Early childhood neurodevelopmental milestones in children with allergic diseases: the Japan Environment and Children's Study (JECS).

This study investigated the potential link between early childhood allergic diseases and neurodevelopmental milestone attainment during the first 3 years of life. Utilizing data from a large-scale prospective birth cohort study in Japan, encompassing 87,986 children, we examined physician-diagnosed and caregiver-reported allergic conditions, including atopic dermatitis (AD), asthma, and food allergy (FA). Neurodevelopmental milestones were assessed using the Ages and Stages Questionnaires at 1, 1.5, 2, 2.5, and 3 years of age. Stabilized inverse probability-weighted generalized estimating equation models were employed to estimate odds ratios (ORs). Our analysis revealed no significant association of AD and asthma with delay in communication, gross motor, fine motor, problem-solving, and personal-social skills during the initial 3 years of life. However, children with FA showed an increased likelihood of experiencing gross motor delay compared with that shown by those without FA (weighted adjusted OR: 1.14). Despite this, no significant association of FA with other developmental domains was observed. Early childhood allergies may not influence neurodevelopmental delays. However, there is a potential association between FA and delays, specifically in gross motor skills, that warrants routine developmental monitoring and additional investigations.

Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero.

Importance: Corticosteroids and ß2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear. Objective: To investigate the association between timing of in utero exposure to corticosteroids and ß2-adrenergic agonists and offspring neurodevelopmental milestones during the first 3 years of life. Design, Setting, and Participants: This cohort study obtained data from the Japan Environment and Children's Study, an ongoing birth cohort study conducted in collaboration with 15 Regional Centers across Japan. Participants were mother-offspring pairs who were recruited between January 1, 2011, and March 31, 2014. Data were analyzed between January and February 2023. Exposure: Corticosteroids and ß2-adrenergic agonists were the exposure of interest. Timing of corticosteroid and ß2-adrenergic agonist exposure included early pregnancy (weeks 0-12), mid- to late pregnancy (weeks >12), and both stages of pregnancy. Main Outcomes and Measures: Offspring neurodevelopmental milestones (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition, at 6, 12, 18, 24, 30, and 36 months. Results: In total, 91 460 mother-offspring pairs were analyzed. Among mothers, the mean (SD) age at delivery was 31.20 (5.05) years. Among offspring, 46 596 (50.9%) were males and 44 864 (49.1%) were females, of whom 66.4% had a gestational age of 39 to 41 weeks. During early, mid- to late, and both stages of pregnancy, 401 (0.4%), 935 (1.0%), and 568 (0.6%) offspring, respectively, were exposed to corticosteroids, whereas 170 (0.2%), 394 (0.4%), and 184 (0.2%), respectively, were exposed to ß2-adrenergic agonists. No association of corticosteroid exposure during early, mid- to late, and both stages of pregnancy with all 5 neurodevelopmental milestones was found. Similarly, no association between ß2-adrenergic agonist use during early pregnancy and all 5 neurodevelopmental milestones was observed. An association was found between ß2-adrenergic agonist exposure during mid- to late pregnancy and delayed personal-social skills (adjusted odds ratio, 1.48; 95% CI, 1.01-2.32; P = .045). Conclusions and Relevance: Results of this study found no association between in utero corticosteroid and ß2-adrenergic agonist exposure and offspring neurodevelopmental outcomes, regardless of the timing of exposure. Despite the limitations and low power of the study, the findings suggest that corticosteroids and ß2-adrenergic agonists are safe for pregnant individuals with asthma and the neurodevelopment of their offspring.

Association between shift work in early pregnancy, snacking, and inappropriate weight gain during pregnancy: The Japan Environment and Children's Study.

OBJECTIVES: This study aimed to investigate the relationship between night shifts and snacking behaviors during pregnancy using Japanese maternal-infant longitudinal data from a large-scale study. METHODS: This study used the Japan Environment and Children's Study dataset jecs-ta-20190930, released in October 2019. After simple analysis using analysis of variance and multiple comparisons, crude odds ratios (cOR) and adjusted odds ratios (aORs) were calculated. To evaluate eating habits, we examined habitual fast food and snacks (e.g., potato chips, corn puffs and tortilla chips) consumption, midnight snacks, and regular missing breakfast. RESULTS: There was no significant association between inappropriate weight gain during pregnancy and night shift work in early pregnancy. The aOR for consuming snacks more than once a week after noticing pregnancy for shift workers was 1.34 (95% confidence interval 1.27-1.41; p < 0.001) compared with worker without night shiftwork. The aOR for shift workers consuming fast food more than three times a week during pregnancy was 1.40 (95% confidence interval 0.79-2.33; p > 0.05). CONCLUSIONS: Pregnant night shift workers did not show excessive weight gain but had an increased frequency of consumption of snack foods compared with pregnant dayshift workers.

Weight-loss behaviors before pregnancy associate with increased risk of postpartum depression from the Japan Environment and Children's Study.

No studies showed the association between weight-loss behaviors before pregnancy and postpartum depression (PPD). We analyzed data from the nation-wide birth cohort study, the Japan Environment and Children's Study. Self-administrated questionnaires answered by 62,446 women was analyzed using logistic regression analysis. PPD was assessed using the Edinburgh Postnatal Depression Scale at 1 month after delivery. Women using at least one weight-loss method had higher risk of PPD than women using no weight-loss methods [women without antenatal psychological distress according to Kessler 6-Item Psychological Distress score: adjusted odds ratio (aOR) 1.318, 95% confidence interval (CI) 1.246-1.394; women with antenatal psychological distress: aOR 1.250, 95% CI 0.999-1.565]. Using extremely unhealthy weight-loss methods was associated with PPD compared with no use of each weight-loss method (vomiting after eating: aOR 1.743, 95% CI 1.465-2.065; smoking: aOR 1.432, 95% CI 1.287-1.591; taking diet pills: aOR 1.308, 95% CI 1.122-1.520). The association between weight-loss behaviors and PPD varied according to pre-pregnancy BMI. In normal-weight women, the weight-loss method score, which indicates the degree of weight-loss method use, was associated with PPD. These results indicate using weight-loss methods before pregnancy is associated with an increased risk of PPD in Japanese women.

Association between frequency of going out and mild cognitive impairment in community-dwelling older adults: a pilot study in frailty prevention groups.

BACKGROUND: Clarifying the role of physical limitations in the relationship between frequency of going out and mild cognitive impairment (MCI) may be useful in supporting early detection and prevention of MCI. However, few studies have explored relatively active populations that are continuously active throughout the year. This study aimed to determine the relationship between frequency of going out and MCI among non-homebound older adults who participated in group activities to prevent frailty. METHODS: This prospective cohort study used frequency of going out as the exposure and MCI as the outcome. The Touch Panel-type Dementia Assessment Scale and questionnaires about daily life were completed by 153 community-dwelling older adults aged ≥65 years participating in frailty prevention groups in a rural town. The baseline survey was conducted from December 2017 to March 2018 and analysed cross-sectionally. Follow-up surveys were conducted at 1- and 2-years and analysed longitudinally. RESULTS: Univariate and binomial logistic regression analyses at baseline showed no association between MCI and frequency of going out in older adults with physical limitations. However, there was a significant association in older adults without physical limitations. A binomial logistic regression analysis of the frequency of going out at baseline and cognitive function at the 2-year follow-up showed no association between MCI and frequency of going out in older adults with physical limitations, but there was a significant association in those without physical limitations. CONCLUSION: Our results suggest that frequency of going out may not be a useful indicator of MCI in older adults with physical limitations, although low frequency of going out may be an indicator of MCI in older adults without physical limitations.

Association between prenatal cadmium exposure and child development: The Japan Environment and Children's study.

Cadmium is a heavy metal that can be found in soil, air, food, and water. Cadmium has toxic effects on the kidneys, bones, and respiratory system. Prenatal exposure to cadmium has been found to affect the mental development of children, but inconsistent results have been found in different studies. Therefore, it is unknown that prenatal cadmium exposure associated with child development after birth. To elucidate whether cadmium affect the child development or not, we analyzed nation-wide cohort study data, the Japan Environment and Children's Study. Prenatal cadmium concentrations in blood from mothers in the second or third trimester were determined by inductively coupled plasma mass spectrometry. Child development was evaluated using "Ages and Stages" questionnaires. The association between cadmium and child development were investigated by performing logistic regression analyses, multinomial logistic regression analyses and generalized linear mixed model using the child development parameters as dependent variables and the cadmium concentrations in maternal blood as the independent variable. There were significant associations between the cadmium concentration and child development at 6 months, 1 year, and 1.5 years after birth. However, the effect had disappeared at 2 years after birth or later. The number of developmental delays was positively associated with the cadmium concentration after adjusting individual difference. The results indicate that prenatal exposure affects child development, but the effect decreases with age.

The Association Between Maternal Shaking Behavior and Inappropriate Infant Parenting: The Japan Environment and Children's Study.

Background: Although many studies have identified risk factors for maternal shaking behavior, it is unknown whether mothers who have shaken their infants repeat shaking behavior or show other inappropriate parenting behaviors. Using data from the Japan Environment and Children's Study (JECS) birth cohort study, we investigated the associations between continuous shaking behavior and the associations between shaking behavior and other inappropriate parenting behaviors. Methods: JECS data starting from 2011 were used. Logistic regression was used to perform a cross-sectional analysis. The explanatory variable was shaking behavior and the dependent variables were leaving the infant home alone and hitting the infant (both at 1 month postpartum), and non-vaccination and infant burns (both at 6 months postpartum). A longitudinal analysis using logistic regression was also performed; here the explanatory variable was shaking behavior at 1 month postpartum and the dependent variables were shaking behavior, non-vaccination of the infant, and infant burns (all at 6 months postpartum). Results: In this study, 16.8% and 1.2% of mothers reported shaking behavior at 1 month and 6 months postpartum, respectively. Mothers who shook their infants at 1 month postpartum were approximately five times more likely to shake them at 6 months postpartum compared with mothers who had not shown previous shaking behavior (OR = 4.92, 95% CI [4.22, 5.73], p < 0.001). In Cross-sectional study, there were associations between shaking behavior and inappropriate parenting behavior such as hitting the infant and infant burns. Conclusion: The findings suggest that mothers who report early shaking behavior tend to subsequently repeat this behavior, and that shaking behavior may be associated with other inappropriate parenting behaviors.

Short- and Long-Term Effects of Drought on Selected Causes of Mortality in Northern Bangladesh.

Drought has exacerbated morbidity and mortality worldwide. Here, a time series study was conducted in northern Bangladesh to evaluate the impact of drought on selected causes of mortality during 2007-2017. Rainfall and temperature data from six meteorological stations were used to analyze drought and non-drought periods and to categorize mild, moderate, severe, and extreme drought based on the 3-month and 12-month Standardized Precipitation Index (SPI) and Standardized Precipitation Evaporation Index (SPEI). A generalized linear model with Poisson regression with log link, a negative binomial with log link, and a zero-inflated Poisson model were used to determine associations between drought severity and mortality. The SPI and SPEI produced slightly different analysis results. Compared with the SPEI, the SPI showed a stronger and more sensitive correlation with mortality. The relative risk for respiratory disease mortality was high, and Saidpur was the most vulnerable area. Health care expenditure was negatively associated with mortality. High temperatures during the drought period were associated with suicide-related mortality in Rajshahi. The impact of drought on mortality differed with small changes in climate. The findings of this study improve our understanding of the differences between the two most used drought indicators and the impact of drought on mortality.

Maternal folic acid supplement use/dietary folate intake from preconception to early pregnancy and neurodevelopment in 2-year-old offspring: the Japan Environment and Children's Study.

We evaluated the association between maternal prenatal folic acid supplementation/dietary folate intake and motor and cognitive development in 2-year-old offspring using data from the Japan Environment and Children's Study database. Neurodevelopment of 2-year-old offspring were evaluated using the Kyoto Scale of Psychological Development 2001. In total, data of 3839 offspring were analysed. For folic acid supplementation, a multiple regression analysis showed that offspring of mothers who started using folic acid supplements before conception had a significantly lower developmental quotient (DQ) in the postural-motor DQ area than offspring of mothers who did not use them at any time throughout their pregnancy (partial regression coefficient (B) -2·596, 95 % CI -4·738, -0·455). Regarding daily dietary folate intake from preconception to early pregnancy, a multiple regression analysis showed that the group with ≥ 200 µg had a significantly higher DQ in the language-social area than the group with <200 µg. The DQ was higher in the ≥ 400 µg group (B 2·532, 95 % CI 0·201, 4·863) than the 200 to <400 µg group (B 1·437, 95 % CI 0·215, 2·660). In conclusion, our study showed that maternal adequate dietary folate intake from preconception to early pregnancy has a beneficial association with verbal cognition development in 2-year-old offspring. On the other hand, mothers who started using folic acid supplements before conception had an inverse association with motor development in 2-year-old offspring. There were no details on the amount of folic acid in the supplements used and frequency of use. Therefore, further studies are required.

The Effects of Drought Severity and Its Aftereffects on Mortality in Bangladesh.

BACKGROUND: Drought has been a considerable problem for many years in northern Bangladesh. However, the health impacts of drought in this region are not well understood. METHODS: This study analyzed the impact of drought duration and severity on select causes of mortality in northern Bangladesh. Rainfall data from three meteorological stations (Rangpur, Dinajpur and Nilphamari) in northern Bangladesh were used to assess drought and non-drought periods, and the Standardized Precipitation Index was used to categorize mild, moderate, severe, and extreme drought. Mortality data from 2007 to 2017 for the three areas were collected from the Sample Vital Registration System, which is a survey of 1 million people. The generalized linear model with Poisson regression link was used to identify associations between mortality and the drought severity and 1-month preceding SPI. RESULTS: Only severe and extreme drought in the short-term drought periods affected mortality. Long-term drought was not associated with natural cause mortality in Rangpur and Nilphamari. In Dinajpur, mild and moderate drought was associated with circulatory- and respiratory-related mortality. CONCLUSION: The impact of drought on mortality varied by region. This study improves our understanding of how droughts affect specific causes of mortality and will help policy makers to take appropriate measures against drought impacts on selected cause of mortality. Future research will be critical to reduce drought-related risks of health.

The Effect of Minimum and Maximum Air Temperatures in the Summer on Heat Stroke in Japan: A Time-Stratified Case-Crossover Study.

An increase in the global surface temperature and changes in urban morphologies are associated with increased heat stress especially in urban areas. This can be one of the contributing factors underlying an increase in heat strokes. We examined the impact of summer minimum air temperatures, which often represent nighttime temperatures, as well as a maximum temperature on a heat stroke. We collected data from the records of daily ambulance transports for heat strokes and meteorological data for July and August of 2017-2019 in the Tottori Prefecture, Japan. A time-stratified case-crossover design was used to determine the association of maximum/minimum air temperatures and the incidence of heat strokes. We used a logistic regression to identify factors associated with the severity of heat strokes. A total of 1108 cases were identified with 373 (33.7%) calls originating in the home (of these, 59.8% were the age of ≥ 75). A total of 65.8% of cases under the age of 18 were related to exercise. Days with a minimum temperature ≥ 25 °C had an odds ratio (95% confidence interval) of 3.77 (2.19, 6.51) for the incidence of an exercise-related heat stroke (reference: days with a minimum temperature < 23 °C). The odds ratio for a heat stroke occurring at home or for calls for an ambulance to the home was 6.75 (4.47, 10.20). The severity of the heat stroke was associated with older age but not with air temperature. Minimum and maximum air temperatures may be associated with the incidence of heat strokes and in particular the former with non-exertional heat strokes.

Plasma Oxytocin Concentrations During and After Gestation in Japanese Pregnant Women Affected by Anxiety Disorder and Endometriosis.

BACKGROUND: Oxytocin has a key role in mother-infant bonding, maternal care, social interaction, and stress-related psychiatric disorders. However, the factors determining oxytocin concentrations during and after pregnancy such as medical history related to nursing or parental behavior are unknown. To elucidate these, we analyzed the relationships between oxytocin concentrations during and after pregnancy, and medical history assessed in the Japan Environment and Children's Study (JECS). METHODS: We then selected the pregnant women with a medical history of anxiety disorder and endometriosis as cases and pregnant women without medical history as controls adjusting the cohort for age and parity for a nested case-control study, after which 162 women remained for analysis. We evaluated 162 pregnant women from JECS using answers provided in a questionnaire and by measuring plasma oxytocin concentration by ELISA during the first (T1) and second (T2) trimesters of pregnancy, and after childbirth (T3). RESULTS: Oxytocin concentration increased in a time dependent manner, consistent with previous reports. There were weak negative correlations between oxytocin concentration at T1 and the mother's age and height, but no correlation with other factors. The mean oxytocin concentrations of pregnant women with a history of an anxiety disorder (n = 7) and endometriosis (n = 13) were significantly lower than those of pregnant women with no such history at T2 and T3. CONCLUSION: These results suggest that oxytocin concentrations during and after pregnancy were affected by a past history of anxiety disorder and endometriosis. This is the first study of the relationship between oxytocin concentration and endometriosis. To elucidate the molecular mechanisms, further study is needed.

The Influence of Income and Livelihood Diversification on Health-Related Quality of Life in Rural Ethiopia.

Examining health-related quality of life (HRQOL) in a rural setting can be beneficial for improving rural household policies and fostering public health promotion. The objective of this study was to measure the HRQOL and associated socioeconomic characteristics as well as test the reliability of the Amharic version of SF-8 (eight-item short form of HRQOL survey). A cross-sectional study was employed in three agroecologically different sites in rural Ethiopia, involving 270 household heads (218 male and 52 female) with a mean age ± standard deviation of 49 ± 12.88 years. The survey material consisted of a structured questionnaire for socioeconomic characteristics and SF-8 for HRQOL. The mean physical and mental component summary score of the whole sample was 30.50 ± 12.18 and 34.40 ± 7.26, respectively, well underneath the instrument average of 50. The SF-8 items showed excellent internal consistency in terms of both Cronbach's α coefficients and item-total correlation. In stepwise multiple linear regression, the low-income group had worse self-perceived physical health than the higher-income groups. Likewise, a diversified livelihood had a profound influence on positive self-perceived physical health. These findings imply that developing and distributing wide-ranging socioeconomic and public health policies is crucial for effective health promotion in rural communities.

Association between dental caries indicators and serum glycated hemoglobin-levels among patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) with poor glycemic control is often linked to oral manifestations. This study aimed to investigate the association between dental caries (DC) and glycated hemoglobin (HbA1c) among patients with type 2 DM (T2DM). A health center-based cross-sectional study was conducted comprising 91 eligible patients with T2DM (21 males and 70 females) with a mean age (± standard deviation) of 61.49 ± 9.71 years. A structured interview, screening for DM-related factors, and oral examination were performed. Serum HbA1c levels were used as an index for glycemic control. A comparison between patients with controlled T2DM, i.e., HbA1c ≤7.0% (n = 46), and uncontrolled T2DM, i.e., HbA1c >7.0% (n = 45), showed significant differences in mean values of decayed teeth (DT) (P = 0.045); missing teeth (P = 0.002); and decayed, missing, and filled teeth (DMFT) index (P < 0.001). Results of multiple linear regression analysis revealed that the number of DT was significantly correlated with serum HbA1c levels (95% confidence interval [CI] 0.173 to 0.972, P = 0.005). Furthermore, DMFT index values and serum HbA1c levels (95% CI 0.532 to 1.658, P < 0.001) showed a significant association. This study provides substantial evidence on the association between DC indicators and serum HbA1c levels.

Impact of Maximum Air Temperature on Ambulance Transports Owing to Heat Stroke During Spring and Summer in Tottori Prefecture, Japan: A Time-stratified Case-crossover Analysis.

BACKGROUND: The frequency and intensity of hot weather have increased. In Japan, there have been many studies of the relationship between ambulance transports owing to heat stroke (ATHS) and high air temperature in the summer season. However, there have been very few reports focusing on ATHS in spring. Therefore, we investigated the effect of the maximum air temperature on ATHS not only in summer but also in spring, to help with development of effective measures to prevent heat stroke. METHODS: We obtained daily ATHS and meteorological data from April to September in 2017 in Tottori Prefecture. We used a time-stratified case-crossover method for data analysis. RESULTS: A total 382 cases of ATHS were identified from April to September in 2017 in Tottori. The number of cases was highest in July, followed by August and May. Maximum air temperature was significantly linked to ATHS. The risk of ATHS was increased 1.13 times when maximum air temperature rose by 1°C. In summer, the risk on extremely hot days (maximum air temperature ≥ 35°C) increased by 5.55 times or more compared with that on days below 30 °C (< 30°C). The risk was approximately four times greater on hot days (≥ 30°C and < 35°C) than that on relatively cooler days (< 30°C) during the spring months of April through May. CONCLUSION: Maximum air temperature was significantly linked to ATHS. It is necessary to pay particular attention to heat stroke prevention not only on extremely hot days in summer but also on hot days in the spring.

Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone.

BACKGROUND INFORMATION: Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. RESULTS: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. PKC activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, PKCα directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. CONCLUSIONS: Our results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone.

Ca(2+)-independent syntaxin binding to the C(2)B effector region of synaptotagmin.

Although synaptotagmin I, which is a calcium (Ca(2+))-binding synaptic vesicle protein, may trigger soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated synaptic vesicle exocytosis, the mechanisms underlying the interaction between these proteins remain controversial, especially with respect to the identity of the protein(s) in the SNARE complex that bind(s) to synaptotagmin and whether Ca(2+) is required for their highly effective binding. To address these questions, native proteins were solubilized, immunoprecipitated from rat brain extracts, and analyzed by immunoblotting. SNARE complexes comprising syntaxin 1, 25-kDa synaptosomal-associated protein (SNAP-25), and synaptobrevin 2 were coprecipitated with synaptotagmin I in the presence of ethylene glycol tetraacetic acid. The amount of coprecipitated proteins was significantly unaltered by the addition of Ca(2+) to the brain extract. To identify the component of the SNARE complex that bound to synaptotagmin, SNARE was coexpressed with synaptotagmin in HEK293 cells and immunoprecipitated. Syntaxin, but not SNAP-25 and synaptobrevin, bound to synaptotagmin in a Ca(2+)-independent manner, and the binding was abolished in the presence of 1M NaCl. Synaptotagmin contains 2 Ca(2+)-binding domains (C(2)A, C(2)B). Mutating the positively charged lysine residues in the putative effector-binding region of the C(2)B domain, which are critical for transmitter release, markedly inhibited synaptotagmin-syntaxin binding, while similar mutations in the C(2)A domain had no effect on binding. Synaptotagmin-syntaxin binding was reduced by mutating multiple negatively charged glutamate residues in the amino-terminal half of the syntaxin SNARE motif. These results indicate that synaptotagmin I binds to syntaxin 1 electrostatically through its C(2)B domain effector region in a Ca(2+)-independent fashion, providing biochemical evidence that synaptotagmin I binds SNARE complexes before Ca(2+) influx into presynaptic nerve terminals.