Osteoporos Int (2014) 25:1419–1420 DOI 10.1007/s00198-013-2542-z
LETTER
Maternal vitamin D status in pregnancy and offspring brain development: the forgotten (but essential) needs of vitamin D era C. Annweiler & O. Beauchet
Received: 17 September 2013 / Accepted: 27 September 2013 / Published online: 18 October 2013 # International Osteoporosis Foundation and National Osteoporosis Foundation 2013
Dear Editor, Recently, Karras et al. [1] provided an extensive narrative review on the relationship between maternal vitamin D status during pregnancy and offspring bone development. The findings showed that only severe maternal hypovitaminosis D predisposes to offspring skeletal deformities and that vitamin D supplementation prevents neonatal rickets only in pregnant women at high risk of hypovitaminosis D [1], prompting the authors to advise incorporating maternal vitamin D supplementation into clinical practice only in high-risk future mothers [1]. Importantly for supplementation reasoning, and in addition to what was reported in this review, it is crucial to keep in mind that, besides its traditional function of bone metabolism regulation, vitamin D also exhibits multiple nonbone biological targets mediated by its nuclear hormone receptor, the Vitamin D Receptor (VDR). In particular, several actions have been described in the brain [2]. This suggests that, beyond bone development, prenatal hypovitaminosis D may also affect the neurocognitive development, which is of course a major concern and significantly determines the offspring's future.
A reply to this comment can be found at doi:10.1007/s00198-013-2543-y. C. Annweiler (*) : O. Beauchet Department of Neuroscience, Angers University Hospital, University Memory Center of Angers, Angers, France e-mail: [email protected] C. Annweiler UPRES EA 4638, University of Angers, UNAM, 49933 Angers Cedex 9, France C. Annweiler Center for Functional and Metabolic Mapping, Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
In the past decade, a wealth of literature has brought evidence that vitamin D acts in the brain as an intracrine hormone of the neurosteroid type [2–9], binding to VDRs present on neurons and glia in cortical and subcortical areas [6]. Experimentation has further shown that vitamin D is involved in numerous brain processes including the genetic regulation of the synthesis of neurotrophins and neurotransmitters [2–6]. It also exhibits neuroprotective, antioxidant and antiinflammatory effects at this level [6]. Adverse impact of maternal hypovitaminosis D on offspring neurocognitive development has been highlighted in animals. Rats born to vitamin D-deficient mothers had profound brain alterations at birth [2], consistent with reduced neurotrophins expression and altered signals for neuronal differentiation [2]. The continuing brain changes after restoration of normal vitamin D diet [3], together with the observation of abnormal adult behaviours [4], suggested that prenatal hypovitaminosis D disrupted not only brain development but also adult brain functioning. Importantly, these experiments were consistent with one human study reporting a direct association between maternal hypovitaminosis D during pregnancy and offspring language impairment at age 5 and 10 years [5]. Other preliminary studies also suggested that gestational hypovitaminosis D could be linked to adult mental disorders [7], specifically schizophrenia [8]. Consistently, epidemiology in adults provides evidence for a role of vitamin D in neurocognitive health and has repeatedly shown associations of hypovitaminosis D with brain morphological alterations [9], schizophrenia [10] and cognitive disorders [11, 12]. Future studies on gestational hypovitaminosis D and maternal supplementation should carefully describe the potential lifelong impact on offspring brain health. Meanwhile, since 70 % of pregnant women have hypovitaminosis D [13] and since the foetus is completely reliant on maternal vitamin D stores [13], these observations are relevant to public health and call for a precautionary approach based on maternal
1420
vitamin D monitoring and eventual repletion to avoid bone but also nonbone adverse health events in offspring. Conflict of interest None.
References 1. Karras SN, Anagnostis P, Bili E, Naughton D, Petroczi A, Papadopoulou F, Goulis DG (2013) Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era. Osteoporos Int. doi:10.1007/s00198-013-2468-5 2. Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F (2003) Vitamin D3 and brain development. Neuroscience 118:641–653 3. Féron F, Burne TH, Brown J, Smith E, McGrath JJ, Mackay-Sim A, Eyles DW (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 65:141–148 4. O'Loan J, Eyles DW, Kesby J, Ko P, McGrath JJ, Burne TH (2007) Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology 32:227–234 5. Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH (2012) Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics 129:485–493
Osteoporos Int (2014) 25:1419–1420 6. Kalueff AV, Tuohimaa P (2007) Neurosteroid hormone vitamin D and its utility in clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care 10:12–19 7. Liu NQ, Hewison M (2012) Vitamin D, the placenta and pregnancy. Arch Biochem Biophys 523:37–47 8. Mackay-Sim A, Féron F, Eyles D, Burne T, McGrath J (2004) Schizophrenia, vitamin D, and brain development. Int Rev Neurobiol 59:351–380 9. Annweiler C, Montero-Odasso M, Hachinski V, Seshadri S, Bartha R, Beauchet O (2013) Vitamin D concentration and lateral cerebral ventricle volume in older adults. Mol Nutr Food Res 57:267–276 10. Belvederi Murri M, Respino M, Masotti M, Innamorati M, Mondelli V, Pariante C, Amore M (2013) Vitamin D and psychosis: mini meta-analysis. Schizophr Res 150(1):235–9. doi:10.1016/j.schres.2013.07.017 11. Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, Beauchet O (2009) Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol 16:1083–1089 12. Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O (2013) Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis 37:147–171 13. Lawlor DA, Wills AK, Fraser A, Sayers A, Fraser WD, Tobias JH (2013) Association of maternal vitamin D status during pregnancy with bone-mineral content in offspring: a prospective cohort study. Lancet 381:2176–2183
LETTER
Maternal vitamin D status in pregnancy and offspring brain development: the forgotten (but essential) needs of vitamin D era C. Annweiler & O. Beauchet
Received: 17 September 2013 / Accepted: 27 September 2013 / Published online: 18 October 2013 # International Osteoporosis Foundation and National Osteoporosis Foundation 2013
Dear Editor, Recently, Karras et al. [1] provided an extensive narrative review on the relationship between maternal vitamin D status during pregnancy and offspring bone development. The findings showed that only severe maternal hypovitaminosis D predisposes to offspring skeletal deformities and that vitamin D supplementation prevents neonatal rickets only in pregnant women at high risk of hypovitaminosis D [1], prompting the authors to advise incorporating maternal vitamin D supplementation into clinical practice only in high-risk future mothers [1]. Importantly for supplementation reasoning, and in addition to what was reported in this review, it is crucial to keep in mind that, besides its traditional function of bone metabolism regulation, vitamin D also exhibits multiple nonbone biological targets mediated by its nuclear hormone receptor, the Vitamin D Receptor (VDR). In particular, several actions have been described in the brain [2]. This suggests that, beyond bone development, prenatal hypovitaminosis D may also affect the neurocognitive development, which is of course a major concern and significantly determines the offspring's future.
A reply to this comment can be found at doi:10.1007/s00198-013-2543-y. C. Annweiler (*) : O. Beauchet Department of Neuroscience, Angers University Hospital, University Memory Center of Angers, Angers, France e-mail: [email protected] C. Annweiler UPRES EA 4638, University of Angers, UNAM, 49933 Angers Cedex 9, France C. Annweiler Center for Functional and Metabolic Mapping, Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
In the past decade, a wealth of literature has brought evidence that vitamin D acts in the brain as an intracrine hormone of the neurosteroid type [2–9], binding to VDRs present on neurons and glia in cortical and subcortical areas [6]. Experimentation has further shown that vitamin D is involved in numerous brain processes including the genetic regulation of the synthesis of neurotrophins and neurotransmitters [2–6]. It also exhibits neuroprotective, antioxidant and antiinflammatory effects at this level [6]. Adverse impact of maternal hypovitaminosis D on offspring neurocognitive development has been highlighted in animals. Rats born to vitamin D-deficient mothers had profound brain alterations at birth [2], consistent with reduced neurotrophins expression and altered signals for neuronal differentiation [2]. The continuing brain changes after restoration of normal vitamin D diet [3], together with the observation of abnormal adult behaviours [4], suggested that prenatal hypovitaminosis D disrupted not only brain development but also adult brain functioning. Importantly, these experiments were consistent with one human study reporting a direct association between maternal hypovitaminosis D during pregnancy and offspring language impairment at age 5 and 10 years [5]. Other preliminary studies also suggested that gestational hypovitaminosis D could be linked to adult mental disorders [7], specifically schizophrenia [8]. Consistently, epidemiology in adults provides evidence for a role of vitamin D in neurocognitive health and has repeatedly shown associations of hypovitaminosis D with brain morphological alterations [9], schizophrenia [10] and cognitive disorders [11, 12]. Future studies on gestational hypovitaminosis D and maternal supplementation should carefully describe the potential lifelong impact on offspring brain health. Meanwhile, since 70 % of pregnant women have hypovitaminosis D [13] and since the foetus is completely reliant on maternal vitamin D stores [13], these observations are relevant to public health and call for a precautionary approach based on maternal
1420
vitamin D monitoring and eventual repletion to avoid bone but also nonbone adverse health events in offspring. Conflict of interest None.
References 1. Karras SN, Anagnostis P, Bili E, Naughton D, Petroczi A, Papadopoulou F, Goulis DG (2013) Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era. Osteoporos Int. doi:10.1007/s00198-013-2468-5 2. Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F (2003) Vitamin D3 and brain development. Neuroscience 118:641–653 3. Féron F, Burne TH, Brown J, Smith E, McGrath JJ, Mackay-Sim A, Eyles DW (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 65:141–148 4. O'Loan J, Eyles DW, Kesby J, Ko P, McGrath JJ, Burne TH (2007) Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology 32:227–234 5. Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH (2012) Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics 129:485–493
Osteoporos Int (2014) 25:1419–1420 6. Kalueff AV, Tuohimaa P (2007) Neurosteroid hormone vitamin D and its utility in clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care 10:12–19 7. Liu NQ, Hewison M (2012) Vitamin D, the placenta and pregnancy. Arch Biochem Biophys 523:37–47 8. Mackay-Sim A, Féron F, Eyles D, Burne T, McGrath J (2004) Schizophrenia, vitamin D, and brain development. Int Rev Neurobiol 59:351–380 9. Annweiler C, Montero-Odasso M, Hachinski V, Seshadri S, Bartha R, Beauchet O (2013) Vitamin D concentration and lateral cerebral ventricle volume in older adults. Mol Nutr Food Res 57:267–276 10. Belvederi Murri M, Respino M, Masotti M, Innamorati M, Mondelli V, Pariante C, Amore M (2013) Vitamin D and psychosis: mini meta-analysis. Schizophr Res 150(1):235–9. doi:10.1016/j.schres.2013.07.017 11. Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, Beauchet O (2009) Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol 16:1083–1089 12. Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O (2013) Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis 37:147–171 13. Lawlor DA, Wills AK, Fraser A, Sayers A, Fraser WD, Tobias JH (2013) Association of maternal vitamin D status during pregnancy with bone-mineral content in offspring: a prospective cohort study. Lancet 381:2176–2183
