Beverly M. Snively

Impact of maternal immunization on influenza hospitalizations in infants

We sought to determine whether maternal vaccination during pregnancy was associated with a reduced risk of laboratory-confirmed influenza hospitalizations in infants <6 months old. Active population-based, laboratory-confirmed influenza surveillance was conducted in children hospitalized with fever and/or respiratory symptoms in 3 US counties from November through April during the 2002 through 2009 influenza seasons. The exposure, influenza vaccination during pregnancy, and the outcome, positive/negative influenza testing among their hospitalized infants, were compared using logistic regression analyses. Among 1510 hospitalized infants <6 months old, 151 (10%) had laboratory-confirmed influenza and 294 (19%) mothers reported receiving influenza vaccine during pregnancy. Eighteen (12%) mothers of influenza-positive infants and 276 (20%) mothers of influenza-negative infants were vaccinated (unadjusted odds ratio, 0.53; 95% confidence interval, 0.32-0.88 and adjusted odds ratio, 0.52; 95% confidence interval, 0.30-0.91). Infants of vaccinated mothers were 45-48% less likely to have influenza hospitalizations than infants of unvaccinated mothers. Our results support the current influenza vaccination recommendation for pregnant women.

Higher Prevalence of Elevated Albumin Excretion in Youth With Type 2 Than Type 1 Diabetes: The SEARCH for Diabetes in Youth Study

OBJECTIVE—To estimate the prevalence of an elevated albumin-to-creatinine ratio (ACR) (≥30 μg/mg) among youth with type 1 or type 2 diabetes and to identify factors associated with elevated ACR and their effect on the relationship between elevated ACR and type of diabetes. RESEARCH DESIGN AND METHODS—Cross-sectional data were analyzed from 3,259 participants with onset of diabetes at <20 years of age in the SEARCH for Diabetes in Youth, a multicenter observational study of diabetes in youth. Multiple logistic regression was used to explore determinants of elevated ACR and factors accounting for differences in this prevalence between type 2 and type 1 diabetes. RESULTS—The prevalence of elevated ACR was 9.2% in type 1 and 22.2% in type 2 diabetes (prevalence ratio 2.4 [95% CI 1.9–3.0]; P < 0.0001). In multiple logistic regression analysis, female sex, A1C and triglyceride values, hypertension, and type of diabetes (type 2 versus type 1) were significantly associated with elevated ACR. Adjustment for variables related to insulin resistance (obesity, hypertension, dyslipidemia, and inflammation) attenuated, but did not completely explain, the association of diabetes type with elevated ACR. CONCLUSIONS—Youth with type 2 diabetes have a higher prevalence of elevated ACR than youth with type 1 diabetes, in an association that apparently does not completely depend on age, duration of diabetes, race/ethnicity, sex, level of glycemic control, or features of insulin resistance.

The Burden of Influenza in Young Children, 2004–2009

OBJECTIVE: To characterize the health care burden of influenza from 2004 through 2009, years when influenza vaccine recommendations were expanded to all children aged ≥6 months. METHODS: Population-based surveillance for laboratory-confirmed influenza was performed among children aged <5 years presenting with fever and/or acute respiratory illness to inpatient and outpatient settings during 5 influenza seasons in 3 US counties. Enrolled children had nasal/throat swabs tested for influenza by reverse transcriptase-polymerase chain reaction and their medical records reviewed. Rates of influenza hospitalizations per 1000 population and proportions of outpatients (emergency department and clinic) with influenza were computed. RESULTS: The study population comprised 2970, 2698, and 2920 children from inpatient, emergency department, and clinic settings, respectively. The single-season influenza hospitalization rates were 0.4 to 1.0 per 1000 children aged <5 years and highest for infants <6 months. The proportion of outpatient children with influenza ranged from 10% to 25% annually. Among children hospitalized with influenza, 58% had physician-ordered influenza testing, 35% had discharge diagnoses of influenza, and 2% received antiviral medication. Among outpatients with influenza, 7% were tested for influenza, 7% were diagnosed with influenza, and <1% had antiviral treatment. Throughout the 5 study seasons, <45% of influenza-negative children ≥6 months were fully vaccinated against influenza. CONCLUSIONS: Despite expanded vaccination recommendations, many children are insufficiently vaccinated, and substantial influenza burden remains. Antiviral use was low. Future studies need to evaluate trends in use of vaccine and antiviral agents and their impact on disease burden and identify strategies to prevent influenza in young infants.

Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.

Prevalence of Increased Arterial Stiffness in Children with Type 1 Diabetes Mellitus Differs by Measurement Site and Sex: The SEARCH for Diabetes in Youth Study

OBJECTIVE To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined. RESULTS Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity-trunk (aorto-femoral) was higher in cases (all P <or= < .05). Increased peripheral stiffness was more common than central stiffness in subjects with T1DM (low BrachD in 33% vs high PWV-trunk in 9.9%). Male subjects with type 1 diabetes had a higher prevalence of VS abnormalities than females. Presence of T1DM, male sex, and increased mean arterial pressure were the most consistent independent determinants of vascular stiffness. CONCLUSIONS Increased vascular stiffness is present in youth with T1DM with peripheral abnormalities predominating especially in males. Traditional risk factors are important correlates. Identifying early vascular abnormalities in youth with T1DM will allow for implementation of more aggressive risk factor management.

Genome-wide meta-analyses of smoking behaviors in African Americans

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n=32 389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β=0.040, s.e.=0.007, P=1.84 × 10−8). This variant is present in the 5′-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10−8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10−9), 7q11 (rs13236689, CD36, p = 2.8×10−9), 10q21 (rs7896518, JMJD1C, p = 2.3×10−12), 11q13 (rs477895, BAD, p = 4.9×10−8), and 20q13 (rs151361, SLMO2, p = 9.4×10−9). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10−8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.

Prevalence and Correlates of Elevated Blood Pressure in Youth with Diabetes Mellitus: The Search for Diabetes in Youth Study

OBJECTIVE To determine the prevalence and correlates of elevated blood pressure (BP) in youth with type 1 or type 2 diabetes mellitus by using data from the SEARCH Study. STUDY DESIGN The analysis included youth aged 3 to 17 years with type 1 (n = 3691) and type 2 diabetes mellitus (n = 410) who attended a research visit. Elevated BP was defined as systolic or diastolic values >or=95 percentile, regardless of drug use. In youth with elevated BP, awareness was defined as self-report of an earlier diagnosis. Control was defined as BP values <90th percentile and <120/90 mm Hg in youth with an earlier diagnosis who were taking BP medications. RESULTS The prevalence of elevated BP in youth with type 1 diabetes mellitus was 5.9%; minority ethnic groups, obese adolescents, and youth with poor glycemic control were disproportionately affected. In contrast, 23.7% of adolescents with type 2 diabetes mellitus had elevated BP (P < .0001), Similarly, 31.9% of youth with type 2 diabetes mellitus and elevated BP were aware, compared with only 7.4% of youth with type 1 diabetes mellitus (P < .0001). Once BP was diagnosed and treated, control was similar in type 1 (57.1%) and type 2 diabetes mellitus (40.6%). CONCLUSIONS Our findings identify high-risk groups of youth with diabetes mellitus at which screening and treatment efforts should be directed.

Housing Characteristics of Farmworker Families in North Carolina

Adequate housing is a basic human right and an important determinant of environmental health. Little research has documented the housing quality of immigrant Latino farmworker families. This analysis uses data from four surveys of North Carolina farmworker communities conducted in 2001 and 2003 to document aspects of housing quality that could affect farmworker family health. Three housing domains are considered: dwelling characteristics, household characteristics, and household behaviors. Most farmworker families live in mobile homes, and few own their dwellings. Many are located near agricultural fields. Most houses are small, but household size is large, containing adults, in addition to the nuclear family. Crowding is common among farmworker families. Many farmworker households lack basic facilities, such as washing machines. Farmworkers attempt to reduce exposure by frequently cleaning their dwellings. These findings suggest that the health of farmworker families is at risk due to inadequate housing. Further research on housing-related health effects among farmworker families is needed.

ATP1A3 mutations in infants: a new rapid-onset dystonia-Parkinsonism phenotype characterized by motor delay and ataxia.

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the ATP1A3 gene. In adults, mutations in ATP1A3 cause rapid‐onset dystonia–Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and samples were collected for mutation analysis. Case 1 presented with fluctuating spells of hypotonia, dysphagia, mutism, dystonia, and ataxia at 9 months. After three episodes of hypotonia, she developed ataxia, inability to speak or swallow, and eventual seizures. Case 2 presented with hypotonia at 14 months and pre‐existing motor delay. At age 4 years, he had episodic slurred speech, followed by ataxia, drooling, and dysarthria. He remains mute. Both children had ATP1A3 gene mutations. To our knowledge, these are the earliest presentations of RDP, both with fluctuating features. Both children were initially misdiagnosed. RDP should be considered in children with discoordinated gait, and speech and swallowing difficulties.