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1.  Physical activity and sedentary behavior patterns using accelerometry from a national sample of United States adults 
This study described the patterns of accelerometer-determined physical activity and sedentary behavior among adults using a nationally representative sample from the United States.
Using 2003-2006 National Health and Nutrition Examination Survey (NHANES) data, 7931 adults at least 18 years old wore an ActiGraph accelerometer for one week, providing at least 3 days of wear for >=8 hours/day. Cutpoints defined moderate to vigorous physical activity (MVPA; >= 2020 and >=760 counts/minute), vigorous physical activity (> = 5999 counts/minute), and sedentary behavior (<100 counts/minute). Latent class analysis (LCA) was used to estimate patterns of physical activity and sedentary behavior. All estimates were weighted to reflect the United States population.
For weighted percent of MVPA out of total wearing time, 5 classes were identified from least to most active: 65.3% of population (weighted mean 9.3 minutes/day), 24.9% (32.1 minutes/day), 3.2% that was low on the weekdays but much higher on the weekends (52.0 minutes/day), 5.9% (59.9 minutes/day), and 0.7% in the highest class (113.6 minutes/day). Using the lower MVPA threshold, 6 classes emerged with each class ranging in population from 1.2% to 43.6%. A vigorous activity class could not be derived due to low prevalence. For weighted percent of sedentary behavior out of total wearing time, 5 classes were identified from most to least sedentary: 6.3% of population (weighted mean 660.2 minutes/day), 25.1% (546.8 minutes/day), 37.7% (453.9 minutes/day), 24.0% (354.8 minutes/day), and 7.0% (256.3 minutes/day). Four of the classes showed generally similar results across every day of the week, with the absolute percents differing across classes. In contrast, the least sedentary class showing a marked rise in percent of time spent in sedentary behavior on the weekend (weighted mean 336.7-346.5 minutes/day) compared to weekdays (weighted mean 255.2-292.4 minutes/day).
The LCA models provided a data reduction process to identify patterns using minute-by-minute accelerometry data in order to explore meaningful contrasts. The models supported 5 or 6 distinct patterns for MVPA and sedentary behavior. These physical activity and sedentary behavior patterns can be used as intervention targets and as independent or dependent variables in future studies of correlates, determinants, or outcomes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-015-0183-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4336769
Accelerometry; Latent class analysis; Moderate to vigorous physical activity; Surveillance; Weekend warrior
2.  Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico 
Environmental Health Perspectives  2014;123(2):186-192.
Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations.
Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children.
Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals.
Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length.
Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.
Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192;
PMCID: PMC4314242  PMID: 25325819
3.  Breast cancer subtypes and previously established genetic risk factors: A Bayesian approach 
Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least 5 immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study.
We used Bayesian polytomous logistic regression to estimate odds ratios (ORs) and 95% posterior intervals (PIs) for the association between each of 78 single nucleotide polymorphisms (SNPs) and 5 breast cancer subtypes. Subtypes were defined using 5 immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2) and cytokeratin (CK) 5/6.
Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2−) or basal-like breast cancer (ER−, PR−, HER2−, HER1 or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), or HER2+/ER− disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1.
Conclusion and Impact
We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes.
PMCID: PMC3947131  PMID: 24177593
breast cancer; single nucleotide polymorphisms; breast cancer subtypes; GWAS; Bayesian analysis
4.  Cervical mucus monitoring prevalence and associated fecundability in women trying to conceive 
Fertility and sterility  2013;100(4):1033-1038.e1.
To assess the use of cervical mucus monitoring (CMM) in women trying to conceive and determine whether monitoring is associated with increased cycle-specific probability of conception (fecundability).
Time-to-pregnancy cohort study.
Population-based cohort.
Three hundred thirty-one women trying to conceive, ages 30 to 44 years, without known infertility
Main Outcome Measure(s)
CMM prevalence and fecundability.
During the first cycle of the study, CMM was performed consistently (checked on >66% of pertinent cycle days) by 20 women (6%), inconsistently (34% to 66% of days) by 60 women (18%), infrequently (≤ 33% of days) by 73 women (22%), and not performed by 178 women (54%). Cycles in which CMM was consistently performed were statistically significantly more likely to result in conception after adjusting for age, race, previous pregnancy, body mass index, intercourse frequency, and urinary luteinizing hormone (LH) monitoring. Fecundability also increased with increasing consistency of CMM.
Among women trying to conceive, CMM is uncommon, but our study suggests that CMM–a free, self-directed method to determine the fertile window–is associated with increased fecundability independent of intercourse frequency or use of urinary LH monitoring.
PMCID: PMC3787999  PMID: 23850303
Cervical mucus monitoring; fertile window; conception; fecundability
5.  Maternal Influences on Nausea and Vomiting in Early Pregnancy 
Maternal and child health journal  2011;15(1):122-127.
Symptoms of nausea and vomiting in early pregnancy (NVP) are common among pregnant women, but whether some women are more likely than others to experience these symptoms has not been well established. We examined potential risk factors for NVP symptom severity, timing of onset, and duration. We included 2,407 newly pregnant women who participated in a prospective cohort study on early pregnancy health between 2000 and 2004 in three U.S. cities. Data on NVP and other health information were collected through telephone interviews, early gestation ultrasound, and medical record abstractions. Generalized linear models were used to model possible risk factors for each NVP characteristic. Eighty-nine percent of women had NVP; for 99% of these, symptoms started in the first trimester. None of the characteristics examined were associated with having NVP. Among those with NVP, increasing risk of delayed symptoms onset was associated with advancing maternal age; increased risks were also seen among non-Hispanic Black [Risk ratio (RR) = 4.3, 95% confidence interval (CI): 1.6,11.6] and Hispanic women (RR = 2.3, 95% CI:0.4,11.5). NVP symptoms for multigravidae were more likely to last beyond the first trimester with each additional pregnancy. Most pregnant women experienced NVP. Nearly all of them, regardless of characteristics examined, had symptoms beginning in the first trimester. Maternal age, race/ethnicity, and gravidity were associated with delayed onset and symptoms that persisted into the second trimester.
PMCID: PMC4182010  PMID: 20012346
Gravidity; Maternal nausea and vomiting; Pregnancy
6.  Association between arsenic, cadmium, manganese, and lead levels in private wells and birth defects prevalence in North Carolina: a semi-ecologic study 
BMC Public Health  2014;14(1):955.
Toxic metals including arsenic, cadmium, manganese, and lead are known human developmental toxicants that are able to cross the placental barrier from mother to fetus. In this population-based study, we assess the association between metal concentrations in private well water and birth defect prevalence in North Carolina.
A semi-ecologic study was conducted including 20,151 infants born between 2003 and 2008 with selected birth defects (cases) identified by the North Carolina Birth Defects Monitoring Program, and 668,381 non-malformed infants (controls). Maternal residences at delivery and over 10,000 well locations measured for metals by the North Carolina Division of Public Health were geocoded. The average level of each metal was calculated among wells sampled within North Carolina census tracts. Individual exposure was assigned as the average metal level of the census tract that contained the geocoded maternal residence. Prevalence ratios (PR) with 95% confidence intervals (CI) were calculated to estimate the association between the prevalence of birth defects in the highest category (≥90th percentile) of average census tract metal levels and compared to the lowest category (≤50th percentile).
Statewide, private well metal levels exceeded the EPA Maximum Contaminant Level (MCL) or secondary MCL for arsenic, cadmium, manganese, and lead in 2.4, 0.1, 20.5, and 3.1 percent of wells tested. Elevated manganese levels were statistically significantly associated with a higher prevalence of conotruncal heart defects (PR: 1.6 95% CI: 1.1-2.5).
These findings suggest an ecologic association between higher manganese concentrations in drinking water and the prevalence of conotruncal heart defects.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-955) contains supplementary material, which is available to authorized users.
PMCID: PMC4190372  PMID: 25224535
Metals; Arsenic; Cadmium; Manganese; Lead; Congenital heart defect; Drinking water; Birth defects; Congenital anomalies
7.  Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer 
Cancer epidemiology  2013;37(4):479-491.
Heavy alcohol consumption increases risk of developing squamous cell carcinoma of the head and neck (SCCHN). Alcohol metabolism to cytotoxic and mutagenic intermediates acetaldehyde and reactive oxygen species is critical for alcohol-drinking-associated carcinogenesis. We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival.
Interview and genotyping data (64 polymorphisms in 12 genes) were obtained from 1227 white and African-American cases from the Carolina Head and Neck Cancer Epidemiology study, a population-based case–control study of SCCHN conducted in North Carolina from 2002 to 2006. Vital status, date and cause of death through 2009 were obtained from the National Death Index. Kaplan–Meier log-rank tests and adjusted hazard ratios were calculated to identify alleles associated with survival.
Most tested SNPs were not associated with survival, with the exception of the minor alleles of rs3813865 and rs8192772 in CYP2E1. These were associated with poorer cancer-specific survival (HRrs3813865, 95%CI = 2.00, 1.33–3.01; HRrs8192772, 95%CI = 1.62, 1.17–2.23). Hazard ratios for 8 additional SNPs in CYP2E1, GPx2, SOD1, and SOD2, though not statistically significant, were suggestive of differences in allele hazards for all-cause and/or cancer death. No consistent associations with survival were found for SNPs in ADH1B, ADH1C, ADH4, ADH7, ALDH2, GPx2, GPx4, and CAT.
We identified some polymorphisms in alcohol and oxidative stress metabolism genes that influence survival in subjects with SCCHN. Previously unreported associations of SNPs in CYP2E1 warrant further investigation.
PMCID: PMC3725265  PMID: 23632049
Head and neck neoplasms/epidemiology; Genes; Survival; Alcohol drinking/metabolism; Oxidative stress
8.  Single Nucleotide Polymorphisms in Nucleotide Excision Repair Genes, Cigarette Smoking, and the Risk of Head and Neck Cancer 
Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC.
Using population-based case-control data from the Carolina Head and Neck Cancer Epidemiology Study (1,227 cases, 1,325 controls), race-stratified (white, African American) conventional and hierarchical logistic regression models were utilized to estimate odds ratios (OR) with 95% intervals (I) for the independent and joint effects of cigarette smoking and 84 single nucleotide polymorphisms (SNPs) from 15 NER genes on HNC risk.
The odds of HNC were elevated among ever cigarette smokers, and increased with smoking duration and frequency. Among whites, rs4150403 on ERCC3 was associated with increased HNC odds (AA+AG vs. GG, OR=1.28, 95% I=1.01,1.61). Among African Americans, rs4253132 on ERCC6 was associated with decreased HNC odds (CC+CT vs. TT, OR=0.62, 95% I=0.45,0.86). Interactions between ever cigarette smoking and three SNPs (rs4253132 on ERCC6, rs2291120 on DDB2, and rs744154 on ERCC4) suggested possible departures from additivity among whites.
We did not find associations between some previously studied NER variants and HNC. We did identify new associations between two SNPs and HNC and three suggestive cigarette-SNP interactions to consider in future studies.
We conducted one of the most comprehensive evaluations of NER variants, identifying a few SNPs from biologically plausible candidate genes associated with HNC and possibly interacting with cigarette smoking.
PMCID: PMC3766549  PMID: 23720401
Head and neck/oral cancers; DNA damage and repair mechanisms; DNA repair polymorphisms and risk; tobacco
9.  Maternal Exposure to Criteria Air Pollutants and Congenital Heart Defects in Offspring: Results from the National Birth Defects Prevention Study 
Environmental Health Perspectives  2014;122(8):863-872.
Background: Epidemiologic literature suggests that exposure to air pollutants is associated with fetal development.
Objectives: We investigated maternal exposures to air pollutants during weeks 2–8 of pregnancy and their associations with congenital heart defects.
Methods: Mothers from the National Birth Defects Prevention Study, a nine-state case–control study, were assigned 1-week and 7-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth controls and 3,328 live-birth, fetal-death, or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics and tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context.
Results: Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the 7-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels.
Conclusions: Using daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy.
Citation: Stingone JA, Luben TJ, Daniels JL, Fuentes M, Richardson DB, Aylsworth AS, Herring AH, Anderka M, Botto L, Correa A, Gilboa SM, Langlois PH, Mosley B, Shaw GM, Siffel C, Olshan AF, National Birth Defects Prevention Study. 2014. Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the National Birth Defects Prevention Study. Environ Health Perspect 122:863–872;
PMCID: PMC4123026  PMID: 24727555
10.  Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival 
Cancer causes & control : CCC  2014;25(4):437-450.
Head and neck cancers (HNC) are commonly treated with radiation and platinum-based chemotherapy, which produce bulky DNA adducts to eradicate cancerous cells. Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment.
Cox proportional hazards models were used to estimate race-stratified (White, African American) hazard ratios (HRs) and 95 % confidence intervals for overall (OS) and disease-specific (DS) survival based on treatment (combinations of surgery, radiation, and chemotherapy) and 84 single nucleotide polymorphisms (SNPs) in 15 NER genes among 1,227 HNC cases from the Carolina Head and Neck Cancer Epidemiology Study.
None of the NER variants evaluated were associated with survival at a Bonferroni-corrected alpha of 0.0006. However, rs3136038 [OS HR = 0.79 (0.65, 0.97), DS HR = 0.69 (0.51, 0.93)] and rs3136130 [OS HR = 0.78 (0.64, 0.96), DS HR = 0.68 (0.50, 0.92)] of ERCC4 and rs50871 [OS HR = 0.80 (0.64, 1.00), DS HR = 0.67 (0.48, 0.92)] of ERCC2 among Whites, and rs2607755 [OS HR = 0.62 (0.45, 0.86), DS HR = 0.51 (0.30, 0.86)] of XPC among African Americans were suggestively associated with survival at an uncorrected alpha of 0.05. Three SNP-treatment joint effects showed possible departures from additivity among Whites.
Our study, a large and extensive evaluation of SNPs in NER genes and HNC survival, identified mostly null associations, though a few variants were suggestively associated with survival and potentially interacted additively with treatment.
PMCID: PMC4096829  PMID: 24487794
Head and neck cancer DNA repair; Nucleotide excision repair; Chemotherapy; Radiation; Survival
11.  Adverse Events Associated with Meropenem versus Imipenem/Cilastatin Therapy in a Large Retrospective Cohort of Hospitalized Infants 
Carbapenems are commonly used in hospitalized infants despite a lack of complete safety data and associations with seizures in older children. We compared the incidence of adverse events in hospitalized infants receiving meropenem versus imipenem/cilastatin.
We conducted a retrospective cohort study of 5566 infants treated with meropenem or imipenem/cilastatin in neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2010. Multivariable conditional logistic regression was performed to evaluate the association between carbapenem therapy and adverse events, controlling for infant factors and severity of illness.
Adverse events were more common with use of meropenem compared with imipenem/cilastatin (62.8/1000 infant days vs. 40.7/1000 infant days, P<0.001). There was no difference in seizures with meropenem vs. imipenem/cilastatin (adjusted odds ratio [OR] 0.96; 95% confidence interval 0.68, 1.32). The incidence of death, as well as the combined outcome of death or seizure, was lower with meropenem use—OR 0.68 (0.50, 0.88) and OR 0.77 (0.62, 0.95), respectively.
In this cohort of infants, meropenem was associated with more frequent but less severe adverse events when compared with imipenem/cilastatin.
PMCID: PMC3708263  PMID: 23838776
meropenem; imipenem/cilastatin; adverse events; infant
12.  Eighteen year weight trajectories and metabolic markers of diabetes in modernising China 
Diabetologia  2014;57(9):1820-1829.
Although obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes.
We used fasting blood samples and longitudinal weight data for 5,436 adults (5,734 observations, aged 18–66 years) from the China Health and Nutrition Survey (1991–2009). Using latent class trajectory analysis, we identified different weight gain trajectories in six age and sex strata, and used multivariable general linear mixed effects models to assess elevated metabolic markers of diabetes (fasting glucose, HbA1c, HOMA-IR, insulin) across weight trajectory classes. Models were fitted within age and sex strata, and controlled for baseline weight (or baseline weight by weight trajectory interaction terms), height, and smoking habit, with random intercepts to control for community-level correlations.
Compared with weight gain, classes with weight maintenance, weight loss, or a switch from weight gain to loss had lower values for metabolic markers of diabetes. These associations were stronger among younger women (aged 18–29 and 30–39 years) and men (18–29 years) than in older (40–66 years) men and women. An exception was HOMA-IR, which showed class differences across all ages (at least p < 0.004).
Trajectory analysis identified heterogeneity in adult weight gain associated with diabetes-related metabolic markers, independent of baseline weight. Our findings suggest that variation in metabolic markers of diabetes across patterns of weight gain is masked by a homogeneous classification of weight gain.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-014-3284-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
PMCID: PMC4119243  PMID: 24891020
Adult; China; Fasting glucose; Insulin resistance; Latent class trajectory analysis
13.  Maternal Dietary Patterns are Associated With Risk of Neural Tube and Congenital Heart Defects 
American Journal of Epidemiology  2013;177(11):1279-1288.
Studying empirically derived dietary patterns is useful in understanding dietary practice. We classified women by their dietary patterns using latent class analysis of 66 foods and studied the association of these patterns with neural tube defects (NTDs) and congenital heart defects (CHDs) in the US National Birth Defects Prevention Study (1997–2005). Logistic regression models used data from 1,047 with an NTD, 6,641 with a CHD, and 6,123 controls that were adjusted for maternal characteristics and tested the effect modification of multivitamin supplement use. Four latent dietary patterns were identified: prudent, Western, low-calorie Western, and Mexican. Among participants who did not use supplements, those in the Mexican, Western, and low-calorie Western classes were significantly more likely (odds ratios of 1.6, 1.5, and 1.4, respectively) to have offspring born with NTDs than were those in the prudent class after adjustment of for dietary folic acid intake. In contrast, among supplement users, there was no difference in the incidence of NTDs between classes. Associations between dietary class and CHD subgroups were not modified by supplement use except for tetralogy of Fallot; among supplement users, those in the Western class were twice as likely (95% confidence interval: 1.4, 2.8) as the prudent class to have offspring with tetralogy of Fallot. Women who adhered to a Western diet were 1.2 (95% confidence interval: 1.03, 1.35) times more likely to have an infant with septal heart defect than were women who adhered to a prudent diet. A prudent dietary pattern, even with folate fortification, may decrease the risk of NTDs and some heart defects.
PMCID: PMC3664332  PMID: 23639938
congenital anomalies; diet; eating patterns; folic acid; latent class analysis
This article presents a multiple imputation method for sensitivity analyses of time-to-event data with possibly informative censoring. The imputed time for censored values is drawn from the failure time distribution conditional on the time of follow-up discontinuation. A variety of specifications regarding the post-discontinuation tendency of having events can be incorporated in the imputation through a hazard ratio parameter for discontinuation versus continuation of follow-up. Multiple-imputed data sets are analyzed with the primary analysis method, and the results are then combined using the methods of Rubin. An illustrative example is provided.
PMCID: PMC4009741  PMID: 24605967
Multiple imputation; Sensitivity analysis; Time-to-event data
15.  Urinary Follicle-Stimulating Hormone as a Measure of Natural Fertility in a Community Cohort 
Reproductive Sciences  2013;20(5):549-556.
High serum follicle-stimulating hormone (FSH) levels have been associated with diminished ovarian reserve; however, the association between high urinary FSH and reduced natural fertility has yet to be established. We sought to characterize the relationship between a single or multiple measurements of early follicular phase urinary FSH and fertility. Women (n = 209), 30 to 44 years old with no history of infertility, who had been trying to conceive for less than 3 months, provided early follicular phase urine. Participants subsequently kept a diary to record bleeding and intercourse and conducted standardized pregnancy testing for up to 6 months. A subset of women (N = 95) collected urine on cycle day 3 for up to 6 cycles. Urine was analyzed for FSH and creatinine (cr) corrected. Proportional hazard models were used to calculate fecundability ratios (FRs). Urinary FSH levels across cycles from the same woman were highly correlated (adjusted intraclass correlation = .77); within-woman variance was 3-fold lower than variance among women. Women with an initial urinary FSH level <7 mIU/mg cr exhibited a nonsignificant reduction in the probability of pregnancy (adjusted FR 0.71, 95% confidence interval [CI]: 0.45-1.13), as did women with elevated urinary FSH (≥12 mIU/mg cr; adjusted FR 0.78, 95% CI: 0.46-1.32). Using the most recent or maximum urinary FSH value did not strengthen the association. In the general population, urinary FSH levels appear to be nonlinearly associated with fertility; however, broad CIs indicate a lack of statistical significance. Repetitive testing appears to be of little benefit.
PMCID: PMC3635071  PMID: 23171685
fecundability; fertility; follicle-stimulating hormone; ovarian reserve; urine
16.  Longitudinal trajectories of BMI and cardiovascular disease risk: The National Longitudinal Study of Adolescent Health 
Obesity (Silver Spring, Md.)  2013;21(11):2180-2188.
In adulthood, excess BMI is associated with cardiovascular disease (CVD); it is unknown whether risk differs by BMI trajectories from adolescence to adulthood.
Design and Methods
The National Longitudinal Study of Adolescent Health, a nationally representative, longitudinal adolescent cohort (mean age: 16.9y) followed into adulthood (mean age: 29.0y) [n=13,643 individuals (40,929 observations)] was examined. Separate logistic regression models for diabetes, hypertension, and inflammation were used to examine odds of risk factors at given adult BMI according to varying BMI trajectories from adolescence to adulthood.
CVD risk factor prevalence at follow-up ranged from 5.5% (diabetes) to 26.4% (hypertension) and 31.3% (inflammation); risk differed across BMI trajectories. For example, relative to men aged 27y (BMI=23 kg/m2 maintained over full study period), odds for diabetes were comparatively higher for men of the same age and BMI≈30 kg/m2 with ≈8 BMI unit gain between 15-20y (OR=2.35; 95% CI, 1.51, 3.66) or in those who maintained BMI≈30 kg/m2 across the study period (OR=2.33; 1.92, 2.83) relative to the same ≈8 BMI unit gain, but between 20-27y (OR=1.44; 1.10, 1.87).
Specific periods and patterns of weight gain in the transition from adolescence to adulthood might be critical for CVD preventive efforts.
PMCID: PMC3947414  PMID: 24136924
Diabetes; Hypertension; Inflammation; Race/ethnicity; Obesity
17.  Latent Transition Models to Study Women's Changing of Dietary Patterns From Pregnancy to 1 Year Postpartum 
American Journal of Epidemiology  2013;177(8):852-861.
Latent class models are useful for classifying subjects by dietary patterns. Our goals were to use latent transition models to identify dietary patterns during pregnancy and postpartum, to estimate the prevalence of these dietary patterns, and to model transition probabilities between dietary patterns as a function of covariates. Women who were enrolled in the Pregnancy, Infection, and Nutrition Study (University of North Carolina, 2000–2005) were followed for 1 year postpartum, and their diets were assessed in the second trimester and at 3 and 12 months postpartum (n = 519, 484, and 374, respectively) by using a food frequency questionnaire. After adjusting for energy intake, parity, smoking status, race, and education, we identified 3 dietary patterns and named them “prudent,” “health conscious Western,” and “Western.” Nulliparas were 2.9 and 2.1 times more likely to be in the “prudent” class than the “health conscious Western” or the “Western” class, respectively. The 3 dietary patterns were very stable, with the “health conscious Western” class being the least stable; the probability for staying in the same class was 0.74 and 0.87 at 3 and 12 months postpartum, respectively. Breastfeeding mothers were more likely than nonbreastfeeding mothers to switch dietary pattern class (P = 0.0286). Except for breastfeeding mothers, most women did not switch dietary patterns from pregnancy to postpartum.
PMCID: PMC3668424  PMID: 23538942
dietary patterns; eating patterns; finite mixture models; hidden Markov models; latent class analysis; latent transition models; postpartum; pregnancy
18.  Longitudinal Consistency in Self-Reported Age of First Vaginal Intercourse Among Young Adults 
Journal of sex research  2012;51(1):97-106.
We examined consistency in self-reports of age at first vaginal sex among 9,399 male and female respondents who participated in Waves III and IV (separated by approximately 7 years) of the National Longitudinal Study of Adolescent Health (Add Health). Respondents were coded as consistent if they reported an age at first vaginal intercourse at Wave IV that was within 1 year of the age they reported at Wave III. Sociodemographic, behavioral, and cognitive predictors of consistency were examined using bivariate and multivariate logistic regression. Overall, 85.43% of respondents were able to provide consistent reports. Among both males and females, consistency was associated with age, years since first vaginal intercourse, race/ethnicity, and lifetime number of other-sex partners in final multivariate models. Respondents who were older and had more recently had their first sexual experience were more likely to be consistent. For females only, those who reported a history of non-parental, physically forced sex were less likely to be consistent. Most young adults consistently report age at first vaginal intercourse, supporting the credibility of retrospective self-reports about salient sexual events such as timing of first vaginal intercourse.
PMCID: PMC3955171  PMID: 23237101
Reliability and Validity of Measures; Quantitative/Statistical/Survey; Childhood, Adolescence, Adolescent Sexuality; Assumptions of sex research
19.  Risk Factors for Invasive Candidiasis in Infants >1500 g Birth Weight 
We describe the incidence, risk factors, and outcomes of invasive candidiasis in infants >1500 g birth weight.
We conducted a retrospective cohort study of infants >1500 g birth weight discharged from 305 NICUs in the Pediatrix Medical Group from 2001–2010. Using multivariable logistic regression, we identified risk factors for invasive candidiasis.
Invasive candidiasis occurred in 330/530,162 (0.06%) infants. These were documented from positive cultures from ≥1 of these sources: blood (n=323), cerebrospinal fluid (n=6), or urine from catheterization (n=19). Risk factors included day of life >7 (OR 25.2; 95% CI 14.6–43.3), vaginal birth (OR 1.6 [1.2–2.3]), exposure to broad-spectrum antibiotics (OR 1.6 [1.1–2.4]), central venous line (OR 1.8 [1.3–2.6]), and platelet count <50,000/mm3 (OR 3.7 [2.1–6.7]). All risk factors had poor sensitivities, low positive likelihood ratios, and low positive predictive values. The combination of broad-spectrum antibiotics and low platelet count had the highest positive likelihood ratio (46.2), but the sensitivity of this combination was only 4%. Infants with invasive candidiasis had increased mortality (OR 2.2 [1.3–3.6]).
Invasive candidiasis is uncommon in infants >1500 g birth weight. Infants at greatest risk are those exposed to broad-spectrum antibiotics and with platelet counts of <50,000/mm3.
PMCID: PMC3578110  PMID: 23042050
candidiasis; candidemia; neonates; neonatal intensive care unit
Midwifery  2012;29(2):139-147.
to examine the associations between total and domain-specific moderate-to-vigorous physical activity (MVPA) during pregnancy and postpartum depressive symptoms.
a prospective cohort study.
data were obtained from 652 women recruited from prenatal clinics at University of North Carolina during 2001–2005 for the Pregnancy, Infection, and Nutrition (PIN) Postpartum Study.
MVPA measured at 17–22 and 27–30 weeks’ gestation was investigated as a predictor of depressive symptoms assessed with the Edinburgh Postnatal Depression Scale at 3 months postpartum.
total MVPA was not associated with depressive symptoms when using either 17–22 weeks’ gestation or 27–30 weeks’ gestation MVPA measures. In general, there were minimal associations for domain-specific MVPA. The direction of associations between depressive symptoms and work, adult and child care, and outdoor household MVPAs differed by time of measurement.
Key Conclusions
the association between physical activity and postpartum depressive symptoms may differ with the timing of assessment. Additional studies (i.e. with a larger sample of women or a sample of at-risk women) following women throughout pregnancy and postpartum are needed to explore differences in the influence of physical activity on depressive symptoms.
Implications for Practice
assessment of potential risk factors for elevated depressive symptoms, such as participation levels in different types of physical activity, throughout pregnancy may assist in determining who may be susceptible to postpartum depression.
PMCID: PMC3459267  PMID: 22726573
21.  The Association between Sequences of Sexual Initiation and the Likelihood of Teenage Pregnancy 
Few studies have examined the health and developmental consequences, including unintended pregnancy, of different sexual behavior initiation sequences. Some work suggests that engaging in oral-genital sex first may slow the transition to coital activity and lead to more consistent contraception among adolescents.
Using logistic regression analysis, we investigated the association between sequences of sexual initiation (i.e., initiating oral-genital or vaginal sex first based on reported ages of first experience) and the likelihood of subsequent teenage pregnancy among 6,069 females who reported vaginal sex before age 20 and participated in Waves I and IV of the National Longitudinal Study of Adolescent Health (Add Health).
Among females initiating vaginal sex first, 31.4% reported a teen pregnancy. Among females initiating two behaviors at the same age, 20.5% reported a teen pregnancy. Among females initiating oral-genital sex first, 7.9% reported a teen pregnancy. In multivariate models, initiating oral-genital sex first, with a delay of at least one year to vaginal sex, and initiating two behaviors within the same year were each associated with a lower likelihood of adolescent pregnancy, relative to teens who initiated vaginal sex first (OR=0.23, 95% CI (0.15, 0.37) and OR=0.78, 95% CI (0.60, 0.92), respectively).
How adolescents begin their sexual lives may be differentially related to positive and negative health outcomes. To develop effective pregnancy prevention efforts for teens and ensure programs are relevant to youths’ needs, it is important to consider multiple facets of sexual initiation and their implications for adolescent sexual health and fertility.
PMCID: PMC3551538  PMID: 23332489
22.  Associations Between Patterns of Emerging Sexual Behavior and Young Adult Reproductive Health 
Identifying young adult outcomes associated with adolescent sexual behavior, including patterns of first oral, vaginal and anal sex, is critical to promoting healthy sexual development.
Associations between patterns of emerging sexual behavior, defined using latent class analysis, and young adult sexual and reproductive health were examined among 9,441 respondents to Waves 1 (1994–1995), 3 (2001–2002) and 4 (2008) of the National Longitudinal Study of Adolescent Health. Logistic regression analyses examined associations between class membership and young adult outcomes, and tested for interactions by race and ethnicity.
Compared with respondents who initiated vaginal sex first and reported other sexual behaviors within two years, those who initiated oral and vaginal sex during the same year had similar odds of having had an STD diagnosis ever or in the last year, of having had concurrent sexual partnerships in the last year and of having exchanged sex for money. However, respondents who postponed sexual activity had reduced odds of each outcome (odds ratios, 0.2–0.4); those who initiated vaginal sex and reported only one type of sexual behavior had reduced odds of reporting STD diagnoses and concurrent partnerships (0.4–0.6). Respondents who reported early initiation of sexual activity combined with anal sex experience during adolescence had elevated odds of having had concurrent partnerships (1.6). The data suggest racial and ethnic disparities even when patterns of emerging sexual behavior were the same.
Patterns of early sexual behavior considered high-risk may not predict poor sexual and reproductive health in young adulthood.
PMCID: PMC3531866  PMID: 23231329
23.  Assessing variance components in multilevel linear models using approximate Bayes factors: A case study of ethnic disparities in birthweight 
Racial/ethnic disparities in birthweight are a large source of differential morbidity and mortality worldwide and have remained largely unexplained in epidemiologic models. We assess the impact of maternal ancestry and census tract residence on infant birth weights in New York City and the modifying effects of race and nativity by incorporating random effects in a multilevel linear model. Evaluating the significance of these predictors involves the test of whether the variances of the random effects are equal to zero. This is problematic because the null hypothesis lies on the boundary of the parameter space. We generalize an approach for assessing random effects in the two-level linear model to a broader class of multilevel linear models by scaling the random effects to the residual variance and introducing parameters that control the relative contribution of the random effects. After integrating over the random effects and variance components, the resulting integrals needed to calculate the Bayes factor can be efficiently approximated with Laplace’s method.
PMCID: PMC3784317  PMID: 24082430
Bayes factors; Laplace approximation; hierarchical; multilevel linear model; variance components
24.  Antimüllerian Hormone as a Predictor of Natural Fecundability in Women Aged 30–42 Years 
Obstetrics and gynecology  2011;117(4):10.1097/AOG.0b013e3182116bc8.
To generate estimates of the association between markers of ovarian aging and natural fertility in a community sample at risk for ovarian aging.
Women aged 30–44 years with no history of infertility who had been trying to conceive for less than 3 months provided early-follicular phase serum and urine (N=100). Subsequently, these women kept a diary to record menstrual bleeding and intercourse and conducted standardized pregnancy testing for up to 6 months. Serum was analyzed for estradiol, follicle-stimulating hormone (FSH), antimüllerian hormone, and inhibin B. Urine was analyzed for FSH and estrone 3-glucuronide (E13G). Diary data on menstrual cycle day and patterns of intercourse were used to calculate day-specific fecundability ratios.
Sixty-three percent of subjects conceived within 6 months. After adjusting for age, 18 women (18%) with serum antimüllerian hormone levels of 0.7 ng/ml or less had significantly reduced fecundability given intercourse on a fertile day compared to women with higher antimüllerian hormone levels (fecundability ratio 0.38, 95% CI:0.08–0.91). The day-specific fecundability for women with early-follicular phase serum FSH values greater than 10 mIU/ml compared to women with lower FSH levels was also reduced, though nonsignificantly (11% of women affected; fecundability ratio 0.44, 95% CI: 0.08, 1.10). The association with urinary FSH was weaker (27% women affected; fecundability ratio 0.61, 95% CI: 0.26, 1.26), and the associations for the other markers were weaker still.
Early-follicular phase antimüllerian hormone appears to be associated with natural fertility in the general population.
PMCID: PMC3825553  PMID: 21422850
25.  Pregravid body mass index, psychological factors during pregnancy, and breastfeeding duration: is there a link? 
Maternal & child nutrition  2011;8(4):423-433.
Breastfeeding rates in the U.S. are low and one possible reason may be the high prevalence of overweight/obesity among women of childbearing age. This analysis examined the association between pregravid body mass index (BMI) and breastfeeding duration and explored whether depressive symptoms, perceived stress and anxiety during pregnancy mediated this relationship. Participants (n = 550) in the Pregnancy, Infection, and Nutrition Postpartum Study were recruited through prenatal clinics prior to 20 weeks gestation and followed to 12 months postpartum. Duration of any breastfeeding was categorized as: none, less than 4 months, 4 to 6 months, 7 to 12 months, and more than 12 months (referent). Exclusive breastfeeding was categorized as less than 1 month, 1 to less than 4 months, and 4 months or more (referent). Being overweight/obese before pregnancy (35.7% of 550) was inversely associated with the durations of any and exclusive breastfeeding. Women who entered pregnancy overweight or obese were more likely to not initiate breastfeeding [RRR =5.39 (95% CI: 2.41, 12.04)] and to breastfeed less than four months [RRR = 2.38 (1.33, 4.27)] compared to women of normal weight status. Among women who initiated breastfeeding, being overweight or obese versus normal weight was related to exclusively breastfeeding less than 1 month [RRR = 2.09 (1.24, 3.51)]. We did not find evidence to support mediation by depressive symptoms, perceived stress or anxiety during pregnancy. Future research needs to explore the reasons behind the association between overweight/obesity and breastfeeding duration.
PMCID: PMC3329574  PMID: 21951308
Overweight; obesity; pregravid BMI; pregnancy; breastfeeding duration; depressive symptoms; stress; anxiety

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