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1.  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
2.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  Pregravid body mass index is associated with early introduction of complementary foods 
To determine whether women who entered pregnancy overweight or obese were less likely to follow American Academy of Pediatrics (AAP) guidelines for introducing complementary foods to infants after four months of age. In addition, to explore whether psychological factors accounted for any of the effect of pregravid body mass index (BMI) on age of complementary food introduction.
A prospective cohort study from 2001 to 2005 which recruited pregnant women between 15 to 20 gestational weeks with follow-up through 12 months postpartum from University of North Carolina hospitals (n = 550).
Multinomial logit models estimated relative risk ratios (RRR). The outcome was age of complementary food introduction, categorized as less than four months of age, four to six, and six months or later (referent). Maternal BMI was categorized as underweight (< 18.5 kg/m2), normal-weight (18.5 kg/m2 to 24.9 kg/m2), and overweight/obese (≥ 25.0 kg/m2). A series of regression analyses tested mediation by psychological factors measured during pregnancy (depressive symptoms, stress and anxiety).
More than a third of the study population (35.7% of 550) entered pregnancy overweight/obese. The majority of participants (75.3%) introduced foods to their infants between four to six months of age. Compared with normal-weight women, those who were overweight/obese before pregnancy were more likely [RRR = 2.22 (1.23, 4.01)] to introduce complementary foods before the infant was four months old, adjusting for race, education, and poverty status. Depressive symptoms, stress and anxiety did not account for any of the effect of pregravid overweight/obesity on early food introduction.
The results suggest that overweight and obese women are more likely to introduce complementary foods early and that psychological factors during pregnancy do not influence this relationship. Future studies need to explore why overweight/obese women are less likely to meet the AAP recommendations for the introduction of complementary food.
PMCID: PMC3433719  PMID: 22939440
Overweight; obesity; pregravid body mass index; complementary food introduction
15.  Correlates of Physical Activity at Two Time Points During Pregnancy 
Correlates of prenatal physical activity can inform interventions, but are not well-understood.
Participants in the Pregnancy, Infection, and Nutrition 3 Study were recruited before 20 weeks gestation. Women self-reported frequency, duration, and mode of moderate and vigorous physical activities. We used logistic regression to identify correlates of any physical activity (≥10 minutes/week of any mode), any recreational activity (≥10 minutes/week), and high volume recreational activity (either ≥150 minutes/week of moderate or ≥75 minutes/week of vigorous). Our analysis included 1752 women at 19-weeks gestation and 1722 at 29 weeks.
Higher education, white race, and enjoyment of physical activity were positively correlated with all 3 outcomes. Any recreational activity was negatively associated with parity, body mass index, and history of miscarriage. The associations of history of miscarriage and body mass index differed at 19 weeks compared with 29 weeks. Single marital status, health professional physical activity advice, and time for activity were associated with high volume recreational activity only.
Correlates of physical activity differed by mode and volume of activity and by gestational age. This suggests that researchers planning physical activity interventions should consider the mode and amount of activity and the gestational age of the participants.
PMCID: PMC3749786  PMID: 22454434
leisure activity; gestational age; intervention; barriers; psychosocial
16.  Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study 
Several epidemiologic studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, we investigated the association between paternal occupation and birth defects in a case-control study of cases comprising over 60 different types of birth defects (n = 9998) and non-malformed controls (n = 4066) with dates of delivery between 1997 and 2004.
Using paternal occupational histories reported by mothers via telephone interview, jobs were systematically classified into 63 groups based on shared exposure profiles within occupation and industry. Data were analyzed using Bayesian logistic regression with a hierarchical prior for dependent shrinkage to stabilize estimation with sparse data.
Several occupations were associated with an increased prevalence of various birth defect categories, including: mathematical, physical and computer scientists; artists; photographers and photo processors; food service workers; landscapers and groundskeepers; hairdressers and cosmetologists; office and administrative support workers; sawmill workers; petroleum and gas workers; chemical workers; printers; material moving equipment operators; and motor vehicle operators.
Findings from this study might be used to identify specific occupations worthy of further investigation, and to generate hypotheses about chemical or physical exposures common to such occupations.
PMCID: PMC3744212  PMID: 22782864
Bayes theorem; congenital abnormalities; occupational exposure; occupations; paternal exposure
17.  Neighbourhood food environment and gestational diabetes in New York City 
The association between neighbourhood characteristics and gestational diabetes has not been examined previously. We investigated the relationship between the number of healthy food outlets (supermarkets; fruit/vegetable and natural food stores), and unhealthy food outlets (fast food; pizza; bodegas; bakeries; convenience, candy/nut and meat stores) in census tract of residence, and gestational diabetes in New York City. Gestational diabetes, census tract and individual-level covariates were ascertained from linked birth-hospital data for 210 926 singleton births from 2001 to 2002 and linked to commercial data on retail food outlets. Adjusted odds ratios (aOR) were estimated using a multilevel logistic model.
No association between food environment measures and gestational diabetes was found, with aORs ranging from 0.95 to 1.04. However, an increased odds of pre-pregnancy weight >200 lbs for women living in a given neighbourhood with no healthy food outlets [aOR = 1.14, 95% CI 1.07, 1.21] or only one healthy food place [aOR = 1.10, 95% CI 1.04, 1.18] relative to two or more healthy food outlets was found. Due to probable misclassification of neighbourhood food environment and pre-pregnancy obesity results are likely to be biased towards the null. Future research, including validity studies, on the neighbourhood food environment, obesity during pregnancy and gestational diabetes is warranted.
PMCID: PMC3734793  PMID: 20415754
gestational diabetes; maternal obesity; healthy food outlets
18.  A Bayesian Latent Variable Mixture Model for Longitudinal Fetal Growth 
Biometrics  2009;65(4):1233-1242.
Fetal growth restriction is a leading cause of perinatal morbidity and mortality that could be reduced if high risk infants are identified early in pregnancy. We propose a Bayesian model for aggregating 18 longitudinal ultrasound measurements of fetal size and blood flow into three underlying, continuous latent factors. Our procedure is more flexible than typical latent variable methods in that we relax the normality assumptions by allowing the latent factors to follow finite mixture distributions. Using mixture distributions also permits us to cluster individuals with similar observed characteristics and identify latent classes of subjects who are more likely to be growth or blood flow restricted during pregnancy. We also use our latent variable mixture distribution model to identify a clinically-meaningful latent class of subjects with low birth weight and early gestational age. We then examine the association of latent classes of intrauterine growth restriction with latent classes of birth outcomes as well as observed maternal covariates including fetal gender and maternal race, parity, body mass index (BMI), and height. Our methods identified a latent class of subjects who have increased blood flow restriction and below average intrauterine size during pregnancy who were more likely to be growth restricted at birth than a class of individuals with typical size and blood flow.
PMCID: PMC3717393  PMID: 19432784
Bayesian methods; birth weight; correlated data; intrauterine growth restriction; pre-term birth; latent variables; small for gestational age
19.  A prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birthweight 
Maternal and Child Health Journal  2012;16(5):1031-1044.
Current U.S. pregnancy-related physical activity recommendations do not provide specific guidance for vigorous intensity activity. Our objective was to examine the associations between vigorous physical activity during pregnancy and length of gestation and birthweight. Women were recruited before 10 weeks gestation. At 13-16 weeks gestation, participants reported the type, frequency, and duration of their typical weekly vigorous physical activities. Activity domains included recreational, occupational, household, and child/adult care. Infant birth date was obtained from medical or vital records; if unavailable, self-report was used. Birthweight (from vital records) was studied among term births. We analyzed gestational age among 1,647 births using discrete-time survival analysis. We used logistic and linear regression to analyze preterm birth (birth at <37 weeks) and birthweight, respectively. Vigorous recreational activity was associated with longer gestation (any vs. none, hazard ratio (HR) [95% CI]: 0.85 [0.70, 1.05]) and we did not detect any dose-response association. Higher frequency of vigorous recreational activity sessions (adjusted for total volume of activity) was associated with a decreased odds of preterm birth (≥ 4 sessions/week vs. 0 or 1, OR [95% CI]: 0.08 (0.006, 1.0). Birthweight was not associated with physical activity measures. In summary, vigorous physical activity does not appear to be detrimental to the timing of birth or birthweight. Our data support a reduced risk of preterm birth with vigorous recreational activity, particularly with increased frequency of recreational activity sessions. Future studies should investigate the components of physical activity (i.e. intensity, duration, and frequency) in relation to birth outcomes.
PMCID: PMC3386423  PMID: 21674218
20.  Effect of Vaginal Lubricants on Natural Fertility 
Obstetrics and gynecology  2012;120(1):44-51.
Over-the-counter vaginal lubricants have been shown to negatively affect in vitro sperm motility. The objective of this study was to estimate the effect of vaginal lubricant use during procreative intercourse on natural fertility.
Women aged 30–44 years with no history of infertility who had been trying to conceive for less than 3 months completed a baseline questionnaire on vaginal lubricant use. Subsequently, women kept a diary to record menstrual bleeding, intercourse, and vaginal lubricant use and conducted standardized pregnancy testing for up to 6 months. Diary data were used to determine the fertile window and delineate lubricant use during the fertile window. A proportional hazards model was used to estimate fecundability ratios with any lubricant use in the fertile window considered as a time-varying exposure.
Of the 296 participants, 75 (25%) stated in their baseline questionnaire that they use vaginal lubricants while attempting to conceive. Based on daily diary data, 57% of women never used a lubricant, 29% occasionally used a lubricant, and 14% used a lubricant frequently. Women who used lubricants during the fertile window had similar fecundability to those women who did not use lubricants (fecundability ratio 1.05, 95% CI: 0.59, 1.85) after adjusting for age, partner race, and intercourse frequency in the fertile window.
Lubricants are commonly used by couples during procreative intercourse. Lubricant use during procreative intercourse does not appear to reduce the probability of conceiving.
PMCID: PMC3427535  PMID: 22914390
21.  Detecting Disease Outbreaks Using Local Spatiotemporal Methods 
Biometrics  2011;67(4):1508-1517.
A real-time surveillance method is developed with emphasis on rapid and accurate detection of emerging outbreaks. We develop a model with relatively weak assumptions regarding the latent processes generating the observed data, ensuring a robust prediction of the spatiotemporal incidence surface. Estimation occurs via a local linear fitting combined with day-of-week effects, where spatial smoothing is handled by a novel distance metric that adjusts for population density. Detection of emerging outbreaks is carried out via residual analysis. Both daily residuals and AR model-based de-trended residuals are used for detecting abnormalities in the data given that either a large daily residual or an increasing temporal trend in the residuals signals a potential outbreak, with the threshold for statistical significance determined using a resampling approach.
PMCID: PMC3698245  PMID: 21418049
Disease surveillance; Local linear estimation; Residual analysis; Lattice Data; Time series modeling
22.  The Effect of Water Disinfection By-products on Pregnancy Outcomes in Two Southeastern U.S. Communities 
To determine if exposure to DBPs during gestation increases the risk of adverse birth outcomes, specifically term small for gestational age (SGA) birth, preterm birth (PTB), and very PTB (<32 weeks gestation).
We used weekly measurements total trihalomethanes (TTHMs), 5 haloacetic acids (HAA5), and total organic halides (TOX) collected from two distribution systems to evaluate the associations between DBP concentrations and term SGA, PTB and very PTB using logistic regression.
We found no associations between DBPs and term-SGA. In the site with higher concentrations of bromine-containing DBPs, we found an association between TOX and PTB; this association was larger, though less precise, for very PTB.
Our results do not support an association between TTHMs or HAA5 and the birth outcomes investigated, but an association was found between increased TOX and PTB.
PMCID: PMC3693937  PMID: 21915074
23.  Effect of Body Image on Pregnancy Weight Gain 
Maternal and child health journal  2011;15(3):324-332.
The majority of women gain more weight during pregnancy than what is recommended. Since gestational weight gain is related to short and long-term maternal health outcomes, it is important to identify women at greater risk of not adhering to guidelines. The objective of this study was to examine the relationship between body image and gestational weight gain. The Body Image Assessment for Obesity tool was used to measure ideal and current body sizes in 1,192 women participating in the Pregnancy, Infection and Nutrition Study. Descriptive and multivariable techniques were used to assess the effects of ideal body size and discrepancy score (current—ideal body sizes), which reflected the level of body dissatisfaction, on gestational weight gain. Women who preferred to be thinner had increased risk of excessive gain if they started the pregnancy at a BMI ≤26 kg/m2 but a decreased risk if they were overweight or obese. Comparing those who preferred thin body silhouettes to those who preferred average size silhouettes, low income women had increased risk of inadequate weight gain [RR = 1.76 (1.08, 2.88)] while those with lower education were at risk of excessive gain [RR = 1.11 (1.00, 1.22)]. Our results revealed that body image was associated with gestational weight gain but the relationship is complex. Identifying factors that affect whether certain women are at greater risk of gaining outside of guidelines may improve our ability to decrease pregnancy-related health problems.
PMCID: PMC3665282  PMID: 20204481
Body image; Body dissatisfaction; Gestational weight gain; Pregnancy
24.  Beyond age at first sex: Patterns of emerging sexual behavior in adolescence and young adulthood 
The Journal of Adolescent Health  2011;50(5):456-463.
Although the emergence of sexual expression during adolescence and early adulthood is nearly universal, little is known about patterns of initiation.
We used latent class analysis to group 12,194 respondents from Waves I and IV of the National Longitudinal Study of Adolescent Health (Add Health) into one of five classes based on variety, timing, spacing, and sequencing of oral-genital, anal, and vaginal sex. Multinomial logistic regression models, stratified by biological sex, examined associations between sociodemographic characteristics and class membership.
Approximately half of respondents followed a pattern characterized predominately by initiation of vaginal sex first, average age of initiation of approximately 16 years, and spacing of one year or more between initiation of the first and second behaviors; almost one third initiated sexual activity slightly later but reported first experiences of oral-genital and vaginal sex within the same year. Classes characterized by postponement of sexual activity, initiation of only one type of behavior, or adolescent initiation of anal sex were substantially less common. Compared to White respondents, Black respondents were more likely to appear in classes characterized by initiation of vaginal sex first. Respondents from lower socioeconomic backgrounds were more likely to be in classes distinguished by early/atypical patterns of initiation.
A small number of typical and atypical patterns capture the emergence of sexual behavior during adolescence, but these patterns reveal complex associations among different elements of emerging sexuality that should be considered in future research.
PMCID: PMC3336094  PMID: 22525108
Oral sex; anal sex; latent class analysis; nationally representative; noncoital; sexuality development; adolescent sexual behavior; sociodemographic differences
25.  Cardiovascular Outcomes and the Physical and Chemical Properties of Metal Ions Found in Particulate Matter Air Pollution: A QICAR Study 
Environmental Health Perspectives  2013;121(5):558-564.
Background: This paper presents an application of quantitative ion character–activity relationships (QICAR) to estimate associations of human cardiovascular (CV) diseases (CVDs) with a set of metal ion properties commonly observed in ambient air pollutants. QICAR has previously been used to predict ecotoxicity of inorganic metal ions based on ion properties.
Objectives: The objective of this work was to examine potential associations of biological end points with a set of physical and chemical properties describing inorganic metal ions present in exposures using QICAR.
Methods: Chemical and physical properties of 17 metal ions were obtained from peer-reviewed publications. Associations of cardiac arrhythmia, myocardial ischemia, myocardial infarction, stroke, and thrombosis with exposures to metal ions (measured as inference scores) were obtained from the Comparative Toxicogenomics Database (CTD). Robust regressions were applied to estimate the associations of CVDs with ion properties.
Results: CVD was statistically significantly associated (Bonferroni-adjusted significance level of 0.003) with many ion properties reflecting ion size, solubility, oxidation potential, and abilities to form covalent and ionic bonds. The properties are relevant for reactive oxygen species (ROS) generation, which has been identified as a possible mechanism leading to CVDs.
Conclusion: QICAR has the potential to complement existing epidemiologic methods for estimating associations between CVDs and air pollutant exposures by providing clues about the underlying mechanisms that may explain these associations.
PMCID: PMC3673192  PMID: 23462649
air pollution; cardiovascular disease; multipollutant; QICAR; QSAR

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