Eczema is a dermatological condition characterized by erythema, swelling, desquamation, and xerosis. Among the various subtypes of eczema, atopic dermatitis (AD) is the most prevalent (1). This chronic inflammatory skin disorder is marked by pruritus, erythema, edema, and exudative lesions. Furthermore, AD affects up to 25% of children under 7 years old, making it one of the most common chronic disorders (2). Current research has linked several prenatal exposures, such as maternal psychosocial stress, passive smoking, dietary patterns, and alcohol consumption, to the development of eczema/AD in offspring (3–6). In particular, some studies indicate that maternal anxiety/depression during pregnancy may be associated with an increased incidence of eczema/AD in children (3, 7). However, a definitive academic consensus on this issue remains elusive (8). Therefore, this study aims to resolve this controversy by reviewing cohort studies to investigate the association between maternal anxiety/ depression during pregnancy and the subsequent development of eczema/AD in offspring.

The primary objective of this meta-analysis is to investigate the relationship between maternal anxiety/depression during pregnancy and offspring suffering from eczema/AD. This study conducted systematic searches in PubMed, Embase, Web of Science, and Cochrane Library from database inception to July 2025 utilizing the following terms: [(offspring OR newborn OR neonate OR infant OR baby OR progeny OR children OR child OR kids OR toddler OR adolescent OR teenager) AND (dermatitis, atopic OR eczema OR atopic dermatitis OR atopic eczema)] AND [(pregnant OR pregnancy OR pregnant woman OR antenatal OR prenatal OR postpartum OR gestation OR perinatal OR pregnancy-related OR maternal) AND (depressive OR depression OR depressive state OR anxiety OR anxious)]. Additionally, to ensure comprehensiveness of searches, the references of all included articles would be also screened for additional eligible studies. A detailed description of the search strategy is available in the Supplementary Search Strategy. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) guidelines with registration on PROSPERO (CRD420251113756).

This meta-analysis aggregated data from 12 high-quality cohort studies to assess the relationship between maternal anxiety/depression during pregnancy and the development of eczema/AD in offspring. Our results demonstrated that maternal anxiety and depression during pregnancy were potentially associated with a higher incidence eczema/AD in children when compared to control groups. The potential underlying mechanisms may include the following:

A study has identified a robust genetic correlation between AD and major depressive disorder (MDD), revealing 11 pleiotropic loci that are jointly associated with both conditions. Of these, six loci exhibited concordant effects in the AD-MDD pair. Notably, a significant pleiotropic region was found within the 5q31.1 cytokine gene cluster, which includes interleukin (IL)-4 and IL-13, both recognized as risk genes for AD. Additionally, gene-set analysis indicated substantial enrichment in inflammatory pathways, such as leukocyte differentiation, which are implicated in both AD and depression (23, 24). This genetic predisposition may be transmitted from mother to offspring which could facilitate T helper 2 (Th2) cell differentiation and may contribute to dysregulated immune responses in subsequent generations (25–27).

Another study suggested that maternal anxiety might influence the onset of AD in descendants by modifying placental DNA methylation. Anxiety is thought to elevate tumor necrosis factor-α levels, which, in turn, induce hypomethylation of a particular CpG site in the matrix metalloproteinase (MMP) 27 gene, resulting in its upregulation (28, 29). MMP27, a member of the MMP family, is implicated in inflammation through the regulation of inflammatory mediators, establishment of chemokine gradients to facilitate inflammatory cell recruitment, and cleavage of endothelial junctional proteins to compromise barrier integrity (30). Consequently, MMP27 protein participation in inflammatory processes may contribute to the pathogenesis of AD. Additionally, genetic factors could also influence impaired skin barrier function. Evidence suggests that Western patients with AD exhibit a higher prevalence of filaggrin gene mutations than their Asian counterparts, resulting in impaired filaggrin function, compromising the skin barrier, and increasing the susceptibility to AD onset and aggravation (31, 32). This trend was consistent with findings from subgroup analysis on anxiety, showing a stronger association of maternal anxiety with offspring eczema/AD development in Western nations (OR = 1.34) than in Eastern regions (OR = 1.13). Conversely, the subgroup analysis on depression indicated a similar influence of maternal depression on offspring eczema and AD in both Eastern and Western countries, albeit the association in the Western subgroup lacked statistical significance. These outcomes could potentially be attributed to inadequate sample sizes.

As previously mentioned, the expression of the IL-4 and IL-13 genes is upregulated. Elevated levels of these pro-inflammatory cytokines, specifically IL-4 and IL-13, have been observed in mothers experiencing depression or anxiety during pregnancy (29, 33–35). These cytokines may traverse the placental barrier and enter fetal circulation. Immunologically, studies have shown that IL-4 and IL-13 facilitate Th2 cell differentiation, IgE synthesis, and the activation of eosinophils and mast cells, thereby inciting inflammation and pruritus (36–39). Concerning skin barrier function, these cytokines downregulate essential proteins, including filaggrin, and impair lipid synthesis, disrupt keratinocyte differentiation, and reduce antimicrobial peptide production (40–42). Collectively, these effects may contribute to xerosis, compromised skin integrity, and heightened susceptibility to infection. Additionally, IL-13 contributes to dermal thickening and lichenification, which are characteristic of chronic AD, by stimulating collagen accumulation and fibrotic processes (43, 44). Beyond genetic factors, researchers have proposed that prenatal stress may contribute to elevated levels of IL-4 and IL-13 through mechanisms such as the activation of the hypothalamic-pituitary-adrenal (HPA) axis and a Th2-skewed immune response, which suggests a potential pathway that could be associated with an increased incidence of eczema/AD in offspring (45, 46). To investigate this multifactorial pathway, a subgroup analysis was conducted, adjusting for a family history of allergic diseases. The results indicated that offspring in the exposed group showed a higher incidence of developing eczema/AD compared to the control group. Taken together, these findings suggest that the development of eczema/AD in offspring involves environmental factors in addition to genetic predisposition.

Apart from the pro-inflammatory cytokine environment, the dysregulation of the maternal HPA axis may represent another crucial pathway linking maternal anxiety/depression during pregnancy to the development of eczema or AD in offspring. Depressed pregnant individuals have been found to exhibit increased levels of placental corticotropin-releasing hormone (pCRH) in their plasma, likely influenced by heightened cortisol levels, the final product of the HPA axis, which elevate in response to maternal anxiety and depression. pCRH is widely recognized as a significant factor in shaping fetal HPA axis development. This increase elevates fetal glucocorticoid levels, resulting in supraphysiological exposure of the fetus (47, 48). Studies on animals indicated that such prenatal exposure to glucocorticoids could alter the fetal HPA axis, resulting in functional disruptions (49). Patients with AD have shown abnormalities in the HPA axis, possibly indicating compromised HPA-mediated immune regulation, thereby increasing the vulnerability of offspring to AD and other inflammatory conditions (50). A recent study detailed a potential pathway from maternal stress to offspring eczema. Maternal prenatal stress similarly elevates maternal HPA-axis activity and systemic glucocorticoid levels, resulting in increased corticosterone concentrations in maternal plasma and amniotic fluid. The excess corticosterone penetrates the fetal environment and interacts with cutaneous mast cells, which express the glucocorticoid receptor abundantly. This interaction activates glucocorticoid receptor-mediated signaling, thereby reprogramming the developmental trajectory of these cells. Consequently, fetal mast cells adopt a transcriptional and functional profile that favors pro-inflammatory activity. Postnatally, these developmentally programmed mast cells exhibit exaggerated responses to otherwise innocuous mechanical stimuli, leading to aberrant cutaneous inflammation and the onset of neonatal eczema (51). It is important to note that the potential role of immune pathways in offspring eczema/AD likely originates during early fetal development. This mechanism is rooted in the fact that the programming and establishment of the fetal immune system are predominantly completed in the early stages of pregnancy and mature by the later stages (52–54). Our subgroup analysis further corroborated this mechanism, indicating a stronger association between maternal exposure to anxiety/depression during early pregnancy and offspring eczema/AD.

According to experimental animal research, airborne Staphylococcus aureus (S. aureus) may play a role in maternal depression through mechanisms involving abnormal neural oscillations and mitochondrial dysfunction (55). Similarly, newborns exposed to this environment may experience cutaneous colonization by S. aureus and disruption of their normal microbial flora. Studies indicate that S. aureus may also contribute to the development and exacerbation of AD through several, pathways, including the release of staphylococcal enterotoxins that activate T cells and induce AD-like lesions on the skin; alteration of Langerhans cell-mediated T cell responses, resulting in a Th2 bias; induction of IL-1α production, which amplifies cutaneous inflammation; and promotion of fibrinogen expression in the skin, thereby enhancing bacterial colonization (56, 57). Furthermore, the gut microbiome merits further investigation. Studies have shown an increased presence of Klebsiella in the gut microbiota of individuals suffering from depression and in children with AD, possibly due to the vertical transmission of gut microorganisms (58, 59). The higher levels of Klebsiella may hinder the colonization of beneficial bacteria such as Bacteroides fragilis (B. fragilis), disrupting the normal gut microbial community structure (60). Studies have demonstrated that B. fragilis exhibits anti-inflammatory properties, which are mediated primarily through the production of a polysaccharide that has been shown to help correct systemic T cell defects and maintain a proper Th1/Th2 balance (61). Therefore, a decrease in B. fragilis abundance may thus reduce its protective role against eczema, possibly by limiting the production of its immunomodulatory polysaccharide (62). Ultimately, lipopolysaccharides from Klebsiella may activate the TLR4 receptor pathway, promoting the release of pro-inflammatory cytokines, worsening immune dysregulation, and allergic responses, potentially serving as an underlying cause of AD (60, 63).

Such psychological stress often does not exist in isolation but may interact with various factors such as environmental conditions and air pollution to influence offspring health. Notably, a recent study provides further insight into the association between parental stress and offspring eczema. The study indicated that this association is mediated through a stress-environment interaction (64). Specifically, while psychosocial stress increased eczema prevalence, socioeconomic stress further amplified the effects of exposure indoor environmental factors and outdoor air pollution on the disease. These findings offer important support and extension to our study. First, this may help explain the substantial heterogeneity across studies, given the varying levels of environmental exposure and types of stress in different populations. Second, the research indicates that maternal depression and anxiety likely correlate with psychosocial stress, socioeconomic stress, and environmental exposures, introducing potential confounding bias.

Eczema refers to a skin condition with various etiologies, often influenced by factors such as friction, chemical stimuli, and sweating (65, 66). Its broad diagnostic criteria may further obscure the association with maternal depression and anxiety. In contrast, AD is a well-defined inflammatory skin condition characterized by specific pathological mechanisms, including S. aureus colonization and genetic factors, which directly initiate and promote inflammatory processes, thereby allowing for a stronger causal inference (57, 67, 68). Supporting this mechanistic distinction, our subgroup analysis indicated that maternal anxiety or depression during pregnancy was significantly associated with offspring AD compared to the control group. However, no significant difference in the prevalence of eczema was observed between these groups.

No significant differences in the prevalence of offspring eczema/AD were observed in the group where maternal anxiety during pregnancy was evaluated using either STAI-S or STAI-T, in comparison to the control group. The primary factor accounting for this lack of differentiation is primarily the insufficient sample size. Furthermore, stricter diagnostic criteria by physicians and potential parental reporting bias led to an association between physician-diagnosed eczema/AD and maternal depression/anxiety in subgroup analysis, while no significant association was evident in the parent-reported subgroup. This disparity implies that the absence of a significant connection in the parent-reported subgroup may stem from under-diagnosis or a stronger impact of confounding variables (69).

The administration of antidepressants or anxiolytics during pregnancy significantly impacts offspring development. Ideally, comparisons should be drawn between medicated and non-medicated groups of mothers experiencing anxiety or depression during pregnancy, accompanied by relevant subgroup analyses. However, due to the fact that not all mothers with anxiety or depression received medication and the included studies lacked pertinent data, such subgroup analyses were not feasible. Furthermore, the potential influence of antidepressants and anxiolytics themselves on the development of eczema and dermatitis in offspring should also be considered, representing a significant limitation of our study. Future research in this area should utilize well-designed observational studies and animal experiments to elucidate the potential relationship. Regarding outcome assessment, the measurement of eczema/AD outcomes presents methodological limitations. The reliance on parental reporting or physician diagnosis in the included studies may introduce information bias, a limitation that should be acknowledged. In addition, our analysis was limited to assessing exposures within specific trimesters and did not evaluate the cumulative effect across the entire pregnancy. Specifically, the available data are insufficient to investigate whether the total duration of maternal anxiety/depression or exposure during a particular trimester is more strongly associated with the development of eczema/AD in offspring. This gap in our analysis constitutes another significant limitation. Given the limited overall sample size and the paucity of studies within individual subgroups, a reliable meta-regression analysis for factors like region, outcome definition, or assessment tools was not feasible, which represents one of the limitations of this study. Additionally, the observed association for maternal anxiety was not stable in sensitivity analyses, calling for a cautious interpretation of this exploratory finding.

Our study surpasses prior meta-analyses in several aspects. By including cohort studies, we bolstered the quality of evidence. Additionally, integrating recently published research enhances result reliability. Furthermore, we performed subgroup analyses considering crucial factors like disease types, region, and timing of exposure to identify factors that may influence the observed association. This research underscores the significance of vigilantly monitoring and promoting maternal psychological health during pregnancy. Prompt interventions to mitigate maternal depression and anxiety may positively impact offspring skin health.

This meta-analysis indicates a potential association between maternal anxiety/depression during pregnancy and the development of eczema/AD in offspring. Furthermore, disease types, region, timing of exposure, eczema/AD assessment method may influence this association.