Limitations in Using Multiple Imputation to Harmonize Individual Participant Data for Meta-Analysis.

Individual participant data (IPD) meta-analysis is a meta-analysis in which the individual-level data for each study are obtained and used for synthesis. A common challenge in IPD meta-analysis is when variables of interest are measured differently in different studies. The term harmonization has been coined to describe the procedure of placing variables on the same scale in order to permit pooling of data from a large number of studies. Using data from an IPD meta-analysis of 19 adolescent depression trials, we describe a multiple imputation approach for harmonizing 10 depression measures across the 19 trials by treating those depression measures that were not used in a study as missing data. We then apply diagnostics to address the fit of our imputation model. Even after reducing the scale of our application, we were still unable to produce accurate imputations of the missing values. We describe those features of the data that made it difficult to harmonize the depression measures and provide some guidelines for using multiple imputation for harmonization in IPD meta-analysis.

Relationship between obesity and anti-Müllerian hormone in reproductive-aged African American women.

OBJECTIVE: To determine whether there is an association between obesity and anti-Müllerian hormone (AMH) among reproductive-aged African American women (AAW). METHODS: From the women participating in an ongoing National Institute of Environmental Health Sciences study, 1,654 AAW aged 23 to 35 were included in this study. Anthropometric measurements, personal health information, and serum AMH and adipokine levels were analyzed. RESULTS: The median body mass index (BMI) was 32.4 kg/m2 , and the median AMH was 3.18 ng/mL. Participants with obesity had AMH concentrations that were 23.7% lower than those with a BMI ≤25 kg/m2 (2.9 ng/mL vs. 3.8 ng/mL). In multivariable linear regression models, current BMI (ß = -0.015; 95% CI -0.021 to -0.009), BMI at age 18 (ß = -0.016; 95% CI -0.024 to -0.008), heaviest reported lifetime weight (ß = -0.002; 95% CI -0.003 to -0.001), and leptin (ß = -0.016; 95% CI -0.025 to -0.007) were inversely associated with AMH. There was no significant association between adiponectin and AMH. AMH was significantly lower (mean log = 0.91, SE = 0.11) in participants with obesity at age 18 and at enrollment when compared with those who were underweight or normal weight at age 18 but had obesity at enrollment (mean log = 1.16, SE = 0.12). CONCLUSIONS: In reproductive-aged AAW there is a significant association between obesity and AMH, suggesting that excess adiposity may compromise ovarian reserve. Effects of obesity on AMH may be cumulative.

Novel correlates between antimüllerian hormone and menstrual cycle characteristics in African-American women (23-35 years-old).

OBJECTIVE: To characterize normative antimüllerian hormone (AMH) levels and ascertain which factors are associated with AMH in a large cohort of reproductive-age women. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): A total of 1,654 African-American women (AAW) ages 23-34 at recruitment. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Serum AMH measured using an ultrasensitive ELISA. RESULT(S): The median AMH was 3.18 ng/mL, and there was a significant, but nonlinear, relationship between age and AMH, with levels peaking at age 25. As AMH was not normally distributed, log transformation was performed and used for all analyses. In a multivariable age-adjusted model, body mass index, current use of hormonal contraception, and history of a thyroid condition were inversely associated with AMH, while history of abnormal menstrual bleeding and menstrual cycles longer than 35 days were positively associated with AMH. CONCLUSION(S): While age is correlated with AMH, it accounts for only a portion of the variation seen. This study adds valuable information to the existing literature on normative AMH levels in young reproductive-age women. While our findings fill a critical data gap for ovarian reserve in AAW, the insights gained will be of benefit for all women.

Neighborhood-level racial/ethnic residential segregation and incident cardiovascular disease: the multi-ethnic study of atherosclerosis.

BACKGROUND: Previous research suggests that neighborhood-level racial/ethnic residential segregation is linked to health, but it has not been studied prospectively in relation to cardiovascular disease (CVD). METHODS AND RESULTS: Participants were 1595 non-Hispanic black, 2345 non-Hispanic white, and 1289 Hispanic adults from the Multi-Ethnic Study of Atherosclerosis free of CVD at baseline (aged 45-84 years). Own-group racial/ethnic residential segregation was assessed by using the Gi* statistic, a measure of how the neighborhood racial/ethnic composition deviates from surrounding counties' racial/ethnic composition. Multivariable Cox proportional hazards modeling was used to estimate hazard ratios for incident CVD (first definite angina, probable angina followed by revascularization, myocardial infarction, resuscitated cardiac arrest, coronary heart disease death, stroke, or stroke death) over 10.2 median years of follow-up. Among blacks, each standard deviation increase in black segregation was associated with a 12% higher hazard of developing CVD after adjusting for demographics (95% confidence interval, 1.02-1.22). This association persisted after adjustment for neighborhood-level characteristics, individual socioeconomic position, and CVD risk factors (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23). For whites, higher white segregation was associated with lower CVD risk after adjusting for demographics (hazard ratio, 0.88; 95% confidence interval, 0.81-0.96), but not after further adjustment for neighborhood characteristics. Segregation was not associated with CVD risk among Hispanics. Similar results were obtained after adjusting for time-varying segregation and covariates. CONCLUSIONS: The association of residential segregation with cardiovascular risk varies according to race/ethnicity. Further work is needed to better characterize the individual- and neighborhood-level pathways linking segregation to CVD risk.