Feasibility and Safety of the Early Introduction of Allergenic Foods in Asian Infants with Eczema.

BACKGROUND: There is a lack of data regarding the early introduction of the consumption of allergenic food among Asian infants. METHODS: We examined infants who had early-onset eczema before 6 months of age and received instructions from certified allergists for the early introduction of hen's eggs, milk, wheat, peanuts, and tree nuts. RESULTS: The consumption rates of hen's eggs were 100% at 24 months. For peanuts and walnuts, the consumption rate was moderate at 12 months (48.5% and 30.3%, respectively), but by 24 months, it had progressed to 78.8% and 81.3%, respectively. In contrast, cashews remained at lower levels than other allergens at 20.7% at 12 months and 41.4% at 24 months. No adverse events related to early introductions occurred. CONCLUSIONS: In infants with eczema, allergenic foods could be introduced early and well tolerated in Asian infants. However, having eczema may indicate a predisposition to food allergies, so caution is necessary when introducing allergenic foods. The early introduction of peanuts and tree nuts was still more challenging in real-world practice in Asia as well as in Western countries.

Management of Infant Atopic Eczema to Prevent Severe Eczema and Food Allergy.

Early intervention and active management of infant atopic eczema may play a crucial role in limiting eczema severity and preventing the onset of immediate-type food allergy. Eczema management involves education, skincare and medications targeting skin inflammation and barrier repair. Topical corticosteroids are the mainstay of anti-inflammatory therapy, with nonsteroidal options available for some infants. Proactive therapy, addressing subclinical inflammation, is useful for preventing eczema flares, especially in infants with recurrent eczema flares despite reactive therapy. In clinical practice, holistic consideration of overall infant and family health is essential. Providing advice on maternal stress management, nutritional guidance and recommendations for proper sleep and lifestyle is crucial for the well-being of children and their families, not limited to eczema treatment alone.

Predictive modeling for cow's milk allergy remission by low-dose oral immunotherapy in young children.

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).

Role of skin management in the prevention of atopic dermatitis and food allergy.

Food allergy is postulated to originate from cutaneous sensitization through a disrupted skin barrier, particularly in atopic dermatitis (AD). Strategies for food allergy prevention currently centre around early allergic food introduction, but there is now increasing evidence for the role of early skin barrier restoration in the form of prophylactic emollient therapy and early aggressive, proactive treatment of established AD for food allergy prevention. Research gaps that remain to be addressed include the type of emollient or anti-inflammatory medication, which confers the greatest efficacy in preventive or proactive skin treatment, respectively, the duration of therapy, and the window of opportunity for these interventions.

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.

Overviewing allergy epidemiology in Japan - Findings from birth cohorts (JECS and T-Child study).

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.

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

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.

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.

Food protein-induced enterocolitis syndrome is an important differential diagnosis of vomiting in pediatric emergency.

BACKGROUND: The aim of this study was to clarify the clinical characteristics and management of infants with suspected acute food protein-induced enterocolitis syndrome (FPIES) who presented to the pediatric emergency department (ED) before and after the guidelines were published. METHODS: This was a retrospective cohort study. We classified the infants as "acute FPIES-like symptoms" who were younger than 12 months of age and visited the pediatric ED of the National Center for Child Health and Development due to vomiting 1-4 h after food ingestion without any causative disease, such as infection. The medical records of those infants in 2015 and 2021 were reviewed. We used the nonparametric Mann-Whitney U test to compare two groups for continuous variables, whereas chi-squared or Fisher's exact tests were used for nominal variables. RESULTS: The number of infants with acute FPIES-like symptoms was 15 (13%) in 2015 and 14 (15%) in 2021. The trigger foods were cow's milk or dairy products in half of the infants, and five as a result of ingestion of hen's eggs in 2021, compared to zero cases in 2015. Five in 2015 and 12 in 2021 required examination at the ED. Three in 2015 and six in 2021 met the diagnostic criteria for acute FPIES in the international consensus guidelines. The emergency physicians did not record at least four minor criteria for acute FPIES in seven in 2015 and five in 2021. No infants (0%) in 2015 and two (14%) in 2021 were referred to the allergy department by an emergency physician. CONCLUSIONS: Acute FPIES should be considered one of the differential diagnoses of vomiting, and pediatric medical staff should be aware of FPIES diagnostic criteria and appropriately refer suspected cases to a specialist.

[ANTIMICROBIAL ALLERGY ASSESSMENT DURING PREGNANCY FOR APPROPRIATE ANTIMICROBIAL USE AT DELIVERY].

BACKGROUND: Avoidance of suspect drugs based solely on a history of drug allergy is detrimental to disease outcomes. Many antimicrobial allergy labels are not usually true allergy. Some studies have demonstrated that antimicrobial allergy assessments can be safely performed on pregnant women. The purpose of this study was to examine the usefulness of antibiotic allergy assessment during pregnancy in Japan. METHODS: We reviewed pregnant women who reported antimicrobial allergies and were referred to the allergy center. Allergists conducted an interview and skin test and selected antibiotics that could be used at delivery. RESULTS: Twenty-four pregnant women were referred to as having antimicrobial allergies. Most of the suspected antimicrobials were cephalosporin (13 cases, 52%) and penicillin (9 cases, 36%). Five women were ruled out only by our interviews. Of the remaining 20 cases, 10 were immediate type, 6 were non-immediate type, and 4 were unknown. All 21 pregnant women who needed antimicrobials were able to use the first-line drugs (ß-lactam antimicrobials) at the time of delivery. No surgical site infections or allergic reactions were observed. CONCLUSION: Pregnant women with antimicrobial allergy labels could be evaluated by antimicrobial allergy assessment during pregnancy, and first-line antimicrobials were safely and properly used at delivery.

[AN ADOLESCENT CASE OF HAE-NL-C1INH (WHO WAS) MISDIAGNOSED WITH WHEAT ALLERGY AND MULTIPLE DRUG ALLERGIES].

Hereditary angioedema (HAE) is frequently misdiagnosed as drug allergy. It is essential to differentiate HAE from allergy. Diagnosing HAE-normal-C1INH (conventional HAE type III), presenting normal C1-INH, is even more difficult. Here, we report a case of a 17-year-old female diagnosed with HAE and having labeled wheat and multiple drug allergies. She had been suffering from skin edema and abdominal symptoms since childhood. After taking wheat at 13 years old, she had multiple episodes of the same symptoms. Wheat allergy was suspected, and she started eliminating wheat. Multiple attacks were observed after several drug use, and drug allergy was labeled. However, her attacks did not improve after eliminating wheat and the suspected drugs. Her C4 and C1-INH activity was normal, but we diagnosed her with HAE-normal-C1INH based on her family history, multiple attacks after dental procedures, ineffective antihistamines, and significant efficacy of C1-INH infusion. A double-blind, placebo-controlled wheat challenge test at our hospital was negative, and wheat removal was lifted. Drugs could be de-labeled by allergic tests and history. Repeated attacks of unexplained edema and abdominal pain should be differentiated from HAE and lead to an appropriate diagnosis.

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.