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We evaluated relationships between preconception adiposity and human offspring sex and sex ratio. Using data from a prospective preconception cohort nested within a randomized controlled trial based at 4 US clinical sites (2006–2012), we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for male:female sex ratio, and log-identity regression to estimate risk differences (RDs) and 95% CIs for male and female livebirth according to preconception adiposity measures. Inverse-probability weights accounted for potential selection bias. Among 603 women attempting pregnancy, there were meaningful reductions in sex ratio for the highest category of each adiposity measure. The lowest sex ratios were observed for obesity (body mass index of ≥30, calculated as weight (kg)/height (m)2, OR = 0.48, 95% CI: 0.26, 0.88) relative to normal body mass index, and the top tertiles (tertile 3) of serum leptin (OR = 0.50, 95% CI: 0.32, 0.80) and skinfold measurements (OR = 0.50, 95% CI: 0.32, 0.79) relative to the lowest tertiles. Reductions were driven by 11–15 fewer male livebirths per 100 women (for obesity, RD = −15, 95% CI: −23, −6.7; for leptin tertile 3, RD = −11, 95% CI: −20, −3.2; and for skinfolds tertile 3, RD = −11, 95% CI: −19, −3.3). We found that relationships between preconception adiposity measures and reduced sex ratio were driven by a reduction in male births. [ABSTRACT FROM AUTHOR]

Earlier age at menopause is associated with increased long-term health risks. Moderate alcohol intake has been suggested to delay menopause onset, but it is unknown whether alcohol subtypes are associated with early menopause onset at age 45 years. Therefore, we aimed to evaluate risk of early natural menopause among 107,817 members of the Nurses' Health Study II who were followed from 1989 to 2011. Alcohol consumption overall and by subtypes, including beer, red wine, white wine, and liquor, was assessed throughout follow-up. We estimated hazard ratios in multivariable models that were adjusted for age, body mass index, parity, smoking, and other potential confounders. Women who reported moderate current alcohol consumption had lower risks of early menopause than did nondrinkers. Those who reported consuming 10.0–14.9 g/day had a lower risk of early menopause than did nondrinkers (hazard ratio = 0.81, 95% confidence interval: 0.68, 0.97). Among specific beverages, evidence of lower early menopause risk was confined to consumption of white wine and potentially red wine and liquor, but not to beer. Data from this large prospective study suggest a weak association of moderate alcohol intake with lower risk of early menopause, which was most pronounced for consumption of white and red wine and liquor. High consumption was not related to lower risk of early menopause. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B and C viruses are well-established risk factors for hepatocellular carcinoma (HCC) but their coordinated etiologic mechanism remains unclear. We aimed to assess the mediation effect of the two viruses on HCC risk.Methods: We conducted a prospective cohort study in Taiwan (R.E.V.E.A.L.-Hepatitis B Virus study), which included 3,851 participants seropositive for hepatitis B surface antigen and 278 incident HCC cases. Serum samples at enrollment or follow-up were tested for seromarkers and viral load of hepatitis B (HBV) and C (HCV). Mediation analyses for HCC risk were performed using Cox proportional hazards and linear regression models.Results: Among participants with chronic hepatitis B, the direct effect of anti-HCV serostatus (positive vs. negative) independent of HBV viral load was associated with increased risk of HCC with a hazard ratio (HR) of 2.5 (95% confidence interval [CI] = 1.7, 3.6), and the indirect effect mediated through suppressing HBV viral load decreased the HCC risk with an HR of 0.75 (95% CI = 0.67, 0.84). Opposite effects led to an attenuated marginal effect with an HR of 1.7 (95% CI = 1.2, 2.5). For an increase in HCV viral load from 800 to 404,000 IU/ml (minimum to median viral level), the HRs were 1.6 (95% CI = 1.2, 2.0) for the direct effect, 0.78 (95% CI = 0.72, 0.85) for the indirect effect, and 1.1 (95% CI = 0.89, 1.5) for the marginal effect.Conclusion: The results support a suppressive effect of HCV on HCC risk mediated through HBV viral load and an adverse direct effect. [ABSTRACT FROM AUTHOR]

Objective: To estimate the association between physical activity and risk of subclinical and clinical pregnancy loss among women with a history of pregnancy loss.Design: Prospective cohort study as a secondary analysis of the Effects of Aspirin in Gestation and Reproduction randomized controlled trial of preconception-initiated low-dose aspirin among women with one or two prior pregnancy losses.Setting: Four U.S. clinical centers, 2007-2011.Patient(s): Women with confirmed pregnancy (n = 785) as determined from hCG testing in longitudinally collected biospecimens.Main Outcome Measure(s): Subclinical loss of pregnancy detected only by hCG testing and clinically recognized loss.Result(s): Among 785 women (mean [SD] age, 28.7 [4.6] years) with an hCG-confirmed pregnancy, 188 (23.9%) experienced pregnancy loss. In multivariable models adjusted for confounders, compared with the first tertile of physical activity (median = 7.7 metabolic equivalent of task hours/week), there was a roughly twofold higher risk of subclinical loss in the second (risk ratio = 2.06; 95% confidence interval, 1.03-4.14) and third tertiles (risk ratio = 1.92; 95% confidence interval, 0.94-3.90), with median metabolic equivalent of task hours/week of 27.8 and 95.7, respectively. No relations were observed between physical activity and clinically recognized loss.Conclusion(s): Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss. Higher physical activity levels were associated with an elevated risk of subclinical loss (i.e., pregnancies detected only by hCG, n = 55); however, no relationship was observed with clinically recognized loss. Further work is required to confirm these findings, assess generalizability to women without prior losses, and evaluate mechanisms.Ethical Approval: Each participating center's Institutional Review Board approved the study, and participants provided written informed consent. The trial was registered on ClinicalTrials.gov (NCT00467363), and a Data Safety and Monitoring Board provided oversight. [ABSTRACT FROM AUTHOR]