Maternal sleep disorders during pregnancy and subsequent risk of allergic diseases in Japanese children: the TMM BirThree Cohort Study

Article information

Clin Exp Pediatr. 2026;69(1):36-45

Publication date (electronic) : 2025 October 22

doi : https://doi.org/10.3345/cep.2025.01165

Ami Uematsu, MHS¹, Masatsugu Orui, PhD^,1,2,3, Mami Ishikuro, PhD^1,2, Keiko Murakami, PhD^2,4, Aoi Noda, PhD^1,2,5, Genki Shinoda, PhD², Taku Obara, PhD^1,2,5, Shinichi Kuriyama, PhD^1,2,3

¹Graduate School of Medicine, Tohoku University, Sendai, Japan

²Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan

³International Research Institute of Disaster Science, Tohoku University, Sendai, Japan

⁴Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

⁵Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan

Corresponding author: Masatsugu Orui, MD, PhD. Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan Email: masatsugu.orui.e5@tohoku.ac.jp

Received 2025 May 27; Revised 2025 July 28; Accepted 2025 August 11.

Abstract

Introduction

Allergic diseases are common chronic diseases that widely affect both children and adults [1,2]. The World Allergy Organization reported that approximately 30%–40% of the global population is affected by one or more allergic conditions [3]. Some allergic diseases persist from childhood to adulthood [4] and are an important public health issue worldwide due to concerns about impaired quality of life, increased medical costs, and loss of productivity [1]. The development of allergic diseases is associated with a variety of environmental factors [5]. Exposure to environmental factors during the perinatal period has been shown to affect future health and susceptibility to disease in children [6], and has also received attention in terms of allergic diseases [7]. For instance, exposure to smoking, passive smoking, air pollution, and stress in pregnant women have been suggested to be associated with the development of allergic diseases in their children [8-10].

Sleep problems, such as extreme lack of sleep and dissatisfaction with sleep quality, have become increasingly prevalent in recent years. Previous research showed that sleep disorders such as sleep deprivation and insomnia are associated with allergic diseases [11,12]. Those studies investigated the association between sleep disorders and subsequent development of allergic diseases in the same individuals. To our knowledge, only one study reported that maternal sleep disorders during pregnancy were associated with allergic diseases in children [13]. That study examined the association between short sleep (less than 8 hours) in pregnant women and the development of respiratory allergic diseases in children including asthma, wheezing, and allergic rhinitis, but not nonrespiratory allergic diseases such as atopic dermatitis or food allergy. Sleep disorders induce activation of the sympathetic nervous system, enhanced secretion of stress hormones, and increased levels of inflammatory cytokines [14,15]. Sleep disorders in pregnant women can affect the immune system of the fetus and lead to the development of allergic diseases. Based on this mechanism, sleep disturbances in pregnant women may also be associated with allergies other than respiratory allergies.

Therefore, we hypothesized that sleep disorders in pregnant women are associated with the development of allergic diseases including respiratory, skin, and ocular allergies in their children. Specifically, we aimed to reveal the association between sleep disorders during pregnancy and the development of bronchial asthma, atopic dermatitis, food allergy, and allergic conjunctivitis/allergic rhinitis/ hay fever in children up to 5 years of age. Moreover, we explored whether this effect is primarily mediated by maternal psychological distress, which strongly influences sleep, using mediation analysis.

Methods

1. Study population

The present study was based on data obtained from the Tohoku Medical Megabank Project Birth and Three Generation Cohort Study (TMM BirThree Cohort Study). Detailed information on the TMM BirThree Cohort Study has been published elsewhere [16]. Pregnant women and their families were recruited from July 2013 to March 2017 at obstetrical clinics and hospitals in Miyagi and Iwate prefectures in Japan. In total, 23,730 mother-child pairs participated in the study.

Among the 23,730 mother-child pairs, 1,608 were excluded because of withdrawal of informed consent, abortion, stillbirth, multiple pregnancies, or chromosome abnormalities. Of the remaining 22,122 mother-child pairs, 917 with missing data on sleep status were excluded, as well as 10,082 with missing data on the following variables: parity, prepregnancy body mass index (BMI), smoking during pregnancy, passive smoking during pregnancy, night shift, parental history of allergic diseases, maternal educational attainment, household income, maternal psychological distress, mode of delivery, exclusive breastfeeding, use of childcare facilities, and respiratory syncytial virus infection in children. Thus, data from 11,123 mother-child pairs were included in the present analyses (Fig. 1).

Fig. 1.

Flow chart of participant selection process. The flowchart shows the exclusion criteria and number of total, excluded, and eligible participant pairs. BMI, body mass index.

Results

Table 1 shows the characteristics of participants according to the presence or absence of sleep disorders during pregnancy. Of the 11,123 mothers included in the analyses, 4,115 (37.0%) had sleep disorders during pregnancy. Among all pregnant women, 53.7% had a history of parity, 8.8% were working night shifts, and 0.4% were using sleep medications. Compared with women without sleep disorders, those experiencing sleep disorders tended to be younger at delivery and tended more to be primiparous, using sleep medications, and having allergic diseases, lower educational attainment, lower household income, and psychological distress.

Table 1.

Participants' characteristics

Fig. 2 shows the results of the Kaplan-Meier curve analysis and log-rank test. The number of children who developed each allergic disease by age 5 and cumulative incidence estimated by the Kaplan-Meier method were as follows: bronchial asthma, 1,186 (14.7%); atopic dermatitis, 1,331 (15.1%); food allergy, 1,021 (10.6%); and allergic conjunctivitis/allergic rhinitis/hay fever, 1,555 (21.4%). For all allergies, the cumulative incidence was higher among children born to mothers with sleep disorders. The results of the log-rank test revealed that the P values were below 0.05 for all allergies.

Fig. 2.

Kaplan-Meier curve and log-rank test results of development of allergic diseases in children by maternal sleep disorder status. Comparison of the incidence rates of allergic diseases for groups with versus without sleep disorders. The dashed line represents the group with sleep disorders, while the solid line represents the group without sleep disorders. Vertical axis: incidence rate of allergic diseases. Horizontal axis: analysis time (months).

Table 2 shows HRs and 95% CIs for each allergic disease. In the crude model, maternal sleep disorders during pregnancy were associated with all allergic diseases analyzed. However, after adjusting for confounders, the associations with bronchial asthma and food allergy were no longer significant (adjusted model I, II). After adjusting for the K6 scale, the associations with atopic dermatitis and allergic conjunctivitis/allergic rhinitis/hay fever remained significant (HR [95% CI], 1.09 [0.97–1.23] for bronchial asthma, 1.17 [1.05–1.31] for atopic dermatitis, 1.11 [0.98–1.26] for food allergy, 1.25 [1.13–1.39] for allergic conjunctivitis/allergic rhinitis/hay fever) (adjusted model III).

Table 2.

Association between maternal sleep disorders and subsequent risk of allergic diseases in their children

Stratified analyses by parity and K6 scale (Supplementary Tables 1, 2) revealed no significant interaction. In the stratified analysis by parity, P values for interaction were 0.418 for bronchial asthma, 0.942 for atopic dermatitis, 0.142 for food allergy, and 0.729 for allergic conjunctivitis/allergic rhinitis/hay fever. In the stratified analysis by K6 scale, P values for interaction were 0.237 for bronchial asthma, 0.719 for atopic dermatitis, 0.414 for food allergy, and 0.896 for allergic conjunctivitis/allergic rhinitis/hay fever.

We also conducted a mediation analysis to examine the extent to which maternal psychological distress during pregnancy mediated the relationship between maternal sleep disorders and the development of allergic diseases in children (Table 3). The total HR of maternal sleep disorders on the development of allergic diseases is broken down into a direct HR and an indirect HR through psychological distress. For bronchial asthma, for example, the total HR of 1.13 was decomposed into a direct HR of 1.08 (95% CI, 0.96–1.22) and an indirect HR of 1.04 (95% CI, 1.01–1.08), with a mediator effect of 34.7%. Similarly, proportions of mediation were 4.7% for atopic dermatitis, 3.8% for food allergy, and -2.1% for allergic conjunctivitis/allergic rhinitis/hay fever.

Table 3.

Mediating effect of maternal psychological distress on association between maternal sleep disorders and subsequent risk of allergic diseases in their children

Discussion

The present study examined the association between maternal sleep disorders during pregnancy and the development of allergic diseases in children under the hypothesis that sleep disorders in pregnant women would be associated with their children developing allergic diseases including respiratory, skin, and ocular allergies. After adjusting for all confounders, significant associations were observed for atopic dermatitis, and allergic conjunctivitis/allergic rhinitis/hay fever. We performed Bonferroni correction for multiple tests; however, atopic dermatitis and allergic conjunctivitis/allergic rhinitis/hay fever remained significant. Stratified analyses by parity and K6 scale revealed no significant interaction, and the observed associations remained unchanged. In the mediation analysis, maternal psychological distress during pregnancy mediated 34.7% of the association between sleep disorders and bronchial asthma in children; however, mediation proportions were between -2.1% and 4.7% for other allergic diseases.

In a previous study reporting an association between sleep problems during pregnancy and the development of allergic diseases in children, Chen et al. [13] examined associations between lifestyles during pregnancy (e.g., maternal sleep duration, physical activity, and screen exposure) and children’s asthma, wheeze, and allergic rhinitis in 6,236 mother-child pairs. They found that short sleep (less than 8 hours) during pregnancy was associated with the development of respiratory allergic disease in males (adjusted odds ratio, 1.317; 95% CI, 1.102–1.573) using the International Study of Asthma and Allergies in Childhood questionnaire. In the present study, we also observed associations of maternal sleep disorders with both bronchial asthma and allergic conjunctivitis/allergic rhinitis/hay fever in the crude models. However, the non-significant association with bronchial asthma after adjustment may be explained by differences in outcome definitions or in the confounders included in the analysis. To the best of our knowledge, this is the first study to reveal the association between maternal sleep disorders during pregnancy and general allergic diseases, including skin and ocular allergies, in children.

Previously, a number of studies have reported on the association between sleep disorders in children and the subsequent development of allergic diseases. Bakour et al. [24] examined the association between sleep duration from adolescence (age 12–18 years) to adulthood (age 24–32 years) and the risk of new-onset asthma. They reported that those experiencing short sleep consistently exhibited a higher risk of asthma compared with those experiencing adequate sleep consistently (adjusted relative risk, 1.52; 95% CI, 1.11–2.10). In a study by Zhang et al. [25], baseline child insomnia (mean age, 9.0±1.8 years old) was associated with frequent asthma in a crude model at 5-year follow-up (crude odds ratio, 6.76; 95% CI, 1.38–33.2). Jernelöv et al. [26] examined the association between sleep disturbances (“has nightmares,” “overtired,” “sleeps less than other kids,” and “trouble sleeping”) and the development of symptoms of asthma, rhinitis, or eczema, and reported that being overtired at age 8 was associated with an increased risk of developing rhinitis symptoms at age 13 (adjusted odds ratio, 2.59; 95% CI, 1.31–5.11). While those studies clearly demonstrated the association of children’s own sleep disorders with the development of allergic diseases, the present study provides new insight that maternal sleep disorders during pregnancy are associated with the development of several allergic diseases in their children.

Psychological distress during pregnancy has been shown to be associated with asthma, atopic dermatitis, and allergic rhinitis in children [10]. As sleep disorders are also associated with psychological distress, the present study used a model adjusted for the K6 scale in addition to other confounders such as maternal age at delivery and the child’s sex. The results revealed that sleep disorders are still associated with atopic dermatitis and allergic conjunctivitis/allergic rhinitis/hay fever, even when the effects of psychological distress are taken into account. We also hypothesized that there would be a mediating effect of psychological distress from sleep disorders and conducted a mediation analysis. Maternal psychological distress mediated about one-third of the effect of bronchial asthma. However, contrary to our hypothesis, the proportions of mediation were smaller for other allergic diseases. It was suggested that sleep disorders might influence the development of allergic diseases in children through direct pathways or pathways other than psychological distress.

The following mechanisms may explain the association of maternal sleep disorders during pregnancy with the development of allergic diseases in children. Sleep disorders such as sleep loss and disruption during pregnancy lead to the activation of the hypothalamic–pituitary–adrenal axis and elevated maternal cortisol [14,27]. This triggers the production of placental cortisol-releasing hormone (CRH), resulting in increased levels of fetal CRH [28]. Persistently high fetal CRH and glucocorticoid levels may impact the developing immune system, shifting the Th1/ Th2 balance toward Th2 dominance and predisposing the child to the development of allergic diseases [28,29]. An overactivation of the sympathetic nervous system and of the proinflammatory system due to sleep disorders may also interact and be involved in this pathway [14,15,27].

In the present study, no significant association was observed between maternal sleep disorders during pregnancy and the development of food allergy in children after adjustment. One possible reason for this may be that the types of allergens differ between food allergy and other allergic diseases. Allergens responsible for the development of bronchial asthma, atopic dermatitis, and allergic conjunctivitis/allergic rhinitis/hay fever are inhalant allergens, such as dust mites, molds, grass, and pollen [8,30,31]. In contrast, food allergy is caused by food allergens, and the development of food allergy is influenced by the timing of when the specific food is introduced. This difference in allergens may account for the difference in the relationship for the development of food allergy and other allergic diseases.

Sleep disorders increase during pregnancy, and further increase as pregnancy progresses [32]. Previous studies reported that sleep disorders in pregnant women are associated with preterm birth and cesarean section [27]. The findings of the present study suggest that interventions for sleep disorders during pregnancy are important also from the perspective of early prevention of allergic diseases in children. In Japan, the Ministry of Health, Labour and Welfare advocates in its Sleep Guidelines for Health Promotion 2023 [33] that pregnant women “engage in low- to medium-intensity exercise that is easy on the body” and “reduce caffeine intake” to prevent sleep disorders. It is important to provide health education, conduct screening for sleep disorders, and offer guidance on appropriate sleep habits through prenatal check-ups and maternal classes.

The present study has some limitations. First, the TMM BirThree Cohort Study was conducted primarily in Miyagi prefecture. Therefore, the generalizability of the findings is limited. Second, the analysis included approximately half of the participating mother-child pairs due to missing data. However, even after imputing the missing values using multiple imputations, the results remained largely similar (Supplementary Table 3). Third, the assessment of exposure and outcome was based on self-reported questionnaire responses. Most of the responses regarding children’s allergic diseases were provided by their mothers. The associations may be confounded by the general health literacy of the responding mothers, as health literacy is associated with health behaviors at a higher level in women than in men [34]. Fourth, the self-reported questionnaire did not allow us to distinguish between women who had sleep disorders before pregnancy and those who developed them after pregnancy. Nonetheless, our hypothesis assumes that both groups are subject to the same mechanism regarding the development of allergies in children. Fifth, the use of sleep medications was treated as a confounder; however, it may be part of a potential causal pathway. We conducted a stratified analysis, but due to the small number of participants using sleep medications (n=48), the results for this group did not converge. The results for the group without sleep medications were consistent with the main findings. Finally, this study used longitudinal data, and participants who did not return for the interim survey were considered to have dropped out at that point. Therefore, we may have underestimated the development of allergic diseases in children. However, the prevalence rates obtained in this study were comparable to those reported by other surveys in Japan [35].

Despite these limitations, our study has several strengths. This study was based on the TMM BirThree Cohort Study, which used a birth cohort design with a large sample size. In addition, participants were recruited during pregnancy, and the study was conducted in a prospective manner, making longitudinal tracking of children’s diseases possible.

In conclusions, this study examined the association between maternal sleep disorders during pregnancy and the development of allergic diseases in children, revealing significant associations with atopic dermatitis and allergic conjunctivitis/allergic rhinitis/hay fever. However, further research is needed to determine whether improving sleep disorders in pregnant women may play a role in reducing the risk of allergic diseases in children.

Supplementary Materials

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