Koshu GRoup Activity, Active Play and Exercise (GRAPE) Study: A Cluster Randomised Controlled Trial Protocol of a School-Based Intervention among Japanese Children.

School-based programmes need to be effective, easy for all, easy to perform within a short duration, and inexpensive. However, no studies have reported whether voluntarily and very short-time active play programmes contribute to improved health outcomes. This study aims to describe the GRoup activity, Active Play and Exercise (GRAPE) cluster randomised controlled trial that examined whether active play interventions of very short durations contribute to increasing physical activity (PA) and bone mass among school-aged children. The trial was conducted in 2018 from January to June, and the activity comprised ≥2 children jumping together for approximately 10 s per session, at least five times a day (approximately 1 min/day). School clusters, pair-matched as per school size (total number of children) and region, were randomly allocated to either intervention or wait-list control groups. The primary outcomes comprised objectively measured changes in PA levels (moderate-to-vigorous PA) evaluated using wrist-worn activity trackers from baseline to the one-year follow-up (six-month post-intervention follow-up) and changes in bone mass evaluated using calcaneus quantitative ultrasound parameters. This study could describe the problems and challenges in school-based PA intervention studies and present findings that could make a potentially important contribution to health education and PA promotion.

Association between Maternal Smoking during Pregnancy and Missing Teeth in Adolescents.

Tooth agenesis and disturbance of tooth eruption is the most prevalent oral defect, and is possibly caused by the interaction of genetic and environmental factors. We hypothesized that prenatal factors may affect tooth development. The objective of this study was to examine whether smoking during pregnancy was associated with missing teeth in the offspring during adolescence. The study population comprised pregnant women and their children registered (N = 1052) at Koshu city, Japan. When the expectant mothers visited the city office for pregnancy registration, a survey was conducted to ascertain their lifestyle habits. Data on missing teeth in the children were obtained from the compulsory dental health checkup during junior high school years. Multivariate logistic regression models were fitted to assess the association between missing teeth and lifestyle habits. A total of 772 children were studied. The prevalence of missing teeth in these children was 4.9%. Children whose mothers smoked six cigarettes or more per day were 4.59 (95% CI: 1.07-19.67) times more likely to present with missing teeth than those children whose mothers did not smoke, after adjustment for possible confounders. Our findings indicate that smoking during pregnancy can be a risk factor for missing teeth in the offspring.

Association of objectively measured physical activity and sedentary behavior with bone stiffness in peripubertal children.

INTRODUCTION: Physical activity (PA) is a key factor of bone mass acquisition in peripubertal children. Sedentary behavior (SB) has been shown to influence bone outcomes. This study aimed to examine the association between objectively measured PA and SB and bone stiffness in Japanese children. MATERIALS AND METHODS: Participants were fifth-grade children aged 10-11 years from Project Koshu. The stiffness index (SI) of the calcaneus was measured by quantitative ultrasound; PA and SB were evaluated by an accelerometer. Each PA parameter was divided into sex-specific tertile or stratified by recommended PA guideline [≥ 60 min/day of moderate-to-vigorous PA (MVPA)]. The SI was compared among PA and SB through analysis of covariance with Bonferroni correction. RESULTS: Of 174 children, complete data were obtained from 134 (60 boys and 74 girls). The SI in boys was higher in the highest tertile of MVPA than that in the other groups. A similar association was found in girls but was not significant. Children who met the PA guideline had higher SI than those who did not, but there was no significant difference. A negative relation was observed in girls, with the SI gradually decreasing along with increasing SB (p for trend = 0.038). This association was not observed among boys. CONCLUSION: This study suggests that MVPA is positively associated with bone stiffness in Japanese schoolchildren in boys and SB is negatively associated with that in girls. Reducing SB might be a brief modifiable factor for preventing lower peak bone mass in girls, in addition to increasing MVPA.

Problematic Internet use and its associations with health-related symptoms and lifestyle habits among rural Japanese adolescents.

AIM: There have been concerns about the increase in problematic Internet use (PIU) and its impact on lifestyle habits and health-related symptoms, given the rapid spread of smartphones. This study aimed to clarify PIU prevalence over 3 years in the same area and investigate lifestyle and health-related factors related to PIU among junior high-school students in Japan. METHODS: Each year during 2014-2016, a survey was conducted with junior high-school students from a rural area of Japan (2014, n = 979; 2015, n = 968; 2016, n = 940). Young's Internet Addiction Test was used to assess participants' PIU. Students scoring 40 or higher on the Internet Addiction Test were classified as showing PIU in this study. The associations between PIU and lifestyle factors (e.g., exercise habits, weekday study time, and sleep time) and health-related symptoms (depressive symptoms and orthostatic dysregulation [OD] symptoms) were studied by logistic regression analyses. RESULTS: Over the 3 years, the prevalence of PIU was 19.9% in 2014, 15.9% in 2015, and 17.7% in 2016 without significant change. PIU was significantly associated with skipping breakfast, having a late bedtime (after midnight), and having OD symptoms among students from all grades. Sleepiness after awakening in the morning, less studying time, and depressive symptoms had significant positive associations with PIU, except among 1st grade junior high-school students. CONCLUSION: Our results suggest that PIU is related to decreased time spent sleeping, studying, and exercising and increased symptoms of depression and OD. Further investigations are needed to develop preventive measures for PIU.

Sex Differences in Birth Weight and Physical Activity in Japanese Schoolchildren.

BACKGROUND: Lower birth weight (BW) is associated with increased chronic disease risk later in life. Previous studies suggest that this may be mediated principally via physical activity (PA). However, the association between BW and PA in children has not been clarified. The purpose of this study was to examine the association between BW and PA in school-aged children in Japan. METHODS: Participants were children from a prospective birth cohort study (Project Koshu) who were born from 1996 through 2002 in rural Japan. BWs were obtained from the Maternal and Child Health Handbook. Data on PA during childhood were collected using a self-reported questionnaire when participants were 9-15 years of age in July 2011. Analysis of covariance was used to evaluate exercise duration; Poisson regression analysis was used to evaluate if the recommended PA amount was met. RESULTS: Data from 657 children (boys: 54.8%, follow-up rate: 77.6%) were analyzed. Compared with the normal BW group, only girls in the low-BW group had significantly lower PA level (normal BW, 11.4 [standard error, 1.0] hours/week; low BW, 5.8 [standard error, 3.6] hours/week, P = 0.010), and were more likely to not meet the recommended PA level (prevalence ratio 1.57; 95% CI, 1.14-2.16). CONCLUSION: Low BW was associated with a lower PA level in school-aged girls but not boys. Earlier consideration of BW may be an important public health strategy to prevent physical inactivity in school-aged girls.

Evaluation of the associations between changes in intraocular pressure and metabolic syndrome parameters: a retrospective cohort study in Japan.

OBJECTIVE: The contributions of highly correlated cardiovascular risk factors to intraocular pressure (IOP) are not clear due to underlying confounding problems. The present study aimed to determine which metabolic syndrome parameters contribute to elevating IOP and to what extent. DESIGN: Retrospective cohort study. SETTING: A private healthcare centre in Japan. PARTICIPANTS: Individuals who visited a private healthcare centre and underwent comprehensive medical check-ups between April 1999 and March 2009 were included (20,007 in the cross-sectional study and 15,747 in the longitudinal study). PRIMARY AND SECONDARY OUTCOME MEASURES: Changes in IOP were evaluated in terms of ageing and changes in metabolic syndrome parameters. Pearson's correlation coefficients and mixed-effects models were used to examine the relationship of changes in IOP with ageing and changes in metabolic syndrome parameters in cross-sectional and longitudinal studies, respectively. RESULTS: In the cross-sectional study, IOP was negatively correlated with age and positively correlated with waist circumference, high-density lipoprotein cholesterol (HDL-C) levels, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting plasma glucose (FPG) levels. In the longitudinal multivariate analysis, the associated IOP changes were -0.12 (p<0.0001) mm Hg with male sex; -0.59 (p<0.0001) mm Hg with 10 years of ageing; +0.42 (p<0.0001) mm Hg with 1 mmol/L increase in HDL-C levels; +0.092 (p<0.0001) mm Hg with 1 mmol/L increase in triglyceride levels; +0.090 (p<0.0001) mm Hg with 10 mm Hg increase in SBP; +0.085 (p<0.0001) mm Hg with 10 mm Hg increase in DBP; and+0.091 (p<0.0001) mm Hg with 1 mmol/L increase in FPG levels. CONCLUSIONS: Elevation of IOP was related to longitudinal worsening of serum triglyceride levels, blood pressure and FPG and improvement in serum HDL-C levels.

Association Between Maternal Smoking During Pregnancy and Birth Weight: An Appropriately Adjusted Model From the Japan Environment and Children's Study.

BACKGROUND: There has been no large nationwide population-based study to examine the effects of maternal smoking status during pregnancy on birth weight that simultaneously controlled for clinical information, socioeconomic status, and maternal weight. Thus, this study aimed to determine the association between maternal smoking status during pregnancy and birth weight, while taking these confounding factors into consideration. METHODS: This study examined the first-year fixed dataset from a large nationwide birth cohort study that commenced in 2011. The dataset consisted of information on 9369 singleton infants born before December 31, 2011. Children were divided into 4 groups for statistical analysis: those born to mothers who did not smoke (NS), who quit smoking before pregnancy, who quit smoking during early pregnancy, and who smoked (SM). Multiple linear regression models were conducted for each sex to examine the association between maternal smoking status during early pregnancy and fetal growth. Birth weight was estimated using the least-squares method after controlling for covariates. RESULTS: After controlling for potential confounding factors, maternal smoking status during pregnancy was significantly associated with birth weight. There was a significant difference in birth weight between NS and SM for both male and female infants (male infants, 3096.2 g [NS] vs 2959.8 g [SM], P < 0.001; female infants, 3018.2 g [NS] vs 2893.7 g [SM], P < 0.001). CONCLUSIONS: Using data from a large nationwide birth cohort study in Japan, we have shown that maternal smoking during pregnancy may reduce birth weight by 125-136 g.

Pubertal timing and a family history of hypertension: Prospective cohort study.

BACKGROUND: Hypertension is heritable, and genetic factors likely exert an effect from childhood. Puberty is an early life milestone that may relate to adult hypertension. Therefore, this study examined whether there is an association between a family history of hypertension and pubertal growth. METHODS: The participants were children from a prospective cohort study called Project Koshu, who were born between 1991 and 1998 in Japan. Data on family history of hypertension, maternal characteristics, birth and early life factors were collected from the questionnaire administered to the mothers at the time of pregnancy registration or medical check-up. Child age at peak height velocity (early or non-early) was calculated from the anthropometric data collected during annual school check-up. RESULTS: Data on 919 children (479 boys and 440 girls) were included in the analysis; 478 participants had a family history of hypertension. After adjustment for potential confounders (birth month, maternal body mass index, maternal work status, maternal education, and paternal education), early age at peak height velocity was found to be associated with a family history of hypertension (OR, 1.52; 95% confidence interval (CI): 1.04-2.24; P = 0.03) and specifically, with having at least one maternal hypertensive relative (OR, 1.81; 95%CI: 1.23-2.68; P = 0.003). CONCLUSIONS: Together with previous reports on the relationship between puberty and adult hypertension, the present results suggest that the timing of pubertal growth is involved in the process of hypertension development in people with a family history of hypertension. Further confirmative studies are needed.

Do body mass index trajectories affect the risk of type 2 diabetes? A case-control study.

BACKGROUND: Although obesity is a well-studied risk factor for diabetes, there remains an interest in whether "increasing body mass index (BMI)," "high BMI per se," or both are the actual risk factors for diabetes. The present study aimed to retrospectively compare BMI trajectories of individuals with and without diabetes in a case-control design and to assess whether increasing BMI alone would be a risk factor. METHODS: Using comprehensive health check-up data measured over ten years, we conducted a case-control study and graphically drew the trajectories of BMIs among diabetic patients and healthy subjects, based on coefficients in fitted linear mixed-effects models. Patient group was matched with healthy control group at the onset of diabetes with an optimal matching method in a 1:10 ratio. Simple fixed-effects models assessed the differences in increasing BMIs over 10 years between patient and control groups. RESULTS: At the time of matching, the mean ages in male patients and controls were 59.3 years [standard deviation (SD) = 9.2] and 57.7 years (SD = 11.2), whereas the mean BMIs were 25.0 kg/m(2) (SD = 3.1) and 25.2 kg/m(2) (SD = 2.9), respectively. In female patients and controls, the mean ages were 61.4 years (SD = 7.9) and 60.1 years (SD = 9.6), whereas the mean BMIs were 24.8 kg/m(2) (SD = 3.5) and 24.9 kg/m(2) (SD = 3.4), respectively. The simple fixed-effects models detected no statistical significance for the differences of increasing BMIs between patient and control groups in males (P = 0.19) and females (P = 0.67). Sudden increases in BMI were observed in both male and female patients when compared with BMIs 1 year prior to diabetes onset. CONCLUSIONS: The present study suggested that the pace of increasing BMIs is similar between Japanese diabetic patients and healthy individuals. The increasing BMI was not detected to independently affect the onset of type 2 diabetes.

Childhood growth trajectories according to combinations of pregestational weight status and maternal smoking during pregnancy: a multilevel analysis.

Pregestational weight status and maternal smoking during pregnancy are significantly associated with fetal and childhood growth. However, few studies have examined associations between childhood growth and combinations of these factors using multilevel analysis. This study aimed to describe differences in childhood growth trajectories according to these combinations, using data from a prospective cohort study in Japan. The study participants were 1,973 women and their singletons, who were born between April 1, 1991 and March 31, 2003. Children were categorized according to whether they were born to normal-weight, nonsmoking mothers (NN); normal-weight, smoking mothers (NS); underweight, nonsmoking mothers (UN); underweight, smoking mothers (US); overweight, nonsmoking mothers (ON); or overweight, smoking mothers (OS). Birth weight and anthropometric data were collected from 1,965 children at birth (99.6%), 1,655 aged 3 (83.9%), 1,527 aged 5 (77.4%), 1,497 aged 7-8 (75.9%), and 1,501 aged 9-10 (76.1%). Multilevel analysis examining both individual and age as different level variables according to sex was used to describe the trajectories of body mass index z scores for statistical analyses. Although children of the OS group were the leanest at birth, their body mass indices had increased rapidly by 3 years of age. Moreover, body mass index was also likely to increase in boys in the NS and ON groups. A different trend was observed in girls. Body mass index decreased from 5 years of age in girls in the US group. There were no remarkable differences in body mass index trajectories between children in the other groups. In conclusion, childhood growth trajectories differed according to combinations of pregestational weight status and maternal smoking during pregnancy. Further, there were sex-related differences in the associations between childhood growth and factor combinations.

Maternal smoking during pregnancy and growth in infancy: a covariance structure analysis.

BACKGROUND: Smoking during pregnancy is related to fetal constraint and accelerated postnatal growth. However, the pathways between these factors have not been clarified. Pathway analyses that link these factors can help us better understand the mechanisms involved in this association. Therefore, this study aimed to examine pathways between maternal smoking during pregnancy and growth in infancy. METHODS: Participants were singletons born between 1993 and 2006 in rural Japan. The outcome was the change in weight z-score between birth and 3 years of age. Pathways from maternal smoking and other maternal factors (such as maternal body mass index and work status) to growth in infancy via birth factors (such as birth weight and gestational age) and breastfeeding were examined using structural equation modeling. RESULTS: Complete data were available for 1524 children (775 boys and 749 girls). The model fit appeared adequate. Lower birth weight and non-exclusive breastfeeding mediated the association between maternal smoking during pregnancy and rapid growth in infancy. Maternal smoking was also directly linked to rapid growth in infancy (standardized direct effects 0.06, P = 0.002). Taking all pathways into account, the standardized total effect of maternal smoking on growth in infancy was 0.11. CONCLUSIONS: Maternal smoking during pregnancy may both indirectly, through birth weight and breastfeeding status, and directly influence growth during infancy; however, there may be other pathways that have not yet been identified.

Association between malocclusion and headache among 12- to 15-year-old adolescents: a population-based study.

OBJECTIVES: Headaches are a common problem among adolescents, and malocclusion is a possible risk factor. The purpose of this study was to investigate the association between malocclusion and headache among Japanese adolescents aged 12-15 years using a population-based sample. METHODS: A total of 938 adolescents (94.7% of the target population in Koshu City) participated. A modified version of the Index of Orthodontic Treatment Need (IOTN) was used by orthodontists to evaluate occlusal characteristics, and the frequency of headaches (none, rarely, sometimes) was assessed via questionnaire (N = 938). Ordered logistic regression analyses were used to analyze the association between malocclusion and headache. RESULTS: The prevalence of malocclusion diagnosed using the modified version of the IOTN was 44.9%. Multiple ordered logistic regression analyses showed that the odds ratio (OR) of having malocclusion for headache was 1.38 (95% confidence interval [CI]: 1.06-1.80), after adjustment for demographics, lifestyle, and dental status including orthodontic treatment history and tooth size. Moreover, among occlusal traits, lower crowding was independently associated with headache (OR: 1.64, 95% CI: 1.07-2.51). CONCLUSIONS: We found that malocclusion, especially lower crowding, was associated with headache in a population-based sample of adolescents aged 12-15 years in Japan. Further study is needed to elucidate the mechanisms by which malocclusion affects headache.

Adolescent growth in overweight and non-overweight children in Japan: a multilevel analysis.

BACKGROUND: A trend towards earlier pubertal growth has been identified along with an increase in childhood obesity rates. The study aimed to identify the differences in growth patterns during adolescence between overweight/obese and non-overweight children in Japan. METHODS: The participants were children from a prospective cohort study called Project Koshu, who were born between 1991 and 1998, in Japan. They were classified as overweight/obese or non-overweight according to their body mass index (BMI) in the first grade of elementary school (6-7 years of age) and were followed until graduation from junior high school (14-15 years of age). Anthropometric data were collected at an annual medical check-up in their school. Height gain trajectories were constructed by BMI categories using multilevel analyses. This analysis was stratified by gender. RESULTS: Overall, 111/850 (13.1%) girls and 109/911(12%) boys were defined as overweight/obese at baseline. Approximately 80% of the children were followed until the third grades of junior high school. Overweight/obese girls gained more height in the first half period, reached their peak height gain about a year earlier than non-overweight girls, and experienced an earlier decline in height gain. Similarly, overweight/obese boys gained more height than non-overweight boys initially. Additionally, non-overweight boys maintained a higher rate of height gain from the age at peak height gain, although the age at peak height gain did not differ between the two groups. CONCLUSIONS: The overweight/obese children grew faster than the non-overweight children in the early pubertal stages, and the non-overweight children caught up and exceeded in height gain at a later stage.

Effect of maternal smoking cessation before and during early pregnancy on fetal and childhood growth.

BACKGROUND: Maternal smoking during pregnancy is a major cause of intrauterine growth restriction and childhood obesity, but only a few studies have examined the association of smoking cessation before and during pregnancy with fetal and childhood growth. We examined this association in a prospective cohort study in Japan. METHODS: Our study included children born between 1991 and 2006 and their mothers. Using a questionnaire, maternal smoking status was recorded at pregnancy. The anthropometric data of the children were collected during a medical check-up at age 3 years. Multiple linear and logistic regression models were used for data analysis stratified by sex. RESULTS: In total, 2663 mothers reported their smoking status during early pregnancy, and data were collected from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was associated with a significant reduction in birth weight (approximately 120-150 g). Body mass index at age 3 years was significantly higher among boys born to smoking mothers than among boys born to nonsmoking mothers. Maternal smoking during pregnancy was associated with overweight at age 3 years among boys (adjusted odds ratio, 2.4; 95% CI, 1.03-5.4). However, among women who stopped smoking in early pregnancy, there was no increase in the risks of a small for gestational age birth or childhood overweight at age 3 years. CONCLUSIONS: Children born to mothers who stopped smoking before or during early pregnancy had appropriate fetal and childhood growth.

Multilevel longitudinal analysis of sex differences in height gain and growth rate changes in Japanese school-aged children.

BACKGROUND: Determining standard pubertal growth patterns using longitudinal anthropometric measures is important in growth assessment. We used an appropriate repeated-measurements method to identify height growth patterns in Japanese school-aged girls and boys. METHODS: The participants were children born during the period from 1991 through 1999 who had entered the first grade of elementary school in the Enzan district in Koshu City, Japan. This study was part of the Project Koshu cohort study. Height was measured annually in April from the first grade of elementary school (age, 6-7 years) to the third grade of junior middle school (age, 14-15 years). Height gain and growth rate trajectories in boys and girls were constructed using multilevel analysis. RESULTS: In total, 1984 children (1036 boys and 948 girls) were included in this study. Height in boys and girls was similar at age 6.5 to 9.5 years. Girls subsequently grew faster and were taller than boys at age 10.5 to 11.5 years. Starting at age 12.5 years, male height caught up and exceeded female height. Height gain trajectories showed that annual height gain among girls increased slowly and peaked during age 9.5 to 11.5 years, while male height gains declined slightly at first and peaked at age 11.5 to 12.5 years. Sex differences in height gains were significant during the period from age 7.5 to 14.5 years (P < 0.0001). Growth rate and height gain trajectories were similar between sexes. CONCLUSIONS: Sex differences in growth trajectory were significant, and female height gain peaked approximately 2 years earlier than male height gain.

Differences in the effect of maternal smoking during pregnancy for childhood overweight before and after 5 years of age.

AIM: This study aimed to clarify the association between maternal smoking during pregnancy and childhood overweight during different periods using two cohort studies from the same population: the birth cohort (the 1st cohort) and the non-overweight children at 5 years of age cohort (the 2nd cohort) by sex. MATERIAL AND METHODS: The study population comprised children born between 1 April 1991 and 31 March 1999 in Koshu City, Yamanashi Prefecture, Japan, and their mothers. The dependent variables were diagnosis of overweight in each cohort. The primary independent variable was maternal smoking during pregnancy. Multiple logistic regression models were applied for these statistical analyses. RESULTS: Mothers who answered the questionnaire during early pregnancy gave birth to a total of 1644 babies during the study period. The 1st cohort consisted of these babies and were followed until 5 years of age. The 2nd cohort consisted of 1131 children who were diagnosed as normal weight at 5 years of age and followed until 9-10 years of age. There was an association between maternal smoking during pregnancy and overweight only in boys in the 1st cohort analysis (adjusted odds ratio, 4.5; 95% confidence interval, 2.0-10.2). CONCLUSIONS: These results suggest that the effects of maternal smoking during pregnancy on childhood overweight tend to appear before 5 years of age, especially in boys. It is necessary for children whose mother smoked during pregnancy, especially in boys, to be careful with their diet and physical activity in order to prevent childhood obesity.

Developmental trajectories of body mass index among Japanese children and impact of maternal factors during pregnancy.

BACKGROUND: The aims of this study were to 1) determine the distinct patterns of body mass index (BMI) trajectories in Japanese children, and 2) elucidate the maternal factors during pregnancy, which contribute to the determination of those patterns. METHODOLOGY/PRINCIPAL FINDINGS: All of the children (1,644 individuals) born in Koshu City, Japan, between 1991 and 1998 were followed in a longitudinal study exploring the subjects' BMI. The BMI was calculated 11 times for each child between birth and 12 years of age. Exploratory latent class growth analyses were conducted to identify trajectory patterns of the BMI z-scores. The distribution of BMI trajectories were best characterized by a five-group model for boys and a six-group model for girls. The groups were named "stable thin," "stable average," "stable high average," "progressive overweight," and "progressive obesity" in both sexes; girls were allocated to an additional group called "progressive average." Multinomial logistic regression found that maternal weight, smoking, and skipping breakfast during pregnancy were associated with children included in the progressive obesity pattern rather than the stable average pattern. These associations were stronger for boys than for girls. CONCLUSIONS/SIGNIFICANCE: Multiple developmental patterns in Japanese boys and girls were identified, some of which have not been identified in Western countries. Maternal BMI and some unfavorable behaviors during early pregnancy may impact a child's pattern of body mass development. Further studies to explain the gender and regional differences that were identified are warranted, as these may be important for early life prevention of weight-associated health problems.

[A survival analysis approach to assess the association between maternal smoking during pregnancy and childhood obesity].

OBJECTIVES: It has been suggested that maternal smoking during pregnancy has an effect on childhood obesity. We previously clarified the association between maternal lifestyle habits practiced during pregnancy, including smoking, and childhood obesity and overweight at 9-10 years of age. In this study, we aimed to demonstrate this association through survival analysis. METHODS: This study was based on an on-going community-based prospective cohort study initiated in the fetal stage called Project Koshu. The study population comprised of the participants of Project Koshu, who were children born in a rural Japanese area between 1991 and 1999 and their mothers. In this project, maternal smoking status during pregnancy was collected through a questionnaire and childhood anthropometric data were measured at annual medical check-ups from 3 years of age to 9-10 years of age. Using these data, we performed a survival analysis using the Kaplan-Meier method to compare the cumulative rate of childhood obesity and overweight between those with mothers who smoked during pregnancy and those who did not. Subsequently, we calculated the hazard ratio (HR) of the effect of maternal smoking during pregnancy on childhood obesity using the Cox proportional hazard model. RESULTS: In the survival analysis of childhood obesity, we analyzed the data of 1428 children and their mothers (follow-up rate: 87.7%). Of these, 290 children (20.3%) became overweight and 92 children (6.4%) became obese between 3 years of age and 9-10 years of age. This shows that the cumulative rate of childhood obesity was significantly different between mothers with and without smoking habits (P < 0.001). Using the Cox proportional hazard model, we analyzed the data of 1204 children and their mothers (follow-up rate: 74.0%). Of these, 255 children (21.2%) became overweight and 76 children (6.3%) became obese between 3 years of age and 9-10 years of age. Maternal smoking during pregnancy was found to be associated with childhood obesity (HR, 2.0; 95% confidence interval (CI): 1.04-4.0). However, there was no significant association between maternal smoking during pregnancy and childhood overweight. CONCLUSION: Our results suggest that the effect of fetal environmental factors on childhood obesity is more pronounced than that on childhood overweight. These results suggest that maternal smoking during pregnancy may be a significant factor in the association between fetal environment and post-delivery development.

Maternal smoking during pregnancy and childhood growth trajectory: a random effects regression analysis.

BACKGROUND: Although maternal smoking during pregnancy has been reported to have an effect on childhood overweight/obesity, the impact of maternal smoking on the trajectory of the body mass of their offspring is not very clear. Previously, we investigated this effect by using a fixed-effect model. However, this analysis was limited because it rounded and categorized the age of the children. Therefore, we used a random-effects hierarchical linear regression model in the present study. METHODS: The study population comprised children born between 1 April 1991 and 31 March 1999 in Koshu City, Japan and their mothers. Maternal smoking during early pregnancy was the exposure studied. The body mass index (BMI) z-score trajectory of children born to smoking and non-smoking mothers, by gender, was used as the outcome. We modeled BMI trajectory using a 2-level random intercept and slope regression. RESULTS: The participating mothers delivered 1619 babies during the study period. For male children, there was very strong evidence that the effect of age in months on the increase in BMI z-score was enhanced by maternal smoking during pregnancy (P < 0.0001). In contrast, for female children, there was only weak evidence for an interaction between age in months and maternal smoking during pregnancy (P = 0.054), which suggests that the effect of maternal smoking during pregnancy on the early-life BMI trajectory of offspring differed by gender. CONCLUSIONS: These results may be valuable for exploring the mechanism of fetal programming and might therefore be clinically important.

Maternal psychosocial factors determining the concentrations of transforming growth factor-beta in breast milk.

BACKGROUND: Cytokines in breast milk may play crucial roles in the beneficial effects of breastfeeding in protecting against allergic and infectious diseases in infants. In particular, breast milk-borne transforming growth factor-beta (TGF-ß) has an important potential role in developing the mucosal immune system in infants. However, little is known about what factors influence TGF-ß expression in human milk. We investigated whether the behavioral and psychosocial characteristics of mothers affect breast milk TGF-ß levels. METHODS: We conducted a survey of all 139 mothers who were lactating between February and October 2010 in Koshu City, Japan. Participants completed a questionnaire and provided breast milk at the health checkups for their 3-month-old child (N = 129, 93%). Breast milk was assayed for total TGF-ß2 levels by ELISA. We took an exploratory approach based on linear and ordered logistic regressions to model TGF-ß2 concentrations with their multiple potential determinants. RESULTS: Mothers with depression or poor self-rated health had higher TGF-ß2 concentrations than mothers without depression (odds ratio for a higher TGF-ß2 quartile: 3.11, 95% confidence intervals: 1.03-9.37) or those reporting better health (odds ratio: 2.34, 1.21-4.55). Smoking, drinking alcohol, probiotics supplementation, social support, and maternal history of allergic diseases were not associated with milk TGF-ß2 levels. Milk gathered between August and October or later in the afternoon (3-4 pm vs. 12-2 pm) contained less TGF-ß2. CONCLUSION: Depression, as the consequence of psychosocial stress, may be a strong determinant of TGF-ß levels in breast milk. Seasonal and daily fluctuations in milk TGF-ß2 concentrations warrant further study.