Zhongzheng Niu

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.

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.

Maternal exercise during pregnancy reduces the risk of preterm birth through the mediating role of placenta

Abstract Objective: The extent of research on maternal exercise during pregnancy and the risk of preterm birth (PTB) have grown substantially, but conclusions still remained controversial. Thus, this study aims to examine the relationship of maternal exercise during pregnancy and PTB and explore whether placenta mediates their relationship. Study design: We investigated 849 pregnant women delivering PTB newborns (cases) and 1306 delivering full-term appropriate for gestational age newborns (controls) in this case–control study. Information concerning maternal exercise during pregnancy, sociodemographics and obstetric characteristics were collected at Women and Children’s Hospitals of Shenzhen and Foshan in Guangdong, China. A series of logistic and linear regressions were used to examine the relationships of maternal exercise during pregnancy, placenta, and PTB. Results: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were negatively associated with PTB. Moreover, compared with mother taking no exercise during pregnancy, those taking exercise lowered the risk of PTB except those taking low/medium frequency and short duration exercise, and their adjusted ORs ranged from 0.43 to 0.65. Furthermore, mediation analysis illustrated that placental weight partially mediated 65.20% of the effects of maternal exercise frequency on PTB, as well as 41.98% of the association between maternal exercise duration and PTB. Conclusions: Maternal exercise during pregnancy is beneficial for lowering the risk of PTB, especially when taking appropriate and enough exercise. Placenta weight may partially mediate the association between maternal exercise during pregnancy and PTB.

CHRNA3 rs6495308 Genotype as an Effect Modifier of the Association between Daily Cigarette Consumption and Hypertension in Chinese Male Smokers

Cigarette smoking is an important risk factor for hypertension. However, the effects on hypertension of the interaction between smoking and the genotype of the nicotinic acetylcholine receptor gene are unclear. The purpose of this study is to determine whether the CHRNA3 rs6495308 genotype affects the association between daily cigarette consumption and hypertension. We recruited 947 male smokers in southern China and used a questionnaire administered in face to face interviews to obtain information on their socio-demographic characteristics and smoking behavior. Blood samples were collected to test for CHRNA3 rs6495308 genotype variations. Three blood-pressure measurements were taken for each participant, and the average values recorded. We found that, compared with light smoking (<15 cigarettes per day), heavy smoking (≥15 cigarettes per day) yielded a greater risk of hypertension. We also observed that the interaction between daily cigarette consumption and the CHRNA3 rs6495308 genotype may affect hypertension. Heavy smokers with the homozygous mutant CHRNA3 rs6495308 genotype exhibited a significantly greater risk of hypertension than light smokers with wild-type CHRNA3 rs6495308 genotypes. The positive interaction between heavy smoking and the homozygous mutant CHRNA3 rs6495308 genotype was found to affect the likelihood of hypertension in Chinese male smokers.

Association between prenatal exposure to cooking oil fumes and full-term low birth weight is mediated by placental weight

Objective: Evidence regarding the association between prenatal exposure to cooking oil fumes (COF) and full‐term low birth weight (FTLBW) is still controversial, and the mechanism remains unclear. This study thus aims to explore the association of prenatal COF exposure with off‐spring FT‐LBW as well as the mediating role of placenta in their association. Methods: A case‐control study enrolling 266 pregnant women delivering FTLBW newborns (cases) and 1420 delivering normal birth weight (NBW) newborns (controls) was conducted. Information on prenatal COF exposure, socio‐demographics, and obstetric conditions were collected at the Womens and Childrens Hospitals of Shenzhen and Foshan in Guangdong, China. Linear and hierarchical logistic regression models were undertaken to explore the associations among COF exposure, placenta and birth weight, as well as the mediation effect of placental weight. Results: After controlling for potential confounders, prenatal COF exposure was significantly associated with the higher risk of FT‐LBW (OR = 1.31, 95% CI= 1.06–1.63) and the lower placental weight (ß = −0.12, 95% CI= −0.23 ˜ −0.005). Compared with mothers who never cooked, those cooking sometimes (OR= 2.99, 95% CI= 1.48–6.04) or often (OR= 3.41, 95% CI= 1.40–8.34) showed a higher risk of FT‐LBW, and likewise, those cooking for less than half an hour (OR= 2.08, 95% CI= 1.14–3.79) or cooking between half to an hour (OR= 2.48, 95% CI= 1.44–4.29) were also more likely to exhibit FT‐LBW. Different cooking methods including pan‐frying (OR= 2.24, 95% CI= 1.30–3.85) or deep‐frying (OR= 1.78, 95% CI= 1.12–2.85) during pregnancy were associated with increased FT‐LBW risks as well. The further mediation analysis illustrated that placental weight mediated 15.96% (95% CI: 12.81˜28.80%) and 15.90% (95% CI= 14.62%˜16.66%) of the associations of cooking during pregnancy and frequency of prenatal COF exposure, respectively, with FT‐LBW. HighlightsPrenatal COF exposure was associated with FT‐LBW and placental weight.Pregnant women cook more frequently or longer showed a higher risk of FT‐LBW.Different cooking methods during pregnancy were associated with FT‐LBW risks.Placental weight mediated the associations of prenatal COF exposure with FT‐LBW.

Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls

BackgroundFibroblast growth factor receptor 2 (FGFR2) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association.ResultsWe conducted analyses for each of the five valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and found that per one standard deviation increase in the DNA methylation of CpG 11 at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in placental surface area (β = − 0.18; standard error = 0.08, p = 0.02). The mediation effect of placental surface area on the association between DNA methylation and full-term low birth weight was significant in girls (OR = 1.38, 95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was 48.38%.ConclusionOur findings suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner. Our study supported the importance of placental epigenetic changes in placental development and fetal growth.