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BACKGROUND/OBJECTIVES The TOPICOP scale is an easy-to-use scale for assessing topical corticosteroid (TCS) phobia in atopic dermatitis (AD) patients and their caretakers. TCS phobia is a common problem among AD patients and their caretakers. The aim of this study was to examine the relationship between TCS phobia in caretakers of children with AD and the characteristics of patients using the TOPICOP scale. METHODS Caretakers of AD patients who visited the allergy clinic at the National Center for Child Health and Development in Tokyo between February 2014 and May 2014 were recruited. Caretakers of patients in follow-up had already attended an education session on treatment at the institution. All participants completed an anonymous questionnaire on the characteristics of the respondents and patients using the Patient-Oriented Eczema Measure (POEM) and the Japanese version of TOPICOP. RESULTS In total, 243 participants (88.9% female) completed the survey. The average TOPICOP score was 40.3 and the median POEM score was 4. The TOPICOP score was significantly higher for patients younger than 12 months old with moderate to very severe AD (POEM ≥ 8) whose caretaker had not attended an educational session (P

Pregnant women with allergies face difficulties, as they tend to avoid medication for symptom control during pregnancy. Moreover, some women experience exacerbations during this period. These difficulties can affect their mental health.This study aimed to investigate the factors influencing allergy exacerbations during pregnancy and examine the effects of allergy symptoms on the mental health of pregnant women.A cross-sectional study was conducted through web-based research in March 2020, amid the COVID-19 pandemic. Pregnant women were collected from 3 groups (target: 150 participants in each group): atopic dermatitis (AD), allergic rhinitis, and without allergies. We evaluated mental health using Kessler Psychological Distress Scale (K6) and health-related quality of life using the Short Form-8 questionnaire.Overall, 202 (49.1%) of 411 pregnant women had depressive symptoms, and 45 (10.9%) had severe depressive symptoms. Women with allergies had significantly worse mental health than those without allergies. Among 119 AD patients, 36 (30.3%) experienced exacerbations during pregnancy. Of them, 11 (30.6%) did not consult a practitioner and endured the exacerbation. A significant association was observed between severe prepregnancy symptoms, job situation, coping with symptoms of AD during pregnancy, and AD exacerbation. Among 210 rhinitis patients, 17.1% experienced rhinitis exacerbation during pregnancy. The presence of rhinitis symptoms in winter and the second trimester was significantly associated with exacerbation.This study revealed higher rates of depressive symptoms among pregnant women with allergies. The psychological well-being of pregnant women with AD or allergic rhinitis should be considered.

BACKGROUND Children with allergic clinical manifestations tend to have behavioral or emotional problems such as hyperactivity or worse mental health. However, previous studies on this association did not adequately adjust for confounders like parenting stress, demographic characteristics, or allergy presentation. This study aimed to investigate the relationship between childhood allergic clinical manifestations and behavioral problems, adjusting for confounders such as demographic characteristics, parenting stress, and allergy-related variables. METHODS We conducted an online cross-sectional survey among caregivers of children aged 2-6 years (n = 633). The Strengths and Difficulties Questionnaire (SDQ) was used to determine children's behavioral characteristics as the primary outcome. Allergic clinical manifestations, wheeze, rash, and nose symptoms were the exposure variables. Associations were estimated using logistic regression analyses with propensity scores to adjust for confounders. RESULTS We analyzed 633 caregivers of children aged 2-6 years (valid rate, 61.5%). Univariate analyses showed that wheezing was associated with conduct problems (odds ratio [OR] = 1.48, 95% confidence interval [CI]:1.01-2.16), a behavioral component of the SDQ. Rash was also associated with hyperactivity (OR = 1.62, 95% CI: 1.02-2.57). Furthermore, nose symptoms were associated with conduct problems (OR = 1.65, 95% CI:1.16-2.33) and emotional symptoms (OR=1.62, 95% CI:1.06-2.45). After adjusting for potential confounders, wheezing (adjusted OR = 1.69, 95% CI:1.04-2.75) and nose symptoms (adjusted OR = 1.56, 95% CI: 1.05-2.34) remained associated with conduct problems. CONCLUSIONS This study revealed that a history of wheezing and nose symptoms in children is associated with an increased risk of behavioral problems, in particular, conduct problems.

In recent years, there has been an increase in the number of problems associated with neurodevelopmental disorders in children, and there has been a growing interest in the relationship between environmental chemicals and children's health. The objective of this study was to examine whether an association exists between occupational or environmental prenatal maternal exposure to volatile organic compounds and the risk of neurodevelopmental disorders in children using Japanese translations of the Ages & Stages Questionnaires, Third Edition (J-ASQ-3). An increase in the risk of neurodevelopmental delay in 12-month-old children associated with maternal exposure to formalin or formaldehyde was identified in terms of problem-solving (odds ratio (OR): 1.76, 95% confidence interval (CI): 0.99-3.12) and personal-social skills (OR: 3.32, 95% CI: 1.46-7.55). It is not clear whether or not this tendency is reversible, and whether it is observed past 12 months of age. Further research and a preventive approach are needed.

Context Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. Objective This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. Methods The Japan Environment and Children’s Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. Results The mean gestational age at blood sampling was 22.7 ± 4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). Conclusion Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

Few epidemiologic studies have examined the role of maternal iron status in allergic diseases in offspring and findings have been inconsistent. We used a large birth cohort in Japan to explore the association of the markers for maternal iron status (maternal hemoglobin, hematocrit and dietary iron intake during pregnancy) with allergy development in offspring during early childhood. We analyzed information on children age 0–3 years from the Japan Environment and Children’s Study (JECS). We used logistic models and generalized estimating equation models to evaluate the effect of maternal hemoglobin and hematocrit levels and dietary iron intake on allergies in children. Models were also fitted with propensity score-matched datasets. Data were collected for a total of 91,247 mother–child pairs. The prevalence (95% confidence interval) of low hemoglobin and hematocrit was 14.0% (13.7–14.2%) and 12.5% (12.3–12.8%), respectively. After adjusting confounders, low hemoglobin and hematocrit during pregnancy were not associated with childhood allergic outcomes. Findings from models with propensity score-matched datasets also indicated that children born to mothers with low hemoglobin or hematocrit levels during pregnancy did not have a higher risk of developing allergic conditions at 3 years old. We found no meaningful associations between low energy adjusted maternal dietary iron intake and allergies in children. In conclusion, using birth cohort data, we found no evidence supporting an association of low maternal hemoglobin, hematocrit and low dietary iron intake with allergy symptoms during early childhood. Further studies with more suitable proxy markers for blood iron status are needed.

Introduction: Clinical trials of dupilumab demonstrated significant clinical improvements with a favorable safety profile in adults and adolescents with moderate-to-severe atopic dermatitis (AD) inadequately controlled with topical medications. Here, we evaluate dupilumab safety and efficacy data in children aged ≥ 6 to < 12 years with severe AD (Investigator’s Global Assessment [IGA] score = 4) inadequately controlled with topical corticosteroids (TCS). Methods: In the double-blinded, phase 3 LIBERTY AD PEDS trial (NCT03345914), children aged ≥ 6 to < 12 years were randomized 1:1:1 to receive either subcutaneous dupilumab every 4 weeks (q4w, 300 mg …

BACKGROUND: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective for preventing eczema or food allergy. OBJECTIVES: Primary objective To assess the effects of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy. SEARCH METHODS: We performed an updated search of the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase in September 2021. We searched two trials registers in July 2021. We checked the reference lists of included studies and relevant systematic reviews, and scanned conference proceedings to identify further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (≤ 12 months) without pre-existing eczema, food allergy, or other skin condition. Eligible comparisons were standard care in the locality or no treatment. Types of skin care interventions could include moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required. DATA COLLECTION AND ANALYSIS: This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured at the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen. MAIN RESULTS: We identified 33 RCTs comprising 25,827 participants. Of these, 17 studies randomising 5823 participants reported information on one or more outcomes specified in this review. We included 11 studies, randomising 5217 participants, in one or more meta-analyses (range 2 to 9 studies per individual meta-analysis), with 10 of these studies providing IPD; the remaining 6 studies were included in the narrative results only. Most studies were conducted at children's hospitals. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although the definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to three years. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported information on our prespecified outcomes, 13 assessed emollients. We assessed most of the evidence in the review as low certainty and had some concerns about risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. We assessed the evidence for the primary food allergy outcome as high risk of bias due to the inclusion of only one trial, where findings varied based on different assumptions about missing data. Skin care interventions during infancy probably do not change the risk of eczema by one to three years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; risk difference 5 more cases per 1000 infants, 95% CI 28 less to 47 more; moderate-certainty evidence; 3075 participants, 7 trials) or time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). Skin care interventions during infancy may increase the risk of IgE-mediated food allergy by one to three years of age (RR 2.53, 95% CI 0.99 to 6.49; low-certainty evidence; 976 participants, 1 trial) but may not change risk of allergic sensitisation to a food allergen by age one to three years (RR 1.05, 95% CI 0.64 to 1.71; low-certainty evidence; 1794 participants, 3 trials). Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial); however, this was only seen for cow's milk, and may be unreliable due to over-reporting of milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.33, 95% CI 1.01 to 1.75; risk difference 17 more cases per 1000 infants, 95% CI one more to 38 more; moderate-certainty evidence; 2728 participants, 6 trials) and may increase the risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) and stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although CIs for slippages and stinging/allergic reactions were wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses showed that the effects of interventions were not influenced by age, duration of intervention, hereditary risk, filaggrin (FLG) mutation, chromosome 11 intergenic variant rs2212434, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and eczema or food allergy development. AUTHORS' CONCLUSIONS: Based on low- to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection. Further study is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy.

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health.

The association between pollen food allergy syndrome (PFAS) and allergic march remains unclear. In this prospective cohort study of the general population in Tokyo (T-Child Study), we found that sensitization to Cry j 1 and Fel d 1 at ages 5 and 9 years was associated with an increased risk of PFAS at 13 years old (at 5 years, Cry j 1: adjusted odds ratio aOR, 2.74; 95% confidence interval CI, 1.53–4.91; Fel d 1: aOR, 2.61; 95% CI, 1.31–5.19; at 9 years, Cry j 1: adjusted odds ratio aOR, 4.28; 95% confidence interval CI, 1.98–9.25; Fel d 1: aOR, 2.40; 95% CI, 1.33–4.32). In particular, sensitization to Bet v 1 at ages 5 and 9 years was associated with a strong risk of PFAS at the age of 13 years (at 5 years: aOR, 10.6; 95% CI, 2.64–42.5; at 9 years: aOR, 9.1; 95% CI, 4.71–17.6). PFAS risk by age 13 years was increased by any allergic symptom at 5 or 9 years, a combination of wheezing, eczema, and rhinitis, and Bet v 1 sensitization. Our findings suggest that PFAS may be associated with allergic march.

OBJECTIVE Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy. DESIGN A prospectively planned individual participant data meta-analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy. DATA SOURCES Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020. ELIGIBILITY CRITERIA FOR SELECTED STUDIES Included studies were randomized controlled trials of infants

Allergic rhino-conjunctivitis with pollen allergy has been prevalent worldwide and Pollen-food allergy syndrome (PFAS) refers to individuals with pollen allergy who develop oral allergy syndrome (OAS) on consuming fruits and vegetables. The prevalence of PFAS varies by region and that in Japanese adolescents remains to be elucidated. In this cross-sectional study, we examined the epidemiological characteristics of PFAS in a general population of Japanese adolescents according to pollen allergy, OAS, and IgE component sensitization. Participants comprised adolescents, at age 13 years, from a prospective birth cohort study in Japan. We administered questionnaires to collect information from parents regarding pollen allergy, PFAS and OAS at each child’s age 13 years. ImmunoCAP ISAC was used to assess IgE component sensitization. Among 506 participants with a complete questionnaire and ISAC measurement results, 56.5% had a history of hay fever, 16.0% had a history of OAS, 51.0% had pollen allergy, and 11.7% had a history of PFAS; additionally, 72.7% were sensitized to one or more tree, grass, and/or weed allergens. The most common sensitization (95.7%) among adolescents with pollen allergy was to Japanese cedar (Cry j 1). The most common causal foods were kiwi and pineapple (both 39.0%). Knowledge levels about PFAS were poor among affected adolescents. We found a high prevalence of PFAS among adolescents in Japan. Although it affects approximately 1/10 adolescents in the general population, public awareness regarding PFAS is poor. Interventional strategies are needed to increase knowledge and to prevent PFAS in the general population.

Atopic dermatitis is a common, chronic inflammatory skin disorder, present in about 12% of children worldwide. Optimizing management of severe atopic dermatitis in pediatric patients is critical to reduce signs of inflammation, alleviate pruritus and sleep disturbance, minimize the development and/or impact of comorbidities, and improve the patient and caregiver's quality of life. Evaluating the longitudinal severity of pediatric atopic dermatitis is an important component of measuring therapeutic response and long-term management, and is different in clinical practice versus clinical trials. This article describes when and how to use different treatments for pediatric patients with severe atopic dermatitis, including topical medications, phototherapy, and systemic medical therapies (traditional immunosuppressants, biologics, and small molecule inhibitors). It also provides recommendations useful in clinical practice for nonpharmacologic interventions for pediatric patients with severe atopic dermatitis.

Background Eosinophilic esophagitis (EoE) has increased rapidly and has been well characterized. However, no nationwide survey has been conducted regarding non–esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs), and they remain poorly understood. Objective To compare the clinical features and natural histories of non-EoE EGIDs and EoE by using the same questionnaire, for all ages. Methods We conducted a nationwide hospital-based survey of patients who visited hospitals from January 2013 through December 2017. We randomly selected 10,000 hospitals that perform endoscopy. We analyzed the demographics, symptoms, gastrointestinal histology, treatments, and natural histories of EoE and non-EoE EGIDs. Results A total of 2906 hospitals responded to the questionnaire. We identified 1542 patients and obtained detailed data for 786 patients, consisting of 39% EoE and 61% non-EoE EGIDs. The clinical characteristics were analyzed for patients who met the "definite" criteria that excluded comorbidities. Non-EoE EGIDs showed no gender difference, whereas EoE was male-predominant. Tissue eosinophilia was often seen in the small intestine (62%) and stomach (49%). The frequency of hypoproteinemia was high (27%) in childhood. Children also had more serious symptoms and complications than adults: restriction of daily life activity (P = .009), failure to grow/weight loss (P = .008), and surgery (P = .01). For both diseases, the most common natural history was the continuous type: 66% (95% confidence interval [CI]: 58-74) in EoE and 64% (95% CI: 55-72) in non-EoE EGIDs. Conclusions The percentage of persistent patients with non-EoE EGIDs was almost the same as those with EoE. Complications were more frequent in children than in adults.

Feelings about pregnancy and mother-infant bonding are associated with maternal mental health before and after childbirth. The current study examined factors associated with persistent distress at 12 months after childbirth among mothers with psychological distress in the first trimester, using data from the Japan Environment and Children's Study (JECS). Feelings about pregnancy were assessed using a questionnaire in the first trimester, and maternal mental health was assessed using the Kessler 6 (K6) in the first trimester and at 12 months after childbirth. In addition, mother-infant bonding was assessed using the Mother-to-Infant Bonding Scale Japanese version (MIBS-J) at 12 months after childbirth, and 5 items from the MIBS-J at one and six months after childbirth. Among the 97,415 mothers registered in the JECS, 24,324 mothers with psychological distress (K6 ≥ 5) in the first trimester were included in this analysis. The relationships between persistence of psychological distress at 12 months after childbirth with feelings about pregnancy and mother-infant bonding were analyzed. Both maternal negative feelings about pregnancy in the first trimester and mother-infant bonding after childbirth were significantly associated with persistent psychological distress at 12 months after childbirth (β = 0.02, p = 0.001 and β = 0.35, p 0.001, respectively). The indirect effect of feelings about pregnancy on persistent distress through mother-infant bonding was also observed (β = 0.06, p 0.001). These findings indicate that mother-infant bonding after childbirth may be important for improving the mental health of mothers with prenatal psychological distress.

It is suggested that maternal mental health during pregnancy may affect offspring immune and respiratory features, based on the developmental origins of health and disease hypothesis.To evaluate whether maternal quality of life (QoL) and depression during pregnancy leads to wheezing, asthma, and food allergy of the offspring at 3 years of age.We conducted a nationwide, multicenter, prospective birth cohort study, Japan Environment and Children's Study. All variables were collected from questionnaires. Health-related QoL was measured using the Medical Outcomes Survey Short Form-8 questionnaire with a physical component summary and a mental component summary score. We conducted logistic regression analyses to evaluate the associations of offspring's wheezing, asthma, and food allergy with maternal QoL and depression.There were 72,685 participants with no missing variables. Maternal physical component summary scores of the Medical Outcomes Survey Short Form-8 questionnaire were negatively associated with offspring's asthma (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.99-1.00), current wheezing (aOR, 0.99; 95% CI, 0.99-0.99), and food allergy diagnoses (aOR, 0.99; 95% CI, 0.98-0.99) in children. Offspring's wheezing and asthma were also associated with maternal depression and anxiety during pregnancy.Poor maternal prenatal QoL increased the risk of wheezing, asthma, and food allergy in offspring. In addition, maternal depression and anxiety increased the risk of offspring's wheezing, asthma, and food allergy.

Background: Children with allergic symptoms tend to have behavioral or emotional problems. However, previous studies on this association did not control for factors such as parenting stress, demographic characteristics, or allergy presentation. This study aimed to investigate the relationship between childhood allergic symptoms and behavioral problems, adjusted for confounders such as demographic characteristics, parenting stress, and allergy-related variables. Methods: We conducted an online cross-sectional survey among caregivers of children aged 2-6 years (n=633). The Strengths and Difficulties Questionnaire (SDQ) score was used as the primary measure of children’s behavioral characteristics. Data on history of wheezing, eczema, and rhinitis were collected from the children’s caregivers, using a standardized questionnaire, based on the International Study of Asthma and Allergies in Childhood. Associations were estimated using logistic regression analyses with propensity score to adjust for confounding factors. Results: Univariate analyses showed that history of wheezing was associated with conduct problems, a behavioral component of the SDQ. History of eczema was also associated with hyperactivity. Furthermore, nose symptoms were associated with conduct and emotional problems. After adjusting for potential confounders, history of wheezing (adjusted odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.04-2.75) and nose symptoms (adjusted OR=1.56, 95% CI: 1.05-2.34) remained associated with increased risk of conduct problems. Conclusions: This study revealed that history of wheezing and rhinitis in children are associated with increased risk of behavioral problems, in particular, that of conduct problems. This evidence may inform future research into childhood allergy symptoms and their behavioral problems.

BackgroundAtopic dermatitis (AD) is a chronic and inflammatory skin disease that commonly affects young children. AD causes health-related burdens associated with pruritus and poor quality of life. The efficacy of moisturizer application shows inconsistency on primary prevention of AD according to previous randomized, controlled trials. Which moisturizer is effective and how often moisturizer should be applied to prevent development of AD in infants remain unclear. We hypothesize that twice daily application of moisturizer using Fam’s Baby is more effective than once daily application and that a sufficient amount of moisturizer application is effective for preventing development of AD in neonates and infants. Therefore, this study aimed to examine whether applying Fam’s Baby twice daily or once daily prevents AD compared with 2e moisturizer once daily in neonates and infants with at least one parent or sibling who has had atopic dermatitis.MethodsThis study is a single-center, three-parallel group, assessor-blind, superiority, individually randomized, controlled, phase II trial. A newborn with at least one parent or sibling who has had AD is randomly assigned to application of Fam’s Baby twice daily, Fam’s Baby once daily, or 2e once daily in a 1:1:1 ratio until 32 weeks old. The primary outcome is the time to the first onset of AD during administration of the moisturizer.DiscussionThis is the first phase II randomized, controlled trial in Japan to investigate whether applying moisturizer (Fam’s Baby) twice daily or once daily can prevent the incidence of AD compared with another moisturizer (2e) once daily in high-risk neonates. In this study, we will use 2e once daily as control moisturizer to confirm the efficacy for primary prevention of AD as found in our previous trial. Evaluation of application of moisturizers for preventing AD in this study is expected to contribute to a reduction in the prevalence of AD and a reduction in health care costs. Trial registrationJapan Registry of Clinical Trials (jRCT); ID: jRCTs031200070. Registered on 20 July 2020.

Background mHealth and uHealth apps are available for children with asthma and their caregivers. However, previous studies on mHealth apps for children older than 7 years old with asthma are limited, and most studies on asthma apps do not consider interactions involving communication between children and caregivers. Therefore, a prototype mHealth child asthma app was developed for children and their caregivers, with features of tailored feedback messages in continuing self-management and interactions between children and caregivers. Objective The aim of this study was to identify the beneficial features of a prototype mHealth app developed for children with asthma and their caregivers. Methods Children diagnosed with persistent asthma by allergy specialists at the National Center for Child Health and Development were recruited. The features of a prototype mHealth app for children with asthma and their caregivers were investigated using semistructured interviews after they tried the app. Data were analyzed using thematic analysis. Content-characteristic words were named and grouped together as categories to explore themes. Results We recruited 27 children with asthma aged 2 to 12 years and 26 their caregivers. Findings on the good aspects of the app for children older than 7 years old and caregivers suggested 4 themes (confirmation of asthma knowledge, child-caregiver interaction, design of the app, and child’s interest), and 6 categories were identified. Findings on the good aspects of app for children 7 to 12 years old and caregivers suggested 5 themes (new knowledge, manga as a Japanese-style comic, child’s interest, trigger of self-management, and design and operability), and 11 categories were identified. Findings on the beneficial features of app suggested 6 themes (asthma knowledge, elements for continuous, universal design, notification, monitoring, and functions), and 12 categories were identified. Conclusions Children with asthma and their caregivers perceived that the good aspects of the app were learning asthma knowledge with fun, including manga; interaction between child and caregiver; and easy-to-read design, such as colors. They wanted not only the asthma knowledge but also the universal design and enhanced elements, monitoring, and notification functions of the app.

Introduction: Previous studies have reported that maternal asthma increases the risk of preterm birth. We hypothesized that inflammatory reactions caused by allergic diseases might affect the uterine environment and, subsequently, perinatal outcomes. The objective of this study was to examine the associations between allergic features among mothers and preterm pregnancy outcomes in a nationwide birth cohort. Methods: We analyzed data from pregnant women obtained from the Japanese Environment and Children’s Study (JECS), a nationwide general birth cohort study. We used binomial and multinomial logistic regression models to examine the associations between maternal allergic features and preterm birth, threatened preterm labor (TPL), and preterm premature rupture of the membrane (PPROM). Results: A total of 97,683 pregnant women were included. Prevalence of preterm birth, TPL, and PPROM was 4.7, 19.6, and 1.2%, respectively. Maternal history of allergic diseases (asthma, allergic rhinitis, allergic conjunctivitis, food allergy, drug allergy, and contact dermatitis) increased the risk of TPL(adjusted odds ratio [aOR] = 1.11 [95% CI: 1.06–1.17], aOR = 1.12 [1.08–1.16], aOR = 1.10 [1.04–1.16], aOR = 1.17 [1.09–1.26], aOR = 1.35 [1.23–1.48], and aOR = 1.34 [1.20–1.49], respectively). Although some maternal allergic features showed a negative association with preterm birth, the variables affecting preterm birth differed according to the gestational age of the fetus (22–33 weeks vs. 34–36 weeks). There were no significant associations between maternal allergic features and PPROM. Conclusion: Maternal allergic disease, except atopic dermatitis, may increase the risk of TPL. Comorbidity of maternal allergic disorders and perinatal adverse outcomes require further investigation.

Background: Atopic dermatitis (AD) and exercise-induced asthma (EIA) are common in asthmatic children, and exercise is the most common trigger other than infection for acute onset asthma attack in children. We examined whether AD is related to exercise-induced wheezing (EIW), some proxy for EIA. Methods: Japanese version of the International Study of Asthma and Allergies in Childhood questionnaires were used. For 12,405 asthmatic school children, AD was defined as itchy rash coming and going for at least 6 months at any time in the last 12 months with affecting places of flexural parts of body, and severity of AD was rated according to frequency of being kept awake at night with the itch as follows: never in the past 12 months, less than one night per week and one or more nights per week. Results: Adjusted for frequency of asthma attack, odds ratios (OR) of children with current AD as compared to those without AD for having EIW were 1.32 (95% confidence interval = 1.15–1.52), 1.35 (1.14–1.68) and 1.10 (0.92–1.31) for primary school, junior high school and high school children, respectively. EIW was more likely observed in accordance with increasing severity of AD in the primary school children with ORs of 1.12, 1.59 and 1.54 (p for trend

Eosinophilic esophagitis has been reported as a complication of oral immunotherapy (OIT), but there are only a few reports of eosinophilic gastroenteritis (EGE) occurring after OIT. EGE causes eosinophil infiltration into the gastrointestinal (GI) tract and is characterized by various digestive symptoms. We report the case of a 6-year-old boy with EGE. He was diagnosed as having immediate-type food allergies (egg, milk and wheat) by oral food challenges at 1 year of age. OIT for each food was carried out, and the amounts of the offending foods were able to be gradually increased without causing any immediate-type allergy symptoms. However, the total IgE and specific IgE values were remarkably increased at the age of 4 years and 4 months. He first developed oral mucosa symptoms and vomiting at 4 years and 10 months of age, and they gradually worsened. Stopping eggs and milk alleviated the symptoms. Nevertheless, he still occasionally vomited. He started Pica eating disorder (sand and sponge) due to anemia from 5 years and 10 months of age and developed eosinophilia without diarrhea or bloody stool. Upper and lower GI tract endoscopic examinations found no bleeding. The GI mucosa showed eosinophil infiltration of more than 40/high-power field in the stomach and duodenum, so he was diagnosed with EGE. No eosinophils were found in the esophageal mucosa. His GI symptoms and anemia improved on a multiple-food-elimination diet. Patients undergoing OIT should be closely followed up for a long time, and those with GI symptoms should be evaluated by GI endoscopy.

BACKGROUND mHealth and uHealth apps are available for children with asthma and their caregivers. However, previous studies on mHealth apps for children older than 7 years old with asthma are limited, and most studies on asthma apps do not consider interactions involving communication between children and caregivers. Therefore, a prototype mHealth child asthma app was developed for children and their caregivers, with features of tailored feedback messages in continuing self-management and interactions between children and caregivers. OBJECTIVE The aim of this study was to identify the beneficial features of a prototype mHealth app developed for children with asthma and their caregivers. METHODS Children diagnosed with persistent asthma by allergy specialists at the National Center for Child Health and Development were recruited. The features of a prototype mHealth app for children with asthma and their caregivers were investigated using semistructured interviews after they tried the app. Data were analyzed using thematic analysis. Content-characteristic words were named and grouped together as categories to explore themes. RESULTS We recruited 27 children with asthma aged 2 to 12 years and 26 their caregivers. Findings on the good aspects of the app for children older than 7 years old and caregivers suggested 4 themes (confirmation of asthma knowledge, child-caregiver interaction, design of the app, and child’s interest), and 6 categories were identified. Findings on the good aspects of app for children 7 to 12 years old and caregivers suggested 5 themes (new knowledge, manga as a Japanese-style comic, child’s interest, trigger of self-management, and design and operability), and 11 categories were identified. Findings on the beneficial features of app suggested 6 themes (asthma knowledge, elements for continuous, universal design, notification, monitoring, and functions), and 12 categories were identified. CONCLUSIONS Children with asthma and their caregivers perceived that the good aspects of the app were learning asthma knowledge with fun, including manga; interaction between child and caregiver; and easy-to-read design, such as colors. They wanted not only the asthma knowledge but also the universal design and enhanced elements, monitoring, and notification functions of the app.

Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring.Our analysis used information of 91,049 mother-child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of0.17 ng/mL, 0.17 to21.5 ng/mL (natural log-transformed values, -1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders.Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio.Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

A decline in the proportion of male births (secondary sex ratio, SSR) has been seen in several countries including Japan in recent years. Although previous studies have reported that the SSR is affected by exposure to chemical substances such as dioxins and polychlorinated biphenyls, as well as heavy metals such as methylmercury, the effects of lead exposure on the SSR have been little studied. The aim of this study was to determine the association between maternal lead exposure and SSR. In a large-scale nationwide birth cohort study, maternal blood lead level (BLL) was determined using whole blood from the second or third trimester of pregnancy. The association between SSR and maternal BLL was estimated using multivariable logistic models. Binomial distribution was applied to examine the differences in SSR by dividing the participants into five groups based on BLL. The primary outcome was SSR, and the child sex was obtained from the medical record transcripts. Of 104,062 fetal records, 85,171 were examined for analysis. The median maternal BLL was 5.85 ng/g (5th-95th percentile 3.45-10.6 ng/g). The overall proportion of males among participating infants was 0.512. In logistic regression models adjusted for covariates, the analysis revealed an increased odds ratio for SSR with higher blood lead concentrations [Group 2: adjusted OR 1.082, 95% confidence interval 1.037 to 1.129, Group 3: 1.122, 1.074 to 1.171, Group 4: 1.214, 1.163 to 1.268, Group 5: 1.279, 1.224 to 1.336]. Compared to the general birth probability in Japan, the group with low BLL had a lower SSR and the group with high BLL had a higher SSR. Higher maternal lead exposures during pregnancy were associated with increased SSR. Further investigations including assessment of paternal lead exposure are necessary to understand the association between lead exposure and SSR.

Pregnant women have more sleep problems compared to non-pregnant women. Our objective was to investigate the differences in sleep patterns by age among Japanese women enrolled in the Japan Environment and Children’s Study during preconception and pregnancy. Questionnaires on sleep status were administered to pregnant women twice in the first, second and/or third trimesters. Wake-up time, bedtime, sleep duration and quality of sleep were analyzed in 103,099 respondents. Women younger than 20 years of age awoke and slept the latest in comparison to all other age groups during preconception and pregnancy. Sleep time of women younger than 20 years of age was the longest in comparison to other age groups. The wake-up time and bedtime of teenage mothers were delayed from preconception to second or third trimester, but they did not display any statistically significant changes in other age groups. Moreover, the younger the pregnant women were the more sleep trouble they had despite reportedly being tired, and felt more sleep-deprived despite having had enough sleep time in both second and third trimesters. The sleep state of pregnant women differed by age, with younger women experiencing more sleep trouble and feeling less rested compared to other groups. In future studies, the influences of sleep during pregnancy on the health and development of the children of these pregnant women will be clarified.

It currently remains unclear whether parabens, which are preservatives added to cosmetics, shampoos, and personal care products that exhibit biocidal activities, exert allergic effects in adults. The aim of the present study was to examine the relationship between the use of parabens and the prevalence of allergic diseases in Japanese adults. This population-based cross-sectional study comprised 2005 participants aged 40 years or older living in Shika Town in Japan who answered a self-administered questionnaire on allergic diseases and the daily use of household goods. The information obtained was then analyzed to assess the exposure to parabens (response rate: 77.9%). The prevalence of nasal allergies, atopic conjunctivitis, and total allergies was significantly higher in women who used parabens. These differences remained significant after adjustments for confounding factors including age, body mass index, smoking, alcohol, exercise, sleep, income, education, and marital status. No relationship between the prevalence of atopic dermatitis and the use of parabens was observed in men or women. However, the present results demonstrated that the prevalence of nasal allergies and atopic conjunctivitis was associated with use of parabens in women, suggesting that parabens may induce allergic responses.

Background Exploring patterns of childhood wheeze may help to clarify the etiology and prognosis of respiratory diseases. The purpose of this study was to classify phenotypes of wheezing in children up to 9 years of age in Japan and to evaluate the individual and environmental risk factors for these phenotypes. Methods Wheeze was evaluated at approximately 1-year intervals based on the mothers' recollection of their child's wheezing or whistling in the chest during the preceding 12 months. The children were aged 1-9 years. In total, 1116 children who had at least five measures of wheezing at all nine time points were used for identifying trajectories. Trajectories were identified with group-based trajectory analysis. A multinomial logit model was built to evaluate the relationships between phenotypes and risk factors. Results Five typical trajectories were identified. The probability of group membership was 43.7%, 32.2%, 6.2%, 8.6%, and 9.2% for the never/infrequent wheeze, transient early wheeze, school-age-onset wheeze, early-childhood-onset remitting wheeze, and persistent wheeze trajectories, respectively. Infant tobacco exposure increased the odds of membership in the transient early wheeze trajectory compared to the never/infrequent wheeze trajectory. Conclusions Using the group-based trajectory modeling approach, we identified five trajectories of childhood wheeze development in a Japanese population. The trajectories shown here are based on formal statistical modeling rather than on subjective classification, and an assessment of its precision suggested that the model has high assignment accuracy.

Introduction: The Modified Pulmonary Index Score (MPIS) was developed as an objective assessment tool for acute asthma exacerbation in children. Although it is considered reliable, there are no known studies of its clinical utility. The objective of this study was to evaluate the validity of the MPIS for children with acute asthma in a clinical setting. Methods: In this retrospective study conducted between July 2009 and June 2011 using electronic medical records at the emergency department of a single pediatric medical center in Tokyo, Japan, the MPIS was recorded for patients with acute asthma at initial assessment and after treatment with an inhaled beta-agonist. We evaluated the responsiveness and predictive validity of the MPIS using disposition as an outcome. Results: A total of 2242 patients were assessed using the MPIS (median age, 3 years; 71.2% patients were 5 years or younger). The mean (SD) MPIS at initial assessment was 7.1 (3.6) and was significantly higher for the admission group than for the non-admission group (9.9 [2.9] vs. 5.9 [3.1]; P < 0.001). The receiver operator characteristic curve of the initial MPIS for hospital admission demonstrated moderate predictive ability (area under the curve, 0.83). An MPIS reduction of 3 or more indicated a clinically significant change when the MPIS at initial assessment was between 6 and 10 (risk ratio for admission [95% CI], 0.41 [0.28–0.60]; P < 0.001). Conclusion: The MPIS demonstrated good concurrent validity, predictive validity, and responsiveness in a wide range of clinical settings.