INTRODUCTION:

Vitamin D is a fat-soluble vitamin present in isoforms: vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). In addition to being created by the skin when exposed to sunshine, vitamin D3 can be obtained from animal sources such as milk, cod liver oil, and fatty fish. Vitamin D2 is found in plant sources, including mushrooms and yeast exposed to sunlight. These components are required for bone growth and calcium metabolism.¹ Apart from playing a role in skeletal growth, it is also a neurosteroid with a vital role in brain function, which includes calcium signalling, homeostasis, and brain development.^2,3

Around 15.7% of the global population is vitamin D deficient (serum levels less than 30 nmol/L), with a higher prevalence in females than males.^4,5 The prevalence of VDD in India is around 61%, the highest among micronutrients like vitamin B12, folic acid, vitamin A, and iodine.⁶ These decreased levels of vitamin D are associated with risk factors of bone diseases, cardiovascular diseases, upper respiratory tract infections, muscle weakness, and neurodevelopmental disorders. The need and demand for nutrition further increase during breastfeeding and the various phases of pregnancy, accompanied by increasing physiological changes.⁷Higher doses of vitamin D during gestation and lactation increase vitamin D levels in breast milk.⁸Daily supplementation of vitamin D, i.e., up to 6400IU/day during the lactating period, lowers the chances of vitamin D insufficiency in infants without causing any adverse effects in lactating mothers.⁹Further, an optimal dose of vitamin D supplementation is needed during pregnancy and lactation to accomplish baseline serum levels of vitamin D in the neonates and infants. ^10,11,12. When these demands are not fulfilled, it hinders the infant's normal development and hampers fetal growth.^13,14,15

Neurodevelopmental disorders (NDDs)/disabilities affect motor, communication, cognition, and behavioural domains during a child's development.¹⁶The disabilities mainly include Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD), as well as cerebral palsy. The prenatal environment, which includes maternal immune activation, stress, drug exposure, inflammatory changes and undernutrition, could be the possible cause of NDDs.^17,18 Nutritional deficiency during prenatal as well as perinatal periods threatens the development of the offspring, increasing the risk of deficits in neurodevelopment. The role of nutrition is vital, even during early childhood, and malnutrition or undernutrition can jeopardise the healthy growth of a child. ^19,20,21.Undernourishment in early childhood also contributes to NDDs like ADHD. ^22,23 Along with supplements for vitamin D, other specific prenatal nutrients such as iron and folic acid are recommended during pregnancy. Of these nutrients, we aimed to focus our review on the function of Vitamin D in neurodevelopment. Apart from playing a role in bone mineralisation and calcium signalling, it is believed to be a neurosteroid active in the brain, influencing cellular proliferation, differentiation, and neurotrophic and neuroprotective functions. This review aims to correlate the association and relationship of maternal vitamin D levels with the neurodevelopmental health of the offspring.

MATERIALS AND METHODS:

In this review, our search was to explore the prevalence of vitamin D deficiency in mothers and the correlation between maternal vitamin D status and early vitamin D status on the neurodevelopmental health of the offspring. We restricted our search to PubMed and Scopus databases to focus our review on good-quality articles. The search in the PubMed database used MeSH terms (maternal) and (Vitamin D deficiency); a (Maternal) and (Vitamin D deficiency) and (Neurodevelopment). In Scopus, the terms search keys were “Maternal” or “Prenatal” and (Vitamin D deficiency) and (Neurodevelopment). We limited our search to articles published between 2010 and June 2024, including those published in the English language only. The search was also filtered to include clinical trials, clinical studies, case studies, RCTs, and observational studies, focusing on full-text articles. Systematic reviews, meta-analyses, and non-English literature were excluded from the review. The flowchart depicts the details of a selection of articles and the number of articles finally retrieved for review. The irrelevant articles that focused on overall nutrition or emphasised other micronutrients were further excluded from the review among the final articles. Also, a few articles associated the effect of maternal vitamin D on pregnancy outcome; other systems of fetal growth, apart from neurodevelopment, were thus excluded.

The details of the process of selecting articles are depicted in Figure 1

Figure 1: Flowchart on the methods of article selection

Prevalence of maternal vitamin D deficiency:

The need for vitamins and minerals increases during pregnancy and lactation. These demands are generally met with supplements. It was noted that despite vitamin D supplementation during pregnancy, factors such as obesity or low vitamin D levels during early pregnancy failed to increase levels throughout pregnancy and in the infants.^24,25Studies globally reveal varying rates of vitamin D deficiency during pregnancy, from Turkey to Iran, Indonesia, India, and beyond. Geography, race, income, and education influence deficiency rates.^11,37,40 Southeast Asian populations, including those from Vietnam and Mongolia, exhibit a high prevalence of vitamin D deficiency (Figure 2). In Western countries, such as the US, rates vary. It was observed that the base limits for vitamin deficiency and insufficiency vary across studies, although levels below 25 nmol/L are generally classified as deficient; most authors have reported different baselines. Deficiency thresholds vary but often fall below 25 nmol/L, though some studies consider higher thresholds due to increased demand during pregnancy. The deficiency baselines also ranged from 50nmol/L to 75nmol/L in a few studies where the target population was pregnant women.

Figure 2: Graphical Representation of the prevalence of maternal Vitamin D deficiency across the globe

Early vitamin D status and its association with Neurodevelopmental disorders:

Most studies in the human population have revealed an association between neurodevelopmental health and alterations in the levels of micronutrients, including vitamins. These behavioural changes suggest alterations in various molecular factors, including neurotransmitter function, gene expression, responses to immunity and inflammation, and calcium metabolism.

Maternal vitamin D status is associated with various physiological consequences in offspring, including fetal bone mass/ density, respiratory issues like Asthma and bronchiolitis, the onset of Type 1 diabetes mellitus, and neurodevelopmental disorders like autism.^26,27 Several animal and human studies showed an association between maternal vitamin status and offspring's neurodevelopmental health (Table 1 and Table 2). Improving the early vitamin D status, either prenatally or at an early age, also improves the neurobehavioural health of the offspring. Sufficient vitamin D supplementation (200IU/day) during pregnancy provides a better neurodevelopmental score in the child.²⁷It is also assumed that higher doses of vitamin D in infants improved serum vitamin D levels and reduced behavioural problems in early childhood.^28,29 On the contrary, a few authors have opined that supplementation of vitamin D during pregnancy does not improve the infant's fetal growth and health outcomes.^30,31 Surprisingly, few research studies also concluded that prenatal maternal vitamin levels were not associated with learning disabilities and neurodevelopment in children.^32,33But the majority of the articles showed a strong correlation with the same, as depicted in Tables 1 and 2. Interestingly, one of the impacts of vitamin D deficiency was speech and hearing disorders among NDDs.³⁴ Such studies in humans could be correlated with animal studies to understand the involvement of a specific gene that was reduced in animals with loss of speech and hearing, i.e. Fox protein.³⁵ (Table 1 and Table 2). An ADHD cohort of children with a mean age of 9 years, when supplemented with vitamin D and magnesium, improved behaviour and mental health compared to the group treated with a placebo.³⁶Most studies have confirmed that vitamin D plays a major role in brain health development, and a few also suggest that it can improve health and thereby reverse deficiency in infants by providing vitamin supplements for a certain duration. The table specifies the correlation of maternal vitamin D levels on the neurodevelopment of the offspring with changes in the behaviour of the brain in the offspring of the human population (Table 1).

Table 1: Association of maternal Vitamin D deficiency with the neurodevelopment of offspring in the Human Population

Authors	Study type	Key Findings
Dhamayanti et al., 2020³⁷	A prospective cohort study in Indonesia to identify the association of vitamin D levels in mothers during 10-14 weeks of gestation with the child's neurodevelopment from birth to one year.	Maternal vitamin Deficiency in the first trimester was associated with delayed motor and problem-solving skills in infants of 3-6 months.
Runyu Zou 2020 ³⁸	A prospective population-based cohort study in the Netherlands to observe the association of preadolescents' brain morphology in relation to their prenatal vitamin D status.	Persistent low vitamin D levels during pregnancy were associated with smaller brains in children at around ten years of age.
Chu et al. 2022³⁹	A randomised clinical trial to explore the association of levels of maternal vitamin D in pregnancy and ADHD in the offspring.	A higher risk of ADHD, especially in male offspring found in mothers with VDD during pregnancy, and sufficient vitamin D in the third trimester decreased the risk of ADHD.
Hanieh et al., 2014 ⁴⁰	A double-blinded cluster RCT in Vietnam on micronutrient supplementation antenatally investigated the social, motor and behavioural scores in the infants.	Low levels of Vitamin D (below 37.5nmol/L) are associated with a decrease in language scores in infants below six months of age.
Aagaard et al; 2024⁴¹	A prospective RCT to investigate the association of supplementation of vitamin D during pregnancy with the risk of ADHD and autism in their children at the age of 10.	Reduced risk of autism, reduced symptom load in autistic individuals, and reduced risk of ADHD were all linked to higher maternal preintervention 25(OH)D.
Sucksdorff et al;2021⁴²	A retrospective case-control study to investigate the association of ADHD with maternal vitamin D levels.	Low vitamin D status during 1^st trimester of pregnancy revealed an increased risk of ADHD.
Cantio et al;2023 ⁴³	Population-based prospective study to probe the association between serum vitamin D levels during pregnancy and childhood on intelligence quotient(IQ) score at 7 years of age.	A lower full-scale IQ score was seen in boys whose mothers had serum vitamin D levels less than 50nmol/L during early pregnancy.
Melough et ., 2021⁴⁴	A prospective cohort research looking for a relationship between vitamin D to find an association between vitamin D plasma concentration and IQ score in offspring.	A strong association was found between lower plasma amounts of vitamin D during the second trimester and IQ scores in children aged 4 to 6 years.
Lee et.,2021⁴⁵	Population-based(Sweden) cohort study to associate the risk of ASD and newborn and mother’s vitamin D levels.	The whole population did not show a correlation between maternal vitamin D and ASD; however, in the subpopulation (Nordic Mothers), mothers with insufficient vitamin D had 1.58 times higher odds of having children with ASD.
McCarthy et al.,2018⁴⁶	Prospective birth cohort study to understand the relationship between newborn and mother’s vitamin D levels on the ND outcome at 5 years of age.	The study found no association between maternal and neonatal vitamin D levels on neurodevelopmental outcomes at 5 years.
Vinkhuyzen etal., 2017 ⁴⁷	A population-based prospective cohort study to inspect the association between gestational vitamin D status and ASD.	Developmental deficiency of vitamin D during mid-gestation increases the risk of ASD by almost two times.
Darling et al., 2017⁴⁸	Longitudinal study of mother and child paired with data of maternal serum vitamin D during pregnancy and one neurodevelopmental outcome between 6 months to 9 years.	Children of vitamin D-deficient mothers showed suboptimal gross and fine motor skills at 32 months and suboptimal social development skills at 42 months of age, concluding the association in early childhood (under 4 years of age).
Whitehouse et al., 2012 ³⁴	To establish the association between maternal vitamin D levels and fetal neurodevelopment, behaviour and language development.	The study did not find an association between maternal vitamin D status and neurodevelopment in the offspring, but a strong correlation was seen in language impairment at 5 to 10 years of age.

FUTURE SCOPE:

The review summarises the major the role of maternal vitamin D in the neurodevelopmental health of the offspring. To understand the role of vitamin D in causing these NDDs, studies can be carried forward to understand the specific molecular pathways that involve Vitamin D, which has a role in neurodevelopment, neurogenesis and also calcium metabolism. Also, there is a future scope to explore and identify the interaction of vitamin D along with other micronutrients. Further, the research can also attempt to understand the susceptibility of vitamin D deficiency in the population and make an effort to study and implement the models to prevent it with lifestyle modifications. By addressing these issues, public healthcare professionals can contribute to reducing one of the multiple factors that cause NDDs.

CONCLUSION:

Vitamin D is pivotal for neuron growth, differentiation, and survival. It also helps modulate the immune system, potentially protecting the developing brain from inflammation and other insults that could impair cognitive functions. The exponential work in research throws light on the critical role of nutrition during pregnancy, influencing both prenatal and postnatal brain development. Vitamin D deficiency has been linked to a host of neurodevelopmental disorders, including attention deficit hyperactivity disorder, autism spectrum disorder, and schizophrenia. Although this review undoubtedly shows that vitamin D is closely associated with neurodevelopmental outcomes, the mechanism and the alterations in biochemical signalling and imbalanced neurotransmitter release need further exploration and experimentation. Further, these associations necessitate the provision of adequate vitamin D supplementation to support optimal brain development. Furthermore, the benefits of sufficient maternal vitamin D extend beyond the immediate neurodevelopmental outcomes; they contribute to the child's long-term cognitive and psychological health. Public health strategies must ensure and implement measures to improve maternal nutritional status. Regular monitoring of vitamin D levels and increasing the awareness in the maternal cohort regarding the importance of vitamin D in the diet and the sources available can play a considerable role in improving neurodevelopmental outcomes in children. Ensuring adequate maternal vitamin D levels is a straightforward yet profoundly impactful measure that can support offspring's cognitive and psychological well-being, thereby fostering healthier communities.

REFERENCES:

1. Indumathi. K. P. S. Sibyl. Vitamin D and its Influence on Oral Health: A Literature Review. Research Journal of Pharmacy and Technology. 2023; 16(5): 2507-2. doi: 10.52711/0974-360X.2023.00412

2. Groves, N. J. McGrath. J. J. and Burne, T. H. J. Vitamin D as a Neurosteroid Affecting the Developing and Adult Brain. Annual Review of Nutrition. 2014; 34(1): 117–141. https://doi.org/10.1146/annurev-nutr-071813-105557

3. Shwetha M. N. Nancy Chandra Priya. P. Knowledge regarding vitamin D deficiency among students. Asian J. Nursing Education and Research. 2019; 9(1): 66-68.

4. Cui X.Groves.NJ. Burne T H. Eyles. DW and Mcgrath, J. J. Low vitamin D concentration exacerbates adult brain dysfunction. Am J Clin Nutr. 2013; May; 97(5): 907-8. doi: 10.3945/ajcn.113.061176.

5. Suha A. AL-Fakhar. Wifaq M. Ali.Khalil Ismail A. Mohammed, Saad Hasan Mohammed Ali.Jinan M. Mousa.Israa Qasim Hussein. Correlation between Toxoplasmosis and Vitamin D Deficiency in women. Research Journal of Pharmacy and Technology. 2022; 15(9): 4073-7. doi: 10.52711/0974-360X.2022.00683

6. Venkatesh, U. Sharma, A.AnanthanVA. Subbiah, P.Durga R. and CSIR Summer Research training team. Micronutrient deficiency in India: A systematic review and meta-analysis. Journal of Nutritional Science. 2021; 10: e110. https://doi.org/10.1017/jns.2021.102

7. PG Jain. SD Patil. Hemakshi Chaudhari. Amol R. Pawar.Anita B. Patil. Physiological and Anatomical changes during Pregnancy. Asian J. Research Chem. 2020; 13(4): 279-282. doi: 10.5958/0974-4150.2020.00054.1

8. Wall CR. Stewart AW.Camargo CA.Scragg R. Mitchell EA. Ekeroma A.Crane J.Milne T. Rowden J.Horst R. and Grant CC.Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy. The American Journal of Clinical Nutrition. 201anna6; 103(2): 382–388. https://doi.org/10.3945/ajcn.115.114603

9. Hollis BW.Wagner CL.Howard CR.Ebeling M. Shary JR.Smith PG.Taylor SN.Morella K. Lawrence RA. and Hulsey, TC.Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial. Pediatrics. 2015; 136(4): 625–634. https://doi.org/10.1542/peds.2015-1669

10. Aghajafari F.Field CJ.Weinberg AR. Letourneau N and APrON Study Team. Both Mother and Infant Require a Vitamin D Supplement to Ensure That Infants’ Vitamin D Status Meets Current Guidelines. Nutrients. 2018; 10(4). https://doi.org/10.3390/nu10040429

11. Perumal N.Al Mahmud A.Baqui AH. and Roth, DE. Prenatal vitamin D supplementation and infant vitamin D status in Bangladesh. Public Health Nutrition. 2015; 20(10): 1865–1873. https://doi.org/10.1017/S1368980015003092

12. Shakiba M. and Iranmanesh MR.Vitamin D requirement in pregnancy to prevent deficiency in neonates: A randomised trial. Singapore Medical Journal. 2013; 54(5): 285–288. https://doi.org/10.11622/smedj.2013110

13. Harvey NC.Javaid K.Bishop N.Kennedy S.Papageorghiou AT.Fraser R.Gandhi SV. Schoenmakers I. Prentice A. and Cooper C. MAVIDOS .Maternal Vitamin D Osteoporosis Study: Study protocol for a randomized controlled trial. The MAVIDOS Study Group. Trials. 2012; 13(1): 13. https://doi.org/10.1186/1745-6215-13-13

14. Mensink-Bout SM.Van Meel ER.de Jongste JC.Voortman T.Reiss IK. De Jong NW.Jaddoe VWV. and Duijts, L. Maternal and neonatal 25-hydroxyvitamin D concentrations and school-age lung function, asthma and allergy. The Generation R Study. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology. 2019; 49(6): 900–910. https://doi.org/10.1111/cea.13384

15. SchollT O.Chen X.and Stein TP.Maternal calcium metabolic stress and fetal growth123. The American Journal of Clinical Nutrition. 2014; 99(4): 918–925. https://doi.org/10.3945/ajcn.113.076034

16. Ismail FY.and ShapiroB K. What are neurodevelopmental disorders? Current Opinion in Neurology. 2019; 32(4): 611–616. doi:10.1097/WCO.0000000000000710

17. Doi M.Usui N. and Shimada S. Prenatal environment and neurodevelopmental disorders. Frontiers in Endocrinology. 2022;13: 860110. doi:10.3389/fendo.2022.860110

18. Samadi M. Gholami F. Seyedi M.Jalali M. Effatpanah M.Yekaninejad MS. Mohammadzadeh Honarvar N.Effect of vitamin D supplementation on inflammatory biomarkers in school-aged children with attention deficit hyperactivity disorder. International Journal of Clinical Practice. 2022; 1256408. doi:10.1155/2022/1256408

19. PG Jain. SD Patil. Hemakshi Chaudhari.Amol R Pawar.Anita B Patil. Physiological and Anatomical changes during Pregnancy. Asian J. Research Chem. 2020; 13(4): 279-282. doi: 10.5958/0974-4150.2020.00054.1

20. Parmjit Kaur.Parampal Kaur Cheema. To Assess Prevalence of Malnutrition and its Contributory factors among Children aged 1-5 Years in selected rural area of District Sangrur, Punjab. Int. J. of Advances in Nur. Management. 2018; 6(3): 175-178. doi: 10.5958/2454-2652.2018.00040.9

21. Pushpaveni NP. Effectiveness of video Assisted Instructional Module on Antenatal Care on the Pregnancy outcome of pregnant women attending Maternity Hospitals, Bangalore. Asian J. Nursing Education and Research. 2018; 8(4): 505-510. doi: 10.5958/2349-2996.2018.00103.9

22. K Maheswari. V Selvanayaki. Prevalence of Malnutrition among under five Children. Int. J. Adv. Nur. Management. 2015; 3(1): 54-55.

23. Liji R Kurian.Anaswara Shaji. Anitta Maria Alex. Sr. Rini VB. Sheeba Mariam Chacko. Sunitha P George. A Descriptive Study to Assess the Knowledge on Attention Deficit Hyperactivity Disorder (ADHD) among primary school teachers in selected schools, Kottayam. Research Journal of Science and Technology. 2022; 14(1): 30-6. doi: 10.52711/2349-2988.2022.00004

24. Alhomaid RM.Mulhern MS.Strain J.Laird E. Healy M.Parker MJ.and McCann MT. Maternal obesity and baseline vitamin D insufficiency alter the response to vitamin D supplementation: A double-blind, randomized trial in pregnant women. The American Journal of Clinical Nutrition. 2021; 114(3): 1208–1218. https://doi.org/10.1093/ajcn/nqab112

25. Mansur JL.OliveriB. Giacoia E.Fusaro D. and Costanzo PR.Vitamin D: Before, during and after Pregnancy: Effect on Neonates and Children. Nutrients. 2022; 14(9): 1900. doi:10.3390/nu14091900

26. Litonjua AA.Carey VJ. Laranjo N. Harshfield, BJ. McElrath TF.O’Connor GT. SandelM. Iverson RE.Lee-Paritz A.Strunk RC.Bacharier, LB.Macones GA.Zeiger RS. Schatz M. Hollis, BW. Hornsby E.Hawrylowicz C.Wu AC. and Weiss ST. Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial. JAMA. 2016; 315(4): 362–370. https://doi.org/10.1001/jama.2015.18589

27. Rodgers MD.Mead MJ. McWhorter CA. Ebeling MD. Shary JR. Newton DA.Baatz JE. Gregoski, MJ.Hollis BW. and Wagner CL.Vitamin D and Child Neurodevelopment—A Post Hoc Analysis. Nutrients. 2023; 15(19): 4250. https://doi.org/10.3390/nu15194250

28. Sandboge S. Räikkönen K.Lahti-Pulkkinen M. Hauta-alus H.Holmlund-Suila E.GirchenkoP. Kajantie E.Mäkitie O. Andersson S. and Heinonen K. Effect of Vitamin D3 Supplementation in the First 2 Years of Life on Psychiatric Symptoms at Ages 6 to 8 Years: A Randomized Clinical Trial. JAMA Network Open. 2023; 6(5): e2314319.

29. Shakiba M.and Iranmanesh MR.Vitamin D requirement in pregnancy to prevent deficiency in neonates: a randomised trial. Singapore Medical Journal. 2013; 54(5): 285–288. doi:10.11622/smedj.2013110

30. Griffiths M.Goldring S. Griffiths C.Shaheen S. O.Martineau A.Cross L. Robinson S. Warner J. O.Devine A. and Boyle RJ. Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial. PLOS ONE.2015; 10(12): e0145303.

31. Roth DE.Morris SK. Zlotkin S.Gernand AD. Ahmed T.Shanta SS.Papp E.Korsiak J.Shi J. Islam MM.Jahan I.Keya FK.Willan AR.Weksberg R.Mohsin M.Rahman QS. Shah PS.Murphy KE.Stimec J.Al Mahmud A. Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth. The New England Journal of Medicine. 2018; 379(6): 535–546. https://doi.org/10.1056/NEJMoa1800927https://doi.org/10.1001/jamanetworkopen.2023.14319

32. Arrhenius B.Upadhyaya S.Hinkka-Yli-Salomäki S. Brown AS.Cheslack-Postava K.Ohman H. and Sourander A. Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders. Nutrients. 2021; 13(10): Article 10. https://doi.org/10.3390/nu13103321

33. Zhang Y. Zhou CY.Wang XR.Jiao XT.Zhang J.Tian Y. Li LL.Chen C.and YuXD.Maternal and neonatal blood vitamin D status and neurodevelopment at 24 months of age: A prospective birth cohort study. World Journal of Pediatrics. 2023; 19(9): 883–893. https://doi.org/10.1007/s12519-022-00682-7

34. Whitehouse AJO. Holt BJ.Serralha M.Holt PG.Kusel, MMH. and Hart PH. Maternal Serum Vitamin D Levels During Pregnancy and Offspring Neurocognitive Development. Pediatrics. 2012; 129(3): 485–493. https://doi.org/10.1542/peds.2011-2644

35. YatesNJ.TesicD.Feindel KW. Smith JT.Clarke, MW.Wale C.Crew RC.Wharfe MD. Whitehouse AJO.and Wyrwoll CS. Vitamin D is crucial for maternal care and offspring social behaviour in rats. Journal of Endocrinology. 2018; 237(2): 73–85. https://doi.org/10.1530/JOE-18-0008

36. Hemamy M.Pahlavani N. Amanollahi A.Islam SMS.McVicar J. Askari G.and Malekahmadi M. The effect of vitamin D and magnesium supplementation on the mental health status of attention-deficit hyperactive children: A randomized controlled trial. BMC Pediatrics. 2021; 21(1). https://doi.org/10.1186/s12887-021-02631-1

37. Dhamayanti M.Noviandhari A. Supriadi S.Judistiani RT.and Setiabudiawan B. Association of maternal vitamin D deficiency and infants’ neurodevelopmental status: A cohort study on vitamin D and its impact during pregnancy and childhood in Indonesia. Journal of Paediatrics and Child Health. 2020; 56(1): 16–21. doi:10.1111/jpc.14481

38. Zou R. El Marroun H. McGrath JJ. Muetzel RL. Hillegers M. White T. and Tiemeier H. A prospective population-based study of gestational vitamin D status and brain morphology in preadolescents. NeuroImage. 2020; 209: 116514. https://doi.org/10.1016/j.neuroimage.2020.116514

39. Chu SH. Huang M.Kelly RS. Kachroo P. Litonjua AA.Weiss ST.and Lasky-Su J.Circulating levels of maternal vitamin D and risk of ADHD in offspring: Results from the Vitamin D Antenatal Asthma Reduction Trial. International Journal of Epidemiology. 2022; 51(3): 910–918. https://doi.org/10.1093/ije/dyab194

40. Hanieh S.Ha TT. Simpson JA.Thuy TT. Khuong NC.Thoang DDand Biggs BA. Maternal vitamin D status and infant outcomes in rural Vietnam: a prospective cohort study. PloS One. 2014; 9(6): e99005.

41. Aagaard K. Møllegaard Jepsen JR.Sevelsted A. Horner D.Vinding R.Rosenberg JB. Brustad N. Eliasen A.Mohammadzadeh P.Følsgaard N. Hernandez-Lorca M.Fagerlund B. Glenthøj B. Y.Rasmussen MA. Bilenberg N. Stokholm J. Bønnelykke K.Ebdrup BH.and Chawes B.High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial. The American Journal of Clinical Nutrition. 2024; 119(2): 362–370. https://doi.org/10.1016/j.ajcnut.2023.12.002

42. Sucksdorff M. Brown AS.Chudal, R.Surcel, HM.Hinkka-Yli-Salomäki S.Cheslack-Postava K.Gyllenberg, D. and Sourander A.Maternal Vitamin D Levels and the Risk of Offspring Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2021; 60(1): 142-151.e2. https://doi.org/10.1016/j.jaac.2019.11.021

43. Cantio E.Bilenberg N.Nørgaard SM.Beck IH. Möller S. Cantio C.Jensen TK.Mortensen NB. Rasmussen A. and Christesen HBT.Vitamin D status in pregnancy and childhood associates with intelligence quotient at age 7 years: An Odense child cohort study. Australian and New Zealand Journal of Psychiatry. 2023; 57(7): 1062–1072. https://doi.org/10.1177/00048674221116027

44. Melough MM.Murphy LE.Graff JC.Derefinko KJ.LeWinn KZ. Bush NR. Enquobahrie DA. Loftus CT. Kocak M. Sathyanarayana S. and Tylavsky FA. Maternal Plasma 25-Hydroxyvitamin D during Gestation Is Positively Associated with Neurocognitive Development in Offspring at Age 4–6 Years. The Journal of Nutrition. 2021; 151(1): 132–139. https://doi.org/10.1093/jn/nxaa309

45. Lee BK. Eyles DW. Magnusson C. Newschaffer CJ. McGrath JJ. Kvaskoff D. Ko P.Dalman C. Karlsson H.and Gardner RM. Developmental vitamin D and autism spectrum disorders: Findings from the Stockholm Youth Cohort. Molecular Psychiatry. 2021; 26(5): 1578–1588. https://doi.org/10.1038/s41380-019-0578-y

46. McCarthy EK.Murray DM.Malvisi L.Kenny LC.,O’B Hourihane J.Irvine AD.and 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. The Journal of Nutrition. 2018; 148(10): 1580–1586. https://doi.org/10.1093/jn/nxy150

47. Vinkhuyzen AAE.Eyles DW.Burne THJ.Blanken LME.Kruithof CJ.Verhulst F. White T. Jaddoe VW.Tiemeier H.and McGrath JJ. Gestational vitamin D deficiency and autism spectrum disorder. BJPsych Open. 2017; 3(2): 85–90. https://doi.org/10.1192/bjpo.bp.116.004077

48. Darling AL. Rayman MP.Steer CD.Golding J.Lanham-New SA.and Bath S.Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomes in childhood: Results from the Avon Longitudinal Study of Parents and Children (ALSPAC). British Journal of Nutrition. 2017; 117(12): 1682–1692. https://doi.org/10.1017/S0007114517001398

49. Yu S.Park M.Kang J. LeeE.Jung J.and Kim T. Aberrant Gamma-Band Oscillations in Mice with Vitamin D Deficiency: Implications on Schizophrenia and its Cognitive Symptoms. Journal of Personalized Medicine. 2022; 12(2). https://doi.org/10.3390/JPM12020318

50. Bernstein HG. Krause S. Krell D.Dobrowolny H.Wolter M Stauch R.Ranft K. Danos P.Jirikowski GF.and Bogerts B. Strongly Reduced Number of Parvalbumin-Immunoreactive Projection Neurons in the Mammillary Bodies in Schizophrenia. Annals of the New York Academy of Sciences. 2007; 1096(1): 120–127. https://doi.org/10.1196/annals.1397.077

51. Nagarathna PKM.Harsha Vardhini N.Babiker Bashir. Mahesh Kumar C S.Chandanam Sreedhar. Development of Subtype Selective GABAA Modulators: A Review Article. 2019; 12(8): 3967-3972. doi: 10.5958/0974-360X.2019.00683.8

52. Nagarathna PKM.Ayesha Rehman.Pasupati Nath Tiwari. Emerging Role of GABA Receptor: A Review Research J. Pharm. and Tech. 2019; 12(7): 3197-3205. doi: 10.5958/0974-360X.2019.00537.7

53. Al-Harbi AN. Khan KM.and Rahman A. Developmental Vitamin D Deficiency Affects Spatial Learning in Wistar Rats. The Journal of Nutrition. 2017; 147(9): 1795–1805. https://doi.org/10.3945/JN.117.249953

54. HawesJE.Tesic D.Whitehouse AJ. Zosky GR. Smith JT.and Wyrwoll CS. Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse. Behavioural Brain Research. 2015; 286: 192–200. https://doi.org/10.1016/j.bbr.2015.03.008

55. Vega MS.Chong S.and BurneTHJ.Prenatal vitamin D deficiency does not exacerbate behavioural impairments associated with prenatal ethanol exposure in juvenile male mice. Behavioural Brain Research. 2019; 356: 127–136.

Received on 24.08.2024 Revised on 06.03.2025

Accepted on 18.06.2025 Published on 01.12.2025

Available online from December 06, 2025

Research J. Pharmacy and Technology. 2025;18(12):5899-5905.

DOI: 10.52711/0974-360X.2025.00852

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Authors	Study	Result
Al Harbi et al 2017⁵³	Experimental study to explore the implications of developmental vitamin D deficiency on brain morphology and cognitive functions.	Developmental vitamin D deficiency in rats showed impaired learning in the offspring and reduced synapses or connections in the molecular layer of the hippocampus.
Yates et al.,2018³⁵	An experimental case-control study to investigate the effect of maternal vitamin D deficiency on maternal care and neurodevelopment of the offspring in Sprague Dawley rats.	The results demonstrated that Vitamin D-deficient dams expressed decreased maternal care. Adult offspring of vitamin D-deficient dams had decreased social interaction behaviour. They also exhibited larger ventricles and decreased expression of relevant genes involved in GABA synthesis and dopamine signalling.
Hawes et al., 2015 ⁵⁴	An experimental study to identify the effect of maternal vitamin D deficiency on neurodevelopment of the offspring	The embryos of BALB/c deficient mothers showed decreased volume in the lateral ventricle. Also, the Fox protein gene was reduced (involved in speech and hearing) at E14 but later increased by E17, along with a decrease in tyrosine hydroxylase.
M.C. Sanchez Vega, 2019⁵⁵	An experimental study to assess and examine if deficiency of Vitamin D in prenatally ethanol-exposed mice causes alteration in behaviour and dopaminergic genes of the offspring.	The prenatal vitamin deficiency in the rats showed alteration in Dopamine-related genes with overexpression of D2R and TH in the offspring.