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Item Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV(Elsevier, 2017-12) Conroy, Andrea L.; McDonald, Chloe R.; Gamble, Joel L.; Olwoch, Peter; Natureeba, Paul; Cohan, Deborah; Kamya, Moses R.; Havlir, Diane V.; Dorsey, Grant; Kain, Kevin C.; Pediatrics, School of MedicineBackground Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings. Objective We sought to determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy. Study Design This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women and adolescents infected with HIV to lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral therapy in Tororo, Uganda. Pregnant women living with HIV were enrolled between 12-28 weeks of gestation. Plasma samples were evaluated for angiogenic biomarkers (angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin) by enzyme-linked immunosorbent assay between: 16-<20, 20-<24, 24-<28, 28-<32, 32-<36, 36-<37 weeks of gestation. The primary outcome was preterm birth. Results In all, 1115 plasma samples from 326 pregnant women and adolescents were evaluated. There were no differences in angiogenic factors according to antiretroviral therapy group (P > .05 for all). The incidence of adverse birth outcomes was 16.9% for spontaneous preterm births, 25.6% for small-for-gestational-age births, and 2.8% for stillbirth. We used linear mixed effect modelling to evaluate longitudinal changes in angiogenic factor concentrations between birth outcome groups adjusting for gestational age at venipuncture, maternal age, body mass index, gravidity, and the interaction between treatment arm and gestational age. Two angiogenic factors–soluble endoglin and placental growth factor–were associated with adverse birth outcomes. Significantly higher concentrations of soluble endoglin throughout gestation were found in study participants destined to deliver preterm [likelihood ratio test, χ2(1) = 12.28, P < .0005] and in those destined to have stillbirths [χ2(1) = 5.67, P < .02]. By contrast, significantly lower concentrations of placental growth factor throughout gestation were found in those destined to have small-for-gestational-age births [χ2(1) = 7.89, P < .005] and in those destined to have stillbirths [χ2(1) = 21.59, P < .0001]. Conclusion An antiangiogenic state in the second or third trimester is associated with adverse birth outcomes, including stillbirth in women and adolescents living with HIV and receiving antiretroviral therapy.Item Provider Adherence to Syphilis Testing Guidelines Among Stillbirth Cases(Wolters Kluwer, 2020-07) Ho, Yenling A.; Allen, Katie; Tao, Guoyo; Patel, Chirag G.; Arno, Janet N.; Broyles, Andrea A.; Dixon, Brian E.; Epidemiology, School of Public HealthBackground The Centers for Disease Control and Prevention (CDC) recommends that all women with a stillbirth have a syphilis test after delivery. Our study seeks to evaluate adherence to CDC guidelines for syphilis screening among women with a stillbirth delivery. Methods We utilized data recorded in electronic health records for women who gave birth between January 1, 2014 and December 31, 2016. Patients were included if they were 18-44 years old and possessed an ICD-9-CM or ICD-10-CM diagnosis of stillbirth. Stillbirth diagnoses were confirmed through a random sample of medical chart reviews. To evaluate syphilis screening, we estimated the proportion of women who received syphilis testing within 300 days before stillbirth, within 30 days after a stillbirth delivery, and women who received syphilis testing both before and after stillbirth delivery. Results We identified 1,111 stillbirths among a population of 865,429 unique women with encounter data available from electronic health records. Among a sample of 127 chart reviewed cases, only 35 (27.6%) were confirmed stillbirth cases, 45 (35.4%) possible stillbirth cases, 39 (30.7%) cases of miscarriage, and 8 (6.3%) cases of live births. Among confirmed stillbirth cases, 51.4% had any syphilis testing conducted, 31.4% had testing before their stillbirth delivery, 42.9% had testing after the delivery, and only 22.9% had testing before and after delivery. Conclusions A majority of women with a stillbirth delivery do not receive syphilis screening adherent to CDC guidelines. Stillbirth ICD codes do not accurately identify cases of stillbirth.Item The Impact of Self-Reported Alcohol, Tobacco, and Recreational Drug Use during Pregnancy on Adverse Pregnancy Outcomes in First-Time Mothers(Thieme Medical Publishers, 2022-09-12) Daggy, Joanne K.; Silver, Robert M.; Guise, David; Haas, David M.; Biostatistics and Health Data Science, School of MedicineObjective: The objective of this study was to derive profiles of alcohol, tobacco, and recreational drug use during pregnancy for first-time mothers with latent class growth analysis (LCGA) and determine the association of these classes with the risk of adverse pregnancy outcomes (APO). Study Design: A secondary analysis of a prospective cohort of Nulliparous Outcomes in Pregnancy: Monitoring Mothers-to-Be was conducted in eight medical centers across the United States from September 30, 2010, to September 23, 2013. Self-reported use of any alcohol, tobacco, or recreational drugs in the 1 month prior to the visit was assessed at up to four visits throughout pregnancy, and APOs included a composite of preterm birth, hypertensive disorder of pregnancy (HDP), small for gestational age (SGA) infant, or stillbirth, and each adverse outcome separately. Results: Four latent classes were identified from the LCGA for 10,031 nulliparous pregnant women that were on average 26.9 years old (standard deviation [SD] = 5.7) and mostly non-Hispanic White (59.7%). Classes included consistent tobacco users (N = 517, 5.2%), nonusers (N = 8,945, 89.2%), alcohol users (N = 500, 5.0%), and a combination of alcohol/tobacco/drug users (N = 69, 0.7%). Logistic regression demonstrated that the class of tobacco users was more likely to have an APO (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.22–1.81), preterm birth (OR = 1.53, 95% CI = 1.15–2.02), and SGA (OR = 1.79, 95% CI = 1.36–2.35) relative to the class of nonusers. The class of alcohol users was more likely to have HDP (OR = 1.37, 95% CI = 1.11–1.70) and less likely to have preterm birth (OR = 0.59, 95% CI = 0.38–0.90) and SGA (OR = 0.61, 95% CI = 0.40–0.93) compared to nonusers. Conclusion: Trajectories of substance use are associated with APOs; thus, interventions to mitigate the use when encountered early in pregnancy are warranted. Key Points: - Four classes of substance use were identified. - Tobacco users were at a higher risk of APO and alcohol users were at higher risk of HDP. - Mitigation strategies are warranted to reduce APO.