Chuanbo Xie

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 CYP2A6 genetic polymorphisms and lung cancer: a meta-analysis of case-control studies.

Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco‐specific carcinogens (such as N‐nitrosamines). CYP2A6 genetic variations are associated with the activity of the CYP2A6 enzyme, which affects smoking behavior and the rate at which some tobacco‐specific carcinogens are metabolized, which in turn determines the incidence of lung cancer. Several studies have investigated the relationship between CYP2A6 genotypes and lung cancer; however, the results are controversial. In this meta‐analysis, we searched for all studies on the association between CYP2A6 genotypes and lung cancer indexed in the MEDLINE, PubMed, Embase, China Biological Medicine, and Wanfang databases from January 1, 1966 to August 1, 2011. The pooled odds ratios (ORs) for one CYP2A6 mutant allele and two CYP2A6 mutant alleles, in comparison with the wild‐type CYP2A6 gene, were 0.82 [95% confidence interval (CI) = 0.73–0.92] and 0.57 (95% CI = 0.48–0.68), respectively. Furthermore, in two studies of participants who were all smokers, the associations of one CYP2A6 mutant allele and two CYP2A6 mutant alleles with reduced risk of lung cancer were strengthened, and the pooled ORs were 0.71 (95% CI = 0.58–0.87) and 0.47 (95% CI = 0.35–0.62), respectively. However, we did not find statistically significant relationships between CYP2A6 genotypes and lung cancer in studies that included both never smokers and smokers (pooled ORone CYP2A6 mutant allele = 0.88, 95% CI = 0.76–1.01; pooled ORtwo CYP2A6 mutant alleles = 0.61, 95% CI = 0.35–1.06). The results of this meta‐analysis suggest that the reduced‐activity CYP2A6 genotype may decrease the risk of lung cancer in smokers only. Environ. Mol. Mutagen., 2013.

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.

Potential pathways by which maternal second-hand smoke exposure during pregnancy causes full-term low birth weight

It is well documented that maternal exposure to second-hand smoke (SHS) during pregnancy causes low birth weight (LBW), but its mechanism remains unknown. This study explored the potential pathways. We enrolled 195 pregnant women who delivered full-term LBW newborns, and 195 who delivered full-term normal birth weight newborns as the controls. After controlling for maternal age, education level, family income, pre-pregnant body mass index, newborn gender and gestational age, logistic regression analysis revealed that LBW was significantly and positively associated with maternal exposure to SHS during pregnancy, lower placental weight, TNF-α and IL-1β, and that SHS exposure was significantly associated with lower placental weight, TNF-α and IL-1β. Structural equation modelling identified two plausible pathways by which maternal exposure to SHS during pregnancy might cause LBW. First, SHS exposure induced the elevation of TNF-α, which might directly increase the risk of LBW by transmission across the placenta. Second, SHS exposure first increased maternal secretion of IL-1β and TNF-α, which then triggered the secretion of VCAM-1; both TNF-α and VCAM-1 were significantly associated with lower placental weight, thus increasing the risk of LBW. In conclusion, maternal exposure to SHS during pregnancy may lead to LBW through the potential pathways of maternal inflammation and lower placental weight.

Placenta mediates the association between maternal second-hand smoke exposure during pregnancy and small for gestational age

INTRODUCTION The causal relationship between maternal second-hand smoke (SHS) exposure during pregnancy and small for gestational-age (SGA) has been affirmed, but the mechanism is still unclear. Previous studies have found that the placenta remarkably affects fetal intrauterine growth and that SHS exposure during pregnancy impairs placental growth and decreases placental weight. Therefore, the placenta may mediate the association between maternal SHS exposure during pregnancy and SGA. This study explores whether and to what extent the association between maternal SHS exposure during pregnancy and SGA is mediated by the placenta. METHODS We investigated 562 pregnant women delivering SGA newborns (cases) and 1581 delivering appropriate-for-gestational-age newborns (controls) in this case-control study. Information on maternal SHS exposure during pregnancy, socio-demographic characteristics and obstetric conditions, including placental weight, were collected at the Maternity and Child Health Care Hospitals of Shenzhen and Foshan in Guangdong, China. Linear and hierarchical logistic regression models were fitted to examine the mediation effects of placental weight on the association between maternal SHS exposure during pregnancy and SGA. RESULTS After controlling for ethnicity, maternal age, educational level, family income, pre-pregnancy body mass index (BMI), parity, gestational age and newborn gender, maternal SHS exposure during pregnancy was associated with a higher SGA risk (adjusted odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.03-1.55) and lower placental weight (standard deviation (SD) = -0.15, SE = 0.04). Regression models illustrated that placental weight partially mediated (49.6%; 95% CI = 35.9-63.3%) the association between SHS exposure during pregnancy and SGA. DISCUSSION Our findings suggest that the placenta plays an intermediary role in how maternal prenatal SHS exposure affects fetal growth.

Influence of CYP2A6*4 Genotypes on Maternal Serum Cotinine Among Chinese Nonsmoking Pregnant Women

INTRODUCTION Serum cotinine is a common biomarker for smoking and secondhand smoke (SHS) exposure, but it can be affected by the activity of nicotine-metabolizing enzymes. This study investigated the influence of CYP2A6*4 genotypes on serum cotinine among nonsmoking pregnant women. METHODS We analyzed the data from 545 Chinese nonsmoking pregnant women in a case-control study on SHS exposure and birth outcomes in southern China. Participants self-reported their status and duration of SHS exposure during pregnancy right after delivery in hospital. Research staff used polymerase chain reaction to genotype CYP2A6*4 and enzyme-linked immunosorbent assay to measure cotinine levels in maternal serum samples collected before delivery. We stratified women by their self-reported SHS exposure status and CYP2A6*4 genotypes and then compared their median levels of serum cotinine. RESULTS Among women who self-reported non-SHS exposure (n = 317), the median serum cotinine levels were 2.83ng/ml for those with CYP2A6*1/*1 genotype, 1.39ng/ml for CYP2A6*1/*4, and 0.77ng/ml for CYP2A6*4/*4, respectively. Among women who self-reported SHS exposure (n = 228), the median cotinine levels were 3.32ng/ml for those with CYP2A6*1/*1 genotype, 2.38ng/ml for CYP2A6*1/*4, and 1.56ng/ml for CYP2A6*4/*4, respectively. Strikingly, self-reported SHS-exposed women with CYP2A6*1/*4 or CYP2A6*4/*4 genotype had significantly lower (rather than higher) median cotinine levels than self-reported non-SHS-exposed women with CYP2A6*1/*1 genotype (p = .012). CONCLUSIONS CYP2A6*4 genotype is associated with lower serum cotinine among Chinese nonsmoking pregnant women. Measuring CYP2A6*4 genotype may help to improve the validity of SHS exposure measurement by serum cotinine in pregnant women and possibly also in other nonpregnant populations.

Mediating role of maternal serum interleukin-1beta and tumor necrosis factor-alpha in the association between environmental tobacco smoke exposure in pregnancy and low birth weight at term

Abstract Objectives: To explore the mediation effects of maternal serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the association between environmental tobacco smoke (ETS) exposure during pregnancy and low birth weight (LBW) at term. Methods: ETS exposure, birth weight, blood sample and covariates were collected from 195 pregnant women delivered term LBW infants and 195 controls delivered normal birth weight infants in two Maternity and Child Hospitals in Guangdong, China. Maternal serum IL-1β and TNF-α were measured by flow cytometry. Logistic regression models and path analyses explored the mediation effects of maternal IL-1β and TNF-α on the association between ETS exposure and LBW. Results: LBW was significantly associated with maternal ETS exposure (OR = 2.14 (95% CI =1.06–4.32)). TNF-α and IL-1β were significantly associated with both LBW (OR = 1.87 (1.41–2.47) and OR = 1.53 (1.14–2.05)) and ETS (β = 0.32 (0.04–0.60) and β = 0.27 (0.05–0.49)). Traditional mediation analyses indicated the separate mediation effect of TNF-α and IL-1β was 32.2% and 24.6%, respectively. Path analysis revealed the combined mediation effects of TNF-α and IL-1β as 29.4% in the pathway from ETS exposure to LBW. Conclusions: Maternal serum IL-1β and TNF-α may play a mediating role in the association between maternal ETS exposure during pregnancy and term LBW.

Stunting at 5 Years Among SGA Newborns.

OBJECTIVE: To compare risk of stunting at 5 years across etiological subgroups of small for gestational age (SGA) newborns. METHODS: We analyzed data of a subsample (N = 1100) of the Early Childhood Longitudinal Study-Birth Cohort. We defined SGA as birth weight <10th percentile, then classified subjects into etiological subgroups by each of 8 risk factors (ie, maternal prepregnancy underweight, short stature, smoking during pregnancy, alcohol use during pregnancy, inadequate gestational weight gain [GWG], hypertension, genital herpes infection, and multiple births) or by cooccurrence of 2 often intertwined risk factors (smoking and inadequate GWG). We defined stunting as 5 years height-for-age z score below –2. We fitted logistic regression models to test whether the risk of stunting differed across SGA subgroups, adjusting for confounders. RESULTS: SGA subgroup with maternal short stature (odds ratio [OR] = 3.88; 95% confidence interval [CI] = 2.16–6.96) or inadequate GWG (OR = 2.18; 95% CI = 1.23–3.84) had higher risk of stunting at 5 years, compared with the SGA subgroup without the corresponding risk factor. SGA newborns with both maternal smoking and inadequate GWG during pregnancy had much higher risk of stunting at 5 years (OR = 3.10; 95% CI = 1.21–7.91), compared with SGA newborns without any of these 2 SGA risk factors. CONCLUSIONS: Etiological subgroups of SGA differed in risk of stunting at 5 years. SGA newborns of inadequate GWG mothers who smoke and SGA newborns of short mothers were at particularly high risk of stunting.

The mediating role of placenta in the relationship between maternal exercise during pregnancy and full-term low birth weight

Abstract Objective: To explore the association of maternal exercise during pregnancy with full-term low birth weight (FT-LBW) and whether placenta mediates their association. Study design: We investigated 326 pregnant women delivering FT-LBW weight newborns (cases) and 1644 delivering full-term normal birth weight newborns (controls) in this case-control study. Information concerning maternal exercise during pregnancy, socio-demographics and obstetric characteristics were collected at Women and Children’s Hospitals of Shenzhen and Foshan in Guangdong, China. Results: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were significantly negatively associated with FT-LBW, respectively. Moreover, compared with mothers taking no exercise during pregnancy, those taking exercises were significantly negatively associated with FT-LBW except those taking low/medium frequency and short duration exercise and high-frequency and long duration exercise, and their adjusted ORs ranged from 0.30 to 0.62. Furthermore, mediation analysis illustrated that placental weight partially mediated 27.20% of the association between maternal exercise frequency during pregnancy and FT-LBW, but not the association between maternal exercise duration during pregnancy and FT-LBW. Conclusions: Maternal exercise during pregnancy is beneficial for lowering FT-LBW risk, especially when taking appropriate and enough exercise. Placenta weight partially mediates the association between maternal exercise frequency during pregnancy and FT-LBW.