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Purpose: The effects of general anesthesia on neurodevelopment in children remain controversial. We explored the relationship between general anesthesia and neurodevelopment in children participating in the Japan Environment and Children's Study (JECS). Methods: This study enrolled children born between 37 and 41 weeks of pregnancy via single-vaginal delivery to pregnant women registered in the JECS between January 2011 and March 2014. Data were collected from mother-completed questionnaires and medical transcripts. Neurodevelopment in five domains was assessed every 6 months between 12 and 48 months of age, using the Ages and Stages Questionnaires. The associations between general anesthesia exposure during early childhood and neurodevelopment in children were evaluated at each time point. Adjusted odds ratios and 95% confidence intervals were estimated after covariate adjustment using logistic regression models. Results: Children who received general anesthesia before age 1 year had higher risks of neurodevelopmental delay in all five domains throughout the observational period. The largest risk was for gross motor delay at 18 months (adjusted odds ratio: 3.51; 95% confidence interval: 2.75–4.49). The effects on the incidence of neurodevelopmental delays after age 3 were not observed except for problem solving at 48 months. The risk of neurodevelopmental delay in children who first received general anesthesia after age 1 was considerably small. Conclusions: This study suggests that general anesthesia administration before age 1 is associated with neurodevelopmental delay during 1–4 years of age. The risk of general anesthesia after age 1 may be small. [ABSTRACT FROM AUTHOR]

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 < 24 months because a clinical study has not been conducted in this population. Methods: This study consisted of a 4-week primary evaluation period in which difamilast 0.3% ointment was applied twice daily to Japanese infants aged 3 to < 24 months (n = 41) and an ongoing 48-week long-term extension period in which difamilast 0.3% or 1% ointment was applied based on existing symptoms. The data on efficacy and safety of difamilast were obtained as of an interim report in the study period. Results: The response rate in Investigator's Global Assessment score was 45.0% at week 1, which was maintained at 56.1% at week 4 and 63.4% at the interim report. Infants achieved the response rate in Eczema Area and Severity Index 75 (improvement of ≥ 75%) of 47.5% at week 1, which further improved to 82.9% at week 4 and 78.1% at the interim report. Adverse events (AEs) were reported in 22 (53.7%) infants in the primary evaluation period: of those the most frequent AE was nasopharyngitis (19.5%) followed by dermatitis contact (7.3%). As of the interim report, 36 (87.8%) infants experienced AEs: of those, nasopharyngitis (70.7%) and gastroenteritis (22.0%) were most frequently observed. The total AEs were mostly mild or moderate in severity. No investigational medicinal product-related AEs and no AEs leading to discontinuation were reported. Conclusion: Difamilast ointments applied twice daily to Japanese infants with AD aged 3 to < 24 months is effective and well tolerated as of the interim report in the study period. The final results will be reported in the near future. Clinical Trial Registration: Clinical Trials. gov identifier: NCT05372653. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the association between atopic dermatitis in pregnant women and preterm births, accounting for maternal ritodrine hydrochloride administration status. Methods: 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 Environment and Children's Study. Atopic dermatitis was defined based on self-reported questionnaire responses obtained during the first trimester. The primary outcome measures were preterm births before 37, 32, and 28 weeks of gestation. Using a multivariable logistic regression model, odds ratios for preterm births in pregnant women with atopic dermatitis were calculated, with women without atopic dermatitis included in the reference group. This analysis considered confounding factors and maternal ritodrine hydrochloride administration. Results: Among pregnant women with atopic dermatitis, the adjusted odds ratios (95% confidence intervals) for preterm births before 37, 32, and 28 weeks of gestation were 0.89 (0.81–0.98), 0.98 (0.74–1.30), and 0.88 (0.50–1.55), respectively. This trend remained consistent after excluding participants who received ritodrine hydrochloride. Conclusions for practice: Atopic dermatitis in pregnant women was significantly associated with a decreased incidence of preterm births before 37 weeks of gestation, even after accounting for the effects of maternal ritodrine hydrochloride administration. Significance: What is already known on this subject?: Atopic dermatitis is among the most prevalent chronic dermatological conditions in pregnant women. The association between atopic dermatitis in pregnant women and obstetric outcomes remains unclear owing to conflicting research findings. What this study adds?: Atopic dermatitis in pregnant women was significantly associated with a decreased incidence of preterm births before 37 weeks of gestation. The trend was the same in participants without maternal ritodrine hydrochloride administration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess the validity of the Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations–Questionnaire (ESSENCE‐Q), a simple screening tool for neurodevelopmental problems, in Japan. Method: Parents/caregivers completed the 11‐item ESSENCE‐Q for 77 612 children aged 2 years 6 months included in a national birth cohort study. Information about neurodevelopmental disorders (NDDs: autism spectrum disorder; intellectual disability and/or developmental language disorder; motor delay/motor disorder) was collected at age 3 years. Each ESSENCE‐Q item was scored on a binary (0,1) scale, with a total score range of 0 to 11. Total scores and individual items were compared across children with and without NDDs. Results: NDDs were recorded in 854 children (1.1%). With a total ESSENCE‐Q score cut‐off of ≥3, receiver operating characteristic curve analysis showed an area under the curve of 0.91, with sensitivity 84.9%, specificity 84.8%, positive predictive value 5.9%, and negative predictive value 99.8%. The proportion of parental concerns at 2 years 6 months differed significantly by NDD status for communication (89.5% vs 14.2%) and general development (80.2% vs 7.4%). ESSENCE‐Q total scores were moderately negatively correlated (−0.36, p < 0.001) with Japanese Ages and Stages Questionnaire scores. Interpretation: The parent/caregiver‐completed ESSENCE‐Q is useful as a tool for screening out children with neurotypical development at this early age. Further research into longer‐term predictive validity will be possible as more NDD diagnoses are given as the children grow up. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: Data for 63,409 women with singleton births at and after 37 weeks of gestation were analyzed using data from the Japan Environment and Children's Study (JECS). We compared maternal characteristics, obstetric outcomes, and offspring childhood outcomes between term and post-term births exposed and not exposed to tocolytic treatment. Additionally, multivariable logistic regression models were used to calculate adjusted odds ratios for offspring childhood outcomes with significant between-group differences in the univariable analysis, with term and post-term births without tocolytic agents as the reference group. Results: We observed differences in maternal characteristics and obstetric outcomes between term and post-term births exposed and not exposed to tocolytic treatment. The incidence of offspring childhood developmental disorders showed no significant between-group differences. However, participants exposed to tocolytic agents had higher incidence of offspring childhood allergic disorders. The adjusted odds ratio for any of the offspring childhood allergic disorders in term and post-term births with tocolytic agents was 1.08 (95% confidence interval, 1.03–1.13). Conclusion: This study found no significant difference in the incidence of offspring developmental disorders between term and post-term births exposed and not exposed to tocolytic treatment. However, tocolytic treatment was associated with differences in maternal characteristics and obstetric outcomes, along with a marginal increase in the incidence of childhood allergic disorders in offspring. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers' breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Otitis media, one of the most common childhood diseases, is characterized by inflammation or infection of the middle ear. Due to their ease of access, daily probiotics are recommended for the prevention of early childhood otitis media. This study aimed to assess the impact of probiotics on the incidence of otitis media using a dataset (n = 95,380) from the Japan Environment and Children's Study, a nationwide birth cohort study. After multiple imputations, the association between the incidence of otitis media in early childhood and the daily frequency of yogurt intake in children and mothers was examined using a generalized linear model after adjusting for several confounders. Repeated incidence of otitis media during the 2 years after birth was found in 14,874 participants (15.6%). Based on participants with the lowest frequency of yogurt intake ("almost never") as the reference group, risk ratios for otitis media incidence decreased with higher frequencies of yogurt intake in children at one year of age, but also independently in mothers during pregnancy. The lowest risk ratio (95% confidence interval) for otitis media incidence at six months of age was observed with the most frequent yogurt intake (once/day or more) (0.54 [0.46–0.63]). Additionally, although a similar association was observed in the subgroup of those with cleft lip and/or palate (CL/P), a high-risk group for severe recurrent otitis media, no statistical significance was observed. Thus, increased regular yogurt intake in both children and mothers was associated with a decrease of otitis media during early childhood. [ABSTRACT FROM AUTHOR]

This article examines the timing of sensitization to hen's eggs and nuts in infants with eczema. The study found that the age of sensitization onset differed between egg white and tree nuts, with sensitization to nuts occurring at older ages. The rate of sensitization to nuts was notably lower than that to egg whites. The study suggests that introducing nuts by 6 months of age may be a safe strategy to reduce the incidence of food allergy. However, the study also acknowledges the challenges of introducing nuts due to their texture during the initial phases of weaning. The authors plan to conduct further research to explore the preventive effects of walnut allergy based on the timing of walnut consumption initiation. [Extracted from the article]

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting young children, with an unclear etiology. We investigated the link between maternal heavy metal exposure and KD incidence in children using the Japan Environment and Children's Study, a large-scale nationwide prospective cohort with approximately 100,000 mother–child pairs. Maternal blood samples collected during the second/third trimester were analyzed for heavy metals [mercury (Hg), cadmium (Cd), lead (Pb), selenium (Se), manganese (Mn)], divided into four quartiles based on concentration levels. KD incidence within the first year of life was tracked via questionnaire. Among 85,378 mother–child pairs, 316 children (0.37%) under one year were diagnosed with KD. Compared with the lowest concentration group (Q1), the highest (Q4) showed odds ratios (95% confidence interval) for Hg, 1.29 (0.82–2.03); Cd, 0.99 (0.63–1.58); Pb, 0.84 (0.52–1.34); Se, 1.17 (0.70–1.94); Mn, 0.70 (0.44–1.11), indicating no concentration-dependent increase. Sensitivity analyses with logarithmic transformation and extended outcomes up to age 3 yielded similar results. No significant association was found between maternal heavy metal levels and KD incidence, suggesting that heavy metal exposure does not increase KD risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 study (n = 38,194) that recruited pregnant women in 15 Regional Centers across Japan (from January 2011 to March 2014). The odds ratios (ORs) for mild/severe HDP according to the cut-off value of leukocyte/neutrophil/monocyte counts by the receiver operating characteristic curve showed high ORs. Furthermore, pregnant women with the highest quartiles of leukocyte and monocyte counts had higher adjusted ORs (aORs) for mild (leukocyte: aOR = 1.27, 95% confidence interval [CI]: 1.02–1.58; monocyte: aOR = 1.30, 95% CI 1.04–1.63) and severe HDP (leukocyte: aOR = 1.51, 95% CI 1.08–2.13; monocyte: aOR = 1.44, 95% CI 1.03–2.01) compared with those with the lowest quartiles of those counts. In addition, pregnant women with the highest neutrophil counts had higher aOR for mild HDP (aOR = 1.26, 95% CI 1.02–1.56) compared with those with the lowest count. In conclusion, high leukocyte and monocyte counts in the first trimester are associated with the development of HDP. Thus, they may be used to predict subsequent HDP. [ABSTRACT FROM AUTHOR]

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 and Children's Study were analysed. Offspring neurodevelopmental delays at 3 years of age were evaluated using the Ages and Stages Questionnaire, Third Edition (ASQ-3). Participants were stratified by tertiles of maternal daily energy intake (DEI) (Groups 1, 2, and 3:< 1400, 1400–1799, and ≥ 1800 kcal, respectively) during pregnancy and by offspring sex. The adjusted odds ratio (aOR) for abnormality in communication among participants with daily breakfast consumption habit was 0.87 (95% confidence interval, 0.80–0.96). A stratified analysis based on total DEI showed no significant differences in the neurodevelopment of Group 1 offspring. The aOR for abnormality in communication was 0.80 (95% confidence interval, 0.68–0.94) in Group 2. The aOR for abnormality in personal–social characteristics was 0.84 (95% confidence interval, 0.71–0.99) in Group 3. Maternal daily breakfast habits are associated with offspring neurodevelopment at 3 years of age, with the association influenced by maternal DEI and offspring sex. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article presents a quantitative risk assessment of egg-white, milk, and wheat in infants with food allergies. The study analyzed data on oral food challenges in infants aged ≤12 months and compared it with data from older children. The study found that the eliciting dose (ED) for egg-white, milk, and wheat tended to decrease with increasing age. The study suggests that low-dose introduction of these allergens could be considered in infants already suspected of developing food allergies. However, the study acknowledges that the causative food for food allergies may vary regionally, and further research is needed to investigate appropriate infant diets. [Extracted from the article]

Background: The role of prenatal diet on childhood wheezing and subsequent risk of asthma is inconclusive, which may be partly due to the heterogeneity in wheezing phenotypes. We aimed to identify wheeze trajectories in early childhood and to examine their associations with periconceptional maternal diet quality. Methods: Data from 70,530 mother–child pairs of liveborn singletons from the Japan Environment and Children's Study were analysed. Wheezing was reported by caregivers using a modified International Study of Asthma and Allergies in Childhood questionnaire yearly from 1 to 4 years of age, from which trajectories were derived using group‐based trajectory modelling. Maternal diet in the year preceding the first trimester of pregnancy was assessed using a validated food frequency questionnaire; overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Bayesian inference of multinomial logistic regression models was performed to examine the association between maternal diet quality and wheeze trajectory in early childhood. Results: We identified four wheeze trajectories: 'never/infrequent' (69.1%; reference group), 'early‐childhood onset' (6.2%), 'transient early' (16.5%) and 'persistent' (8.2%). After adjustment for confounders, a higher quartile of maternal balanced diet score was associated with a lower risk of belonging to the 'transient early' and 'persistent' wheeze trajectories compared with the 'never/infrequent' wheeze trajectory by 10% of both. Maternal balanced diet score was not associated with belonging to the 'early‐childhood onset' wheeze trajectory. Conclusion: Improving maternal diet quality prior to conception may reduce certain wheeze phenotypes in early childhood. [ABSTRACT FROM AUTHOR]

Aim: While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25‐hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). Methods: Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto‐scale developmental quotient scores <70 were calculated, for postural–motor, cognitive–adaptive, and language–social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. Results: Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto‐scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive–adaptive, and 1.69 (p = 0.024) for language–social domains. For girls, results were inconclusive. Conclusion: Only boys showed a clear and cross‐modal association between vitamin D deficiency and NDPs. [ABSTRACT FROM AUTHOR]

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 < 18 years) were randomized 1:1:1 to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo through week 16 (all in combination with topical corticosteroids). At week 16, patients who received placebo were rerandomized 1:1 to upadacitinib 15 mg or 30 mg; topical corticosteroids were optional per investigator discretion from weeks 16–160. Safety was assessed by monitoring adverse events (AEs). Efficacy assessments included patients who achieved ≥ 75%/≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), clear/almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), or a ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (WP-NRS). Results: Of 272 patients enrolled, 230 completed the study. Through week 160, the long-term incidence rate of overall AEs was numerically higher with upadacitinib 30 mg than 15 mg; rates of serious AEs, AEs considered possibly related to study drug, AEs leading to discontinuation, and AEs of special interest were generally low and similar between dose groups. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were generally greater with upadacitinib 30 mg than 15 mg and maintained through week 160 with either dose. Conclusion: For up to 3 years of continuous treatment, upadacitinib was well tolerated in Japanese patients, with a similar safety profile to that of short-term studies and durable long-term response rates for skin clearance and itch improvement. Trial Registration: ClinicalTrials.gov identifier, NCT03661138. [ABSTRACT FROM AUTHOR]

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 logistic regression analysis was employed to search for correlations between FC development and dog and/or cat ownership in early childhood. Results: A total of 8,459 toddlers (11.6%) met the Rome III criteria for FC at 3 years of age. Overall, 57,264 (77.5%) participants had never owned a dog or cat. We identified 7,715 (10.4%) infant-period owners, 1,295 (1.8%) current owners, and 7,762 (10.5%) long-term owners. Multivariate analysis showed that infant-period ownership remained significantly associated with the risk of developing FC at 3 years of age after adjusting for covariates (adjusted OR [95% CI] 1.09 [1.01–1.19] based on non-ownership). Conclusions: This Japanese large nationwide survey uncovered a possible adverse effect of infant-period dog and/or cat ownership prior to 6 months of age on FC status at 3 years of age. [ABSTRACT FROM AUTHOR]

We evaluated the association between gestational age at threatened preterm birth (TPTB) diagnosis and preterm birth (PTB) incidence using a nationwide birth cohort. Data of 94,236 women with singleton deliveries from the Japan Environment and Children's Study (enrolled between 2011 and 2014) were analysed. Participants were divided based on parity and gestational age at TPTB diagnosis (22–24, 25–27, 28–30, 31–33, and 34–36 weeks). Multivariable logistic regression models were used to calculate the odds ratios (ORs) for PTB before 37 and 34 weeks in women from all groups, using participants without TPTB as the reference. The adjusted ORs for PTB before 37 weeks were the highest in the latest gestational age group in nulliparous and multiparous women without previous PTB, while those before 34 weeks were the highest in the earliest and latest gestational age group in multiparous women without previous PTB and in the earliest gestational age group in multiparous women with previous PTB. The association between gestational age at TPTB diagnosis and PTB incidence varies based on maternal parity and PTB before 37 or 34 weeks. Further studies with detailed clinical data and a unified TPTB diagnosis protocol are necessary to clarify this association. [ABSTRACT FROM AUTHOR]

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 Japan Environment and Children's Study. In total, 82,698 pregnant mothers who provided data on lifestyle, anthropometry, and socioeconomic status before pregnancy and the first trimester were included in the study. We employed machine learning methods as AI algorithms, such as random forest (RF), gradient boosting decision tree (GBDT), and support vector machine (SVM), along with logistic regression (LR) as a reference. GBDT displayed the highest accuracy, followed by LR, RF, and SVM. Exploratory analysis of the JECS data revealed that health-related quality of life in early pregnancy and maternal birthweight, which were rarely reported to be associated with GDM, were found along with variables that were reported to be associated with GDM. The results of decision tree-based algorithms, such as GBDT, have shown high accuracy, interpretability, and superiority for predicting GDM using birth cohort data. [ABSTRACT FROM AUTHOR]

Background: There is a lack of large, nationwide, birth cohort studies in Japan that examine the relationships of initial feeding habits and breastfeeding period duration with offspring functional constipation at 3 years of age. This study assessed the impact of breastfeeding during infancy on early childhood functional constipation. Methods: The fixed data of 70,078 singleton births from the ongoing Japan Environment and Children's Study cohort study that commenced in 2011 were used to identify functional constipation as estimated by Rome III at 3 years of age. The exposure variables were breastfeeding period duration until 12 months of age (never, up to 6 months, or ≥ 7 months) as well as breastfeeding status at 1 month and 6 months of age (breastfeeding exclusively, partial breastfeeding, or infant formula feeding only). Multiple logistic regression analysis was employed to search for correlations for functional constipation development with breastfeeding period duration until 12 months of age and breastfeeding status during infancy. Results: We identified 8,118 toddlers (11.6%) who met the Rome III criteria at 3 years of age. After controlling for potential covariates, a breastfeeding period duration of 7 months or more was inversely related to functional constipation development (≥ 7 months: adjusted odds ratio [OR] [95% confidence interval (CI)] 0.76 [0.65, 0.88] versus never breastfed, P for trend < 0.001). Other initial feeding methods were significantly related to an increased risk of functional constipation as compared with breastfeeding exclusively at 1 month of age (partial breastfeeding: adjusted OR [95% CI] 1.17 [1.11, 1.23], formula feeding only: 1.23 [1.07, 1.40]) and 6 months of age (partial breastfeeding: adjusted OR [95% CI] 1.18 [1.12, 1.24], formula feeding only: adjusted OR [95% CI] 1.42 [1.20, 1.68]). Conclusion: This large nationwide survey revealed a possible protective effect of a prolonged breastfeeding period duration and early exclusive breastfeeding in infancy on functional constipation at 3 years. [ABSTRACT FROM AUTHOR]

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 Japan Environment and Children's Study. In total, 82,698 pregnant mothers who provided data on lifestyle, anthropometry, and socioeconomic status before pregnancy and the first trimester were included in the study. We employed machine learning methods as AI algorithms, such as random forest (RF), gradient boosting decision tree (GBDT), and support vector machine (SVM), along with logistic regression (LR) as a reference. GBDT displayed the highest accuracy, followed by LR, RF, and SVM. Exploratory analysis of the JECS data revealed that health-related quality of life in early pregnancy and maternal birthweight, which were rarely reported to be associated with GDM, were found along with variables that were reported to be associated with GDM. The results of decision tree-based algorithms, such as GBDT, have shown high accuracy, interpretability, and superiority for predicting GDM using birth cohort data. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti‐IL‐4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti‐IL‐31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti‐IL‐13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board‐certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the associations between cord serum total cholesterol (TC) and triglyceride (TG)levels and perinatal factors and determine the reference levels of cord blood TC and TG in Japanese neonates. This was a prospective birth cohort study using data from the Japan Environment and Children's Study, which included data on births from 2011 to 2014 in Japan. TC and TG levels were determined in cord blood samples. A total of 70,535 pairs of neonates (male: 36,001, female: 34,524) and mothers were included. The mean cord blood TC and TG levels were 72.2 mg/dL and 24.4 mg/dL, respectively. Multiple regression analyses revealed that gestational age and birth weight were significantly associated with cord blood TC (coefficient −2.35, 95% confidence interval [CI] −2.40 – −2.22 and coefficient 0.002, 95% CI 0.002–0.003, respectively) and TG (coefficient 3.09, 95% CI 3.01–3.17 and coefficient − 0.009, 95% CI − 0.009–0.008, respectively) levels. Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories. Conclusion: Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories in Japanese newborns. Maternal complications such as maternal parity, HDP, PROM, maternal obesity and income level were associated with cord TC and TG levels. What is Known: • No studies have ascertained the reference levels of cord blood lipid levels in Japan. What is New: • Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. [ABSTRACT FROM AUTHOR]

Background: Mother-to-infant bonding (MIB) is critical for the health and well-being of the mother and child. Furthermore, MIB has been shown to boost the social-emotional development of infants, while also giving mothers a sense of happiness in raising their children. Nausea and vomiting during pregnancy (NVP) is a normal complication of pregnancy, occurring in approximately 50–90% of pregnant women in the early stages of pregnancy. Despite widespread knowledge of MIB and postpartum depression, little research attention has been given to the effects of NVP on MIB. This study aimed to investigate the relationship between NVP and MIB and the mediating effects of postpartum depression. Methods: We analyzed the data of 88,424 infants and 87,658 mothers from the Japan Environment and Children's Study (JECS), which is a government-funded nationwide birth prospective cohort study. The Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) was used to assess MIB, and the Edinburgh Postpartum Depression Scale (EPDS) was utilized to assess postpartum depression. We divided participants into four groups according to a self-reported questionnaire assessing NVP (No NVP, Mild NVP, Moderate NVP, and Severe NVP). MIB disorder was defined as a MIBS-J score ≥ 5. Logistic analysis was performed to evaluate the effect of NVP on MIB disorder at one year after delivery. A mediation analysis was conducted to examine whether postpartum depression mediated the association between NVP and MIBS-J scores. Results: The logistic regression analysis results revealed reduced risks of MIB disorder among mothers with Moderate NVP (adjusted OR 0.93; 95% confidence interval, 0.86–0.99) and Severe NVP (adjusted OR 0.81; 95% confidence interval, 0.74–0.89), compared to those with No NVP. The mediation analysis revealed that NVP positively correlated with MIBS-J score in the indirect effect via postpartum depression, while NVP (Mild NVP, Moderate NVP, and Severe NVP) negatively correlated with MIBS-J score in the direct effect. Conclusion: The risks of MIB disorder were reduced in the Moderate NVP and Severe NVP mothers, although NVP inhibited the development of MIB via postpartum depression. The development of effective interventions for postpartum depression is important to improve MIB among mothers with NVP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 severity on disease burden. Methods: Children and adolescents aged 6 months to 17 years (or their caregivers/parents) completed an online survey between September 26, 2018, and March 5, 2019. Patients with diagnosed AD (i.e., met International Study of Asthma and Allergies in Childhood criteria and had a self‐reported AD diagnosis) were evaluated for disease severity using the Patient‐Oriented Eczema Measure (POEM). Impact of AD severity on AD symptoms (itching, pain, and sleep disturbance), disease flares, atopic comorbidities, healthcare resource utilization, school days missed, and HRQoL were assessed. Results: Of 5702 Japanese pediatric patients, 547 had diagnosed AD and were included in this analysis. Based on POEM scores, AD severity was clear/mild in 346 patients (63.3%), moderate in 177 (32.5%), and severe in 24 (4.4%). Across all age groups (i.e., less than 6, 6–11, and 12–17 years), increased AD severity was associated with increased AD symptom severity, number of flares, atopic comorbidities, healthcare resource utilization, and school absences, as well as worsened HRQoL. Conclusions: This population‐based study of Japanese children and adolescents showed that greater AD severity had a high impact on disease burden. [ABSTRACT FROM AUTHOR]

Although it remains debatable, exogenous oxytocin, commonly used for labour induction and augmentation, reportedly increases risks of neurodevelopment delay, attention-deficit/hyperactivity disorder, and autism spectrum disorder among children prenatally exposed to exogenous oxytocin. However, only few studies have objectively examined exogenous oxytocin's impact on early childhood development through scoring evaluations. This study investigated the association between exogenous oxytocin exposure and neurodevelopment in 3-year-old children using the Ages and Stages Questionnaires, Third Edition. In this nationwide prospective cohort study, we extracted data from 104,062 foetal records regarding exogenous oxytocin use during labour from the Japan Environment and Children's Study. Participants completed questionnaires throughout the pregnancy and postpartum periods. Outcomes comprised the developmental status less than each cut-off value for the five domains of the Ages and Stages Questionnaire, Third Edition. We conducted multivariable logistic regression analyses on the data of 55,400 children after controlling for confounders. Among the 55,400 included women, 19.0% (n = 10,506) used exogenous oxytocin during labour and 81.0% (n = 44,894) did not. Children exposed to exogenous oxytocin showed no significantly increased risk of developmental delay in any domain (communication: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.92–1.16; gross motor: OR 0.97, 95% CI 0.87–1.08; fine motor: OR 1.00, 95% CI 0.92–1.09; problem-solving: OR 1.02, 95% CI 0.94–1.11; personal-social: OR 0.91, 95% CI 0.80–1.03). Conclusion: Exogenous oxytocin for labour induction did not adversely affect early childhood development. Further studies accounting for the degree of exogenous oxytocin exposure are required to confirm these results. What is Known: • In developed countries, labour is induced in 20–25% of all pregnancies, for which oxytocin is commonly used. • Studies have associated risks of neurodevelopment delay, attention-deficit/hyperactivity disorder, and autism spectrum disorder with exposure to exogenous oxytocin. What is New: • Evaluation with the Ages and Stages Questionnaire, Third Edition, revealed that exogenous oxytocin use did not adversely affect early childhood development. • This prospective study reinforced the lack of evidence of an association between exogenous oxytocin use and early childhood development after adjustment for confounding and rigorous bias elimination. [ABSTRACT FROM AUTHOR]

This article discusses the predictors of oral food challenge (OFC) outcomes in young children with food allergies. The study evaluated 1478 OFCs conducted at a single center in Tokyo. The researchers found that regular intake history was associated with a reduced risk of allergic reactions during OFCs for eggs and peanuts. They also observed that the threshold doses for severe reactions differed among different allergenic foods. The authors recommend updating current OFC protocols based on previous history and modifying the standardized loading dose of total protein for each allergenic food to improve the safety and effectiveness of OFCs. [Extracted from the article]

A study published in the journal Clinical & Experimental Allergy examined the effectiveness and safety of low-dose oral immunotherapy (OIT) protocols in children with milk and egg allergies. The study included 217 children and found that ultra-low dose OIT was effective and safe, with no cases of anaphylaxis or severe adverse events. The study also compared different dosing strategies and found that the ultra-low dose group had the highest rate of increased cumulative tolerated dose and the lowest rate of adverse events. The study suggests that even tiny doses of allergenic foods may be sufficient to induce immunotolerance in childhood egg and milk allergies. However, the study has limitations, including its retrospective design and small, heterogeneous population. Further research is needed to standardize OIT methods and understand the immune mechanisms underlying the anti-allergic response. The study was funded by the National Center for Child Health and Development and the authors declare no conflicts of interest. [Extracted from the article]

We evaluated the association between gestational age at threatened preterm birth (TPTB) diagnosis and preterm birth (PTB) incidence using a nationwide birth cohort. Data of 94,236 women with singleton deliveries from the Japan Environment and Children's Study (enrolled between 2011 and 2014) were analysed. Participants were divided based on parity and gestational age at TPTB diagnosis (22–24, 25–27, 28–30, 31–33, and 34–36 weeks). Multivariable logistic regression models were used to calculate the odds ratios (ORs) for PTB before 37 and 34 weeks in women from all groups, using participants without TPTB as the reference. The adjusted ORs for PTB before 37 weeks were the highest in the latest gestational age group in nulliparous and multiparous women without previous PTB, while those before 34 weeks were the highest in the earliest and latest gestational age group in multiparous women without previous PTB and in the earliest gestational age group in multiparous women with previous PTB. The association between gestational age at TPTB diagnosis and PTB incidence varies based on maternal parity and PTB before 37 or 34 weeks. Further studies with detailed clinical data and a unified TPTB diagnosis protocol are necessary to clarify this association. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Methods: Two commercial laundry detergents and two commonly used surfactants for cleaning and cosmetics (sodium lauryl sulfate and sodium dodecyl benzene sulfonate) were intranasally administered to mice. Lungs were analyzed using flow cytometry, histology, ELISA, and quantitative PCR. Human bronchial epithelial cells were stimulated with laundry detergents and analyzed using quantitative PCR and western blotting. Involvement of oxidative stress was assessed using an antioxidant. Dust samples from homes were analyzed to determine their detergent content by measuring their critical micelle concentration (CMC). Results: The administered laundry detergents and surfactants‐induced eosinophilic airway inflammation accompanied by increased IL‐33 expression and activation of group 2 innate lymphoid cells (ILC2s). Detergent‐induced eosinophilic airway inflammation was significantly attenuated in Rag2−/−Il2rg−/−, Il33−/− mice, and also in wild‐type mice treated with NAC. Detergent‐induced IL‐33 expression in airways was attenuated by NAC treatment, both in vivo and in vitro. CMCs were found in all of the tested dust extracts, and they differed significantly among the homes. Conclusion: The laundry detergents and surfactants‐induced eosinophilic airway inflammation in vivo through epithelial cell and ILC2 activation. They induced IL‐33 expression in airway epithelial cells through oxidative stress. Furthermore, detergent residues were present in house dust and are presumably inhaled into the airway in daily life. [ABSTRACT FROM AUTHOR]

Background: Placental weight to birthweight ratio (PW/BW ratio), or its inverse, is used as an indicator of placental efficiency. Past studies have shown an association between an abnormal PW/BW ratio and adverse intrauterine environment, however, no previous studies have examined the effect of abnormal lipid levels during pregnancy on PW/BW ratio. We aimed to evaluate the association between maternal cholesterol levels during pregnancy and placental weight to birthweight ratio (PW/BW ratio). Methods: This study was a secondary analysis using the data from the Japan Environment and Children's Study (JECS). 81 781 singletons and their mothers were included in the analysis. Maternal serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels during pregnancy were obtained from participants. Associations between maternal lipid levels and placental weight and PW/BW ratio were assessed by regression analysis using restricted cubic splines. Results: Dose–response relationships were observed between maternal lipid level during pregnancy and placental weight and PW/BW ratio. High TC and LDL-C levels were associated with heavy placental weight and high PW/BW ratio, i.e., inappropriately heavy placenta for birthweight. Low HDL-C level was also associated with inappropriately heavy placenta. Low TC and LDL-C levels were associated with low placental weight and low PW/BW ratio, i.e., inappropriately light placenta for birthweight. High HDL-C was not associated with PW/BW ratio. These findings were independent of pre-pregnancy body mass index and gestational weight gain. Conclusions: Abnormal lipid levels such as elevated TC and LDL-C, and low HDL-C level, during pregnancy were associated with inappropriately heavy placental weight. [ABSTRACT FROM AUTHOR]

Background: The long-term effects of a Cesarean section (CS) birth on child neurodevelopment are of increasing interest. In this study, we examined the associations between mode of delivery and presence of neurodevelopmental disorders in toddlers. Moreover, given that the prevalence of several neurodevelopmental disorders such as autism spectrum disorder (ASD) is known to differ by sex, we also investigated these associations separately in male and female toddlers. Methods: We investigated 65,701 mother–toddler pairs from the Japan Environment and Children's Study, a nationally representative children's cohort study. To investigate the associations between mode of delivery (CS or vaginal delivery) and neurodevelopmental disorders (motor delay, intellectual disability, and ASD) in 3-year-old toddlers as a whole and stratified by sex, we used logistic regression models to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: The morbidity of ASD at age 3 years was higher for children delivered by CS than those delivered vaginally (aOR 1.38, 95% CI 1.04–1.83). However, no such difference was evident in the case of motor delay or intellectual disability (aOR 1.33, 95% CI 0.94–1.89; aOR 1.18, 95% CI 0.94–1.49, respectively). In the analysis by sex, CS was not associated with increased risk of any of the neurodevelopmental disorders in males, but it was associated with increased risks of motor delay (aOR 1.88, 95% CI 1.02–3.47) and ASD (aOR 1.82, 95% CI 1.04–3.16) in females. Conclusions: This study provides evidence of significant associations between mode of delivery and neurodevelopmental disorders in early childhood. Females may be more sensitive to the effects of CS than males. [ABSTRACT FROM AUTHOR]

We evaluated the association between maternal prenatal folic acid supplement use/dietary folate intake and cognitive development in 4-year-old offspring (N = 3445) using data from the Japan Environment and Children's Study. Cognitive development was evaluated using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis revealed that offspring of mothers who started using folic acid supplements pre-conception had a significantly higher language-social developmental quotient (DQ) (partial regression coefficient 1.981, 95% confidence interval 0.091 to 3.872) than offspring of mothers who did not use such supplements at any time throughout their pregnancy (non-users). Offspring of mothers who started using folic acid supplements within 12 weeks of gestation had a significantly higher cognitive-adaptive (1.489, 0.312 to 2.667) and language-social (1.873, 0.586 to 3.159) DQ than offspring of non-users. Regarding daily dietary folate intake from preconception to early pregnancy, multiple regression analysis revealed that there was no significant association with any DQ area in the 200 to < 400 µg and the ≥ 400 µg groups compared with the < 200 µg group. Maternal prenatal folic acid supplementation starting within 12 weeks of gestation (but not adequate dietary folate intake from preconception to early pregnancy) is positively associated with cognitive development in 4-year-old offspring. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Allergic conjunctivitis, allergy, atopic dermatitis, birth cohort study, allergic rhinitis, food allergy, meconium-stained amniotic fluid Keywords: allergic conjunctivitis; allergic rhinitis; allergy; atopic dermatitis; birth cohort study; food allergy; meconium-stained amniotic fluid EN allergic conjunctivitis allergic rhinitis allergy atopic dermatitis birth cohort study food allergy meconium-stained amniotic fluid 1 5 5 05/30/23 20230501 NES 230501 PEER REVIEW The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/pai.13956. Data on MSAF at childbirth were retrieved from medical record transcripts, by answering yes or no to the question "Was there MSAF?". [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]