{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:29Z","timestamp":1787027849416,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Padjadjaran","award":["1595\/UN6.3.1\/PT.00\/202"],"award-info":[{"award-number":["1595\/UN6.3.1\/PT.00\/202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Short stature remains a global problem and is associated with vitamin D status. Vitamin D is also a neurosteroid with regard to neurotrophic factors but its role in development is unclear. Therefore, this study analyzed the relationships between vitamin D, NGF, GDNF, and BDNF and developmental status in children with a history of short stature (&lt;2 years). Methods: This research is a prospective cross-sectional study conducted in March 2022. The vitamin D, NGF, GDNF, and BDNF levels were measured in stored biological materials from children aged 2\u20134 years, and their Ages and Stages Questionnaire (ASQ-3) scores were also assessed. The results were analyzed via the chi-square test, Fisher\u2019s exact test, Mann\u2013Whitney test for NGF, unpaired t-test, and Spearman rank correlation. Results: Among the 85 study subjects, 41.2% were short in stature, with 37% having developmental deviation. Male sex (p = 0.038) and low maternal education (p = 0.024) were associated with short stature. The mean vitamin D level was lower (p = 0.041) in children with short stature (27.65 ng\/dL). The risk factors associated with short stature were vitamin D levels \u2264 32.7 ng\/dL, GDNF levels \u2264 12.99 ng\/mL, male sex, and low maternal education. Children with short stature (&lt;2 years old) also demonstrated impaired problem-solving as assessed by the ASQ-3 (p = 0.005). Vitamin D was also associated with gross motor skills (p = 0.035) and personal social development (p = 0.038). Conclusions: There was no association of vitamin D with NGF, GDNF, or BDNF levels. Vitamin D levels are associated with short stature and development in children, especially gross motor skills, personal social development, and problem solving.<\/jats:p>","DOI":"10.3390\/children12010060","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:17:02Z","timestamp":1736155022000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Association of Vitamin D, Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Cell-Derived Neurotrophic Factor (GDNF) with Development in Children"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5646-9145","authenticated-orcid":false,"given":"Mia Milanti","family":"Dewi","sequence":"first","affiliation":[{"name":"Child Health Department, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung 40161, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhmad","family":"Imron","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung 40161, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly Amalia","family":"Risan","sequence":"additional","affiliation":[{"name":"Child Health Department, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung 40161, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Mediana","sequence":"additional","affiliation":[{"name":"Bandung City Health Service, Bandung 40161, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-0708","authenticated-orcid":false,"given":"Raden Tina Dewi","family":"Judistiani","sequence":"additional","affiliation":[{"name":"Public Health Department, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4842-2451","authenticated-orcid":false,"given":"Budi","family":"Setiabudiawan","sequence":"additional","affiliation":[{"name":"Child Health Department, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung 40161, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018). Reducing Stunting in Children:Equity Considerations for Achieving the Global Nutrition Targets 2025, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Huang, S., Chen, Z., Chen, R., Zhang, Z., Sun, J., and Chen, H. (2022). Analysis of Risk Factors and Construction of a Prediction Model for Short Stature in Children. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.1006011"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Atamou, L., Rahmadiyah, D.C., Hassan, H., and Setiawan, A. (2023). Analysis of the Determinants of Stunting among Children Aged below Five Years in Stunting Locus Villages in Indonesia. Healthcare, 11.","DOI":"10.3390\/healthcare11060810"},{"key":"ref_4","unstructured":"Kementerian Kesehatan (2022, March 20). Profil Kesehatan Indonesia 2019. Available online: https:\/\/www.kemkes.go.id\/id\/profil-kesehatan-indonesia-2019."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3126\/jdean.v4i1.30075","article-title":"An Integrated Approach to Management of Short Stature in Children","volume":"4","author":"Bajracharya","year":"2020","journal-title":"J. Diabetes Endocrinol. Assoc. Nepal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/mcn.12231","article-title":"Childhood Stunting: A Global Perspective","volume":"12","author":"Branca","year":"2016","journal-title":"Matern. Child Nutr."},{"key":"ref_7","first-page":"25","article-title":"Effects of Stunting on Child Development: A Meta-Analysis","volume":"6","author":"Rosyidah","year":"2021","journal-title":"J. Matern. Child Heal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1542\/peds.2016-2828D","article-title":"Neurodevelopment, Nutrition, and Inflammation: The Evolving Global Child Health Landscape","volume":"139","author":"Bhutta","year":"2017","journal-title":"Pediatrics"},{"key":"ref_9","first-page":"7","article-title":"ASQ-3: Validation of the Ages and Stages Questionnaire for the Detection of Neurodevelopmental Disorders in Argentine Children","volume":"116","author":"Otalvaro","year":"2018","journal-title":"Arch. Argent. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Moretti, R., Morelli, M.E., and Caruso, P. (2018). Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201806.0460.v1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Caccamo, D., Ricca, S., Curr\u00f2, M., and Ientile, R. (2018). Health Risks of Hypovitaminosis D: A Review of New Molecular Insights. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030892"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neulet.2013.12.026","article-title":"Serum Nerve Growth Factor (NGF) Levels in Children with Attention Deficit\/Hyperactivity Disorder (ADHD)","volume":"560","author":"Guney","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/imm.12717","article-title":"Nerve Growth Factor: A Neuroimmune Crosstalk Mediator for All Seasons","volume":"151","author":"Skaper","year":"2017","journal-title":"Immunology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.12688\/wellcomeopenres.15730.1","article-title":"Effects of Vitamin D Deficiency on Neurobehavioural Outcomes in Children: A Systematic Review","volume":"5","author":"Mutua","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e11030","DOI":"10.1097\/MD.0000000000011030","article-title":"Prevalence of Vitamin D Insufficiency among Children in Southern China: A Cross-Sectional Survey","volume":"97","author":"Guo","year":"2018","journal-title":"Medicine"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Judistiani, R.T.D., Madjid, T.H., Irianti, S., Natalia, Y.A., Indrati, A.R., Ghozali, M., Sribudiani, Y., Yuniati, T., Abdulah, R., and Setiabudiawan, B. (2019). Association of First Trimester Maternal Vitamin D, Ferritin and Hemoglobin Level with Third Trimester Fetal Biometry: Result from Cohort Study on Vitamin D Status and Its Impact during Pregnancy and Childhood in Indonesia. BMC Pregnancy Childbirth, 19.","DOI":"10.1186\/s12884-019-2263-1"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Supriadi, S., Gumilang, L., Setiabudi, D., Dewi, R.T., Setiabudiawan, B., and Dhamayanti, M. (2020). Cord Blood Vitamin D Is Correlated with Problem Solving Domain in Early Childhood Neurodevelopment: A Cohort Study on Vitamin D Status and Its Impact during Pregnancy and Childhood in Indonesia. Preprint.","DOI":"10.21203\/rs.3.rs-18033\/v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4161\/derm.24054","article-title":"Vitamin D Status and Sun Exposure in Southeast Asia","volume":"5","author":"Nimitphong","year":"2013","journal-title":"Dermato-Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tofail, F., Islam, M.M., Mahfuz, M., Ashraful Alam, M., Aktar, S., Haque, R., Hossain, M.I., Mondal, D., Petri, W.A., and Ahmed, T. (2019). Association of Vitamin D Nutrition with Neuro-Developmental Outcome of Infants of Slums in Bangladesh. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221805"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/jpc.14481","article-title":"Association of Maternal Vitamin D Deficiency and Infants\u2019 Neurodevelopmental Status: A Cohort Study on Vitamin D and Its Impact during Pregnancy and Childhood in Indonesia","volume":"56","author":"Dhamayanti","year":"2020","journal-title":"J. Paediatr. Child Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13537","DOI":"10.1111\/mcn.13537","article-title":"Patterns in Child Stunting by Age: A Cross-Sectional Study of 94 Low- and Middle-Income Countries","volume":"19","author":"Karlsson","year":"2023","journal-title":"Matern. Child Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Laksono, A., Wulandari, R., Amaliah, N., and Wisnuwardani, R. (2022). Stunting among Children under Two Years in Indonesia: Does Maternal Education Matter?. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271509"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Quah, S.W., Abdul Majid, H., Al-Sadat, N., Yahya, A., Su, T.T., and Jalaludin, M.Y. (2018). Risk Factors of Vitamin D Deficiency among 15-Year-Old Adolescents Participating in the Malaysian Health and Adolescents Longitudinal Research Team Study (MyHeARTs). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200736"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2333794X211034075","DOI":"10.1177\/2333794X211034075","article-title":"The Association of Vitamin D and Neurodevelopmental Status Among 2 Years Old Infants","volume":"8","author":"Juwita","year":"2021","journal-title":"Glob. Pediatr. Health"},{"key":"ref_25","first-page":"10","article-title":"A Systematic Review and Meta-Analysis of Prevalence of Vitamin D Deficiency among Indonesian Pregnant Women: A Public Health Emergency","volume":"3","author":"Octavius","year":"2023","journal-title":"AJOG Glob. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1001\/jamapediatrics.2022.4581","article-title":"Influence of Vitamin D Supplementation on Growth, Body Composition, and Pubertal Development among School-Aged Children in an Area with a High Prevalence of Vitamin D Deficiency: A Randomized Clinical Trial","volume":"177","author":"Ganmaa","year":"2023","journal-title":"JAMA Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3399\/bjgp23X732525","article-title":"Assessment of Childhood Short Stature","volume":"73","author":"Storr","year":"2023","journal-title":"Br. J. Gen. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1017\/S1368980017002816","article-title":"Vitamin D Status Is Associated with Underweight and Stunting in Children Aged 6\u201336 Months Residing in the Ecuadorian Andes","volume":"21","author":"Mokhtar","year":"2018","journal-title":"Public Health Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/mcn.12088","article-title":"Contextualising Complementary Feeding in a Broader Framework for Stunting Prevention","volume":"9","author":"Stewart","year":"2013","journal-title":"Matern. Child Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.18203\/2349-3291.ijcp20174733","article-title":"Effect of Vitamin D Supplementation on Growth Parameters of Children with Vitamin D Deficiency: A Community Based Randomized Controlled Trial","volume":"4","author":"Mugunthan","year":"2017","journal-title":"Int. J. Contemp. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3126\/ajms.v6i1.10199","article-title":"Vitamin D Deficiency in Children","volume":"6","author":"Ashraf","year":"2015","journal-title":"Asian J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Czerwinska, A., and Krzyscin, J. (2020). Numerical Estimations of the Daily Amount of Skin-Synthesized Vitamin D by Pre-School Children in PolandNo Title. J. Photochem. Photobiol., 208.","DOI":"10.1016\/j.jphotobiol.2020.111898"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lewin, G., and Carter, B. (2014). NGF, BDNF, NT3, and NT4. Neurotrophic Factors. Handbook of Experimental Pharmocology, Springer.","DOI":"10.1007\/978-3-642-45106-5_1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13034-016-0097-4","article-title":"Association of Peripheral BDNF Level with Cognition, Attention and Behavior in Preschool Children","volume":"10","author":"Yeom","year":"2016","journal-title":"Child Adolesc. Psychiatry Ment. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2174\/1871527318666190703103709","article-title":"The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine, and Serotonin in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"18","author":"Seyedi","year":"2019","journal-title":"CNS Neurol. Disord. Targets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"784040","DOI":"10.1155\/2012\/784040","article-title":"NGF, Brain and Behavioral Plasticity","volume":"2012","author":"Berry","year":"2012","journal-title":"Neural Plast."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1479-5876-10-239","article-title":"Nerve Growth Factor: From the Early Discoveries to the Potential Clinical Use","volume":"10","author":"Aloe","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_38","first-page":"157","article-title":"The Effect of Vitamin D Treatment on Nerve Growth Factor (NGF) Release from Hippocampal Neurons","volume":"51","author":"Dursun","year":"2014","journal-title":"N\u00f6ro Psikiyatr. Ar\u015fivi"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00787-016-0898-2","article-title":"Serum Brain-Derived Neurotrophic Factor, Glial-Derived Neurotrophic Factor, Nerve Growth Factor, and Neurotrophin-3 Levels in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"26","author":"Toker","year":"2017","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"331","DOI":"10.14336\/AD.2015.0825","article-title":"The Involvement of BDNF, NGF and GDNF in Aging and Alzheimer\u2019s Disease","volume":"6","author":"Budni","year":"2015","journal-title":"Aging Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e038182","DOI":"10.1136\/bmjopen-2020-038182","article-title":"Screening Tools for Early Identification of Children with Developmental Delay in Low-and Middle-Income Countries: A Systematic Review","volume":"10","author":"Faruk","year":"2020","journal-title":"BMJ Open"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1530\/JOE-18-0008","article-title":"Vitamin D Is Crucial for Maternal Care and Offspring Social Behaviour in Rats","volume":"237","author":"Yates","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41398-019-0626-z","article-title":"1,25-Dihydroxyvitamin D Modulates L-Type Voltage-Gated Calcium Channels in a Subset of Neurons in the Developing Mouse Prefrontal Cortex","volume":"9","author":"Gooch","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_44","unstructured":"El Baba, R., and Schury, M.P. (2023). Neuroanatomy, Frontal Cortex. StatPearls, StatPearls Publishing."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12937-017-0285-y","article-title":"Vitamin-D Status and Neurodevelopment and Growth in Young North Indian Children: A Secondary Data Analysis","volume":"16","author":"Chowdhury","year":"2017","journal-title":"Nutr. J."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/1\/60\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:23:20Z","timestamp":1759919000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/1\/60"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,6]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["children12010060"],"URL":"https:\/\/doi.org\/10.3390\/children12010060","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,6]]}}}