超出生体重児に対する早期デキサメサゾン投与の有用性 : National Institute of Child Health and Human Development Neonatal research Network報告 (海外誌掲載論文の和文概要とそれに対するコメント)

Summary
This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures.

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Global vitamin D status and determinants of hypovitaminosis D.

Is vitamin D deficiency a major global public health problem

Objectives To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes. Data sources MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006). Review methods Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted. Results 167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of /= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women. Conclusions The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

http://www.reboundhealth.com/cms/images/pdf/MedicalAbstract/effectiveness%20and%20safety%20of%20vitamin%20d%20in%20relation%20to%20bone%20health%20id%2016060.pdf

Effectiveness and safety of vitamin D in relation to bone health.

Physical inactivity is a key determinant of health across the lifespan. A lack of activity increases the risk of heart disease, colon and breast cancer, diabetes mellitus, hypertension, osteoporosis, anxiety and depression and others diseases. Emerging literature has suggested that in terms of mortality, the global population health burden of physical inactivity approaches that of cigarette smoking. The prevalence and substantial disease risk associated with physical inactivity has been described as a pandemic.The prevalence, health impact, and evidence of changeability all have resulted in calls for action to increase physical activity across the lifespan. In response to the need to find ways to make physical activity a health priority for youth, the Institute of Medicine's Committee on Physical Activity and Physical Education in the School Environment was formed. Its purpose was to review the current status of physical activity and physical education in the school environment, including before, during, and after school, and examine the influences of physical activity and physical education on the short and long term physical, cognitive and brain, and psychosocial health and development of children and adolescents. Educating the Student Body makes recommendations about approaches for strengthening and improving programs and policies for physical activity and physical education in the school environment. This report lays out a set of guiding principles to guide its work on these tasks. These included: recognizing the benefits of instilling life-long physical activity habits in children; the value of using systems thinking in improving physical activity and physical education in the school environment; the recognition of current disparities in opportunities and the need to achieve equity in physical activity and physical education; the importance of considering all types of school environments; the need to take into consideration the diversity of students as recommendations are developed.This report will be of interest to local and national policymakers, school officials, teachers, and the education community, researchers, professional organizations, and parents interested in physical activity, physical education, and health for school-aged children and adolescents.

Educating the Student Body: Taking Physical Activity and Physical Education to School

Background: There has been a resurgence of nutritional rickets in children in many developing countries and some of the developed countries. Children between 6 and 18 months old are commonly affected. In order to find out the association between vitamin D and rickets we studied the vitamin D status of the neonates and their mothers in Kuwait.



Methods: Two hundred and fourteen full-term pregnant mothers and their neonates were selected from two hospitals in Kuwait. All mothers had normal vaginal delivery. On the day of delivery 2.5 mL of maternal blood and 2.5 mL of cord blood samples were withdrawn. Serum 25-hydroxyvitamin D (25OHD) was determined in duplicate by radioimmunoassay using an Incstar kit. Quality control analyses were done using several between and within run experiments.



Results: A total of 128 mother–neonate pairs were selected from the Al-Adan hospital and 86 from the Maternity Hospital. The mean age and parity of the mothers were similar in both hospitals. The mean (± SD) 25OHD levels of the mothers and the neonates in the Adan hospital were 13.3 (6.5) ng/mL and 8.2 (6.5) ng/mL, respectively. The corresponding values in the Maternity Hospital were 17.6 (12.4) and 8.1 (7.3) ng/mL for the mothers and the neonate, respectively. Serum 25OHD of the mothers and their newborn infants were highly correlated (r = 0.790, P < 0.001).



Conclusions: Results demonstrate that 40% of the mothers and 60% of the neonates are vitamin D deficient on the day of delivery. The vitamin D of the mothers and neonates are highly correlated (r = 0.790, P < 0.001).

Vitamin D status of mothers and their neonates in Kuwait.

Objective Neonatal sepsis is a major cause of neonatal deaths in Asia but data remain scarce. We aimed to investigate the causative organisms and antibiotic resistance in neonatal care units in China, Malaysia, Hong Kong and Thailand. Methods Prospective cohort study of neonatal sepsis defined as positive culture of a single potentially pathogenic organism from blood or cerebrospinal fluid differentiated into early-onset sepsis (EOS) occurring Results During the study period, there were 963 episodes of neonatal sepsis. The incidence of EOS was 0.62 (95% CI 0.45 to 0.82) per 1000 live births or 4.91 (95% CI 4.22 to 5.68) per 1000 admissions while the incidence of LOS was 5.00 (95% CI 4.51 to 5.53) per 1000 live births or 21.22 (95% CI 19.79 to 22.77) per 1000 admissions. The incidence of Group B Streptococcus (GBS) sepsis was low but remained the most common single pathogen for EOS among inborn babies. Klebsiella spp. was the most common Gram-negative organism causing most deaths. The case-fatality was 7.0% (95% CI 3.9% to 12.0%) for EOS and 16.0% (95% CI 13.7% to 19.0%) for LOS, and was significantly different between participating units after adjusting for potential confounders. Of all Gram-negative organisms, 47%, 37% and 32% were resistant to third-generation cephalosporins, gentamicin or both, respectively. Conclusions The pattern of EOS in Asian settings is similar to that in industrialised countries with low incidence of GBS sepsis. The important features of neonatal sepsis in Asia are the burden of Klebsiella spp. and high level of antibiotic resistance. These should be addressed while developing measures to reduce neonatal mortality due to infection.

https://fn.bmj.com/content/fetalneonatal/early/2012/08/30/archdischild-2012-301767.full.pdf

Neonatal infections in China, Malaysia, Hong Kong and Thailand

Objective: To study the epidemiology (including incidence, antibiotic sensitivity and mortality) of neonatal unit infections in countries in Asia. Methods: One year prospective study of neonatal infections in eight neonatal units in Asia. Results: There were 453 episodes of sepsis affecting 394 babies. Mortality from neonatal sepsis was 10.4%, with an incidence of 0.69 deaths/1000 live births. Group B streptococcus was the most common early-onset organism causing 38% of episodes of early-onset ( Staphlococcus aureus caused only 5.4%. Gram-negative bacilli caused 189 episodes (46.6%). Only 44% of Gram-negative bacilli were sensitive to both gentamicin and a third-generation cephalosporin, whereas 30% were resistant to both antibiotics. Meningitis occurred in 17.2% of episodes of late sepsis, with a mortality of 20%. Conclusions: The incidence of late-onset sepsis was higher in Asia than in resource-rich countries, but the organisms isolated and mortality were similar. Over half of all Gram-negative bacilli were antibiotic resistant.

https://fn.bmj.com/content/fetalneonatal/early/2008/09/19/adc.2008.139865.full.pdf

Neonatal infections in Asia.

Vitamin D deficiency in mothers, neonates and children.

Aim: Investigate the incidence, etiological pattern and the antimicrobial resistance of late-onset neonatal infections over a period of 5 years.

Methods:  Longitudinal audit of neonatal sepsis from January 2005 to December 2009, in the main maternity hospital in Kuwait. Late-onset neonatal infection was defined as the culture of a single potentially pathogenic organism from blood or cerebrospinal fluid from an infant older than 6 days in association with clinical or laboratory findings consistent with infection.

Results:  The overall incidence was 16.9 (95% confidence interval: 15.8–18.0) episodes per 1000 live births. The commonest pathogen was coagulase-negative Staphylococcus, 339 (35.7%), while Klebsiella was the most common gram-negative infection, 178 (18.8%). Escherichia coli, Enterococcus and Enterobacter spp were each responsible for 6% of all infections. Candida caused 104 (11.0%) infections. The general pattern of infection remained unchanged over the study period. Case fatality was 11.7% (95% confidence interval: 9.7–13.9%) and was high for Pseudomonas (18.4%) and Candida (22.1%) infections. Approximately 24 and 20% of Klebsiella infections were resistant to cefotaxime and gentamicin, respectively, while 28 and 24% of Escherichia coli infections were resistant to cefotaxime and gentamicin, respectively.

Conclusion:  The incidence of late-onset infection in Kuwait is high, resembling that in resource-poor countries. The high incidence coupled with low case fatality provides an example for settings where tertiary care is introduced without strict measures against nosocomial infections. Prevention against nosocomial infections in neonatal units has the potential to further reduce neonatal mortality in these settings.

Majeda S. Hammoud

Papers

Vitamin D status of mothers and their neonates in Kuwait.

Neonatal infections in China, Malaysia, Hong Kong and Thailand

Neonatal infections in Asia.

Vitamin D deficiency in mothers, neonates and children.

Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study.