Long-term effectiveness of eliglustat treatment: A real-world analysis from the International Collaborative Gaucher Group Gaucher Registry.

Gaucher disease type 1 (GD1) is known for phenotypic heterogeneity and varied natural history. Registrational clinical trials enrolled narrowly defined phenotypes, but greater diversity is encountered in clinical practice. We report real-world outcomes with long-term eliglustat treatment in adults with GD1 in the International Collaborative Gaucher Group Gaucher Registry. Among 5985 GD1 patients in the Registry as of January 6, 2023, 872 started eliglustat at ≥18 years old; of these, 469 met inclusion criteria. We compared clinical parameters at eliglustat initiation (i.e., baseline) and follow-up in treatment-naïve patients and used linear mixed models to estimate annual change from baseline in parameters among patients who switched to eliglustat after ≥1 year on enzyme replacement therapy. Over 4 years of follow-up in non-splenectomized treatment-naïve patients, hemoglobin and platelet count increased, liver and spleen volume decreased, and total lumbar spine bone mineral density (BMD) Z-score decreased slightly. Among non-splenectomized switch patients, on average, hemoglobin decreased -0.030 (95% CI: -0.053, -0.008) g/dL (N = 272) and platelet count increased 2.229 (95% CI: 0.751, 3.706) × 103/mm3 (N = 262) annually up to 10 years; liver volume decreased (-0.009 [95% CI: -0.015, -0.003] MN) (N = 102) and spleen volume remained stable (-0.070 [95% CI: -0.150, 0.010] MN) (N = 106) annually up to 7 years; and total lumbar spine BMD Z-score increased 0.041 (95% CI: 0.015, 0.066) (N = 183) annually up to 8 years. Among splenectomized switch patients, clinical parameters were stable over time. These long-term, real-world outcomes are consistent with the eliglustat clinical trials and emerging real-world experience across the GD phenotypic spectrum.

Associations of urinary metabolite concentrations of phthalates and phthalate replacements with body composition from mid-childhood to early adolescence.

BACKGROUND: Phthalates may adversely influence body composition by lowering anabolic hormones and activating peroxisome-proliferator activated receptor gamma. However, data are limited in adolescence when body mass distributions rapidly change and bone accrual peaks. Also, potential health effects of certain phthalate/replacements [e.g., di-2-ethylhexyl terephthalate (DEHTP)] have not been well studied. METHODS: Among 579 children in the Project Viva cohort, we used linear regression to evaluate associations of urinary concentrations of 19 phthalate/replacement metabolites from mid-childhood (median: 7.6 years; 2007-2010) with annualized change in areal bone mineral density (aBMD) and lean, total fat, and truncal fat mass as measured by dual-energy X-ray absorptiometry between mid-childhood and early adolescence (median: 12.8 years). We used quantile g-computation to assess associations of the overall chemical mixture with body composition. We adjusted for sociodemographics and tested for sex-specific associations. RESULTS: Urinary concentrations were highest for mono-2-ethyl-5-carboxypentyl phthalate [median (IQR): 46.7 (69.1) ng/mL]. We detected metabolites of most replacement phthalates in a relatively small number of participants [e.g., 28% for mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP; metabolite of DEHTP)]. Detectable (vs. non-detectable) MEHHTP was associated with less bone and greater fat accrual in males and greater bone and lean mass accrual in females [e.g., change in aBMD Z-score/year (95% CI): -0.049 (-0.085, -0.013) in males versus 0.042 (0.007, 0.076) in females; pinteraction<0.01]. Children with higher concentrations of mono-oxo-isononyl phthalate and mono-3-carboxypropyl phthalate (MCPP) had greater bone accrual. Males with higher concentrations of MCPP and mono-carboxynonyl phthalate had greater accrual of lean mass. Other phthalate/replacement biomarkers, and their mixtures, were not associated with longitudinal changes in body composition. CONCLUSIONS: Concentrations of select phthalate/replacement metabolites in mid-childhood were associated with changes in body composition through early adolescence. As use of phthalate replacements such as DEHTP may be increasing, further investigation can help better understand the potential effects of early-life exposures.

Serum PFAS and Urinary Phthalate Biomarker Concentrations and Bone Mineral Density in 12-19 Year Olds: 2011-2016 NHANES.

CONTEXT: Per- and polyfluoroalkyl substances (PFAS) and phthalates are 2 families of environmental endocrine disruptors that may be associated with areal lower bone mineral density (aBMD). OBJECTIVE: To examine associations between serum PFAS and urinary phthalate biomarker concentrations and their mixtures with aBMD Z-scores in adolescents. DESIGN, PATIENTS, AND MEASURES: We examined serial cross-sectional data from male (n = 453) and female (n = 395) 12- to 19-year-old participants in the 2011 through 2016 National Health and Nutrition Examination Survey with measures of serum PFAS, urinary phthalate metabolites, and dual-energy X-ray absorptiometry aBMD Z-scores (total body less head). In sex-specific models, we used linear regression to examine associations of individual PFAS and phthalate biomarkers with aBMD Z-scores, and Bayesian kernel machine regression to examine the association of the overall PFAS/phthalate biomarker mixture with aBMD Z-scores. We replicated the analysis, stratifying by race/ethnicity. RESULTS: Participants were (mean ±â€…SD) 15 ±â€…2.1 years of age. In males, each doubling of serum perfluorooctanoate (PFOA), perfluorooctane sulfonate, urinary mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate, and the overall PFAS/phthalate mixture was associated with a lower aBMD Z-score (eg, for PFOA: -0.24; 95% CI, -0.41 to -0.06). Serum PFOA and urinary MiBP were associated with higher aBMD Z-scores in females (eg, for PFOA: 0.09; 95% CI, -0.07 to 0.25). Findings did not differ by race/ethnicity. CONCLUSIONS: Certain PFAS and phthalates may be associated with reduced bone mineral density in adolescent males. Bone mineral density tracks across the life course, so if replicated in longitudinal cohorts, this finding may have implications for lifelong skeletal health.

Out-of-hospital births and infant mortality in the United States: Effect measure modification by rural maternal residence.

BACKGROUND: Out-of-hospital births have been increasing in the United States, and home births are almost twice as common in rural vs. urban counties. Planned home births and births in rural areas have each been associated with an increased risk of infant mortality. OBJECTIVES: To estimate the effect of birth setting on infant mortality in the United States and how this is modified by rural-urban county of maternal residence. METHODS: We conducted a population-based cohort study of infants born in the United States during 2010-2017 using the National Center for Health Statistics' period-linked birth-infant death files. Unadjusted and adjusted Poisson regression models were used to calculate infant mortality rate ratios and 95% confidence intervals for out-of-hospital births vs. hospital births stratified by maternal residence. Relative excess risk due to interaction (RERI) was calculated to assess effect measure modification on the additive scale. RESULTS: The study included 25,210,263 live births. Of rural births, 97.8% was in hospitals, 0.5% was in birth centres, and 1.5% was planned home births; of urban births, 98.6% was in hospitals, 0.5% was in birth centres, and 0.7% was planned home births. After adjusting for maternal demographics and markers of high-risk pregnancy and stratifying by maternal residence, infant mortality rates were generally higher for out-of-hospital as compared to hospital births (e.g. rural planned home births aRR 1.62, 95% confidence interval [CI] 1.42, 1.85, and rural birth centre aRR 1.33, 95% CI 1.05, 1.68). There were positive additive effects of rural residence on infant mortality for planned home births and birth centre births. CONCLUSIONS: Within both rural and urban areas, out-of-hospital births generally had higher rates of infant mortality than hospital births after accounting for maternal demographics and markers of high-risk pregnancy. The risks associated with planned home births and birth centre births were more pronounced for women in rural counties.

Sexual Orientation and Age at Menarche in Three U.S. Longitudinal Cohorts.

PURPOSE: The aim of this study is to examine age at menarche across sexual orientation groups. METHODS: Data were obtained from 131,090 female participants, born 1947-2001, in 3 longitudinal studies-the Growing Up Today Study and Nurses' Health Study 2 and 3. We estimated the association between sexual orientation and age at menarche using regression models adjusted for age, race/ethnicity, birthweight, height, and body mass index. RESULTS: Compared to heterosexual participants, sexual minorities were younger at menarche. Sexual minorities were more likely to have early menarche (≤11 years) and less likely to have late menarche (≥14 years) compared to heterosexual girls. As an example of this pattern, Nurses' Health Study 3 bisexual participants were >30% more likely than heterosexuals to have early versus average menarche (odds ratio 1.37, 95% confidence interval 1.09-1.72). CONCLUSION: Sexual minority girls have a younger age at menarche than heterosexual girls and may benefit from screening for adverse outcomes associated with early menarche.

Dietary correlates of urinary phthalate metabolite concentrations in 6-19 Year old children and adolescents.

BACKGROUND: Children are vulnerable to adverse health effects associated with phthalates, and food is one source of exposure. A comprehensive analysis investigating urinary phthalate metabolite concentrations in relation to food type and source has yet to be undertaken. OBJECTIVES: We use reduced rank regression, a dimension reduction method, to identify dietary patterns associated with urinary phthalate metabolites in children in a large US study. METHODS: We used data from 2369 participants 6-19 years old from the 2011-2016 National Health and Nutrition Examination Survey who recalled their diet over the 24 h prior to urine collection. We used dietary data to estimate intake and source (i.e., prepared at a restaurant vs. purchased from a grocery store) of 136 food groups. We used reduced rank regression to identify dietary patterns explaining variation in overall urinary concentrations of ∑di-2-ethylhexyl phthalate and seven phthalate metabolites. We also examined pairwise associations between food groups and urinary phthalate metabolites. RESULTS: We identified eight dietary patterns that cumulatively explained 12.1% of variation in urinary phthalate metabolites, including a dietary pattern characterized by certain starchy vegetables (e.g., plantains and lima beans), quick breads, and citrus juice prepared at a restaurant. A one SD increase in this food pattern score was associated with a 37.2% higher monocarboxyoctyl phthalate (MCOP) concentration (95% CI: 30.3, 44.4). We also observed weak associations between certain food groups and urinary phthalate metabolites (e.g., a one SD increase in intake of certain starchy vegetables prepared at a restaurant was associated with a 1.8% [95% CI: 0.7, 2.8] higher MCOP). CONCLUSIONS: Children whose diets were characterized by higher consumption of certain starchy vegetables, quick breads, and citrus juices prepared at a restaurant had higher urinary phthalate metabolites. More detailed information on the specific methods of food processing and details on packaging materials is needed.

Prospective associations of mid-childhood plasma per- and polyfluoroalkyl substances and pubertal timing.

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS) may disrupt pubertal timing. Higher PFAS plasma concentrations have been associated with later pubertal timing in girls, but cross-sectional findings may be explained by reverse causation. OBJECTIVES: To assess prospective associations between PFAS plasma concentrations in mid-childhood and markers of pubertal timing in male and female adolescents. METHODS: We studied 640 children in Project Viva, a Boston-area prospective cohort. We examined associations of plasma concentrations of 6 PFAS measured at mean 7.9 (SD 0.8) years (2007-2010) with markers of pubertal timing. Parents reported a 5-item pubertal development score at early adolescence (mean 13.1 (SD 0.8) years) and reported age at menarche annually. We calculated age at peak height velocity using research and clinical measures of height. We used sex-specific linear and Cox proportional hazards regression to estimate associations of single PFAS with outcomes, and we used Bayesian Kernel Machine Regression (BKMR) to estimate associations of the PFAS mixture with outcomes. RESULTS: Plasma concentrations were highest for perfluorooctane sulfonate (PFOS) [median (IQR) 6.4(5.6) ng/mL], followed by perfluorooctanoate (PFOA) [4.4(3.0) ng/mL]. In early adolescence, girls were further along in puberty than boys [pubertal development score mean (SD) 2.9 (0.7) for girls and 2.2(0.7) for boys; age at peak height velocity mean (SD) 11.2y (1.0) for girls and 13.1y (1.0) for boys]. PFAS was associated with later markers of pubertal timing in girls only. For example, each doubling of PFOA was associated with lower pubertal development score (-0.18 units; 95% CI: -0.30, -0.06) and older age at peak height velocity (0.23 years; 95% CI: 0.06, 0.40)]. We observed similar associations for PFOS, perfluorodecanoate (PFDA), and the PFAS mixture. PFAS plasma concentrations were not associated with age at menarche or markers of pubertal timing in boys. DISCUSSION: Higher PFAS plasma concentrations in mid-childhood were associated with later onset of puberty in girls.

Dietary patterns and PFAS plasma concentrations in childhood: Project Viva, USA.

BACKGROUND: Diet is thought to account for most adult human exposure to per- and polyfluoroalkyl substances (PFAS). Children are particularly vulnerable to adverse health effects of PFAS and may have different eating habits than adults. However, studies of dietary patterns and PFAS in children are limited. METHODS: We studied 548 Boston-area children with food frequency questionnaire data (89 food items) in early childhood (median age 3.3 years) and plasma concentrations of 6 PFAS quantified in mid-childhood (median age 7.7 years). We used univariate linear regression to examine associations between each food item and PFAS, accounting for multiple comparisons. We next used reduced rank regression (RRR) to estimate overall percent variation in PFAS explained by diet and identify dietary patterns most correlated with PFAS. All models were adjusted for race/ethnicity, maternal education, and household income. RESULTS: In univariate analyses, 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA) plasma concentrations were 17.8% (95% CI: 7.2, 29.5) and 17.0% (95% CI: 6.4, 28.7) higher per SD increment in intake of ice cream and soda, respectively. RRR identified 6 dietary patterns that together explained 18% variation in the plasma concentrations of the 6 PFAS, of which 50% was explained by a dietary pattern consisting of primarily packaged foods (including ice cream and soda) and fish. Children with higher intake of the packaged foods and fish dietary pattern had higher plasma concentrations of all PFAS, particularly MeFOSAA and PFOS. CONCLUSIONS: Our analysis examined food intake in association with several PFAS in children and identified dietary determinants that may be sources of PFAS exposure or reflect correlated lifestyle or toxicokinetic factors. Further investigation may help inform measures to modify childhood PFAS exposure.

Predictors of Plasma Fluoride Concentrations in Children and Adolescents.

Despite increasing concerns about neurotoxicity of fluoride in children, sources of fluoride exposure apart from municipal water fluoridation are poorly understood. We aimed to describe the associations of demographics, drinking water characteristics, diet, and oral health behaviors with plasma fluoride concentrations in U.S. children. We used data from 3928 6-19-year-olds from the 2013-2016 National Health and Nutrition Examination Survey. We used a 24-h dietary recall to estimate recent consumption of fluoridated tap water and select foods. We estimated the associations of fluoridated tap water, time of last dental visit, use of toothpaste, and frequency of daily tooth brushing with plasma fluoride concentrations. The participants who consumed fluoridated (≥0.7 mg/L) tap water (n = 560, 16%) versus those who did not had 36% (95% CI: 22, 51) higher plasma fluoride. Children who drank black or green tea (n = 503, 13%) had 42% higher plasma fluoride concentrations (95% CI: 27, 58) than non-tea drinkers. The intake of other foods and oral health behaviors were not associated with plasma fluoride concentrations. The consumption of fluoridated tap water and tea substantially increases plasma fluoride concentrations in children. Quantifying the contribution of diet and other sources of fluoride is critical to establishing safe target levels for municipal water fluoridation.

Rural-Urban Differences in Hospitalizations for Opioid Use-Associated Infective Endocarditis in the United States, 2003-2016.

BACKGROUND: The incidence of infective endocarditis, a serious heart infection that can result from injection drug use, has increased in step with the opioid epidemic. Harm reduction services aimed at decreasing infectious complications of injection drug use are limited in rural areas; however, it is unknown whether the burden of opioid use-associated infective endocarditis varies between rural and urban populations. METHODS: We used 2003-2016 National (Nationwide) Inpatient Sample data and joinpoint regression to compare trends in hospitalization for opioid use-associated infective endocarditis between rural and urban populations. RESULTS: Rates of US hospitalizations for opioid use-associated infective endocarditis increased from 0.28 to 3.86 per 100 000 rural residents, as compared with 1.26 to 3.49 for urban residents (overall difference in annual percent change P < .01). We observed 2 distinct trend periods, with a period of little change between 2003 and 2009/2010 (annual percent change, 0.0% rural vs -0.08% urban) followed by a large increase in hospitalization rates between 2009/2010 and 2016 (annual percent change, 0.35% rural vs 0.36% urban). Over the study period, opioid use-associated infective endocarditis hospitalizations shifted toward younger age groups for both rural and urban residents, and rural resident hospitalizations increasingly occurred at urban teaching hospitals. For both groups, Medicaid was the most common payer. CONCLUSIONS: The increase in US hospitalizations for opioid use-associated infective endocarditis over the past decade supports the importance of public health efforts to reduce injection-related infections in both urban and rural areas. Future studies should examine factors affecting the higher increase in rate of these hospitalizations in rural areas.

Reproductive and developmental health effects of prenatal exposure to tetrachloroethylene-contaminated drinking water.

Tetrachloroethylene (PCE) is a common contaminant in both occupational and community settings. High exposure levels in the workplace have been shown to have adverse impacts on reproduction and development but few epidemiological studies have examined these effects at the lower levels commonly seen in community settings. We were presented with a unique opportunity to examine the reproductive and developmental effects of prenatal exposure to PCE-contaminated drinking water resulting from the installation of vinyl-lined water pipes in Massachusetts and Rhode Island from the late 1960s through 1980. This review describes the methods and findings of two community-based epidemiological studies, places their results in the context of the existing literature, and describes the strengths and challenges of conducting epidemiological research on a historical pollution episode. Our studies found that prenatal exposure to PCE-contaminated drinking water is associated with delayed time-to-pregnancy, and increased risks of placental abruption, stillbirths stemming from placental dysfunction, and certain birth defects. No associations were observed with pregnancy loss, birth weight, and gestational duration. Important strengths of this research included the availability of historical data on the affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little opportunity for recall bias and confounding. Challenges arose mainly from the retrospective nature of the exposure assessments. This research highlights the importance of considering pregnant women and their developing fetuses when monitoring, regulating, and remediating drinking water contaminants.

Residential Proximity to Roadways and Ischemic Placental Disease in a Cape Cod Family Health Study.

Exposure to air pollution may adversely impact placental function through a variety of mechanisms; however, epidemiologic studies have found mixed results. We examined the association between traffic exposure and placental-related obstetric conditions in a retrospective cohort study on Cape Cod, MA, USA. We assessed exposure to traffic using proximity metrics (distance of residence to major roadways and length of major roadways within a buffer around the residence). The outcomes included self-reported ischemic placental disease (the presence of at least one of the following conditions: preeclampsia, placental abruption, small-for-gestational-age), stillbirth, and vaginal bleeding. We used log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We found no substantial association between traffic exposure and ischemic placental disease, small-for-gestational-age, preeclampsia, or vaginal bleeding. We found some evidence of an increased risk of stillbirth and placental abruption among women living the closest to major roadways (RRs comparing living <100 m vs. ≥200 m = 1.75 (95% CI: 0.82-3.76) and 1.71 (95% CI: 0.56-5.23), respectively). This study provides some support for the hypothesis that air pollution exposure adversely affects the risk of placental abruption and stillbirth; however, the results were imprecise due to the small number of cases, and may be impacted by non-differential exposure misclassification and selection bias.

Childhood and adolescent fish consumption and adult neuropsychological performance: An analysis from the Cape Cod Health Study.

OBJECTIVE: This exploratory analysis examines the relationship between childhood and adolescent fish consumption and adult neuropsychological performance. DESIGN: Data from a retrospective cohort study that assessed fish consumption from age 7 to 18years via questionnaire were analyzed. A subset of the population underwent domain-specific neuropsychological assessment. Functions evaluated included omnibus intelligence, academic achievement, language, visuospatial skills, learning and memory, attention and executive function, fine motor coordination, mood, and motivation to perform. SETTING: Eight towns in the Cape Cod region of Massachusetts, USA, an area characterized by high fish consumption and an active seafood industry. SUBJECTS: A cohort of 1245 subjects was recruited based on Massachusetts birth records from 1969 to 1983. Sixty-five participants from the original cohort underwent neuropsychological testing in adulthood (average age=30years). RESULTS: Participant report of consuming fish at least twice per month was associated with better performance on tests of visual learning, memory, and attentional abilities. However, self-report of consuming fish at rates higher than twice per month was not associated with improved abilities. No statistically significant associations were observed between type of fish consumed (e.g., species known to be high in methylmercury content) and test outcomes. CONCLUSIONS: The results suggest that moderate fish consumption during childhood and adolescence may be associated with some cognitive benefits and that consumption of fish during this exposure window may potentially influence adult neuropsychological performance. Future prospective studies should take into account this time period of exposure.

Childhood Fish Consumption and Learning and Behavioral Disorders.

Fish is a major source of nutrients critical for brain development during early life. The importance of childhood fish consumption is supported by several studies reporting associations of n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation with better behavior and school performance. However, fish may have a different effect than n-3 PUFA alone due to the neurotoxic effects of methylmercury, a frequent contaminant. We investigated associations of childhood fish consumption with learning and behavioral disorders in birth cohort study of the neurotoxic effects of early life exposure to solvent-contaminated drinking water. Childhood (age 7-12 years) fish consumption and learning and behavioral problems were reported in self-administered questionnaires (age 23-41 at questionnaire completion). Fish consumption was not meaningfully associated with repeating a grade, tutoring, attending summer school, special class placement, or low educational attainment. However, participants who ate fish several times a week had an elevated odds of Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (odds ratio: 5.2; 95% confidence interval: 1.5-18) compared to participants who did not eat fish. While these findings generally support the safety of the observed level of fish consumption, the absence of a beneficial effect may be attributed to insufficient fish intake or the choice of relatively low n-3 PUFA fish.

Milk Consumption after Age 9 Years Does Not Predict Age at Menarche.

BACKGROUND: Regular milk consumption during childhood and adolescence is recommended for bone health. However, milk consumption increases circulating insulin-like growth factor I concentrations, and may also accelerate puberty. OBJECTIVE: We prospectively investigated the association between milk consumption and age at menarche in the Growing Up Today Study. METHODS: Study participants were 5583 US girls who were premenarcheal and ages 9-14 y in 1996. Girls were followed through 2001, at which time 97% of noncensored participants had reported menarche. Frequency of milk and meat consumption was calculated with the use of annual youth/adolescent food frequency questionnaires from 1996-1998. Intake of related nutrients was also measured. Age at menarche was self-reported annually through 2001. RESULTS: During follow-up, 5227 girls attained menarche over 10,555 accrued person-years. In models adjusted for dietary and sociodemographic predictors of menarche, frequency of milk consumption did not predict age at onset of menarche (for >3 glasses of milk/d vs. 1.1-4 glasses/wk, HR: 0.93; 95% CI: 0.83, 1.04). After additional adjustment for body size, premenarcheal girls consuming >3 glasses of milk daily were 13% less likely (95% CI: -3%, -23%; P-trend: <0.01) to attain menarche in the next month relative to those consuming 1.1-4 glasses/wk. Neither total meat nor red meat consumption was associated with age at menarche. CONCLUSIONS: Our findings suggest that regular consumption of milk in girls aged ≥9 y is unlikely to substantially affect age at onset of menarche. Studies assessing associations between diet in early childhood and pubertal timing may be more illuminating.

Prenatal drinking-water exposure to tetrachloroethylene and ischemic placental disease: a retrospective cohort study.

BACKGROUND: Prenatal drinking water exposure to tetrachloroethylene (PCE) has been previously related to intrauterine growth restriction and stillbirth. Pathophysiologic and epidemiologic evidence linking these outcomes to certain other pregnancy complications, including placental abruption, preeclampsia, and small-for-gestational-age (SGA) (i.e., ischemic placental diseases), suggests that PCE exposure may also be associated with these events. We examined whether prenatal exposure to PCE-contaminated drinking water was associated with overall or individual ischemic placental diseases. METHODS: Using a retrospective cohort design, we compared 1,091 PCE-exposed and 1,019 unexposed pregnancies from 1,766 Cape Cod, Massachusetts women. Exposure between 1969 and 1990 was estimated using water distribution system modeling software. Data on birth weight and gestational age were obtained from birth certificates; mothers self-reported pregnancy complications. RESULTS: Of 2,110 eligible pregnancies, 9% (N = 196) were complicated by ≥1 ischemic placental disease. PCE exposure was not associated with overall ischemic placental disease (for PCE ≥ sample median vs. no exposure, risk ratio (RR): 0.90; 95% confidence interval (CI): 0.65, 1.24), preeclampsia (RR: 0.36; 95% CI: 0.12-1.07), or SGA (RR: 0.98; 95% CI: 0.66-1.45). However, pregnancies with PCE exposure ≥ the sample median had 2.38-times the risk of stillbirth ≥27 weeks gestation (95% CI: 1.01, 5.59), and 1.35-times of the risk of placental abruption (95% CI: 0.68, 2.67) relative to unexposed pregnancies. CONCLUSIONS: Prenatal PCE exposure was not associated with overall ischemic placental disease, but may increase risk of stillbirth.

Early and late menarche and risk of depressive symptoms in young adulthood.

We investigated whether girls experiencing early menarche have an increased risk of depression during young adulthood. This study used data collected in the Growing Up Today Study (N = 9,039), an ongoing prospective cohort of the daughters of women enrolled in the Nurses' Health Study II. After excluding girls who were postmenarcheal at baseline in 1996, <20 or ≥26 years old in 2007, or missing data on key covariates, the final sample size was 3,711. Self-reported age at menarche was collected annually. Depressive symptomatology was measured in 2007 using the 10-item Center for Epidemiologic Studies Depression (CES-D-10) score. Sixteen percent of girls (N = 596) reported high levels of depressive symptoms (CES-D-10 ≥ 14) in 2007. Neither early nor late menarche was associated with high depressive symptoms (for early vs. normative menarche, odds ratio (OR) = 1.08, 95 % confidence interval (CI) = 0.85-1.38; for late vs. normative menarche, OR = 0.91, 95 % CI = 0.70-1.18) or with differences in continuous CES-D-10 score in young adulthood. Although previous studies suggest that girls with early menarche suffer from an increased risk of adolescent depression, this does not appear to persist into young adulthood.

Use of a simple visual distraction to reduce pain and anxiety in patients undergoing colposcopy.

OBJECTIVE: We hypothesized that a passive visual distraction would reduce pain and anxiety among women undergoing colposcopy. MATERIALS AND METHODS: We assessed the association between exposure to a passive visual distraction during colposcopy and procedure-related pain and anxiety using a nonrandomized intervention design. Women presenting for initial or repeat colposcopy at Brigham and Women's Hospital Colposcopy Clinics were eligible for participation. Women undergoing colposcopy during the first 6 months of the study (n=168) were not exposed to the visual distraction, whereas women undergoing colposcopy during the second 6 months of the study (n=153) were exposed to a pleasing, passive visual distraction consisting of images on a light diffuser installed within the examination room's ceiling light. We used ordinal logistic regression to compare self-reported pain, measured using the visual analog scale, and anxiety, measured using the Spielberger State-Trait Anxiety Inventory-6, among women receiving and not receiving the intervention. RESULTS: Two hundred sixteen women with complete data were included in the final analyses. Women in both groups reported high levels of colposcopy-related anxiety. Compared to women who did not receive the visual distraction, women receiving the visual distraction during colposcopy had a 54% reduction in the odds of experiencing a given level of postexamination pain, holding preprocedure pain constant (odds ratio=0.46, 95% confidence interval=0.28-0.77). Visual distraction was not associated with postexamination anxiety (odds ratio=0.95, 95% confidence interval=0.60-1.51). CONCLUSIONS: A passive visual distraction reduced perceived pain, but not anxiety, after colposcopy.