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Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother–child cohort study in Crete, Greece
  1. Mariza Kampouri1,
  2. Katerina Margetaki1,
  3. Katerina Koutra1,2,
  4. Andriani Kyriklaki1,
  5. Polyxeni Karakosta1,
  6. Despoina Anousaki1,
  7. Georgia Chalkiadaki1,
  8. Marina Vafeiadi1,
  9. Manolis Kogevinas3,4,5,
  10. Leda Chatzi1,6,7
  1. 1 Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece
  2. 2 Department of Psychology, University of Crete School of Social Sciences, Rethimno, Greece
  3. 3 Instituto de Salud Global Barcelona, Barcelona, Spain
  4. 4 Hospital del Mar Institute for Medical Research, Barcelona, Spain
  5. 5 Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain
  6. 6 Preventive Medicine, University of Southern California, Los Angeles, California, USA
  7. 7 Department of Genetics and Cell Biology, Maastricht University Faculty of Health Medicine and Life Sciences, Maastricht, Netherlands
  1. Correspondence to Mariza Kampouri, Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion 71003, Crete, Greece; mar.kabouri{at}


Background Maternal thyroid hormones’ supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid dysfunction with child neuropsychological development from infancy to early childhood.

Methods We included 757 mother–child pairs from the prospective ‘Rhea’ cohort on Crete, Greece. Maternal thyroid functioning was assessed by quantitative analysis of serum thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies and thyroglobulin antibodies at early gestation (mean=14 weeks). Neuropsychological assessment was based on Bayley Scales of Infant Development (18 months of age), McCarthy Scales of Children’s Abilities (4 years of age), Raven’s Coloured Progressive Matrices, Trail Making Test and Finger Tapping Test (6 years of age).

Results In multivariate adjusted linear regression analyses, maternal hypothyroxinemia was associated with decreased verbal scores at 4 years and reduced motor speed at 6 years of age. Maternal thyroid autoimmunity was associated with decreased child perceptual and motor ability at 4 years of age. Four trajectories of longitudinal non-verbal cognitive development were identified and children exposed to maternal thyroid autoimmunity had increased risk for belonging to an adverse trajectory (‘low’: adjusted relative risk ratio (RRR) = 2.7 95% CI: (1.4, 5.2), ‘high-decreasing’: adjusted RRR = 2.2 95% CI: (1.2, 4.0), ‘low-increasing’: adjusted RRR = 1.8 95% CI: (1.0, 3.2)).

Conclusion Maternal hypothyroxinemia is associated with reduced offspring verbal and motor ability. Maternal thyroid autoimmunity is associated with decreased offspring perceptual performance and motor ability and increased risk for adverse non-verbal cognitive development from infancy to childhood.

  • Cohort studies
  • Pregnancy
  • Hormones
  • Cognition

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  • Contributors MKa contributed to the design of this work, data acquisition, analysis and interpretation and drafted the manuscript. KM contributed to the design of this work, data analysis and interpretation. KK, AK, DA, PK and GC contributed to data acquisition, analysis and interpretation. MV contributed to the design of this study and data interpretation. MKo contributed to the conception and design of this study. LC contributed to the conception and design of this study and directed its implementation. All authors have critically revised and edited the manuscript and approved its final version.

  • Funding The ‘Rhea’ project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007. Project No. 211250 Escape, EU FP7-2008-ENV- Envirogenomarkers, EU FP7-HEALTH-2009—single-stage CHICOS, EU FP7 ENV.2008. Proposal No 226285 ENRIECO, EU FP7.2007–2013—-Project No 308333-The Helix Project and the Greek Ministry of Health (Programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014), (‘Rhea Plus’: Primary prevention programme of environmental risk factors for reproductive health, and child health: 2012–2015). The funding bodies had no involvement in the production of this article.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.