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1.  Vitamin D Status and Related Factors in Newborns in Shanghai, China 
Nutrients  2014;6(12):5600-5610.
With the increasing recognition of the importance of the non-skeletal effects of vitamin D (VitD), more and more attention has been drawn to VitD status in early life. However, the VitD status of newborns and factors that influence VitD levels in Shanghai, China, remain unclear. A total of 1030 pregnant women were selected from two hospitals in Shanghai, one of the largest cities in China located at 31 degrees north latitude. Umbilical cord serum concentrations of 25-hydroxy vitamin D [25(OH)D] were measured by LC-MS-MS, and questionnaires were used to collect information. The median cord serum 25(OH)D concentration was 22.4 ng/mL; the concentration lower than 20 ng/mL accounted for 36.3% of the participants, and the concentration lower than 30 ng/mL for 84.1%. A multivariable logistic regression model showed that the determinants of low 25(OH)D status were being born during autumn or winter months and a lack of VitD-related multivitamin supplementation. The relative risk was 1.7 for both autumn (95% CI, 1.1–2.6) and winter (95% CI, 1.1–2.5) births (p < 0.05). VitD-related multivitamin supplementation more than once a day during pregnancy reduced the risk of VitD deficiency [adjusted OR (aOR) = 0.6, 95% CI (0.45–1.0) for VitD supplementation] (p < 0.05). VitD deficiency and insufficiency are common in newborns in Shanghai, China, and are independently associated with season and VitD supplementation. Our findings may assist future efforts to correct low levels of 25(OH)D in Shanghai mothers and their newborn children.
PMCID: PMC4276986  PMID: 25486368
vitamin D; related factors; newborn
2.  Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups 
To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes.
Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34–36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37–44 weeks) in multinomial regression. To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes.
Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001). After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB. These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes. For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]).
Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB. Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB.
PMCID: PMC4022544  PMID: 24779674
Maternal obesity; Prepregnancy BMI; Medically-induced preterm birth; Spontaneous preterm birth; Late preterm birth
3.  Parent-adolescent interaction and risk of adolescent internet addiction: a population-based study in Shanghai 
BMC Psychiatry  2014;14:112.
Family-based intervention is essential for adolescents with behavioral problems. However, limited data are available on the relationship between family-based factors and adolescent internet addiction (AIA). We aimed to examine this relationship using a representative sample of Shanghai adolescents.
In October 2007, a total of 5122 adolescents were investigated from 16 high schools via stratified-random sampling in Shanghai. Self-reported and anonymous questionnaires were used to assess parent-adolescent interaction and family environments. AIA was assessed by DRM-52 Scale, developed from Young’s Internet-addiction Scale, using seven subscales to evaluate psychological symptoms of AIA.
Adjusting for adolescents’ ages, genders, socio-economic status, school performances and levels of the consumption expenditure, strong parental disapproval of internet-use was associated with AIA (vs. parental approval, OR = 2.20, 95% CI: 1.24-3.91). Worse mother-adolescent relationships were more significantly associated with AIA (OR = 3.79, 95% CI: 2.22-6.48) than worse father-adolescent relationships (OR = 1.76, 95% CI: 1.10-2.80). Marital status of “married-but-separated” and family structure of “left-behind adolescents” were associated with symptoms of some subscales. When having high monthly allowance, resident students tended to develop AIA but commuter students did not. Family social-economic status was not associated with the development of AIA.
The quality of parent-adolescent relationship/communication was closely associated with the development of AIA, and maternal factors were more significantly associated with development of AIA than paternal factors. Family social-economic status moderated adolescent internet-use levels but not the development of AIA.
PMCID: PMC3999889  PMID: 24731648
Adolescents; Internet addiction; Mother-child relations; Father-child relations; China; Marital status; Family structure
4.  Placental Weight Mediates the Effects of Prenatal Factors on Fetal Growth: the Extent Differs by Preterm Status 
Obesity (Silver Spring, Md.)  2013;21(3):10.1002/oby.20254.
Elevated pre-pregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre-pregnancy BMI, GWG, and GDM with birthweight-for-gestational age, and whether the relationships differ by preterm status. We examined 1035 mother-infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status. We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. 41% were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking and stress during pregnancy, birthweight-for-gestational age z-score was 0.55 (0.30, 0.80) units higher for pre-pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre-pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre-pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birthweight-for-gestational age z-score, but pre-pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM. These results suggest that placental weight partially mediates the effects of pre-pregnancy obesity, GDM and excessive GWG on fetal growth among term infants.
PMCID: PMC3418379  PMID: 23592670
pre-pregnancy BMI; gestational weight gain; gestational diabetes; placental weight; fetal growth; birth weight z-score
5.  Diabetes and Perinatal Mortality in Twin Pregnancies 
PLoS ONE  2013;8(9):e75354.
Diabetes in pregnancy has been associated with a paradoxically reduced risk of neonatal death in twin pregnancies. Risk “shift” may be a concern in that the reduction in neonatal deaths may be due to an increase in fetal deaths (stillbirths). This study aimed to clarify the impact of diabetes on the risk of perinatal death (neonatal death plus stillbirth) in twin pregnancies.
This was a retrospective cohort study of twin births using the largest available dataset on twin births (the U.S. matched multiple birth data 1995-2000; 19,676 neonates from diabetic pregnancies, 541,481 from non-diabetic pregnancies). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death accounting for twin cluster-level dependence.
Comparing diabetic versus non-diabetic twin pregnancies, overall perinatal mortality rate was counterintuitively lower [2.1% versus 3.3%, aHR 0.70 (95% confidence intervals 0.63-0.78)]. Individually, both stillbirth and neonatal mortality rates were lower in diabetic pregnancies, but we identified significant differences by gestational age and birth weight. Diabetes was associated with a survival benefit in pregnancies completed before 32 weeks [aHR 0.55 (0.48-0.63)] or with birth weight <1500 g [aHR 0.61 (0.53-0.69)]. In contrast, diabetes was associated with an elevated risk of perinatal death in pregnancies delivered between 32 and 36 weeks [aHR 1.38 (1.10-1.72)] or with birth weight >=2500 g [aHR 2.20 (1.55-3.13)].
Diabetes in pregnancy appears to be “protective” against perinatal death in twin pregnancies ending in very preterm or very low birth weight births. Prospective studies are required to clarify whether these patterns of risk are real, or they are artifacts of unmeasured confounders. Additional data correlating these outcomes with the types of diabetes in pregnancy are also needed to distinguish the effects of pre-gestational vs. gestational diabetes.
PMCID: PMC3776783  PMID: 24058678
6.  Gestational Diabetes, Atopic Dermatitis and Allergen Sensitization in Early Childhood 
The relationship between the prenatal environment, maternal-fetal interaction, and allergic disease in the offspring remains understudied.
We sought to determine whether gestational diabetes modifies the risk of early childhood atopic manifestations including atopic dermatitis and allergen sensitization.
This study includes 680 children from the Boston Birth Cohort. Mother-child dyads were recruited at birth and followed prospectively to a mean age of 3.2±2.3 years with study visits aligned with the pediatric primary care schedule. The primary outcomes were physician diagnosed atopic dermatitis on standardized medical record abstraction and allergen sensitization based on Immunocap to 7 common foods and 5 common aeroallergens (sIgE≥0.10 kUA/L, Phadia). Gestational diabetes was determined by standardized medical record review. Logistic regression analysis, stratified by term/preterm status, evaluated the association of gestational diabetes with atopic dermatitis and allergen sensitization respectively, controlling for maternal pre-pregnancy BMI, fetal growth, and pertinent covariates.
Of the 680 children, 488 were term and 192 were preterm (<37 weeks gestation). Overall, 4.9% of the mothers developed gestational diabetes. Among the 680 children, 34.4% developed atopic dermatitis and 51% developed allergen sensitization. In term births, gestational diabetes was significantly associated with atopic dermatitis (OR, 95%CI=7.2, 1.5-34.5) and allergen sensitization (OR, 95%CI=5.7, 1.2-28.0). Adjusting for fetal growth had little effect. The association with sensitization was driven primarily by food sensitization (OR, 95%CI=8.3, 1.6-43.3). The above associations were not observed in preterm births.
In term births, gestational diabetes increased the risk of atopic dermatitis and early childhood allergen sensitization, independent of maternal pre-pregnancy BMI and fetal growth.
PMCID: PMC3756674  PMID: 19733904
atopic dermatitis; eczema; food allergen sensitization; gestational diabetes
7.  Association between Short Sleep Duration and the Risk of Sensitization to Food and Aero Allergens in Rural Chinese Adolescents 
Both long and short sleep duration have been associated with obesity, cardiovascular disease, and diabetes. However, there have been no previous studies investigating the potential relationship between altered sleep duration and allergen sensitization.
To explore the association between sleep duration and sensitization to food and aeroallergens.
This study includes 1534 rural Chinese adolescent twins aged 12 to 21 years who completed standard sleep questionnaires and skin prick tests (SPTs) to 9 food and 5 aeroallergens. Total sleep time was defined as the interval from bedtime to wake-up time minus sleep latency. Sensitization was defined as having at least one positive SPT.
Compared to individuals with the highest (3rd) tertile of sleep duration, those who slept less were more likely to be sensitized to any food allergen with odds ratios (ORs) of 1.9 (95% confidence interval(CI):1.3–2.7) and 1.4 (95%CI:1.0–1.9) for the 1st and 2nd tertiles (trend test Ptrend=3×10−4), respectively. The corresponding ORs for sensitization to any aeroallergen were 1.5 (95%CI: 1.1–2.0) and 1.3 (95%CI:1.0–1.7) (Ptrend=8×10−3). These associations were independent of percent body fat. In addition, we observed a significant dose-response association between the number of positive SPTs and percentage of shortest sleep duration (1st tertile) (Ptrend=1×10−3).
Conclusions and Clinical Relevance
In this sample of relatively lean rural Chinese adolescents, we found that short sleep duration was associated with increased risk of sensitization to food and aeroallergens, independent of percent body fat. Longitudinal studies are needed to further determine the temporal and causal relationships. If short sleep duration indeed is one of the risk factors for allergic sensitization, the global burden of allergic diseases could be dramatically reduced by providing appropriate guidance on sleep duration for youth.
PMCID: PMC3056931  PMID: 21255141
sleep duration; skin prick test; allergen; sensitization; adolescent
8.  The patterns of glucose tolerance and insulin resistance among rural Chinese twin children, Adolescents and young adults 
Metabolism: clinical and experimental  2010;59(12):1752-1759.
Pubertal insulin resistance (IR) is well recognized but little data is available for glucose and insulin pattern from a large, unselected lean population. This report describes the age- and gender-specific distributions of glucose tolerance and IR in a rural Chinese twin population. This report includes 4,488 subjects aged 6 to 24 years. The primary variables of interest are fasting plasma glucose (FPG), 2h post-load plasma glucose (2h PG), fasting serum insulin (FSI), 2h post-load insulin (2h PI) and the homeostatic model assessment for IR (HOMA-IR) index. Age- and gender-specific patterns for the primary variables are described using smoothing plot, arithmetic or geometric mean, and percentiles. There is an increase in FPG, 2h PG and IR during puberty (10–19years) and return to pre-puberty level by the age of 20 years. IR peaks around age of 14 years in girls, and 16 years in boys. 2h PG and 2h PI are higher in girls than in boys from early puberty, and the gender differences are more pronounced afterward. Moreover, the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) increase after puberty, and higher in girls than in boys. In this community based, non-obese rural Chinese twin population, we observed gender-specific remarkable pubertal surge of IR and modest increase in plasma glucose as well as increasing prevalence of IFG and IGT with age. Notably, females had higher 2h PG and higher prevalence of IFG and IGT. Our study underscored that adolescence (even more so in females) is a critical period for developing IR and pre-diabetes.
PMCID: PMC2974012  PMID: 20580383
adolescents; glucose tolerance; insulin resistance; Chinese
9.  Maternal obesity, diabetes mellitus and cord blood biomarkers in large-for-gestational age infants 
Infants born large-for-gestational age (LGA) are at risk for early childhood obesity. The aims of this study were to investigate factors associated with LGA status and their relationship to inflammatory biomarkers that have been implicated in the LGA infant at birth. Included were 364 mother-infant pairs enrolled as part of an ongoing longitudinal cohort study of infant birth weight being conducted at Boston Medical Center (BMC). LGA was defined as birth weight (BW) ≥90th percentile of the reference population at BMC (N=45). Appropriate-for-gestational age (AGA) was defined as BW<90th and >10th percentile (N=319). Cord blood IL-6, IL-8, TNF-alpha and RANTES levels were analyzed from a larger panel of immune biomarkers measured using multiplex immunoassay. Multivariate regression models were used to determine the associations between LGA status, maternal BMI and diabetes (DM), which included either gestational or type 2 diabetes (T2DM), and cord blood biomarkers, with adjustment for important demographic and clinical variables. Maternal pre-pregnancy BMI within the obesity range (≥30 kg/m2), as well as DM, were each associated with increased risk of LGA (OR=2.64, 95%CI 1.31-6.20; OR=5.58, 95%CI 2.06-15.13, respectively). Among the 4 biomarkers, only RANTES (regulated on activation, normal T cell express and secreted upon uptake), which is a chemokine secreted by white adipose tissue, was significantly increased in LGA infants (beta-coefficient=0.37; 95% CI: 0.09, 0.65; P<0.01). This association remained essentially unchanged after adjustment for maternal DM and BMI (beta-coefficient=0.37; 95% CI: 0.08, 0.65; P=0.01). Ponderal index (PI=BW×100/length3) was also positively correlated with RANTES. Cord blood RANTES is selectively elevated with fetal macrosomia, independent of maternal factors. Further investigation of RANTES as a marker of LGA and future childhood health is warranted.
PMCID: PMC3148069  PMID: 21814537
Birth weight; large-for-gestational age; cord blood; inflammation; obesity; diabetes
10.  Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children 
The effect of food introduction timing on the development of food allergy remains controversial. We sought to examine whether the presence of childhood eczema changes the relationship between timing of food introduction and food allergy. The analysis includes 960 children recruited as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick testing/specific IgE. Physician diagnosis of eczema and timing of formula and solid food introduction were obtained by standardized interview. Cox Regression analysis provided hazard ratios for the development of food allergy for the same subgroups. Logistic regression models estimated the association of eczema and formula/food introduction with the risk of food allergy, individually and jointly. Of the 960 children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95% CI: 8.4, 5.9–12.1). Among all children, later (>6 months) formula and rice/wheat cereal introduction lowered the risk of food allergy. In joint analysis, children without eczema who had later formula (OR, 95% CI: 0.5, 0.3–0.9) and later (>1 year) solid food (OR, 95% CI: 0.5, 0.3–0.95) introduction had a lower risk of food allergy. Among children with eczema, timing of food or formula introduction did not modify the risk of developing food allergy. Later food introduction was protective for food allergy in children without eczema but did not alter the risk of developing food allergy in children with eczema.
PMCID: PMC3281290  PMID: 22375277
11.  Sleep Patterns Among Rural Chinese Twin Adolescents 
Sleep medicine  2008;10(4):479-489.
To examine sleep patterns and influencing factors (age, gender, Tanner Stage, weekday vs. weekend, and pre-sleep activity) among rural Chinese adolescents.
This is a prospective study among 621 adolescents aged 11–20 years (341 males) using both a questionnaire and sleep diary to obtain bedtime, wake-up time, sleep latency, and total sleep time (TST).
The median TST was 8.6 hours on weekdays and 9.4 hours on weekends. Despite absence of late night social pressure and computers, a U-shaped TST pattern was observed across age and Tanner stage, with a nadir around age 15–16 years or Tanner IV. Bedtimes became progressively later with age and Tanner Stage, while wake-up time was considerably earlier for school students or up to Tanner IV. Later wake-up times and longer TST on weekends were seen in school students, but not in non-school adolescents (>17 years). Pre-sleep activity, like reading or studying, was related to later bedtime, earlier wake-up time, and shorter TST in both genders.
Age, Tanner stage, and pre-sleep activity affected sleep patterns in this sample of rural Chinese adolescents. Later bedtime coupled with earlier wake-up time associated with academic demand appear to be important contributors to sleep loss among school students.
PMCID: PMC2753967  PMID: 18752997
Age; gender; puberty; Tanner stages; sleep patterns; wake-up time; bedtime; total sleep time
12.  Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women 
Obesity and allergic diseases have increased dramatically in recent decades. While adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.
To examine the association of adiposity and lipid profiles with allergic sensitization.
This study included 1,187 rural Chinese twins (653 men) aged 18-39 years, with skin prick tests (SPT), anthropometric and DEXA-assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to ≥1 allergen (9 foods and 5 aeroallergens tested). We applied gender-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations.
Males had lower percent body fat (%BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs. 36.7%) than females. Males in the highest %BF quartile were 2.1 times more likely sensitized than the lowest quartile (95%CI 1.3-3.5, P-trend=0.003). In males, the risk of allergic sensitization increased with HDL<40 mg/dl (OR=4.0, 95%CI 1.8-9.2) and higher LDL quartiles (P-trend=0.007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization.
In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in males. The observed associations between adiposity, serum lipids and allergic sensitization in males appear to be partially explained by common genetic influences on these traits.
PMCID: PMC2697621  PMID: 19135238
DEXA; Body mass index; Adiposity; Serum lipids; Sensitization
13.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests

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