Sungduk Kim

Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.

The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; obtaining environmental data across sensitive windows of reproduction and development; home-based biospecimen collection; and development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e., fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424,423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ∼ 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time.

The relationship between male BMI and waist circumference on semen quality: data from the LIFE study

Michael L. Eisenberg1,*, Sungduk Kim2, Zhen Chen2, Rajeshwari Sundaram2, Enrique F. Schisterman2, and Germaine M. Buck Louis2 Departments of Urology, Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5118, USA Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Blvd., Room 7B03, Rockville, MD 20852, USA

Racial/ethnic standards for fetal growth: The NICHD Fetal Growth Studies

OBJECTIVE Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. STUDY DESIGN We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. RESULTS EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). CONCLUSION Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Persistent Environmental Pollutants and Couple Fecundity: The LIFE Study

Background: Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured. Objectives: We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy. Methods: A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples completed daily journals on lifestyle and provided biospecimens for the quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7 perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we estimated fecundability odds ratios (FORs) and 95% CIs separately for each partner’s concentrations adjusting for age, body mass index, serum cotinine, serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity models were further adjusted for left truncation or time off of contraception (≤ 2 months) before enrollment. Results: The adjusted reduction in fecundability associated with standard deviation increases in log-transformed serum concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and perfluorooctane sulfonamide in females; and between 17% and 29% for p,p´-DDE and PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males. Conclusions: In this couple-based prospective cohort study with preconception enrollment and quantification of exposures in both female and male partners, we observed that a subset of persistent environmental chemicals were associated with reduced fecundity.

The Green Ocean Amazon Experiment (GoAmazon2014/5) Observes Pollution Affecting Gases, Aerosols, Clouds, and Rainfall over the Rain Forest

AbstractThe Observations and Modeling of the Green Ocean Amazon 2014–2015 (GoAmazon2014/5) experiment took place around the urban region of Manaus in central Amazonia across 2 years. The urban pollution plume was used to study the susceptibility of gases, aerosols, clouds, and rainfall to human activities in a tropical environment. Many aspects of air quality, weather, terrestrial ecosystems, and climate work differently in the tropics than in the more thoroughly studied temperate regions of Earth. GoAmazon2014/5, a cooperative project of Brazil, Germany, and the United States, employed an unparalleled suite of measurements at nine ground sites and on board two aircraft to investigate the flow of background air into Manaus, the emissions into the air over the city, and the advection of the pollution downwind of the city. Herein, to visualize this train of processes and its effects, observations aboard a low-flying aircraft are presented. Comparative measurements within and adjacent to the plume followed t...

Lipid concentrations and semen quality: the LIFE study

The decline in sperm count rates over the last 50 years appears to parallel the rising prevalence of obesity. As lipid levels are strongly associated with obesity, high lipids levels or hyperlipidaemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between mens serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately 1 month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of spermatozoa with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity.

Perfluorochemicals and human semen quality: the LIFE study.

Background: The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. Objectives: We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. Methods: Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log–transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points. Results: Six PFCs [2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. Conclusions: Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions. Citation: Buck Louis GM, Chen Z, Schisterman EF, Kim S, Sweeney AM, Sundaram R, Lynch CD, Gore-Langton RE, Barr DB. 2015. Perfluorochemicals and human semen quality: the LIFE Study. Environ Health Perspect 123:57–63; http://dx.doi.org/10.1289/ehp.1307621

Bayesian Variable Selection and Computation for Generalized Linear Models with Conjugate Priors

In this paper, we consider theoretical and computational connections between six popular methods for variable subset selection in generalized linear models (GLMs). Under the conjugate priors developed by Chen and Ibrahim (2003) for the generalized linear model, we obtain closed form analytic relationships between the Bayes factor (posterior model probability), the Conditional Predictive Ordinate (CPO), the L measure, the Deviance Information Criterion (DIC), the Aikiake Information Criterion (AIC), and the Bayesian Information Criterion (BIC) in the case of the linear model. Moreover, we examine computational relationships in the model space for these Bayesian methods for an arbitrary GLM under conjugate priors as well as examine the performance of the conjugate priors of Chen and Ibrahim (2003) in Bayesian variable selection. Specifically, we show that once Markov chain Monte Carlo (MCMC) samples are obtained from the full model, the four Bayesian criteria can be simultaneously computed for all possible subset models in the model space. We illustrate our new methodology with a simulation study and a real dataset.

Properties and Implementation of Jeffreys's Prior in Binomial Regression Models.

We study several theoretical properties of Jeffreys’s prior for binomial regression models. We show that Jeffreys’s prior is symmetric and unimodal for a class of binomial regression models. We characterize the tail behavior of Jeffreys’s prior by comparing it with the multivariate t and normal distributions under the commonly used logistic, probit, and complementary log–log regression models. We also show that the prior and posterior normalizing constants under Jeffreys’s prior are linear transformation-invariant in the covariates. We further establish an interesting theoretical connection between the Bayes information criterion and the induced dimension penalty term using Jeffreys’s prior for binomial regression models with general links in variable selection problems. Moreover, we develop an importance sampling algorithm for carrying out prior and posterior computations under Jeffreys’s prior. We analyze a real data set to illustrate the proposed methodology.

The association between a medical history of depression and gestational diabetes in a large multi-ethnic cohort in the United States.

BACKGROUND Both major depression and gestational diabetes mellitus (GDM) are prevalent among women of reproductive age. Our objective was to determine whether a medical history of depression is related to subsequent development of GDM. METHODS The Consortium on Safe Labor was a US retrospective cohort study of 228,562 births between 2002 and 2008. Exclusion criteria for the present analysis included multiple gestation pregnancies (n = 5059), pre-existing diabetes (n = 12,771), deliveries <24 weeks (n = 395), site GDM prevalence (<1%) (n = 20, 721) and missing data on pre-pregnancy body mass index (BMI) (n = 61,321). Using generalised estimating equations, we estimated the association between a history of depression and a pregnancy complicated by GDM. RESULTS The final analytic population included 121, 260 women contributing 128 295 pregnancies, of which 5606 were affected by GDM. A history of depression was significantly associated with an increased risk of developing GDM (multivariate odds ratio [aOR] = 1.42 [95% confidence interval (CI) 1.26, 1.60]). Adjusting for pre-pregnancy BMI and weight gain during pregnancy attenuated the association, although it remained statistically significant (aOR = 1.17 [95% CI 1.03, 1.33]). CONCLUSIONS A history of depression was significantly associated with an increased GDM risk among a large multi-ethnic US cohort of women. If the association is confirmed, depression presents a potentially modifiable risk factor of GDM and provides additional clues to the underlying pathophysiology of GDM.