Vitamin D status in early childhood is not associated with cognitive development and linear growth at 6-9 years of age in North Indian children: a cohort study

Ranadip Chowdhury, Sunita Taneja, Ingrid Kvestad, Mari Hysing, Nita Bhandari, Tor A Strand, Ranadip Chowdhury, Sunita Taneja, Ingrid Kvestad, Mari Hysing, Nita Bhandari, Tor A Strand

Abstract

Background: Vitamin D is important for brain function and linear growth. Vitamin D deficiency during pregnancy has been linked with impaired neurodevelopment during early childhood. However, there is limited evidence from population-based studies on the long-term impact of vitamin D deficiency on cognitive development and linear growth. The objective of the current analysis is to examine whether vitamin D deficiency during infancy and early childhood is associated with cognitive development and linear growth measured in school age.

Methods: This is a follow-up study of a placebo-controlled trial among 1000 North Indian children 6-30 months of age. We measured growth and neurodevelopment in 791 of these children when they were 6-9 years old. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children, 4th edition INDIA, the Crichton Verbal Scale, NEPSY-II subtests, and the BRIEF 2. We categorized vitamin D concentrations during infancy and early childhood according to the US Institute of Medicine's recommendations; serum 25(OH)D < 12 ng/ml as deficient; 12-20 ng/ml as inadequate; > 20 ng/ml as sufficient. In multivariable regression models, adjusting for relevant confounders, we estimated the association between vitamin D status, growth and neurodevelopmental outcomes.

Results: Among the 791 children, baseline vitamin D status was available for 716. Of these, 45.8% were vitamin D deficient, 32.7% were inadequate, and 21.5% were sufficient. Vitamin D status was not associated with any of the cognitive outcomes or linear growth [Adjusted β coefficient for height for age z-score between deficient and sufficient children was - 0.06 (95% CI - 0.24 to 0.11)] at follow up.

Conclusion: Our findings do not support the notion that poor vitamin D status in early childhood is an important limitation for cognitive development and linear growth.

Trial registration: The trial was first registered at www.clinicaltrials.gov as NCT00717730 in July, 2008, and at CTRI/2010/091/001090 in August, 2010 and then as CTRI/2016/11/007494 in November 2016.

Keywords: 4th edition INDIA; A developmental neuropsychological assessment II; Crichton verbal scale; Linear growth; School age; The behavior rating inventory of executive function 2; Vitamin D; Wechsler intelligence scale for children.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Participant Flow
Fig. 2
Fig. 2
Association between baseline vitamin D level and the combined WISC IVINDIA and Crichton Vocabulary Scale (CVS) z-score, the combined NEPSY II z scores and the BRIEF P Global Executive composite score at follow up in North Indian children 6 to 9 years. The graph was constructed using generalized additive models in R, the solid line depicts the association of vitamin D level at baseline and Global BRIEF score at follow up. The shaded area spans the 95% confidence interval of this association

References

    1. Holick MF. Vitamin D: extraskeletal health. Rheum Dis Clin N Am. 2012;38:141–160. doi: 10.1016/j.rdc.2012.03.013.
    1. Kamboj P, Dwivedi S, Toteja GS. Prevalence of hypovitaminosis D in India & way forward. IJMR. 2018;48(5):548–556.
    1. Pike JW, Meyer MB. The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D(3) Endocrinol Metab Clin N Am. 2010;39(2):255–269. doi: 10.1016/j.ecl.2010.02.007.
    1. Kesby JP, Eyles DW, Burne TH, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol. 2011;347(1–2):121–127. doi: 10.1016/j.yfrne.2012.07.001.
    1. O’Loan J, Eyles DW, Kesby J, Ko P, McGrath JJ, Burne TH. Vitamin-D status during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology. 2007;32:227–234. doi: 10.1016/j.psyneuen.2006.12.006.
    1. Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. Vitamin-D3 and brain development. Neuroscience. 2003;118:641–653. doi: 10.1016/s0306-4522(03)00040-x.
    1. Strom M, Halldorsson TI, Hansen S, Granström C, Maslova E, Petersen SB, Cohen AS, Olsen SF. Vitamin D measured in maternal serum and offspring neurodevelopmental outcomes: a prospective study with long-term follow-up. Ann Nutr Metab. 2014;64:254–261. doi: 10.1159/000365030.
    1. Morales E, Guxens M, Llop S, Rodríguez-Bernal CL, Tardón A, Riaño I, Ibarluzea J, Lertxundi N, Espada M, Rodriguez A. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics. 2012;130:e913–e920. doi: 10.1542/peds.2011-3289.
    1. Keim SA, Bodnar LM, Klebanoff MA. Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child development and behaviour. Paediatr Perinat Epidemiol. 2014;28:434–444. doi: 10.1111/ppe.12135.
    1. Whitehouse AJ, Holt BJ, Serralha M. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics. 2012;129:485–493. doi: 10.1542/peds.2011-2644.
    1. Hanieh S, Ha TT, Simpson JA, Thuy TT, Khuong NC, Thoang DD, Tran TD, Tuan T, Fisher J, Biggs BA. Maternal vitamin D status and infant outcomes in rural Vietnam: a prospective cohort study. PLoS One. 2014;9:e99005. doi: 10.1371/journal.pone.0099005.
    1. Brouwer-Brolsma EM, Vrijkotte TG, Feskens EJ. Maternal vitamin D concentrations are associated with faster childhood reaction time and response speed, but not with motor fluency and flexibility, at the age of 5–6 years: the Amsterdam born children and their development (ABCD) study. Br J Nutr. 2018;120(3):345–352. doi: 10.1017/S0007114518001319.
    1. Chowdhury R, Taneja S, Bhandari N, Kvestad I, Strand TA. Bhan MK. Vitamin-D status and neurodevelopment and growth in young north Indian children: a secondary data analysis. Nutr J, 2017; 16: 59 doi: 10.1186/s12937-017-0285-y.
    1. Månsson Johanna, Stjernqvist Karin, Serenius Fredrik, Ådén Ulrika, Källén Karin. Agreement Between Bayley-III Measurements and WISC-IV Measurements in Typically Developing Children. Journal of Psychoeducational Assessment. 2018;37(5):603–616. doi: 10.1177/0734282918781431.
    1. Schneider W, Niklas F, Schmiedeler S. Intellectual development from early childhood to early adulthood: The impact of early IQ differences on stability and change over time. Learn Individ Differ 2014;32:156–162. doi: .
    1. Winje BA, Kvestad I, Krishnamachari S, Manji K, Taneja S, Bellinger DC, et al. Does early vitamin B&lt;sub&gt;12&lt;/sub&gt; supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania. BMJ Open. 2018;8(2):e018962. doi: 10.1136/bmjopen-2017-018962.
    1. Chowdhury R, Taneja S, Bhandari N, Sinha B, Upadhyay RP, Bhan M, Strand TA. Vitamin-D deficiency predicts infections in young north Indian children: a secondary data analysis. PLoS One. 2017;12(3):e0170509. doi: 10.1371/journal.pone.0170509.
    1. Taneja S, Strand TA, Kumar T, Mahesh M, Mohan S, Manger MS. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial. Am J Clin Nutr. 2013;98(3):731–737. doi: 10.3945/ajcn.113.059592.
    1. Wechsler D. WISC-IV India. Wechsler intelligence scale for children - fourth (India edition) New Delhi: Pearson; 2016.
    1. Raven J, Rust J, Squire A. Manual for Coroured progressive matrices and Crichton vocabulary scale. NCS Pearson Inc: UK; 2008.
    1. Raven J, Rust J, Squire A. Raven’s Coloured Progressive Matrices and Crichton Vocabulary Scales (Hindi Edition). Chennai, India: Pearson Clinical & Talent Assessment; 2015.
    1. Brooks Brian L., Sherman Elisabeth M. S., Strauss Esther. NEPSY-II: A Developmental Neuropsychological Assessment, Second Edition. Child Neuropsychology. 2009;16(1):80–101. doi: 10.1080/09297040903146966.
    1. Gioia Gerard A., Isquith Peter K., Roth Robert M. Encyclopedia of Clinical Neuropsychology. Cham: Springer International Publishing; 2018. Behavior Rating Inventory for Executive Function; pp. 532–538.
    1. Cobas E411 Vitamin-D Total Reagent Insert (06268668001V1). Roche Diagnostics Web site. Available online: Accessed 17 April 2019.
    1. Shipchandler MT, Moore EG. Rapid, fully automated measurement of plasma homocyst (e) ine with the Abbott IMx analyzer. Clin Chem. 1995;41(7):991e4. doi: 10.1093/clinchem/41.7.991.
    1. O'broin S, Kelleher B. Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol. 1992;45(4):344e7. doi: 10.1136/jcp.45.4.344.
    1. Kelleher BP, Walshe KG, Scott JM, O'Broin SD. Microbiological assay for vitamin B12 with use of a colistin-sulfate-resistant organism. Clin Chem. 1987;33(1):52e4. doi: 10.1093/clinchem/33.1.52.
    1. Cotton F, Thiry P, Boeynaems J. Measurement of soluble transferrin receptor by immunoturbidimetry and immunonephelometry. Clin Biochem. 2000;33(4):263e7. doi: 10.1016/S0009-9120(00)00071-0.
    1. Spiro A., Buttriss J. L. Vitamin D: An overview of vitamin D status and intake in Europe. Nutrition Bulletin. 2014;39(4):322–350. doi: 10.1111/nbu.12108.
    1. Onis M. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr 2006; 95(S450): 76–85 doi: .
    1. International Institute for Population Sciences (IIPS) and Macro International. National Family Health Survey (NFHS-4), 2015-16. Mumbai: International Institute for Population Sciences (IIPS) and Macro International; 2015.
    1. Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159(7):702–706. doi: 10.1093/aje/kwh090.
    1. Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol and Med. 2008;3:17. doi: 10.1186/1751-0473-3-17.
    1. Hosmer DW, Lemeshow S, Sturdivant RX. Applied logistic regression. New York: Wiley; 2013.
    1. Wood SN. Modelling and smoothing parameter estimation with multiple quadratic penalties. J Royal Stat Soc. 2000;62:413–428 doi: .
    1. Filteau S, Rehman AM, Yousafzi A, Chugh R, Kaur M, Sachdev HPS, Trilok-Kumar G. Association of vitamin D status, bone health and anthropometry, with gross motor development and performance of school-aged Indian children who were born at term low birth weight. BMJ Open. 2016;6:e009268. doi: 10.1136/bmjopen-2015-009268.
    1. Zhu P, Tong SL, Hao JH, Tao RX, Huang K, Hu WB, Zhou QF, Jiang XM, Tao FB. Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers. J Nutr. 2015;145(6):1232–1238. doi: 10.3945/jn.114.208801.
    1. Gould JF, Anderson AJ, Yelland LN, Smithers LG, Skeaff CM, Zhou SJ, Gibson RA, Makrides M. Association of cord blood vitamin-D with early childhood growth and neurodevelopment. J Paediatr Child Health. 2017;53(1):75–83. doi: 10.1111/jpc.13308.
    1. Darling AL, Rayman MP, Steer CD, Golding J, Lanham-New SA, Bath SC. Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomesin childhood: results from the Avon longitudinal study of parents and children (ALSPAC) Br J Nutr. 2017;117(12):1682–1692. doi: 10.1017/S0007114517001398.
    1. Avagyan D, Neupane SP, Gundersen TE, Madar AA. Vitamin D status in preschool children in rural Nepal. Public Health Nutr. 2016;19(3):470–476. doi: 10.1017/S136898001500083X.
    1. Sudfeld CR, Duggan C, Abound S, Kupka R, Manji KP, Kisenge R, Fawzi WW. Vitamin D status is associated with mortality, morbidity, and growth failure among a prospective cohort of HIV-infected and HIV-exposed Tanzanian infants. J Nutr. 2015;145(1):121–127. doi: 10.3945/jn.114.201566.
    1. Kumar GT, Sachdev HS, Chellani H, Rehman AM, Singh V, Arora H, Filteau S. Effect of weekly vitamin-D ements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial. BMJ. 2011;342:d2975. doi: 10.1136/bmj.d2975.
    1. Esposito S, Leonardi A, Lanciotti L, Cofini M, Muzi G, Penta L. Vitamin D and growth hormone in children: a review of the current scientific knowledge. J Transl Med. 2019;17(1):87. doi: 10.1186/s12967-019-1840-4.
    1. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–329. doi: 10.1016/j.chembiol.2013.12.016.
    1. Eaton JC, Rothpletz-Puglia P, Dreker MR, Iannotti L, Lutter C, Kaganda J, Rayco-Solon P. Effectiveness of provision of animal-source foods for supporting optimal growth and development in children 6 to 59 months of age. Cochrane Database of Systematic Reviews. 2019(2):CD012818. 10.1002/14651858.CD012818.pub2.
    1. Agarwal KS, Mughal MZ, Upadhyay P, Berry JL, Mawer EB, Puliyel JM. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi. India. 2002;87(2):111–113.
    1. Ritu G, Gupta A. Vitamin-D deficiency in India: prevalence, causalities and interventions. Nutrients. 2014;6:729–775. doi: 10.3390/nu6020729.
    1. Khadilkar A, Khadilkar V, Chinnappa J, Rathi N, Khadgawat R, Balasubramanian S, et al. Prevention and treatment of vitamin D and calcium deficiency in children and adolescents: Indian academy of pediatrics (IAP) guidelines. Indian Pediatr. 2017;54:567–573. doi: 10.1007/s13312-017-1070-x.
    1. Li L, Zeng Q, Yuan J, Xie Z. Performance evaluation of two immunoassays for 25-hydroxyvitamin D. J Clin Biochem Nutr. 2016;58(3):186–192. doi: 10.3164/jcbn.15-61.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren