Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study

Context  The duration of protection from tuberculosis of BCG vaccines is not known. Objective  To determine the long-term duration of protection of a BCG vaccine that was previously found to be efficacious. Design  Retrospective record review using Indian Health Service records, tuberculosis registries, death certificates, and supplemental interviews with trial participants. Setting and Participants  Follow-up for the period 1948-1998 among American Indians and Alaska Natives who participated in a placebo-controlled BCG vaccine trial during 1935-1938 and who were still at risk of developing tuberculosis. Data from 1483 participants in the BCG vaccine group and 1309 in the placebo group were analyzed. Main Outcome Measures  Efficacy of BCG vaccine, calculated for each 10-year interval using a Cox regression model with time-dependent variables based on tuberculosis events occurring after December 31, 1947 (end of prospective case finding). Results  The overall incidence of tuberculosis was 66 and 138 cases per 100 000 person-years in the BCG vaccine and placebo groups, respectively, for an estimate of vaccine efficacy of 52% (95% confidence interval, 27%-69%). Adjustments for age at vaccination, tribe, subsequent BCG vaccination, chronic medical illness, isoniazid use, and bacille Calmette-Guérin strain did not substantially affect vaccine efficacy. There was slight but not statistically significant waning of the efficacy of BCG vaccination over time, greater among men than women. Conclusion  In this trial, BCG vaccine efficacy persisted for 50 to 60 years, suggesting that a single dose of an effective BCG vaccine can have a long duration of protection.      

Temporal trends in early clinical manifestations of perinatal HIV infection in a population-based cohort

Context  The effect of early antiretroviral therapy (ART) on the early progression of perinatal human immunodeficiency virus (HIV) infection is not well defined. Objective  To examine early disease progression and survival in a population-based cohort with perinatal HIV infection in relation to year of birth and use of ART. Design, Setting, and Patients  Retrospective study of temporal trends in early progression of perinatal HIV infection among 205 HIV-infected children in Northern California born between January 1, 1988, and December 31, 2001, and followed up through age 3 years. Main Outcome Measures  Prevalence of and age at progression to a first US Centers for Disease Control and Prevention category C diagnosis relative to year of birth, type of ART, and age at initiation of therapy. Results  Of 205 children, 134 (65%) received ART and/or Pneumocystis jiroveci pneumonia prophylaxis. By age 3 years, 81 (40%) progressed to a category C diagnosis, 41 (51%) of whom died. Untreated children were significantly more likely to progress to a category C diagnosis (62% [44/71] untreated vs 28% [37/134] treated children, P<.001); none of 23 infants who received triple ART progressed to category C. However, even without triple ART, very early mono/dual ART (by age 2 months vs 3-4 months) was associated with delayed and decreased progression to category C (P = .02). Of 33 children born between January 1, 1996, and December 31, 2001, only 7 (21%) progressed to category C (P = .02 compared with 1988-1995), 6 of 7 of whom received no therapy. More recent year of birth and more advanced therapy were associated with improved survival. Conclusions  This population-based cohort demonstrated decreased early HIV progression and improved survival at age 3 years, associated with more advanced therapy. Although limited by small sample size, the findings suggest that very early treatment, even without triple ART, was associated with improved outcome.      

Timeliness of childhood vaccinations in the United States: days undervaccinated and number of vaccines delayed

Context  Only 18% of children in the United States receive all vaccinations at the recommended times or acceptably early. Objective  To determine the extent of delay of vaccination during the first 24 months of life. Design, Setting, and Participants  The 2003 National Immunization Survey was conducted by random-digit dialing of households and mailings to vaccination providers to estimate vaccination coverage rates for US children aged 19 to 35 months. Data for this study were limited to 14 810 children aged 24 to 35 months. Main Outcome Measures  Cumulative days undervaccinated during the first 24 months of life for each of 6 vaccines (diphtheria and tetanus toxoids and acellular pertussis; poliovirus; measles, mumps, and rubella; Haemophilus influenzae type b; hepatitis B; and varicella) and all vaccines combined, number of late vaccines, and risk factors for severe delay of vaccination. Results  Children were undervaccinated a mean of 172 days (median, 126 days) for all vaccines combined during their first 24 months of life. Approximately 34% were undervaccinated for less than 1 month and 29% for 1 to 6 months, while 37% were undervaccinated for more than 6 months. Vaccine-specific undervaccination of more than 6 months ranged from 9% for poliovirus vaccine to 21% for Haemophilus influenzae type b vaccine. An estimated 25% of children had delays in receipt of 4 or more of the 6 vaccines. Approximately 21% of children were severely delayed (undervaccinated for more than 6 months and for 4 vaccines). Factors associated with severe delay included having a mother who was unmarried or who did not have a college degree, living in a household with 2 or more children, being non-Hispanic black, having 2 or more vaccination providers, and using public vaccination provider(s). Conclusions  More than 1 in 3 children were undervaccinated for more than 6 months during their first 24 months of life and 1 in 4 children were delayed for at least 4 vaccines. Standard measures of vaccination coverage mask substantial shortfalls in ensuring that recommendations are followed regarding age at vaccination throughout the first 24 months of life.      

Effectiveness over time of varicella vaccine

Context  Reports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine. Objective  To assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination. Design  Case-control study conducted from March 1997 through June 2003. Setting  Twenty different group practices in southern Connecticut. Participants  Case subjects, identified by active surveillance of all practices, consisted of 339 eligible children 13 months or older who were clinically diagnosed as having chickenpox and who also had a polymerase chain reaction (PCR) test result that was positive for varicella-zoster virus DNA. For each case subject, 2 controls were selected, matched by both age and pediatric practice. Main Outcome Measures  The effectiveness of the vaccine, especially the effects of time since vaccination and age at the time of vaccination, adjusted for possible confounders. Results  Although the adjusted overall effectiveness of the vaccine was 87% (95% confidence interval, 81%-91%; P<.001), there was a substantial difference in the vaccine's effectiveness in the first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P = .003). The vaccine's effectiveness in year 1 was substantially lower if the vaccine was administered at younger than 15 months (73%) than if it was administered at 15 months or older (99%, P = .01), although the difference in effectiveness overall for children immunized at younger than 15 months was not statistically significantly different than for those immunized at 15 months or older (81% vs 88%, P = .17). Most cases of chickenpox in vaccinees were mild. Conclusions  Although varicella vaccine is effective, its effectiveness decreases significantly after 1 year, although most cases of breakthrough disease are mild. If administered at younger than 15 months, the vaccine's effectiveness was lower in the first year after vaccination, but the difference in effectiveness was not statistically significant for subsequent years.      

Chorioamnionitis and cerebral palsy in term and near-term infants

Context  Half of all cases of cerebral palsy (CP) occur in term infants, for whom risk factors have not been clearly defined. Recent studies suggest a possible role of chorioamnionitis. Objective  To determine whether clinical chorioamnionitis increases the risk of CP in term and near-term infants. Design, Setting, and Patients  Case-control study nested within a cohort of 231 582 singleton infants born at 36 or more weeks' gestation between January 1, 1991, and December 31, 1998, in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were identified from electronic records and confirmed by chart review by a child neurologist, and comprised all children with moderate to severe spastic or dyskinetic CP not due to postnatal brain injury or developmental abnormalities (n = 109). Controls (n = 218) were randomly selected from the study population. Main Outcome Measure  Association between clinical chorioamnionitis and increased risk of CP in term and near-term infants. Results  Most CP cases had hemiparesis (40%) or quadriparesis (38%); 87% had been diagnosed by a neurologist and 83% had undergone neuroimaging. Chorioamnionitis, considered present if a treating physician made a diagnosis of chorioamnionitis or endometritis clinically, was noted in 14% of cases and 4% of controls (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.5-10.1; P = .001). Independent risk factors identified in multiple logistic regression included chorioamnionitis (OR, 4.1; 95% CI, 1.6-10.1), intrauterine growth restriction (OR, 4.0; 95% CI, 1.3-12.0), maternal black ethnicity (OR, 3.6; 95% CI, 1.4-9.3), maternal age older than 25 years (OR, 2.6; 95% CI, 1.3-5.2), and nulliparity (OR, 1.8; 95% CI, 1.0-3.0). The population-attributable fraction of chorioamnionitis for CP is 11%. Conclusion  Our data suggest that chorioamnionitis is an independent risk factor for CP among term and near-term infants.      

Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial

Context  Neisseria meningitidis is a common cause of meningitis and septicemia in infants worldwide. Whether a meningococcal C conjugate vaccine protects infants against the serogroup C strain is unknown. Objectives  To determine whether a meningococcal C conjugate vaccine is safe and immunogenic and induces immunologic memory in infants. Design  Single-center, double-blind, randomized controlled trial in 1995 and 1996. Setting  Community, Oxfordshire, England. Participants  One hundred eighty-two healthy infants. Interventions  Participants were randomly assigned to receive vaccination with 0.5-mL doses of 1 of 2 lots of meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or a hepatitis B control vaccine (group 3; n=62), administered with routine immunizations at 2, 3, and 4 months of age. Approximately half of each group received meningococcal C conjugate vaccine and half received plain meningococcal polysaccharide vaccine (MPS) at 12 months of age. Main Outcome Measures  Serum antibodies to meningococcal C polysaccharide, assayed by enzyme-linked immunosorbent assay, and serum bactericidal activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and systemic reactions, recorded for 6 days after each vaccination, compared by intervention group. Results  Meningococcal C conjugate vaccine was well tolerated. After 3 doses, children in groups 1 and 2 achieved significantly higher meningococcal C IgG geometric mean concentrations (21 and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and 420, respectively, vs 4.1; P<.001) than controls. At 12 months, antibody concentrations had decreased in all groups but remained significantly higher in children vaccinated with meningococcal C conjugate vaccine (SBA, 24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001). Following vaccination with MPS at 12 months of age, SBA in the meningococcal C conjugate vaccine group was significantly higher than in controls (SBA, 789 vs 4.5; P<.001). Conclusions  Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age.      

Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s

Context  Information on the school-age functioning and special health care needs of extremely low-birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services. Objective  To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls). Design, Setting, and Participants  A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio. Main Outcome Measures  Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children. Results  In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001). Conclusion  The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long-term health and educational needs.      

Risk factors for pediatric human immunodeficiency virus-related malignancy

Context  Although cancers occur with increased frequency in children with human immunodeficiency virus (HIV) infection, the specific clinical, immunological, and viral risk factors for malignancy have not been identified. Objective  To identify risk factors for malignancy among HIV-infected children. Design, Setting, and Patients  A multicenter case-control study of children with HIV at 26 institutions participating in the Pediatric Oncology Group. Forty-three case patients with a new malignancy and 74 control patients without a malignancy were matched based on the duration of their infection. Patients were enrolled between January 1992 and July 1998. Main Outcome Measures  Clinical and laboratory factors assessed as putative risk factors included demographic characteristics, HIV characteristics, prior antiretroviral treatment, and CD4 cell count. Coviral infections with Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus 6 were assessed by semiquantitative polymerase chain reaction assays and serological testing. Results  Case malignancy diagnoses included 28 non-Hodgkin lymphoma, 4 B-cell acute lymphoblastic leukemia, 1 Hodgkin disease, 8 leiomyosarcoma, 1 hepatoblastoma, and 1 schwannoma. Epstein-Barr virus viral load of more than 50 viral genome copies per 10⁵ peripheral blood mononuclear cells was strongly associated with cancer risk but only for children with CD4 cell counts of at least 200/µL (odds ratio [OR], 11.33; 95% confidence interval [CI], 2.09-65.66, P<.001). High EBV viral load was not associated with cancer for children with CD4 cell counts of less than 200/µL (OR, 1.12; 95% CI, 0.13-9.62; P = .99). Zidovudine antiretroviral therapy did not confer a significant protective effect for either the high (OR, 0.81; 95% CI, 0.22-3.09; P = .77) or the low CD4 cell count groups (OR, 0.27; 95% CI, 0.04-1.46; P = .16). The route of HIV infection was not associated with increased cancer risk. Conclusions  Route of infection, demographic characteristics, and zidovudine use were not associated with the development of malignancy in HIV-infected children. High viral burden with EBV was associated with the development of malignancy in HIV-infected children although the effect was modified by CD4 cell count. The pathogenesis of HIV-related pediatric malignancies remains unclear and other contributing risk factors can be elucidated only through further study.      

Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age

Context  Childhood asthma is strongly associated with allergic sensitization. Studies have suggested that animal exposure during infancy reduces subsequent allergic sensitization. Objective  To evaluate the relationship between dog and cat exposure in the first year of life and allergic sensitization at 6 to 7 years of age. Design, Setting, and Subjects  Prospective birth cohort study of healthy, full-term infants enrolled in a health maintenance organization in suburban Detroit, Mich, who were born between April 15, 1987, and August 31, 1989, and followed up yearly to a mean age of 6.7 years. Of 835 children initially in the study at birth, 474 (57%) completed follow-up evaluations at age 6 to 7 years. Main Outcome Measures  Atopy, defined as any skin prick test positivity to 6 common aeroallergens (dust mites [Dermatophagoides farinae, D pteronyssinus], dog, cat, short ragweed [Ambrosia artemisiifolia], and blue grass [Poa pratensis]); seroatopy, defined as any positive allergen-specific IgE test result for the same 6 allergens or for Alternaria species. Results  The prevalence of any skin prick test positivity (atopy) at age 6 to 7 years was 33.6% with no dog or cat exposure in the first year of life, 34.3% with exposure to 1 dog or cat, and 15.4% with exposure to 2 or more dogs or cats (P = .005). The prevalence of any positive allergen-specific IgE test result (seroatopy) was 38.5% with no dog or cat exposure, 41.2% with exposure to 1 dog or cat, and 17.9% with exposure to 2 or more dogs or cats (P = .003). After adjustment for cord serum IgE concentration, sex, older siblings, parental smoking, parental asthma, bedroom dust mite allergen levels at 2 years, and current dog and cat ownership, exposure to 2 or more dogs or cats in the first year of life was associated with a significantly lower risk of atopy (adjusted odds ratio, 0.23; 95% confidence interval, 0.09-0.60) and seroatopy (adjusted odds ratio, 0.33; 95% confidence interval, 0.13-0.83). Conclusion  Exposure to 2 or more dogs or cats in the first year of life may reduce subsequent risk of allergic sensitization to multiple allergens during childhood.      

Safety of trivalent inactivated influenza vaccine in children 6 to 23 months old

Context  Beginning with the winter season of 2004-2005, influenza vaccination has been recommended for all children 6 to 23 months old in the United States. However, its safety in young children has not been adequately studied in large populations. Objective  To screen for medically attended events in the clinic, emergency department, or hospital after administration of trivalent inactivated influenza vaccine in children 6 to 23 months old. Design, Setting, and Participants  Retrospective cohort using self-control analysis, with chart review of significant medically attended events at 8 managed care organizations in the United States that comprise the Vaccine Safety Datalink. Participants were all children in the Vaccine Safety Datalink cohort 6 to 23 months old who received trivalent inactivated influenza vaccine between January 1, 1991, and May 31, 2003 (45 356 children with 69 359 vaccinations). Main Outcome Measure  Any medically attended event significantly associated with trivalent inactivated influenza vaccine in risk windows 0 to 3 days, 1 to 14 days (primary analysis), 1 to 42 days, or 15 to 42 days after vaccination, compared with 2 control periods, one before vaccination and the second after the risk window. All individual ICD-9 codes as well as predefined aggregate codes were examined. Results  Before chart review, only 1 diagnosis, gastritis/duodenitis, was more likely to occur in the 14 days after trivalent inactivated influenza vaccine (matched odds ratio [OR], 5.50; 95% confidence interval [CI], 1.22-24.81 for control period 1, and matched OR, 4.33; 95% CI, 1.23-15.21 for control period 2). Thirteen medically attended events were less likely to occur after trivalent inactivated influenza vaccine, including acute upper respiratory tract infection, asthma, bronchiolitis, and otitis media. After chart review, gastritis/duodenitis was not significantly associated with trivalent inactivated influenza vaccine (matched OR, 4.00; 95% CI, 0.85-18.84 for control period 1; matched OR, 3.34; 95% CI, 0.92-12.11 for control period 2). Conclusions  In the largest population-based study to date of the safety of trivalent inactivated influenza vaccine in young children, there were very few medically attended events, none of which were serious, significantly associated with the vaccine. This study provides additional evidence supporting the safety of universally immunizing all children 6 to 23 months old with influenza vaccine.      

Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease

Context  Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. Objectives  To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. Design, Setting, and Participants  Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. Main Outcome Measures  The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. Results  The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by ² test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD. Conclusions  In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.      

Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes

Context  Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study. Objective  To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children. Design, Setting, and Participants  A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes. The mean age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. A case-cohort study (N = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (as a percentage of total lipids) was examined. Main Outcome Measure  Risk of IA, defined as being positive for insulin, glutamic acid decarboxylase, or insulinoma-associated antigen-2 autoantibodies on 2 consecutive visits and still autoantibody positive or having diabetes at last follow-up visit. Results  Fifty-eight children developed IA. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was inversely associated with risk of IA (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21-0.96; P = .04). The association was strengthened when the definition of the outcome was limited to those positive for 2 or more autoantibodies (HR, 0.23; 95% CI, 0.09-0.58; P = .002). In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was also inversely associated with IA risk (HR, 0.63; 95% CI, 0.41-0.96; P = .03). Conclusion  Dietary intake of omega-3 fatty acids is associated with reduced risk of IA in children at increased genetic risk for type 1 diabetes.      

Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials

Context  Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. Objective  To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. Data Sources and Study Selection  MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. Data Extraction  Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding). Data Synthesis  Among 51 342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44 114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). Conclusions  For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.      

Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children

Context  Widespread pneumococcal conjugate vaccination may bring about epidemiologic changes in upper respiratory tract flora of children. Of particular significance may be an interaction between Streptococcus pneumoniae and Staphylococcus aureus, in view of the recent emergence of community-acquired methicillin-resistant S aureus. Objective  To examine the prevalence and risk factors of carriage of S pneumoniae and S aureus in the prevaccination era in young children. Design, Setting, and Patients  Cross-sectional surveillance study of nasopharyngeal carriage of S pneumoniae and nasal carriage of S aureus by 790 children aged 40 months or younger seen at primary care clinics in central Israel during February 2002. Main Outcome Measures  Carriage rates of S pneumoniae (by serotype) and S aureus; risk factors associated with carriage of each pathogen. Results  Among 790 children screened, 43% carried S pneumoniae and 10% carried S aureus. Staphylococcus aureus carriage among S pneumoniae carriers was 6.5% vs 12.9% in S pneumoniae noncarriers. Streptococcus pneumoniae carriage among S aureus carriers was 27.5% vs 44.8% in S aureus noncarriers. Only 2.8% carried both pathogens concomitantly vs 4.3% expected dual carriage (P = .03). Risk factors for S pneumoniae carriage (attending day care, having young siblings, and age older than 3 months) were negatively associated with S aureus carriage. Conclusions  Streptococcus pneumoniae carriage, specifically of vaccine-type strains, is negatively associated with S aureus carriage in children. The implications of these findings in the pneumococcal vaccine era require further investigation.      

Antepartum dental radiography and infant low birth weight

Context  Both high- and low-dose radiation exposures in women have been associated with low-birth-weight offspring. It is unclear if radiation affects the hypothalamus-pituitary-thyroid axis and thereby indirectly birth weight, or if the radiation directly affects the reproductive organs. Objective  To investigate whether antepartum dental radiography is associated with low-birth-weight offspring. Design  A population-based case-control study. Participants and Setting  Enrollees of a dental insurance plan with live singleton births in Washington State between January 1993 and December 2000. Cases were 1117 women with low-birth-weight infants (<2500 g), of whom 336 were term low-birth-weight infants (1501-2499 g and gestation =" BORDER="0">37 weeks). Four control pregnancies resulting in normal-birth-weight infants (=" BORDER="0">2500 g) were randomly selected for each case (n = 4468). Main Outcome Measures  Odds of low birth weight and term low birth weight by dental radiographic dose during gestation. Results  An exposure higher than 0.4 milligray (mGy) during gestation occurred in 21 (1.9%) mothers of low-birth-weight infants and, when compared with women who had no known dental radiography, was associated with an adjusted odds ratio (OR) for a low-birth-weight infant of 2.27 (95% confidence interval [CI], 1.11-4.66, P = .03). Exposure higher than 0.4 mGy occurred in 10 (3%) term low-birth-weight pregnancies and was associated with an adjusted OR for a term low-birth-weight infant of 3.61 (95% CI, 1.46-8.92, P = .005). Conclusion  Dental radiography during pregnancy is associated with low birth weight, specifically with term low birth weight.      

Maternal and infant characteristics associated with perinatal arterial stroke in the infant

Janet Lee, MS; Lisa A. Croen, PhD; Kendall H. Backstrand, BA; Cathleen K. Yoshida, MS; Louis H. Henning, BA; Camilla Lindan, MD; Donna M. Ferriero, MD; Heather J. Fullerton, MD; A. J. Barkovich, MD; Yvonne W. Wu, MD, MPH

JAMA. 2005;293:723-729.

Context  Perinatal arterial ischemic stroke (PAS) is a common cause of hemiplegic cerebral palsy. Risk factors for this condition have not been clearly defined.

Objective  To determine maternal and infant characteristics associated with PAS.

Design, Setting, and Patients  Case-control study nested within the cohort of all 199 176 infants born from 1997 through 2002 in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were confirmed by review of brain imaging and medical records (n = 40). Three controls per case were randomly selected from the study population.

Main Outcome Measure  Association of maternal and infant complications with risk of PAS.

Results  The population prevalence of PAS was 20 per 100 000 live births. The majority (85%) of infants with PAS were delivered at term. The following prepartum and intrapartum factors were more common among case than control infants: primiparity (73% vs 44%, P = .002), fetal heart rate abnormality (46% vs 14%, P<.001), emergency cesarean delivery (35% vs 13%, P = .002), chorioamnionitis (27% vs 11%, P = .03), prolonged rupture of membranes (26% vs 7%, P = .002), prolonged second stage of labor (25% vs 4%, P<.001), vacuum extraction (24% vs 11%, P = .04), cord abnormality (22% vs 6%, P = .01), preeclampsia (19% vs 5%, P = .01), and oligohydramnios (14% vs 3%, P = .01). Risk factors independently associated with PAS on multivariate analysis were history of infertility (odds ratio [OR], 7.5; 95% confidence interval [CI], 1.3-45.0), preeclampsia (OR, 5.3; 95% CI, 1.3-22.0), prolonged rupture of membranes (OR, 3.8; 95% CI, 1.1-12.8), and chorioamnionitis (OR, 3.4; 95% CI, 1.1-10.5). The rate of PAS increased dramatically when multiple risk factors were present.

Conclusions  Perinatal arterial ischemic stroke in infants is associated with several independent maternal risk factors. How these complications, along with their potential effects on the placenta and fetus, may play a role in causing perinatal stroke deserves further study.

     

Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood

Context  Hospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown. Objective  To investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years. Design and Setting  Population-based, prospective, cohort study conducted in Sisimiut, Greenland. Participants  Two hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance. Main Outcome Measure  Risk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles. Results  A 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P<.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively. Conclusion  These data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.      

Effectiveness of Haemophilus influenzae type b Conjugate vaccine introduction into routine childhood immunization in Kenya

Context  Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001. Objective  To define invasive Hib disease incidence and Hib vaccine program effectiveness in Kenya. Design, Setting, and Patients  Culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 through 2005 was linked to demographic surveillance of 38 000 children younger than 5 years in Kilifi District, Kenya. Human immunodeficiency virus (HIV) infection and Hib vaccination status were determined for children with Hib disease admitted 2002-2005. Interventions  Introduction of conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10, and 14 weeks beginning November 2001. Main Outcome Measures  Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness. Results  Prior to vaccine introduction, the median age of children with Hib was 8 months; case fatality was 23%. Among children younger than 5 years, the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47, and 7.6 per 100 000, respectively. For children younger than 2 years, incidence was 119, 82, and 16 per 100 000, respectively. In 2004-2005, vaccine effectiveness was 88% (95% confidence interval, 73%-96%) among children younger than 5 years and 87% (95% confidence interval, 66%-96%) among children younger than 2 years. Of 53 children with Hib admitted during 2002-2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received 2 or more doses of vaccine (2 were HIV positive). Conclusions  In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children younger than 5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction.      

Risk factors for parvovirus B19 infection in pregnancy

Context  Parvovirus B19 infection during pregnancy has been associated with fetal death. However, the incidence of and risk factors for infection in pregnant women have not been well studied. Objectives  To estimate a pregnant woman's risk of infection with parvovirus B19 in epidemic and endemic situations and to study risk factors for infection. Design  Population-based cohort study conducted between November 1992 and June 1994. Setting  Three regions in Denmark. Participants  A total of 30,946 pregnant women from a consecutive and population-based screening. Main Outcome Measures  Specific IgG antibodies in serum samples obtained in the first trimester of pregnancy and from the newborn infant to assess past infection and seroconversion. Information on family structure, educational background, socioeconomic status, and pregnancy outcome was obtained from national registers. Results  Based on 30,946 serum samples, 65.0% of pregnant women had evidence of past infection. Annual seroconversion rates among susceptible women during endemic and epidemic periods were 1.5% (95% confidence interval [CI], 0.2%-1.9%) and 13.0% (95% CI, 8.7%-23.1%), respectively. Baseline seropositivity was significantly correlated with increasing number of siblings, having a sibling of the same age, number of own children, and occupational exposure to children. Risk of acute infection increased with the number of children in the household as follows: 0 children odds ratio (OR), 1 (reference); 1 child OR, 3.17 (95% CI, 2.24-4.49); 2 children OR, 5.47 (95% CI, 3.55-8.45); 3 or more children OR, 7.54 (95% CI, 3.80-14.94). Having children aged 6 to 7 years resulted in the highest rate of seroconversion among mothers (6.8%; OR, 4.07; 95% CI, 1.89-8.73). Compared with other pregnant women, nursery school teachers had a 3-fold increased risk of acute infection (OR, 3.09; 95% CI, 1.62-5.89). Population-attributable risk of seroconversion was 55.4% for number of own children and 6.0% for occupational exposure. Conclusions  The risk of infection is high for susceptible pregnant women during epidemics and associated with the level of contact with children. Nursery school teachers have the highest occupational risk, but most infections seem to be the result of exposure to the woman's own children.      

Cognitive outcomes of preschool children with prenatal cocaine exposure

Context  Because of methodological limitations, the results of the few prospective studies assessing long-term cognitive effects of prenatal cocaine exposure are inconsistent. Objective  To assess effects of prenatal cocaine exposure and quality of caregiving environment on 4-year cognitive outcomes. Design  Longitudinal, prospective, masked comparison cohort study from birth (September 1994-June 1996) to 4 years. Setting  Research laboratory of a US urban county teaching hospital. Participants  A total of 415 consecutively enrolled infants identified from a high-risk population screened for drug use through clinical interview, urine, and meconium screens. Ninety-three percent retention for surviving participants at 4 years of age resulted in 376 children (190 cocaine-exposed and 186 nonexposed). Main Outcome Measure  The Wechsler Preschool and Primary Scales of Intelligence-Revised. Results  After control for covariates, prenatal cocaine exposure was not related to lower full-scale IQ (cocaine exposed [80.7] vs nonexposed [82.9]; P = .09) scores or summary verbal (cocaine exposed [79.9] vs nonexposed [81.9]; P = .11) or performance (cocaine exposed [85.5] vs nonexposed [87.5]; P = .18) IQ scores at age 4 years. However, prenatal cocaine exposure was related to small but significant deficits on several subscales (mean [SE]): visual-spatial skills (cocaine exposed [7.3 (0.22)] vs nonexposed [8.2 (0.22)]; P = .01), general knowledge (cocaine exposed [6.1 (0.18)] vs nonexposed [6.7 (0.17)]; P = .04), and arithmetic skills (cocaine exposed [6.2 (0.20)] vs nonexposed [6.8 (0.20)]; P = .05). Prenatal cocaine exposure was also associated with a lower likelihood of achievement of IQ above normative means (odds ratio, 0.26 [95% confidence interval, 0.10-0.65]; P = .004). The quality of the caregiving environment was the strongest independent predictor of outcomes. Cocaine-exposed children placed in nonrelative foster or adoptive care lived in homes with more stimulating environments and had caregivers with better vocabulary scores, and they attained full-scale and performance IQ scores (83 and 87, respectively) similar to nonexposed children in biological maternal or relative care (full-scale IQ, 82; performance IQ, 88) and higher than cocaine-exposed children in biological maternal or relative care (full-scale IQ, 79; performance IQ, 84). Conclusions  Prenatal cocaine exposure was not associated with lower full-scale, verbal, or performance IQ scores but was associated with an increased risk for specific cognitive impairments and lower likelihood of IQ above the normative mean at 4 years. A better home environment was associated with IQ scores for cocaine-exposed children that are similar to scores in nonexposed children.