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Early-onset atopic dermatitis increases an individual’s risk of food allergies, suggesting that transcutaneous sensitization may occur through inflamed skin. Regarding food allergy causation, the dual allergen exposure hypothesis proposes that oral allergen exposure leads to immune tolerance, whereas allergen exposure via inflamed skin causes food allergies. This hypothesis suggests that it is important to induce oral immune tolerance and prevent allergic food sensitization through the skin. This review focuses on the breakthrough evidence based on the dual allergen exposure hypothesis that involves both skin and oral interventions for food allergy prevention.

Background: The association between pet exposure in infancy, early childhood eczema, and FLG mutations remains unclear. Methods: This was a birth cohort study performed in Tokyo, Japan. The primary outcome was current eczema based on questionnaire responses collected repeatedly from birth to 5 years of age. Generalized estimating equations and generalized linear modeling were used to evaluate the association. Results: Data from 1448 participants were used for analyses. Household dog ownership during gestation, early infancy, and 18 months of age significantly reduced the risk of current eczema. Household cat ownership also reduced the risk of current eczema, albeit without statistical significance. The combined evaluation of children from households with pets, be it cats, dogs or both, the risk of current eczema at 1–5 years of age was lower in those with household pet exposure ownership during gestation (RR = 0.59, 95 % CI 0.45–0.77) and at 6 months (RR = 0.49, 95 % CI 0.36–0.68). , Reduced risks of eczema were also observed at 2–5 (RR = 0.52, 95 % CI 0.37–0.73) and 3–5 years of age (RR = 0.50 95 % CI 0.35–0.74) when the respective household pet ownership were evaluated at 18 months and 3 years of age. These protective associations of reduced risk of eczema were only observed in children without FLG mutations. Conclusions: Household dog and pet (dog, cat, or both) ownership was protective against early childhood eczema in a birth cohort dataset. This protective association was observed only in children without FLG mutations, which should be confirmed in studies with larger cohorts.

Abstract Introduction Difamilast is the first selective phosphodiesterase 4 inhibitor approved for atopic dermatitis (AD) in Japan. A phase 3, 52-week, open-label study is ongoing to establish efficacy and safety of difamilast ointments in infants with AD aged 3 to

IntroductionCleft lip and/or palate (CL/P), the most prevalent congenital anomaly, has been associated with higher rates of child maltreatment. In particular, the presence of cleft lip has more of an impact on external appearance and may increase the risks of negative health outcomes such as parental postpartum depression; however, this concept remains controversial. Item #10 of the Edinburgh Postpartum Depression Scale is the assessment of parental self-harm ideation, and its presence in postpartum mothers merits risk assessments as an emergent issue that may affect the health of both mothers and infants. This study focused on the impact of CL/P on maternal self-harm ideation.MethodsOf 100,300 live births from a nationwide birth cohort in Japan, 238 mothers of infants with CL/P [186 children born with cleft lip (CL ± P) and 52 born with isolated cleft palate (CP)] were included in the analyses. The prospective association of children with CL/P and maternal self-harm ideation, which were acquired using item #10 in the Edinburgh Postpartum Depression Scale at 1 and 6 months postpartum, was examined using binomial logistic regression analyses after multiple imputations and with adjustments for several maternal (age at delivery, smoking habit, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables.ResultsThe prevalence of self-harm ideation in 238 mothers of infants with CL/P at 1 and 6 months were 14.7% (35/238) and 18.8% (45/238) [8.2% (8,185/100,062) and 12.9% (12,875/100,062) in the control group], respectively. The odds ratio (95% confidence interval) for maternal self-harm ideation increased with CL/P prevalence [1.80 (1.22–2.65) and 1.47 (0.98–2.18)] at 1 and 6 months of age, respectively. After stratified by the prevalence of cleft lip, we found significant differences in the CL ± P group but not in the CP group. Furthermore, persistent self-harming ideation was associated with a higher risk in the CL ± P group [2.36 (1.43–3.89)].ConclusionCL/P, particularly cleft lip, which is more noticeable externally, was associated with an increased prevalence of maternal self-harm ideation. The findings in this study indicate some potential benefits of increasing support for mothers who have infants with CL/P.

Objectives To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study.Design This study was a prospective birth cohort study.Setting This study population included 104 059 fetal records who participated in The Japan Environment and Children’s Study from 2011 to 2014.Participants Pregnant women whose children had undergone developmental testing were included in this analysis.Primary and secondary outcome measures Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development.Results Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers.Conclusion An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world.

Background: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. Methods: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). Results: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about “diagnosis-probable” patient cohort (n = 402) and the “diagnosis-confirmed” patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. Conclusions: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Background: N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. Methods: Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. Results: Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-

Background: Adults with food-protein-induced enterocolitis syndrome (FPIES) often develop severe abdominal symptoms after eating seafood. However, no investigation of a food elimination strategy for adult FPIES patients has been performed to date. Methods: We conducted a retrospective cohort study of seafood–avoidant adults by telephone interview, based on the diagnostic criteria for adult FPIES reported by González et al. We compared the clinical profiles, abdominal symptoms, and causative seafoods between FPIES and immediate-type food allergy (IgE-mediated FA) patients. We also profiled the detailed intake-status of seafoods in adult FPIES patients. Results: Twenty-two (18.8 %) of 117 adults with seafood-allergy were diagnosed with FPIES. Compared with the IgE-mediated FA patients, FPIES patients had an older age of onset, more pre-existing gastrointestinal and atopic diseases, more episodes, longer latency and duration of symptoms, more nausea, abdominal distention, and severe abdominal pain, and more frequent vomiting and diarrhea. In particular, abdominal distention—reflecting intestinal edema and luminal fluid retention—may be the most distinctive characteristic symptom in adult FPIES (p

To assess the risk of food allergies in foods processed under the Japanese food labeling system, estimating exposure to hidden allergens is necessary. We assessed exposure to egg protein in foods processed according to the Japanese food labeling system. First, we estimated the concentration distribution of egg protein by Bayesian methods using data from the literature and the measurement of food products with precautional declarations in the labeling margin. We then estimated the food-intake portion-size distribution under two scenarios: soft drink consumption as an example of single, high-intake consumption, and confections, which are frequently consumed by children, as a realistic example of low-intake consumption. Finally, we estimated the distribution of unexpected intake of egg proteins in the form of single consumption. The mean exposure to egg protein under the high-intake scenario was estimated to be 0.0164 mg for 1–15-year-olds, 0.0171 mg for 4–15-year-olds, 0.0181 mg for 7–15-year-olds, and ≥0.0188 mg for 16-year-olds. The mean exposure to egg protein under the low-intake scenario was estimated to be 0.0018 mg for 1–15-year-olds, 0.0019 mg for 4–15-year-olds, 0.0020 mg for 7–15-year-olds, and ≥0.0022 mg for 16-year-olds. Compared to the reference dose of 2.0 mg proposed by the Joint the Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee, the risk of onset of food allergies due to egg protein contamination from foods without egg labeling is considered to be extremely low under the current Japanese food labeling system.

Objective The primary objective of this study was to investigate the parenting attitudes towards children with autism spectrum disorders in early childhood in Japan.Design This study was a cohort study. The participants were enrolled from January 2011 to March 2014. We obtained the prevalence of autism spectrum disorders at 3 years of age, parenting attitudes and other factors from questionnaires. We divided the participants into two groups, an autism spectrum disorders group and a non-autism spectrum disorders group, and compared the parenting attitudes.Setting This study used data from a Japanese birth cohort study: the Japan Environment and Children’s Study, conducted across 15 regional centres in Japan.Participants The full dataset of the Japan Environment and Children’s Study comprised 104 059 records. We excluded 17 889 records because the answer for the autism spectrum disorders in the questionnaire was blank. As a result, we analysed the remaining 82 411 mother–child pairs.Main outcome measures The primary outcome variable was parenting attitudes at 3.5 years of age, which was assessed using a questionnaire. We asked respondents 16 questions related to parenting attitudes, and they answered based on their behaviours. The independent variable was the prevalence of autism spectrum disorders at 3 years of age.Results Of the 82 411 participants, the children with autism spectrum disorders at 3 years of age were 372 (0.45%). In most questions about parenting attitudes, the autism spectrum disorders group had unfavourable responses. The difference was particularly noticeable when the parents taught their children social discipline. Unfavourable parenting attitudes were 16.6% in the autism spectrum disorders group and 0.8% in the non-autism spectrum disorders group in the question item with the largest difference between the two groups, a significant difference.Conclusions Parents of children with autism spectrum disorders tended to have unfavourable attitudes, suggesting the importance of parental training.

Background: The effectiveness of slow low-dose oral immunotherapy (SLOIT) for cow's milk (CM) allergy has been reported. Most OIT studies have discussed the target populations over 4 years old. Furthermore, no predicting modeling is reported for CM allergy remission by CM-SLOIT under 4 years of age. Objective: We sought to develop a predictive model for CM allergy remission by SLOIT after 3 years in young children who started CM-SLOIT under 4 years of age. Methods: We included young children with cow's milk allergy or cow's milk sensitization (development modeling set with 120 children and validation modeling set with 71 children). We did logistic regression analysis to develop the models. We calculated the area under the receiver operating curves (ROC-AUCs) to evaluate the predictive modeling performance. Results: The model (CM-sIgE before SLOIT + age at beginning SLOIT + serum TARC before starting SLOIT + CM-sIgE titer one year after OIT) showed good discrimination with the ROC-AUC of 0.83 (95% CI:0.76–0.91) on internal validation. Applying the model to the validation set gave good discrimination (ROC-AUC = 0.89, 95% CI:0.80–0.97) and a reasonable calibration (intraclass correlation coefficient = 0.88, 95% CI:0.62–0.97). Conclusion: We developed and validated predictive modeling for determining the remission rate of CM allergy at 3 years after SLOIT under 4 years of age in children with CM allergy. This predictive model is highly accurate and can support CM allergy management. (226 words)

The escalating global allergy epidemic has emerged as a pressing and persistent challenge, exerting a profound impact on human health systems across centuries. This burgeoning predicament can be attributed to contemporary lifestyles, environmental influences, and genetic predispositions. The manifestation of allergy-related factors exhibits dynamic fluctuations contingent on temporal shifts, geographical distinctions, cultural variances, and diverse demographic strata. In this review, we present recent epidemiological insights derived from two distinct birth cohorts: the Japan Environment and Children's Study (JECS), encompassing the entirety of Japan, and the Tokyo Children's Health, Illness, and Development Study (T-Child Study) within Tokyo. Through this comprehensive review, we offer a comprehensive overview of the latest epidemiological discoveries stemming from these pivotal Japanese birth cohorts, thereby affording a unique opportunity to deliberate on imperative strategies for the optimal management of the allergy epidemic.

Abstract Introduction Upadacitinib is an oral Janus kinase inhibitor approved in multiple countries for moderate-to-severe atopic dermatitis (AD). Here we present long-term data for up to 3 years of continuous upadacitinib treatment in Japanese patients with AD. Methods Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upadacitinib in patients with moderate-to-severe AD. Patients aged 12–75 years (weight ≥ 40 kg if

Abstract Objective: Pre-pregnancy weight status is related to offspring health and may influence dietary patterns during pregnancy. We aimed to evaluate the link between pre-pregnancy weight status and dietary patterns during pregnancy. Design: Dietary data were collected using a FFQ during middle or late pregnancy. Dietary patterns were identified using principal component analysis. Anthropometric data were extracted from medical charts. Multiple linear regression was used to assess associations between pre-pregnancy weight status (severely or moderately underweight, mildly underweight, normal weight, overweight and obese) and dietary patterns during pregnancy after adjusting for socio-demographic characteristics. Setting: Nationwide Japan. Participants: Pregnant Japanese women enrolled in the Japan Environment and Children’s Study, a prospective birth cohort study (n 90 765). Results: We identified three dietary patterns. Compared with women with pre-pregnancy normal weight, those with pre-pregnancy obesity were less likely to habitually consume ‘fruits and vegetables’ pattern (coefficient, –0·18; 95 % CI, –0·21, –0·14) and ‘confectionery’ pattern (coefficient, –0·18; 95 % CI, –0·21, –0·14) and more likely to consume ‘white rice and soy products’ pattern (coefficient, 0·08; 95 % CI, 0·04, 0·11), and those with severely or moderately pre-pregnancy underweight were more likely to consume ‘confectionery’ pattern (coefficient, 0·06; 95 % CI, 0·03, 0·09) during pregnancy, after adjusting for confounders. Conclusion: We found that moderately and severely pre-pregnancy underweight women and those with obesity had unhealthy dietary patterns compared to those with pre-pregnancy normal weight. Our findings suggest that prenatal dietary advice is important and should be based on the pre-pregnancy weight status.

Abstract Background Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. Methods The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children’s Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. Results After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. Conclusions The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.

Background: The nature of itch sensation varies depending upon the patient and the disease. However, few studies have focused on verbal expressions describing itch of atopic dermatitis (AD) in quality.Objectives: To investigate itch quality in patients with AD compared with that of urticaria.Methods: We conducted an online questionnaire survey describing itch experiences in June 2021. Participants were Japanese patients who had visited hospitals for their consultations and treatments of AD or urticaria in the last 6 months, and 295 and 290 responses, respectively, to questions using 12 terms describing itch quality were analyzed.Results: The most suitable expression describing intense itch that patients could not help scratching differed between the diseases, where most AD patients selected “muzumuzu” (a mimetic word for creepy–crawly itch) (27%) or “painful itch” (20%), and most urticaria patients selected “muzumuzu” (24%) or “itch like mosquito bites” (22%). The most suitable expressions describing itch that would make patients happiest if improved was “painful itch” (27%) in AD patients, significantly higher than urticaria patients (19%). More AD patients (55%) responded that they sometimes felt itch even after the skin symptoms had subsided than urticaria patients (41%). The most suitable expression of remnant itch selected was “muzumuzu” for AD (58/161 patients, 36%) and urticaria (29/120 patients, 24%).Conclusion: The quality of itch sensations can be classified not only between diseases but also during the clinical course of each disease. Significant expressions that patients with AD use to describe itch sensations could promote more appropriate treatment for itch.

Objectives To evaluate the association between urinary 8-hydroxy-2′-deoxyguanosine (U8-OHdG) level—a marker of oxidative stress—and the incidence of preterm births (PTBs).Design Prospective cohort study.Setting The Japan Environment and Children’s Study (JECS).Participants Data from 92 715 women with singleton pregnancies at and after 22 weeks of gestation who were enrolled in the JECS, a nationwide birth cohort study, between 2011 and 2014 were analysed. U8-OHdG levels were assessed once in the second/third trimester using liquid chromatography–tandem mass spectrometry. Participants were categorised into the following three or five groups: low (

Abstract Background The level of child development may be associated with the risk of poor maternal health-related quality of life (HRQoL). The objective of this study was to describe the developmental characteristics of very low birth weight (VLBW) children at 2.5 years of age and to examine associations between maternal HRQoL and the degree of child development based on the Japanese version of Ages and Stages Questionnaire (J-ASQ-3). Methods A cross-sectional study was performed using the data from a nationwide prospective birth cohort study in Japan. Among a total of 104,062 fetal records, the VLBW infants (birth weight ≤ 1500 g) were analyzed using linear regression models, adjusted for potential covariates. Subgroup analysis was also conducted to assess the association between social connection or cooperation of the partner and maternal HRQoL by the level of child development. Results The final study subjects included 357 VLBW children and mothers. The suspected developmental delays (SDDs) in at least two domains was significantly associated with lower maternal mental HRQoL regression coefficient –2.314 (95%CI: –4.065 to –0.564). There was no association between the status of child development and maternal physical HRQoL. After adjusting for child and maternal covariates, the maternal HRQoL was not significantly associated with child development. Amongst women who indicated having some social support, having a child with a SDD in two or more domains was negatively associated with mental HRQoL compared with women whose child was less developmental delay, regression coefficient –2.337 (95%CI: –3.961 to –0.714). Amongst women who indicated having partner’s cooperation to child-rearing, having a child with a SDD in two or more domains was negatively associated with mental HRQoL compared with women whose child was less developmental delay, regression coefficient –3.785 (95%CI: –6.647 to –0.924). Conclusions Our findings indicate that the lower maternal mental HRQoL was independently associated with the SDDs evaluated by the J-ASQ-3, whereas there was no association after adjusting for covariates. Further research is warranted to elucidate the impact of social connection and partner’s cooperation on maternal HRQoL and child development. This study urges that particular attention should be paid to mothers of VLBW children with SDDs and also to provide early intervention and continued support.

Objectives We examined literacy related to healthy gestational weight gain (GWG) in immigrant and native Japanese mothers and determined whether it is associated with children’s birth weight.Design Longitudinal cohort study.Setting As the baseline survey in the Japan Environment and Children’s Study (JECS), mothers completed self-administered questionnaires distributed by hand during pregnancy. The self-administered questionnaires used in this study were distributed by mail 6 months after delivery. Children’s birth weight, actual GWG and any complications during delivery were recorded by obstetricians collaborating with JECS.Participants Of 97 452 mothers who consented to participate in the JECS during pregnancy between January 2011 and March 2014, 67 953 were included in this study after exclusions for multiple births, multiple instances of consent by the same pregnant woman, miscarriages/stillbirths or withdrawal from the study within 3 years after participating. In total, 324 immigrant mothers and 963 native Japanese mothers were selected by propensity score matching for analysis.Primary and secondary outcome measures Data were collected on maternal literacy related to healthy GWG at the baseline survey, and data on actual GWG and children’s birth weight were collected by obstetricians. The associations of knowledge about healthy GWG and mothers’ actual GWG with maternal nativity status were examined using a χ2 or Student’s t-test.Results More native Japanese mothers than immigrant mothers knew the appropriate GWG and reason the for needing to know this. Actual GWG was significantly higher among the immigrant mothers, but was within the recommended range. The low birthweight (LBW) incidence was significantly higher among the native mothers.Conclusions Immigrant mothers to Japan had less knowledge about appropriate GWG, but their actual GWG was appropriate and they delivered fewer LBW infants than native Japanese mothers. These findings may indicate the presence of other protective factors for pregnancy or delivery among immigrant mothers.

Background: The association of maternal antibiotic exposure during pregnancy with childhood allergic diseases remains unclear. Objective: We aimed to evaluate the association of maternal exposure to antibiotic use during pregnancy with childhood allergic diseases up to the age of 3 years by using data from a large Japanese birth cohort. Methods: We analyzed data on 78,678 pregnant women and their offspring aged 0 to 3 years. Prenatal antibiotic exposure was defined as the use of any antimicrobial agent during pregnancy. Information was collected from maternal interviews and medical record transcripts. The outcome variables in this study included preschool asthma, wheezing, food allergy, atopic dermatitis, eczema, allergic rhinoconjunctivitis, and any allergic disease. We used logistic regression analysis to evaluate the association of antibiotic exposure during pregnancy with childhood allergic diseases. Results: Among the participating mothers, 28.5% used antibiotics during pregnancy. Antibiotic exposure during pregnancy was associated with preschool asthma (adjusted odds ratio [aOR] = 1.12 [95% CI = 1.06-1.19]), wheezing (aOR = 1.11 [95% CI = 1.07-1.15]), allergic rhinoconjunctivitis (aOR = 1.10 [95% CI = 1.03-1.17]) and any allergic disease (aOR = 1.09 [95% CI = 1.05-1.14]) in offspring up to age 3 years. In contrast, maternal antibiotic use was not associated with food allergies, atopic dermatitis, or eczema. Additionally, the significant associations were not influenced by the timing of antibiotic exposure, sex of the infants, or maternal history of allergies. Conclusion: Maternal antibiotic exposure during pregnancy is associated with an increased risk of childhood respiratory allergies.

Background: Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the “Rainbow Elimination Diet (ED).” The aims of this study were to evaluate the tolerability and safety of this diet. Methods: A retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2–17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated. Results: Nineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14–30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median −0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9–3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium. Conclusions: The Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.

Background: Eczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns. Methods: This birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC. Results: Persistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome. Conclusions: Early-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.

This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. “Infant and preschool asthma” is diagnosed when young children (

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

BackgroundAnimal studies have shown that maternal low-fiber diets during pregnancy may impair brain development and function in offspring, but this has not been validated by epidemiological studies. The aim of this study was to investigate the link between maternal dietary fiber intake during pregnancy and neurodevelopmental delay in offspring using a large birth cohort.MethodsA total of 76,207 mother-infant pairs were analyzed using data from the Japan Environment and Children's Study, a nationwide prospective cohort study. Maternal dietary fiber intake was estimated using the food frequency questionnaire in mid-pregnancy. Maternal dietary fiber intake was adjusted for energy and classified into quintiles. Developmental delay was assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition at the age of 3 years. The logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the link between dietary fiber intake during pregnancy and developmental delay at the age of 3 years.ResultsThe lowest intake group of total dietary fiber had a higher risk of delayed communication [adjusted OR (aOR), 1.51; 95% CI, 1.32–1.74], fine motor (aOR, 1.45; 95% CI, 1.32–1.61), problem-solving (aOR, 1.46; 95% CI, 1.32–1.61), and personal-social skills (aOR, 1.30; 95% CI, 1.12–1.50) than did the highest intake group. An analysis that excluded the effects of insufficient folic acid intake during pregnancy also showed a similar trend.ConclusionThis study showed that maternal dietary fiber deficiency during pregnancy might influence an increased risk of neurodevelopmental delay in offspring.

Background: Allergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed. Objective: We sought to detect genetic variants associated with differences in immune responsiveness against allergen components. Methods: The participants of the present study were recruited from the Tokyo Children’s Health, Illness, and Development study, and allergen component–specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16). Results: We performed GWAS on 564 participants of the Tokyo Children’s Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10−8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10−8). Conclusions: Our data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.

Reports of food protein–induced enterocolitis syndrome (FPIES) in Japan have been increasing. However, the disease itself and the treatment options are poorly understood by both patients and medical professionals. The objective of this study is to develop an action plan for acute FPIES in Japan. We prepared a single–sheet action plan that describes the management of acute FPIES episodes for caregivers on one side and medical professionals on the reverse side. To evaluate the content of the action plan, we distributed a questionnaire to caregivers of patients with FPIES and to physicians who would encounter patients with FPIES. Changes to the FPIES action plan were made based on the feedback from the participants. The Delphi method was utilized to finalize the action plan. The participants of the initial survey found the action plan to be useful but the process for determining severity to be impractical. After discussion, the authors made appropriate improvements. By the Delphi method, consensus was reached on the revised FPIES action plan. In conclusion, this Japanese FPIES action plan was created by physicians from multiple subspecialties and caregivers of patients with FPIES. The action plan may improve the management of acute FPIES reactions in the Japanese community.

Background: Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood. Methods: This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles. Results: The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels. Conclusions: The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins.

Background: Systemic atopic dermatitis treatments that have acceptable safety are needed. Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis. Methods: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16). Adverse events and laboratory data were assessed for safety. Results: In 272 treated patients, the serious adverse event rates were similar for 15- and 30-mg upadacitinib + TCS at week 24 (15 mg, 56%; 30 mg, 64%) but greater than those for placebo + TCS (42%). Acne (all mild or moderate; none leading to discontinuation) occurred more frequently with upadacitinib + TCS (15 mg, 13.2%; 30 mg, 19.8%) than with placebo + TCS (5.6%). Furthermore, herpes zoster infection (4.4% vs 0%), anemia (1.1% vs 0%), neutropenia (4.4% vs 1.1%), and creatine phosphokinase elevations (2.2% vs 1.1%) occurred more frequently with 30-mg upadacitinib + TCS than with 15-mg upadacitinib + TCS; none of these events were reported with placebo + TCS. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred. Limitations: The limitations included a small sample size and short observation period as well as nongeneralizability of the results beyond Japanese populations. Conclusions: The results were generally consistent with those of previous reports; no new safety risks were detected.

IntroductionPhysical examinations to assess pubertal development are challenging in large epidemiological surveys. This study aimed to assess the reliability of judgment of pubertal onset in Japanese children by the original pubertal self-assessment sheet.MethodsA total of 144 children aged 10 or 12 years were recruited between March 2019 and September 2020 from the pediatric endocrine outpatient clinics of participating institutions. Agreement between the physician- and participantassessed pubertal onsets was determined using unweighted kappa (UK) and Gwet's agreement coefficient (AC1).ResultsThe physician's assessment of pubertal onset was in slight agreement with that of the self-assessment sheet in 10-year-old boys (UK: 0.23 and AC1: 0.14), whereas the agreement between the physician's assessment and self-assessment sheet results was good and the physician's assessment was fair (UK: 0.64 and AC1: 0.94) in 12-year-old boys. The physician's assessment of pubertal onset were in good and moderate agreement with the self-assessment sheet in 10-year-old girls (UK/AC1: 0.74/0.78, respectively). In 12-year-old girls, although it showed poor agreement with UK (0.46), there was a very good agreement with AC1 (0.88).ConclusionsAlthough self-assessment of breast development was in good agreement with that of the physician's assessment for determining pubertal onset in girls, large-scale epidemiological studies are difficult to conduct for adolescent boys, especially for those in the early pubertal stage.

Abstract Background The study aim was to obtain epidemiological data on vitamin D levels for the pediatric population in Japan. We assessed the prevalence of vitamin D deficiency and insufficiency in 2-year-old Japanese children using data from a large ongoing birth cohort study. Methods Data for analysis was obtained from the Japan Environment and Children’s Study (JECS) and a Sub-Cohort Study (SCS) of JECS. We evaluated the children’s serum 25(OH) D levels by 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, and the rates of vitamin D deficiency or insufficiency. We also presented a weighted prevalence rate for vitamin D deficiency or insufficiency among all children in JECS. Results After excluding children with missing 25(OH)D2 or 25(OH)D3 data, we analyzed 4655 remaining children, of whom 24.7% (95% CI, 23.5–26.0%) had vitamin D deficiency (

Background: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. Methods: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. Results: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1–10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270–1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341–2.078; asthma: 1–10 cigarettes/day: aOR 1.389, 95% CI 1.087–1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045–2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083–1.256; asthma: aOR 1.258, 95% CI 1.075–1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739–2.317; asthma: aOR 1.995, 95% CI 1.528–2.605). Conclusions: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.

Background: Wheezing is a common symptom in infants, which may occasionally develop into asthma. There are many factors related to infant wheezing, including anatomical features, viral infections, and passive smoking. There are only a few reports on the association between renovation and pregnancy worldwide, and reports on this association are inadequate in Japan. This study aimed to examine the association between house renovation and new construction during pregnancy and wheezing in infants during the first year of life using data from the Japan Environment and Children's Study (JECS). Methods: Data of pregnant women registered in JECS were collected using self-administered questionnaires during the second/third trimester and 1 month after delivery. Childbirth records were completed by the doctors. Similarly, wheezing in infants was evaluated using self-administered questionnaires 1 year after birth. Logistic regression analysis was used to determine the primary outcome. Results: In total, 75,731 infants, excluding those with unknown gender, who were not singleton infants, and who relocated during pregnancy and the first month of life, were examined in this study. Renovation during pregnancy increased the prevalence of wheezing (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.20–1.48) and recurrent wheezing (OR: 1.22, 95% CI: 1.00–1.48) in the first year of life. The relationship between new construction during pregnancy and wheezing in infants was insignificant (OR: 0.98, 95% CI: 0.90–1.06). Conclusions: Renovation during pregnancy may be a risk factor for wheezing in infants, and should be avoided.

Background: Treatment options for adolescents with moderate-to-severe atopic dermatitis (AD) are limited. Oral corticosteroid therapies are used to treat children and adolescents with moderate-to-severe AD; however, long-term use is not recommended because of potential growth impairment. Upadacitinib, an oral Janus kinase inhibitor, is approved to treat moderate-to-severe AD in the United States, Japan, and Europe. To investigate potential effects of upadacitinib on growth, we analyzed height and height velocity in 6 adolescent patients in the phase 3 Rising Up study who were in the decline phase of pubertal growth at the time of study entry. Methods: The randomized, double-blind, Rising Up (NCT03661138) study compared upadacitinib plus topical corticosteroids (TCS) to placebo plus TCS in adolescents and adults with moderate-to-severe AD in Japan. Eligible adolescents (aged 12–17 years) were randomized 1:1:1 to receive once-daily upadacitinib 15 mg, upadacitinib 30 mg, or placebo in combination with TCS for 16 weeks. After 16 weeks, patients randomized to receive placebo were rerandomized 1:1 to receive upadacitinib 15 mg or upadacitinib 30 mg. Historical height measurements were obtained when available. Individual growth and growth velocity curves were compared with standard curves for Japanese youths. This non-prespecified analysis used 52-week data. Results: Of the 29 adolescents enrolled, 6 were in the decline phase of pubertal growth at enrollment. Growth curves and growth velocity curves for these 6 patients remained within the normal range for Japanese adolescents throughout the study. Biomarkers of bone metabolism generally remained stable over the course of the study. No musculoskeletal adverse events were reported. Conclusions: No cases suggested that upadacitinib negatively affected adolescent growth. Ongoing studies will continue to assess height and adverse effects related to bone growth to further inform on this patient group. Trial registration: ClinicalTrials.gov Identifier NCT03661138.

Abstract Background A variety of dietary supplements are commercially available. However, the efficacy and safety of dietary supplement use in children are not well established. Understanding dietary supplement use is important for developing public health policy regarding dietary supplements. This study aimed to investigate the types of dietary supplements used and characteristics of dietary supplement users among Japanese elementary school children. Method We conducted a cross-sectional web-based questionnaire study. Dietary supplement use, socio-demographics, and health-related behaviors were assessed through mother-reported questionnaire. Types of dietary supplements were identified based on ingredient using product barcodes and brand names. Multivariate logistic regression analysis was conducted to investigate the socio-demographics and health-related behaviors associated with supplement use. Results Among 4933 children, 333 (6.8%) were identified as dietary supplement users. The most common supplement was amino acids or protein (1.4%), followed by n–3 fatty acids or fish oil (1.0%), probiotics (1.0%), multivitamins (0.9%), multivitamin-minerals (0.8%), and botanicals (0.8%). Overall, any dietary supplement use was significantly associated with the highest frequency of sports participation (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.65–4.02), highest household income (OR, 1.87; 95% CI, 1.13–3.10), highest maternal educational level (OR, 1.82; 95% CI, 1.31–2.52), and male sex (OR, 1.38; 95% CI, 1.09–1.75). The highest frequency of sports participation was significantly associated with higher odds of use of amino acids or protein (OR, 6.06; 95% CI, 1.78–20.6) and multivitamins (OR, 3.56; 95% CI, 1.11–11.5), compared to the lowest frequency of sports participation. Conclusion This study showed that Japanese children primarily use non-vitamin, non-mineral supplements. Non-vitamin, non-mineral supplements should thus be included in future studies aimed at monitoring dietary supplement use. We also found that dietary supplement use in children was associated with sports participation. Guidelines for dietary supplement use for children, in particular sport participants, are needed.

ObjectivesInfants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants.Study DesignThe Japan Environment and Children’s Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight

BackgroundMobile health apps can support the self-management of pediatric asthma. Previous studies on mobile apps for children aged >7 years with asthma are limited, and most reports on asthma apps do not consider interactions between the children and their caregivers. Therefore, we developed an asthma app for children aged 0-12 years and their caregivers based on the results of our previous study regarding user needs. ObjectiveThe aim of this study was to evaluate the feasibility of a developed mobile app for children with asthma and their caregivers and to modify and complete the app according to the feasibility results. MethodsWe recruited children diagnosed with persistent asthma by an allergy specialist at 2 children’s hospitals, 1 university hospital, 2 general hospitals, and 1 pediatric clinic. Thereafter, the app usage was assessed, and questionnaires were administered. This study used convergent mixed methods, including providing user feedback about the pediatric asthma app, completing questionnaire surveys regarding preferences, and obtaining quantitative data about app usage. Quantitative data were analyzed based on the ratings provided for the app features used by the participants, and the usage of the app features was analyzed using descriptive statistics. Qualitative data were analyzed via a descriptive qualitative research analysis and were used to identify codes from the content-characteristic words. ResultsIn total, 30 pairs of children aged 2-12 years and their caregivers responded to the 3-month survey, and 20 pairs of children aged 4-12 years and their caregivers responded to the 6-month survey. In the 3- and 6-month surveys, “record” was the most commonly used feature by both caregivers and children. The average access logs per month among the 20 pairs ranged from 50 to 79 in the 6-month survey. The number of access logs decreased over time. In the qualitative results, app utilization difficulties were identified for 6 categories: record, preparing, alert settings, change settings, mobile phone owner, and display and motivation. Regarding app feasibility, 60% (12/20) of the caregivers strongly agreed or agreed for all evaluation items, while 63% (7/11) of the children strongly agreed or agreed for 6 items, excluding satisfaction. In the qualitative results, feasibility evaluation of the app was classified into 3 categories: high feasibility of the app, improvement points for the app, and personal factors preventing app utilization. Based on the results of the feasibility analysis, the final version of the app was modified and completed. ConclusionsThe app feasibility among children with asthma and their caregivers was generally good. Children aged 7-12 years used elements such as record, quiz, and manga. This app can support the continuous self-management of pediatric asthma. However, efforts must be taken to maintain and improve the app quality. Trial RegistrationUMIN Clinical Trials Registry UMIN000039058; https://tinyurl.com/3na9zyf8

Abstract Aims/Introduction We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers of participants in the Japan Environment and Children’s Study, a nationwide, multicenter, pregnancy and birth cohort. Materials and Methods Pregnant women aged 14–50 years were studied in 15 centers across Japan. Clinical information was obtained using self‐administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. Results Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. Glycated hemoglobin, total cholesterol, low‐density lipoprotein cholesterol and triglyceride across all the percentiles increased as prepregnancy body mass index increased, whereas high‐density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. Glycated hemoglobin was high in participants with type 1 diabetes or type 2 diabetes only, but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high‐density lipoprotein cholesterol, whereas participants with dyslipidemia only showed high total cholesterol and low‐density lipoprotein cholesterol throughout. Conclusions Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The Japan Environment and Children’s Study will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies.

Objectives: We conducted a multicenter study using the same questionnaire in 1999 and 2014 to investigate changes in the characteristics of patients with latex allergy. Methods: We mailed questionnaires on latex allergy to hospitals in Japan that were members of the Japanese Latex Allergy Society. Results: We compared the 25 responses received in 2014 and the 81 responses received in 1999. With regard to the age distribution, the number of patients with latex allergy in their 20s declined significantly from 1999 to 2014 (P=0.004). The largest proportion of latex allergy cases was observed among those aged

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.

Abstract Background Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. Methods We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children’s Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. Results Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028–1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149–2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094–1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007–1.299; four or five vaccines vs. a single vaccine). Conclusions Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. Trial registration UMIN000030786 .

The Japanese Guideline for Childhood Asthma (JGCA) 2020 is a translation of the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL) 2017 into English, which was published by the Japanese Society of Pediatric Allergy and Clinical Immunology. It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. These guidelines will be of interest to non-specialist physicians involved in the care of children with asthma. In JPGL, JPGL2017 is the first evidence-based guidelines updated according to the GRADE system and Minds approach, and it addresses eight clinical questions about the treatment of childhood asthma. In children aged ≤5 years, infant and preschool asthma is diagnosed according to the response to short acting beta2 agonists or the effect of a therapeutic trial during 1 month with controller treatment and worsening after treatment cessation. Long-term management both promotes pharmacological therapy and measures against risk factors that induce exacerbation, better patient education and a partnership with trinity. In addition, long-term management should not be carried out without review but rather be based on a cycle of evaluation, adjustment and treatment. In JPGL2017, the transdermal patch and oral beta2 agonists are positioned as drugs within the concept of “short-term additional treatment” to be used until the symptoms are stabilized when the control state transiently deteriorates.

BackgroundAtopic dermatitis (AD) is a chronic and inflammatory skin disease that causes health-related burdens associated with pruritus and poor quality of life. Our previous study demonstrated that moisturizer (2e) application has a primary preventive effect on AD. However, this effect was not observed in recent randomized control trials. Thus, the ideal moisturizer type and application frequency for preventing AD development in infants remains unclear. We hypothesize that twice daily application of moisturizer is more effective than once daily application. We predict that applying sufficient amounts of high-quality moisturizer may be effective for preventing AD development in neonates and infants. Here, we describe a protocol for comparing the efficacy of twice daily and once daily application of Fam's Baby™ moisturizer and once daily application of 2e moisturizer for preventing AD in neonates.MethodsThis study is a single-center, three-parallel group, assessor-blind, superiority, individually randomized, controlled, phase II trial. Sixty newborns 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 estimate how effective the twice daily or once daily application of Fam's Baby moisturizer is in preventing AD compared to the once daily application of 2e moisturizer. In this study, we will use 2e once daily as a control to confirm the efficacy for primary prevention of AD as found in our previous trial. Based on the results of this study, we hope to conduct a phase III study to determine the optimal method for preventing AD via moisturizer application. 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.

Background:. 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. Objective:. 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. Methods:. 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. Results:. 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. Conclusion:. 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.