IMPORTANCE Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. OBJECTIVE To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. DESIGN, SETTING, AND PARTICIPANTS The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. INTERVENTIONS Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10 348) or a tablet containing enalapril, 10 mg, alone (n = 10 354). MAIN OUTCOMES AND MEASURES The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. RESULTS During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.

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Prenatal anemia and iron deficiency are associated with adverse birth outcomes, but no previous studies have examined the relation between preconception anemia, iron deficiency, and pregnancy outcome in healthy women. We measured hemoglobin (Hb), ferritin, transferrin receptor (TfR), and vitamins B-6, B-12, and folate concentrations before pregnancy in 405 Chinese women (median time from sample collection to gestation end = 316 d). Both mild (95 /=60 microg/L) ferritin were also significantly associated with lower birthweight (106 and 123 g, respectively). The risks of low birthweight (LBW) and fetal growth restriction (FGR) were significantly greater among women with moderate anemia compared with nonanemic controls [odds ratio (OR): 6.5; 95% CI: 1.6, 26.7; P = 0.009 and OR: 4.6; 95% CI: 1.5, 13.5; P = 0.006, respectively]. TfR and low ferritin were not associated with adverse birth outcome, but elevated ferritin, which could be a marker of inflammation, was associated with increased risk of LBW (OR: 2.2; 95% CI: 0.9, 5.7; P = 0.09) and FGR (OR: 2.7; 95% CI: 1.3, 5.6; P = 0.008). Preconception anemia, particularly iron-deficiency anemia, was associated with reduced infant growth and increased risk of adverse pregnancy outcome in Chinese women.

BackgroundAnti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China.Methodology/Principal FindingsIn a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%–3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69–15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI,1.23–3.60) risk of prolonged intensive treatment phase.Conclusions/SignificanceATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.

Elevated homocysteine and suboptimal vitamin B-12 and B-6 status may increase the risk of preterm birth. These results need to be confirmed in larger prospective studies.

Results of studies on paternal smoking and spontaneous abortions have been inconsistent. The authors examined the effect of paternal smoking on the risk of pregnancy loss in a prospective cohort of 526 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. Subjects were grouped by the number of cigarettes that husbands reported smoking daily: nonsmokers (group 1, n = 216), fewer than 20 cigarettes (group 2, n = 239), and 20 or more cigarettes (group 3, n = 71). Compared with that for group 1, the adjusted odds ratio of early pregnancy loss of any conception for group 2 was 1.04 (95% confidence interval (CI): 0.67, 1.63) and for group 3 was 1.81 (95% CI: 1.00, 3.29). The adjusted hazard ratio of conception for group 2 was 0.90 (95% CI: 0.70, 1.18) and for group 3 was 0.96 (95% CI: 0.66, 1.39), while the adjusted hazard ratio of clinical pregnancy for group 2 was 0.93 (95% CI: 0.72, 1.20) and for group 3 was 0.78 (95% CI: 0.55, 1.12). The authors conclude that heavy paternal smoking increased the risk of early pregnancy loss through maternal and/or paternal exposure.

Esophageal carcinoma is characterized by a widely ranged incidence variation among the different geographic regions. Anyang is a county in Henan Province of North China with the highest prevalence of esophageal carcinoma. Human papillomavirus (HPV) infection has been linked to the etiology of esophageal cancer in this area. In this study, we investigated correlations of the polymorphisms at low molecular weight polypeptide (LMP) and transporters with antigen processing (TAP) genes, with the risk of esophageal carcinoma. DNA extracted from either tumor specimens or esophageal epithelial cells was used to test HPV infection. Peripheral blood lymphocyte DNA was used for LMP/TAP genotyping. Polymerase chain reaction was performed to analyze HPV infection and LMP/TAP gene polymorphisms. The combined effect of LMP/TAP gene polymorphisms and HPV infection on esophageal carcinoma was analyzed by using unconditional logistic regression models. The TAP2 codons 379 isoleucine carriers and LMP7 codons 145 lysine carriers were found to be more susceptible to esophageal carcinoma (OR = 2.74, 95% CI = 1.15-6.49, P = 0.023 for TAP2; OR = 2.19, 95% CI = 1.09-4.37, P = 0.027 for LMP7). Patients carrying homozygous LMP7/TAP2 haplotype C, which contained the glutamine at LMP7 codons 145 and the isoleucine at TAP2 codons 379, were more prone to develop esophageal carcinoma (OR = 2.96, 95% CI = 1.13-7.81, P = 0.027). An additive effect on the risk of esophageal carcinoma development was found among individuals carrying LMP7/TAP2 haplotype C and infected by HPV (OR = 4.33, 95% CI = 2.53-7.42, P < 0.0001). LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.

Low maternal prepregnancy BMI is associated with adverse birth outcomes, but the BMI at which risk increases is not well defined. We assessed whether the relationship between prepregnancy BMI and birth outcomes is influenced by the extent to which mothers were underweight in a prospective study in Anhui, China. The women (n = 575) were 20-34 y old, married, nulliparous and nonsmokers. All measures of infant growth increased with increasing maternal BMI until a plateau was reached at a BMI of 22-23 kg/m2. Infants born to the 27% of women who were severely underweight before pregnancy (BMI < or = 18.5 kg/m2) were at increased risk for fetal growth deficits associated with infant morbidity. Compared with a normal BMI, being severely underweight was associated with mean (+/- SEM) reductions of 219 +/- 40 g in infant birthweight and 6.7 +/- 1.3% in the birthweight ratio and an 80% increase in risk of intrauterine growth restriction [odds ratio (OR) 1.8; 95% CI: 1.0, 3.3; P = 0.05]. Being severely underweight was also associated with smaller infant head circumference and lower ponderal index. Being moderately underweight (18.5 < BMI < 19.8 kg/m2) was not significantly associated with adverse pregnancy outcomes. Gestational age and risk of preterm birth were not associated with maternal BMI. More than half of the women in this study were underweight before pregnancy. Although being moderately underweight was not associated with increased risk of adverse pregnancy outcomes, being severely underweight was an important risk factor for reduced fetal growth.