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The influence of family allergic history on food allergy in offspring in Japan is unknown. We analyzed data from a nationwide birth cohort study using logistic regression models to examine the associations of maternal, paternal, and both parental histories of allergic diseases (food allergy, atopic dermatitis, asthma, and rhinitis) with their child’s food allergy at 1.5 and 3 years of age. This analysis included 69,379 singleton full-term mothers and 37,179 fathers and their children. All parental histories of allergic diseases showed significant positive associations with their child’s food allergy. When both parents had a history of allergic diseases, the adjusted odds ratio (aOR) tended to be higher than when either parent had allergic diseases (p for trend < 0.0001). The highest aOR was detected when both parents had food allergy (2.60; 95% confidential interval, 1.58–4.27), and the aOR was 1.71 when either parent had food allergy (95% confidential interval, 1.54–1.91). The aORs were attenuated but still had significant positive associations after adjusting for the child’s atopic dermatitis, a risk factor for allergy development. In conclusion, all parental allergic diseases were significantly positively associated with their child’s food allergy. The effect of family history showed a stepwise increase in risk from either parent to both parents, and the highest risk of allergic disease was a parental history of food allergy.

Previous epidemiological studies have reported an increased risk of anemia in people with allergic disorders. However, previous studies have followed a cross-sectional design. The aim of this study was to investigate the association between the two conditions with a cohort dataset. We used data of 80,943 children in the Japan Environment and Children’s Study, the largest birth cohort in Japan. The association between anemia and allergic disorders was evaluated with a logistic regression model and propensity score analysis. After adjusting for potential confounders, children with asthma (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.32–2.60), atopic dermatitis (OR, 2.18; 95% CI, 1.66–2.85), allergic rhinitis (OR, 1.35; 95% CI, 1.05–1.74), allergic rhinoconjunctivitis (OR, 2.95; 95% CI, 1.91–4.54), and food allergies (OR, 1.92; 95% CI, 1.44–2.56) at 2 years of age predicted high odds of developing anemia in the next year. Any allergy at 2 years of age was associated with an increased risk of anemia at the age of 3 years (OR, 1.80; 95% CI, 1.41–2.29). The findings remained stable in the propensity score analysis. Results suggest that allergic diseases were related to caregiver-reported anemia in children.

Background A variety of dietary supplements are commercially available. However, the efficacy and safety of dietary supplement use in children are not well established. Understanding dietary supplement use is important for developing public health policy regarding dietary supplements. This study aimed to investigate the types of dietary supplements used and characteristics of dietary supplement users among Japanese elementary school children. Method We conducted a cross-sectional web-based questionnaire study. Dietary supplement use, socio-demographics, and health-related behaviors were assessed through mother-reported questionnaire. Types of dietary supplements were identified based on ingredient using product barcodes and brand names. Multivariate logistic regression analysis was conducted to investigate the socio-demographics and health-related behaviors associated with supplement use. Results Among 4933 children, 333 (6.8%) were identified as dietary supplement users. The most common supplement was amino acids or protein (1.4%), followed by n–3 fatty acids or fish oil (1.0%), probiotics (1.0%), multivitamins (0.9%), multivitamin-minerals (0.8%), and botanicals (0.8%). Overall, any dietary supplement use was significantly associated with the highest frequency of sports participation (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.65–4.02), highest household income (OR, 1.87; 95% CI, 1.13–3.10), highest maternal educational level (OR, 1.82; 95% CI, 1.31–2.52), and male sex (OR, 1.38; 95% CI, 1.09–1.75). The highest frequency of sports participation was significantly associated with higher odds of use of amino acids or protein (OR, 6.06; 95% CI, 1.78–20.6) and multivitamins (OR, 3.56; 95% CI, 1.11–11.5), compared to the lowest frequency of sports participation. Conclusion This study showed that Japanese children primarily use non-vitamin, non-mineral supplements. Non-vitamin, non-mineral supplements should thus be included in future studies aimed at monitoring dietary supplement use. We also found that dietary supplement use in children was associated with sports participation. Guidelines for dietary supplement use for children, in particular sport participants, are needed.

Excessive screen media use has been reported to cause shorter sleep; however, the types of media environments that affect early childhood sleep are less known. This study examined the association of multiple media use, screen time for each device, and the purpose of smartphone and tablet use with delayed bedtime among 4–8-year-olds. Participants were recruited from the Japan Environment and Children’s Study, a nationwide birth cohort study. Mothers of 1837 children reported screen media use and bedtime in a questionnaire. The association between delayed bedtimes (after 22:00 h) and media device use (smartphones, tablets, portable and console games, and TV/DVDs) was examined by logistic regression analysis. Children who used three or more devices besides TV/DVDs were more likely to have delayed bedtimes. Delayed bedtimes were associated with smartphone use, even with a 0.1–1 h/day screen time, and with prolonged screen time for tablets, portable games, and console games, but not for TV/DVDs. Gaming on smartphones and tablets was also associated with delayed bedtime. To ensure adequate sleep for young children, families must develop feasible measures to discourage children’s use of multiple devices and prolonged device use, especially for games, and a social environment that supports such measures.

Aims/Introduction We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers of participants in the Japan Environment and Children’s Study, a nationwide, multicenter, pregnancy and birth cohort. Materials and Methods Pregnant women aged 14–50 years were studied in 15 centers across Japan. Clinical information was obtained using self‐administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. Results Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. Glycated hemoglobin, total cholesterol, low‐density lipoprotein cholesterol and triglyceride across all the percentiles increased as prepregnancy body mass index increased, whereas high‐density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. Glycated hemoglobin was high in participants with type 1 diabetes or type 2 diabetes only, but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high‐density lipoprotein cholesterol, whereas participants with dyslipidemia only showed high total cholesterol and low‐density lipoprotein cholesterol throughout. Conclusions Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The Japan Environment and Children’s Study will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies., This is the first study to describe the metabolic status of a large cohort of pregnant women aged 14–50 years and living in Japan.

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 ( 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.

This study aimed to describe the distribution of pregnancies with medical and obstetric complications based on the Japan Environment and Children's Study (JECS). We evaluated the distribution of the history of obstetric/gynaecological diseases, the history of obstetric labour complications, pregnancy with medical and surgical complications, and obstetric labour complications in participants in the JECS. Of 100,818 pregnant women with medical record entries after delivery, 15,305 (15.2%) had medical and surgical complications in pregnancy and 46,756 (46.4%) experienced obstetric labour complications. The proportion of pregnancies with heart disease, kidney disease and hepatitis was 0.3%, 0.3% and 0.1%, respectively. Gestational diabetes was diagnosed in 2715 (2.7%) women. The proportion of women with mild and severe gestational hypertension was 2.3% and 1%, respectively. The JECS is the largest birth cohort in Japan. These data will provide useful, basic information for perinatal care in Japan.IMPACT STATEMENTWhat is already known on this subject? Epidemiological studies have suggested that pre-existing diseases and complications of pregnancy, such as heart disease in pregnancy, gestational hypertension and gestational diabetes, may have implications for pregnancy outcomes, as well as for children's health and development.What the results of this study add? We evaluated the distribution of the history of obstetric/gynaecological diseases, the history of obstetric labour complications, medical and surgical complications in pregnancy, and obstetric labour complications using data from the Japan Environment and Children's Study (JECS).What the implications are of these findings for clinical practice and/or further research? The JECS is the largest birth cohort in Japan. Our data will provide useful, basic information for perinatal care in Japan.

Background This study assessed the psychometric profile of 10 questionnaires (every 6 months, from 6 to 60 months) from the Japanese translation of the Ages and Stages Questionnaires, third edition (J‐ASQ‐3). Methods Data from 439 children in a birth cohort were used to identify the J‐ASQ‐3 score distribution, establish cut‐off scores, and calculate the instrument's internal consistency. Data were also collected from 491 outpatients to examine J‐ASQ‐3 test–retest reliability and concurrent validity, which was examined using the Kyoto Scale of Psychological Development (KSPD) and the Japanese version of the Denver Developmental Screening Test II (J‐Denver II). Both the original and the alternative screening criteria of the ASQ‐3 were used (failure in at least one and at least two domains, respectively). Results Cronbach's alpha for each J‐ASQ‐3 subscale on each questionnaire ranged from 0.45 to 0.89. Test–retest reliability was >0.75 for the subscales on almost all questionnaires. Concurrent validity was also adequate. In comparison with the screening results of the KSPD, the overall sensitivity and specificity were 96.0% and 48.8%, respectively, when the ASQ‐3 original criterion was used, and 92.1% and 74.9%, respectively, when the alternative criterion was used. In comparison with the screening results of the J‐Denver II, the overall sensitivity and specificity were 75.6% and 74.7%, respectively, when the ASQ‐3 original criterion was used, and 56.3% and 93.0%, respectively, when the alternative criterion was used. Conclusions This study quantified the psychometric profiles of the Japanese translations of 10 ASQ‐3 questionnaires. We demonstrated the validity of the J‐ASQ‐3 and determined new cut‐off scores. Further studies with larger samples from a greater range of locations are required to clarify the suitability of this tool for all Japanese children.

Background The aims of the present report were to estimate the prevalence of congenital anomalies (CAs) among infants in Japan using data from the Japan Environment and Children's Study (JECS) and to evaluate the validity of CA classification within JECS. Methods Data on CAs were collected at delivery and at age 1 month from the medical records of 101,825 infants at 15 regional centers. The analyses focused on 61 CAs, selected on the basis of reported associations with environmental exposure. Prevalence per 10,000 pregnancies (including miscarriages, stillbirths, and live births) was stratified according to four reporting patterns (at delivery, at age 1 month, at either, and at both). To evaluate the accuracy of observed CA prevalence, the medical records of 179 cases from a single JECS regional center underwent independent, retrospective re-evaluation. Results The prevalence of major CAs in four reporting patterns (at delivery, at age 1 month, at either, and at both) was 2.4, 2.6, 3.5, and 1.4 for myelomeningocele/spina bifida; 4.3, 4.2, 5.3, and 3.2 for cleft palate; 18.1, 17.4, 19.5, and 15.1 for cleft lip with or without cleft palate; 73.4, 100.3, 120.8, and 52.8 for congenital heart disease; and 10.5, 14.1, 15.0, and 9.6 for Down's syndrome, respectively. In the subsample re-evaluation, CA diagnoses were confirmed for 92.7%, 93.3%, 90.5%, and 97.8% of cases in the four reporting patterns (at delivery, at age 1 month, at either, and at both), respectively. Conclusions The present report generated reliable data concerning the prevalence of major CAs in JECS.

Few studies have investigated the risky health behaviors and psychosocial characteristics of teenage mothers in countries with a low teenage birth rate, like Japan. We examined the differences in maternal prenatal risky health behaviors and psychosocial characteristics, and birth weight of infants between teenage and adult mothers. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We identified 1159 teenage (age younger than 20 years) and 73,547 adult mothers (20-34 years) who participated a nationwide birth cohort study between 2011 and 2014. Behavioral and psychosocial characteristics were ascertained using questionnaires during pregnancy. Birth weight of infants was verified through medical records. Univariate and multivariable logistic regression were used to assess the association of teenage motherhood and birth weight of infants with parity, marital status, household income, maternal education, job status, preconception body mass index, gestational weight gain, psychological distress, and smoking status.Teenage mothers were significantly more likely to smoke and have psychological distress and less likely to use alcohol than adult mothers (9.9% vs 4.6%, P .001; 8.9% vs 3.4%, P .001; 1.3% vs 2.5%, P .001, respectively). No association was found between teenage motherhood and low birth weight in infants (odds ratio 0.99; 95% confidence interval, 0.73-1.32). Further, no association was found after adjusting for covariates.A substantially greater number of Japanese teenage mothers smoked and experienced severe psychological distress than adult mothers. Our findings will be useful for future research and for developing effective policies and programs for teenage mothers and their children.

Background Although pregnancies conceived by assisted reproductive technology (ART) have a higher risk of maternal/perinatal complications, the overall risk of adverse outcomes necessitating advanced obstetric care has not been closely examined. The present study aimed to assess and compare the risk of maternal/perinatal complications and adverse outcomes in pregnancy and childbirth conceived by ART with those conceived naturally. Methods This study was conducted as a part of the Japan environment and children’s study (JECS), an ongoing nationwide birth cohort study in Japan. The risk of maternal/perinatal complications and adverse outcomes was assessed by mode of conception (natural conception, ovulation induction [OI] without ART, conventional in vitro fertilization and embryo transfer [IVF-ET], or intracytoplasmic sperm injection [ICSI]) using logistic regression and generalized estimating equations controlling for potential confounders. Results The final dataset included women who conceived naturally (N = 90,506), by OI without ART (N = 3939), by conventional IVF-ET (N = 1476), and by ICSI (N = 1671). Compared with women who conceived naturally, those who conceived by conventional IVF-ET were at higher risk of placenta previa (adjusted OR 2.90 [95% CI 1.94, 4.34]), morbidly adherent placenta (6.85 [3.88, 12.13]), and pregnancy-induced hypertension (1.40 [1.10, 1.78]) whereas those who conceived by ICSI had a higher risk of placental abruption (2.16 [1.20, 3.88]) as well as placenta previa (2.01 [1.29, 3.13]) and morbidly adherent placenta (7.81 [4.56, 13.38]). Women who conceived by ART had a higher risk of blood transfusion (conventional IVF-ET: 3.85 [2.52, 5.88]; ICSI: 3.76 [2.49, 5.66]) and ICU admission (conventional IVF-ET: 2.58 [1.11, 6.01]; ICSI: 3.45 [1.68, 7.06]) even after controlling for potential confounders. Neonates conceived by ART had a higher risk of preterm birth (conventional IVF-ET: 1.42 [1.13, 1.78]; ICSI: 1.31 [1.05, 1.64]). Conclusions Women who conceived by ART had a higher risk of maternal/perinatal complications necessitating advanced obstetric care. Obstetricians should be aware of the increased risk of adverse outcomes among this population.

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health.

Few epidemiologic studies have examined the role of maternal iron status in allergic diseases in offspring and findings have been inconsistent. We used a large birth cohort in Japan to explore the association of the markers for maternal iron status (maternal hemoglobin, hematocrit and dietary iron intake during pregnancy) with allergy development in offspring during early childhood. We analyzed information on children age 0–3 years from the Japan Environment and Children’s Study (JECS). We used logistic models and generalized estimating equation models to evaluate the effect of maternal hemoglobin and hematocrit levels and dietary iron intake on allergies in children. Models were also fitted with propensity score-matched datasets. Data were collected for a total of 91,247 mother–child pairs. The prevalence (95% confidence interval) of low hemoglobin and hematocrit was 14.0% (13.7–14.2%) and 12.5% (12.3–12.8%), respectively. After adjusting confounders, low hemoglobin and hematocrit during pregnancy were not associated with childhood allergic outcomes. Findings from models with propensity score-matched datasets also indicated that children born to mothers with low hemoglobin or hematocrit levels during pregnancy did not have a higher risk of developing allergic conditions at 3 years old. We found no meaningful associations between low energy adjusted maternal dietary iron intake and allergies in children. In conclusion, using birth cohort data, we found no evidence supporting an association of low maternal hemoglobin, hematocrit and low dietary iron intake with allergy symptoms during early childhood. Further studies with more suitable proxy markers for blood iron status are needed.

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children’s Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year.

Skin inflammation leads to altered cytokine/chemokine production and causes systemic inflammation. The systemic mechanism of atopic dermatitis (AD) is recognized to affect systemic metabolism. This study aimed to examine the relationship between early-onset persistent eczema and body weight, height, and body mass index (BMI), in addition to food allergy in a birth cohort among infants. This study design was a nationwide, multicenter, prospective birth cohort study—the Japan Environment and Children’s Study (JECS). Generalized linear models were fitted for z scores of weight, height, BMI, and food allergy to evaluate the relationship between eczema and these outcomes for infants at age1, 2, and 3 years. Persistent eczema was negatively associated with height at the age of 2 years (estimated coefficient, −0.127; 95% confidence interval [CI], −0.16 to −0.095) and 3 years (−0.177; 95% CI, −0.214 to −0.139). The same tendency was also observed with weight and BMI. Early disease onset at younger than 1 year and persistent eczema had the strongest association with development of food allergy at age 3 years (OR, 11.794; 95% CI, 10.721–12.975). One phenotype of eczema with early-onset and persistent disease creates a risk of both physical growth impairment and development of food allergy. Infants who present with the early-onset and persistent type of eczema should be carefully evaluated daily for impaired physical growth and development of food allergy.

Introduction: Previous studies have reported that maternal asthma increases the risk of preterm birth. We hypothesized that inflammatory reactions caused by allergic diseases might affect the uterine environment and, subsequently, perinatal outcomes. The objective of this study was to examine the associations between allergic features among mothers and preterm pregnancy outcomes in a nationwide birth cohort. Methods: We analyzed data from pregnant women obtained from the Japanese Environment and Children’s Study (JECS), a nationwide general birth cohort study. We used binomial and multinomial logistic regression models to examine the associations between maternal allergic features and preterm birth, threatened preterm labor (TPL), and preterm premature rupture of the membrane (PPROM). Results: A total of 97,683 pregnant women were included. Prevalence of preterm birth, TPL, and PPROM was 4.7, 19.6, and 1.2%, respectively. Maternal history of allergic diseases (asthma, allergic rhinitis, allergic conjunctivitis, food allergy, drug allergy, and contact dermatitis) increased the risk of TPL(adjusted odds ratio [aOR] = 1.11 [95% CI: 1.06–1.17], aOR = 1.12 [1.08–1.16], aOR = 1.10 [1.04–1.16], aOR = 1.17 [1.09–1.26], aOR = 1.35 [1.23–1.48], and aOR = 1.34 [1.20–1.49], respectively). Although some maternal allergic features showed a negative association with preterm birth, the variables affecting preterm birth differed according to the gestational age of the fetus (22–33 weeks vs. 34–36 weeks). There were no significant associations between maternal allergic features and PPROM. Conclusion: Maternal allergic disease, except atopic dermatitis, may increase the risk of TPL. Comorbidity of maternal allergic disorders and perinatal adverse outcomes require further investigation.

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 .

The present study established a nomogram of fetal thyroid circumference (FTC) and the appearance timing of fetal distal femoral and proximal tibial ossification to assess fetal thyroid function in Japan. Between April 2015 and July 2019, normal pregnant women at our hospital were recruited for the study. FTC was measured by the automatic ellipse outline and plotted against gestational age (GA). Fetal distal femoral and proximal tibial ossification measurements were obtained with standard electronic calipers from outer-to-outer margins (> 1 mm as the presence of ossification). A total of 199 pregnant women were examined. FTC increased logarithmically to GA. A nomogram of FTC was expressed by a logarithmic formula: $${\ln}\left( {{\text{FTC}}} \right)\, = \,{\exp}\left( {{4}.{679}0{-}{3}0.{3961}/{\text{GA}}} \right)$$ . The respective 5–95th percentiles of FTC at each GA were 20.2–36.2 mm at 22 weeks, 25.0–44.8 mm at 26 weeks, 29.2–52.3 mm at 30 weeks, and 32.9–59.0 mm at 34 weeks. The fetal distal femoral epiphysis was not visualized before 30 weeks, but was visualized in 100% of fetuses after 35 weeks of gestation. The fetal proximal tibial epiphysis was not visualized before 33 weeks, but was visualized in 73.7% of fetuses at 37 weeks of gestation. We generated a GA-dependent FTC nomogram for Japanese fetuses. We also confirmed the appearance timing of fetal distal femoral and proximal tibial ossification to assess bone maturation. These assessments may be very useful for evaluating fetal thyroid function in Japan.

Nutritional requirements increase during pregnancy. However, relatively few studies have examined longitudinal changes in dietary intake from periconception to pregnancy. Here, we investigated changes in the intake of food and nutrients, and compliance with dietary reference intakes (DRIs) in pregnant women. The Japan Environment and Children’s Study, a nationwide multicenter prospective cohort study, included 30,373 pregnant women who answered a validated food frequency questionnaire repeatedly to assess changes in dietary intake in periconception and pregnancy. Energy-adjusted intakes of food groups and nutrients were described using the density method. The percentage of women not meeting DRIs was calculated. Of all foods groups examined, intake of food significantly increased from periconception to pregnancy for dairy products (mean difference 23.5 g/1000 kcal, 95% confidence interval [CI] 22.0–25.0 g/1000 kcal), confectionaries (2.0 g/1000 kcal, 1.8–2.2 g/1000 kcal), and soft drinks (1.3 g/1000 kcal, 0.3–2.3 g/1000 kcal). Of all nutrients examined, intake was significantly increased for calcium (mean difference 27 mg/1000 kcal, 95% CI 25–29 mg/1000 kcal), vitamin A (15 μgRE/1000 kcal, 13–18 g/1000 kcal), and saturated fat (0.4% energy, 0.4–0.4% energy). The percentage of women not meeting DRIs increased for vitamin B group, vitamin C, saturated fat and salt. We found that energy-adjusted intakes of calcium, vitamin A, and saturated fat increased from periconception to pregnancy, while intake of other nutrients did not increase. The percentage of women not meeting DRIs increased for water-soluble vitamins, saturated fat, and salt.

We examined the socio-demographic and behavioral factors associated with alcohol consumption before and after pregnancy awareness in pregnant women. 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. 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. 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.

Vitamin D (VitD) may affect immune system modulation and result in the development of atopic dermatitis (AD). However, published findings have remained controversial. We investigated the association between early-life 25-hydroxyvitamin D (25(OH)D) levels and AD risk at childhood with a birth cohort. The data were obtained from “the Japan Environment and Children’s Study (JECS)” and “the Sub-Cohort study of JECS” performed with children aged 2 years. “Liquid chromatography-tandem mass spectrometry” was used to measure VitD. The information on AD was obtained from parents’ answers to a questionnaire when their children were aged 3 years. In order to explain the seasonal effects on VitD levels, a deseasonalized continuous variable was further calculated. The logistic regression models were fitted to evaluate the effect of VitD on childhood AD. The study included 4378 children with complete data on VitD and AD. The results from models indicated that low VitD at 2 years was not a risk factor for the development of AD at 3 years, after adjusting for potential confounders. Moreover, there was no U-shape relationship between deseasonalized VitD and childhood AD. Overall, early-life 25(OH)D levels were not link to the increased risk of developing childhood AD.

Background In recent years, a resurgence in the number of infants with vitamin D deficiency has been noted. In addition to seasonal differences in exposure to ultraviolet (UV) rays, regional differences in dietary habits and lifestyles may affect susceptibility to vitamin D deficiency. However, no studies have been conducted on infants in multiple regions of Japan to determine the extent of differences in vitamin D status. Methods The levels of 25-hydroxyvitamin D (25OHD) were measured by radioimmunoassay in 126 infants aged 2 to 4 years, who participated in the Pilot Study of the Japan Environment and Children's Study (JECS) by the Ministry of Environment of Japan. A multiple regression model with 25OHD level as the outcome variable, and season and region as explanatory variables was generated. Results A Wald test revealed that both region and season during which infants participated in this study significantly affected 25OHD levels (p-value = 0.0087 and

Objective Although environmental lead exposure has decreased, several studies have shown that low-level lead exposure can result in adverse psychological symptoms. However, few studies have examined lead neurotoxicity in pregnant women. We investigated the association between lead exposure and psychological symptoms in pregnant women, and between socio-economic status and blood lead levels. Methods Blood lead levels were measured in 17,267 pregnant women in the Japan Environment and Children’s Study. Odds ratios (ORs) for high blood lead levels were calculated using multinomial logistic regression. Psychological symptoms were assessed using the Kessler Psychological Distress Scale (K6). ORs for depression (K6 ≥ 13 or ≥5) were calculated using logistic regression with adjustment for potential confounders. Results The geometric mean of whole blood lead levels was 0.58 μg/dl (range 0.14–6.75 μg/dl). Higher blood lead levels were associated with older age (OR 1.79, 9 5% confidence interval [CI] 1.46–2.19), unmarried status (OR 1.75, 95 % CI 1.31–2.33), lower household income (OR 1.76, 95 % CI 1.38–2.24), and lower educational attainment (OR 1.34, 95 % CI 1.20–1.48). The percentage of women with K6 scores ≥13 and ≥5 was 3 % and 28.2 %, respectively. There was no significant association between lead exposure and K6 score (K6 ≥ 13: OR 1.00, 95 % CI 0.76–1.32; K6 ≥ 5: OR 0.98, 95 % CI 0.88–1.09). Conclusion Our results indicate a small but significant association between higher blood lead levels and lower socio-economic status in a population with low blood lead levels, but no association between low-level lead exposure and psychological symptoms.

Background: Programmed death-ligand 1 (PD-L1) is expressed not only on some cancer cells, but also on the outer surface of placental syncytiotrophoblasts, which is assumed to induce maternal immune tolerance to fetal tissue via programmed death-1 (PD-1) receptors on T cells. Recently, levels of soluble forms of PD-L1 (sPD-L1) were reported to be higher in the serum of pregnant women (PW) than in non-pregnant women (non-PW). However, there have been no reports of the functional significance of PW's serum containing high sPD-L1 levels. Therefore, the aim of the present study was to clarify the role of sPD-L1 in the sera of PW as an immunosuppressive molecule by in vitro assays.Methods: As a post-hoc analysis of our previous cohort study, 330 pairs of serum from PW during the third trimester and cord blood (CB) from paired offspring without major complications were examined. Serum levels of sPD-L1 and sPD-1 were measured by ELISA. On mixed lymphocyte culture (MLC), 3H-thymidine uptakes in the presence of PW's, offspring's, or non-PW's serum were compared. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of PW's serum stimulated with PHA, and then cytokine levels were measured in supernatants by multiple cytokine analysis with or without anti-PD-L1blocking antibody.Results: The median sPD-L1 level was 8.3- and 6.9-fold higher in PW than in offspring and non-PW, respectively, whereas sPD-1 levels were lower in PW and offspring than in non-PW. On MLC, 3H-thymidine uptake in the presence of autoantigen was strongly reduced by co-culture with serum of both PW and offspring, compared with serum of non-PW. In contrast, uptake in the presence of alloantigen was moderately inhibited by PW's serum, whereas it was less suppressed by offspring's serum, compared with non-PW's serum. In the culture of PBMCs, tumor necrosis factor-α, interferon gamma, interleukin (IL)-2, and IL-4 levels were significantly higher in the presence of anti-PD-L1 blocking antibody than in culture not treated with antibody (all P < 0.05) or culture treated with isotype control antibody (all P < 0.05).Conclusion: The levels of sPD-L1 are elevated in PW's serum, which may, at least in part, suppress maternal immunity.

Objective The purpose of the study was to extend our understanding of the Kyoto Scale of Psychological Development (KSPD) by comparison with a parent-rated scale, the Kinder Infant Development Scale (KIDS). Methods The participants of this study were 229 children aged 0–4, who were referred to the Developmental Evaluation Center of the National Center for Child Health and Development, due to a suspected developmental disorder/delay. The participants were divided into subgroups, depending on age and overall DQ. For each group separately, correlation analyses were conducted between the Developmental Quotient (DQ) of each KSPD domain and DQ of each KIDS subscale. Results For high DQ group, in all ages, the KSPD Postural-Motor (P-M) domain DQ demonstrated a high correlation with the KIDS Physical–Motor DQ, and at young ages, it was also found to be moderately or strongly associated with the KIDS Manipulation DQ. For high DQ group, the KSPD Cognitive–Adaptive (C–A) domain DQ was most consistently related to the KIDS Manipulation DQ, and was also moderately correlated with the KIDS Physical–Motor DQ, Receptive Language DQ, Social Relationship with Adults DQ, Discipline DQ, and Feeding DQ, depending on age. For high DQ group, the KSPD Language–Social (L–S) DQ most consistently showed a moderate or high correlation with the KIDS Receptive Language DQ and the Manipulation DQ, and also related to Physical–Motor DQ, Expressive Language DQ, Language Conception DQ, Social Relationship with Adults DQ, and Social Relationship with Children DQ for some age groups. The low DQ group demonstrated stronger relationships on many of the pairs of the DQ of a KSPD subdomain and the DQ of a KIDS subscale, regardless of the type of subdomains and subscales. Conclusions For high DQ group, the KSPD P-M domain was consistently related to parent-reported physical/motor development, the C–A domain primarily reflected a child’s fine motor skills and his/her ability to understand and follow verbal instructions provided by adults, while the L–S domain was associated with parent-reported language ability. For low DQ group, the effect of global delay increased overall correlations between each domain and subscale. Further studies are necessary to replicate the findings in a larger sample including typical children.

Background In our prior randomized trial on preventing influenza, asthma attacks as a secondary outcome occurred less often in the vitamin D group than in the placebo group. We aimed to clarify whether low-dose, short-term vitamin D supplementation, in addition to standard treatments, improves control of childhood asthma. Methods We conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D3 supplements (800 IU/day) with placebo for 2 months in schoolchildren with asthma. The primary outcomes were frequency and severity of asthma judging from changes in asthma control levels defined by the Global Initiative for Asthma (GINA) by collaborating doctors at 2 and 6 months. Results Japanese schoolchildren with asthma (n = 89) were randomly assigned to receive vitamin D (n = 54) or placebo (n = 35). At 2 months, GINA asthma control was significantly more improved in the vitamin D group compared with the placebo group (P = 0.015). Childhood asthma control test (CACT) scores, a secondary outcome, were also significantly (P = 0.004) improved in the vitamin D group compared with the placebo group at 2 months, and differences remained significant (P = 0.012) at 6 months. The proportion of patients with a peak expiratory flow rate

Because vitamin D may have beneficial effects on glucose metabolism in pregnant women with gestational diabetes mellitus, we explored whether maternal 25-hydroxyvitamin D (25OHD) levels in normal pregnancy have association with diabetes-related hormone levels and glycated albumin (GA). A prospective cohort study was performed to collect serum samples from 612 pairs of pregnant women and cord blood of their offspring. Levels of 25OHD and GA in maternal and cord blood were measured by radioimmunoassay and enzyme assay, respectively. Using cord serum, 12 diabetes-related hormones were assayed. Spearman’s rank correlation coefficient was used to quantify the strength of association between biomarkers. A prominent association between maternal and cord 25OHD levels (r = 0.76, 95% confidence intervals (CIs): 0.73–0.79, P < 0.0001) and weak association between maternal and cord GA (r = 0.22, 95% CIs: 0.14–0.30, P < 0.0001) were shown. Among the 12 diabetes-related hormones, both maternal and cord 25OHD levels showed prominent negative associations with glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These results suggest that decreased maternal 25OHD may be associated with decreased cord 25OHD and increased cord GLP-1 and GIP levels, which may be involved with the transfer of maternal glucose to the fetus.

Objectives: No previous study has used repeated measures data to examine the associations of dog/cat ownership with wheezing and asthma prevalence among children. This prospective study used repeated measurers analysis to determine whether dog/cat ownership in childhood is an independent risk factor for wheezing and asthma, after adjustment for gestational, socio-economical, and demographical confounders confounders, in Japan. Methods: We conducted a multicenter pilot study of the Japan Environment and Children's Study (JECS) during 2009-2010. Among 440 newborn infants enrolled, 410 (52.8% males) were evaluated for dog/cat ownership in the home and history of wheezing and asthma in five follow-up questionnaire surveys (until age 6 years). Dog/cat ownership during follow-up period was categorized into four groups: 7.6% were long-term dog/cat owners, 5.9% were toddler-age owners, 5.9% were preschool-age owners, and 80.7% were never owners. Results: The prevalence of wheezing during follow-up period increased from 20.8% to 35.4% and the prevalence of asthma increased from 1.3% to 16.3%. A fitted logistic generalized estimating equation models including important confounders showed no significant associations of the interaction between dog and/or cat ownership and follow-up time with the risks of wheezing and asthma. However, the risks of wheezing and asthma were slightly lower for long-term and toddler-age dog/cat owners than for preschool-age and never owners. Conclusions: The present findings suggest that dog and cat ownership from toddler-age does not increase the risks of wheezing and asthma compared with never owners among Japanese children.

Importance Cow’s milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice. Objective To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow’s milk protein and/or clinical food allergy, including cow’s milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels. Design, Setting, and Participants The Atopy Induced by Breastfeeding or Cow’s Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. Participants included 330 newborns at risk for atopy; of these, 312 were included in the analysis. Data were analyzed from September 1 through October 31, 2018. Interventions Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid–based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (BF plus CMF group). Main Outcomes and Measures The primary outcome was sensitization to cow’s milk (IgE level, ≥0.35 allergen units [UA]/mL) at the infant’s second birthday. Secondary outcomes were immediate and anaphylactic types of food allergy, including CMA, diagnosed by oral food challenge test or triggered by food ingestion, with food-specific IgE levels of at least 0.35 UA/mL. Subgroup analysis was prespecified by tertiles of serum 25(OH)D levels at 5 months of age. Results Of the 312 infants included in the analysis (160 female [51.3%] and 152 male [48.7%]), 151 of 156 (96.8%) in the BF/EF and BF plus CMF groups were followed up until their second birthday. The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81). The middle tertile of the 25(OH)D subgroup, but not the low and high tertiles, had a significant interaction with the intervention (RR, 0.19; 95% CI, 0.07-0.50;P = .02). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types. Conclusions and Relevance The evidence suggests that sensitization to cow’s milk and food allergy, including CMA and anaphylaxis, are primarily preventable by avoiding CMF supplementation for at least the first 3 days of life. Trial Registration http://umin.ac.jpIdentifier:UMIN000011577

As a new screening tool for neuromotor development in children aged two, we developed the Neuromotor 5 min Exam 2-year-old version (N5E2), which can be easily administered by pediatricians or primary care physicians. In this study, as an initial attempt to examine the utility of the N5E2, the inter-rater reliability on scoring for the individual items in this scale was assessed.The participants of the study were 29 children (aged 1-5 years, mean age = 2.79) diagnosed with a variety of neuromotor/developmental disorders/high-risk conditions. Inter-rater reliability was examined on the following 11 items in the N5E2: (1) Retrieving a rolling ball, (2) Gait, (3) Toe-walking, (4) Asymmetries of posture and/or movement, (5) Age at unsupported walking, (6) Speaking in two-word understandable sentences, (7) Hypotonus, (8) Hypertonus, (9) Eye movement, (10) Vision problem, (11) Hearing problem. The items were administered to children by two pediatricians with different expertise and clinical experience, separately.The results showed that among the eleven items in the N5E2 examined, a high level of agreement (κ ≥ 0.60) was found on 4 items, and a moderate level of agreement (0.40 ≤ κ 0.60) was found on 5 items. The level of agreement somewhat improved after the dichotomization of the score; using this format, a high level of rater agreement (κ ≥ 0.60) was found on 6 out of 11 items. The analyses also revealed high inter-rater reliability on the sum score of the 11 items (r = 0.84).The results suggest the possibility that this brief screening tool could be feasible in settings where clinicians' experience varies, based on its inter-rater reliability on individual items between the clinicians with different expertise and amount of clinical experiences.

Background Several guidelines, including the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL), recommend salmeterol/fluticasone combination therapy (SFC) as step 3 to 4 treatment for moderate to severe asthma. However, the optimal step-down approach to SFC remains unclear. In the current study, we examined step-down approaches in asthmatic children whose symptoms had been stabilized by SFC 100/200 μg/day. Methods This randomized, multicenter, open-label, parallel-group study was conducted over 12 weeks. For step-down therapy, subjects aged 5–15 years were randomly assigned to an SFC group (25/50 μg b.i.d.) or an FP group (100 μg b.i.d.), and treated for 12 weeks. Childhood Asthma Control Test (C-ACT) scores, lung function, and exhaled nitric oxide (FeNO) levels were monitored. Results Of 131 enrolled subjects, 128 completed the study and were included in the analysis. Decreases in % peak expiratory flow rate and % forced expiratory flow at 50% of vital capacity (V50) were observed in the FP group at each time point. There was a significant difference between the two groups for the change in %V50 from its previous value at each time point. There were no significant changes in FeNO levels (range 15–20 ppb) or C-ACT scores (∼26 points) within or between groups. Conclusions A high level of asthma control was maintained with both approaches. The use of SFC step-down resulted in somewhat better respiratory function, with no worsening of airway inflammation. However, halving the dose of SFC and switching to FP alone are both optimal step-down approaches.

Children with Down syndrome (DS), who are likely to suffer from a large number of musculoskeletal problems, tend to have a unique pattern of walking in clinical settings. Despite such apparent uniqueness, few studies have empirically investigated gait development pattern in DS children, especially at an earlier age. We therefore conducted gait analysis in young DS children who are prescribed insoles, to explore how their gait patterns develop, using the gait parameters identified by Sutherland et al. as determinants of gait maturity of typical children.Participants consisted of 63 DS children (31 boys) aged 1-6 years (mean, 4 years 1 month) with a diagnosis of flat feet who were prescribed orthotic insoles. A 2.4 m sheet-type gait analyzer was used to analyze gait pattern. We measured the following variables: walking velocity (cm/min), cadence (steps/min), step length (cm), and single-limb stance phase ratio (%), and examined their relationship with age on regression analysis.Walking velocity and step length were significantly and positively related to age. Cadence was also significantly, but negatively associated with age. In contrast, SLS phase ratio did not have a statistically significant relationship with age.Down syndrome children have unique gait development patterns. Although walking velocity, cadence, and step length were found to develop with age, as in typical children, SLS phase ratio did not change with age in DS children. Further studies with a larger sample are necessary to replicate these findings.

Background Tobacco and alcohol consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that smoking increased TP53 and other mutations in HNSCC; however, the effects of alcohol consumption on these genetic alterations remain unknown. We explored the association between alcohol consumption and somatic copy-number alterations (SCNAs) across the whole genome in human papillomavirus (HPV)-negative HNSCCs, and compared with the effects of smoking on genetic alterations. Methods SCNA and TP53 mutations in tumor samples were examined by high-resolution comparative genomic hybridization microarray 180K and by direct sequencing, respectively, and statistically analyzed for associations with alcohol consumption and smoking during the 20 years preceding diagnosis of HNSCC. Probes with a corrected p-value (=q-value) less than 0.05 and fold change greater than 1.2 or less than -1.2 were considered statistically significant. Results A total of 248 patients with HNSCC were enrolled. In the HPV-negative patients (n=221), heavy alcohol consumption was significantly associated with SCNAs of oncogenes/oncosuppressors that were previously reported to occur frequently in HNSCCs: CDKN2A (q=0.005), FHIT (q=0.005), 11q13 region including CCND1, FADD and CTTN (q=0.005), ERBB2 (HER2) (q=0.009), 3q25-qter including CCNL1, TP63, DCUN1D1 and PIK3CA (q=0.014), and CSMD1 (q=0.019). But, TP53 mutations were not affected. In contrast, smoking was associated with increased risk of TP53 mutations, but did not induce any significant SCNAs of oncogenes/oncosuppressors. Conclusion These results suggest that both alcohol consumption and smoking had distinct effects on genetic alterations in HNSCCs. Heavy alcohol consumption may trigger previously known and unknown SCNAs, but may not induce TP53 mutation. In contrast, smoking may induce TP53 mutation, but may not trigger any SCNAs.

Background Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer. Methods We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined. Results Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, P = 0.027). Conclusions These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer.

When an effective pain relief cannot be achieved by systemic administration of analgesics, which provide adequate pain relief for up to 70 to 90 percent of patients, alternative remedies should be offered. We reported a patient with colon cancer who was effective for pain control using an epidural catheter with subcutaneous reservoir (epidural subcutaneous catheter implantation). Four other patients with an epidural catheter with subcutaneous reservoir during 2007 to 2008 also showed significant improvement in their pain level calculating by numerical rating scale (NRS). Furthermore we were able to minimize the risk of infection for homecare. However the epidural catheter with subcutaneous reservoir should be needed not only to manage dosages of epidural morphine accurately but also to prevent the incidence of catheter obstruction by general practitioners in home care service. This solution is necessary to establish the common strict guidelines between hospital doctors and general practitioners.

In a prior randomized trial, we found that the incidence of influenza A was less in the vitamin D3 group than among those on placebo, but the total incidence of either influenza A or B did not differ between groups. In this trial, the incidence of influenza A or B was less in the vitamin D3 group than in the placebo group only during the first half of the study. To elucidate whether vitamin D3 has preventive actions against influenza A, we conducted another trial during the 2009 pandemic of the H1N1 subtype of influenza A. Students (n = 247) of a Japanese high school were randomly assigned to receive vitamin D3 supplements (n = 148; 2000 IU per day) or a placebo (n = 99) in a double-blind study for 2 months. The primary outcome was incidence of influenza A diagnosed by a rapid influenza diagnostic test by medical doctors. Influenza A was equally likely in the vitamin D3 group (20/148: 13.5%) compared with the placebo group (12/99: 12.1%). By post hoc analysis, influenza A occurred significantly less in the vitamin D3 group (2/148: 1.4%) compared with the placebo group (8/99: 8.1%) (risk ratio, 0.17; 95% confidence interval, 0.04 to 0.77; P = 0.009) in the first month. However, during the second month, the vitamin D3 group experienced more events and effectively caught up with the placebo group. Vitamin D3 supplementation did not lower the overall incidence of influenza A during the 2009 H1N1 pandemic. A post hoc analysis suggests that the initial benefit during the first month of treatment was lost during the second month.

BackgroundMorbid obesity may be associated with hospitalization and possibly death from the 2009 pandemic H1N1 infection, suggesting a yet unknown association between obesity and the severity of viral infections. Thus, we examined association between obesity ratios and duration of disease in children with Respiratory Syncytial Virus (RSV) infection.MethodsA retrospective survey of 243 children admitted for bronchitis, bronchiolitis, pneumonia, and those who tested positive for a RSV test, were observed from a single institute in Japan. Primary outcome was set as the total days of wheezing in both the outpatient clinic and during hospitalization. Secondary outcomes were as follows: 1) total days of fever (37.5°C