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Background: Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects., Objectives: To reveal new regulatory genes for platelet count (PLT)., Methods: Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes., Results: Of 1588 significantly associated variants ( P  < 5 × 10 -8 ) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block ( r 2 ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K)., Conclusion: Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology., (© 2023 The Authors.)

Objective: Women who have direct exposure to incarceration or indirect exposure through their partner are at high risk for poor health behaviors and outcomes, which may have lasting impacts on their children. The objectives of this study were to estimate the prevalence of recent incarceration exposure among women with a recent live birth and assess the relationship between incarceration exposure and maternal and child health., Methods: We used data from the Pregnancy Risk Assessment Monitoring System (36 states and New York City, 2012-2015; N = 146 329) to estimate the prevalence of women reporting that they or their husband/partner spent time in jail during the 12 months before giving birth. We used multivariable logistic regression to assess associations between incarceration exposure and maternal and infant health conditions., Results: The prevalence of incarceration exposure shortly before or during pregnancy was 3.7% (95% CI, 3.6%-3.9%). Women with incarceration exposure had increased odds of prepregnancy hypertension (adjusted odds ratio [aOR] = 1.51; 95% CI, 1.26-1.81), prepregnancy and postpartum depressive symptoms (aOR = 1.95 [95% CI, 1.73-2.19] and 1.49 [95% CI, 1.32-1.67], respectively), and having an infant admitted to the neonatal intensive care unit (aOR = 1.18; 95% CI, 1.04-1.33)., Conclusion: Because a parent's incarceration exposure is an adverse childhood experience with the potential to disrupt important developmental periods and have negative impacts on the socioemotional and health outcomes of children, it is critical for researchers and health care providers to better understand its impact on maternal and infant health. Prenatal and postnatal care may provide opportunities to address incarceration-related health risks.

Objective: This study aimed to analyze prenatal human immunodeficiency virus (HIV) testing rates over time and describe the impact of state HIV testing laws on prenatal testing., Methods: During 2004-2011, self-reported prenatal HIV testing data for women with live births in 35 states and New York City were collected. Prevalence of testing was estimated overall and by state and year. An annual percent change was calculated in states with at least 6 years of data to analyze testing changes over time. An attorney-coder used WestlawNext to identify states with laws that direct prenatal care providers to screen all pregnant women or direct all women to be tested for HIV and document changes in laws to meet this threshold., Results: The overall prenatal HIV testing rate for 2004 through 2011 combined was 75.7%. State-level data showed a wide range of testing rates (43.2%-92.8%) for 2004 through 2011 combined. In areas with 6 years of data, 4 experienced an annual drop in testing (Alaska, Arkansas, Colorado, and Illinois). States that changed laws to meet the threshold generally had the highest testing rates, averaging 80%, followed by states with a preexisting law, at approximately 70%. States with no law, or no law meeting the threshold, had an average prenatal testing rate of 65%., Conclusions: Prenatal HIV testing remained stable between 2004 and 2011 but remained below universal recommendations. Testing varied widely across states and was generally higher in areas that changed their laws to meet the threshold or had preexisting prenatal HIV testing laws, compared with those with no or limited prenatal HIV testing language.

Introduction: There have been dramatic improvements in reducing infant sleep-related deaths since the 1990s, when recommendations were introduced to place infants on their backs for sleep. However, there are still approximately 3,500 sleep-related deaths among infants each year in the United States, including those from sudden infant death syndrome, accidental suffocation and strangulation in bed, and unknown causes. Unsafe sleep practices, including placing infants in a nonsupine (on side or on stomach) sleep position, bed sharing, and using soft bedding in the sleep environment (e.g., blankets, pillows, and soft objects) are modifiable risk factors for sleep-related infant deaths., Competing Interests: No conflicts of interest were reported.

Thrombomodulin-associated coagulopathy (TM-AC) is a newly recognized dominant bleeding disorder in which a p.Cys537Stop variant in the thrombomodulin (TM) gene THBD , results in high plasma TM levels and protein C-mediated suppression of thrombin generation. Thrombin in complex with TM also activates thrombin-activatable fibrinolysis inhibitor (TAFI). However, the effect of the high plasma TM on fibrinolysis in TM-AC is unknown. Plasma from TM-AC cases and high-TM model control samples spiked with recombinant soluble TM showed reduced tissue factor-induced thrombin generation. Lysis of plasma clots from TM-AC cases was significantly delayed compared with controls but was completely restored when TM/thrombin-mediated TAFI activation was inhibited. Clots formed in blood from TM-AC cases had the same viscoelastic strength as controls but also showed a TAFI-dependent delay in fibrinolysis. Delayed fibrinolysis was reproduced in high-TM model plasma and blood samples. Partial restoration of thrombin generation with recombinant activated factor VII or activated prothrombin complex concentrate did not alter the delayed fibrinolysis in high-TM model blood. Our finding of a previously unrecognized fibrinolytic phenotype indicates that bleeding in TM-AC has a complex pathogenesis and highlights the pivotal role of TM as a regulator of hemostasis., (© 2016 by The American Society of Hematology.)

Although clinic-based studies have used biochemical validation to estimate the percentage of pregnant women who deny smoking but are actually smokers, a population-based estimate of nondisclosure of smoking status in US pregnant women has not been calculated. The authors analyzed data from the 1999-2006 National Health and Nutrition Examination Survey and estimated the percentage of 994 pregnant and 3,203 nonpregnant women 20-44 years of age who did not report smoking but had serum cotinine levels that exceeded the defined cut point for active smoking (nondisclosure). Active smoking was defined as self-reporting smoking or having a serum cotinine concentration that exceeded the cut point for active smoking. Overall, 13.0% (95% confidence interval (CI): 8.8, 17.1) of pregnant women and 29.7% (95% CI: 27.3, 32.1) of nonpregnant women were active smokers. Nondisclosure was higher among pregnant active smokers (22.9%, 95% CI: 11.8, 34.6) than among nonpregnant smokers (9.2%, 95% CI: 7.1, 11.2). Among pregnant active smokers, nondisclosure was associated with younger age (20-24 years). Among nonpregnant active smokers, nondisclosure was associated with Mexican-American and non-Hispanic black race/ethnicity. Studies and surveillance systems that rely on self-reported smoking status are subject to underestimation of smoking prevalence, especially among pregnant women, and underreporting may vary by demographic characteristics.