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

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

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

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

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

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

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.

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

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

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

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

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

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

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.

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

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

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

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

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

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

Fluctuations of aeroallergen-specific immunoglobulins and children's allergic profiles: Japan Environment & Children's Study of a pilot cohort.

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

Better maternal quality of life in pregnancy yields better offspring respiratory outcomes: A birth cohort.

BACKGROUND: It is suggested that maternal mental health during pregnancy may affect offspring immune and respiratory features, based on the developmental origins of health and disease hypothesis. OBJECTIVE: To evaluate whether maternal quality of life (QoL) and depression during pregnancy leads to wheezing, asthma, and food allergy of the offspring at 3 years of age. METHODS: We conducted a nationwide, multicenter, prospective birth cohort study, Japan Environment and Children's Study. All variables were collected from questionnaires. Health-related QoL was measured using the Medical Outcomes Survey Short Form-8 questionnaire with a physical component summary and a mental component summary score. We conducted logistic regression analyses to evaluate the associations of offspring's wheezing, asthma, and food allergy with maternal QoL and depression. RESULTS: There were 72,685 participants with no missing variables. Maternal physical component summary scores of the Medical Outcomes Survey Short Form-8 questionnaire were negatively associated with offspring's asthma (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.99-1.00), current wheezing (aOR, 0.99; 95% CI, 0.99-0.99), and food allergy diagnoses (aOR, 0.99; 95% CI, 0.98-0.99) in children. Offspring's wheezing and asthma were also associated with maternal depression and anxiety during pregnancy. CONCLUSION: Poor maternal prenatal QoL increased the risk of wheezing, asthma, and food allergy in offspring. In addition, maternal depression and anxiety increased the risk of offspring's wheezing, asthma, and food allergy.

25-Hydroxyvitamin D levels among 2-year-old children: findings from the Japan environment and Children's study (JECS).

BACKGROUND: The study aim was to obtain epidemiological data on vitamin D levels for the pediatric population in Japan. We assessed the prevalence of vitamin D deficiency and insufficiency in 2-year-old Japanese children using data from a large ongoing birth cohort study. METHODS: Data for analysis was obtained from the Japan Environment and Children's Study (JECS) and a Sub-Cohort Study (SCS) of JECS. We evaluated the children's serum 25(OH) D levels by 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, and the rates of vitamin D deficiency or insufficiency. We also presented a weighted prevalence rate for vitamin D deficiency or insufficiency among all children in JECS. RESULTS: After excluding children with missing 25(OH)D2 or 25(OH)D3 data, we analyzed 4655 remaining children, of whom 24.7% (95% CI, 23.5-26.0%) had vitamin D deficiency (< 20 ng/mL), and 51.3% (95% CI, 49.8-52.7%) were at risk of vitamin D insufficiency (20-30 ng/mL). The estimated prevalence of vitamin D deficiency and insufficiency among all children in JECS were 25.4% (95% CI, 24.1-26.7%) and 50.9% (95% CI, 49.4-52.4%). Vitamin D deficiency was found in 22.9% of boys and 26.5% of girls. Median serum 25(OH) D concentrations were lower among participants measured during winter and spring than among those measured in summer and autumn. The highest rate of vitamin D deficiency was observed in Hokkaido, the northernmost prefecture of Japan. CONCLUSION: We analyzed data on serum 25(OH) D levels from a birth cohort study and found that vitamin D deficiency and insufficiency are very common among 2-year-old Japanese children. Sex, season, and latitude affect serum 25(OH) D concentrations.

Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study.

This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification.

Determinants of Alcohol Consumption in Women Before and After Awareness of Conception.

OBJECTIVES: We examined the socio-demographic and behavioral factors associated with alcohol consumption before and after pregnancy awareness in pregnant women. METHODS: This cross-sectional study included 91,828 pregnant women in a nationwide Japanese birth cohort study from 2011 to 2014. Alcohol consumption before and after pregnancy awareness, and sociodemographic behavioral characteristics were assessed through self-reported questionnaires. Determinants of alcohol consumption were investigated using logistic regression. RESULTS: Prevalence of alcohol consumption before and after pregnancy awareness was 50.0% and 2.8%, respectively. Most women consumed low to moderate levels of alcohol. Before pregnancy awareness, high educational level (odds ratios [OR] 1.11, 95% confidence interval [CI] 1.07 to 1.15), high household income (OR 1.16, 95% CI 1.09 to 1.24), and smoking (OR 1.77, 95% CI 1.65 to 1.90) were significantly associated with increased odds of alcohol consumption. After pregnancy awareness, older age (OR 1.73, 95% CI 1.54 to 1.94) and smoking (OR 5.57, 95% CI 4.88 to 6.37) were significantly associated with increased odds of alcohol consumption, and high education level (OR 0.72, 95% CI 0.64 to 0.81) and high household income (OR 0.75, 95% CI 0.63 to 0.89) were significantly associated with decreased odds of alcohol consumption. CONCLUSION: A half of women consumed alcohol before pregnancy awareness. Guidelines recommend abstinence from alcohol consumption in pregnant women for precaution, although influence of low to moderate levels of prenatal alcohol exposure on the fetus is inconclusive. Social-demographic characteristics differed between women who consumed alcohol before pregnancy awareness and women who continued alcohol after pregnancy awareness.

Reference values for salivary cortisol in healthy young infants by liquid chromatography-tandem mass spectrometry.

BACKGROUND: Sampling of salivary cortisol is non-invasive and important for the evaluation of the hypothalamic-pituitary-adrenal axis function and stress levels. However, the reference values for salivary cortisol measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in healthy infants are unclear. The aim of this study was to establish the reference values for salivary cortisol levels in healthy infants. METHODS: This study was a prospective observational cohort study following the participants until the age of 6 months. We analyzed 71 healthy, full-term infants at age 1 month between December 2017 and March 2018. We repeated saliva sampling every month, measured the salivary cortisol levels in the early morning by LC-MS/MS, and took the subjects' medical history by questionnaire. RESULTS: The minimum, 25th, 50th, 75th percentile, and maximum salivary cortisol levels were 0.08, 1.11, 2.21, 5.18, and 30.35 nmol/L, respectively. CONCLUSIONS: We established the reference values for salivary cortisol in young infants using LC-MS/MS.

Cumulative inactivated vaccine exposure and allergy development among children: a birth cohort from Japan.

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

Topical corticosteroid phobia among caretakers of children with atopic dermatitis: A cross-sectional study using TOPICOP in Japan.

BACKGROUND/OBJECTIVES: The TOPICOP scale is an easy-to-use scale for assessing topical corticosteroid (TCS) phobia in atopic dermatitis (AD) patients and their caretakers. TCS phobia is a common problem among AD patients and their caretakers. The aim of this study was to examine the relationship between TCS phobia in caretakers of children with AD and the characteristics of patients using the TOPICOP scale. METHODS: Caretakers of AD patients who visited the allergy clinic at the National Center for Child Health and Development in Tokyo between February 2014 and May 2014 were recruited. Caretakers of patients in follow-up had already attended an education session on treatment at the institution. All participants completed an anonymous questionnaire on the characteristics of the respondents and patients using the Patient-Oriented Eczema Measure (POEM) and the Japanese version of TOPICOP. RESULTS: In total, 243 participants (88.9% female) completed the survey. The average TOPICOP score was 40.3 and the median POEM score was 4. The TOPICOP score was significantly higher for patients younger than 12 months old with moderate to very severe AD (POEM ≥ 8) whose caretaker had not attended an educational session (P < 0.01, respectively). There was no significant difference in the family history of AD, age, or gender of the respondents. In multivariable analysis, preattendance at an education session was the only significant factor accounting for a higher TOPICOP score (P < 0.001). CONCLUSIONS: Regardless of their background, caretakers of AD patients can be affected from TCS phobia. Attending an educational session might ease their anxiety.