Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients.

Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist. Seasonal variations of 25-(OH)-D serum concentrations were modelled by sinusoidal regression and seasonal variability in the prevalence of relapse by cubic regression. The mean 25-(OH)-D serum concentration was 24.8ng/ml (range 8.3-140ng/ml) with peak levels of 32.2ng/ml in July/August and nadir in January/February (17.2ng/ml). The lowest modelled prevalence of relapse was in September/October (28%) and the highest modelled prevalence in March/April (47%). The nadir of 25-(OH)-D serum concentrations preceded the peak in prevalence of relapses by two months. In summary, seasonal variation of 25-(OH)-D serum levels were inversely associated with clinical disease activity in MS patients. Future studies should investigate whether vitamin D supplementation in MS patients may decrease the seasonal risk for MS relapses.

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease.

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the index case.

Health economic potential of early nutrition programming: a model calculation of long-term reduction in blood pressure and related morbidity costs by use of long-chain polyunsaturated fatty acid-supplemented formula.

BACKGROUND: The reported effect sizes of early nutrition programming on long-term health outcomes are often small, and it has been questioned whether early interventions would be worthwhile in enhancing public health. OBJECTIVE: We explored the possible health economic consequences of early nutrition programming by performing a model calculation, based on the only published study currently available for analysis, to evaluate the effects of supplementing infant formula with long-chain polyunsaturated fatty acids (LC-PUFAs) on lowering blood pressure and lowering the risk of hypertension-related diseases in later life. DESIGN: The costs and health effects of LC-PUFA-enriched and standard infant formulas were compared by using a Markov model, including all relevant direct and indirect costs based on German statistics. We assessed the effect size of blood pressure reduction from LC-PUFA-supplemented formula, the long-term persistence of the effect, and the effect of lowered blood pressure on hypertension-related morbidity. RESULTS: The cost-effectiveness analysis showed an increased life expectancy of 1.2 quality-adjusted life-years and an incremental cost-effectiveness ratio of -630 Euros (discounted to present value) for the LC-PUFA formula in comparison with standard formula. LC-PUFA nutrition was the superior strategy even when the blood pressure-lowering effect was reduced to the lower 95% CI. CONCLUSIONS: Breastfeeding is the recommended feeding practice, but infants who are not breastfed should receive an appropriate infant formula. Following this model calculation, LC-PUFA supplementation of infant formula represents an economically worthwhile prevention strategy, based on the costs derived from hypertension-linked diseases in later life. However, because our analysis was based on a single randomized controlled trial, further studies are required to verify the validity of this thesis.

Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age--IPD meta-analysis of 4 large clinical trials.

OBJECTIVES: To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. MATERIALS AND METHODS: Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. RESULTS: There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively. CONCLUSIONS: These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.

IPD meta-analysis shows no effect of LC-PUFA supplementation on infant growth at 18 months.

AIM: Clinical trials on the effects of long-chain polyunsaturated fatty acids (LC-PUFA) supplementation of formula milk on growth of term and preterm children have shown conflicting results. We examined the effects of LC-PUFAs-- especially docosahexaenoic acid (DHA) and arachidonic acid (AA)--on growth at 18 months. METHODS: We performed a meta-analysis based on individual patient data (IPD) of 901 children from four large, randomised clinical trials of formula milk with and without LC-PUFAs. Anthropometrics were assessed by z-scores based on weight for age, length for age, head circumference for age and body mass index (BMI) for age at 18 months. The studies differed in LC-PUFA composition and infant characteristics (two studies on preterm children, two on term children). RESULTS: Multivariate regression analyses including the possible confounders, sex, gestational age, birth weight, smoking in the last trimester and maternal age, as well as interaction terms showed no significant effects of LC-PUFA supplementation on any z-score. Subgroup analyses on trials with high amounts of DHA and on studies with duration of supplementation of at least 6 months yielded the same result. These findings cannot be explained by the lack of power. CONCLUSION: Our IPD meta-analysis shows no evidence that LC-PUFA supplementation affects children's growth at 18 months of age.

A decreasing rate of neural tube defects following the recommendations for periconceptional folic acid supplementation.

BACKGROUND/AIM: Neural tube defects (NTDs) are the most common birth defects, resulting in severe mortality and morbidity. In 1995, the supplementation of folic acid periconceptionally was officially recommended in Germany. The impact of the recommendations on the rate of NTDs was assessed. METHODS: An active surveillance system was established in the northern Rhine area. From 1996, all departments of obstetrics were asked to report cases of NTDs in all abortions, live births and stillbirths. Compliance with the recommendations was evaluated in a sample of mothers who delivered at the Department of Obstetrics of Düsseldorf University in 2001. RESULTS: From 1996-2003, 520 NTDs were reported. Compared to the rate of NTDs in 1996 (10.5/10,000), the average incidence in the years 1997 to 2003 dropped (6.8/10,000). The intake of folic acid, as recommended, was low among the general population (21.1%). CONCLUSION: Active surveillance data on the rate of NTDs are compatible with the maximum decrease of about 20% to be expected from data on the implementation of the recommendations. A much greater decrease in NTDs should be the challenge for the future.

Assessment of vitamin K deficiency in CF--how much sophistication is useful?

BACKGROUND: Due to maldigestion of dietary lipids, fat soluble vitamins are prone to malabsorption in cystic fibrosis (CF) patients with pancreatic insufficiency (PICF). Routine supplementation of vitamin K(1) in PICF is presently subject of discussion. METHODS: Serum vitamin K, prothrombin time, PIVKA-II ('liver marker', by two different ELISAs), hydroxyapatite binding capacity (HBC, 'bone marker') and ApoE genotypes were measured in 32 PICF patients (age: 7 months to 25 years) with (PICFK) or without (PICFN) oral vitamin K(1) supplementation, all receiving lipase supplementation, and in 18 healthy controls (C). RESULTS: PIVKA-II was positive only in 4/7 PICFN. HBC medians of all groups were 57-60%. HBC values of PIVKA-II positive patients were below HBC median of their group. There was no correlation between HBC and PIVKA-II. There was no correlation between prothrombin time and other measurements. HBC medians with regard to ApoE were ApoE2/3 (62.9%)>ApoE3/3 (57.6%)>ApoE3/4+ApoE4/4=(56.65%). CONCLUSIONS: Vitamin K deficiency of liver or bone may occur independently. Prothrombin time is an insensitive marker. Individuals with ApoE4 allels might be more susceptible to osteopenia. As high expenditures are necessary to detect patients at risk, routine vitamin K supplementation for all PICF patients appears appropriate.