A multi-pollutant assessment of preconception persistent endocrine disrupting chemicals and incident pregnancy loss.

BACKGROUND: A few endocrine disrupting chemicals (EDCs) have been associated with pregnancy loss often as reported by women, though there has been no study of EDC mixtures and pregnancy loss in keeping with the nature of human exposure. OBJECTIVES: To investigate preconception exposure to a mixture of EDCs to identify important drivers and inform multi-pollutant models of EDCs in relation to incident human gonadrophin chorionic (hCG) pregnancy loss. METHODS: A cohort of 501 couples were recruited from the general population and prospectively followed until a hCG-confirmed pregnancy or 12 months of trying to become pregnant. Pregnant (n = 344; 69%) women were followed daily through seven weeks post-conception then monthly until delivery. Loss was defined as conversion to negative pregnancy test or a clinical diagnosis. Preconception exposure assessment of EDCs included sixty-three serum chemicals and three blood metals. EDCs were measured using isotope dilution gas chromatography-high resolution mass spectrometry or high-performance liquid chromatography-tandem mass spectrometry, and inductively coupled plasma-mass spectrometry, respectively. Using elastic net variable selection to identify important factors from the exposure mixture, EDC levels and covariates were then included in Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of time-to-pregnancy loss in multi-pollutant models. RESULTS: Incidence of hCG pregnancy loss was 28%. Nine EDCs of the sixty-six chemical mixture were associated with pregnancy loss; HRs were elevated for polychlorinated biphenyl 194, 2-(N-methyl-perfluorooctane sulfonamido) acetate, polybrominated diphenyl ether 28, and cadmium, even in sensitivity models adjusting for male partners' EDC concentrations. In final multivariable multi-pollutant Cox proportional hazard models, female partners'polybrominated diphenyl ether 28 (aHR = 1.16, 95% CI: 1.02, 1.31) and cadmium (aHR = 1.23, 95% CI: 1.07, 1.40) remained associated with hCG pregnancy loss. Female partners' preconception serum polychlorinated biphenyl 194 and 2-(N-methyl-perfluorooctane sulfonamido) acetate concentrations were consistently inversely associated with loss [(aHR = 0.72, 95% CI: 0.56, 0.92) and (aHR = 0.79, 95% CI: 0.65, 0.95), respectively]. CONCLUSION: Assessing exposure to a mixture of 66 persistent EDCs, females' preconception concentrations of polybrominated diphenyl ether 28 and cadmium were positively associated with incident hCG pregnancy loss in a cohort of couples from the general population trying for pregnancy.

Estimating menarcheal age distribution from partially recalled data.

In a cross-sectional study, adolescent and young adult females were asked to recall the time of menarche, if experienced. Some respondents recalled the date exactly, some recalled only the month or the year of the event, and some were unable to recall anything. We consider estimation of the menarcheal age distribution from this interval-censored data. A complicated interplay between age-at-event and calendar time, together with the evident fact of memory fading with time, makes the censoring informative. We propose a model where the probabilities of various types of recall would depend on the time since menarche. For parametric estimation, we model these probabilities using multinomial regression function. Establishing consistency and asymptotic normality of the parametric maximum likelihood estimator requires a bit of tweaking of the standard asymptotic theory, as the data format varies from case to case. We also provide a non-parametric maximum likelihood estimator, propose a computationally simpler approximation, and establish the consistency of both these estimators under mild conditions. We study the small sample performance of the parametric and non-parametric estimators through Monte Carlo simulations. Moreover, we provide a graphical check of the assumption of the multinomial model for the recall probabilities, which appears to hold for the menarcheal data set. Our analysis shows that the use of the partially recalled part of the data indeed leads to smaller confidence intervals of the survival function.

Estimating peer density effects on oral health for community-based older adults.

BACKGROUND: As part of a long-standing line of research regarding how peer density affects health, researchers have sought to understand the multifaceted ways that the density of contemporaries living and interacting in proximity to one another influence social networks and knowledge diffusion, and subsequently health and well-being. This study examined peer density effects on oral health for racial/ethnic minority older adults living in northern Manhattan and the Bronx, New York, NY. METHODS: Peer age-group density was estimated by smoothing US Census data with 4 kernel bandwidths ranging from 0.25 to 1.50 mile. Logistic regression models were developed using these spatial measures and data from the ElderSmile oral and general health screening program that serves predominantly racial/ethnic minority older adults at community centers in northern Manhattan and the Bronx. The oral health outcomes modeled as dependent variables were ordinal dentition status and binary self-rated oral health. After construction of kernel density surfaces and multiple imputation of missing data, logistic regression analyses were performed to estimate the effects of peer density and other sociodemographic characteristics on the oral health outcomes of dentition status and self-rated oral health. RESULTS: Overall, higher peer density was associated with better oral health for older adults when estimated using smaller bandwidths (0.25 and 0.50 mile). That is, statistically significant relationships (p < 0.01) between peer density and improved dentition status were found when peer density was measured assuming a more local social network. As with dentition status, a positive significant association was found between peer density and fair or better self-rated oral health when peer density was measured assuming a more local social network. CONCLUSIONS: This study provides novel evidence that the oral health of community-based older adults is affected by peer density in an urban environment. To the extent that peer density signifies the potential for social interaction and support, the positive significant effects of peer density on improved oral health point to the importance of place in promoting social interaction as a component of healthy aging. Proximity to peers and their knowledge of local resources may facilitate utilization of community-based oral health care.

Nonparametric estimation of time-to-event distribution based on recall data in observational studies.

In a cross-sectional observational study, time-to-event distribution can be estimated from data on current status or from recalled data on the time of occurrence. In either case, one can treat the data as having been interval censored, and use the nonparametric maximum likelihood estimator proposed by Turnbull (J R Stat Soc Ser B 38:290-295, 1976). However, the chance of recall may depend on the time span between the occurrence of the event and the time of interview. In such a case, the underlying censoring would be informative, rendering the Turnbull estimator inappropriate. In this article, we provide a nonparametric maximum likelihood estimator of the distribution of interest, by using a model adapted to the special nature of the data at hand. We also provide a computationally simple approximation of this estimator, and establish the consistency of both the original and the approximate versions, under mild conditions. Monte Carlo simulations indicate that the proposed estimators have smaller bias than the Turnbull estimator based on incomplete recall data, smaller variance than the Turnbull estimator based on current status data, and smaller mean squared error than both of them. The method is applied to menarcheal data from a recent Anthropometric study of adolescent and young adult females in Kolkata, India.