Neonatal sepsis, antibiotic therapy and later risk of asthma and allergy.

Neonatal sepsis and early antibiotic therapy affect bacterial colonisation and immune activation after birth. This could have implications for later risk of allergy and asthma. Using a validated questionnaire (International Study of Asthma and Allergies in Children, ISAAC), we screened for asthma and allergy in three cohorts (total n = 834; median age 12, range 7-23 years) with different perinatal exposures as regards infection and antibiotics. Asthma, but not hay fever, was more prevalent after neonatal sepsis with adjusted odds ratio (OR) 1.63 [95% confidence interval (CI) 1.04, 2.56] and early antibiotic therapy (OR 1.48 [0.93, 2.35]) as compared with a control group. There was a trend towards increased atopic eczema after neonatal sepsis (OR = 1.39 [CI = 0.98, 1.98]). We conclude that neonatal sepsis is associated with an increased risk for later development of asthma. Early antibiotic exposure may contribute to this association.

Transmission-dependent tolerance to multiclonal Plasmodium falciparum infection.

Whether the number of concurrent clones in asymptomatic Plasmodium falciparum infections reflects the degree of host protection was investigated in children living in areas with different levels of transmission on the coast of Kenya. The number of concurrent clones was determined on the basis of polymorphism in msp2, which encodes the vaccine candidate antigen merozoite surface protein 2. In a low-transmission area, most children had monoclonal infections, and diversity did not predict a risk of clinical malaria. In an area of moderate transmission, asymptomatic infections with 2 clones were, compared with 1 clone, associated with an increased risk of subsequent malaria. In a comparative assessment in a high-transmission area in Tanzania, multiclonal infections conferred a reduced risk. The different nonlinear associations between the number of clones and malaria morbidity suggest that levels of tolerance to multiclonal infections are transmission dependent as a result of cumulative exposure to antigenically diverse P. falciparum infections.

Decreasing incidence of tibial shaft fractures between 1998 and 2004: information based on 10,627 Swedish inpatients.

BACKGROUND AND PURPOSE: There is a lack of national epidemiological data on the characteristics of patients with tibial shaft fractures. We therefore analyzed data on Swedish patients with tibial shaft fractures in this nationwide population study based on data from 1998 through 2004. METHODS: Data on all patients with tibial shaft fractures were extracted from the Swedish National Hospital Discharge Register. RESULTS: We identified 10,627 hospital admissions for tibial shaft fractures, corresponding to an annual incidence rate of 17 per 100,000 person-years (pyr). The number of hospital admissions decreased by 12% during the period 1998-2004, mostly from a reduction in male incidence. The median (SD) age at admission was 28 (22) years for men and 51 (26) years for women. The two major mechanisms of injury were falls on the same level (48%) and transport accidents (21%). Surgical procedures were dominated by osteosynthesis with nail (48%), followed by closed reduction and plaster cast (27%), and external fixation (12%). 12% of all tibial shaft fractures were classified as open, corresponding to an incidence rate of 2.3 per 100,000 pyr, which declined during 1998-2004. INTERPRETATION: This nationwide study of tibial shaft fractures shows a falling off of fracture incidence, a finding that can be used to advantage by healthcare providers.

Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. METHODS: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. RESULTS: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). CONCLUSIONS: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

Paternal smoking is associated with a decreased prevalence of type 1 diabetes mellitus among offspring in two national British birth cohort studies (NCDS and BCS70).

AIMS: An association between paternal age and type 1 diabetes (IDDM) among their offspring was recently reported as well as transgenerational responses in humans. This paper aims to assess the association of markers for prenatal exposures with IDDM. METHODS: We analysed data from two birth cohorts in Great Britain on 5214 cohort members from the National Child Development Study (NCDS) and 6068 members of the 1970 British Birth Cohort Study (BCS70) with full information on IDDM and explanatory variables using multivariate logistic regression. RESULTS: IDDM prevalence was 0.7% (95% CI 0.5-1.0%; n=38) in the NCDS and 0.4% (95% CI 0.3-0.6%; n=27) in the BCS70 cohort. Paternal age was not associated with IDDM possibly due to lack of sample power. Unexpectedly, a lowered prevalence of IDDM was observed among offspring of smoking fathers in both cohorts, with a combined odds ratio of 0.44 (95% CI 0.25-0.75). This association could not be explained by maternal smoking prior to, during or after pregnancy, number of siblings, parental social class, maternal and paternal age, or cohort. Maternal smoking in pregnancy did not alter the IDDM prevalence among offspring. CONCLUSIONS: This unexpected finding may be explained by germ-line mutations or other mechanisms associated with paternal smoking. This phenomenon should be investigated and these results should not be used as a justification for smoking. Paternal exposures may be important in determining IDDM risk.

Does height modify the risk of angina associated with economic adversity?

Adult height partly reflects childhood exposures, and we hypothesise that some exposures impairing growth may also increase susceptibility to coronary heart disease--angina pectoris (angina)--risks, such that shorter adults may be more susceptible to some exposures in adulthood that are risks for heart disease. This hypothesis is tested among all adults who participated in the National Health Interview Survey (USA), 1997-2000 [The National Health Survey, 1997-2000. Data file documentation, National Health Interview Survey (machine-readable data file and documentation). National Center for Health Statistics, Hyattsville, Maryland, ]. In the entire study population, height was negatively associated with angina and after adjustment for potential confounding factors; the odds ratio (and 95% confidence interval) for angina risk associated with the tallest height fifth compared with the shortest fifth is 0.77 (0.97, 0.88). The association of low income (less than US 20,000 dollars) with angina was assessed separately in each of five height strata defined by fifths of the height distribution. The magnitude of this association is lower in the shortest than the tallest height fifth, with odds ratios of 1.18 and 1.60, respectively (effect modification). The unexpected results may be explained by the following: childhood adversity resulting in shorter stature may confer resilience against adult economic adversity; the relative disadvantage of low income may be perceived more keenly by those of taller stature thereby increasing stress and thus disease risk; or health-promoting characteristics associated with taller stature may be less effective in the face of adult economic adversity in the low-income group.

Smoking during pregnancy and bulimia nervosa in offspring.

Because smoking during pregnancy is implicated in influencing appetite and impulse control in offspring, the aim of this study was to establish if it is associated with bulimia nervosa in offspring. Bulimia was identified at age 30 years among 4046 females, born 5-11 April, 1970. After adjustment for potential confounding factors including body mass index (BMI) and maternal psychiatric morbidity, smoking during pregnancy was associated with bulimia in offspring by age 30 years. Compared with non-smoking mothers, the adjusted odds ratios (95% confidence intervals) for bulimia in offspring were 0.74 (0.25-2.21) for those who gave up before pregnancy, 3.04 (1.16-7.95) for giving up during pregnancy and 2.64 (1.47-4.74) for smoking throughout pregnancy. Smoking during pregnancy was not associated with anorexia nervosa in offspring. Neither BMI nor variation between childhood and adult BMI explain the association. If the association of smoking during pregnancy with bulimia in offspring is causal, then it may operate through compromised central nervous system development and its influence on impulse or appetite control. The increased risk associated with mothers who gave up smoking during pregnancy emphasizes the importance of smoking cessation prior to conception.

Germ-cell testicular cancer in offspring of Finnish immigrants to Sweden.

Variation in testicular cancer incidence can be used to assist in identification of risks. Finland has a significantly lower germ-cell testicular cancer risk than Sweden. Finns who immigrate to Sweden maintain their lower risk irrespective of age at immigration. We investigated difference in risk between Finland and Sweden by examining germ-cell testicular cancer incidence in males born in Sweden to Finnish immigrant parents. Swedish general population registers were used to identify 11,662 males born in Sweden where both Finnish parents immigrated to Sweden from Finland from 1969 or afterward. All of these offspring were at least 15 years old by final follow-up in 2001. Some six offspring (all diagnosed between ages 20 and 24 years) had a diagnosis of germ-cell testicular cancer. Comparison with the Swedish population rate produced standardized incidence ratios [SIR (95% confidence interval)] of 0.85 (0.31-1.84) for all the men and 1.75 (0.64-3.81) for the 20- to 24-year age group. SIRs calculated using the Finnish population rates produced an overall SIR (95% confidence interval) of 1.11 (0.41-2.41) and 2.95 (1.08-6.42) for the 20- to 24-year age group. Although the substantially reduced risk of testicular cancer previously observed in Finnish immigrant to Sweden was not found, this study had insufficient statistical power to conclude that environmental exposures explain the difference in germ-cell testicular cancer risk between Finland and Sweden.

Number of siblings and risk of Hodgkin's lymphoma.

BACKGROUND: Epidemiologic evidence indicates that risk of Hodgkin's lymphoma (HL) in young adults is associated with correlates of delayed exposure to infection during childhood. In contrast, HL among children and older adults may be associated with earlier childhood infection. This study examines the associations of HL risk with having older or younger siblings. METHODS: We conducted a case-control study in Sweden comparing 2,140 HL patients identified from the Swedish Cancer Register with 10,024 controls identified from national population registers. The Swedish Multi-Generation Register was used to link individuals to their parents and siblings. RESULTS: Among young adults ages 15 to 39 years, the odds ratios (OR) associated with having one, two, and three or more older siblings, compared with none, were 0.96 [95% confidence interval (CI), 0.82-1.13], 0.88 (95% CI, 0.72-1.09), and 0.72 (95% CI, 0.55-0.93), respectively (P value for trend = 0.01). In contrast, number of older siblings was not associated with HL risk among children or older adults. Number of younger or total siblings, mother's age at birth, and father's occupation were not associated with HL at any age. The decreased risk of young-adult HL did not vary appreciably by age difference or sex of older siblings. CONCLUSIONS: Risk of HL was lower among young adults with multiple older but not younger siblings. Having older siblings is associated with earlier exposure to common childhood pathogens. Pediatric and older-adult HL were not associated with number of siblings, suggesting a different pathogenesis of disease in these age groups.

Maternal smoking during pregnancy and appetite control in offspring.

AIMS: Intrauterine exposure to tobacco smoke products has been associated with long-term neurobehavioral effects. Modified appetite control might explain the recently observed association between maternal smoking during pregnancy and obesity in offspring. METHODS: Some 10,557 British adults aged 42 years born between 3-9 March 1958 were followed up in a birth cohort study (NCDS). The main outcome measure was self-reported poor appetite at age 42 years and main exposure was maternal smoking during pregnancy. RESULTS: The proportion of offspring with poor appetite increased with maternal smoking during pregnancy: non-smoking 4.5%; (4.0%-5.0%), medium smoking 5.6%; (4.5%-6.8%), variable smoking 6.8%; (4.9%-9.1%) and heavy smoking 7.7%; (6.3%-9.4%). The unadjusted odds ratios for maternal smoking during pregnancy (ever/never) and poor appetite is 1.49 (1.25-1.77) and after adjustment for BMI at 42 years and other potential confounding factors it is 1.22 (1.01-1.48). CONCLUSIONS: Offspring of mothers who smoked during pregnancy were more likely to report a poor appetite independent of a number of potential confounding factors. Although not in the expected direction, the results suggest maternal smoking during pregnancy may influence appetite perception through a developmental influence or through confounding by social factors.