Associations of per- and polyfluoroalkyl substances with maternal metabolic and inflammatory biomarkers in early-to-mid-pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. METHODS: Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. RESULTS: In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with -31.3% lower insulin (95%CI: -45.8, -12.9), -31.9% lower HOMA-IR (95%CI: -46.4, -13.4), and -9.4% lower leptin (95%CI: -17.3, -0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. IMPLICATIONS: Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings.

Associations of maternal anthropometrics with newborn anogenital distance and the 2:4 digit ratio.

STUDY QUESTION: Are maternal anthropometrics associated with anogenital distance (AGD) and 2:4 digit ratio (2:4D) in newborns? SUMMARY ANSWER: Select maternal anthropometrics indicative of obesity or increased adiposity are associated with elongated AGD in daughters. WHAT IS KNOWN ALREADY: Excessive maternal weight or adiposity before or in early pregnancy may impact child reproductive, and other hormonally mediated, development. AGD and 2:4D are proposed markers of in utero reproductive development. STUDY DESIGN, SIZE, DURATION: This study includes 450 mother/newborn dyads participating in the Illinois Kids Development Study (I-KIDS), a prospective pregnancy cohort from Champaign-Urbana, IL, USA. Participants included in the current study enrolled between 2013 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Most mothers in this study were college-educated (82%) and non-Hispanic White (80%), and 55% were under- or normal weight before pregnancy. Pregnant women aged 18-40 years reported pre-pregnancy weight and height to calculate pre-pregnancy BMI. At 8-15 weeks gestation, we measured waist and hip circumference, and evaluated weight, % body fat, visceral fat level, % muscle and BMI using bioelectrical impedance analysis. Within 24 h of birth, we measured newborn 2nd and 4th left/right digits to calculate the 2:4D. In daughters, we measured AGDAF (anus to fourchette) and AGDAC (anus to clitoris). In sons, we measured AGDAS (anus to scrotum) and AGDAP (anus to base of the penis). MAIN RESULTS AND THE ROLE OF CHANCE: Select maternal anthropometrics were positively associated with AGD in newborn daughters, but not sons. For example, AGDAC was 0.73 mm (95% CI: 0.15, 1.32) longer for every interquartile range (IQR) increase in pre-pregnancy BMI and 0.88 mm (95% CI: 0.18, 1.58) longer for every IQR increase in hip circumference, whereas AGDAF was 0.51 mm (95% CI: 0.03, 1.00) and 0.56 mm (95% CI: 0.03, 1.09) longer for every IQR increase in hip and waist circumference, respectively. Quartile analyses generally supported linear associations, but additional strong associations emerged in Q4 (versus Q1) of maternal % body fat and visceral fat levels with AGDAC. In quartile analyses, we observed only a few modest associations of maternal anthropometrics with 2:4D, which differed by hand (left versus right) and newborn sex. Although there is always the possibility of spurious findings, the associations for both measures of female AGD were consistent across multiple maternal anthropometric measures, which strengthens our conclusions. LIMITATIONS, REASONS FOR CAUTION: Our study sample was racially and ethnically homogenous, educated and relatively healthy, so our study may not be generalizable to other populations. Additionally, we may not have been powered to identify some sex-specific associations, especially for 2:4D. WIDER IMPLICATIONS OF THE FINDINGS: Increased maternal weight and adiposity before and in early pregnancy may lengthen the female AGD, which warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This publication was made possible by the National Institute for Environmental Health Sciences (NIH/NIEHS) grants ES024795 and ES022848, the National Institute of Child Health and Human Development grant R03HD100775, the U.S. Environmental Protection Agency grant RD83543401 and National Institute of Health Office of the Director grant OD023272. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA or NIH. Furthermore, the US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. This project was also supported by the USDA National Institute of Food and Agriculture and Michigan AgBioResearch. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Maternal diet quality moderates associations between parabens and birth outcomes.

BACKGROUND/OBJECTIVE: Maternal paraben exposure and diet quality are both independently associated with birth outcomes, but whether these interact is unknown. We assessed sex-specific associations of parabens with birth outcomes and differences by maternal diet quality. METHODS: Illinois pregnant women (n = 458) provided five first-morning urines collected at 8-40 weeks gestation, which we pooled for quantification of ethylparaben, methylparaben, and propylparaben concentrations. We collected/measured gestational age at delivery, birth weight, body length, and head circumference within 24 h of birth, and calculated sex-specific birth weight-for-gestational-age z-scores and weight/length ratio. Women completed three-month food frequency questionnaires in early and mid-to-late pregnancy, which we used to calculate the Alternative Healthy Eating Index (AHEI)-2010. Linear regression models evaluated sex-specific associations of parabens with birth outcomes, and differences in associations by average pregnancy AHEI-2010. RESULTS: In this predominately non-Hispanic white, college-educated sample, maternal urinary paraben concentrations were only modestly inversely associated with head circumference and gestational length. However, methylparaben and propylparaben were inversely associated with birth weight, birth weight z-scores, body length, and weight/length ratio in female, but not male newborns. For example, each 2-fold increase in methylparaben concentrations was associated with -46.61 g (95% CI: -74.70, -18.51) lower birth weight, -0.09 (95% CI: -0.15, -0.03) lower birth weight z-scores, -0.21 cm (95% CI: -0.34, -0.07) shorter body length, and -0.64 g/cm (95% CI: -1.10, -0.19) smaller weight/length ratio in females. These inverse associations were more prominent in females of mothers with poorer diets (AHEI-2010 < median), but attenuated in those with healthier diets (AHEI-2010 ≥ median). In newborn males of mothers with healthier diets, moderate inverse associations emerged for propylparaben with gestational length and head circumference. CONCLUSIONS: Maternal diet may moderate associations of parabens with birth size in a sex-specific manner. Additional studies may consider understanding the inflammatory and metabolic mechanisms underlying these findings.

Costs of a Train-the-Trainer Program to Teach Primary Care Faculty Mental Health Care.

BACKGROUND: Mental health care must improve in this country. With the worsening shortage of psychiatrists and other mental health professionals, the next generation of physicians in primary care will need to be better trained in mental health care. OBJECTIVES: We estimate the direct cost of implementing an evidence-based Train-the-Trainer (3T) program to disseminate mental health training to allopathic medical school faculty; once trained, faculty can teach a much-enhanced curriculum of mental health care to medical students and residents. METHODS: A combination of published standardized unit costs and an activity-based costing approach is used to estimate the direct costs (labor and nonlabor) for implementing the 3T program. RESULTS: The estimated direct cost of implementing the 3T program at one prototypical school, including the 12-month start-up period (1.1 million) and 18-month rollout period (8.6 million), is ∼9.7 million dollars. CONCLUSIONS: Successfully adopted in all US allopathic medical schools, the 3T program will provide over 3800 attitudinally competent and mental health skills-qualified primary care faculty members. They would then be available to train nearly 100,000 medical students per year and 55,000 primary care residents to be as competent in basic mental health care as in medical care. This 3T program will begin to meet the needs each year for the millions of adults with major mental disorders that now are largely unrecognized and untreated.

Feelings of safety during daytime walking: associations with mental health, physical activity and cardiometabolic health in high vacancy, low-income neighborhoods in Detroit, Michigan.

INTRODUCTION: Individuals living in low-income neighborhoods have disproportionately high rates of obesity, Type-2 diabetes, and cardiometabolic conditions. Perceived safety in one's neighborhood may influence stress and physical activity, with cascading effects on cardiometabolic health. METHODS: In this study, we examined relationships among feelings of safety while walking during the day and mental health [perceived stress (PSS), depression score], moderate-to-vigorous physical activity (PA), Body Mass Index (BMI), and hemoglobin A1C (A1C) in low-income, high-vacancy neighborhoods in Detroit, Michigan. We recruited 69 adults who wore accelerometers for one week and completed a survey on demographics, mental health, and neighborhood perceptions. Anthropometrics were collected and A1C was measured using A1CNow test strips. We compiled spatial data on vacant buildings and lots across the city. We fitted conventional and multilevel regression models to predict each outcome, using perceived safety during daytime walking as the independent variable of interest and individual or both individual and neighborhood-level covariates (e.g., number of vacant lots). Last, we examined trends in neighborhood features according to perceived safety. RESULTS: In this predominantly African American sample (91%), 47% felt unsafe during daytime walking. Feelings of perceived safety significantly predicted PSS (ß = - 2.34, p = 0.017), depression scores (ß = - 4.22, p = 0.006), and BMI (ß = - 2.87, p = 0.01), after full adjustment. For PA, we detected a significant association for sex only. For A1C we detected significant associations with blighted lots near the home. Those feeling unsafe lived in neighborhoods with higher park area and number of blighted lots. CONCLUSION: Future research is needed to assess a critical pathway through which neighborhood features, including vacant or poor-quality green spaces, may affect obesity-via stress reduction and concomitant effects on cardiometabolic health.

A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria.

BACKGROUND: Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital. METHODS: Children 24-83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects. The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken. RESULTS: Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 µg/mL) and all were above 6 µg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose. Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects. CONCLUSION: Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital. TRIAL REGISTRATION: NCT01660672 . NCT01982812 .

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.

Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective Cohort Analysis.

Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ≤64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the study's matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.

A non-parametric approach for detecting gene-gene interactions associated with age-at-onset outcomes.

BACKGROUND: Cox-regression-based methods have been commonly used for the analyses of survival outcomes, such as age-at-disease-onset. These methods generally assume the hazard functions are proportional among various risk groups. However, such an assumption may not be valid in genetic association studies, especially when complex interactions are involved. In addition, genetic association studies commonly adopt case-control designs. Direct use of Cox regression to case-control data may yield biased estimators and incorrect statistical inference. RESULTS: We propose a non-parametric approach, the weighted Nelson-Aalen (WNA) approach, for detecting genetic variants that are associated with age-dependent outcomes. The proposed approach can be directly applied to prospective cohort studies, and can be easily extended for population-based case-control studies. Moreover, it does not rely on any assumptions of the disease inheritance models, and is able to capture high-order gene-gene interactions. Through simulations, we show the proposed approach outperforms Cox-regression-based methods in various scenarios. We also conduct an empirical study of progression of nicotine dependence by applying the WNA approach to three independent datasets from the Study of Addiction: Genetics and Environment. In the initial dataset, two SNPs, rs6570989 and rs2930357, located in genes GRIK2 and CSMD1, are found to be significantly associated with the progression of nicotine dependence (ND). The joint association is further replicated in two independent datasets. Further analysis suggests that these two genes may interact and be associated with the progression of ND. CONCLUSIONS: As demonstrated by the simulation studies and real data analysis, the proposed approach provides an efficient tool for detecting genetic interactions associated with age-at-onset outcomes.

Assessing interchangeability at cluster levels with multiple-informant data.

Studies examining the relationship between neighborhood social disorder and health often rely on multiple informants. Such studies assume interchangeability of the latent constructs derived from multiple-informant data. Existing methods examining this assumption do not clearly delineate the uncertainty at individual levels from that at neighborhood levels. We propose a multilevel variance component factor model that allows this delineation. Data come from a survey of a representative sample of children born between 1983 and 1985 in the inner city of Detroit and nearby middle-class suburbs. Results indicate that the informant-level models tend to exaggerate the effect of places because of differences between persons. Our evaluations of different methodologies lead to the recommendation of the multilevel variance component factor model whenever multiple-informant reports can be aggregated at a neighborhood level.

Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones.

BACKGROUND/AIMS: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development. METHODS: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp). RESULTS: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9). CONCLUSION: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings.

Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones.

BACKGROUND/OBJECTIVES: Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. METHODS: Illinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8-40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. RESULTS: In women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with -5.65% (95% CI: -9.79, -1.28) lower testosterone and -0.09 µIU/mL (95% CI: -0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: -0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with -1.77% (95% CI: -4.08, 0.58) lower TT4 and -0.18 µIU/mL (95% CI: -0.33, -0.03) lower TSH. We also identified select chemical interactions. CONCLUSION: Some biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

Feasibility of a Food Delivery Intervention during Pregnancy in a Rural US Population: The PEAPOD Pilot Study.

Pregnancy nutrition is important for maternal and child health and may affect the development of the infant gut microbiome. Our objective was to assess the feasibility of implementing a food-based intervention designed to increase fiber intake among pregnant women in a rural setting. Participants were enrolled (N = 27) mid-pregnancy from a prenatal care clinic in rural Michigan, randomized to intervention (N = 13) or usual care (N = 14), and followed to 6 weeks postpartum. The intervention was designed to be easily replicable and scalable by partnering with hospital foodservices and included non-perishable high fiber foods and recipes, as well as weekly delivery of salads, soup, and fresh fruit. Surveys, maternal blood, urine, and stool were collected at 24- and 36-weeks gestation and at 6 weeks postpartum. Infant stool was collected at 6 weeks. Participants were 100% White (7% Hispanic White, 7% Native American and White); 55% with education < 4-year college degree. Data on dietary intake and urinary trace elements are presented as evidence of feasibility of outcome measurement. Retention was high at 93%; 85% reported high satisfaction. The intervention described here can be replicated and used in larger, longer studies designed to assess the effects of pregnancy diet on the establishment of the infant gut microbiome and related health outcomes.

Understanding the Impact of Perceived Social Support for Breastfeeding Among African American Women: Results From the Mama Bear Feasibility Trial.

PURPOSE: Perceived Social Support (PSS) can impact breastfeeding behaviors, and a lack of PSS potentially contributes to disparities in breastfeeding rates for African American women (AA). Objectives were to describe PSS at two timepoints and test associations between PSS and breastfeeding intensity for AA. METHODS: Data are from a feasibility trial of breastfeeding support among AA. The Hughes Breastfeeding Support Scale was used to measure PSS (Emotional, Informational, Tangible; total range = 30-120) in pregnancy (T1, n = 32) and early postpartum (T2, n = 31). Scale means were compared with t-tests. Associations between PSS at T1 and breastfeeding intensity (ie, quantitative measure of breastfeeding) were assessed with linear regression. RESULTS: Total PSS (mean ± SE) was high at both time points (T1 = 90.5 ± 4.8; T2 = 92.8 ± 3.1). At T2, older participants or those living with a partner had higher total PSS scores compared to those younger or living alone. Emotional PSS was significantly higher at T2 than T1 with no differences in tangible or informational PSS over time. Mixed-feeding, exclusive breastfeeding, and exclusive formula feeding was distributed at 39%, 32%, and 29%, respectively. Total PSS was not associated with breastfeeding intensity. CONCLUSION: Women reported high levels of social support, and emotional PSS increased over time in this small sample of AA. PSS and sources of PSS are understudied, especially among AA, and future studies should explore quantitative methods to assess PSS. The results of such assessments can then be used to design breastfeeding support interventions.

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.

Modeling hospital length of stay by Coxian phase-type regression with heterogeneity.

Hospital length of stay (LOS) is an important measure of healthcare utilization and is generally positively skewed and heterogeneous. We fit a Coxian phase-type distribution to LOS and identify the hidden states of the underlying latent homogeneous Markov model. We demonstrate that selecting an appropriate number of phases and a regression model for hazard rates can account for some heterogeneity in LOS. Reversible jump MCMC method enables us to dynamically uncover the hidden stochastic Markov structure. A classification method is used to assign patients to different LOS groups. The methodology is illustrated with application to hospital admissions for acute myocardial infarction in the 2003 Nationwide Inpatient Sample from the Healthcare Utilization Project.

A nonparametric test for equality of survival medians.

In clinical trials, researchers often encounter testing for equality of survival medians across study arms based on censored data. Even though Brookmeyer and Crowley introduced a method for comparing medians of several survival distributions, still some researchers misuse procedures that are designed for testing the homogeneity of survival curves. These procedures include the log-rank, Wilcoxon, and Cox models. This practice leads to inflation of the probability of a type I error, particularly when the underlying assumptions of these procedures are not met. We propose a new nonparametric method for testing the equality of several survival medians based on the Kaplan-Meier estimation from randomly right-censored data. We derive asymptotic properties of this test statistic. Through simulations, we compute and compare the empirical probabilities of type I errors and the power of this new procedure with those of the Brookmeyer-Crowley, log-rank, and Wilcoxon methods. Our simulation results indicate that the performance of these test procedures depends on the level of censoring and appropriateness of the underlying assumptions. When the objective is to test homogeneity of survival medians rather than survival curves and the assumptions of these tests are not met, some of these procedures severely inflate the probability of a type I error. In these situations, our test statistic provides an alternative to the Brookmeyer-Crowley test.

Breastfeeding Self-Efficacy as a Predictor of Breastfeeding Intensity Among African American Women in the Mama Bear Feasibility Trial.

Background: Improving breastfeeding rates among African American (AA) families is an important public health goal. Breastfeeding self-efficacy, a known predictor of breastfeeding behavior, has seldom been assessed among AAs, in relation to breastfeeding intensity (% breastfeeding relative to total feeding) or as a protective factor in combating the historical breastfeeding challenges faced by people of color. We aimed to test the association between breastfeeding self-efficacy assessed during pregnancy and breastfeeding intensity assessed in the early postpartum period. Methods: This was a secondary data analysis of a randomized controlled feasibility trial of breastfeeding support and postpartum weight management. AA women were recruited during pregnancy from a prenatal clinic in Detroit, MI. Data presented, in this study, were collected at enrollment (n = 50) and ∼6 weeks postpartum (n = 31). Linear regression models were used, adjusting for potential confounders. Results: There were no differences in breastfeeding intensity by study arm; data are from all women with complete data on targeted variables. Age ranged from 18 to 43 years, 52% were Women, Infant's, and Children program enrollees, and 62% had ≥ some college. Breastfeeding self-efficacy during pregnancy was a significant predictor of breastfeeding intensity in the early postpartum period (ß = 0.125, p < 0.05) with only slight attenuation in the fully adjusted model (ß = 0.123, p < 0.05). Implications for Practice: Our results confirm that self-efficacy is an important predictor of breastfeeding practice. Furthermore, the simple act of assessing breastfeeding self-efficacy permits an opportunity for women to reflect on breastfeeding possibilities, and can inform individualized confidence-building interventions to improve the disproportionately low breastfeeding rates among AAs. Clinical Trial Registration number NCT03480048.

The Prevalence and Factors Associated with Prophylactic Antibiotic Use during Delivery: A Hospital-Based Retrospective Study in Palembang, Indonesia.

Prophylactic antibiotic usage during delivery is a common practice worldwide, especially in low- to middle-income countries. Guidelines have been published to reduce antibiotic overuse; however, data describing the use of prophylactic antibiotics and clinician adherence to guidelines in low- to middle-income countries remain limited. This study aimed to describe the prevalence of prophylactic antibiotic use, factors associated with its use, and clinician adherence to guidelines. A retrospective review was conducted for all deliveries from 1 January 2016 to 31 December 2018 at a tertiary level hospital in Indonesia. The prevalence of prophylactic antibiotic use during delivery was 47.1%. Maternal education level, Ob/Gyn specialist-led delivery, a history of multiple abortions, C-section, premature membrane rupture, and antepartum hemorrhage were independently associated with prophylactic antibiotic use. Clinician adherence to the guidelines was 68.9%. Adherence to guidelines was the lowest in conditions where the patient had only one indication for prophylactic antibiotics (aOR 0.36, 95% CI 0.24-0.54). The findings showed that the prevalence of prophylactic antibiotic use during delivery was moderate to high. Adherence to local guidelines was moderate. Updating the local prescribing guidelines may improve clinician adherence.

Outbreaks of foodborne Salmonella enteritidis in the United States between 1990 and 2015: An analysis of epidemiological and spatial-temporal trends.

OBJECTIVES: To evaluate the role of eggs and other food vehicles as risk factors associated with Salmonella enteritidis (SE) outbreaks in order to address the endemicity of SE infections in the USA. METHODS: We retrieved and analyzed data relating to all SE outbreaks reported to the Centers for Disease Control and Prevention (CDC) between 1990 and 2015. We then used descriptive and analytical statistical methods, including negative binomial regression models for the estimation of rate-ratios, to analyze the data. RESULTS: Analyses showed that egg-based dishes were the most common food vehicle associated with outbreaks of SE in the USA (273 cases [24%]); this was followed by several other food items, including meat (130 cases [11%]), vegetables (96 cases [8%]), chicken items (95 cases [8%]), dairy products (55 cases [5%]), and bakery items (8 cases [1%]). Compared to egg-based dishes, other food items such as meat (exp(ß) = 0.51, 95% CI 0.37, 0.69), chicken (exp(ß) = 0.42, 95% CI 0.30, 0.58), vegetables (exp(ß) = 0.41, 95% CI 0.29, 0.55), and dairy items (exp(ß) = 0.27, 95% CI 0.18, 0.40) were significantly associated with outbreaks of SE in the USA. Of 1144 SE outbreaks, 402 (35%) occurred in the Northeast region of the USA, followed by the South (253 [22%]), West (250 [22%]), and Midwestern regions (239 [21%]). CONCLUSIONS: Epidemiological and spatiotemporal trends analyses demonstrated that a significant proportions of Salmonella enteritidis outbreaks in the USA are attributed to food vehicles other than eggs. Our findings can be used to plan effective strategies to mitigate the increasing occurrence of foodborne SE outbreaks.