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High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother–child cohort, Crete, Greece

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Abstract

Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother–child pairs from the prospective pregnancy cohort, “Rhea” in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children’s Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity–impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p trend = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p trend = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (<38.4 nmol/l), after adjustment for several confounders. Similar associations were found with the hyperactivity/inattention score of the SDQ questionnaire. Children of mothers with high 25(OH) D levels had also fewer total behavioral difficulties (beta-coeff: −1.25, 95% CI −2.32, −0.19) and externalizing symptoms (beta-coeff: −0.87, 95% CI −1.58, −0.15) at preschool age. The observed associations were stronger in girls than in boys (p for interaction < 0.1). No association was observed between maternal 25(OH) D concentrations and cognitive function in preschoolers. Our results suggest that high maternal vitamin D levels in early pregnancy may protect against behavioral difficulties, especially ADHD-like symptoms at preschool age.

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Abbreviations

ADHD:

Attention deficit hyperactivity disorder

BMI:

Body mass index

CI:

Confidence interval

DSM-IV:

Diagnostic and Statistical Manual of Mental Disorders

GAMs:

Generalized additive models

IQ:

Intelligence quotient

IRR:

Incidence rate ratio

MSCA:

McCarthy Scales of Children’s Abilities

SDQ:

Strengths and Difficulties Questionnaire

SD:

Standard deviation

TSH:

Thyroid stimulating hormone

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Acknowledgements

The authors would particularly like to thank all the cohort participants for their generous collaboration. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EUFP7- HEALTH-2012 Proposal No 308333 HELIX), MeDALL (FP7 European Union project, No. 264357), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015).

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Authors and Affiliations

  1. Department of Social Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003, Heraklion, Crete, Greece

    Vasiliki Daraki, Theano Roumeliotaki, Katerina Koutra, Georgia Chalkiadaki, Andriani Kyriklaki, Mariza Kampouri, Katerina Margetaki, Marina Vafeiadi & Leda Chatzi

  2. Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Crete, Heraklion, Crete, Greece

    Vasiliki Daraki & Stathis Papavasiliou

  3. Laboratory of Clinical Chemistry-Biochemistry, University Hospital of Crete, Heraklion, Crete, Greece

    Marianna Katrinaki

  4. Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain

    Manolis Kogevinas

  5. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

    Manolis Kogevinas

  6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Leda Chatzi

  7. Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands

    Leda Chatzi

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  1. Vasiliki Daraki
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Correspondence to Vasiliki Daraki.

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Daraki, V., Roumeliotaki, T., Koutra, K. et al. High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother–child cohort, Crete, Greece. Eur Child Adolesc Psychiatry 27, 79–88 (2018). https://doi.org/10.1007/s00787-017-1023-x

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