High expression of B3GALT5 suppresses the galectin-4-mediated peritoneal dissemination of poorly differentiated gastric cancer cells.

Peritoneal metastasis frequently accompanies metastatic and/or recurrent gastric cancer, leading to a poor prognosis owing to a lack of effective treatment. Hence, there is a pressing need to enhance our understanding of the mechanisms and molecules driving peritoneal metastasis. In a previous study, galectin-4 inhibition impeded peritoneal metastasis in a murine model. This study examined the glycan profiles of cell surface proteins and glycosphingolipids (GSLs) in cells with varying tumorigenic potentials to understand the intricate mechanisms underlying galectin-4-mediated regulation, particularly glycosylation. Detailed mass spectrometry analysis showed that galectin-4 knockout cells exhibit increased expression of lacto-series GSLs with ß1,3-linked galactose while showing no significant alterations in neolacto-series GSLs. We conducted real-time polymerase chain reaction (PCR) analysis to identify candidate glycosyltransferases that synthesize increased levels of GSLs. Subsequently, we introduced the candidate B3GALT5 gene and selected the clones with high expression levels. B3GALT5 gene-expressing clones showed GSL glycan profiles like those of knockout cells and significantly reduced tumorigenic ability in mouse models. These clones exhibited diminished proliferative capacity and showed reduced expression of galectin-4 and activated AKT. Moreover, co-localization of galectin-4 with flotillin-2 (a raft marker) decreased in B3GALT5-expressing cells, implicating GSLs in galectin-4 localization to lipid rafts. D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (a GSL synthase inhibitor) also affected galectin-4 localization in rafts, suggesting the involvement of GSL microdomains. We discovered that B3GALT5 plays a crucial role in regulating peritoneal metastasis of malignant gastric cancer cells by suppressing cell proliferation and modulating lipid rafts and galectin-4 via mechanisms that are yet to be elucidated.

Periconceptional omega-6 and omega-3 polyunsaturated fatty acid intake plane and postpartum depression: a nationwide birth cohort-the Japan Environment and Children's Study.

Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects on the prevention of postpartum depression, but fish, the principal source of omega-3 PUFAs, are becoming a depleted resource. We therefore examined whether lower periconceptional intake of omega-6 PUFAs, whose metabolic pathways are antagonistic to those of omega-3 PUFAs, is associated with lower prevalence of postpartum depression while simultaneously considering omega-3 PUFA intake. The participants were 92,595 mothers involved in the ongoing Japan Environment and Children's Study. Periconceptional intakes of omega-6 and -3 PUFA were measured using a food frequency questionnaire. Postpartum depression was assessed using the Edinburgh Postnatal Depression Scale. Generalized additive mixed model analysis was used to draw contour plots of postpartum depression on a plane with omega-6 and omega-3 PUFA intakes on the x- and y-axes, respectively. The adjusted prevalence ranged from 11.0% to 26.3% within the respective 1st to 99th percentile intake ranges and monotonously decreased with decreasing omega-6 PUFA intake. In contrast, the prevalence decreased with increasing omega-3 PUFA intake, but the trend almost disappeared above 2 g/day. Our results highlight the potential importance of focusing on omega-6 PUFAs as well as omega-3 PUFAs prior to conception to reduce postpartum depression.

Maternal exposure to smoking and wheezing phenotypes in children: a cohort study of the Japan Environment and Children's Study.

BACKGROUND: Previous studies have shown that prenatal maternal smoking and maternal secondhand smoke exposure during pregnancy were associated with an increased risk of wheezing and asthma development. However, few studies have examined the influence of different sources of tobacco exposure in different perinatal timeframes (preconception, prenatal, and postnatal) on wheezing phenotypes in children. Using national survey data from Japan, we investigated the effects of exposure to tobacco smoke during pregnancy on wheezing phenotypes in children before the age of 3 years. METHODS: Pregnant women who lived in the 15 regional centers in the Japan Environment and Children's Study were recruited. We obtained information on prenatal and postnatal exposure to active and secondhand smoke (SHS) and wheeze development up to 3 years of age. Multiple logistic regression analysis was performed to determine the association between tobacco smoke exposure and wheezing phenotypes in children. RESULTS: We analyzed 73,057 singleton births and identified four longitudinal wheezing phenotypes: never wheezing; early transient wheezing (wheezing by age 1 year but not thereafter); late-onset wheezing (wheezing by age 2-3 years but not beforehand); and persistent wheezing. Maternal smoking during pregnancy was significantly associated with early transient and persistent wheezing in children compared with no maternal smoking [early transient wheezing: 1-10 cigarettes per day, adjusted odds ratio (aOR) 1.43, 95% confidence interval (CI) 1.23-1.66; ≥ 11 cigarettes per day, aOR 1.67, 95% CI 1.27-2.20; persistent wheezing: 1-10 cigarettes per day, aOR 1.64, 95% CI 1.37-1.97; ≥ 11 cigarettes per day, aOR 2.32, 95% CI 1.70-3.19]. Smoking cessation even before pregnancy was also significantly associated with increased risk of early transient wheezing, late-onset wheezing, and persistent wheezing in children. Moreover, maternal exposure to SHS during pregnancy was significantly associated with increased risk of early transient and persistent wheezing compared with no such exposure. CONCLUSIONS: Maternal smoking before and throughout pregnancy was associated with wheeze development in children up to 3 years of age. It appears that smoking is detrimental compared to never smoking, regardless of whether individuals quit smoking before or after becoming aware of the pregnancy.

Maternal fermented food intake and infant neurodevelopment: The Japan Environment and Children's Study.

BACKGROUND AND OBJECTIVES: Fermented foods play an important role in establishing intestinal bacterial flora, and the composition of the intestinal bacterial flora might be associated with neurodevelopment. This study investigated the association between maternal intake of fermented foods during pregnancy and early neuro-development in offspring. METHODS AND STUDY DESIGN: Data were analyzed for 73,522 pregnant women participating in the Japan Environment and Children's Study. Their intake of four common fermented foods during pregnancy was assessed using a semi-quantitative FFQ. Neurodevelopment in their infants at 1 year of age was estimated using the Ages and Stages Questionnaires. RESULTS: Multivariable logistic regression analysis showed that maternal intake of miso soup and fermented soybeans was each associated with a significantly reduced risk of delay in infant communication skills. Maternal intake of fermented soybeans and cheese was each associated with a significantly reduced risk of delay in fine motor skills in the third and fourth quartiles. For problem-solving, preventive associations were observed with maternal intake of fermented soybeans in the second and third quartiles and with maternal intake of cheese in the third and fourth quartiles. Maternal intake of yogurt was associated with a significantly reduced risk of delay in personal-social skills in the third and fourth quartiles, while that of cheese was associated with a reduced risk in the third quartile. No reductions in risk were observed for gross motor skills. CONCLUSIONS: Our results suggest that fermented food intake during pregnancy may have beneficial associations with several areas of psychomotor development in children.

Lectin-Based Approaches to Analyze the Role of Glycans and Their Clinical Application in Disease.

Lectin-based approaches remain a valuable tool for analyzing glycosylation, especially when detecting cancer-related changes. Certain glycans function as platforms for cell communication, signal transduction, and adhesion. Therefore, the functions of glycans are important considerations for clinical aspects, such as cancer, infection, and immunity. Considering that the three-dimensional structure and multivalency of glycans are important factors for their function, their binding characteristics toward lectins provide vital information. Glycans and lectins are inextricably linked, and studies on lectins have also led to research on the roles of glycans. The applications of lectins are not limited to analysis but can also be used as drug delivery tools. Moreover, mammalian lectins are potential therapeutic targets because certain lectins change their expression in cancer, and lectin regulation subsequently regulates several molecules with glycans. Herein, we review lectin-based approaches for analyzing the role of glycans and their clinical applications in diseases, as well as our recent results.

Association of allergies in children younger than 3 years with levels of maternal intake of n-3 polyunsaturated fatty acids or fish during pregnancy: A nationwide birth cohort study, the Japan Environment and Children's Study.

BACKGROUND: N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. METHODS: Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. RESULTS: Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-<2 years of age and current eczema at 1-<2 and 0-<3 years of age. However, for food allergies, no significant associations were observed in the incidence in each group compared with the lowest intake group at any age. CONCLUSIONS: The findings suggest that n-3 PUFA intake during pregnancy may reduce the risk of developing allergic diseases and symptoms in children. In addition, consumption of n-3 PUFAs or fish is very unlikely to increase the risk of allergy given that the results are from a country with high fish consumption. TRIAL REGISTRATION: UMIN000030786 https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000030786.

Maternal Dietary Vitamin D Intake during Pregnancy Is Associated with Allergic Disease Symptoms in Children at 3 Years Old: The Japan Environment and Children's Study.

INTRODUCTION: Vitamin D plays an important role in the immune system, and postnatal vitamin D insufficiency is one of the risk factors for the development of allergic disease. However, the effects of women's vitamin D intake during pregnancy on the prevalence of allergic disease in their children remain controversial. METHODS: From the Japan Environment and Children's Study, an ongoing nationwide birth cohort study, we obtained information on maternal dietary vitamin D intake determined using a food frequency questionnaire and parent-reported allergic disease symptoms based on the ISAAC questionnaire in children at 3 years of age. RESULTS: From the full dataset of 103,060 pregnancies, we analyzed complete data for 73,309 mother-child pairs. The prevalence of current wheeze, current rhinitis, current rhino-conjunctivitis, current eczema, ever asthma, ever pollinosis, and ever atopic dermatitis in the children was 17.2%, 29.7%, 3.8%, 15.2%, 9.6%, 3.7%, and 11.0%, respectively. The ORs for current rhinitis were significantly lower in the 3rd, 4th, and 5th quintiles than in the 1st quintile after adjustment for various covariates and showed a linear association. The ORs for ever pollinosis were significantly lower in the 2nd, 3rd, and 4th quintiles than in the 1st quintile, showing a U-shaped curve. There was no clear association between mothers' dietary vitamin D intake and symptoms of asthma or atopic dermatitis in their 3-year-old children. CONCLUSION: Maternal dietary vitamin D intake during pregnancy is associated with the ORs for nasal allergies in children at the age of 3 years. Further studies are warranted to evaluate the appropriate intake dose of vitamin D for pregnant women to prevent the development of nasal allergies in their children.

Omega-3 fatty acid intake during pregnancy and risk of infant maltreatment: a nationwide birth cohort - the Japan Environment and Children's Study.

BACKGROUND: Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects, including reducing violent and aggressive behaviors, but its association with infant maltreatment is unknown. We therefore tested the hypothesis that maternal intake of omega-3 PUFAs is associated with a lower risk of infant maltreatment. METHODS: Participants were 92 191 mothers involved in the ongoing Japan Environment and Children's Study. Omega-3 PUFA intake during pregnancy was measured using a food frequency questionnaire. Infant maltreatment was assessed using a self-reported questionnaire administered at 1 and 6 months postpartum. RESULTS: Analysis using the lowest quintile of intake as a reference revealed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cases of 'hitting' decreased as quintiles increased, with values for the second to fifth quintiles of 0.93 (95% CI 0.77-1.13), 0.79 (95% CI 0.64-0.97), 0.78 (95% CI 0.64-0.96), and 0.72 (95% CI 0.59-0.89), respectively. Adjusted ORs (95% CIs) for 'shaking very hard' at 6 months were 0.87 (0.73-1.04), 0.81 (0.67-0.97), 0.73 (0.61-0.89), and 0.78 (0.65-0.94), respectively. Adjusted ORs for 'leaving alone at home' for the second to fifth quintiles were 0.92 (0.87-0.98), 0.91 (0.86-0.97), 0.94 (0.88-0.99), and 0.85 (0.80-0.90), respectively. CONCLUSIONS: Higher maternal intake of omega-3 PUFAs during pregnancy was associated with fewer cases of hitting and violent shaking and leaving the child alone at home, implying a lower risk of infant maltreatment. Our results indicate the potential applicability of omega-3 PUFAs in reducing infant maltreatment.

Association of soap use when bathing 18-month-old infants with the prevalence of allergic diseases at age 3 years: The Japan Environment and Children's Study.

BACKGROUND: Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. METHODS: Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18-month-old infants and the prevalence of allergic diseases when they were aged 3 years. RESULTS: Data for 74,349 children were analyzed. Most 18-month-old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05-1.34; sometimes: aOR 1.72, 95% CI 1.46-2.03; seldom: aOR 1.99, 95% CI 1.58-2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. CONCLUSIONS: Frequent soap use when bathing 18-month-old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well-designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases.

Suppression of galectin-4 attenuates peritoneal metastasis of poorly differentiated gastric cancer cells.

BACKGROUND: Peritoneal dissemination, most often seen in metastatic and/or recurrent gastric cancer, is an inoperable condition that lacks effective treatment. The use of molecular targeted drugs is also limited; therefore, identifying novel therapeutic targets and improving our understanding of this metastatic cancer are an urgent requirement. In this study, we focused on galectin-4, which is specifically expressed in poorly differentiated cells with high potential for peritoneal dissemination. METHODS: We knocked out the galectin-4 gene in NUGC4 cells using CRISPR/Cas9-mediated genome editing. Proliferation and peritoneal cancer formation in knockout cells were compared with those in wild-type and galectin-4 re-expressing cells. Western blotting and proximity ligation assays were performed to identify associated molecules affected by the expression of galectin-4. The effect of galectin-4 knockdown on cell proliferation and peritoneal metastasis was studied using a specific siRNA. Expression of galectin-4 in peritoneal metastatic tumors from 10 patients with gastric cancer was examined by immunohistochemistry. RESULTS: Suppression of galectin-4 expression reduced proliferation and peritoneal metastasis of malignant gastric cancer cells. Galectin-4 knockout and knockdown reduced the expression of activated c-MET and CD44. Galectin-4 was found to interact with several proteins on the cell surface, including CD44 and c-MET, via its carbohydrate-binding ability. Immunohistochemistry showed galectin-4 expression in peritoneal metastatic tumor cells in all patients examined. CONCLUSIONS: We clarified the role of galectin-4 in the development of peritoneal dissemination of poorly differentiated gastric cancer cells. Our data highlight the diagnostic and therapeutic potential of galectin-4 in the peritoneal dissemination of gastric cancer.

Effect Estimate of Time-varying Social Support and Trust on the Physical and Mental Health of Mothers at 2.5 Years Postpartum: The Japan Environment and Children's Study (JECS).

BACKGROUND: Many epidemiological studies have reported the association between various social factors and health status in mothers during and after pregnancy. However, little is known about their joint and longitudinal impact. We examined the association of lack of social support and trust during pregnancy and at 2.5 years postpartum with health status in mothers. METHODS: To adequately address time-varying exposure, marginal structural models were fitted to a pseudopopulation constructed using inverse probability weighting. The model included records of 90,071 mothers participating in the Japan Environment and Children's Study. Social support and trust were measured using a 9-item questionnaire (Q1-9). Mental and physical health were measured using Mental and Physical Component Summary scores from the 8-item Short-Form Health Survey. RESULTS: For the Mental Component Summary, the magnitude of the effect estimate was largest when participants lacked close friends/neighbors (Q4) at only 2.5 years postpartum (effect estimate, -6.23), followed by a lack in emotional support (Q2) at the same time point (effect estimate, -4.94). For the Physical Component Summary, effect estimates were negligible. The magnitude of the effect estimates of lack of social support and trust tended to be larger when there was a lack at only 2.5 years postpartum than at both time points. CONCLUSION: These findings suggest that, after childbirth, a loss in social support, particularly in an emotional aspect, carries high risk, especially for mental health. Our results highlight the importance of supporting mothers for more than a few years after pregnancy.

Longitudinal study of the relationship between number of prior miscarriages or stillbirths and changes in quality of life of pregnant women: the Japan Environment and Children's Study (JECS).

BACKGROUND: Although a history of miscarriage or stillbirth has been reported to negatively affect quality of life (QOL) during the subsequent pregnancy, the association between the number of previous miscarriages or stillbirths and QOL, as well as trends in QOL during pregnancy, has not been clarified. This study sought to determine this association during early and mid- to late pregnancy. METHODS: Data from 82,013 pregnant women who participated in the Japan Environment and Children's Study (JECS) from January 2011 to March 2014 were analyzed. In early and mid/late pregnancy, participants completed questionnaires and QOL was assessed using the Physical and Mental Component Summary (PCS and MCS, respectively) scores from the 8-item Short-Form Health Survey (SF-8). The pregnant women were divided into four groups according to number of previous miscarriages or stillbirths (0, 1, 2, and ≥ 3), and the PCS and MCS scores in early pregnancy and mid/late pregnancy were compared between group 0 and groups 1, 2, and ≥ 3. Generalized linear mixed models were used for analysis. RESULTS: PCS score in early pregnancy was lower in group 1 (ß = - 0.29, 95% confidence interval [CI] - 0.42 to - 0.15), group 2 (ß = - 0.45, 95% CI - 0.73 to - 0.18), and group ≥ 3 (ß = - 0.87, 95% CI - 1.39 to - 0.35) than in group 0. Group 1 and group ≥ 3 showed a trend for increased PCS score during pregnancy (ß = 0.22, 95% CI 0.07 to 0.37 and ß = 0.75, 95% CI 0.18 to 1.33, respectively) compared with group 0. CONCLUSIONS: PCS score in early pregnancy was lower with a more frequent history of miscarriage or stillbirth. However, in terms of changes in QOL during pregnancy, pregnant women with a history of miscarriage or stillbirth showed greater increases in PCS score during mid/late pregnancy than pregnant women with no history of miscarriage or stillbirth.

Season of birth and atopic dermatitis in early infancy: results from the Japan Environment and Children's Study.

BACKGROUND: Atopic dermatitis (AD) is reported to be more prevalent in children who were born in autumn than in spring. Here, we investigated how early the association between season of birth and eczema or AD can be observed in the postnatal period. We also examined whether specific prevalence outcomes for infant eczema and AD differed according to sex and maternal history of allergic disease in a large Japanese cohort. METHODS: Using data of 81,615 infants from the Japan Environment and Children's Study, we examined the associations of birth month or season with four different outcomes-eczema at 1 month, 6 months, and 1 year of age and physician-diagnosed AD up to 1 year of age-using multiple logistic regression analysis. We also analyzed the effect of maternal history of allergic disease on these outcomes stratified by infant sex. RESULTS: The risk of eczema at 1 month was highest in infants born in July. In contrast, infants born in autumn had higher risks of eczema at 6 months (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 2.10-2.30) and at 1 year (aOR, 1.08; 95% CI, 1.02-1.14) and of physician-diagnosed AD up to 1 year of age (aOR, 1.33; 95% CI, 1.20-1.47) compared with infants born in spring. Eczema and AD were more prevalent in infants with a maternal history of allergic disease, particularly boys. CONCLUSIONS: Our findings suggest that the prevalence of AD is associated with the season of observation. Eczema is prevalent in infants born in autumn, and this phenomenon was observed in infants as young as 6 months old. The risk associated with being born in autumn was particularly clear in boys with a maternal history of allergic disease. TRIAL REGISTRATION: UMIN000030786.

Galectin-4 Is Involved in the Structural Changes of Glycosphingolipid Glycans in Poorly Differentiated Gastric Cancer Cells with High Metastatic Potential.

Gastric cancer with peritoneal dissemination is difficult to treat surgically, and frequently recurs and metastasizes. Currently, there is no effective treatment for this disease, and there is an urgent need to elucidate the molecular mechanisms underlying peritoneal dissemination and metastasis. Our previous study demonstrated that galectin-4 participates in the peritoneal dissemination of poorly differentiated gastric cancer cells. In this study, the glycan profiles of cell surface proteins and glycosphingolipids (GSLs) of the original (wild), galectin-4 knockout (KO), and rescue cells were investigated to understand the precise mechanisms involved in the galectin-4-mediated regulation of associated molecules, especially with respect to glycosylation. Glycan analysis of the NUGC4 wild type and galectin-4 KO clones with and without peritoneal metastasis revealed a marked structural change in the glycans of neutral GSLs, but not in N-glycan. Furthermore, mass spectrometry (MS) combined with glycosidase digestion revealed that this structural change was due to the presence of the lacto-type (ß1-3Galactosyl) glycan of GSL, in addition to the neolacto-type (ß1-4Galactosyl) glycan of GSL. Our results demonstrate that galectin-4 is an important regulator of glycosylation in cancer cells and galectin-4 expression affects the glycan profile of GSLs in malignant cancer cells with a high potential for peritoneal dissemination.

Change in cholesterol level during pregnancy and risk of postpartum depressive symptoms: the Japan Environment and Children's Study (JECS).

OBJECTIVE: Women with postpartum depressive symptoms (PDS) are at higher risk of postpartum depression (PPD) and require further assessment. Emerging evidence indicates a relationship between the total cholesterol (TC) level of blood and PPD but the results are inconsistent. In this study, we investigated the possible association of change in serum TC levels during pregnancy with the risk of PDS in a Japanese population. METHODS: We analyzed complete data on questionnaire responses and serum lipid profiles of pregnant women from 12 datasets obtained from the Japan Environment and Children's Study (n = 61,585 to n = 72,406; 103,063 pregnancies in total). TC was measured at 3 time points-during early pregnancy, during mid-late pregnancy, and after delivery-and we calculated changes in TC in 3 ways: by subtracting early pregnancy from mid-late pregnancy, subtracting mid-late pregnancy from delivery, and subtracting early pregnancy from delivery. These 6 factors were used as predictors to estimate the risk of PDS at 1 and 6 months after delivery. RESULTS: In multivariable logistic regression analysis, point serum cholesterol level did not predict PDS at any time point except for during mid-late pregnancy in the second quintile, indicating an increased risk at 6 months. As for change in TC levels, subtracting mid-late pregnancy from delivery and early pregnancy from delivery showed significant risk reduction for PDS at 1 month. A significant risk reduction was also found for subtracting early pregnancy from mid-late pregnancy and early pregnancy from delivery at 6 months. CONCLUSIONS: Increased cholesterol level during pregnancy is associated with reduced risk of PDS.

Association between mothers' fish intake during pregnancy and infants' sleep duration: a nationwide longitudinal study-The Japan Environment and Children's Study (JECS).

PURPOSE: N-3 polyunsaturated fatty acids (n-3 PUFAs), which are an important nutrient for humans, are particularly essential to the growth and development of the central nervous system (CNS) in fetuses and infants. Consequently, sufficient n-3 PUFA intake by mothers during pregnancy is considered to contribute to CNS development in their infants. CNS development is known to be associated with sleep, but no large epidemiological studies have yet confirmed that n-3 PUFA intake during pregnancy is associated with infants' sleep. METHODS: After exclusion and multiple imputation from a dataset comprising 104 065 records from the Japan Environment and Children's Study (JECS), we examined 87 337 mother-child pairs for the association between mothers' fish and n-3 PUFA intakes and risk of their infants sleeping less than 11 h at 1 year of age. RESULTS: Multiple logistic regression analysis with the lowest quintile used as a reference revealed odds ratios for the second through fifth quintiles of 0.81 (95% confidence interval [95% CI] 0.76-0.87), 0.81 (95% CI 0.76-0.87), 0.78 (95% CI 0.72-0.84), and 0.82 (95% CI 0.76-0.88) for fish intake (p for trend < 0.001) and 0.90 (95% CI 0.84-0.97), 0.88 (95% CI 0.81-0.94), 0.88 (95% CI 0.82-0.95), and 0.93 (95% CI 0.86-0.998) for n-3 PUFA intake (p for trend = 0.04). CONCLUSIONS: Low fish intake during pregnancy may increase the risk of infants sleeping less than 11 h at 1 year of age. This relationship may have been mediated by maternal n-3 PUFA intake and infant neurodevelopment, but further evidence from interventional and other studies is needed to determine the appropriate level of fish intake during pregnancy. TRIAL REGISTRATION: The Japan Environment and Children's Study, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035091 (Registration no. UMIN000030786).

Association between maternal fermented food consumption and child sleep duration at the age of 3 years: the Japan Environment and Children's Study.

BACKGROUND: Using cohort data from the Japan Environment and Children's Study (JECS), we previously reported that the risk of sleep deprivation in 1-year-old children was reduced with a higher maternal intake of fermented foods, particularly miso. The present study, which evaluates children from the same cohort at 3 years of age, is a continuation of that work. METHODS: After applying exclusion criteria to 104,062 records in the JECS dataset, we evaluated 64,200 mother-child pairs in which the child was 3 years old. We examined the association of the dietary intake of fermented foods during pregnancy with child sleep duration < 10 h at the age of 3 years. RESULTS: Multivariable logistic regression analysis with the lowest quartile used as a reference revealed adjusted odds ratios (95% confidence intervals) for the second through fourth quartiles of 0.98 (0.90-1.06), 0.93 (0.85-1.01), and 0.85 (0.78-0.94) for cheese intake. CONCLUSIONS: The consumption of fermented foods during pregnancy is associated with reduced risk of sleep deprivation in 3-year-old children, albeit in a limited way.

Dietary intake of yogurt and cheese in children at age 1 year and sleep duration at age 1 and 3 years: the Japan Environment and Children's Study.

BACKGROUND: We previously reported that 1-year-old infants born to mothers who regularly consumed fermented food during pregnancy had a lower risk of sleep deprivation. However, it is not known if these positive effects are enhanced when infants themselves eat fermented foods or the long-term effects of such consumption. In this study, we examined the association between the frequency of fermented food intake during the child's weaning period and sleep deprivation at age 1 and 3 years. METHODS: This birth cohort study used data from a nationwide, government-funded study called the Japan Environment and Children's Study (JECS), covering 65,210 mother-child pairs. We examined the association between infants' consumption of fermented foods at 1 year of age and sleep deprivation at 1 and 3 years of age. RESULTS: There was no association between yogurt or cheese intake and sleep duration at age 1; at age 3, there was no group difference, although a trend test showed that yogurt intake at age 1 was significantly associated with sleep duration at age 3. There was also no association between the frequency of cheese intake and inadequate sleep duration at age 3. CONCLUSION: Frequency of children's yogurt and cheese intake at age 1 was not associated with sleep duration at age 1 or 3. However, a trend test showed a significant association between the frequency of yogurt intake at age 1 and sleep duration at age 3.

Association of cesarean birth with prevalence of functional constipation in toddlers at 3 years of age: results from the Japan Environment and Children's Study (JECS).

BACKGROUND: The association between delivery mode and subsequent development of diseases is a growing area of research. Cesarean delivery affects the diversity of the microbiota in the infant gut, which may be associated with gastrointestinal disorders, including functional constipation, in infants. In this study, we investigated the association between delivery mode and prevalence of functional constipation in 3-year-old Japanese toddlers. METHODS: This study used data from the Japan Environment and Children's Study, an ongoing nationwide birth cohort study. We analyzed 71,878 toddler-mother pairs. The presence of functional constipation was determined according to the Rome III diagnostic criteria. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. RESULTS: The prevalence of functional constipation in 3-year-old Japanese toddlers was estimated to be 12.3%. Logistic regression analysis revealed that the prevalence of functional constipation was higher in toddlers born by cesarean delivery (13.1%) compared with those born by vaginal delivery (12.1%), independent of 22 confounders (adjusted odds ratios = 1.064, 95% confidence interval = 1.004-1.128). CONCLUSIONS: We determined the prevalence of functional constipation in 3-year-old Japanese toddlers and found that delivery mode was associated with the prevalence of functional constipation in Japanese toddlers.

Maternal exposure to smoking and infant's wheeze and asthma: Japan Environment and Children's Study.

BACKGROUND: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. METHODS: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. RESULTS: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1-10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270-1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341-2.078; asthma: 1-10 cigarettes/day: aOR 1.389, 95% CI 1.087-1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045-2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083-1.256; asthma: aOR 1.258, 95% CI 1.075-1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739-2.317; asthma: aOR 1.995, 95% CI 1.528-2.605). CONCLUSIONS: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.