Maternal Use of Antibiotics, Hospitalisation for Infection during Pregnancy, and Risk of Childhood Epilepsy: A Population-Based Cohort Study

BACKGROUND: Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection. METHODOLOGY/PRINCIPAL FINDINGS: To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived ≥29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191,383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100,000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22-1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count. CONCLUSIONS/SIGNIFICANCE: Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs

Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

Background: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. Methods: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. Results: Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. Conclusion: Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele

Multigene phylogeny of the Mustelidae: Resolving relationships, tempo and biogeographic history of a mammalian adaptive radiation

<p>Abstract</p> <p>Background</p> <p>Adaptive radiation, the evolution of ecological and phenotypic diversity from a common ancestor, is a central concept in evolutionary biology and characterizes the evolutionary histories of many groups of organisms. One such group is the Mustelidae, the most species-rich family within the mammalian order Carnivora, encompassing 59 species classified into 22 genera. Extant mustelids display extensive ecomorphological diversity, with different lineages having evolved into an array of adaptive zones, from fossorial badgers to semi-aquatic otters. Mustelids are also widely distributed, with multiple genera found on different continents. As with other groups that have undergone adaptive radiation, resolving the phylogenetic history of mustelids presents a number of challenges because ecomorphological convergence may potentially confound morphologically based phylogenetic inferences, and because adaptive radiations often include one or more periods of rapid cladogenesis that require a large amount of data to resolve.</p> <p>Results</p> <p>We constructed a nearly complete generic-level phylogeny of the Mustelidae using a data matrix comprising 22 gene segments (~12,000 base pairs) analyzed with maximum parsimony, maximum likelihood and Bayesian inference methods. We show that mustelids are consistently resolved with high nodal support into four major clades and three monotypic lineages. Using Bayesian dating techniques, we provide evidence that mustelids underwent two bursts of diversification that coincide with major paleoenvironmental and biotic changes that occurred during the Neogene and correspond with similar bursts of cladogenesis in other vertebrate groups. Biogeographical analyses indicate that most of the extant diversity of mustelids originated in Eurasia and mustelids have colonized Africa, North America and South America on multiple occasions.</p> <p>Conclusion</p> <p>Combined with information from the fossil record, our phylogenetic and dating analyses suggest that mustelid diversification may have been spurred by a combination of faunal turnover events and diversification at lower trophic levels, ultimately caused by climatically driven environmental changes. Our biogeographic analyses show Eurasia as the center of origin of mustelid diversity and that mustelids in Africa, North America and South America have been assembled over time largely via dispersal, which has important implications for understanding the ecology of mustelid communities.</p

Tubular diskectomy vs conventional microdiskectomy for the treatment of lumbar disk herniation: 2-Year results of a double-blind randomized controlled trial

BACKGROUND: Transmuscular tubular diskectomy has been introduced to increase the rate of recovery, although evidence is lacking. OBJECTIVE: To evaluate the 2-year results of tubular diskectomy compared with conventional microdiskectomy. METHODS: Three hundred twenty-eight patients with persistent leg pain caused by lumbar disk herniation were randomly assigned to undergo tubular diskectomy (167 patients) or conventional microdiskectomy (161 patients). Main outcome measures were scores from Roland-Morris Disability Questionnaire for Sciatica, Visual Analog Scale for leg pain and low-back pain, and Likert self-rating scale of global perceived recovery. RESULTS: On the basis of intention-to-treat analysis, there was no significant difference between tubular diskectomy and conventional microdiskectomy in Roland-Morris Disability Questionnaire for Sciatica scores during 2 years after surgery (between-group mean difference [Δ] = 0.6; 95% confidence interval [CI], -0.3-1.6). Patients treated with tubular diskectomy reported more leg pain (Δ = 3.3 mm; 95% CI, 0.2-6.2) and more low-back pain (Δ = 3.0 mm; 95% CI, -0.2-6.3) than those patients treated with conventional microdiskectomy. At 2 years, 71% of patients assigned to tubular diskectomy documented a good recovery vs 77% of patients assigned to conventional microdiskectomy (odds ratio, 0.76; 95% CI, 0.45-1.28; P = .35). Repeated surgery rates within 2 years after tubular diskectomy and conventional microdiskectomy were 15% and 10%, respectively (P = .22). CONCLUSION: Tubular diskectomy and conventional microdiskectomy resulted in similar functional and clinical outcomes. Patients treated with tubular diskectomy reported more leg pain and low-back pain, although the differences were small and not clinically relevant