UNVEILING CONNECTIONS: THE IMPACT OF VITAMIN D ON LANGUAGE DEVELOPMENT IN PEDIATRIC NEURODEVELOPMENTAL CONTEXTS

UNVEILING CONNECTIONS: THE IMPACT OF VITAMIN D ON LANGUAGE
DEVELOPMENT IN PEDIATRIC NEURODEVELOPMENTAL CONTEXTS

Sevdzhihan Eyubova1,2, Antoniya Hachmeriyan2,3, Albena Toneva2,4
1Department of Pedagogy and Management in Education, Faculty of Education, Konstantin Preslavsky University of Shumen, 115 Universitetska Str., 9700 Shumen, Bulgaria 2Research Group Nutrilect, Department of Neuroscience, Research Institute, Medical University – Varna, 55 Marin Drinov Str., 9000 Varna, Bulgaria 3 Department of physiology and pathophysiology, Faculty of Medicine, Medical University of Varna
4 Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna

ABSTRACT
Purpose: This literature review aims to investigate the impact of vitamin D on language development in pediatric neurodevelopmental contexts by analyzing a selection of articles published between 2012 and 2024. Material/Methods: The review includes studies with various designs, such as crosssectional studies, prospective cohort studies, and randomized controlled trials. The populations studied encompass infants and children with and without autism spectrum disorders. Vitamin D levels were measured using blood samples, and language development was assessed using tools such as the Bayley Scales of Infant and Toddler Development and the Autism Treatment Evaluation Checklist.
Results:The review found results suggesting that vitamin D status may play a role in language development, particularly during pregnancy and early childhood. Several studies indicated that higher vitamin D levels were associated with improved language outcomes, including vocabulary, grammar, and syntax. However, the outcomes was not consistent across all studies, with some finding no significant effect of vitamin D supplementation on language development. Conclusions: The review highlights the need for further research to determine the optimal vitamin D levels for language development and the potential benefits of vitamin D supplementation during pregnancy and early childhood. The findings have implications for clinical practice and public health policy, particularly in populations at risk of vitamin D deficiency.

Keywords: Vitamin D, Language Development, Neurodevelopment, Pediatrics, Pregnancy, Infants, Children, Autism Spectrum Disorder.

INTRODUCTION
Neurodevelopment refers to the complex process involving structural changes and functional maturation of neural circuits throughout life, shaping cognition, emotion, perception, learning, memory, attention, communication, social interaction, and executive functions. Among numerous environmental influences affecting brain growth and function, nutritional components like vitamin D have gained considerable interest due to their pleiotropic effects beyond bone metabolism [1]. Recent years have seen growing scientific exploration regarding the connection between vitamin D and neurodevelopmental processes, especially concerning language acquisition—one of the most critical aspects of human intellectual capacity. This literature review seeks to uncover current knowledge surrounding the influence of vitamin D on language development in pediatric neurodevelopmental settings. Specifically, we aimed to address two primary objectives: firstly, investigating whether
variations in prenatal and postnatal vitamin D exposure correlate with differences in child language abilities; secondly, evaluating if interventions targeting vitamin D insufficiency could improve linguistic competency in vulnerable groups. To achieve our goals, we conducted extensive search in three prominent databases – PubMed, Scopus, and ScienceDirect – yielding relevant publications spanning from 2012 to 2024. Our focus centered on empirical studies employing sound experimental techniques, primarily comprising longitudinal observations, case-control comparisons, and 90 intervention strategies. Furthermore, given the scope of this paper, priority has been accorded to peerreviewed journals reporting original research rather than reviews or commentaries. In sum, understanding how vitamin D impacts language development holds substantial promise towards informing preventative measures against suboptimal neurological functioning and improving therapeutics tailored specifically toward individuals suffering from impaired verbal capacities.

MATERIALS AND METHODS
The articles were identified through search in PubMed (n = 27), Scopus (n = 72), and ScienceDirect (n = 47). A total of 146 articles were identified, with 135 unique articles screened. After the screening and selection process, 13 articles were included in the final review. The screening and selection of studies for the final inclusion were carried out using Rayyan's Blind On option. The PICO descriptions for the narrative review are as follows: Population (P): Children with neurodevelopmental disorders, typically developing children. Intervention (I): Vitamin D supplementation, varying vitamin D levels. Comparison (C): Adequate vs. deficient vitamin D levels, placebo vs. active treatment. Outcome (O): Primary outcomes related to neurodevelopmental contexts and language development. The included articles were a mix of study designs, including longitudinal cohort studies, retrospective surveys, retrospective reviews, randomized controlled trials, and case-control studies. The age range of the study samples varied from 6-8 months to 5 years. The interventions and exposures studied
included vitamin D supplementation, varying vitamin D levels, and the effect of umbilical cord essential and toxic elements. The vitamin D measures included serum vitamin 25(OH)D levels in infants, maternal blood values of vitamin D during pregnancy, and serum 25-hydroxyvitamin D (25(OH)D) levels in children. The language and/or neurodevelopmental measures used in the studies encompassed a wide range of assessments, such as the Bayley Scale of Infant and Toddler Development, MacArthur Communicative Development Inventories, Peabody Picture Vocabulary Test—Revised, Kyoto Scale of Psychological Development 2001.

RESULTS
The studies included in this article demonstrated significant differences in language development between participants with vitamin D deficiency and those without. Tofail et al., 2019 found that vitamin-D-deficient children had significantly lower scores in activity and soothability subscales of temperament, understood a lesser number of words, and were less active during developmental assessments compared to group of children without vitamin D deficiency [2]. Some authors [3] reported that children of mothers with vitamin D deficiency (<30 nmol/L) scored significantly lower on cognitive and language scales in 1st trimester, and all language scales in 3rd trimester, compared to children of mothers with sufficient levels of vitamin D (>50 nmol/L). Other research group found a significant linear trend between quartiles of maternal vitamin D levels and language impairment at 5 and 10 years of age [4]. The risk of women with vitamin D insufficiency during pregnancy having a child with clinically significant language difficulties was increased close to twofold compared with
women with vitamin D levels >70 nmol/L. Hart & All, 2015 reported that maternal vitamin D deficiency at 18 weeks gestation was significantly associated with reduced neurocognitive development in the offspring, including language impairment at ages 5 and 10 [5]. Guo et al., 2019 found that children with autism spectrum disorders (ASD) and vitamin D deficiencies had lower language scores compared to those without deficiencies [6] [7] [8]. These findings suggest an association between vitamin D deficiency and impaired language development in children.

DISCUSSION
The review of the studies on vitamin D and neurodevelopmental outcomes yielded several findings on association with language development [2] ; effect on neurodevelopmental skills [3]; language 91 impairment risk [4, 5]; vitamin D supplementation effects [9-13] observed substantial improvement in ASD rating scales in patients with higher final 25-(OH)D levels, indicating the potential efficacy of
vitamin D supplementation in improving neurodevelopmental outcomes in children with autism spectrum disorders. The positive outcomes from the review provide valuable insights into the potential influence of vitamin D on language development and neurodevelopmental skills [12, 14], as well as the implications for maternal vitamin D status and supplementation in improving offspring's neurodevelopment.
Limitations of the narrative review on vitamin D and neurodevelopmental outcomes include the following: Sample Size Discrepancies: The studies exhibit variations in sample sizes, which may influence the generalizability of the findings. Gender Disparities: The gender distribution within the study populations was not always balanced, with some studies having a significantly higher proportion of male participants. This imbalance may introduce gender-related biases in the outcomes and limit the generalizability of the findings to both genders. Retrospective Design: Several studies employed a retrospective design, which can be susceptible to recall bias and limitations in establishing causal relationships. This design may restrict the strength of evidence compared to prospective or interventional studies. Outcome Measures: The diversity of neurodevelopmental outcome measures used across the studies, such as language assessments, cognitive scales, and behavioral inventories,
makes it challenging to directly compare the results and draw overarching conclusions. Standardization of outcome measures could enhance the consistency and comparability of findings.Vitamin D Assessment Timing: Variability in the timing of vitamin D assessment, including prenatal, infancy, and childhood periods, may introduce complexities in interpreting the impact of vitamin D on neurodevelopmental outcomes. A standardized approach to vitamin D assessment timing could provide more cohesive insights. Confounding Factors: The potential influence of confounding
variables, such as socioeconomic status, maternal education, and dietary habits, was not consistently addressed across all studies. Failing to account for these factors could introduce bias and limit the accuracy of the associations between vitamin D and neurodevelopmental outcomes. These limitations collectively suggest that while the studies offer valuable insights into the relationship between vitamin D and neurodevelopmental outcomes, caution should be exercised in generalizing the findings. Addressing these limitations through larger, well-controlled prospective studies with standardized measures and comprehensive consideration of confounding factors is essential to strengthen the evidence base.

CONCLUSIONS
Several practical implications and areas for further research regarding the relationship between vitamin D and neurodevelopmental outcomes are highlighted.
Implications for Practice. Healthcare providers should consider monitoring and addressing vitamin D levels in pregnant women and infants to potentially improve language development. There may be benefits from using vitamin/mineral supplements, including vitamin D, for individuals with autism spectrum disorders, especially in cognitive and language-related symptoms. Targeted interventions for
pregnant women with low vitamin D levels may help reduce the risk of language impairment in their children.
Implications for Further Research. More longitudinal studies are needed to understand the causal link between vitamin D status and language development while considering factors such as socioeconomic status and maternal education. Research exploring the relationship between vitamin D supplementation and language development in children, especially those with neurodevelopmental disorders, could provide valuable insights for clinical practice. Future studies should conduct subgroup analyses based 92 on age, gender, and socioeconomic backgrounds to understand the varying effects of vitamin D on language development across diverse populations.

Funding: This study is financed by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0009-C02.

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