Ruby H.N. Nguyen

Prevalence of symptoms consistent with a diagnosis of vulvodynia: population-based estimates from 2 geographic regions

OBJECTIVE We used validated sensitive and specific questions associated with clinically confirmed diagnoses of unexplained vulvar pain (vulvodynia) to compare the cumulative incidence of vulvar pain and prevalence of care-seeking behavior in Boston metropolitan area (BMA) and in Minneapolis/Saint Paul metropolitan area (MSP) from 2001 through 2005 using census-based data, and 2010 through 2012, using outpatient community-clinic data, respectively. STUDY DESIGN We received self-administered questionnaires from 5440 women in BMA and 13,681 in MSP, 18-40 years of age, describing their history of vulvar burning or pain on contact that persisted >3 months that limited/prevented intercourse. RESULTS By age 40 years, 7-8% in BMA and MSP reported vulvar pain consistent with vulvodynia. Women of Hispanic origin compared to whites were 1.4 times more likely to develop vulvar pain symptoms (95% confidence interval, 1.1-1.8). Many women in MSP (48%) and BMA (30%) never sought treatment, and >50% who sought care with known health care access received no diagnosis. CONCLUSION Using identical screening methods, we report high prevalence of vulvar pain in 2 geographic regions, and that access to health care does not increase the likelihood of seeking care for chronic vulvar pain.

Co-morbid pain conditions and feelings of invalidation and isolation among women with vulvodynia.

Many women with vulvodynia also suffer from other chronic co-morbid pain conditions. Alone, these pain conditions are associated with feeling invalidated by others and feeling socially isolated. It is unclear, however, how the presence of additional pain co-morbidities are associated with the psychosocial wellbeing of women with vulvodynia. We used data from a survey administered by the National Vulvodynia Association. Women reported clinician-diagnosed vulvodynia, presence of co-morbid pain, and how often they felt that they felt no one believed their pain existed (invalidated) and isolated. Analyses determined prevalence of feeling invalidated or isolated, and the difference in prevalence when co-morbidities existed. Forty-five percent of these 1847 women with vulvodynia reported having at least one of the following five chronic pain conditions, chronic fatigue syndrome, endometriosis, fibromyalgia, interstitial cystitis, or irritable bowel syndrome. Adjusted baseline prevalence among all women of feeling invalidated was 9% and of feeling isolated was 14%. Having a co-morbid condition with vulvodynia, as well as having an increasing number of co-morbid conditions with vulvodynia, was significantly associated with the presence of feeling both invalidated and isolated. Chronic fatigue syndrome was the co-morbidity most strongly associated with feelings invalidation and isolation. One or more co-morbid pain conditions in addition to vulvodynia were significantly associated with psychosocial wellbeing. However, the temporality of the association could not be elucidated and therefore we cannot conclude that these pain conditions cause poor psychosocial wellbeing. Despite this, future studies should explore the utility of promoting validation of womens pain conditions and reducing social isolation for women with chronic pain.

Anogenital distance and penile width measurements in The Infant Development and the Environment Study (TIDES): methods and predictors

BACKGROUND Anogenital distance (AGD) is an androgen responsive anatomic measurement that may have significant utility in clinical and epidemiological research studies. We describe development of standardized measurement methods and predictors of AGD outcomes. METHODS We examined infants born to 758 participants in The Infant Development and the Environment Study (TIDES cohort) in four clinical centers in 2011-2013. We developed and implemented a detailed training protocol that incorporated multiple quality control (QC) measures. In males, we measured anoscrotal distance (AGDAS), anopenile distance (AGDAP), and penile width (PW) and in females, anofourchette distance (AGDAF,) and anoclitoral distance (AGDAC). A single examiner obtained three repetitions of all measurements, and a second examiner obtained independent measurements for 14% of infants. We used the intra-rater ICC to assess within-examiner variability and the inter-rater ICC to assess between-examiner variability. We used multivariable linear regression to examine predictors of AGD outcomes including: gestational age at birth, birth weight, gestational age, several measures of body size, race, maternal age, and study center. RESULTS In the full TIDES cohort, including 758 mothers and children, significant predictors of AGD and PW included: age at exam, gestational age at birth, weight-for-length Z-score, maternal age and study center. In 371 males, the mean (SD) AGDAS, AGDAP, and PW were 24.7 (4.5), 49.6 (5.9), and 10.8 (1.3) mm, respectively. In 387 females, the mean (SD) AGDAF and AGDAC were 16.0 (3.2) mm and 36.7 (3.8) mm, respectively. The intra-examiner ICC and inter-examiner ICC averaged over all subjects and examiners were between 0.89-0.92 and 0.69-0.84 respectively. CONCLUSIONS Our study confirms that with appropriate training and quality control measures, AGD and PW measurements can be performed reliably and accurately in male and female infants. In order for reliable interpretation, these measurements should be adjusted for appropriate covariates in epidemiologic analysis.

Latent class analysis of comorbidity patterns among women with generalized and localized vulvodynia: preliminary findings

Background The pattern and extent of clustering of comorbid pain conditions with vulvodynia is largely unknown. However, elucidating such patterns may improve our understanding of the underlying mechanisms involved in these common causes of chronic pain. We sought to describe the pattern of comorbid pain clustering in a population-based sample of women with diagnosed vulvodynia. Methods A total of 1457 women with diagnosed vulvodynia self-reported their type of vulvar pain as localized, generalized, or both. Respondents were also surveyed about the presence of comorbid pain conditions, including temporomandibular joint and muscle disorders, interstitial cystitis, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, endometriosis, and chronic headache. Age-adjusted latent class analysis modeled extant patterns of comorbidity by vulvar pain type, and a multigroup model was used to test for the equality of comorbidity patterns using a comparison of prevalence. A two-class model (no/single comorbidity versus multiple comorbidities) had the best fit in individual and multigroup models. Results For the no/single comorbidity class, the posterior probability prevalence of item endorsement ranged from 0.9% to 24.4%, indicating a low probability of presence. Conversely, the multiple comorbidity class showed that at least two comorbid conditions were likely to be endorsed by at least 50% of women in that class, and irritable bowel syndrome and fibromyalgia were the most common comorbidities regardless of type of vulvar pain. Prevalence of the multiple comorbidity class differed by type of vulvar pain: both (37.6% prevalence, referent), generalized (21.6% prevalence, adjusted odds ratio 0.41, 95% confidence interval 0.27–0.61), or localized (12.5% prevalence, adjusted odds ratio 0.31, 95% confidence interval 0.21–0.47). Conclusion This novel work provides insight into potential shared mechanisms of vulvodynia by describing that a prominent comorbidity pattern involves having both irritable bowel syndrome and fibromyalgia. In addition, the prevalence of a multiple comorbidity class pattern increases with increasing severity of vulvar pain.

Allergic Reactions and Risk of Vulvodynia

PURPOSE A recent histological study of vestibular tissue from women with localized vulvodynia found universal presence of mast cells compared to no presence in vestibular tissue among controls. Since histamine is generated by mast cells, and mast cells contribute to the production of cytokines during chronic inflammation, we assessed the association between conditions that elicit a clinically relevant histamine response and vulvodynia. METHODS We studied 239 women with and 239 women without vulvodynia to assess the influence of self-reported allergic reactions antecedent to first development of vulvar pain symptoms among cases, and a matched reference age among controls. RESULTS Women with self-reported hives prior to first report of vulvar pain or reference age among controls were 2.5 times more likely to develop vulvodynia (95% confidence interval [CI], 1.7-4.4). Those reporting a history of allergic reactions to insect bites were 2.1 times more likely (95%CI, 1.1-4.0), and those reporting a history of seasonal allergies were 2.0 times (95%CI, 1.3-3.2) more likely to develop vulvodynia. Findings were similar in a restricted subset of clinically confirmed cases and matched controls. CONCLUSIONS An altered immuno-inflammatory response to environmentally induced allergic reactions may predispose women to the development of vulvodynia or may be markers of an already heightened immuno-inflammatory response.

Environmental health attitudes and behaviors: findings from a large pregnancy cohort study

OBJECTIVE Environmental chemicals are widely found in food and personal care products and may have adverse effects on fetal development. Our aim was to examine womens attitudes about these chemicals and ask whether they try to limit their exposure during pregnancy. STUDY DESIGN A multi-center cohort of women in the first trimester of pregnancy completed questionnaires including items on attitudes and behaviors related to environmental chemicals. Multivariable logistic regression models were used to examine: (1) whether sociodemographic variables predict environmental health attitudes and behaviors; and (2) whether womens attitudes about environmental chemicals affect their lifestyle behaviors, particularly diet and personal care product use. RESULTS Of the 894 subjects, approximately 60% strongly agreed that environmental chemicals are dangerous and 25% strongly felt they were impossible to avoid. Adjusting for covariates, educated women were more likely to believe that environmental chemicals are dangerous (OR 1.74, 95% CI 1.13, 2.66), and that belief, in turn, was associated with a number of healthy behaviors including choosing organic foods, foods in safe plastics, and chemical-free personal care products, and limiting fast food intake. Younger women were more likely to believe that environmental chemicals are impossible to avoid (OR 1.04, 95% CI 1.00, 1.08). CONCLUSIONS Womens attitudes about environmental chemicals may impact their choices during pregnancy. Overcoming a lack of concern about environmental chemicals, particularly among certain sociodemographic groups, is important for the success of clinical or public health prevention measures.

Reduced fertility among HIV-infected women associated with viral load in Rakai district, Uganda.

We assessed whether HIV-1 viral load affects the likelihood of live birth among HIV-positive women in a nested case–control study of HIV-positive women from a community cohort in Rakai District, Uganda. Cases were women who had a live birth (n = 270), and controls were sexually active women who did not use contraception and did not become pregnant during follow-up (n = 263). In women with a live birth and non-pregnant controls, median HIV viral loads were 4.12 log10 copies/mL and 4.41 log10 copies/mL, respectively (P = 0.001). A non-linear association was observed, and a segmented linear regression with spline knot at 4.5 log10 copies/mL was fit. We observed a decline in the log (adjusted odds ratio [adj. OR])= −0.08 (95% confidence interval [CI]: −0.36, 0.20) between 3.0 and 4.49 log10 viral load and −0.92 (95% CI: −1.21, −0.63) between 4.5 and 6.5 log10 viral load. The two reductions differed significantly from one another (P < 0.001). Each increase in log10 viral load after 4.5 log10 resulted in an adj. OR of live birth which was 12% of the previous viral load category. Our data suggest that there may be considerable differences in the ability to produce a live birth among HIV-positive women with high viral loads.

Dietary phthalate exposure in pregnant women and the impact of consumer practices

Phthalates are ubiquitous endocrine-disrupting chemicals that are contaminants in food and contribute to significant dietary exposures. We examined associations between reported consumption of specific foods and beverages and first trimester urinary phthalate metabolite concentrations in 656 pregnant women within a multicenter cohort study, The Infant Development and Environment Study (TIDES), using multivariate regression analysis. We also examined whether reported use of ecofriendly and chemical-free products was associated with lower phthalate biomarker levels in comparison to not following such practices. Consumption of one additional serving of dairy per week was associated with decreases of 1% in the sum of di-2-ethylhexyl phthalate (DEHP) metabolite levels (95% CI: −2.0, −0.2). Further, participants who reported sometimes eating homegrown food had monoisobutyl phthalate (MiBP) levels that were 16.6% lower (95% CI: −29.5, −1.3) in comparison to participants in the rarely/never category. In contrast to rarely/never eating frozen fruits and vegetables, participants who reported sometimes following this practice had monobenzyl phthalate (MBzP) levels that were 21% higher (95% CI: 3.3, 41.7) than rarely/ever respondents. Future study on prenatal dietary phthalate exposure and the role of consumer product choices in reducing such exposure is needed.

Similar DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology: a cross-sectional study.

BackgroundWhile a possible link between assisted reproductive technology (ART) and rare imprinting disorders has been found, it is not clear if this is indicative of subtler disruptions of epigenetic mechanisms. Results from previous studies have been mixed, but some methylation differences have been observed.MethodsChildren conceived through ART and children conceived spontaneously were recruited for this cross-sectional study. Information about reproductive history, demographic factors, birth characteristics, and infertility treatment was obtained from maternal interview and medical records. Peripheral blood lymphocytes and buccal cell samples were collected from participating children. Methylation analysis was performed on five loci using pyrosequencing. Statistical analysis of methylation differences was performed using linear regression with generalized estimating equations. Results are reported as differences with 95% confidence intervals (CI).ResultsA total of 67 ART children and 31 spontaneously conceived (SC) children participated. No significant difference in methylation in lymphocyte samples was observed between groups for any loci. Possible differences were found in buccal cell samples for IGF2 DMR0 (Difference: 2.07; 95% confidence interval (CI): -0.28, 4.42; p = 0.08) and IGF2R (Difference: -2.79; 95% CI: -5.74, 0.16; p = 0.06). Subgroup analysis indicated potential lower methylation in those whose parents used ART for unexplained infertility.ConclusionsObserved differences in methylation between the ART and SC groups were small for all loci in the two sample types examined and no statistical differences were observed. It is still unclear whether or not small differences observed in several studies represent a real difference between groups and if this difference is biologically meaningful. Larger studies with long term follow-up are needed to fully answer these questions.

Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns

Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS) and anopenile distance (AGPAP) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono‐2‐ethyl‐5‐oxohexyl (MEOHP, β=−0.48; 95% confidence interval, −0.93, −0.02), MEHHP (−0.48; −0.92, −0.05), mono‐2‐ethyl‐5‐carboxypentyl (MECPP, −0.51; −1.01, −0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono‐2‐ethyl‐5‐hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (β = −1.73; 95% confidence interval, −3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these associations in humans.