Eczema is a chronic and recurring inflammatory skin disease. Clinically, atopic dermatitis and contact dermatitis have eczema-like symptoms (1, 2). In China, conditions such as milk tinea, infantile eczema, eczema, flexural dermatitis, and neurodermatitis are predominantly considered forms of AD. Thus, the distinction between eczema and AD is not well-defined, indicating that eczema could essentially be a manifestation of AD (3, 4). Atopic eczema [or atopic dermatitis (AD)] is the most common form of eczema in children, witnessing a yearly increase in incidence (5). The consequences of eczema surpass mere physical manifestations, impacting children's psychological health and placing financial strain on families. Research has demonstrated that persistent eczema can hinder the physical and mental development of children (6). Consequently, assessing early-life risks and devising prevention strategies continue to be the primary areas of focus for reducing the global burden of allergic diseases (7, 8).

The exact cause of eczema remains elusive. Initial studies posited that an imbalance between helper T1 (Th1) (e.g., interleukin-2, Interferon-γ (IFN-γ)) and Th2 (e.g., IL-4, IL-13) cells was a primary factor in the disease's development (9). Th2 cells are pivotal in the pathogenesis of eczema (10). For example, Dupilumab effectively treats eczema by targeting IL-4 and IL-13 secretion from Th2 cells (11). However, as research has evolved, this Th1/Th2 cell imbalance theory is increasingly seen as insufficient for a comprehensive understanding of eczema's pathogenesis (12). More recent studies have identified an independent T-helper cell subgroup, Th22, thereby opening a new avenue for researching the disease's origins (13). IL-22, part of the IL-10 family, is primarily secreted by Th22 cells and plays a role in skin inflammation, host defense, and tissue homeostasis. It is expressed in various tissues, including the skin, intestines, lungs, liver, kidneys, and pancreas (14). Earlier research posited that IL-22 was primarily secreted by Th17 cells and functioned in conjunction with IL-17 (15). Existing literature indicates that IL-22 may contribute to skin inflammation in eczema patients (16). More recent studies, however, indicate that IL-22 is predominantly produced by Th22 cells. IL-22 exacerbates eczema through binding to IL-22R and activating a range of signaling pathways, including extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen activated protein kinases (p38MAPK), nuclear transcription factor-κB (NF-κB), and activator protein-1 (AP-1) (17–19).

Umbilical cord blood, an early and accessible biological fluid, may offer valuable insights into potential biomarkers for infant eczema. The 42-day mark, coinciding with infants’ first medical follow-up, presents an opportune moment for evaluating eczema incidence and aligns with diagnostic criteria. Yet, no studies have explored the correlation between IL-22 levels in umbilical cord blood and the onset of eczema in 42-day-old infants. This approach seeks to inform early prevention and treatment strategies, potentially reducing the severity or preventing the onset of eczema.

Eczema, an immune-mediated skin disorder, affects 15%–30% of children worldwide, with its prevalence increasing (20, 21). Of the 157 subjects included in this study, 86 developed eczema within 42 days, while 71 did not, yielding an incidence rate of 54.8%. Although the underlying causes of eczema can only be speculated to involve environmental, genetic, and skin barrier factors (22), this study has established a significant link between a family history of allergies and the early onset of infant eczema (p < 0.05). Logistic regression analysis confirmed that a family history of allergies significantly increases the risk of developing early infant eczema, in agreement with existing literature. Research indicates that when both parents have allergic diseases, their children's risk of experiencing allergic diseases is 19.03 times greater than in families without a genetic history of allergies. When only the mother has allergic diseases, the risk for the children rises to 12.55 times (23). An Asian study demonstrated that children with a family history of allergies are at a higher risk of experiencing persistent wheezing, early allergic symptoms, and eczema (24).

IL-22, a member of the IL-10 family, is primarily produced by innate lymphoid cells (ILCs) and CD4+ T cells. The levels of IL-22 in the skin of children with eczema are considerably higher than in adults and correlate significantly with disease activity (25). Recent advancements have shown that inhibiting IL-22 expression can effectively treat eczema (26), and IL-22 has emerged as a crucial factor in eczema evaluation and treatment (27). RyomaKishi (28) et al. discovered a correlation between IL-22 levels and the severity of epidermal thickening and itching in eczema patients.

Consequently, we explored the potential role of IL-22 in eczema's etiology, hypothesizing that its levels in neonatal cord blood could serve as an early marker of immune function. Our findings revealed significantly lower IL-22 levels in the cord blood of infants with eczema compared to those without the condition. This suggests that reduced IL-22 levels could be a predictive factor for the early onset of eczema. However, this finding conflicts with prior studies that report elevated IL-22 levels in eczema patients. This discrepancy might arise from differences in cytokine production at different stages of immune development. Th17 cytokines dominate IL-22 production in early immune processes, and their levels in the cord blood of infants in the eczema group were lower than in those without eczema (8). Furthermore, our findings indicate that IL-22 levels do not correlate with the severity of early infant eczema, likely because the cases studied were predominantly mild to moderate. Logistic regression analysis and ROC curve results suggest that low umbilical cord blood IL-22 levels may play a role in the development of infant eczema within 42 days, indicating a limited predictive value. This limited correlation may be due to the predictive nature of the indicator, as eczema had not manifested at the time of measurement. Despite its modest predictive efficiency, this research is at the forefront of exploring early indicators for eczema, highlighting its innovative yet preliminary nature.

Nevertheless, the study has limitations. The sample size is small, and the IL-22 levels were not reassessed in infants at 42 days. The short follow-up period and inconsistent parental compliance also limit the data's accuracy. Moreover, selection bias was introduced as most participants were children of Beijing Army members. Future studies should increase the sample size, measure additional cytokines in cord blood, extend the follow-up period, and examine venous blood IL-22 levels at different ages to elucidate its role in eczema more comprehensively.

In summary, both low levels of IL-22 and Family history of allergy serve as risk factors for eczema in infants at 42 days old. Additionally, reduced levels of IL-22 in umbilical cord blood moderately predict the occurrence of 42-day infant eczema. However, several limitations should be acknowledged. The study had a small sample size and did not re-examine IL-22 levels in the venous blood of infants when they reached 42 days. The follow-up duration was brief, and non-compliance among some parents led to data inaccuracies. Moreover, a selection bias existed, as most participants were children of Beijing Army personnel. Future research should enlarge the sample size, measure additional cord blood cytokines, and extend the follow-up to include observations at 3, 6, and 12 months. Researchers should also collect venous blood at these time points to further investigate the role of IL-22 in eczema development.