By skyforbes 
There has been increased evidence showing that maternal vitamin D deficiency during pregnancy impacts the infant’s immune system, increasing the risk of atopic dermatitis in infants. A study shows that vitamin D dysregulates the infant immune system by suppressing FOXP3 gene and protein expression and upregulating the PI3K/AKT/mTOR signaling pathway. Vitamin D deficiency also weakens the skin barrier through decreased cathelicidin production, increasing risk of atopic dermatitis. As a fetus receives vitamin D from its mother, a similar implication could be made surrounding maternal vitamin D deficiency during pregnancy and risk of infant atopic dermatitis. Clinical evidence also shows an association, but it has yet to confirm causation. A cohort study reported that maternal vitamin D deficiency during pregnancy increased the risk of infant atopic dermatitis in the first 6 months by 53%. Another study, the MAVIDOS trial, discovered that vitamin D supplementation during pregnancy reduced the risk of atopic dermatitis in breastfeeding infants at 12 months. However, the benefit was insignificant at 24 months and 48 months, suggesting that the positive effect of supplementation comes from the possibility that vitamin D transferred to infants via breast milk. This literature review aims to evaluate the mechanistic and clinical research surrounding maternal vitamin D deficiency during pregnancy and its effects on infant immune responses and atopic dermatitis risk. Although promising mechanistic and observational data exist, further research would be needed to confirm causality.
Keywords: vitamin D, atopic dermatitis, pregnancy, infant immune development
Keywords: vitamin D, atopic dermatitis, pregnancy, infant immune development
Introduction
Atopic dermatitis is a common chronic, inflammatory skin disorder (Kim et al., 2019). The pathophysiology of atopic dermatitis is not completely known. Current evidence points to skin barrier dysregulation and immune dysregulation (Kim et al., 2019). A disturbed skin barrier, perhaps from an environmental trigger, stimulates keratinocytes to begin a cascade of reactions that produce inflammatory signals (Kim et al., 2019). In atopic dermatitis, these signals further skin barrier dysfunction, which leads to itching symptoms and impairs keratinocyte differentiation. Th2 cytokines will also downregulate the expression of antimicrobial peptides (AMPs), further weakening the skin barrier (Kim et al., 2019). One component that has emerged as an important factor in infant atopic dermatitis is maternal vitamin D deficiency during pregnancy. Vitamin D deficiency is defined as a total 25-hydroxyvitamin D level below 12 ng/mL, although exact definitions differ in various studies (El-Heis et al., 2022; Kaur J et al., 2025). This review aims to examine current findings on the impact of maternal vitamin D status on the development of atopic dermatitis in infants.
Environmental, Nutritional and Ethnic Determinants of Maternal Vitamin D Status
Environmental modifiers and ethnicity can impact maternal vitamin D levels during pregnancy, so it is important to understand their role in the vitamin D levels/absorption of the mother and the impact on the infant. Humans acquire most of their vitamin D from sunlight exposure. Therefore, limited ultraviolet B radiation exposure due to factors such as latitude, season, time of day, and ozone pollution in the atmosphere reduces cutaneous production of vitamin D3. Increased skin pigmentation, aging, and sunscreen application also have the same effect (Holick, 1995). Vitamin D production is also impacted by diet, where vitamin D deficiency is more common in lactose-intolerant individuals, people who have a milk allergy, and ovo-vegetarian and vegan individuals (National Institutes of Health, 2025). Ethnicity also has an impact on the risk of vitamin D deficiency; for example, African Americans show lower levels of vitamin D compared to white Americans, as the cutaneous vitamin D synthesis pathway is less efficient on darker skin (Thamattoor, 2021). Environmental modifiers and ethnicity can increase the risk of vitamin D deficiency in pregnant mothers, thereby impacting fetal development as well.
Immune System Dysregulation
Atopic dermatitis may be caused by immune system dysregulation related to vitamin D deficiency during pregnancy. A study by Ding et al. demonstrated that infants born to mothers with low prenatal vitamin D levels had reduced FOXP3 gene and protein expression in both umbilical cord blood and placental tissue. These infants were also more likely to develop atopic dermatitis.
The FOXP3 gene is a forkhead transcription factor that binds to protein and regulates gene expression (Kim, 2009). FOXP3 works to block pro-inflammatory transcription factors (NFAT and NF-κB), which reduces the production of some immune-activating genes like IL-2 and the production of cytokines, thereby suppressing inflammation. Infants whose mothers had less vitamin D also had reduced FOXP3 expression, which would result in an increase of inflammatory responses (Ding et al., 2023). Therefore, low prenatal vitamin D raises infant atopic dermatitis risk by lowering FOXP3 gene expression, which increases inflammatory responses (Ding et al., 2023).
Placental tissue from vitamin D-deficient pregnancies also showed increased activity in the PI3K/AKT/mTOR signaling pathway, a pathway that primarily regulates cell proliferation, differentiation, and migration (Ding et al., 2023; Teng et al., 2021). The PI3K/AKT/mTOR signaling pathway was also abnormally activated in the peripheral T cells of patients with atopic dermatitis (Teng et al., 2021). Activating the pathway is linked to T-cell proliferation and cytokine secretion, which all lead to inflammation and can increase the likelihood of atopic dermatitis. According to Ding et al., low levels of maternal vitamin D upregulated the PI3K/AKT/mTOR signaling pathway in the placenta. The researchers believe this upregulation may potentially impair the differentiation of embryonic Treg cells, therefore contributing to a higher risk of atopic dermatitis. In conclusion, low maternal vitamin D downregulates FOXP3 expression and upregulates the PI3K/AKT/mTOR signaling pathway, all of which cause inflammation to increase atopic dermatitis risk in infants (Ding et al., 2023).
Skin Barrier Integrity (via Cathelicidin)
Vitamin D deficiency may cause atopic dermatitis through the disruption of skin barrier integrity, via cathelicidin (Schauber & Gallo, 2008). A significant part of our innate immune system is antimicrobial peptides (AMPs), namely cathelicidin. Cathelicidin has two main functions: acting as a direct microbial agent and regulating inflammatory responses (Schauber & Gallo, 2008). Vitamin D3 directly targets and upregulates cathelicidin in keratinocytes, therefore increased vitamin D leads to increased cathelicidin. Cathelicidin has been shown to offer the skin increased protection from bacterial and viral infections; in healthy skin, there are generally low levels of cathelicidin until infection or barrier disruption occurs (Schauber & Gallo, 2008).
Skin lesions in patients with atopic dermatitis exhibited significantly diminished AMP induction; in atopic dermatitis, Th2-type cytokines will actively suppress AMPs such as cathelicidin, leading to a weaker skin barrier. This increased the susceptibility of patients to microbial infections, such as Staphylococcus aureus colonization (Schauber & Gallo, 2008; Kim et al., 2019). Increased microbial invasion leads to increased inflammation, resulting in diseases like atopic dermatitis. This suggests that vitamin D supplementation during pregnancy has the potential to enhance cathelicidin expression and reduce infant atopic dermatitis risk; as well as that maternal vitamin D deficiency may compromise the development of the infant’s skin barrier and immune function.
Clinical Outcomes
Clinical research has investigated the relationship between maternal vitamin D levels during pregnancy and atopic dermatitis in infants (El‐Heis, 2022; Zhang et al., 2024).
A prospective birth cohort study (n=4051) explored the link between maternal vitamin D levels during the first trimester and the risk of atopic dermatitis in infants within the first six months of life. It was found that the risk of atopic dermatitis in infants at 6 months was higher with mothers who were vitamin D-deficient in the first trimester of pregnancy (Zhang et al., 2024). However, this pattern was only seen in naturally conceived pregnancies, not in those of assisted reproductive technology, such as IVF. The occurrence of atopic dermatitis in infants decreased when mothers took multivitamins and vitamin D supplements compared to mothers who did not. Mothers with deficient levels had a 53% higher risk of infants developing atopic dermatitis within 6 months. The study suggests that vitamin D deficiency during pregnancy can increase the risk of atopic dermatitis in infants (Zhang et al., 2024).
On the contrary, MAVIDOS, a double-blind randomized placebo-controlled trial, had less clear results. MAVIDOS examined the relationship between maternal vitamin D supplementation during pregnancy and infant atopic dermatitis at 12, 24, and 48 months (El‐Heis, 2022). Researchers asked pregnant women to take 1000 IU of vitamin D supplementation (cholecalciferol) daily or a placebo, starting from around 14 weeks of pregnancy until birth. Within the sample (n=703), 351 women took a placebo, and 352 women took cholecalciferol, and their infants were then assessed for atopic dermatitis at ages 12, 24, and 48 months. It was found that babies whose mothers took 1000 IU of vitamin D daily had a 43% lower chance of atopic dermatitis at 12 months, yet this effect was only seen in babies who were breastfed for at least one month (El‐Heis, 2022). There was no significant impact of vitamin D supplementation on atopic dermatitis risk at 24 or 48 months old; this may be because the protective effect of cholecalciferol supplementation is only from the transfer of vitamin D via breastmilk after birth (El‐Heis, 2022). These results suggest that the protective effect is not from prenatal vitamin D supplementation, but instead from postnatal vitamin D exposure.
Ultimately, the authors of MAVIDOS concluded that this is not enough evidence to confirm a causal relationship between prenatal vitamin D levels and infant atopic dermatitis, particularly because there were no notable findings at 24 and 48 months. However, the previously mentioned cohort study by Zhang et al showed more promising results of the correlation between vitamin D deficiency and infant atopic dermatitis occurrence. More research is required to further understand the practical effects of vitamin D on infant atopic dermatitis.
Limitations
These studies may be showing inconclusive results because of methodological and population limitations. Firstly, multiple studies that were reviewed in this paper had small sample sizes. The study by Ding et. al had only enrolled 219 mother-child pairs, and the sample size for measuring cytokines and gene expression in cord blood was only 32 samples (Ding et al., 2023). The same is true in the MAVIDOS study; the available data decreases consecutively; there was data available for 635 children at 12 months, 610 at 24 months, and only 449 at 48 months, which may have reduced the statistical power of the study (El‐Heis, 2022). Additionally, in the MAVIDOS trial, women with higher vitamin D levels (>100 nmol/L) were excluded (El‐Heis, 2022). A smaller sample size in a study results in less accurate results, which limit the reliability and applicability of the results; it increases the chance of random variation that may impact results.
Other methodological limitations include short follow up periods; for instance, the prospective birth cohort study by Zhang et al. checked for atopic dermatitis at only 6 months. Atopic dermatitis that may develop after 6 months would be excluded, which ignores possibly insightful data surrounding atopic dermatitis incidence after 6 months. The study by Zhang et al. also used questionnaires to evaluate infants for atopic dermatitis, which introduces possible bias and error as parents/guardians may not interpret symptoms accurately.
Two studies mentioned in this review were also only observational: the study by Ding et al. and the study by Zhang et al. Although the observational studies were indicative of an association between maternal vitamin D deficiency during pregnancy and infant atopic dermatitis, it cannot confirm a causal relationship. Observational studies have no control over other variables that may influence an outcome, and so they cannot fully be exempt from confounding factors.
Some studies evaluated in this literary review include population limitations. Both the study by Ding et al. and the study by Zhang et al. were conducted in only one hospital. The MAVIDOS trial, although conducted in 3 different locations, was only conducted in the UK (El‐Heis, 2022). Limiting the population of the study reduced the generalizability of the results to alternative populations, especially those of different ethnicities, climates, or diets.
Conclusion
Maternal vitamin D deficiency during pregnancy has a negative impact on infant immune systems, and appears to increase the likelihood of atopic dermatitis. Low maternal vitamin D reduces infant FOXP3 gene and protein expression, as well as upregulates the PI3K/AKT/mTOR signaling pathway, which increases inflammatory responses. Low vitamin D also decreases cathelicidin function, an AMP that protects the skin barrier, which leads to an increased risk of atopic dermatitis (Schauber & Gallo, 2008). Furthermore, clinical trials have shown evidence between the relationship of prenatal vitamin D and infant atopic dermatitis, although the results were not clear. A cohort study found that there was a 53% increase in infant atopic dermatitis in vitamin D-deficient mothers, yet the MAVIDOS trial explained that prenatal vitamin D supplementation had no effect on infants aged 24 months and 48 months (El-Heis, 2022; Zhang et al., 2024). There are many limitations before a causal relationship between vitamin D and infant atopic dermatitis can be confirmed. Future research should prioritize multiple international randomized control trials with larger sample sizes to confirm causality.
References
Ding, Y.-J., Li, X.-N., Xiao, Z., Li, C.-Y., & Jia, L.-H. (2023, November 22). Low vitamin D during pregnancy is associated with infant eczema by up-regulation of PI3K/AKT/mTOR signaling pathway and affecting FOXP3 expression: A bidirectional cohort study. https://www.sciencedirect.com/science/article/abs/pii/S0955286323002498
El‐Heis, S. (2022, August 3). Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial. https://pmc.ncbi.nlm.nih.gov/articles/PMC9804289/
Holick, M. (1995, March). Environmental factors that influence the cutaneous production of vitamin D. PubMed. Retrieved August 11, 2025, from https://pubmed.ncbi.nlm.nih.gov/7879731/
Kaur, J., Khare, S., Sizar, O., & Givler, A. (2025, February 15). Vitamin D Deficiency — StatPearls. NCBI. Retrieved August 4, 2025, from https://www.ncbi.nlm.nih.gov/books/NBK532266/
Kim, C. H. (2009). FOXP3 and its role in the immune system. Retrieved August 9, 2025, from https://pubmed.ncbi.nlm.nih.gov/20429413/
Kim, J., Kim, B. E., & Leung, D. Y. M. (2019, March 1). Pathophysiology of atopic dermatitis: Clinical implications — PMC. PubMed Central. Retrieved August 9, 2025, from https://pmc.ncbi.nlm.nih.gov/articles/PMC6399565/
National Institutes of Health. (2025, June 27). Vitamin D — Health Professional Fact Sheet. NIH Office of Dietary Supplements. Retrieved August 11, 2025, from https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Ou, L.-S., Govela, E., Hall, C., & Leung, D. Y. M. (2004, January 23). T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. Retrieved August 9, 2025, from https://www.jacionline.org/article/S0091-6749(04)00929-7/fulltext
Schauber, J., & Gallo, R. L. (2008). The vitamin D pathway: a new target for control of the skin’s immune response? PubMed Central. Retrieved August 4, 2025, from https://pmc.ncbi.nlm.nih.gov/articles/PMC2729115/
Teng, Y., Fan, Y., Ma, J., Lu, W., Liu, N., Chen, Y., Pan, W., & Tao, X. (2021, May 17). The PI3K/Akt Pathway: Emerging Roles in Skin Homeostasis and a Group of Non-Malignant Skin Disorders. PubMed Central. Retrieved August 9, 2025, from https://pmc.ncbi.nlm.nih.gov/articles/PMC8156939/
Thamattoor, A. (2021, January 4). Race/ethnicity differences in vitamin D levels and impact on cardiovascular disease, bone health, and oral health. medRxiv. https://www.medrxiv.org/content/10.1101/2021.01.02.21249149v1.full
Zhang, Q. (2024, July 8). Correlation of Maternal Vitamin D Status in Early Pregnancy and Vitamin D Supplementation during Pregnancy with Atopic Dermatitis in Infants: A Prospective Birth Cohort Study. MDPI. https://www.mdpi.com/2072-6643/16/13/2168#:~:text=The incidence of AD decreased,risk of AD in offspring