The prevalence of gastroschisis in Norway, as reported to the Medical Birth Registry of Norway, increased regularly and sixfold from 0.5 to 2.9 per 10,000 births during 1967-1998. The prevalence was also consistently higher among children of younger mothers. The authors used age-period-cohort analysis to assess effects of both parents' age and year of birth (parental cohorts). Mother's and father's age were included in three different regression models. Apart from a significantly higher risk at a young maternal age, the authors also found higher risk at a young paternal age (1.6-fold per 10 years' reduction in father's age, 95% confidence interval: 1.0, 2.4). The time trend was highly significant regardless of whether it was ascribed to period, mother's year of birth, or father's year of birth. However, when father's year of birth was used to describe the time trend, no apparent additional effect of father's age was found, only for mother's age. The time trend is likely caused by environmental factors. Persistently increasing risks among children of young mothers may hypothetically be related to lifestyle factors. A contribution to risk also from fathers born in more recent years or from young fathers increases the likelihood that a factor related to modern lifestyles of young couples may be related to risk.

Objective: The serum 25-hydroxyvitamin D (25(OH)D) level is not only dependent on vitamin D intake and production in the skin but also dependent on genetic factors. Thus, in large genome-wide association studies, it has been shown that single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), as well as in enzymes related to activation or degradation of vitamin D and its metabolites, are as important for the serum 25(OH)D level as the effect of season. How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain. Design and methods: Data were pooled from three randomized controlled trials where 40 000 IU vitamin D/week was given for 6 months. Serum 25(OH)D was measured before and at the end of the intervention, and the subjects were genotyped for SNPs related to the serum 25(OH)D level. Results: Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2R1 genes. Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase (delta) after supplementation. Those with the lowest baseline serum 25(OH)D (without regard to genotypes) had the highest increase (delta) after supplementation. Subjects with high BMI had lowest baseline 25(OH)D levels and also the smallest increase (delta) after supplementation. Conclusions: The serum 25(OH)D response to supplementation depends on genes, baseline level, and BMI. However, whether this is clinically important or not depends on the therapeutic window of vitamin D, an issue that is still not settled.

Objective: The objective was to assess the amount of vitamin D 3 stored in adipose tissue after long-term supplementation with high dose vitamin D 3 . Design: A cross-sectional study on 29 subjects with impaired glucose tolerance who had participated in a randomized controlled trial with vitamin D 3 20 000 IU (500 mg) per week vs placebo for 3-5 years.

Vitamin D and 25(OH)D stored in adipose tissue after 3 to 5 years of vitamin D supplementation may have a clinically relevant effect on serum 25(OH)D level the following year.

Objectives: To compare the effectiveness of adalimumab monotherapy and adalimumab and methotrexate (MTX) combination therapy in patients with established rheumatoid arthritis. Methods: Data from an ongoing longitudinal observational study in Norway were used to compare response to treatment with two different adalimumab regimens (monotherapy, n = 84; combination with MTX, n = 99). Patients were assessed with measures of disease activity, health status and utility scores. Within-group changes were analysed from baseline to follow-up at 3 and 6 months and the changes were compared between groups after adjustment for the propensity score. The groups were also compared for the proportions of patients achieving European League Against Rheumatism (EULAR) good response, Disease Activity Score (DAS)28 remission and treatment terminations. Results: The improvement from baseline was significant for all measures in the adalimumab and MTX group, but only for DAS28, joint counts, two Short-form Health Survey with 36 questions (SF-36) dimensions and patient's and investigator's global assessment in the monotherapy group. All betweengroup differences were numerically in favour of combination therapy and significant for C reactive protein, joint counts, DAS28, Modified Health Assessment Questionnaire, investigator's global assessment, four SF-36 dimensions and Short Form 6D at 6 months. More patients in the combination therapy group reached EULAR good response (p,0.001) and remission (p = 0.07). At 6 months, 80.8% of the patients in the combination therapy group and 59.5% in the monotherapy group remained on treatment (p = 0.002). More withdrawals in the monotherapy group were due to adverse events. Conclusions: Our results were consistent across several categories of end points and suggest that adalimumab combined with MTX is effective in patients with rheumatoid arthritis treated in daily clinical practice and is superior to adalimumab monotherapy.