Jason L. Salemi

Mortality Resulting From Congenital Heart Disease Among Children and Adults in the United States, 1999 to 2006

Background— Previous reports suggest that mortality resulting from congenital heart disease (CHD) among infants and young children has been decreasing. There is little population-based information on CHD mortality trends and patterns among older children and adults. Methods and Results— We used data from death certificates filed in the United States from 1999 to 2006 to calculate annual CHD mortality by age at death, race-ethnicity, and sex. To calculate mortality rates for individuals ≥1 year of age, population counts from the US Census were used in the denominator; for infant mortality, live birth counts were used. From 1999 to 2006, there were 41 494 CHD-related deaths and 27 960 deaths resulting from CHD (age-standardized mortality rates, 1.78 and 1.20 per 100 000, respectively). During this period, mortality resulting from CHD declined 24.1% overall. Mortality resulting from CHD significantly declined among all race-ethnicities studied. However, disparities persisted; overall and among infants, mortality resulting from CHD was consistently higher among non-Hispanic blacks compared with non-Hispanic whites. Infant mortality accounted for 48.1% of all mortality resulting from CHD; among those who survived the first year of life, 76.1% of deaths occurred during adulthood (≥18 years of age). Conclusions— CHD mortality continued to decline among both children and adults; however, differences between race-ethnicities persisted. A large proportion of CHD-related mortality occurred during infancy, although significant CHD mortality occurred during adulthood, indicating the need for adult CHD specialty management.

Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009.

STUDY OBJECTIVES A recent trend in increasing rates of severe maternal morbidity and mortality despite quality improvements has been noted. The goal of this study is to estimate the national prevalence of obstructive sleep apnea (OSA) in pregnant women and examine associations between OSA and pregnancy-related morbidities, including in-hospital maternal mortality. DESIGN A retrospective, cross-sectional analysis. SETTING A nationally representative sample of maternal hospital discharges from 1998-2009. PATIENTS OR PARTICIPANTS The analytic sample included 55,781,965 pregnancy-related inpatient hospital discharges. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS The Nationwide Inpatient Sample (NIS) database was used to identify hospital stays for women who were pregnant or gave birth. Among these women, we determined length of hospital stay, in-hospital mortality, and used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify OSA and other outcome measures. Multivariable logistic regression modeling was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between OSA and each outcome. The overall rate of OSA was 3.0 per 10,000; however, the rate climbed substantially from 0.7 in 1998 to 7.3 in 2009, with an average annual increase of 24%. After controlling for obesity and other potential confounders, OSA was associated with increased odds of pregnancy-related morbidities including preeclampsia (OR, 2.5; 95% CI, 2.2-2.9), eclampsia (OR, 5.4; 95% CI, 3.3-8.9), cardiomyopathy (OR, 9.0; 95% CI, 7.5-10.9), and pulmonary embolism (OR, 4.5; 95% CI, 2.3-8.9). Women with OSA experienced a more than fivefold increased odds of in-hospital mortality (95% CI, 2.4-11.5). The adverse effects of OSA on selected outcomes were exacerbated by obesity. CONCLUSIONS Obstructive sleep apnea is associated with severe maternal morbidity, cardiovascular morbidity, and in-hospital death. Targeted interventions may improve pregnancy outcomes in this group.

Associations between Male Anogenital Human Papillomavirus Infection and Circumcision by Anatomic Site Sampled and Lifetime Number of Female Sex Partners

BACKGROUND Male circumcision may lower mens risk of human papillomavirus (HPV) infection and reduce transmission to sex partners. Reported associations between circumcision and HPV infection in men have been inconsistent. METHODS Four hundred sixty-three men in 2 US cities were tested at 6 anogenital sites and in semen for 37 types of HPV. Men were eligible if they reported sex with a woman within the past year, no history of genital warts or penile or anal cancer, and no current diagnosis of a sexually transmitted infection. Participants completed a self-administered questionnaire. Circumcision status was assessed by the study clinician. Logistic regression was used to examine associations between circumcision and HPV detection at each site and in semen, with adjustment for potential confounders. RESULTS Seventy-four men (16.0%) were uncircumcised. Adjusted odds ratios (AORs) for any HPV genotype and circumcision were 0.53 (95% confidence interval [CI], 0.28-0.99) for any anatomic site/specimen, 0.17 (95% CI, 0.05-0.56) for the urethra, 0.44 (95% CI, 0.23-0.82) for the glans/corona, and 0.53 (95% CI, 0.28-0.99) for the penile shaft. AORs were <1.0 but not statistically significant for the scrotum, semen, anal canal, and perianal area. CONCLUSIONS Circumcision may be protective against HPV infection of the urethra, glans/corona, and penile shaft.

Prevalence and correlates of gastroschisis in 15 states, 1995 to 2005.

OBJECTIVE: To identify trends in the prevalence and epidemiologic correlates of gastroschisis using a large population-based sample with cases identified by the National Birth Defects Prevention Network over the course of an 11-year period. METHODS: This study examined 4,713 cases of gastroschisis occurring in 15 states during 1995–2005, using public use natality data sets for denominators. Multivariable Poisson regression was used to identify statistically significant risk factors, and Joinpoint regression analyses were conducted to assess temporal trends in gastroschisis prevalence by maternal age and race and ethnicity. RESULTS: Results show an increasing temporal trend for gastroschisis (from 2.32 per 10,000 to 4.42 per 10,000 live births). Increasing prevalence of gastroschisis has occurred primarily among younger mothers (11.45 per 10,000 live births among mothers younger than age 20 years compared with 5.35 per 10,000 among women aged 20 to 24 years). In the multivariable analysis, using non-Hispanic whites as the referent group, non-Hispanic black women had the lowest risk of having a gastroschisis-affected pregnancy (prevalence ratio 0.42, 95% confidence interval [CI] 0.37–0.48), followed by Hispanics (prevalence ratio 0.86, 95% CI 0.81–0.92). Gastroschisis prevalence did not differ by newborn sex. CONCLUSIONS: Our findings demonstrate that the prevalence of gastroschisis has been increasing since 1995 among 15 states in the United States, and that higher rates of gastroschisis are associated with non-Hispanic white maternal race and ethnicity, and maternal age younger than 25 years (particularly younger than 20 years of age). LEVEL OF EVIDENCE: III

Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes

Background and aims: To examine the association between maternal hepatitis B and C mono‐ and co‐infections with singleton pregnancy outcomes in the state of Florida.

Mortality in First 5 Years in Infants With Functional Single Ventricle Born in Texas, 1996 to 2003

Background— Infants with functional single ventricle have a high risk of death during the early years of life. Studies have reported improvement in postoperative survival, but they do not include preoperative deaths or those occurring before transfer. The purpose of this population-based study was to estimate 5-year survival in infants with functional single ventricle, to define factors associated with survival, and to estimate improvement in outcome. Methods and Results— Patients with hypoplastic left heart syndrome, pulmonary atresia intact ventricular septum, single ventricle, and tricuspid atresia born in 1996 to 2003 were identified from the Texas Birth Defects Registry and linked to state and national birth and death vital records. We examined the effects of defect type, birth era, birth weight, gestational age, maternal race/ethnicity, extracardiac anomalies, sex, and maternal age and education on survival. Five-year survival varied by defect type: hypoplastic left heart syndrome, 38.0% (95% confidence interval, 32.6 to 43.5); single ventricle, 56.1% (95% confidence interval, 49.9 to 61.7); pulmonary atresia intact ventricular septum, 55.7% (95% confidence interval, 45.8 to 64.4); and tricuspid atresia, 74.6% (95% confidence interval, 62.4 to 83.4). The presence of extracardiac defects increased the adjusted risk of death by 84%. Non-Hispanic blacks had an adjusted risk of death that was 41% higher than that for non-Hispanic whites, and Hispanics had a 26% higher risk. Patients born in 2001 to 2003 had a 47% lower risk than those born in 1996 to 2000. Conclusions— This population-based study demonstrates significant improvement in overall 5-year survival, particularly in cases of hypoplastic left heart syndrome and single ventricle. Additional studies are needed to determine the factors causing racial/ethnic and regional differences in outcome.

A pilot, double-blind, placebo-controlled trial of pregabalin (Lyrica) in the treatment of essential tremor.

We performed a pilot, double‐blind, placebo‐controlled, randomized trial to evaluate the efficacy and tolerability of pregabalin (PGB, Lyrica), an antiepileptic agent, in treating essential tremor (ET). Twenty two patients with ET were randomly assigned to receive PGB or placebo. PGB was initiated at 50 mg/day and was escalated by 75 mg/day every 4 days to a maximum dose of 600 mg/day. Patients were evaluated by accelerometry and the Fahn–Tolosa–Marin (FTM) rating scale. There was a significant reduction in tremor amplitude in the PGB group compared with the placebo group, as measured by accelerometry, at a mean dose of 286.76 ± 100.05 mg/day. Action tremor limb scores on the FTM also improved in the PGB group compared with the placebo group (P‐value for multilevel modeling = 0.04). PGB was fairly well tolerated, with about one‐third of patients dropping out of the study because of adverse events. PGB provided significant improvements in accelerometry and in action tremor limb scores on the FTM. However, larger studies are needed to further evaluate the potential effect of PGB on ET.

Racial/Ethnic Disparities in Risk of Early Childhood Mortality Among Children With Congenital Heart Defects

BACKGROUND: Infants with congenital heart defects (CHDs) have increased risk of childhood morbidity and mortality. However, little is known about racial/ethnic differences in early childhood mortality. PATIENTS AND METHODS: We conducted a retrospective cohort study with data from the Texas Birth Defect Registry on 19 530 singleton, live-born infants with a CHD and born January 1, 1996, to December 31, 2003, to non-Hispanic (NH) white, NH black, and Hispanic women. Texas Birth Defect Registry data were linked to Texas death records and the National Death Index to ascertain deaths between January 1, 1996, and December 31, 2005. Kaplan-Meier survival estimates were computed, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable Cox-proportional hazard regression models to determine the effect of maternal race/ethnicity on mortality for selected CHD phenotypes. RESULTS: After adjusting for covariates, compared with NH white children, NH black children had increased early childhood mortality risk for transposition of the great arteries (HR: 2.04 [95% CI: 1.40–2.97]), tetralogy of Fallot (HR: 1.85 [95% CI: 1.09–3.12]), pulmonary valve atresia without ventricular septal defect (VSD) (HR: 2.60 [95% CI: 1.32–5.12]), VSD (HR: 1.56 [95% CI: 1.19–2.03]), and atrial septal defect (HR: 1.34 [95% CI: 1.08–1.66]). Hispanic children had higher mortality risk for pulmonary valve atresia without VSD (HR: 1.76 [95% CI: 1.06–2.91]) and hypoplastic left heart syndrome (HR: 1.51 [95% CI: 1.13–2.02]). CONCLUSIONS: We provide evidence that supports racial/ethnic disparities in early childhood mortality among infants with CHDs. Identifying infants with the greatest risk of early childhood mortality will facilitate development of interventions and policies to mitigate these risks.

Maternal nativity as a risk factor for gastroschisis: A population‐based study

BACKGROUND The prevalence of gastroschisis is increasing in many parts of the world, although the etiology is largely unexplained. Young maternal age has been the only consistently identified, strong risk factor. The objective of this study was to examine the role of maternal nativity in relation to other suspected risk factors for gastroschisis in Florida. METHODS We conducted a retrospective cohort study of singleton infants born in Florida from 1998-2003. Gastroschisis cases were identified from the Florida Birth Defects Registry. Demographic and perinatal data were obtained from birth records. Multivariable Poisson regression was used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for each factor of interest. RESULTS The 6-year birth prevalence of gastroschisis was 3.26 per 10,000 live births, and the annual rate increased 41% during the study period. In addition to maternal age and marital status, maternal race/ethnicity and nativity were significantly associated with the risk of delivering an infant with gastroschisis. Compared with non-Hispanic white women, non-Hispanic black women had the lowest risk of delivering an infant with gastroschisis (PR, 0.19; 95% CI, 0.13-0.26), followed by Hispanic women (PR, 0.60; 95% CI, 0.43-0.83). Women born outside the United States were significantly less likely than U.S.-born women to deliver an infant with gastroschisis (PR, 0.59; 95% CI, 0.41-0.86). CONCLUSIONS Although young maternal age remains a strong significant risk factor for gastroschisis in Florida, other factors such as maternal race/ethnicity and nativity could be important in explaining the increasing prevalence of gastroschisis.

Variation in the prevalence of congenital heart defects by maternal race/ethnicity and infant sex.

OBJECTIVE To determine the prevalence of major congenital heart defects (CHD) by ethnicity and sex. STUDY DESIGN Data from the Florida Birth Defects Registry was used to conduct a retrospective cohort study with 8029 singleton infants with 11 CHDs born 1998-2003 to resident non-Hispanic (NH) white, NH-black, and Hispanic women aged 15 to 49. Defect-specific prevalence rates, ratios, and 95% confidence intervals were calculated. Poisson regression was used to calculate adjusted ethnic-specific rate ratios (RR) for each CHD. Statistical significance was P < .0001. RESULTS Compared with NH-whites, NH-black males had significantly increased rates of pulmonary valve atresia/stenosis (RR = 1.66) but lower prevalence of aortic valve atresia/stenosis (RR = 0.33) and ventricular septal defect (VSD; RR = 0.78). Hispanic males had lower rates of aortic valve atresia/stenosis (RR = 0.28), coarctation of the aorta (RR = 0.61) and VSD (RR = 0.79). NH-black females had statistically significantly lower rates of VSD (RR = 0.75), and Hispanic females had lower rates of tetralogy of Fallot (RR = 0.54), VSD (RR = 0.84) and atrioventricular septal defects (RR = 0.53) compared with NH-whites. CONCLUSIONS We found differences in ethnic susceptibilities to CHD by sex, but the cause remains unclear.