Yukihiro Ohya

• Doctor of Medicine
• chief at National Center for Child Health and Development

Understanding the influence of both genetics and environment on human health, especially early in life, is essential for shaping long-term health. Here, we utilize a nationwide prospective birth cohort, the Japan Environment and Children's Study (JECS), to conduct a large-scale population-based genetic study using biannual questionnaire surveys and...

A study demonstrated that drug provocation tests could be conducted in children with underlying diseases, enabling accurate diagnosis of drug allergy. The study investigators hope that their work will allow more children with underlying conditions to undergo drug provocation tests.

Multiple etiologies of West syndrome have been reported; however, there are cases of unknown etiologies. Exposure to volatile organic compounds (VOCs) increases the risk of epilepsy; however, their effects on children remain unknown. This study aimed to investigate the association between maternal occupational usage of VOCs and West syndrome develo...

This is the English version of the 2024 clinical practice guidelines for the management of atopic dermatitis (AD). AD is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this,...

Down syndrome (DS) is a risk factor for severe food protein-induced enterocolitis syndrome (FPIES), with DS patients tending to have multiple-food FPIES. This is the first case where a DS infant with a history of severe chronic FPIES to milk and soy could effectively be introduced with some untested high-risk foods through hospital-based oral food...

The Asia Allergy Birth Cohort (A2BC) network consolidates data from multiple independently established birth cohorts across Asia to enhance research on host–environment interactions in allergic diseases. These cohorts, established at different times with various methodologies, are reliable data sources. Our aim is to introduce the content, variable...

Objective To quantify the association between a combination of modifiable prepregnancy lifestyle factors and the risk of adverse pregnancy outcomes (APOs). Design Prospective cohort study. Setting The Japan Environment and Children's Study. Population A total of 79 703 pregnant Japanese women without chronic disease. Methods Maternal lifestyle...

The effect of smoking on hypertensive disorders of pregnancy is a public concern. Recent evidence suggests that the risk of hypertensive disorders of pregnancy is influenced by the presence of uterine fibroids. We explored the association between maternal smoking exposure and the risk of hypertensive disorders of pregnancy in relation to the presen...

In cases of moderate to severe atopic dermatitis that does not respond to topical therapy, temporary systemic administration of molecular targeted drugs (biological agents or oral Janus kinase[JAK]inhibitors) may be necessary. However, topical therapy forms the basis of the treatment for atopic dermatitis, and if topical therapy is appropriately es...

Background and objective: The aim of this study was to evaluate the basic performance and accuracy as a screening test by comparing SiLIS Allergy 45+1 with View Allergy 39. Methods: Measurements were performed with reagents and measuring instruments for View Allergy 39 and SiLIS Allergy 45+1 using blood samples of individuals with a previous his...

Introduction Similar to other countries, in Japan, the demand for primary care pediatricians has increased due to the surge in pediatric allergic diseases, and with the change in a paradigm shift regarding the prevention of pediatric allergic disease in the last 20 years, they have had an increased need for retraining. To offer better support to ch...

This study aimed to evaluate the association between atopic dermatitis in pregnant women and preterm births, accounting for maternal ritodrine hydrochloride administration status. Data of 83,796 women with singleton pregnancies at and after 22 weeks of gestation (enrolled between 2011 and 2014) were analyzed. These data were obtained from the Japan...

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 < 24 months because a clinical study has not been conducted in this population. This study consisted of a...

There are few studies on the parenting of fathers with autism traits. To investigate this issue, we examined the type of parenting performed by fathers with autism traits using data from a nationwide birth cohort study, the Japan Environment and Children’s Study. Paternal parenting was evaluated by mothers or caregivers when the child was 2 years o...

Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-β1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, bu...

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 the...

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...

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...

Background: The effectiveness of slow low-dose oral immunotherapy (SLOIT) for cow's milk (CM)

Context Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). Objective To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. Design...

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 de...

Hypertensive disorders of pregnancy (HDP) increase the risk of preterm births and cesarean delivery. This study aimed to investigate whether maternal blood leukocyte, monocyte, or neutrophil counts in the first trimester are related to the development of HDP. Data were collected from the Japan Environment and Children’s Study, a large birth cohort...

Although the prevalence of allergic diseases is rapidly increasing, the full picture of the associated factors remains unclear. The birth cohort study, i.e., a prospective, rather than a retrospective, study of the general population close to the population, preventing bias, is considered the highest level of evidence for capturing disease changes...

The association between daily breakfast habits during pregnancy and offspring neurodevelopment remains unknown. We evaluated the association between breakfast habits during pregnancy and offspring neurodevelopment. Data of 72,260 women with singleton deliveries at and after 37 weeks of gestation enrolled during 2011–2014 in the Japan Environment an...

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 prophylacti...

Background: Intrauterine exposure to hypertensive disorders of pregnancy (HDP) may increase the risk of neuropsychiatric disorders. This investigation examined for associations between maternal HDP and febrile seizures (FS) in offspring by the age of three years. Methods: The present cohort study analyzed data from the Japan Environment and Chil...

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 For...

Background: Itch is the most troublesome symptom of atopic dermatitis, and it is important to assess it appropriately for optimal treatment. We discussed issues regarding itch and the most appropriate methods of assessment at the Atopic Itch Consensus Meeting (AICOM), attended by physicians and researchers with expertise in itch treatment and rese...

Objective: Quality of life (QOL) questionnaires for parents of children with food allergies have been developed in the United States and Europe. However, no original Japanese QOL questionnaire has been developed till date. We aimed to develop an original questionnaire to evaluate the QOL in parents of children with food allergies in Japan. Method...

Objective: No questionnaire aimed at evaluating the quality of life (QOL) of children with food allergies has been developed in Japan. Therefore, this study was aimed at developing a Japanese version of a QOL questionnaire for children with food allergies to be responded to by their parents. Methods: A 59-question primary questionnaire was devel...

Importance Kawasaki disease is an acute systemic vasculitis that primarily affects infants and young children. No reproducible risk factors have yet been identified, but a possible association between maternal folic acid supplementation and Kawasaki disease has been reported previously. Objective To investigate the associations of exposure to mate...

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. Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upad...

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 inf...

Purpose This investigation assessed the impact of dog and/or cat ownership during infancy on the presence of functional constipation (FC) at 3 years of age. Methods The fixed data of 73,936 singleton births from a large national birth cohort study commencing in 2011 were used to identify FC as estimated by Rome III at 3 years of age. Multiple logi...

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...

Importance Corticosteroids and β2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear. Objective To investigate the association between timing of in utero exposure to corticosteroids and β2-adrenergic agonists and offs...

Background: The association between prenatal metal exposure and congenital anomalies is unclear. We aimed to examine the association between exposure to cadmium, lead, mercury, selenium, and manganese and physical abnormalities. Methods: Data from 89,887 pregnant women with singleton pregnancies who participated in the Japan Environment and Chil...

Recently, prediction of gestational diabetes mellitus (GDM) using artificial intelligence (AI) from medical records has been reported. We aimed to evaluate GDM-predictive AI-based models using birth cohort data with a wide range of information and to explore factors contributing to GDM development. This investigation was conducted as a part of the...

To evaluate differences in maternal characteristics and obstetric and offspring childhood outcomes between births at and after 37 weeks of gestation (referred to as term and post-term births) according to the use of tocolytic treatment. Data for 63,409 women with singleton births at and after 37 weeks of gestation were analyzed using data from the...

Oral immunotherapy (OIT) is an established and successful treatment regimen for food allergy. 1 However, the occurrence of adverse events (AEs), such as anaphylaxis, due to overdose of allergenic foods is a major issue during OIT. 1 In a prevention trial for hen egg allergy, we confirmed that a 'tiny' dose of hen egg can induce F I G U R E 1 Rates...

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...

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. Meth...

Importance It is unclear whether increased television (TV) and DVD viewing in early childhood from age 1 year decreases development or whether poor development increases TV/DVD viewing. Objective To investigate the directional association between TV/DVD screen time and performance on developmental screeners in children aged 1 to 3 years. Design,...

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)-4 and IL-13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL-31 is a cytokine mainly produced by activated T cells and is known to be involved...

Background The primary objective of this study was to examine risk factors for toddler’s hypertension. Methods Subjects of this study were children and parents participating in a national birth cohort study in Japan, the Japan Environment and Children’s Study. We measured the children’s blood pressure (BP) at 2 and 4 years old. We obtained childre...

Background: Atopic dermatitis (AD) is a chronic skin condition that is associated with significant patient burden and decreased health-related quality of life (HRQoL). We report results of the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience study in Japanese pediatric patients, focusing on the impact of AD...

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 devel...

Background: In developed countries, the time fathers spend on childcare has increased steadily in recent decades. However, studies on the relationship between paternal care and child outcomes remain scarce. Thus, we examined the association between paternal involvement in childcare and children's developmental outcomes. Methods: We used Japan's...

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...

Early-onset atopic dermatitis increases the 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-route allergen exposure leads to immune tolerance, whereas allergen exposure via the inflamed skin causes food al...

Background: Food-protein-induced enterocolitis syndrome (FPIES) is increasingly seen in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported. Objective: To compare the clinical presentations and causative cr...

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 74,94...

Introduction: Epidemiological studies demonstrated that cleaning work and frequent use of cleaning products are risk factors for asthma. Laundry detergents have been reported to have epithelial barrier-opening effects. However, whether laundry detergents directly induce airway inflammation and its mechanisms in vivo remain to be elucidated. Metho...

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 food frequency questionnaire during middle or late pregnancy. Dietary patte...

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...

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 a...

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 p...

Background: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. Objective: We tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive tre...

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-...

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 c...

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 imm...

The association between maternal pre-pregnancy smoking status and asthma risk is unclear. This study aimed to investigate the association between pre- and post-pregnancy maternal smoking status and bronchial asthma at 3 years of age in a large birth cohort. Data of 75,411 mother–child pairs from the Japan Environment and Children's Study (JECS) wer...

Background: The current study aimed to assess the association between low maternal protein intake during pregnancy and child developmental delay at age 3 years. Methods: This research used data obtained from the Japan Environment and Children's Study. In total, we analyzed 77,237 mother-child pairs. Dietary intake was assessed using the Food Fre...