Left ventricular diastolic dysfunction in HIV-uninfected infants exposed in utero to antiretroviral therapy.

Objectives: To longitudinally measure LV diastolic function in HIV-exposed but uninfected (HEU) children perinatally exposed to ART.

Design: HEU children who were perinatally exposed to antiretroviral therapy (ART) may be at risk for adverse cardiac effects. We have previously reported that those children have decreased left ventricular (LV) mass, dimension, and septal thickness with increased contractility.

Third Trimester Vitamin D Status Is Associated With Birth Outcomes and Linear Growth of HIV-Exposed Uninfected Infants in the United States.

Background: Vitamin D status in pregnancy may influence the risk of prematurity, birth size, and child postnatal growth, but few studies have examined the relationship among pregnant women living with HIV.

Methods: We conducted a prospective cohort study of 257 HIV-infected mothers and their HIV-exposed uninfected infants who were enrolled in the 2009-2011 nutrition substudy of the Surveillance Monitoring for ART Toxicities (SMARTT) study. HIV-infected pregnant women had serum 25-hydroxyvitamin D (25(OH)D) assessed in the third trimester of pregnancy, and their infants' growth and neurodevelopment were evaluated at birth and approximately 1 year of age.

Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents.

Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth.

Setting: The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites.

Methods: Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage.

A Comparison of Metabolic Outcomes Between Obese HIV-Exposed Uninfected Youth From the PHACS SMARTT Study and HIV-Unexposed Youth From the NHANES Study in the United States.

Background: Metabolic perturbations in HIV-exposed uninfected (HEU) obese youth may differ from those in the general obese pediatric population.

Methods: Metabolic parameters of obese (body mass index Z-score >95th percentile) HEU youth in the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study were compared with a matched sample of obese youth from the US National Health and Nutrition Examination Survey (NHANES). We evaluated systolic and diastolic hypertension (blood pressure ≥90th percentile for age, sex, and height), total cholesterol >200 mg/dL, high-density lipoprotein cholesterol <35 mg/dL, low-density lipoprotein cholesterol >130 mg/dL, triglycerides (TGs) >150 mg/dL, and Homeostatic Model Assessment-Insulin Resistance >4.

A randomized clinical trial to evaluate the single-dose pharmacokinetics, pharmacodynamics, and safety of sitagliptin in pediatric patients with type 2 diabetes.

Objective: To evaluate the single-dose pharmacokinetics (PK), pharmacodynamics (PD), and safety of sitagliptin in pediatric patients with type 2 diabetes mellitus (T2DM).

Study Design: This was a randomized, placebo-controlled, double-blind evaluation of sitagliptin in 35 patients 10 to 17 years old with T2DM at 7 clinical research sites. The safety, tolerability, PK, and PD (dipeptidyl peptidase-4 [DPP-4] inhibition and aspects of glucose metabolism) of single doses of 50, 100, and 200 mg were assessed.

Longitudinal Changes in Body Composition by Dual-energy Radiograph Absorptiometry Among Perinatally HIV-infected and HIV-uninfected Youth: Increased Risk of Adiposity Among HIV-infected Female Youth.

Background: Combination antiretroviral therapy has allowed youth with perinatal HIV infection (PHIV+) to live into adulthood, but many youth may experience metabolic and body composition changes that predispose to greater cardiovascular disease (CVD) risk. This longitudinal study evaluated changes in body composition measured by dual-energy radiograph absorptiometry (DXA) in a cohort of PHIV+ youth compared with HIV- controls over a 7-year period.

Methods: PHIV+ youth and HIV- controls were prospectively enrolled in a single-site study to assess nutrition and CVD risk.

No Obesity Paradox in Pediatric Patients With Dilated Cardiomyopathy.

Objectives: This study aimed to examine the role of nutrition in pediatric dilated cardiomyopathy (DCM).

Background: In adults with DCM, malnutrition is associated with mortality, whereas obesity is associated with survival.

Methods: The National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry was used to identify patients with DCM and categorized by anthropometric measurements: malnourished (MN) (body mass index [BMI] <5% for age ≥2 years or weight-for-length <5% for <2 years), obesity (BMI >95% for age ≥2 years or weight-for-length >95% for <2 years), or normal bodyweight (NB).

Changes in insulin sensitivity over time and associated factors in HIV-infected adolescents.

Objective: To compare prevalence of insulin resistance between perinatally HIV-infected (PHIV+) and perinatally HIV-exposed, but uninfected adolescents (PHEU), determine incidence of and contributory factors to new and resolved cases of insulin resistance in PHIV+, and evaluate glucose metabolism.

Design: Cross-sectional design for comparison of prevalence among PHIV+ and PHEU. Longitudinal design for incidence and resolution of insulin resistance among PHIV+ at risk for these outcomes.

Cardiac Effects of Highly Active Antiretroviral Therapy in Perinatally HIV-Infected Children: The CHAART-2 Study.

Background: Before the introduction of highly active antiretroviral therapy (HAART), cardiac mortality and morbidity were common in HIV-infected children.

Objectives: This study sought to identify long-term cardiovascular effects of HAART in HIV-infected children.

Methods: The CHAART-2 (HAART-Associated Cardiotoxicity in HIV-Infected Children) study prospectively compared 148 echocardiograms from 74 HAART-exposed children to 860 echocardiograms from 140 HAART-unexposed but HIV-infected children from the Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (PC HIV) study.

Associations of Low Vitamin D and Elevated Parathyroid Hormone Concentrations With Bone Mineral Density in Perinatally HIV-Infected Children.

Background: Perinatally HIV-infected (PHIV) children have, on average, lower bone mineral density (BMD) than perinatally HIV-exposed uninfected (PHEU) and healthy children. Low 25-hydroxy vitamin D [25(OH)D] and elevated parathyroid hormone (PTH) concentrations may lead to suboptimal bone accrual.

Methods: PHIV and PHEU children in the Pediatric HIV/AIDS Cohort Study had total body (TB) and lumbar spine (LS) BMD and bone mineral content (BMC) measured by dual-energy x-ray absorptiometry; BMD z-scores (BMDz) were calculated for age and sex.

Associations Between Dietary Intake Before 6 Months of Age and Rapid Weight Gain Among HIV-exposed Uninfected Infants.

Introduction: HIV-exposed, uninfected (HEU) infants are potentially at risk for cardiovascular disease due to in utero exposures. Feeding practices of the infant could compound this risk. Few studies have, however, evaluated dietary intake of HEU infants.

A multicenter study of diet quality on birth weight and gestational age in infants of HIV-infected women.

We determined factors associated with diet quality and assessed the relationship between diet quality, birth weight, and gestational age in a prospective national multicenter cohort study. We evaluated diet quality with the Healthy Eating Index (HEI, scale 0-100) in the third trimester of pregnancy with three 24-hr multiple-pass dietary recalls in 266 HIV+ women enrolled in the Pediatric HIV/AIDS Cohort Study. Covariates included demographics, food security, pre-pregnancy body mass index, HIV disease severity, substance use, and antiretroviral exposures.

Growth at 2 Years of Age in HIV-exposed Uninfected Children in the United States by Trimester of Maternal Antiretroviral Initiation.

Background: Abnormal childhood growth may affect future health. Maternal tenofovir (TFV) use was associated with lower body length and head circumference at 1 year of age in HIV-exposed uninfected (HEU) US children.

Methods: We studied 509 HEU children in the US-based Surveillance Monitoring of Antiretroviral Therapy Toxicities cohort whose HIV-infected mothers were not using antiretrovirals at the last menstrual period and began combination antiretroviral therapy (cART) in pregnancy (cART initiators).

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration.

Objective: To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth.

Design: Case-control study.

Methods: Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2-5, 25 youth with IR (IR+) and 50 without IR (IR-) who were enrolled in the Pediatric HIV/AIDS Cohort Study.

HIV Infection and Carotid Artery Intima-media Thickness: Pooled Analyses Across 5 Cohorts of the NHLBI HIV-CVD Collaborative.

Background: Age and human immunodeficiency virus (HIV) treatment may affect the association of HIV infection with atherosclerosis.

Methods: We used identical carotid artery B-mode ultrasonographic methods in 5 cohorts participating in the National Heart, Lung, and Blood Institute HIV-CVD Collaborative to measure intima-media thickness of the right far wall of the common carotid artery (CCA-IMT) and carotid artery bifurcation (BIF-IMT) between 2010 and 2013. Participants aged 6-75 years were either HIV infected or uninfected.

Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors.

Background: Impaired cardiac function in doxorubicin-treated childhood cancer survivors is partly mediated by the disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) and disrupts genes encoding for polypeptides that make adenosine triphosphate.

Methods: This cross-sectional study examined mtDNA copy numbers per cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high-risk acute lymphoblastic leukemia (ALL) who had been treated on Dana-Farber Cancer Institute childhood ALL protocols and had received doxorubicin alone (42%) or doxorubicin with the cardioprotectant dexrazoxane (58%).

Health-Related Quality of Life and Functional Status Are Associated with Cardiac Status and Clinical Outcome in Children with Cardiomyopathy.

Objectives: To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes.

Study Design: Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥ 5 years) and Functional Status II (Revised) (age ≤ 18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL.

Prenatal Cocaine Exposure and Cardiometabolic Disease Risk Factors in 18- to 20-Year-Old African Americans.

Objective: The long-term effects of prenatal cocaine exposure (PCE) on physical health are largely unknown. No human studies support or refute a relationship between PCE and the long-term risk for cardiovascular and/or metabolic disease. We investigated the association of PCE on primary cardiometabolic disease risk factors in African Americans (AA) aged 18 to 20 years.

Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy.

Background: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero.

Methods: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites.

Cardiovascular disease in adult survivors of childhood cancer.

Treatment advances have increased survival in children with cancer, but subclinical, progressive, irreversible, and sometimes fatal treatment-related cardiovascular effects may appear years later. Cardio-oncologists have identified promising preventive and treatment strategies. Dexrazoxane provides long-term cardioprotection from doxorubicin-associated cardiotoxicity without compromising the efficacy of anticancer treatment.

Cardiotoxicity and cardioprotection in childhood cancer.

Children diagnosed with cancer are now living longer as a result of advances in treatment. However, some commonly used anticancer drugs, although effective in curing cancer, can also cause adverse late effects. The cardiotoxic effects of anthracycline chemotherapy, such as doxorubicin, and radiation can cause persistent and progressive cardiovascular damage, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity.

Body mass index and waist circumference of HIV-infected youth in a Miami cohort: comparison to local and national cohorts.

Objectives: Human immunodeficiency virus (HIV)-infected youth are healthier because of effective antiretroviral therapies. We compared anthropometric measurements and prevalence of overweight and obesity between perinatally HIV-infected youth, a local HIV-uninfected comparison group, and 2007 to 2010 National Health and Nutrition Examination Survey (NHANES) data. In addition, we compared only African American HIV-infected youth with NHANES African Americans.

Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth: a structural equation model analysis.

Objective: To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth.

Design: Cross-sectional design within a prospective, 15-site US-based cohort study.

Methods: Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU).

Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus.

Background: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy.

Methods And Results: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed.