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Higher maternal plasma β-cryptoxanthin concentration is associated with better cognitive and motor development in offspring at 2 years of age

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Abstract

Purpose

Current literature on the roles of α-, β-carotene and β-cryptoxanthin in neurocognitive function has largely focused on preventing cognitive decline in older people, and less on neuro-development in children. We examined the relations of maternal plasma carotenoids concentrations with offspring cognitive development up to age 4.5 years in the Growing Up in Singapore Towards healthy Outcomes mother–offspring cohort study.

Methods

Maternal plasma α-, β-carotene and β-cryptoxanthin concentrations at delivery were determined by ultra-performance liquid chromatography. Children’s cognition was assessed at ages 2 (Bayley Scales of Infant and Toddler Development) and 4.5 (Kaufman Brief Intelligence Test) years. Associations were examined in 419 mother–offspring pairs using linear regressions adjusting for key confounders.

Results

Median and interquartile range of maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032, 0.081), β-carotene 0.189 (0.134, 0.286), and β-cryptoxanthin 0.199 (0.123, 0.304). In 2 years old children, higher maternal carotenoids [per standard deviation (SD) log-concentration] were positively associated with neurocognitive functions: β-cryptoxanthin with higher scores in cognitive [β = 0.18, (0.08, 0.28) SD], receptive language [β = 0.17 (0.07, 0.27) SD], fine motor [β = 0.16 (0.05, 0.26) SD], and gross motor [β = 0.16 (0.06, 0.27) SD] scales; β-carotene with higher cognitive score [β = 0.17 (0.05, 0.29) SD]. No significant associations were observed with neurocognitive functions at age 4.5 years.

Conclusion

Our study provides novel data suggesting a potential role of prenatal carotenoids, particularly β-cryptoxanthin, on early offspring cognitive and motor development. Whether the prenatal influences sustain beyond early childhood requires further investigation in longer term studies.

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Acknowledgements

This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore – NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), and Ministry of Education’s Academic Research Fund Tier 1. KMG is supported by the National Institute for Health Research (NIHR) through the NIHR Southampton Biomedical Research Centre and by the European Union’s Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition under grant agreement n°289346. The funding bodies had no influence on the study design, data collection, analysis, interpretation and content of the manuscript. We will like to acknowledge the contribution of the GUSTO study group: Allan Sheppard, Amutha Chinnadurai, Anne Eng Neo Goh, Anqi Qiu, Arijit Biswas, Bee Wah Lee, Boon Long Quah, Borys Shuter, Chai Kiat Chng, Cheryl Ngo, Choon Looi Bong, Christiani Jeyakumar Henry, Claudia Chi, Cornelia Yin Ing Chee, Yam Thiam Daniel Goh, Doris Fok, E Shyong Tai, Elaine Tham, Elaine Quah Phaik Ling, Evelyn Chung Ning Law, Evelyn Xiu Ling Loo, Falk Mueller-Riemenschneider, George Seow Heong Yeo, Helen Chen, Heng Hao Tan, Hugo P S van Bever, Iliana Magiati, Inez Bik Yun Wong, Ivy Yee-Man Lau, Izzuddin Bin Mohd Aris, Jeevesh Kapur, Jenny L. Richmond, Jerry Kok Yen Chan, Joanna D. Holbrook, Joanne Yoong, Joao N. Ferreira., Jonathan Tze Liang Choo, Jonathan Y. Bernard, Joshua J. Gooley, Kenneth Kwek, Krishnamoorthy Niduvaje, Kuan Jin Lee, Leher Singh, Lieng Hsi Ling, Lin Lin Su, Ling-Wei Chen, Lourdes Mary Daniel, Marielle V. Fortier, Mark Hanson, Mary Rauff, Mei Chien Chua, Melvin Khee-Shing Leow, Mya Thway Tint, Neerja Karnani, Ngee Lek, Oon Hoe Teoh, P. C. Wong, Paulin Tay Straughan, Pratibha Agarwal, Queenie Ling Jun Li, Rob M. van Dam, Salome A. Rebello, Seang-Mei Saw, See Ling Loy, S. Sendhil Velan, Seng Bin Ang, Shang Chee Chong, Sharon Ng, Shiao-Yng Chan, Shu-E Soh, Sok Bee Lim, Stella Tsotsi, Chin-Ying Stephen Hsu, Sue Anne Toh, Swee Chye Quek, Victor Samuel Rajadurai, Walter Stunkel, Wayne Cutfield, Wee Meng Han, Wei Wei Pang, Yin Bun Cheung, Yiong Huak Chan and Yung Seng Lee.

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Author notes

  1. Birit F. P. Broekman and Mary F. F. Chong Co-senior authors.

Authors and Affiliations

  1. Singapore Institute for Clinical Sciences, Agency for Science and Technology Research, Singapore, Singapore

    Jun S. Lai, Shirong Cai, Peter D. Gluckman, Lynette P. Shek, Yap Seng Chong, Michael J. Meaney, Birit F. P. Broekman & Mary F. F. Chong

  2. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore

    Shirong Cai & Yap Seng Chong

  3. Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, 12 Science Drive 2, #09-01Q, Singapore, 117549, Singapore

    Bee Lan Lee, Choon Nam Ong & Mary F. F. Chong

  4. MRC Lifecourse Epidemiology Unit, NIHR Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK

    Keith M. Godfrey

  5. Liggins Institute, University of Auckland, Grafton, Auckland, New Zealand

    Peter D. Gluckman

  6. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore

    Lynette P. Shek

  7. Duke-NUS Medical School, Singapore, Singapore

    Fabian Yap

  8. Department of Paediatric Endocrinology, KK Women’s and Children’s Hospital, Singapore, Singapore

    Fabian Yap

  9. Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

    Kok Hian Tan

  10. Department of Psychiatry and Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

    Michael J. Meaney

  11. Department Office of Education Research, National Institute of Education, Singapore, Singapore

    Anne Rifkin-Graboi

  12. Department of Psychiatry, OLVG and VU Medical Centre, Amsterdam, The Netherlands

    Birit F. P. Broekman

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  1. Jun S. Lai
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Contributions

JSL, CNO, BFPB, AR-G and MFFC designed the research. JSL performed statistical analysis and wrote the manuscript. MFFC, BFPB and AR-G reviewed and edited the manuscript. JSL and MFFC had primary responsibility for final content. BLL and CNO designed the methodology and provided essential reagents for plasma carotenoids assay; SC, MJM, AR-G and BFPB designed the protocol and provided essential materials for the cognitive assessments. LPS, FY, KHT, PDG, YSC and KMG led the GUSTO study. All authors critically reviewed the manuscript for scientific content, read and approved the final manuscript.

Corresponding author

Correspondence to Mary F. F. Chong.

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Conflict of interest

FY, KMG, PDG and YSC have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG, PDG and YSC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestlé and Danone. All other authors (JSL, SC, BLL, LPS, KHT, CNO, MJM, AR-G, BFPB, MFFC) declared that they have no competing interests.

Ethical standards

The GUSTO study received ethics approval from the Institutional Review Board of NUH and KKH, and all procedures were conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants at each study visit.

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Lai, J.S., Cai, S., Lee, B.L. et al. Higher maternal plasma β-cryptoxanthin concentration is associated with better cognitive and motor development in offspring at 2 years of age. Eur J Nutr 60, 703–714 (2021). https://doi.org/10.1007/s00394-020-02277-2

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