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.

Background: Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large‐scale birth cohorts. Methods and Results: We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30–14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51–15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74–8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14–2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03–1.17]) were associated with CHD in offspring. Conclusions: Using a Japanese large‐scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.

For preventing Vitamin D (VD) insufficiency, several VD supplementation guidelines were established worldwide. In Japan, no nationwide guidelines for preventing VD insufficiency have been implemented, whereas guidelines for preventing vitamin K (VK) deficiency-related bleeding recommend weekly supplementation of VK. The aim of this study is to clarify whether weekly VD plus VK supplementation during the early neonatal period prevents VD insufficiency at one month of age. We retrospectively analyzed serum 25-hydroxyvitamin D (25(OH)D) levels of 555 one-month-old infants born between 2017 and 2023. Infants were classified into the control group (not supplemented), weekly group (1000 IU/week), and daily group (240 IU/day). We compared serum 25(OH)D levels among the three groups. Multivariable logistic regression analyses adjusted for formula intake and BMI were performed to better estimate the effect of VD supplementation on the prevention of VD insufficiency. We included 414, 55, and 86 infants in the control, weekly, and daily groups, respectively. All infants received weekly supplementation of VK. Serum 25(OH)D levels in the weekly and daily groups were higher than those in the control group (median (ng/mL): control 9.7 vs weekly 22.2, P < 0.001; control vs daily 23.0, P < 0.001). The frequencies of VD insufficiency were 370/414 (89.4 %), 11/55 (20.0 %), and 22/86 (25.6 %) in the control, weekly, and daily groups, respectively. Adjusted odds ratios of VD insufficiency compared to the control were 0.038 (95 % confidence intervals (95 %CI): 0.017, 0.085) and 0.036 (95 %CI: 0.019, 0.067) in the weekly and daily groups, respectively. No infant with VD excess was observed. Our results demonstrated that combined weekly supplementation of VD and VK during early infancy can prevent VD insufficiency at one month of age without causing VD excess. This finding may provide evidence for the development of nationwide prophylaxis for VD insufficiency in regions lacking specific guidelines.

Background: The rate of recurrent spontaneous preterm delivery (sPTD) ranges between 27% and 34% and is 22.3% in Japan. Although it currently remains unclear whether probiotics prevent sPTD, retrospective studies recently reported a reduction in the rate of recurrent sPTD with the administration of probiotics including Clostridium spp., which induce regulatory T cells that play an important role in maintaining pregnancy. Objective: The objective of this trial is to evaluate the preventative effects of available oral probiotics, including Clostridium butyricum, on recurrent sPTD. Methods: This is a prospective, single-arm, nonblinded, multicenter trial in Japan. The sample size required for this trial is 345 pregnant women with a history of sPTD, considering a clinically significant reduction in the relative risk of 30% (risk ratio=0.7). The primary endpoint is the rate of recurrent sPTD at <37 weeks of gestation. The secondary endpoints are the rate of sPTD at <34 weeks of gestation, the rate of recurrent sPTD at <28 weeks of gestation, the ratio of intestinal Clostridium spp. (detected by next-generation sequencing), and bacterial vaginosis (using the Nugent score). Results: The trial procedures were approved by the Clinical Research Review Board of Toyama University Hospital (SCR2020008) on March 31, 2021. The trial was registered on the Japan Registry of Clinical Trial website on April 28, 2021. Recruitment began on May 1, 2021, and the trial is estimated to finish on March 31, 2025. Conclusions: The findings will clarify the rate of recurrent sPTD following probiotic administration including Clostridium butyricum. Outcomes from this trial will inform clinical practice and guide future randomized controlled trials. Trial Registration: Japan Registry of Clinical Trials jRCTs041210014; https://jrct.niph.go.jp/latest-detail/jRCTs041210014 International Registered Report Identifier (IRRID): DERR1-10.2196/59928