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Gestational Folate and Offspring Bone Health; The Vitamin D in Pregnancy Study

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Abstract

Maternal nutritional intake, such as folate and folic acid supplementation, during pregnancy may affect offspring bone health during childhood. We aimed to determine the associations between maternal dietary and supplementary folate intake and offspring bone health measures, including fracture risk. Data were obtained from 160 of 475 mother–child pairs who had returned for the 11-year follow up of the Vitamin D in Pregnancy Study, an observational cohort study. Incident fractures were ascertained from radiological records and dual X-ray absorptiometry was used to measure bone mineral density and content at 11 years of age. Maternal dietary folate intake during pregnancy was determined by Food Frequency Questionnaire and folate supplementation was determined through self-report. Both measures were undertaken at recruitment (before 16 weeks gestation) and at 28–32 weeks’ gestation. Multivariable linear regression models and Cox regression models were used to examine associations. Results are presented as per 1000 µg folate for dietary measures. There were significant associations between maternal folate supplementation in early pregnancy (< 16 weeks gestation) and offspring spine bone mineral content (BMC) (β = 1.53, 95% CI 0.21, 2.86), spine area (β = 1.10, 95% CI 0.37, 1.82) and total body less head area (β = 329.30, 95% CI 3.50, 55.20) at the 11-year follow-up. The association between spine BMC was attenuated after adjustment for bone size (β = 0.13 95% CI − 0.85, 1.10). There was no association between maternal folate supplementation at 28–32 weeks’ or maternal dietary intake at either time point with any offspring bone outcome. These data suggest that folate supplementation in early pregnancy may be associated with offspring bone size, but not other bone measures.

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Data will be made available upon reasonable requests and subject to ethical approval.

References

  1. Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, Weaver C (2000) Peak bone mass. Osteoporos Int 11(12):985–1009. https://doi.org/10.1007/s001980070020

    Article  CAS  PubMed  Google Scholar 

  2. Pasco JA, Lane SE, Brennan-Olsen SL, Holloway KL, Timney EN, Bucki-Smith G, Morse AG, Dobbins AG, Williams LJ, Hyde NK, Kotowicz MA (2015) The epidemiology of incident fracture from cradle to senescence. Calcif Tissue Int 97(6):568–576. https://doi.org/10.1007/s00223-015-0053-y

    Article  CAS  PubMed  Google Scholar 

  3. Barker DJ (2007) The origins of the developmental origins theory. J Intern Med 261(5):412–417. https://doi.org/10.1111/j.1365-2796.2007.01809.x

    Article  CAS  PubMed  Google Scholar 

  4. Woolford SJ, Cooper C, Harvey N, Moon RJ (2019) Prenatal influences on bone health in children. Expert Rev Endocrinol Metab 14(3):193–202. https://doi.org/10.1080/17446651.2019.1607727

    Article  CAS  PubMed  Google Scholar 

  5. Hyde NK, Brennan-Olsen SL, Wark JD, Hosking SM, Pasco JA (2017) Maternal dietary nutrient intake during pregnancy and offspring linear growth and bone: the Vitamin D in Pregnancy Cohort Study. Calcif Tissue Int 100(1):47–54. https://doi.org/10.1007/s00223-016-0199-2

    Article  CAS  PubMed  Google Scholar 

  6. Greenberg JA, Bell SJ, Guan Y, Yu Y-H (2011) Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol 4(2):52–59

    PubMed  PubMed Central  Google Scholar 

  7. Ganpule A, Yajnik CS, Fall CHD, Rao S, Fisher DJ, Kanade A, Cooper C, Naik S, Joshi N, Lubree H, Deshpande V, Joglekar C (2006) Bone mass in indian children—relationships to maternal nutritional status and diet during pregnancy: the Pune Maternal Nutrition Study. J Clin Endocrinol Metab 91(8):2994–3001. https://doi.org/10.1210/jc.2005-2431

    Article  CAS  PubMed  Google Scholar 

  8. Steer CD, Tobias JH (2011) Insights into the programming of bone development from the Avon Longitudinal Study of Parents and Children (ALSPAC). Am J Clin Nutr 94(6 Suppl):1861s–1864s. https://doi.org/10.3945/ajcn.110.001495

    Article  CAS  PubMed  Google Scholar 

  9. Tobias JH, Steer CD, Emmett PM, Tonkin RJ, Cooper C, Ness AR (2005) Bone mass in childhood is related to maternal diet in pregnancy. Osteoporos Int 16(12):1731–1741. https://doi.org/10.1007/s00198-005-1912-6

    Article  CAS  PubMed  Google Scholar 

  10. Hossein-nezhad A, Mirzaei K, Maghbooli Z, Najmafshar A, Larijani B (2011) The influence of folic acid supplementation on maternal and fetal bone turnover. J Bone Miner Metab 29(2):186–192. https://doi.org/10.1007/s00774-010-0205-0

    Article  CAS  PubMed  Google Scholar 

  11. Hyde NK, Brennan-Olsen SL, Wark JD, Hosking SM, Vuillermin PJ, Williams LJ, Pasco JA (2020) Cohort profile: the Vitamin D in Pregnancy Study. BMJ Open 10:e036003

    Article  Google Scholar 

  12. Giles G, Ireland P (1996) Dietary questionnaire for epidemiological studies (Version 3.2). Cancer Council Victoria, Melbourne

    Google Scholar 

  13. Hyde NK, Brennan-Olsen SL, Bennett K, Moloney DJ, Pasco JA (2017) Maternal nutrition during pregnancy: intake of nutrients important for bone health. Matern Child Health J 21(4):845–851. https://doi.org/10.1007/s10995-016-2178-7

    Article  PubMed  Google Scholar 

  14. Pasco JA, Henry MJ, Gaudry TM, Nicholson GC, Kotowicz MA (1999) Identification of incident fractures: the Geelong Osteoporosis Study. Aust N Z J Med 29(2):203–206. https://doi.org/10.1111/j.1445-5994.1999.tb00684.x

    Article  CAS  PubMed  Google Scholar 

  15. Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235):291–303. https://doi.org/10.1136/adc.44.235.291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45(239):13–23. https://doi.org/10.1136/adc.45.239.13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chavarro JE, Watkins DJ, Afeiche MC, Zhang Z, Sánchez BN, Cantonwine D, Mercado-García A, Blank-Goldenberg C, Meeker JD, Téllez-Rojo MM, Peterson KE (2017) Validity of self-assessed sexual maturation against physician assessments and hormone levels. J Pediatr 186:172-178.e173. https://doi.org/10.1016/j.jpeds.2017.03.050

    Article  PubMed  PubMed Central  Google Scholar 

  18. Behera J, Bala J, Nuru M, Tyagi SC, Tyagi N (2017) Homocysteine as a pathological biomarker for bone disease. J Cell Physiol 232(10):2704–2709. https://doi.org/10.1002/jcp.25693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kim DJ, Koh JM, Lee O, Kim NJ, Lee YS, Kim YS, Park JY, Lee KU, Kim GS (2006) Homocysteine enhances apoptosis in human bone marrow stromal cells. Bone 39(3):582–590. https://doi.org/10.1016/j.bone.2006.03.004

    Article  CAS  PubMed  Google Scholar 

  20. Vacek TP, Kalani A, Voor MJ, Tyagi SC, Tyagi N (2013) The role of homocysteine in bone remodeling. Clin Chem Lab Med 51(3):579–590. https://doi.org/10.1515/cclm-2012-0605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Clark EM, Ness AR, Bishop NJ, Tobias JH (2006) Association between bone mass and fractures in children: a Prospective Cohort Study. J Bone Miner Res 21(9):1489–1495. https://doi.org/10.1359/jbmr.060601

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank the participants and staff of the Vitamin D in Pregnancy Study. This study has received funding from the National Health and Medical and Research Council (NHMRC) and Bupa Health Foundation. SMH and KLH-K were funded by an Alfred Deakin Postdoctoral Research Fellowship (Deakin University), LJW is supported by an NHMRC Career Development Fellowship (1064272) and a NHMRC Investigator grant (1174060). NKH was supported by a Dean’s Research Fellowship (Deakin University). The authors also thank Professor Graham Giles of the Cancer Epidemiology Centre of The Cancer Council Victoria, for permission to use the Dietary Questionnaire for Epidemiological Studies (Version 2), Melbourne: The Cancer Council Victoria 1996.

Funding

This study has received funding from the National Health and Medical and Research Council (NHMRC) and Bupa Health Foundation. SMH and KLH-K were funded by an Alfred Deakin Postdoctoral Research Fellowship (Deakin University), LJW is supported by an NHMRC Career Development Fellowship (1064272) and a NHMRC Investigator Grant (1174060).

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Correspondence to Natalie K. Hyde.

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Mia A. Percival, Julie A. Pasco, Sarah M. Hosking, Lana J. Williams, Kara L. Holloway-Kew and Natalie K. Hyde declares that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This study was approved by Barwon Health Human Research Ethics Committee and all mothers and/or guardians provided consent on behalf of themselves and their child. At 11 years of age the children provided optional assent.

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Percival, M.A., Pasco, J.A., Hosking, S.M. et al. Gestational Folate and Offspring Bone Health; The Vitamin D in Pregnancy Study. Calcif Tissue Int 108, 605–609 (2021). https://doi.org/10.1007/s00223-020-00795-z

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