Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Green Space and Internalizing or Externalizing Symptoms Among Children.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

Airborne Lead Exposure and Childhood Cognition: The Environmental Influences on Child Health Outcomes (ECHO) Cohort (2003-2022).

Objectives. To examine whether a previously reported association between airborne lead exposure and children's cognitive function replicates across a geographically diverse sample of the United States. Methods. Residential addresses of children (< 5 years) were spatially joined to the Risk-Screening Environmental Indicators model of relative airborne lead toxicity. Cognitive outcomes for children younger than 8 years were available for 1629 children with IQ data and 1476 with measures of executive function (EF; inhibitory control, cognitive flexibility). We used generalized linear models using generalized estimating equations to examine the associations of lead, scaled by interquartile range (IQR), accounting for individual- and area-level confounders. Results. An IQR increase in airborne lead was associated with a 0.74-point lower mean IQ score (b = -0.74; 95% confidence interval = -1.00, -0.48). The association between lead and EF was nonlinear and was modeled with a knot at the 97.5th percentile of lead in our sample. Lead was significantly associated with lower mean inhibitory control but not with cognitive flexibility. This effect was stronger among males for both IQ and inhibitory control. Conclusions. Early-life exposure to airborne lead is associated with lower cognitive functioning. (Am J Public Health. 2024;114(3):309-318. https://doi.org/10.2105/AJPH.2023.307519).

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

The prevalence of mental health disorders in people with HIV and the effects on the HIV care continuum.

OBJECTIVE: To describe the prevalence of diagnosed depression, anxiety, bipolar disorder, and schizophrenia in people with HIV (PWH) and the differences in HIV care continuum outcomes in those with and without mental health disorders (MHDs). DESIGN: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design. METHODS: PWH (≥18 years) contributed data on prevalent schizophrenia, anxiety, depressive, and bipolar disorders from 2008 to 2018 based on International Classification of Diseases code mapping. Mental health (MH) multimorbidity was defined as having two or more MHD. Log binomial models with generalized estimating equations estimated adjusted prevalence ratios (aPR) and 95% confidence intervals for retention in care (≥1 visit/year) and viral suppression (HIV RNA ≤200 copies/ml) by presence vs. absence of each MHD between 2016 and 2018. RESULTS: Among 122 896 PWH, 67 643 (55.1%) were diagnosed with one or more MHD: 39% with depressive disorders, 28% with anxiety disorders, 10% with bipolar disorder, and 5% with schizophrenia. The prevalence of depressive and anxiety disorders increased between 2008 and 2018, whereas bipolar disorder and schizophrenia remained stable. MH multimorbidity affected 24% of PWH. From 2016 to 2018 (N = 64 684), retention in care was marginally lower among PWH with depression or anxiety, however those with MH multimorbidity were more likely to be retained in care. PWH with bipolar disorder had marginally lower prevalence of viral suppression (aPR = 0.98 [0.98-0.99]) as did PWH with MH multimorbidity (aPR = 0.99 [0.99-1.00]) compared with PWH without MHD. CONCLUSION: The prevalence of MHD among PWH was high, including MH multimorbidity. Although retention and viral suppression were similar to people without MHD, viral suppression was lower in those with bipolar disorder and MH multimorbidity.

Trimethylamine N-Oxide and Its Precursors Are Associated with Gestational Diabetes Mellitus and Pre-Eclampsia in the Boston Birth Cohort.

Background: Trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine have been associated with cardiometabolic disease in nonpregnant adults. However, studies examining TMAO and its precursors in relation to cardiometabolic conditions during pregnancy are lacking. Objectives: The primary objective was to estimate the association of TMAO and its precursors in maternal and cord plasma with gestational diabetes mellitus (GDM) and pre-eclampsia (PE) among women in the Boston Birth Cohort. A secondary objective was to determine whether associations vary by race/ethnicity. Methods: ORs for each outcome according to tertiles and to an SD increment of TMAO, choline, betaine, and carnitine were estimated using logistic regression. Final models were adjusted for covariates. Results: Among 1496 women, 115 women had GDM and 159 had PE during the index pregnancy. Intermetabolite correlations of TMAO and its precursors were stronger within cord plasma (r = 0.38-0.87) than within maternal plasma (r = 0.08-0.62). Maternal TMAO was associated with higher odds of GDM (third compared with first tertile OR: 1.75; 95% CI: 1.04, 2.94), whereas maternal choline, betaine, and carnitine were not associated with GDM. Maternal TMAO and choline were not associated with PE, whereas carnitine was associated with higher (OR: 1.86; 95% CI: 1.18, 2.94) and betaine with lower odds of PE (OR: 0.37; 95% CI: 0.23, 0.59). In cord plasma, TMAO was not associated with GDM or PE, but choline, betaine, and carnitine were associated with higher odds of PE (OR: 3.11; 95% CI: 1.62, 5.96; OR: 2.65; 95% CI: 1.42, 4.93; OR: 2.56; 95% CI: 1.39, 4.69, respectively). Cord choline was associated with lower odds of GDM (OR: 0.52; 95% CI: 0.27, 0.99), whereas other cord metabolites were not significantly associated with GDM. Associations did not vary by race/ethnicity. Conclusions: TMAO and its precursors were associated with GDM and PE, but the associations differed based on the metabolite medium (maternal compared with cord plasma).This trial was registered at clinicaltrials.gov as NCT03228875.

Hormone Therapy, Mental Health, and Quality of Life Among Transgender People: A Systematic Review.

We sought to systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people. We searched PubMed, Embase, and PsycINFO through June 10, 2020 for studies evaluating quality of life (QOL), depression, anxiety, and death by suicide in the context of gender-affirming hormone therapy among transgender people of any age. We excluded case studies and studies reporting on less than 3 months of follow-up. We included 20 studies reported in 22 publications. Fifteen were trials or prospective cohorts, one was a retrospective cohort, and 4 were cross-sectional. Seven assessed QOL, 12 assessed depression, 8 assessed anxiety, and 1 assessed death by suicide. Three studies included trans-feminine people only; 7 included trans-masculine people only, and 10 included both. Three studies focused on adolescents. Hormone therapy was associated with increased QOL, decreased depression, and decreased anxiety. Associations were similar across gender identity and age. Certainty in this conclusion is limited by high risk of bias in study designs, small sample sizes, and confounding with other interventions. We could not draw any conclusions about death by suicide. Future studies should investigate the psychological benefits of hormone therapy among larger and more diverse groups of transgender people using study designs that more effectively isolate the effects of hormone treatment.

Effects of antiandrogens on prolactin levels among transgender women on estrogen therapy: A systematic review.

BACKGROUND: Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy. METHODS: We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence. FINDINGS: We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas. INTERPRETATION: Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.

Recruitment of trial participants through electronic medical record patient portal messaging: A pilot study.

BACKGROUND/AIM: Cost-efficient methods are essential for successful participant recruitment in clinical trials. Patient portal messages are an emerging means of recruiting potentially eligible patients into trials. We assessed the response rate and complaint rate from direct-to-patient, targeted recruitment through patient portals of an electronic medical record for a clinical trial, and compared response rates by differences in message content. METHODS: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) trial is a National Institutes of Health-sponsored, community-based study of vitamin D supplementation for fall prevention in older adults conducted at Johns Hopkins. Potential participants were identified using the Epic electronic medical record at the Johns Hopkins Health System based on age (≥70 years), ZIP code (30-mile radius of study site), and prior activation of a patient portal account. We prepared a shorter message and a longer message. Both had basic information about study participation, but the longer message also contained information about the significance of the study and a personal invitation from the STURDY principal investigator. The Hopkins Institutional Review Board did not require prior consent from the patient or their providers. We calculated the response rate and tracked the number of complaints and requests for removal from future messages. We also determined response rate according to message content. RESULTS: Of the 5.5 million individuals receiving care at the Johns Hopkins Health System, a sample of 6896 met our inclusion criteria and were sent one patient portal recruitment message between 6 April 2017 and 3 August 2017. Assessment of enrollment by this method ended on 1 December 2017. There were 116 patients who expressed interest in the study (response rate: 1.7%). Twelve (0.2%) recipients were randomized. There were two complaints (0.03%) and one request to unsubscribe from future recruitment messages (0.01%). Response rate was higher with the longer message than the shorter message (2.1% vs 1.2%; p = 0.005). CONCLUSION: Patient portal messages inviting seniors to participate in a randomized controlled trial resulted in a response rate similar to commercial email marketing and resulted in very few complaints or opt-out requests. Furthermore, a longer message with more content enhanced response rate. Recruitment through patient portals might be an effective strategy to enroll trial participants.