Brain-derived neurotrophic factor (BDNF) and the capute scales in offspring of mothers with normal and deficient vitamin D levels

Julian Dewantiningrum; Fitri Hartanto; Maria Mexitalia; Ariawan Soejoenoes; Annastasia Ediati; Suharyo Hadisaputro; Dwi Pudjonarko

doi:10.15562/bmj.v12i1.3711

Brain-derived neurotrophic factor (BDNF) and the capute scales in offspring of mothers with normal and deficient vitamin D levels

Julian Dewantiningrum ,

Fitri Hartanto ,

Maria Mexitalia ,

Ariawan Soejoenoes ,

Annastasia Ediati ,

Suharyo Hadisaputro ,

Dwi Pudjonarko ,

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DOI: https://doi.org/10.15562/bmj.v12i1.3711 |
Published: 2023-01-27

Abstract

Background: Vitamin D deficiency during pregnancy is associated with a child's neurocognitive development. During the COVID-19 pandemic, the Capute Scales have become ineffective because requiring face-to-face interaction to examine children's neurocognitive development. Brain-Derived Neurotrophic Factor (BDNF) is an alternative method to determine children's neurocognitive development through blood sampling. This study aims to evaluate the relationships between BDNF and the Capute Scales in the offspring of mothers with vitamin D levels.

Methods: A diagnostic study from 14 community health centers in Semarang City, Central Java, Indonesia, was conducted. The study was performed from August 2017 until August 2018 and included vitamin D level records at 20–24 weeks of normal gestation in 2017 from all single births at these community health centers. The cases were divided into two groups: 30 children born to mothers with normal vitamin D levels (25(OH)D > 20 ng/mL) and 30 children born to mothers with vitamin D deficiency (25(OH)D < 20 ng/ml). This study aimed to assess the relationship between BDNF levels and the Capute Scales of children aged 2 years and to determine the cut-off value based on each group's examination of BDNF levels.

Results: The mean age of pregnant women whose vitamin D levels were checked was 29.32 years. The cut-off value of BDNF among the two groups was 7968 pg/mL. Of the 55 samples that met the Capute Scales criteria, 44 had a BDNF value less than the cut-off value, and 11 samples had a BDNF value more than the cut-off value. Meanwhile, of the five samples that met the Capute Scales criteria and were suspected of mental retardation, three had a BDNF value less than the cut-off value, and two had a BDNF value more than the cut-off value. The sensitivity, specificity, positive, and negative predictive values were 80%, 60%, 0.93, and 0.15, respectively.

Conclusions: BDNF levels can be an alternative neurocognitive examination in children born to mothers with normal and deficient vitamin D levels. BDNF is a growth factor that plays an important role in neurons' differentiation, growth, and survival in the postnatal phase.

References

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Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH HP. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics 2012;129(3):485–93.
Morales E, Guxens M, Llop S, Rodríguez-Bernal CL, Tardón A, Riaño I et al. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics 2012;130(4):e913–20.
Hanieh S, Ha TT, Simpson JA, Thuy TT, Khuong NC, Thoang DD, et al. Maternal vitamin D status and infant outcomes in rural vietnam: A prospective cohort study. PLOS ONE 2014;9(6):e99005.
Laird E, Thurston SW, van Wijngaarden E, Shamlaye CF, Myers GJ, Davidson PW, et al. Maternal vitamin D status and the relationship with neonatal anthropometric and childhood neurodevelopmental outcomes: Results from the Seychelles child development nutrition study. Nutrients 2017;9(11).
McCarthy EK, Murray DM, Malvisi L, Kenny LC, O'B Hourihane J, Irvine AD, Kiely ME. Antenatal vitamin D status is not associated with standard neurodevelopmental assessments at age 5 years in a well-characterized prospective maternal-infant cohort. J Nutr 2018;148(10):1580–6.
Gale CR, Robinson SM, Harvey NC, Javaid MK, Jiang B, Martyn CN et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 2008;62(1):68–77.
Veena SR, Krishnaveni GV, Srinivasan K, Thajna KP, Hegde BG, Gale CR, Fall CH. Association between maternal vitamin D status during pregnancy and offspring cognitive function during childhood and adolescence. Asia Pac J Clin Nutr 2017;26(3):438–49.
Melough MM, Murphy LE, Graff JC, Derefinko KJ, Lewinn KZ, Bush NR, et al. Maternal Plasma 25-hydroxyvitamin D during gestation is positively associated with neurocognitive development in offspring at age 4–6 years. J Nutr 2021;151(1):132–9.
Tylavsky FA, Kocak M, Murphy LE, Graff JC, Palmer FB, Völgyi E, et al. Gestational vitamin 25(OH)D status as a risk factor for receptive language development: A 24-month, longitudinal, observational study. Nutrients 2015;7(12):9918–30.
Chawla D, Fuemmeler B, Benjamin-Neelon SE, Hoyo C, Murphy S, Daniels JL. Early prenatal vitamin D concentrations and social-emotional development in infants. J Matern Fetal Neonatal Med 2019;32(9):1441–8.
Brouwer-Brolsma EM, Vrijkotte TGM, Feskens EJM. 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):345–52.
Kesby JP, Eyles DW, Burne THJ, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol 2011;347(1–2):121–7.
Cui X, Gooch H, Petty A, McGrath JJ, Eyles D. Vitamin D and the brain: Genomic and non-genomic actions. Mol Cell Endocrinol 2017;453:131–43.
Harms LR, Burne THJ, Eyles DW, McGrath JJ. Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab 2011;25(4):657–69.
Eyles D, Burne T, Mcgrath J. Vitamin D in fetal brain development. Semin Cell Dev Biol 2011;22(6):629–36.
Semrud-Clikeman M. The Capute scales. Pediatr Neurol 2006;34(1):79–80.
Bekinschtein P, von Bohlen Und Halbach O. Editorial. Editorial: Cellular and molecular mechanisms of neurotrophin function in the nervous system. Front Cell Neurosci 2020;14:101.
Mitchelmore C, Gede L. Brain derived neurotrophic factor: Epigenetic regulation in psychiatric disorders. Brain Res 2014;1586:162–72.
Chen HJ, Lee YJ, Huang CC, Lin YF, Li ST. Serum brain-derived neurotrophic factor and neurocognitive function in children with type 1 diabetes. J Formos Med Assoc 2021;120(1 Pt 1):157–64.
As S, Hadju V, Tammasse J. The correlation between brain derived neurotrophic factor (BDNF) level and motor development of children aged under 2 years in Timor Tengah selatan Nusa Tenggara Timur. Ijsbar 2015;23(1):164–72.
Subedi L, Huang H, Pant A, Westgate PM, Bada HS, Bauer JA, et al. Plasma brain-derived neurotrophic factor levels in newborn infants with neonatal abstinence syndrome. Front Pediatr 2017;5:238.
Khairy EY, Attia MM. Protective effects of vitamin D on neurophysiologic alterations in brain aging: Role of brain-derived neurotrophic factor (BDNF). Nutr Neurosci 2021;24(8):650–9. https://doi.org/10.1080/1028415X.2019.1665854.
Sakata K, Overacre AE. Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, CHRM2, and CHRM5: Effects of drug and environmental treatments. J Neurochem 2017;143(1):49–64.
Silakarma D, Sudewi AAR. The role of brain-derived neurotrophic factor (BDNF) in cognitive functions. Bali Medical Journal. 2019;8(2):427-434.

[1] Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 2017;18(2):153–65.

[2] Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH HP. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics 2012;129(3):485–93.

[3] Morales E, Guxens M, Llop S, Rodríguez-Bernal CL, Tardón A, Riaño I et al. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics 2012;130(4):e913–20.

[4] Hanieh S, Ha TT, Simpson JA, Thuy TT, Khuong NC, Thoang DD, et al. Maternal vitamin D status and infant outcomes in rural vietnam: A prospective cohort study. PLOS ONE 2014;9(6):e99005.

[5] Laird E, Thurston SW, van Wijngaarden E, Shamlaye CF, Myers GJ, Davidson PW, et al. Maternal vitamin D status and the relationship with neonatal anthropometric and childhood neurodevelopmental outcomes: Results from the Seychelles child development nutrition study. Nutrients 2017;9(11).

[6] McCarthy EK, Murray DM, Malvisi L, Kenny LC, O'B Hourihane J, Irvine AD, Kiely ME. Antenatal vitamin D status is not associated with standard neurodevelopmental assessments at age 5 years in a well-characterized prospective maternal-infant cohort. J Nutr 2018;148(10):1580–6.

[7] Gale CR, Robinson SM, Harvey NC, Javaid MK, Jiang B, Martyn CN et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 2008;62(1):68–77.

[8] Veena SR, Krishnaveni GV, Srinivasan K, Thajna KP, Hegde BG, Gale CR, Fall CH. Association between maternal vitamin D status during pregnancy and offspring cognitive function during childhood and adolescence. Asia Pac J Clin Nutr 2017;26(3):438–49.

[9] Melough MM, Murphy LE, Graff JC, Derefinko KJ, Lewinn KZ, Bush NR, et al. Maternal Plasma 25-hydroxyvitamin D during gestation is positively associated with neurocognitive development in offspring at age 4–6 years. J Nutr 2021;151(1):132–9.

[10] Tylavsky FA, Kocak M, Murphy LE, Graff JC, Palmer FB, Völgyi E, et al. Gestational vitamin 25(OH)D status as a risk factor for receptive language development: A 24-month, longitudinal, observational study. Nutrients 2015;7(12):9918–30.

[11] Chawla D, Fuemmeler B, Benjamin-Neelon SE, Hoyo C, Murphy S, Daniels JL. Early prenatal vitamin D concentrations and social-emotional development in infants. J Matern Fetal Neonatal Med 2019;32(9):1441–8.

[12] Brouwer-Brolsma EM, Vrijkotte TGM, Feskens EJM. 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):345–52.

[13] Kesby JP, Eyles DW, Burne THJ, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol 2011;347(1–2):121–7.

[14] Cui X, Gooch H, Petty A, McGrath JJ, Eyles D. Vitamin D and the brain: Genomic and non-genomic actions. Mol Cell Endocrinol 2017;453:131–43.

[15] Harms LR, Burne THJ, Eyles DW, McGrath JJ. Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab 2011;25(4):657–69.

[16] Eyles D, Burne T, Mcgrath J. Vitamin D in fetal brain development. Semin Cell Dev Biol 2011;22(6):629–36.

[17] Semrud-Clikeman M. The Capute scales. Pediatr Neurol 2006;34(1):79–80.

[18] Bekinschtein P, von Bohlen Und Halbach O. Editorial. Editorial: Cellular and molecular mechanisms of neurotrophin function in the nervous system. Front Cell Neurosci 2020;14:101.

[19] Mitchelmore C, Gede L. Brain derived neurotrophic factor: Epigenetic regulation in psychiatric disorders. Brain Res 2014;1586:162–72.

[20] Chen HJ, Lee YJ, Huang CC, Lin YF, Li ST. Serum brain-derived neurotrophic factor and neurocognitive function in children with type 1 diabetes. J Formos Med Assoc 2021;120(1 Pt 1):157–64.

[21] As S, Hadju V, Tammasse J. The correlation between brain derived neurotrophic factor (BDNF) level and motor development of children aged under 2 years in Timor Tengah selatan Nusa Tenggara Timur. Ijsbar 2015;23(1):164–72.

[22] Subedi L, Huang H, Pant A, Westgate PM, Bada HS, Bauer JA, et al. Plasma brain-derived neurotrophic factor levels in newborn infants with neonatal abstinence syndrome. Front Pediatr 2017;5:238.

[23] Khairy EY, Attia MM. Protective effects of vitamin D on neurophysiologic alterations in brain aging: Role of brain-derived neurotrophic factor (BDNF). Nutr Neurosci 2021;24(8):650–9. https://doi.org/10.1080/1028415X.2019.1665854.

[24] Sakata K, Overacre AE. Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, CHRM2, and CHRM5: Effects of drug and environmental treatments. J Neurochem 2017;143(1):49–64.

[25] Silakarma D, Sudewi AAR. The role of brain-derived neurotrophic factor (BDNF) in cognitive functions. Bali Medical Journal. 2019;8(2):427-434.

Brain-derived neurotrophic factor (BDNF) and the capute scales in offspring of mothers with normal and deficient vitamin D levels

Abstract

References

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