Influence of household pet ownership and filaggrin loss-of-function mutations on eczema prevalence in children: A birth cohort study.

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.

Parental stress and food allergy phenotypes in young children: A National Birth Cohort (JECS).

BACKGROUND: Food allergy children and their families tend to have emotional distress and anxiety. There have been few reports of differences in parenting stress and a child's food allergy phenotypes. METHODS: We examined the associations between food allergy phenotypes in children and parenting stress assessed by the Parenting Stress Index-Short Form (PSI-SF) from a national birth cohort (Japan Environment and Children's Study). RESULTS: We included 65,805 children for statistical analysis. Of them, 7.2% of children had a food allergy diagnosis at 2 years old. The means of the total PSI-SF (39.9 ± 10.3, 39.1 ± 9.9), CD-SF (19.5 ± 5.4, 19.1 ± 5.2), and PD-SF (20.5 ± 6.3, 20.0 ± 6.1) scores are similar for caregivers in the with and without food allergy groups. Food allergy diagnosis resulted in significantly higher total PSI scores (coefficient .47, 95% CI 0.19-0.75, p = .001), CD-SF (coefficient .22, 95% CI 0.07-0.38, p = .004), and PD-SF (coefficient .24, 95% CI 0.08-0.41, p = .004). A similar trend was observed for allergy reactions to hen's egg. However, there was no clear relationship between allergic reactions to milk, wheat, nuts, and PSI-SF. CONCLUSIONS: Parental stress was significantly related to a child's food allergy. Furthermore, hen's egg allergy increased parental stress. Multiple food avoidance might also increase parental stress. Healthcare providers need to be aware of parental stress in our daily clinic.

Teenage and young adult pregnancy and depression: findings from the Japan environment and children's study.

Teenage pregnancy increases the threat of depression because of its many factors. Pregnancy during young adulthood may also have several risk factors for depression compared to older pregnancies. However, data on depression in young adult pregnancies are lacking. This study investigated the association between teenage and young adult pregnancy and depression. Data from the Japan Environment and Children's study was used as a nationwide multicenter prospective cohort study. A multivariate logistic regression was performed to investigate the association between age groups (14-19, 20-24, 25-29, 30-34, ≥ 35 years) and depression, adjusted for behavioral and sociodemographic characteristics. Depression was assessed using the Kessler Psychological Distress Scale. In total, 96,808 pregnant women responded to the questionnaire. Teenage (14-19 years) and young adult (20-24 years) pregnancy were associated with an increased risk of depression compared to older pregnancy (≥ 35 years) (teenage: OR 4.28, 95% confidence interval, CI [3.24-5.64]; young adult: OR 3.00, 95% CI [2.64-3.41]). After adjusting for covariates, the magnitude of the risk of depression was attenuated. However, teenage and young adult pregnancy remained at a significantly increased risk of depression compared to older pregnancy (teenage: OR 2.38, 95% CI [1.77-3.21]; young adult: OR 2.14, 95% CI [1.87-2.46]). Our findings indicate that teenage and young adults' pregnancy are at an increased risk of depression compared to older pregnancy. These findings suggest prioritizing teenage and young pregnant women for prevention and interventions related to depression.

A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations.

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.

Congenital hypothyroidism and thyroid function in a Japanese birth cohort: data from The Japan Environment and Children's Study.

The most common hormonal and metabolic disease in early childhood is congenital hypothyroidism (CH). This study aimed to describe CH in large-scale birth cohort data and summarize the results of serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels in 2-yr-old children. Data were obtained from the Japan Environment and Children's Study (JECS), and we identified 171 children with CH detected in newborn screenings or medical records (170.5 per 100,000 population). Infants with CH are at higher risk of developing congenital diseases than those without CH. Of 171 children with CH, 20 (11.7%) were diagnosed with congenital heart defects, 33 (19.3%) had chromosomal or other congenital abnormalities, and 23 (13.5%) had Down syndrome. At the age of 2 yr old, the median and 95% reference range values for TSH and fT4 were 2.13 (0.78-5.52) µIU/mL and 1.2 (1.0-1.5) ng/dL, respectively. Moreover, boys had slightly higher TSH and fT4 levels than did girls. Data on the distribution of TSH and fT4 in 2-yr-old children should be useful for decreasing the misclassification of thyroid disorders in the pediatric population. Trial-off treatment and re-evaluation of thyroid function are needed to classify permanent congenital hypothyroidism and transient congenital hypothyroidism after 3 yr of age.

Sex steroid hormones and allergic diseases in children: a pilot birth cohort study in the Japan Environment and Children's Study cohort.

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.

Health-related quality of life of mothers and developmental characteristics of very low birth weight children at 2.5 years of age: results from the Japan Environment and Children's Study (JECS).

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.

Maternal Dietary Zinc Intake during Pregnancy and Childhood Allergic Diseases up to Four Years: The Japan Environment and Children's Study.

Maternal dietary zinc intake and childhood allergy have inconsistent relationships. Thus, this study aimed to evaluate the influence of low maternal dietary zinc intake during pregnancy on developing pediatric allergic diseases. This study was designed using the Japan Environment and Children's Study dataset. The model building used data from 74,948 mother-child pairs. Maternal dietary zinc intake was estimated based on the food frequency questionnaire, collecting the intake information of 171 food and beverage items. Fitted logistic regression models and generalized estimating equation models (GEEs) estimated the association between energy-adjusted zinc intake and childhood allergic conditions. The energy-adjusted zinc intake did not affect the risk of developing allergic disorders (wheeze, asthma, atopic dermatitis, rhinitis, and food allergy) in offspring. The GEE model revealed similar insignificant odds ratios. No significant association was found between zinc intake during pregnancy and allergic diseases in offspring in early childhood. Further study remains necessary to examine the association between zinc and allergy with reliable zinc status biomarkers in the body.

Reference blood pressure values obtained using the auscultation method for 2-year-old Japanese children: from the Japan Environment and Children's Study.

BACKGROUND: Reference blood pressure (BP) values for Japanese children based on a large number of measurements by auscultation have not yet been established. METHODS: This was a cross-sectional analysis of data from a birth-cohort study. The data from the sub-cohort study conducted for children at the age of 2 years in the Japan Environment and Children's Study from April 2015 to January 2017 were analyzed. BP was measured via auscultation using an aneroid sphygmomanometer. Each participant was measured in triplicate, and the average value of two consecutive measurements with a difference of less than 5 mmHg was recorded. The reference BP values were estimated using the lambda-mu-sigma (LMS) method and compared with those obtained via the polynomial regression model. RESULTS: Data from 3361 participants were analyzed. Although the difference between the estimated BP values by the LMS and the polynomial regression model was small, the LMS model was more valid based on the results of the fit curve of the observed values and regression models for each model. For 2-year-old children with heights in the 50th percentile, the 50th, 90th, 95th, and 99th percentile reference values of systolic BP (mmHg) for boys were 91, 102, 106, and 112, and that for girls were 90, 101, 103, and 109, respectively, and those of diastolic BP for boys were 52, 62, 65, and 71, and that for girls were 52, 62, 65, and 71, respectively. CONCLUSION: The reference BP values for 2-year-old Japanese children were determined based on auscultation and were made available.

Association between pre-pregnancy weight status and dietary patterns during pregnancy: results from the Japan Environment and Children's Study.

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.

Comparison of physician- and self-assessed pubertal onset in Japanese children.

Introduction: Physical 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. Methods: A 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). Results: The 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). Conclusions: Although 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.

Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy.

BACKGROUND: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. OBJECTIVES: This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. METHODS: This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. RESULTS: This study enrolled 650 infants and analyzed 640 infants (enhanced [n = 318] or conventional [n = 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P = .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. CONCLUSIONS: This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

mRNAs in skin surface lipids unveiled atopic dermatitis at 1 month.

BACKGROUND: The molecular pathogenesis of atopic dermatitis (AD), presenting skin barrier dysfunction and abnormal inflammations around 1-2 months, is unreported. OBJECTIVE: We aimed to examine the molecular pathogenesis of very early-onset AD by skin surface lipid-RNA (SSL-RNA) using a non-invasive technology in infants aged 1 and 2 months from a prospective cohort. METHODS: We collected sebum by oil-blotting film of infants aged 1 and 2 months and analysed RNAs in their sebum. We diagnosed AD according to the United Kingdom Working Party's criteria. RESULTS: Infants with AD aged 1 month showed lower expression of genes related to various lipid metabolism and synthesis, antimicrobial peptides, tight junctions, desmosomes and keratinization. They also had higher expression of several genes involved in Th2-, Th17- and Th22-type immune responses and lower expression of negative regulators of inflammation. In addition, gene expressions related to innate immunity were higher in AD infants. Infants aged 1 month with neonatal acne and diagnosed with AD aged 2 months already had gene expression patterns similar to AD aged 1 month in terms of redox, lipid synthesis, metabolism and barrier-related gene expression. CONCLUSION: We identified molecular changes in barrier function and inflammatory markers that characterize the pathophysiology of AD in infants aged 1 month. We also revealed that neonatal acne at 1 month could predict the subsequent development of AD by sebum transcriptome data.

[A CASE OF INDUCIBLE LARYNGEAL OBSTRUCTION UNSUCCESSFULLY TREATED AS SEVERE ASTHMA WAS WELL CONTROLLED AFTER APPROPRIATE DIAGNOSIS AND INSTRUCTION OF THERAPEUTIC BREATHING MANEUVERS].

BACKGROUND: Inducible laryngeal obstruction (ILO) refers to respiratory disorders caused by airflow limitation in the larynx, including vocal cord dysfunction, and may sometimes be misdiagnosed as bronchial asthma (BA). Here, we report the case of an 11-year-old boy diagnosed with BA in infancy. He was referred to our Allergy Center and was taking a high dose of inhaled corticosteroids (ICS) due to frequent coughing from the age of 10 years and persistent coughing following COVID-19 infection at the age of 11. However, the patient continued to experience frequent coughing attacks and repeated visits to the emergency department after inhalation of ß2-stimulants failed to improve his cough. We admitted him to the allergy center for examinations to assess the BA severity. In the airway hypersensitiveness test, saline inhalation performed prior to methacholine inhalation caused expiratory stridor and respiratory distress in the larynx, which worsened with ß2-stimulant inhalation. Based on these results, we ruled out BA and diagnosed ILO. We instructed him on breathing maneuvers, and he was able to respond appropriately when symptoms appeared. We then started reducing his ICS dose.

Relationship between Food Allergy and Endotoxin Concentration and the Toleration Status at 2 Years: The Japan Environment and Children's Study.

Changes in household endotoxin concentration may affect the prognosis of food allergy (FA), but data on the association between household endotoxin concentration and an already-developed FA are scarce. Thus, we investigated the association between environmental endotoxin exposure and tolerance to hen's egg (HE) and cow's milk (CM) using data from children participating in the Japan Environment and Children's Study who had HE allergies (n = 204) and CM allergy (n = 72) in their first year of life. We grouped the endotoxin results into quartiles 1-4 (Q1-Q4). In children with HE allergy and with CM allergy, there was no significant difference in the prevalence of tolerance to HE and CM at 2 years old when comparing endotoxin levels of the children in Q1 with those in Q2, Q3, and Q4, respectively. However, subgroup analyses by the presence of eczema and causal foods revealed that children in Q1 had a lower prevalence of tolerance to foods in some subgroup analyses and lower causal allergen-specific immunoglobulin G4 levels. Although an individually based approach against endotoxin according to background characteristics, such as eczema and causal foods, is necessary, preventing excessive endotoxin removal might contribute to FA resolution in some children.

Endotoxin concentration and persistent eczema in early childhood.

Although endotoxin concentration in the environment is negatively associated with atopic dermatitis (AD) onset in early childhood, the association between endotoxin concentration in the environment and eczema resolution in children with preexisting eczema is unclear. The aim of this study was to evaluate the association between endotoxin concentration in house dust and eczema persistence in young children. The authors used data from children participating in JECS (Japan Environment and Children's Study). In children who had AD or AD-like lesions at the age of 1 year, the authors investigated the association between the prevalence of eczema at the age of 3 years and endotoxin concentration (categorized by quartiles) in the dust on children's mattresses at the ages of 1.5 and 3 years. This study included 605 children. Eczema was significantly less prevalent among children whose mattresses were in the second and third quartiles of endotoxin concentration when they were 18 months old than among children whose mattresses were in the first quartile (adjusted odds ratio, 0.57 [95% confidence interval, 0.35-0.93] and adjusted odds ratio, 0.49 [95% confidence interval, 0.29-0.83], respectively). Moreover, of the children with eczema at age 3 years, those whose mattresses had endotoxin concentrations in the first quartile had significantly worse sleep disturbance caused by itchy rash (>1 time per week) than did those whose mattresses were in the third and fourth quartiles (20.0% vs 3.3% and 3.7%, both p values < 0.01). The findings indicate that low endotoxin exposure is associated with a higher prevalence of persistent eczema during early childhood.

Eczema phenotypes and IgE component sensitization in adolescents: A population-based birth cohort.

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.

Remission of Acute Food Protein-Induced Enterocolitis Syndrome Confirmed by Oral Food Challenges in Japan.

The oral food challenge test (OFC) is the gold standard for evaluating the remission of food protein-induced enterocolitis syndrome (FPIES). Few acute FPIES remissions confirmed by OFC were reported. This study aimed to examine the OFC for Japanese children with acute FPIES to evaluate its remission. A retrospective cohort study was performed on children with acute FPIES with remission evaluation by OFC based on one food challenge dose (1/50, 1/10, 1/2, and full dose per day). Acute FPIES remission was observed in 65.2% of patients (15/23 patients). Vomiting episodes occurred with 1/50 full doses on the first day among 75% of positive patients. The median duration between the onset and OFC was 14 months (IQR, 8-24 months). Soy was the most common causative food, followed by egg yolk, milk, and wheat. All patients could receive OFC safely without intensive care unit care, based on the FPIES OFC protocol. The remission rate of acute FPIES was high. However, vomiting episodes commonly occurred with 1/50 full doses on the first day. This study suggested that our OFC protocol for acute FPIES was safe and feasible, but it might be safer for some patients to start at a minimal loading dose.