Is the Risk of Intrahepatic Cholestasis Increased with Supplemental Progesterone?

OBJECTIVE: This study aimed to evaluate the relationship between supplemental progesterone use during pregnancy and the development of intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: A retrospective, matched case-control study was conducted among a population of women who delivered at George Washington University Hospital (GW) between 2012 and 2022. Women diagnosed with ICP (cases) were identified using International Statistical Classification of Diseases (ICD) codes, and data were collected via chart abstraction. Descriptive data included patient demographics, pregnancy characteristics, and medical history. Laboratory values related to ICP were collected. Cases were matched on a 1:3 ratio by maternal age, body mass index, and gravidarum to women who delivered at GW during the same month and did not carry a diagnosis of ICP (controls). A univariate logistic regression model was created to assess the use of supplemental progesterone between groups, adjusting for the use of assisted reproductive technology in the current pregnancy, and a history of liver disease. RESULTS: One hundred and twenty women who delivered during the study period were confirmed to have a diagnosis of ICP. Cases were matched with 360 controls and measures compared between the two groups. Cases were significantly more likely to have a history of liver disease (5.9 vs. 1.7%, p = 0.0021), multiple gestation (10.0 vs. 3.3%, p < 0.0001), a history of ICP in a previous pregnancy (10.0 vs. 0%, p < 0.0001), and to have delivered at an earlier gestational age (mean 37.1 vs. 38.6 weeks, p < 0.0001) as compared with controls. No differences were seen in the odds of supplemental progesterone use in both unadjusted and adjusted models (OR 1.14, 95% CI 0.30-4.34; adjusted Odds Ratio [aOR] 0.98 0.24-3.94). CONCLUSION: Contrary to recent evidence, no association was seen with the use of supplemental progesterone. It is possible that the associated risk with supplemental progesterone is dependent on medication formulation or route of administration. KEY POINTS: · Supplemental progesterone use in pregnancy may increase the risk of developing ICP.. · Previous investigations of progesterone and ICP have demonstrated mixed results.. · The association may be dependent on the route of administration and formulation of progesterone..

Maternal asthma in relation to infant size and body composition.

Background: Asthma affects 10% of pregnancies and may influence offspring health, including infant size and body composition, through hypoxic and inflammatory pathways. Objective: We sought to determine associations between maternal asthma and asthma phenotypes during pregnancy and infant size and body composition. Methods: The B-WELL-Mom study (2015-19) is a prospective cohort of 418 pregnant persons with and without asthma recruited in the first trimester of pregnancy from 2 US obstetric clinics. Exposures were maternal self-reported active asthma (n = 311) or no asthma (n = 107), and asthma phenotypes were classified on the bases of atopy, onset, exercise induced, control, severity, symptomology, and exacerbations. Outcomes were infant weight, length, head circumference, and skinfold measurements at birth and postnatal follow-up, as well as fat and lean mass assessed by air displacement plethysmography at birth. Adjusted multivariable linear regression examined associations of maternal asthma and asthma phenotypes with infant outcomes. Results: Offspring were born at a mean ± SD of 38 ± 2.3 weeks' gestation and were 18 ± 2.2 weeks of age at postnatal follow-up. Infants of participants with asthma had a mean ± SD fat mass of 11.0 ± 4.2%, birth weight of 3045.8 ± 604.3 g, and postnatal follow-up weight of 6696.4 ± 964.2 g, which were not different from infants of participants without asthma (respectively, ß [95% confidence interval]: -0.1 [-1.4, 1.3], -26.7 [-156.9, 103.4], and 107.5 [-117.3, 332.3]). Few associations were observed between asthma or asthma phenotypes and infant size or body composition. Conclusions: In a current obstetric cohort, maternal asthma during pregnancy was not associated with differential infant size or body composition.

Pediatric Eye Care Treatment Rates and Community Compliance to a Spectacle Provision Program in an Underserved School District in San Diego, CA.

Significance: The need for early identification and treatment of young children's refractive error needs has become a public health concern. The UCSD Eyemobile for Children (EyeMobile) provides vision screenings and comprehensive eye exams on the Eyemobile among a population of underserved, predominantly Hispanic preschool and elementary school children. The program also provides spectacles for children who fail eye exams due to refractive error. Methods: We performed a retrospective cross-sectional analysis of all children screened from 2011 to 2017 by the Eyemobile across 10 San Diego elementary schools. We examined demographics, distance and near visual acuity, autorefraction, stereopsis, and color vision. To measure compliance to our spectacle program, we checked if children who were prescribed spectacles were wearing them, as instructed, at the following year's screening. Differences between compliance measures with respect to school, age, ethnicity, and gender were determined using chi-square analysis, while all other measures were fit to a binary logistic regression to determine statistically significant factors. Results: A total of 12,176 elementary school children were screened between 2011 and 2017. Of these children, 5269 (43.3%) were referred for a comprehensive eye examination. Across six years, 3163 (60.0%) of the children referred completed their eye examinations. There was a significant increase (p < 0.001) in exam completion in the successive years. Exam completion was significantly higher in ten-year-olds (p = 0.0278) and in 3 of the 10 schools (p < 0.0001, p = 0.0027, and p = 0.0309). A total of 1089 (8.9% of screened) children were prescribed spectacles. Of the 409 children that were recorded with the compliance method, 342 (83.6%) were found to be fully compliant and wearing their spectacles as prescribed. Conclusion: The Eyemobile program demonstrated high levels of compliance for both eye examination completion and prescribed spectacle wear in underserved populations in the San Diego region, compared to similar national programs.

The Association of Periconception Asthma Medication Discontinuation with Adverse Obstetric Outcomes.

OBJECTIVE: This study aimed to investigate asthma medication reduction in the periconceptional period as it relates to asthma status and adverse outcomes in pregnancy. STUDY DESIGN: In a prospective cohort study, self-reported current and past asthma medications were collected and analyzes compared measures of asthma status in women who discontinued asthma medication in the 6 months prior to enrollment ("step-down") versus those who did not ("no change"). Evaluation of asthma was done at three study visits (one per trimester) and by daily diaries, including measures of lung function (percent predicted forced expiratory volume in 1 and 6 s [%FEV1, %FEV6], peak expiratory flow [%PEF], forced vital capacity [%FVC], FEV1 to FVC ratio [FEV1/FVC]), lung inflammation (fractional exhaled nitric oxide [FeNO], ppb), rate of asthma symptoms (activity limitation, night symptoms, rescue inhaler use, wheeze, shortness of breath, cough, chest tightness, chest pain), and rate of asthma exacerbations. Adverse pregnancy outcomes were also evaluated. Adjusted regression analyses examined whether adverse outcomes differed by periconceptional asthma medication changes. RESULTS: Of 279 participants included in analyses, 135 (48.4%) did not change asthma medication in the periconceptional period, whereas 144 (51.6%) reported a step down in medication. Those in the step-down group were more likely to have milder disease (88 [61.1%] in the step-down vs. 74 [54.8%] in the no change group), exhibited less activity limitation (rate ratio [RR]: 0.68, 95% confidence interval [CI]: 0.47-0.98), and experienced fewer asthma attacks (RR: 0.53, 95% CI: 0.34-0.84) during pregnancy. The step-down group had a nonsignificant increase in overall odds of experiencing an adverse pregnancy outcome (odds ratio: 1.62, 95% CI: 0.97-2.72). CONCLUSION: Over half of women with asthma reduce asthma medication in the periconceptional period. Although these women typically have milder disease, a step down in medication may be associated with an increased risk of adverse pregnancy outcomes. KEY POINTS: · Many women reduce their asthma medication in pregnancy.. · Reduction is more common among those with mild disease.. · Medication reduction may lead to adverse pregnancy outcomes..

Asthma Medication Regimens in Pregnancy: Longitudinal Changes in Asthma Status.

OBJECTIVE: This study aimed to assess the impact of common asthma medication regimens on asthma symptoms, exacerbations, lung function, and inflammation during pregnancy. STUDY DESIGN: A total of 311 women with asthma were enrolled in a prospective pregnancy cohort. Asthma medication regimen was categorized into short-acting ß agonist (SABA) alone, SABA + inhaled corticosteroid (ICS), SABA + ICS + long-acting ß agonist (LABA), and no asthma medications (reference). We evaluated asthma control at enrollment (< 15 weeks' gestation) and its change into trimesters 2 and 3, including per cent predicted forced expiratory volume in 1 second (%FEV1) and peak expiratory flow (%PEF), pulse oximetry, fractional exhaled nitric oxide (FeNO), asthma symptoms (asthma attacks/month, night symptoms/week), and severe exacerbations. Linear mixed models adjusted for site, age, race, annual income, gestational age, body mass index, and smoking, and propensity scores accounted for asthma control status at baseline. RESULTS: Women taking SABA + ICS and SABA + ICS + LABA had better first trimester %PEF (83.5% [75.7-91.3] and 84.6% [76.9-92.3], respectively) compared with women taking no asthma medications (72.7% [66.0-79.3]). Women taking SABA + ICS + LABA also experienced improvements in %FEV1 (+11.1%, p < 0.01) in the third trimester and FeNO in the second (-12.3 parts per billion [ppb], p < 0.01) and third (-11.0 ppb, p < 0.01) trimesters as compared with the trajectory of women taking no medications. SABA + ICS use was associated with increased odds of severe exacerbations in the first (odds ratio [OR]: 2.22 [1.10-4.46]) and second (OR: 3.15 [1.11-8.96]) trimesters, and SABA + ICS + LABA use in the second trimester (OR: 7.89 [2.75-21.47]). Women taking SABA alone were similar to those taking no medication. CONCLUSION: Pregnant women taking SABA + ICS and SABA + ICS + LABA had better lung function in the first trimester. SABA + ICS + LABA was associated with improvements in lung function and inflammation across gestation. However, both the SABA + ICS and SABA + ICS + LABA groups had a higher risk of severe exacerbation during early to mid-pregnancy. KEY POINTS: · Medication regimens may affect perinatal asthma control.. · Intensive regimens improved lung function/inflammation.. · Women on intensive regimens had more acute asthma events..

Maternal body composition and gestational weight gain in relation to asthma control during pregnancy.

BACKGROUND: Poor asthma control is common during pregnancy and contributes to adverse pregnancy outcomes. Identification of risk factors for poor gestational asthma control is crucial. OBJECTIVE: Examine associations of body composition and gestational weight gain with asthma control in a prospective pregnancy cohort (n = 299). METHODS: Exposures included pre-pregnancy body mass index (BMI), first trimester skinfolds, and trimester-specific gestational weight gain. Outcomes included percent predicted forced expiratory volumes (FEV1, FEV6), forced vital capacity (FVC), peak expiratory flow (PEF), FEV1/FVC, symptoms (activity limitation, nighttime symptoms, inhaler use, and respiratory symptoms), and exacerbations (asthma attacks, medical encounters). Linear and Poisson models examined associations with lung function (ß (95% confidence interval (CI)), asthma symptom burden (relative rate ratio (RR (95%CI)), and exacerbations (RR (95%CI)). RESULTS: Women with a BMI ≥ 30 had lower percent predicted FVC across pregnancy (ßThirdTrimester: -5.20 (-8.61, -1.78)) and more frequent night symptoms in the first trimester (RR: 1.66 (1.08, 2.56)). Higher first trimester skinfolds were associated with lower FEV1, FEV6, and FVC, and more frequent night symptoms and inhaler use across pregnancy. Excessive first trimester gestational weight gain was associated with more frequent activity limitation in the first trimester (RR: 3.36 (1.15, 9.80)) and inhaler use across pregnancy (RRThirdTrimester: 3.49 (1.21, 10.02)). CONCLUSIONS: Higher adiposity and first trimester excessive gestational weight gain were associated with restrictive changes in lung function and symptomology during pregnancy.

Chronic exposure to air pollution and risk of mental health disorders complicating pregnancy.

BACKGROUND: Air pollution is associated with mental health in the general population, but its influence on maternal mental health during pregnancy has not been assessed. OBJECTIVE: We evaluated the relationship between unspecified mental disorders complicating pregnancy and depression with average air pollution exposure during 3-months preconception, first trimester and whole pregnancy. METHODS: Ambient air pollution was derived from a modified Community Multiscale Air Quality model and mental health diagnoses were based on electronic intrapartum medical records. Logistic regression models assessed the odds of unspecified mental disorder complicating pregnancy (n = 11,577) and depression (n = 9793) associated with an interquartile range increase in particulate matter (PM) less than 2.5 µm (PM2.5), PM10, carbon monoxide (CO), nitrogen dioxide (NO2), nitrogen oxide (NOx), sulfur dioxide (SO2), and ozone (O3). Pregnancies without mental health disorders were the reference group (n = 211,645). Models were adjusted for maternal characteristics and study site; analyses were repeated using cases with no additional mental health co-morbidity. RESULTS: Whole pregnancy exposure to PM10, PM2.5, NO2, and NOx was associated with a 29%-74% increased odds of unspecified mental disorders complicating pregnancy while CO was associated with 31% decreased odds. Results were similar for depression: whole pregnancy exposure to PM10, PM2.5, NO2, and NOx was associated with 11%-21% increased odds and CO and O3 were associated with 16%-20% decreased odds. SO2 results were inconsistent, with increased odds for unspecified mental disorders complicating pregnancy and decreased odds for depression. While most findings were similar or stronger among cases with no co-morbidity, PM2.5 and NOx were associated with reduced risk and SO2 with increased risk for depression only. DISCUSSION: Whole pregnancy exposure to PM10, PM2.5, NO2, and NOx were associated with unspecified mental disorder complicating pregnancy and depression, but some results varied for depression only. These risks merit further investigation.

Gestational and Postpartum Weight Trajectories Among Women With and Without Asthma.

Asthma leads to increased weight gain in nonpregnant populations, but studies have not examined this association within the context of pregnancy. The association between asthma and perinatal weight trajectories was examined in the Breathe-Wellbeing, Environment, Lifestyle, and Lung Function Study (2015-2019). Multilevel linear spline models were adjusted for age, race/ethnicity, income, marital status, education, cigarette smoking, parity, study site, and prepregnancy body mass index were used to examine differences in perinatal weight trajectories between women with (n = 299) and without (n = 101) asthma. Secondary analyses were conducted to assess whether associations differed by asthma phenotypes. At 40 weeks' gestation, women with asthma gained 16.2 kg (95% confidence interval (CI): 14.6, 17.7) and women without asthma gained 13.1 kg (95% CI: 10.9, 15.4). At 3 months postpartum, women with asthma retained 10.4 kg (95% CI: 8.9, 11.9) and women without asthma retained 8.0 kg (95% CI: 5.9, 10.2). Among women with asthma, exercise-induced asthma and step 3 asthma medications were associated with excess gestational weight gain. These study findings suggest women with asthma gain and retain more weight during pregnancy and postpartum than do women without asthma.

On the Mechanism of Self-Assembly by a Hydrogel-Forming Peptide.

Self-assembling peptide-based hydrogels are a class of tunable soft materials that have been shown to be highly useful for a number of biomedical applications. The dynamic formation of the supramolecular fibrils that compose these materials has heretofore remained poorly characterized. A better understanding of this process would provide important insights into the behavior of these systems and could aid in the rational design of new peptide hydrogels. Here, we report the determination of the microscopic steps that underpin the self-assembly of a hydrogel-forming peptide, SgI37-49. Using theoretical models of linear polymerization to analyze the kinetic self-assembly data, we show that SgI37-49 fibril formation is driven by fibril-catalyzed secondary nucleation and that all the microscopic processes involved in SgI37-49 self-assembly display an enzyme-like saturation behavior. Moreover, this analysis allows us to quantify the rates of the underlying processes at different peptide concentrations and to calculate the time evolution of these reaction rates over the time course of self-assembly. We demonstrate here a new mechanistic approach for the study of self-assembling hydrogel-forming peptides, which is complementary to commonly used materials science characterization techniques.

Effect of systemically administered oxytocin on dose response for methylphenidate self-administration and mesolimbic dopamine levels.

The neuropeptide oxytocin (OT) alters behaviors related to the administration of drugs of abuse, including stimulants. OT also plays a key role in social bonding, which involves an interaction between OT and dopamine (DA) in the nucleus accumbens (NAc). The nature of the interaction between OT and DA in the striatum in the context of psychostimulants is unclear. We investigated the effect of OT, delivered intraperitoneally, on the methylphenidate (MP) dose-response function for self-administration in rats. Food was used as a control condition. In a microdialysis study, we measured the effect of intraperitoneal OT on MP-stimulated striatal DA levels. Systemic OT pretreatment caused a downward shift in the MP dose-response function for self-administration, while having no effect on motor activity. OT also caused a reduction in food self-administration, although a significantly higher dose of OT was required for this effect compared with that required for a reduction of MP self-administration. Systemic OT pretreatment caused a potentiation of MP-stimulated DA levels in the NAc shell but not in the core. The significance of these findings is discussed, including the potential of OT as a therapeutic agent for addictive disorders.

Depression and quality of life in a community-based glaucoma-screening project.

OBJECTIVE: To identify the prevalence and risk factors of depression among individuals given a glaucoma-related diagnosis at a screening program. DESIGN: Cross-sectional community-based in a university hospital. PARTICIPANTS: Volunteers from a community glaucoma-screening program. METHODS: After collecting sociodemographic information, participants were administered the Geriatric Depression Scale-15 (GDS-15) and the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). RESULTS: Participants were predominantly African American (73.5%), older than 65 years (65.7%), single (75.4%), and female (66.8%). Among 268 participants, 89 were diagnosed with glaucoma and 179 as glaucoma suspects. The frequency of depression among the glaucoma and glaucoma suspect participants was 18% and 16.2%, respectively. The mean GDS-15 score was 2.4 ± 2.7 with no difference between glaucoma and glaucoma suspect groups, p = 0.654. The mean VFQ-25 score was 78.6 ± 15.9 and was lower in glaucoma (74.7 ± 19.7) than glaucoma suspect participants (80.4 ± 13.6), p = 0.003. Risk factors for depression included difficulties with paying expenses (p = 0.017), Asian race (p < 0.001), and poorer scores on the VFQ-25 subscales of "General Health" (p < 0.001), "Distance Activities" (p = 0.024), and "Dependency" (p = 0.001). CONCLUSIONS: Prevalence of depression in those diagnosed with glaucoma or glaucoma suspect was higher than previous estimates of the general population. Glaucoma-screening programs might benefit from including depression-screening protocols along with referral services or low-cost treatments of depression.

Differences Between Treatment-Seeking and Nontreatment-Seeking Alcohol-Dependent Research Participants: An Exploratory Analysis.

BACKGROUND: Alcoholism is a chronic relapsing disorder with complex behavioral and functional heterogeneity. To date, attempts to characterize subgroups of alcohol-dependent (AD) individuals have largely been focused on categorical distinctions based on behaviors such as ability to abstain, age of onset, and drinking motives, but these have failed to yield predictors of treatment response and disease course. The distinction between AD individuals who are or are not interested in treatment holds significant implications for interpreting results of human laboratory studies with nontreatment seekers and clinical trials with treatment-seeking AD patients. However, despite their crucial role in alcohol-related research, these 2 groups are poorly defined. In this exploratory analysis, we attempt to better define the phenotypic differences between these 2 experimentally relevant populations. METHODS: We analyzed data from AD individuals who participated in screening protocols to evaluate their suitability for participation in either treatment or nontreatment research studies at NIAAA. Scores on individual measures from a battery of behavioral, neuropsychological, and blood laboratory measures were compared between those who presented seeking treatment for AD and those who were not seeking treatment. Differences in each measure were assessed between the 2 groups. In addition, we explored whether significant differences were apparent when drinking behavior was used as a covariate. RESULTS: Treatment seekers manifested more impairment compared to nontreatment seekers on a wide variety of measures in the following categories: alcohol drinking, personality, impulsivity, trauma/stress, cognition, aggression, mood, and liver enzyme tests. Treatment seekers endorsed a greater number of AD criteria. Several measures including elevations in liver enzyme tests remained significantly different between the 2 groups when average daily alcohol consumption per drinking day was used as a covariate. CONCLUSIONS: Treatment-seeking, compared to nontreatment-seeking AD subjects who present for alcohol-related research studies, differ in characteristics beyond the quantity of alcohol consumption. Implications of these differences with respect to clinical research for treatments of AD are discussed.

Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date.

The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning, and memory processes. As such, there is increasing interest in oxytocin as a potential treatment for addictions. The endogenous oxytocin system is itself altered by short- or long-term exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin administration on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis, and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction.