Xiaozhong Wen

Childhood body mass index trajectories: modeling, characterizing, pairwise correlations and socio-demographic predictors of trajectory characteristics

BackgroundModeling childhood body mass index (BMI) trajectories, versus estimating change in BMI between specific ages, may improve prediction of later body-size-related outcomes. Prior studies of BMI trajectories are limited by restricted age periods and insufficient use of trajectory information.MethodsAmong 3,289 children seen at 81,550 pediatric well-child visits from infancy to 18 years between 1980 and 2008, we fit individual BMI trajectories using mixed effect models with fractional polynomial functions. From each childs fitted trajectory, we estimated age and BMI at infancy peak and adiposity rebound, and velocity and area under curve between 1 week, infancy peak, adiposity rebound, and 18 years.ResultsAmong boys, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.2 (0.9) and 49.2 (11.9) months, respectively. Among girls, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.4 (1.1) and 46.8 (11.0) months, respectively. Ages at infancy peak and adiposity rebound were weakly inversely correlated (r = -0.09). BMI at infancy peak and adiposity rebound were positively correlated (r = 0.76). Blacks had earlier adiposity rebound and greater velocity from adiposity rebound to 18 years of age than whites. Higher birth weight z-score predicted earlier adiposity rebound and higher BMI at infancy peak and adiposity rebound. BMI trajectories did not differ by birth year or type of health insurance, after adjusting for other socio-demographics and birth weight z-score.ConclusionsChildhood BMI trajectory characteristics are informative in describing childhood body mass changes and can be estimated conveniently. Future research should evaluate associations of these novel BMI trajectory characteristics with adult outcomes.

Decreasing Prevalence of Obesity Among Young Children in Massachusetts From 2004 to 2008

OBJECTIVE: To examine whether the obesity prevalence is increasing, level, or decreasing among young US children (aged <6 years) in the past decade; and to compare regional data to those of 2 national databases. METHODS: We analyzed data from 108 762 well-child visits (36 827 children) at a multisite pediatric practice in eastern Massachusetts during 1999–2008. By using the Centers for Disease Control and Prevention 2000 gender-specific growth charts, we defined obesity as weight-for-length ≥95th percentile for children aged <24 months and BMI ≥95th percentile for children aged 24 to <72 months. By using multivariable logistic regression, we estimated gender-specific obesity trends in 2 separate periods, 1999–2003 and 2004–2008, adjusting for age group, race/ethnicity, health insurance, and practice site. RESULTS: From 1999 to 2003, the obesity prevalence was fairly stable among both boys and girls. From 2004 to 2008, the obesity prevalence substantially decreased among both boys and girls. The decline in obesity prevalence during 2004–2008 was more pronounced among children insured by non-Medicaid health plans than among those insured by Medicaid. CONCLUSIONS: Among children aged <6 years at this multisite pediatric practice, obesity prevalence decreased during 2004–2008, which is in line with national data showing no increase in prevalence during this time period. The smaller decrease among Medicaid-insured children may portend widening of socioeconomic disparities in childhood obesity.

Prenatal Factors for Childhood Blood Pressure Mediated by Intrauterine and/or Childhood Growth?

OBJECTIVE: Some prenatal factors may program an offsprings blood pressure, but existing evidence is inconclusive and mechanisms remain unclear. We examined the mediating roles of intrauterine and childhood growth in the associations between childhood systolic blood pressure (SBP) and 5 potentially modifiable prenatal factors: maternal smoking during pregnancy; prepregnancy BMI; pregnancy weight gain; chronic hypertension; and preeclampsia-eclampsia. METHODS: The sample contained 30 461 mother-child pairs in the Collaborative Perinatal Project. Prenatal data were extracted from obstetric forms, and childrens SBP was measured at 7 years of age. Potential mediation by intrauterine growth restriction (IUGR) and childhood growth was examined by the causal step method. RESULTS: Heavy maternal smoking during pregnancy was significantly associated with higher offspring SBP (adjusted mean difference versus nonsmoking: 0.73 mm Hg [95% confidence interval (CI): 0.32–1.14]), which attenuated to null (0.13 [95% CI: −0.27–0.54]) after adjustment for changes in BMI from birth to 7 years of age. Prepregnancy overweight-obesity was significantly associated with higher offspring SBP (versus normal weight: 0.89 mm Hg [95% CI: 0.52–1.26]), which also attenuated to null (−0.04 mm Hg [95% CI: −0.40–0.31]) after adjustment for childhood BMI trajectory. Adjustment for BMI trajectory augmented the association between maternal pregnancy weight gain and offspring SBP. Adjustment for childhood weight trajectory similarly changed these associations. However, all these associations were independent of IUGR. CONCLUSIONS: Childhood BMI and weight trajectory, but not IUGR, may largely mediate the associations of maternal smoking during pregnancy and prepregnancy BMI with an offsprings SBP.

Associations of CYP2A6 genotype with smoking behaviors in southern China

AIMS To investigate the association of CYP2A6 genetic polymorphisms with smoking-related phenotypes in Chinese smokers. DESIGN Case-only genetic association study. SETTING Southern China. PARTICIPANTS A total of 1328 Han Chinese smokers who participated in a community-based chronic disease screening project in Guangzhou and Zhuhai from 2006 to 2007. MEASUREMENTS All participants answered a structured questionnaire about socio-demographic status and smoking behaviors and informative alleles were genotyped for the cytochrome P450 2A6 (CYP2A6) gene (CYP2A6*4,*5,*7,*9 and *10). FINDINGS The frequencies of CYP2A6*4, *5, *7, *9 and *10 alleles were 8.5, 1.2, 6.3, 13.5 and 2.4%, which corresponded to 48.9, 15.4, 24.2 and 11.5% of participants being classified as normal, intermediate, slow and poor metabolizers, respectively. Multivariate analyses in male smokers demonstrated that compared with normal metabolizers, poor metabolizers reported smoking fewer cigarettes per day [adjusted odds ratio (OR) = 0.49; 95% confidence interval (CI): 0.32-0.76], started smoking regularly later in life (adjusted OR = 1.55; 95% CI: 1.06-2.26) and, among former smokers, reported smoking for a shorter duration prior to quitting (adjusted OR = 0.33; 95% CI: 0.12-0.94). However, poor metabolizers were less likely to quit smoking and remain abstinent than normal metabolizers (adjusted OR = 0.54; 95% CI: 0.34-0.86). CONCLUSIONS Reduced metabolism function of cytochrome P450 2A6 in smokers appears to be associated with fewer cigarettes smoked, later initiation of smoking regularly, shorter smoking duration and lower likelihood of smoking cessation.

Systematic Review and Meta-Analysis on the Association between Outpatient Statins Use and Infectious Disease-Related Mortality

Background To update and refine systematic literature review on the association between outpatient statins use and mortality in patients with infectious disease. Materials and Methods We searched articles published before September 31, 2012, on the association between statins and infectious disease-related mortality through electronic databases. Eligible articles were analyzed in Review Manager 5.1. We conducted stratification analysis by study design, infection types, clinical outcomes and study locations. Results The pooled odds ratio (OR) for death (statins use vs. no use) across the 41 included studies was 0.71 (95% confidence interval: 0.64, 0.78). The corresponding pooled ORs were 0.58 (0.38, 0.90), 0.66 (0.57, 0.75), 0.71 (0.57, 0.89) and 0.83 (0.67, 1.04) for the case-control study, retrospective cohort studies, prospective cohort studies and RCTs; 0.40 (0.20, 0.78), 0.61 (0.41, 0.90), 0.69 (0.62, 0.78) and 0.86 (0.68, 1.09) for bacteremia, sepsis, pneumonia and other infections; 0.62 (0.534, 0.72), 0.68 (0.53, 0.89), 0.71 (0.61, 0.83) and 0.86 (0.70, 1.07) for 30-day, 90-day, in-hospital and long-term (>1 year) mortality, respectively. Conclusions Outpatient statins use is associated with a lower risk of death in patients with infectious disease in observational studies, but in a less extent in clinical trials. This association also varies considerably by infection types and clinical outcomes.

Sociodemographic Differences and Infant Dietary Patterns

OBJECTIVES: To identify dietary patterns in US infants at age 6 and 12 months, sociodemographic differences in these patterns, and their associations with infant growth from age 6 to 12 months. METHODS: We analyzed a subsample (760 boys and 795 girls) of the Infant Feeding Practices Study II (2005–2007). Mothers reported their infants’ intakes of 18 types of foods in the past 7 days, which were used to derive dietary patterns at ages 6 and 12 months by principal component analysis. RESULTS: Similar dietary patterns were identified at ages 6 and 12 months. At 12 months, infants of mothers who had low education or non-Hispanic African American mothers (vs non-Hispanic white) had a higher score on “High sugar/fat/protein” dietary pattern. Both “High sugar/fat/protein” and “High dairy/regular cereal” patterns at 6 months were associated with a smaller increase in length-for-age z score (adjusted β per 1 unit dietary pattern score, −1.36 [95% confidence interval (CI), −2.35 to −0.37] and −0.30 [−0.54 to −0.06], respectively), while with greater increase in BMI z score (1.00 [0.11 to 1.89] and 0.32 [0.10 to 0.53], respectively) from age 6 to 12 months. The “Formula” pattern was associated with greater increase in BMI z score (0.25 [0.09 to 0.40]). The “Infant guideline solids” pattern (vegetables, fruits, baby cereal, and meat) was not associated with change in length-for-age or BMI z score. CONCLUSIONS: Distinct dietary patterns exist among US infants, vary by maternal race/ethnicity and education, and have differential influences on infant growth. Use of “Infant guideline solids” with prolonged breastfeeding is a promising healthy diet for infants after age 6 months.

Interaction between Maternal Passive Smoking during Pregnancy and CYP1A1 and GSTs Polymorphisms on Spontaneous Preterm Delivery

Objective The present study aimed to examine the association between maternal passive smoking during pregnancy and the risk of spontaneous PTD and to explore the potential interaction of the single or joint gene polymorphism of CYP1A1 and GSTs with maternal passive smoking on the risk of spontaneous PTD. Method We investigated whether the association between maternal passive smoking and PTD can be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic regression to test gene-passive smoking interaction, adjusting for maternal socio-demographics and prepregnancy body mass index. Results Overall, maternal passive smoking during pregnancy was associated with higher risk of PTD (adjusted odds ratio = 2.20 [95% confidence interval: 1.56–3.12]). This association was modified by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher risk of PTD among those women with CYP1A1 “TC/CC”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 2.66 [95% CI: 1.19–5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs, maternal passive smoking was associated with higher risk of PTD only among those women with CYP1A1“AG/GG”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 3.00 [95% CI: 1.17–7.74]; P-value: 0.023). Conclusions Our findings suggest that the combined genotypes of CYP1A1 and GSTs can help to identify vulnerable pregnant women who are subject to high risk of spontaneous PTD due to passive smoking.

Association Between Placental Morphology and Childhood Systolic Blood Pressure

We tested hypotheses that disproportionately large placental size and vascular lesions were associated with high systolic blood pressure (SBP); and these associations might be more evident with age. The sample included 13 273 of 40 666 full-term singletons in the Collaborative Perinatal Project. Placentas were examined by pathologists blinded of pregnancy courses and outcomes. The 4-month and 7-year SBPs were measured with palpation and auscultation methods, respectively. We found that placental weight (adjusted mean difference corresponding to an increase by 1 SD 0.50 [95% CI, 0.33 to 0.68]) and placenta–fetus weight ratio (0.37 [95% CI, 0.19 to 0.54]) was positively associated with 7-year SBP but not associated with 4-month SBP. Placental largest and smallest diameters and area were negatively associated with 4-month SBP but positively with 7-year SBP. Placental thickness was negatively associated with 4-month SBP only. Placental volume was negatively associated with 4-month SBP (−0.60 [95% CI, − 0.85 to −0.35]) but positively associated with 7-year SBP (0.48 [95% CI, 0.30 to 0.67]). Thrombi in cord vessels (adjusted mean difference versus absence 2.73 [95% CI, − 0.03 to 5.50]) and decidual vessels (2.58 [95% CI, 0.24 to 4.91]), villous microinfarcts (1.63 [95% CI, 0.71 to 2.55]), necrosis at the decidual margin (1.57 [95% CI, 0.54 to 2.59]), and basalis (3.44 [95% CI, 1.55 to 5.32]) were associated with higher 4-month SBP only. We conclude that placental inefficiency, reflected by disproportionately large weight and size, predicts long-term blood pressure, whereas vascular resistance and lesions may only influence short-term blood pressure.

2-Year BMI Changes of Children Referred for Multidisciplinary Weight Management

Objective. To examine body mass index (BMI) changes among pediatric multidisciplinary weight management participants and nonparticipants. Design. In this retrospective database analysis, we used multivariable mixed effect models to compare 2-year BMI z-score trajectories among 583 eligible overweight or obese children referred to the One Step Ahead program at the Boston Childrens Primary Care Center between 2003 and 2009. Results. Of the referred children, 338 (58%) attended the program; 245 (42%) did not participate and were instead followed by their primary care providers within the group practice. The mean BMI z-score of program participants decreased modestly over a 2-year period and was lower than that of nonparticipants. The group-level difference in the rate of change in BMI z-score between participants and nonparticipants was statistically significant for 0–6 months (P = 0.001) and 19–24 months (P = 0.008); it was marginally significant for 13–18 months (P = 0.051) after referral. Younger participants (<5 years) had better outcomes across all time periods examined. Conclusion. Children attending a multidisciplinary program experienced greater BMI z-score reductions compared with usual primary care in a real world practice; younger participants had significantly better outcomes. Future research should consider early intervention and cost-effectiveness analyses.

Comparison of secondhand smoke exposure measures during pregnancy in the development of a clinical prediction model for small-for-gestational-age among non-smoking Chinese pregnant women

Objective To compare predictive values of small-for-gestational-age (SGA) by different measures for secondhand smoke (SHS) exposure during pregnancy and to develop and validate a prediction model for SGA using SHS exposure along with sociodemographic and pregnancy factors. Methods We compared the predictability of different measures of SHS exposure during pregnancy for SGA among 545 Chinese pregnant women, and then used the optimal SHS measure along with other clinically available factors to develop and validate a prediction model for SGA. We fit logistic regression models to predict SGA by single measures of SHS exposure (self-report, serum cotinine and CYP2A6*4) and different combinations (self-report+cotinine, cotinine+CYP2A6*4, self-report+CYP2A6*4 and self-report+cotinine+CYP2A6*4). Results We found that self-reported SHS exposure alone predicted SGA (area under the receiver operating characteristic curve or area under the receiver operating curve (AUROC), 0.578) better than the other two single measures (cotinine, 0.547; CYP2A6*4, 0.529) or as accurately as combined SHS measures (0.545–0.584). The final prediction model that contained self-reported SHS exposure, prepregnancy body mass index, gestational weight gain velocity during the second and third trimesters, gestational diabetes, gestational hypertension and the third-trimester biparietal diameter Z-score could predict SGA fairly accurately (AUROC, 0.698). Conclusions Self-reported SHS exposure at peribirth performs better in predicting SGA than a single measure of serum cotinine at the same time, although repeated biochemical cotinine assessments throughout pregnancy may be optimal. Our simple prediction model is fairly accurate and can be potentially used in routine prenatal care.