Jacob Krabbe Pedersen

Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study.

BACKGROUND Although animal studies have indicated that general anesthetics may result in widespread apoptotic neurodegeneration and neurocognitive impairment in the developing brain, results from human studies are scarce. We investigated the association between exposure to surgery and anesthesia for inguinal hernia repair in infancy and subsequent academic performance. METHODS Using Danish birth cohorts from 1986-1990, we compared the academic performance of all children who had undergone inguinal hernia repair in infancy to a randomly selected, age-matched 5% population sample. Primary analysis compared average test scores at ninth grade adjusting for sex, birth weight, and paternal and maternal age and education. Secondary analysis compared the proportions of children not attaining test scores between the two groups. RESULTS From 1986-1990 in Denmark, 2,689 children underwent inguinal hernia repair in infancy. A randomly selected, age-matched 5% population sample consists of 14,575 individuals. Although the exposure group performed worse than the control group (average score 0.26 lower; 95% CI, 0.21-0.31), after adjusting for known confounders, no statistically significant difference (-0.04; 95% CI, -0.09 to 0.01) between the exposure and control groups could be demonstrated. However, the odds ratio for test score nonattainment associated with inguinal hernia repair was 1.18 (95% CI, 1.04-1.35). Excluding from analyses children with other congenital malformations, the difference in mean test scores remained nearly unchanged (0.05; 95% CI, 0.00-0.11). In addition, the increased proportion of test score nonattainment within the exposure group was attenuated (odds ratio = 1.13; 95% CI, 0.98-1.31). CONCLUSION In the ethnically and socioeconomically homogeneous Danish population, we found no evidence that a single, relatively brief anesthetic exposure in connection with hernia repair in infancy reduced academic performance at age 15 or 16 yr after adjusting for known confounding factors. However, the higher test score nonattainment rate among the hernia group could suggest that a subgroup of these children are developmentally disadvantaged compared with the background population.

Educational outcome in adolescence following pyloric stenosis repair before 3 months of age: a nationwide cohort study

Immature animals exposed to anesthetics display apoptotic neurodegeneration with subsequent long‐term cognitive dysfunctions. Young age at anesthetic exposure is believed to be critical, but human studies are scarce. This study investigated the association between exposure to surgery and anesthesia for pyloric stenosis (PS) before 3 months of age and subsequent educational outcome in adolescence.

Risk of Oral Clefts in twins

Background: Small studies have indicated that twinning increases the risk of oral cleft. Methods: We used data from a Danish national population-based cohort study to investigate whether twinning was associated with isolated oral cleft, and to estimate the twin probandwise concordance rate and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion ratio for twins versus singletons, stratified for 3 subphenotypes. Probandwise concordance rates and heritability for twins were estimated for 2 phenotypes—cleft lip with or without cleft palate (CL/P) and cleft palate (CP). Results: The prevalence of oral cleft was 15.8 per 10,000 twins and 16.6 per 10,000 singletons (prevalence proportion ratio = 0.95; 95% confidence interval = 0.83–1.1). This prevalence was similar for monozygotic and dizygotic twins. The probandwise concordance rate was higher for CL/P for monozygotic twins than for dizygotic twins (50% vs. 8%, respectively). A similar contrast was present for CP. Recurrence risk for both types of clefts was greater in dizygotic twins than in non-twin siblings. Heritability estimates were above 90% for both CL/P and CP. Conclusions: No excess risk of oral cleft could be demonstrated for twins compared with singletons. The concordance rates and heritability estimates for both types of clefts show a strong genetic component.

Heritability and Familial Aggregation of Diverticular Disease: A Population-Based Study of Twins and Siblings

BACKGROUND & AIMS Little is known about the role of heritable factors in diverticular disease. We evaluated the contribution of heritable factors to the development of diverticular disease diagnosed at a hospitalization or outpatient visit. METHODS Using nationwide patient registries, we identified 142,123 incident cases of diverticular disease diagnosed at a hospitalization (1977-2011) or an outpatient hospital visit (1995-2011) in Denmark, including cases in 10,420 index siblings and 923 twins. We calculated standardized incidence ratios for siblings versus the general population and concordance rates for monozygotic versus dizygotic twin pairs as measures of relative risk (RR). RESULTS The RR for diverticular disease in siblings of index cases was 2.92 (95% confidence interval [CI], 2.50-3.39) compared with the general population. The RRs were similar irrespective of the sex of the sibling or index case and were particularly strong in siblings of hospitalized cases and cases that underwent surgery. The proband-wise concordance rate for monozygotic twins was double that of dizygotic twins (0.16 [95% CI, 0.11-0.22] vs 0.07 [95% CI, 0.05-0.11], respectively). The RR of diverticular disease in one twin when the other had diverticular disease was 14.5 (95% CI, 8.9-23) for monozygotic twins compared with 5.5 (95% CI, 3.3-8.6) for dizygotic twins. Associations were stronger in female monozygotic twins compared with male twins (tetrachoric correlation, 0.60 [95% CI, 0.49-0.70] vs 0.33 [95% CI, 0.13-0.51]; P = .03 in an analysis stratified by sex and zygosity). We estimate that 53% (95% CI, 45%-61%) of susceptibility to diverticular disease results from genetic factors. CONCLUSIONS Based on a population-based study in Denmark, genetic factors appear to contribute to development of diverticular disease.

Influence of Host Genetics and Environment on Nasal Carriage of Staphylococcus aureus in Danish Middle-Aged and Elderly Twins

Background. Nasal carriage is a major risk factor for Staphylococcus aureus infection. Approximately, one-quarter of adults carry S. aureus. However, the role of host genetics on S. aureus nasal carriage is unknown. Methods. Nasal swabs were obtained from a national cohort of middle-aged and elderly Danish twins. Subjects colonized with S. aureus were identified by growth on selective plates and spa typing. A second sample was obtained from twins initially concordant for carriage. Twins found to again be colonized with S. aureus were defined as persistent carriers. Results. The prevalence of S. aureus carriage among 617 twin pairs (monozygotic/dizygotic pairs: 112/505) was 26.3% (95% confidence interval [CI], 24.0%–28.9%). The concordance rate for carriage did not differ significantly between pairs of monozygotic (37.5%; 95% CI, 22.3%–53.8%) twins and same sex (24.2%; 95% CI, 15.4%–34.5%), and opposite sex (21.4%; 95% CI, 12.0%–33.4%) dizygotic twins. Despite shared childhoods, only 1 of 617 pairs was concordant with respect to lineage. Although heritability increased for S. aureus and lineage persistency, no significant heritability was detected. Conclusion. In this study, host genetic factors exhibited only a modest influence on the S. aureus carrier state of middle-aged and elderly individuals.

Recurrence risk for offspring of twins discordant for oral cleft: a population-based cohort study of the Danish 1936-2004 cleft twin cohort.

Our objective in this Danish population‐based cohort study was to estimate the recurrence risk of isolated oral cleft (OC) for offspring of the unaffected co‐twins of OC discordant twin pairs and to compare this risk to the recurrence risk in the offspring of the affected co‐twin as well as to the risk in the background population. During 1936–2004, 207 twin pairs were ascertained, among whom at least one twin had an OC. The index persons were twins discordant for OC who had children (N = 117), and their offspring (N = 239). The participants were ascertained by linkage between The Danish Facial Cleft Database, The Danish Twin Registry and The Danish Civil Registration System. In the study OC recurrence risk for offspring of the affected and unaffected twin and relative risk were compared to the background prevalence. We found that among 110 children of the 54 OC affected twins, two (1.8%) children had OC corresponding to a significantly increased relative risk (RR = 10; 95% CI 1.2–35) when compared to the frequency in the background population. Among the 129 children of the 63 unaffected twins, three (2.3%) children were affected, corresponding to a significantly increased relative risk (RR = 13; 95% CI 2.6–36) when compared the background prevalence. We concluded that in OC discordant twin pairs similar increased recurrence risks were found among offspring of both OC affected and OC unaffected twins. This provides further evidence for a genetic component in cleft etiology and is useful information for genetic counseling of twin pairs discordant for clefting.

Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes

Objective. Glutathione peroxidase 1 (GPX1) is one of the major oxidative enzymes. Our aim was to characterize factors influencing its activity and to determine whether or not the activity is associated with asthma. Material and methods. Serum selenium concentration was measured, GPX1 polymorphisms were genotyped and smoking history was obtained in a Danish population‐derived case‐base cohort of 1,191 subjects designed to evaluate risk factors for asthma. GPX1 activity was measured in 134 male and 164 female subjects equally distributed according to genotype of GPX1. Among these subjects, 82 (28 %) had doctor‐diagnosed asthma. Results. The average serum selenium concentration was too low for optimal enzyme activity (mean (SE), 83.4 (0.76) ng/mL). GPX1 activity in men was lower than in women, 52.6 (0.66) and 56.4 (0.59) U/g protein, respectively (p<0.001). In men, activity was positively associated with serum selenium concentration (p = 0.005) and negatively associated with both active smoking (p = 0.009) and exposure to environmental tobacco smoke (p = 0.02). In women, activity was associated with genotypes with 59.2 (1.4), 56.0 (1.4) and 54.2 (1.4) U/g protein in the homozygote wild‐type, the heterozygote and the homozygote variant type, respectively (p = 0.001). Doctor‐diagnosed asthma was unrelated to GPX1 activity in either sex. Conclusion. Determinants for activity in the oxidative enzyme GPX1 show marked differences between the sexes, but the activity is not associated with asthma. Sex ought to be taken into consideration when analysing the activity of the enzyme.

Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: A nationwide cohort study

Few human cohort studies on anesthesia‐related neurotoxicity and the developing brain have focused on and compared specific surgeries and conditions. These studies cannot disentangle the effects of anesthesia from those of the surgery and underlying conditions. This study aimed at assessing the impact of specific neurosurgical conditions and procedures in infancy on mortality and academic achievements in adolescence.

Oral Clefts and Academic Performance in Adolescence: The Impact of Anesthesia-Related Neurotoxicity, Timing of Surgery, and Type of Oral Clefts

Objective Early life exposure to anesthesia and surgery is suspected to associate with cognitive impairment later in life. We compared academic achievement among adolescents with cleft lip only (CL), cleft palate only (CP), and cleft lip and cleft palate (CLP) with a noncleft control group to investigate whether outcome depends on timing and number of operations during childhood and/or type of oral cleft. Design Nationwide register-based follow-up study. Setting Danish birth cohort 1986 to 1990. Participants Five hundred fifty-eight children with isolated CL (n = 171), CLP (n =222), or CP (n = 195), of which 509 children had been exposed to anesthesia and one or more cleft operation(s), and a 5% sample of the birth cohort (n = 14,677). Main Outcome Measure(s) Test score in the Danish standardized ninth-grade exam and proportion of nonattainment, defined as “results for ninth-grade exam unavailable.” Data adjusted for sex, birth weight, parental age, and parental level of education. Results Compared to controls, children with CL achieved higher scores (mean difference 0.12, 95% CI –0.05; 0.29) and children with CLP presented with lower scores (mean difference –0.06, 95% CI –0.21; 0.09), albeit both statistically insignificant. Children with CP achieved significantly lower scores, mean difference –0.20 (95% CI –0.38; –0.03). Odds ratios for nonattainment at final exam were: CL 0.79 (95% CI 0.46; 1.35), CLP 1.07 (95% CI 0.71; 1.61), CP 2.59 (95% CI 1.78; 3.76). Conclusions Oral cleft type rather than number and timing of anesthesia and operations associate to poorer academic performance. Although a potential neurotoxic effect due to anesthetic agents is not reflected in the data, it cannot be completely excluded.

Cancer and Longevity—Is There a Trade-off? A Study of Cooccurrence in Danish Twin Pairs Born 1900–1918

BACKGROUND Animal models and a few human studies have suggested a complex interaction between cancer risk and longevity indicating a trade-off where low cancer risk is associated with accelerating aging phenotypes and, vice versa, that longevity potential comes with the cost of increased cancer risk. This hypothesis predicts that longevity in one twin is associated with increased cancer risk in the cotwin. METHODS A total of 4,354 twin pairs born 1900-1918 in Denmark were followed for mortality in the Danish Civil Registration System through 2008 and for cancer incidence in the period 1943-2008 through the Danish Cancer Registry. RESULTS The 8,139 twins who provided risk time for cancer occurrence entered the study between ages 24 and 43 (mean 33 years), and each participant was followed up to death, emigration, or at least 90 years of age. The total follow-up time was 353,410 person-years and, 2,524 cancers were diagnosed. A negative association between age at death of a twin and cancer incidence in the cotwin was found in the overall analyses as well as in the subanalysis stratified on sex, zygosity, and random selection of one twin from each twin pair. CONCLUSIONS This study did not find evidence of a cancer-longevity trade-off in humans. On the contrary, it suggested that longevity in one twin is associated with lower cancer incidence in the cotwin, indicating familial factors associated with both low cancer occurrence and longevity.