Interrogating Components of 2 Diet Quality Indices in Pregnancy using a Supervised Statistical Mixtures Approach.

BACKGROUND: The Healthy Eating Index (HEI)-2015 and Alternative Healthy Eating Index (AHEI)-2010 evaluate diet holistically in pregnancy. However, it remains unclear how individual index components interact to contribute to health. OBJECTIVES: To evaluate associations of HEI-2015 and AHEI-2010 components with gestational length using traditional and novel statistical methods in a prospective cohort. METHODS: Pregnant women completed a 3-mo food-frequency questionnaire (FFQ) at median 13 wk gestation to calculate the HEI-2015 or AHEI-2010. Covariate-adjusted linear regression models evaluated associations of HEI-2015 and AHEI-2010 total scores and individual components (one at a time and simultaneously adjusted) with gestational length. Covariate-adjusted weighted quantile sum regression models evaluated 1) associations of HEI-2015 or AHEI-2010 components as mixtures with gestational length and 2) contributions of components to these associations. RESULTS: Each 10-point increase in HEI-2015 and AHEI-2010 total score was associated with 0.11 (95% CI: -0.05, 0.27) and 0.14 (95% CI: 0.00, 0.28) wk longer gestation, respectively. In individual or simultaneously adjusted HEI-2015 models, higher intakes of seafood/plant proteins, total protein foods, greens/beans, and saturated fats but lower intakes of added sugars and refined grains were associated with longer gestational length. For the AHEI-2010, higher intake of nuts/legumes and lower intake of sugar-sweetened beverages (SSBs)/fruit juice were associated with longer gestational length. Jointly, 10% increases in HEI-2015 or AHEI-2010 mixtures were associated with 0.17 (95% CI: 0.001, 0.34) and 0.18 (95% CI: 0.05, 0.30) wk longer gestational length, respectively. Seafood/plant protein, total protein foods, dairy, greens/beans, and added sugars were the largest contributors to the HEI-2015 mixture. Nuts/legumes, SSBs/fruit juice, sodium, and DHA/EPA were the largest contributors to the AHEI-2010 mixture. Associations were less precise but consistent in women with spontaneous labors. CONCLUSIONS: Compared to traditional methods, associations of diet index mixtures with gestational length were more robust and identified unique contributors. Additional studies could consider interrogating these statistical approaches using other dietary indices and health outcomes.

Peroral cricopharyngeal myotomy for the management of Zenker's diverticulum in the hands of a general surgeon.

BACKGROUND: The treatment of Zenker's diverticulum has been shifted from open cricopharyngeal myotomy and rigid endoscopy to the use of flexible endoscopy. Few studies evaluate general surgeon's performance of flexible endoscopic management of Zenker's diverticulum as the majority are performed by gastroenterologists. The objective of our case series is to show that general surgeons trained in surgical endoscopy can perform this procedure with favorable outcomes. METHODS: A retrospective review of peroral cricopharyngeal myotomies performed at Spectrum Health hospital in Grand Rapids, Michigan by a single surgical endoscopist between the 2018 and 2021 was conducted. The primary outcome was the improvement of dysphagia. Intra-procedural complications, post-procedural complications, hospital length of stay, time to oral intake, and recurrence were also evaluated. Age, sex, body mass index, diverticulum size, and procedure time were abstracted. Median (ranges) and frequencies (percentages) are used to describe the patient population and outcomes. RESULTS: Forty patients were included in the study. Median age was 74 years old (60-95) with a male predominance (n = 27, 67.5%). Median BMI was 28 kg/m2 (18-43), average procedure length of 64 min (41-119), diverticulum size of 28 mm (19-90), and average length of stay of 0.9 days (0-8). There were no intra-procedural complications. All patients had a post-procedural esophagram prior to initiation of diet. Esophageal leak was the only complication that occurred, which was found on post-procedural esophagram (n = 5). Only two patients had clinical sequelae. All leaks closed without additional surgical intervention. The majority of patients had their diet resumed and discharged the same day of the procedure. Frequency of recurrence was 17.5% (n = 7). CONCLUSION: Our study demonstrates that general surgeons trained in endoscopy can perform endoscopic myotomies for Zenker's diverticula on a wide range of sizes, with favorable patient outcomes, and few complications.

Associations of individual and cumulative urinary phthalate and replacement biomarkers with gestational weight gain through late pregnancy.

BACKGROUND/AIMS: Phthalates and their replacements are endocrine/metabolic disruptors that may impact gestational weight gain (GWG) - a pregnancy health indicator. We investigated overall and fetal sex-specific associations of individual and cumulative phthalate/replacement biomarkers with GWG. METHODS: Illinois women (n = 299) self-reported their weight pre-pregnancy and at their final obstetric appointment before delivery (median 38 weeks). We calculated pre-pregnancy body mass index and gestational age-specific GWG z-scores (GWGz). We quantified 19 phthalate/replacement metabolites (representing 10 parent compounds) in pools of up-to-five first-morning urine samples, collected approximately monthly between 8 and 40 weeks gestation. We used linear regression, quantile-based g-computation (QGComp), and weighted quantile sum regression (WQSR) to evaluate associations of ten biomarkers (individual metabolites or parent molar-sums) individually or as mixtures (in interquartile range intervals) with GWGz. We evaluated associations in all women and stratified by fetal sex. RESULTS: Individually, sums of metabolites of di(2-ethylhexyl) phthalate (Æ©DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (Æ©DiNCH), and di(2-ethylhexyl) terephthalate (Æ©DEHTP) had consistent inverse associations with GWGz, and some associations were fetal sex-specific. When evaluating phthalates/replacements as a mixture, QGComp identified Æ©DEHP, Æ©DEHTP, and mono-(3-carboxypropyl) phthalate, along with sum of di(isononyl) phthalate metabolites (Æ©DiNP) and monobenzyl phthalate as notable contributors to lower and higher GWGz, respectively, resulting in a marginal inverse joint association in all women (ß: -0.29; 95% CI: -0.70, 0.12). In women carrying females, Æ©DEHP contributed to the marginal inverse joint association (ß: -0.54; 95% CI: -1.09, 0.03). However, there was no overall association in women carrying males (ß: 0.00; 95% CI: -0.60, 0.59), which was explained by approximately equal negative (driven by Æ©DEHTP) and positive (driven by Æ©DiNP) partial associations. WQSR analyses consistently replicated these QGComp findings. CONCLUSIONS: Biomarkers of phthalates/replacements were fetal sex-specifically associated with GWGz. Because Æ©DEHTP contributed substantively to mixture associations, additional studies in pregnant women may be needed around this plasticizer replacement.

Determinants of urinary phthalate biomarker concentrations in pre- and perimenopausal women with consideration of race.

BACKGROUND/OBJECTIVES: Phthalates are endocrine disruptors in consumer plastics and personal care products. Our objectives were to identify determinants of phthalate biomarkers in women during the hormonally-sensitive midlife period, and to consider differences between non-Hispanic White and Black women. METHODS: We used information from the Midlife Women's Health Study of pre- and peri-menopausal women from Baltimore, Maryland (enrolled 2006-2015). We collected sociodemographic/health information via baseline questionnaires or during clinic visits and measured nine phthalate metabolites in pools of 2-4 urines collected across one menstrual cycle. We calculated molar sums of metabolites to estimate exposure to di(2-ethylhexyl) phthalate (ΣDEHP), personal care product phthalates (ΣPCPs), and phthalates in plastics (ΣPlastics). Accounting for meaningful predictors from bivariable analyses, our multivariable linear regression models evaluated determinants of phthalate biomarkers in all women (n = 689), non-Hispanic White women only (n = 467), or non-Hispanic Black women only (n = 195). RESULTS: In multivariable analyses of all women, those who were perimenopausal, widowed/divorced, non-Hispanic Black, with higher family income, with lower BMI, or who reported more frequent nausea had higher monoethyl phthalate (MEP) and ΣPCP. Non-Hispanic White women who were perimenopausal had lower mono-(3-carboxypropyl) phthalate (MCPP) and monobutyl phthalate (MBP), those who consume alcohol had higher mono-isobutyl phthalate (MiBP), and those with higher BMI had lower MEP and higher MCPP. Alternatively, widowed/divorced Black women had higher ΣDEHP, monobenzyl phthalate (MBzP), and ΣPlastics, whereas Black women with higher income had higher MEP and ΣPCP. Black women who described themselves as having "as much" physical activity as others or who reported a skin condition had lower MBzP and MCPP, respectively. CONCLUSION: We identified important determinants of phthalate biomarkers in midlife women and observed some differences by race. Future studies could consider reasons for these differences when developing interventions to reduce phthalate disparities and related health effects.

Identification of profiles and determinants of maternal pregnancy urinary biomarkers of phthalates and replacements in the Illinois Kids Development Study.

BACKGROUND/OBJECTIVES: Pregnant women are exposed to multiple phthalates and their replacements, which are endocrine disrupting chemicals associated with adverse maternal and child health outcomes. Identifying maternal characteristics associated with phthalate/replacement exposure during pregnancy is important. METHODS: We evaluated 13 maternal sociodemographic and lifestyle factors, enrollment year, and conception season as determinants of exposure biomarkers of phthalates and their replacements in 482 pregnant women from the Illinois Kids Development Study (I-KIDS, enrolled 2013-2018). We quantified 19 phthalate/replacement metabolites in pools of five first-morning urines collected across pregnancy. K-means clustering identified women with distinct patterns of biomarker concentrations and principal component analysis (PCA) identified principal component (PC) profiles of biomarkers that exist together. We used multivariable regression models to evaluate associations of predictors with identified k-means clusters and PCs. RESULTS: K-means clustering identified two clusters of women: 1) low phthalate/di(2-ethylhexyl) terephthalate (∑DEHTP) and 2) high phthalate/∑DEHTP biomarker concentrations. PCA identified four PCs with loadings heaviest for biomarkers of plasticizer phthalates [di-isononyl, di-isodecyl, di-n-octyl phthalates] (PC1), of other phthalates [dibenzyl, di-n-butyl, di-iso-butyl phthalates] (PC2), of phthalate replacements [∑DEHTP, di(isononyl) cyclohexane-1,2-dicarboxylate (∑DiNCH)] (PC3), and of monoethyl phthalate [MEP] (PC4). Overall, age, marital status, income, parity, pre-pregnancy BMI, caffeine intake, enrollment year, and conception season were independently associated with k-means cluster membership and at least one PC. Additionally, race/ethnicity, education, employment, pregnancy intention, smoking status, alcohol intake, and diet were associated with at least one PC. For instance, women who conceived in the spring, summer, and/or fall months had lower odds of high phthalate/∑DEHTP cluster membership and had lower plasticizer phthalate, phthalate replacement, and MEP PC scores. CONCLUSIONS: Conception season, enrollment year, and several sociodemographic/lifestyle factors were predictive of phthalate/replacement biomarker profiles. Future studies should corroborate these findings, with a special focus on replacements to which pregnant women are becoming increasingly exposed.

REPRODUCTIVE TOXICOLOGY: Pregnancy exposure to endocrine disrupting chemicals: implications for women's health.

Women are ubiquitously exposed to non-persistent endocrine disrupting chemicals (EDCs) from food contact materials and personal care products. Understanding the impacts of exposure to these chemicals on pregnancy and long-term health outcomes in women is a critical area of research that has been largely overlooked. This brief review focuses on the epidemiologic literature exploring associations of non-persistent EDCs - including phthalates, parabens, bisphenols, and triclosan - with maternal pregnancy outcomes and long-term health outcomes in women. We focus on the challenges of this research, particularly assessing non-persistent EDC exposures, aspects of study design, and statistical approaches. We conclude by reviewing the best practices for non-persistent EDC research with regards to pregnancy and women's health. Though limited, we found some evidence indicating that exposure to non-persistent EDCs is associated with pregnancy health. However, findings from these studies have been inconsistent and require corroboration. Recent studies have also proposed that non-persistent EDC exposures in pregnancy may adversely affect postnatal maternal health. To date, only a few studies have been conducted and have only focused on postpartum weight. More research is needed in this area to inform efforts to promote optimal health across the lifespan of women.

Prenatal phthalate exposures and autism spectrum disorder symptoms in low-risk children.

BACKGROUND: Prenatal exposure to environmental chemicals has been associated with Autism Spectrum Disorder (ASD) symptoms in some, but not all, studies, but most research has not accounted for other childhood behavior problems. OBJECTIVES: To evaluate the specific associations of prenatal phthalate exposures with ASD symptoms in children (ages 3-6) accounting for other behavior problems, and to assess sex differences in these associations. METHODS: We measured phthalate metabolites in prenatal urine samples. Mothers completed the Social Responsiveness Scale-2nd edition (SRS-2) to assess child ASD symptoms and the Child Behavior Checklist (CBCL) to assess general behavior problems. We assessed associations of the sum of di-(2-ethylhexyl) phthalate metabolites, monobutyl phthalate, mono-isobutyl phthalate, and monoethyl phthalate (mEP) with ASD symptoms, adjusting for other behavior problems, using linear regression models (n=77). RESULTS: Most associations were null, and the sample size limited power to detect associations, particularly in the stratified analyses. After adjusting for internalizing and externalizing problems from the CBCL, ASD symptoms increased for each doubling of prenatal mEP concentration among boys only. CONCLUSIONS: Further investigation of maternal prenatal urinary phthalate metabolite concentrations and ASD symptoms while adjusting for other behavioral problems is warranted.

Phthalate exposures and one-year change in body mass index across the menopausal transition.

BACKGROUND: The menopausal transition is a hormonally sensitive period associated with changes in body weight. Phthalates are ubiquitous endocrine disrupting chemicals that could disrupt weight homeostasis, but it is unknown whether this occurs during the menopausal transition. OBJECTIVES: Our objectives were to (1) determine if phthalate exposure in pre- and perimenopausal women was associated with one-year change in body mass index (BMI), and (2) determine if these associations differed across the menopausal transition. METHODS: We addressed our objectives using data from 524 participants enrolled in the Midlife Women's Health Study. We calculated change in BMI from baseline to first follow-up visit approximately one year later. Phthalate exposures were approximated by measuring urinary metabolites in pools of two-to-four spot urine samples collected across a four-week period at baseline. We molar-converted and summed mono-(2-ethylhexyl) phthalate (mEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mono (2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (mECPP) to approximate exposure to di-(2-ethylhexyl) phthalate (∑DEHP); ∑DEHP, mono (3-carboxypropyl) phthalate (mCPP), and monobenzyl phthalate (mBzP) to approximate exposure to plasticizer phthalates (∑Plastics); and monoethyl phthalate (mEP), monobutyl phthalate (mBP), and monoisobutyl phthalate (miBP) to approximate exposure to phthalates from personal care products (∑PCP). We used multivariable linear regression models to evaluate associations of specific gravity-adjusted ln-transformed phthalate metabolites or sums with one-year BMI change, and also considered whether associations differed depending on each woman's menopausal status change from baseline to first follow-up. RESULTS: At baseline, most women were premenopausal (67.8%), non-Hispanic white (67.9%), and college educated (65.8%). Overall, urinary phthalate metabolites or sums were not associated with one-year BMI change. Stratified analysis identified positive associations between ∑DEHP (and three of its metabolites: MEHP, MEHHP, and MEOHP) and one-year BMI change among women who transitioned from peri-to post-menopause from baseline to first follow-up. For example, in these women, with each doubling of ∑DEHP, BMI increased by 0.65 kg/m2 (95%CI: 0.17, 1.13) from baseline to first follow-up. Personal care product-associated phthalate metabolites (mBP and mEP) were negatively associated with one-year BMI change among women who remained perimenopausal from baseline to first follow-up, while miBP and mEP were positively associated with one-year BMI change among women who transitioned from peri-to post-menopause. CONCLUSION: We found the strongest associations between some phthalates and one-year BMI change in women who transitioned from peri-to post-menopause from baseline to first follow-up. This supports previous evidence that the menopausal transition is a hormonally sensitive period in women's lives. To establish whether phthalate exposure contributes to body weight changes associated with the menopausal transition, substantially more research is needed to corroborate our findings.

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review.

Phthalates are esters of phthalic acid which are used in cosmetics and other daily personal care products. They are also used in polyvinyl chloride (PVC) plastics to increase durability and plasticity. Phthalates are not present in plastics by covalent bonds and thus can easily leach into the environment and enter the human body by dermal absorption, ingestion, or inhalation. Several in vitro and in vivo studies suggest that phthalates can act as endocrine disruptors and cause moderate reproductive and developmental toxicities. Furthermore, phthalates can pass through the placental barrier and affect the developing fetus. Thus, phthalates have ubiquitous presence in food and environment with potential adverse health effects in humans. This review focusses on studies conducted in the field of toxicogenomics of phthalates and discusses possible transgenerational and multigenerational effects caused by phthalate exposure during any point of the life-cycle.

Incidence of hospital-acquired pressure ulcers - a population-based cohort study.

Our study sought to estimate the association between race, gender, comorbidity and body mass index (BMI) on the incidence of hospital-acquired pressure ulcer (PU) from a population-based retrospective cohort comprising 242 745 unique patient hospital discharges in two fiscal years from July 2009 to June 2010 from 15 general and tertiary care hospitals. Cases were patients with a single inpatient encounter that led to an incident PU. Controls were patients without a PU at any encounter during the two fiscal years with the earliest admission retained for analysis. Logistic regression models quantified the association of potential risk factors for PU incidence. Spline functions captured the non-linear effects of age and comorbidity. Overall 2·68% of patients experienced an incident PU during their inpatient stay. Unadjusted analyses revealed statistically significant associations by age, gender, race, comorbidity, BMI, admitted for a surgical procedure, source of admission and fiscal year, but differences by gender and race did not persist in adjusted analyses. Interactions between age, comorbidity and BMI contributed significantly to the likelihood of PU incidence. Patients who were older, with multiple comorbidities and admitted for a surgical diagnosis-related groups (DRG) were at greater risk of experiencing a PU during their stay.