A longitudinal examination of perinatal testosterone, estradiol and vitamin D as predictors of handedness outcomes in childhood and adolescence

ABSTRACT

The developmental origins of handedness remain elusive, though very early emergence suggests individual differences manifesting in utero could play an important role. Prenatal testosterone and Vitamin D exposure are considered, yet findings and interpretations remain equivocal. We examined n = 767 offspring from a population-based pregnancy cohort (The Raine Study) for whom early biological data and childhood/adolescent handedness data were available. We tested whether 18-week maternal circulatory Vitamin D (25[OH]D), and testosterone and estradiol from umbilical cord blood sampled at birth predicted variance in direction of hand preference (right/left), along with right- and left-hand speed, and the strength and direction of relative hand skill as measured by a finger-tapping task completed at 10 (Y10) and/or 16 (Y16) years. Although higher concentrations of Vitamin D predicted more leftward and less lateralized (regardless of direction) relative hand skill profiles, taken as a whole, statistically significant findings typically did not replicate across time-point (Y10/Y16) or sex (male/female) and were rarely detected across different (bivariate/multivariate) levels of analysis. Considering the number of statistical tests and generally inconsistent findings, our results suggest that perinatal testosterone and estradiol contribute minimally, if at all, to subsequent variance in handedness. Vitamin D, however, may be of interest in future studies.

KEYWORDS:

• Estradiol
• Handedness
• Testosterone
• Vitamin D
• Prenatal development

Acknowledgements

We would like to acknowledge The Raine Study participants and their families for their ongoing participation in the study and The Raine Study team for study co-ordination and data collection. We also thank the NHMRC for their long-term contribution to funding the study over the last 30 years. The core management of The Raine Study is funded by The University of Western Australia, Curtin University, Telethon Kids Institute, Women and Infants Research Foundation, Edith Cowan University, Murdoch University, The University of Notre Dame Australia and the Raine Medical Research Foundation. The collection and analysis of prenatal hormone data were funded by The University of Western Australia, School of Women’s and Infants’ Health, King Edward Memorial Hospital, The University of Western Australia, Medical School, Royal Perth Hospital, and Telethon Kids Institute. The NHMRC project grant 1022134 funded the serum 25(OH)D assays that were conducted by RDDT in Melbourne, Victoria, Australia. The Raine Study Gen2-10 year follow-up was funded by the NHMRC and the Raine Medical Research Foundation. The Raine Study Gen2-22 year follow-up was funded by NHMRC project grants 1027449, 1044840 and 1021858. Funding was also generously provided by Safe Work Australia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author roles

GR, LL, DT, and AJOW obtained funding for the study. GR and DT wrote the manuscript. GR and ICM devised the statistical analysis plan, which was affirmed by the other co-authors prior to pre-registration. GR analysed the data. AAB, MH, MM, and ML revised the manuscript for important intellectual content. All authors read and approved the final version of the manuscript.

Data availability statement

The data that support the findings of this research are available from The Raine Study (https://rainestudy.org.au/information-for-researchers/). Restrictions apply to the availability of these data, which were used under license for this study. The R script that accompanies our analysis is available on the Open Science Framework (https://osf.io/yru2s/).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Our access to data from The Raine Study was made possible by a British Academy/Leverhulme Trust Small Research Grant (SRG1819\190620) awarded to Gareth Richards, and was approved under the project “Foetal testosterone, maternal gestational vitamin D levels, and offspring hand preference” (reference number PER0381). The funder was not involved in study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. Diana Tan was supported by a BrightSpark Research Collaboration Award from the Raine Medical Research Foundation (BRCA01-19), and research funding providing by the Faculty of Science in the University of Western Australia allocated to Murray Maybery. Lauren Lawson’s position was supported by the Cooperative Research Centre for Living with Autism (Autism CRC), which is established and supported under the Australian Government’s Cooperative Research Centres Program. Andrew Whitehouse is supported by an Investigator Grant from the National Health and Medical Research Council (1173896).