Lihua Wang

Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study

OBJECTIVE To examine rates of conception and pregnancy loss and their relations with time to clinical pregnancy and reproductive outcomes. DESIGN A prospective observational study. SETTING Population-based cohort in China. PATIENT(S) Five hundred eighteen healthy newly married women who intended to conceive. Upon stopping contraception, daily records of vaginal bleeding and daily first-morning urine specimens were obtained for < or =1 year or until a clinical pregnancy was achieved. Daily urinary hCG was assayed to detect early pregnancy loss (EPL). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Conception, pregnancy loss, and time to clinical pregnancy. RESULT(S) The conception rate per cycle was 40% over the first 12 months. Of the 618 detectable conceptions, 49 (7.9%) ended in clinical spontaneous abortion, and 152 (24.6%) in EPL. Early pregnancy loss was detected in 14% of all the cycles without clinically recognized pregnancy, but the frequencies were lower among women with delayed time to clinical pregnancy. Early pregnancy loss in the preceding cycle was associated with increased odds of conception (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.9), clinical pregnancy (OR, 2.0; 95% CI, 1.3-3.0), and EPL (OR, 2.4; 95% CI, 1.4-4.2) but was not associated with spontaneous abortion, low birth weight, or preterm birth in the subsequent cycle. CONCLUSION(S) We demonstrated substantial EPL in the non-clinically pregnant cycles and a positive relation between EPL and subsequent fertility.

A Common Haplotype of the Nicotine Acetylcholine Receptor α4 Subunit Gene Is Associated with Vulnerability to Nicotine Addiction in Men

Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.

Polymorphisms of the paraoxonase gene and risk of preterm delivery.

Background: Human paraoxonase (PON) is an enzyme involved in vasodilation and thrombosis. Disruption of blood blow through the placenta could be part of the pathophysiological mechanism leading to preterm delivery. The purpose of this study was to examine the association between polymorphisms in 2 paraoxonase genes (PON1 and PON2) and preterm delivery. Methods: We conducted a case-control study using infant-parents triads in Anqing, China. Between July 1999 and June 2001, we enrolled the families of 105 infants born at term and 80 infants born preterm. Genotyping was performed for the polymorphisms of PON1 Q192R, PON2 A148G, and PON2 S311C using standard techniques. We used log-linear modeling to analyze the association of PON1 and PON2 gene polymorphisms with the risk of preterm delivery. Results: In the analysis of children’s genotypes, the relative risk was 3.6 (95% confidence interval [CI] = 1.3–11) for PON1 RR compared with PON1 QQ. An association was also seen for PON2 CC compared with PON2 SS (relative risk = 4.6; CI = 1.5–14). There was no association between the mother’s PON1 and PON2 genotypes and preterm delivery, and we did not observe an interaction between mothers’ and children’s genotypes. Analysis of control triads suggests Mendelian transmissions of the variant alleles of PON1 192R, PON2 148G, and PON2 311C. Conclusion: Infant PON1 RR and PON2 CC genotypes were associated with preterm delivery in our study population, which suggests a possible role for human paraoxonase variability in the etiology of preterm delivery.

Large-Scale Genome-Wide Linkage Analysis for Loci Linked to BMD at Different Skeletal Sites in Extreme Selected Sibships†

Few genome‐wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome‐wide scan involving 3093 adult siblings with at least one sib‐pair extremely concordant or discordant for hip BMD. Our results indicated four genome‐wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance.

Effect of environmental tobacco smoke on levels of urinary hormone markers

Our recent study showed a dose–response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a ±10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (β= –0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (β= –0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.

Does standing at work during pregnancy result in reduced infant birth weight

Learning ObjectivesRecall the results of previous studies relating work-related activities to pregnancy outcomes.Describe the findings of the present study and to what degree they are influenced by possible confounding factors such as gestational age.Explain the mechanisms by which prolonged standing at work might influence pregnancy, and for whom preventive measures might be appropriate.The purpose of this study was to investigate the association between infant birth weight and standing at work during pregnancy. A total of 1222 pregnant women employed in a large petrochemical corporation in Beijing, China, were enrolled in the study after receiving permission from the government to have a child. The subjects were followed up from that time through their entire pregnancy, for a total of up to 12 months. All subjects delivered at the company staff hospital between 1996 and 1998. Various work-related physical activities during pregnancy were assessed using a structured questionnaire, and generalized additive models (GAMs) were performed to examine their association with birth weight. Of the assessed activities, only standing was significantly associated with birth weight. After adjusting for potential confounders, maternal standing hours per day at work was found to be significantly associated with reduced birth weight (−17.7 g, P = 0.03).

Petrochemical exposure and menstrual disturbances

BACKGROUND An exploratory, cross-sectional retrospective study was conducted to examine the effects of benzene exposure on menstrual problems. METHODS The study was based on a survey administered to over 3,000 women who worked in a large petrochemical company in Beijing, China. An abnormal menstrual cycle length (AMCL), defined as an average menstrual cycle length of greater than 35 days or less than 21 days, is the major outcome of interest. RESULTS After 7 years of benzene exposure, the adjusted odds ratio of having AMCL for each additional 5 years of exposure was 1.71 (95% CI 1.27-2.31). Feeling stressed at work was also an important predictor. CONCLUSIONS This study suggests a significant association of benzene exposure and perceived stress with menstrual disturbance. A prospective study is needed to confirm this finding.

Association of combined maternal-fetal TNF-alpha gene G308A genotypes with preterm delivery: a gene-gene interaction study.

Preterm delivery (PTD) is a complicated perinatal adverse event. We were interested in association of G308A polymorphism in tumor necrosis factor-α (TNF-α) gene with PTD; so we conducted a genetic epidemiology study in Anqing City, Anhui Province, China. Case families and control families were all collected between July 1999 and June 2002. To control potential population stratification as we could, all eligible subjects were ethnic Han Chinese. 250 case families and 247 control families were included in data analysis. A hybrid design which combines case-parent triads and control parents was employed, to test maternal-fetal genotype (MFG) incompatibility. The method is based on a log-linear modeling approach. In summary, we found that when the mothers or childs genotype was G/A, there was a reduced risk of PTD; however when the mothers or childs genotype was genotype A/A, there was a relatively higher risk of PTD. Combined maternal-fetal genotype GA/GA showed the most reduced risk of PTD. Comparison of the LRTs showed that the model with maternal-fetal genotype effects fits significantly better than the model with only maternal and fetal genotype main effects (log-likelihood = −719.4, P = .023, significant at 0.05 level). That means that the combined maternal-fetal genotype incompatibility was significantly associated with PTD. The model with maternal-fetal genotype effects can be considered a gene-gene interaction model. We claim that both maternal effects and fetal effects should be considered together while investigating genetic factors of certain perinatal diseases.