are regulatory problems in infancy precursors of later hyperkinetic symptoms? Acta Paediatr. 93, 1463–1469 (2004).

  3. 3.

    Liu, J. et al. Neonatal neurobehavior predicts medical and behavioral outcome. Pediatrics 125, e90–e98 (2010).

  4. 4.

    Schmid, G. et al. A prospective study on the persistence of infant crying, sleeping and feeding problems and preschool behaviour. Acta Paediatr. 99, 286–290 (2010).

  5. 5.

    Thunstrom, M. Severe sleep problems in infancy associated with subsequent development of attention-deficit/hyperactivity disorder at 5.5 years of age. Acta Paediatr. 91, 584–592 (2002).

  6. 6.

    Wolke, D., Rizzo, P. & Woods, S. Persistent infant crying and hyperactivity problems in middle childhood. Pediatrics 109, 1054–1060 (2002).

  7. 7.

    Barnevik Olsson, M. et al. Autism before diagnosis: crying, feeding and sleeping problems in the first two years of life. Acta Paediatr. 102, 635–639 (2013).

  8. 8.

    Wolke, D. et al. Crying and feeding problems in infancy and cognitive outcome in preschool children born at risk: a prospective population study. J. Dev. Behav. Pediatr. 30, 226–238 (2009).

  9. 9.

    Rao, M. R. et al. Long term cognitive development in children with prolonged crying. Arch. Dis. Child 89, 989–992 (2004).

  10. 10.

    Bilgin, A. & Wolke, D. Regulatory problems in very preterm and full-term infants over the first 18 months. J. Dev. Behav. Pediatr. 37, 298–305 (2016).

  11. 11.

    Goldenberg, R. L. et al. Epidemiology and causes of preterm birth. Lancet 371, 75–84 (2008).

  12. 12.

    Rodriguez, A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J. Child Psychol. Psychiatry 51, 134–143 (2010).

  13. 13.

    Jo, H. et al. Maternal prepregnancy body mass index and child psychosocial development at 6 years of age. Pediatrics 135, e1198–e1209 (2015).

  14. 14.

    Krakowiak, P. et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 129, e1121–e1128 (2012).

  15. 15.

    Girchenko, P., et al., Maternal early pregnancy obesity and related pregnancy and pre-pregnancy disorders: associations with child developmental milestones in the prospective PREDO Study. Int. J. Obes. 42, 995–1007 (2018).

  16. 16.

    Rivera, H. M., Christiansen, K. J. & Sullivan, E. L. The role of maternal obesity in the risk of neuropsychiatric disorders. Front. Neurosci. 9, 194 (2015).

  17. 17.

    Aubuchon-Endsley, N., et al. Maternal pre-pregnancy obesity and gestational weight gain influence neonatal neurobehaviour. Matern. Child Nutr. 13:e12317 (2016).

  18. 18.

    Girchenko, P. et al. Cohort profile: prediction and prevention of preeclampsia and intrauterine growth restriction (PREDO) study. Int. J. Epidemiol. 46, 1380–1381g (2017).

  19. 19.

    Gissler, M. Finnish health and social welfare registers in epidemiological research. Nor. Epidemiol. 14, 113–120 (2004).

  20. 20.

    Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ. Tech. Rep. Ser. 894 i-xii, 1–253 (2000).

  21. 21.

    Broussard, E. R. & Hartner, M. S. Maternal perception of the neonate as related to development. Child Psychiatry Hum. Dev. 1, 16–25 (1970).

  22. 22.

    Povedano, N. & Pinheiro, G., Mother’s perceptions and expectations regarding their newborn infants: the use of Broussard’s neonatal perception inventory. Rev. Paul. Pediatr. 29 vol.29, n.2 (2011).

  23. 23.

    Raikkonen, K. et al. Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors. Psychol. Med. 45, 3217–3226 (2015).

  24. 24.

    Squires, J., Bricker, D. & Potter, L. Revision of a parent-completed development screening tool: Ages and Stages Questionnaires. J. Pediatr. Psychol. 22, 313–328 (1997).

  25. 25.

    Bricker, D. et al. The validity, reliability, and cost of a parent-completed questionnaire system to evaluate at-risk infants. J. Pediatr. Psychol. 13, 55–68 (1988).

  26. 26.

    Charkaluk, M. L., et al. Ages and Stages Questionnaire at 3 years for predicting IQ at 5-6 years. Pediatrics 139 vol 139 n.4 (2017).

  27. 27.

    Hayes, A. F. & Rockwood, N. J. Regression-based statistical mediation and moderation analysis in clinical research: observations, recommendations, and implementation. Behav. Res. Ther. 98, 39–57 (2016).

  28. 28.

    Schmid, G. et al. Predictors of crying, feeding and sleeping problems: a prospective study. Child Care Health Dev. 37, 493–502 (2011).

  29. 29.

    Wolf, M. J. et al. Neurobehavioral and developmental profile of very low birthweight preterm infants in early infancy. Acta Paediatr. 91, 930–938 (2002).

  30. 30.

    Bilgin, A. & Wolke, D. Development of comorbid crying, sleeping, feeding problems across infancy: Neurodevelopmental vulnerability and parenting. Early Hum. Dev. 109, 37–43 (2017).

  31. 31.

    Gillman, M. W. Developmental origins of health and disease. N. Engl. J. Med. 353, 1848–1850 (2005).

  32. 32.

    Jing, Y. H. et al. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals. Int J. Dev. Neurosci. 37, 15–20 (2014).

  33. 33.

    Borre, Y. E. et al. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol. Med 20, 509–518 (2014).

  34. 34.

    Neri, C. & Edlow, A. G. Effects of maternal obesity on fetal programming: molecular approaches. Cold Spring Harb. Perspect. Med 6, a026591 (2015).

  35. 35.

    Catalano, P. M. & Shankar, K. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. Bmj 356, j1 (2017).

  36. 36.

    Nomura, Y. et al. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod. Sci. 21, 131–137 (2014).

  37. 37.

    Cuffe, J. S. M. et al. Review: placental derived biomarkers of pregnancy disorders. Placenta 54, 104–110 (2017).

  38. 38.

    Raikkonen, K. et al. Associations between maternal level of education and occupational status with placental glucocorticoid regeneration and sensitivity. Clin. Endocrinol. 81, 175–182 (2014).

  39. 39.

    Jauniaux, E., Poston, L. & Burton, G. J. Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum. Reprod. Update 12, 747–755 (2006).

  40. 40.

    Malti, N. et al. Oxidative stress and maternal obesity: feto-placental unit interaction. Placenta 35, 411–416 (2014).

  41. 41.

    Marchlewicz, E. H. et al. Lipid metabolism is associated with developmental epigenetic programming. Sci. Rep. 6, 34857 (2016).

  42. 42.

    Jonakait, G. M. The effects of maternal inflammation on neuronal development: possible mechanisms. Int J. Dev. Neurosci. 25, 415–425 (2007).

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The PREDO study would not have been possible without the dedicated contribution of the PREDO Study group members: A. Aitokallio-Tallberg, A.-M. Henry, V.K. Hiilesmaa, T. Karipohja, R. Meri, S. Sainio, T. Saisto, S. Suomalainen-Konig, V.-M. Ulander, T. Vaitilo (Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland), L. Keski-Nisula, Maija-Riitta Orden (Kuopio University Hospital, Kuopio, Finland), E. Koistinen, T. Walle, R. Solja (Northern Karelia Central Hospital, Joensuu, Finland), M. Kurkinen (Päijät-Häme Central Hospital, Lahti, Finland), P. Taipale, P. Staven (Iisalmi Hospital, Iisalmi, Finland), and J. Uotila (Tampere University Hospital, Tampere, Finland). We also thank the PREDO cohort mothers, fathers, and children for their enthusiastic participation. This work was supported by the Academy of Finland (K.R., grant numbers 284859, 2848591, and 312670), (E.K., grant numbers 127437, 129306, 130326, 134791, 263924, and 274794), (H.L., grant numbers 121196, 134957, and 278941), (M.L.-P., grant number 12853241), (A.-K.P.); University of Helsinki Research Funds (M.L.-P.), (H.L.), British Heart Foundation (R.M.R.); Tommy’s (R.M.R.); European Commission (E.K., K.R., Horizon 2020 Award SC1-2016-RTD-733280 RECAP); Foundation for Pediatric Research (E.K.); Juho Vainio Foundation (E.K.); Novo Nordisk Foundation (E.K.); Signe and Ane Gyllenberg Foundation (K.R., E.K.); Sigrid Jusélius Foundation (E.K.); Finnish Medical Foundation (H.L.); Jane and Aatos Erkko Foundation (H.L.); Päivikki and Sakari Sohlberg Foundation (H.L.); and Doctoral Program of Psychology, Learning, and Communication (P.G.).

Author information


  1. Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland

    • Polina Girchenko
    • , Marius Lahti-Pulkkinen
    • , Jari Lahti
    • , Anu-Katriina Pesonen
    •  & Katri Räikkönen
  2. HUSLAB and Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland

    • Esa Hämäläinen
  3. Obstetrics and Gynaecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    • Pia M. Villa
  4. National Institute for Health and Welfare, Helsinki and Oulu, Helsinki, Finland

    • Eero Kajantie
  5. Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    • Hannele Laivuori
  6. Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

    • Rebecca M. Reynolds


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Competing interests

The authors declare that they have no competing interests.

Corresponding author

Correspondence to Polina Girchenko.

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