title: Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Vitamin-D-deficiency rickets in Kuwait: the prevalence of a preventable disease. Nutritional rickets and vitamin D deficiency--association with the outcomes of childhood very severe pneumonia: a prospective cohort study. Cord Blood Vitamin D Deficiency Is Associated With Respiratory Syncytial Virus Bronchiolitis Vitamin D supplementation for severe pneumonia — A randomized controlled trial
abstract: Background : Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency , but the vitamin D status that fully normalizes absorption is not known for humans . Objective : To quantify calcium absorption at two levels of vitamin D repletion , using pharmacokinetic methods and commercially marketed calcium supplements . Design : Two experiments performed in the spring of the year , one year apart . In the first , in which participants were pretreated with 25-hydroxyvitamin D ( 25OHD )  , mean serum 25OHD concentration was 86.5 nmol/L ; and in the other , with no pretreatment , mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a st and ard low calcium breakfast . A low calcium lunch was provided at mid-day . Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter . Methods : Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve ( AUC ) for the load-induced increment in serum total calcium . Results : AUC9 ( ± SEM ) , was 3.63 mg hr/dL ± 0.234 in participants pretreated with 25OHD  and 2.20 ± 0.240 in those not pretreated ( P < 0.001 ) . In brief , absorption was 65 % higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L ( both values within the nominal reference range for this analyte ) . Conclusions : Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges , calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus , individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake . We conclude that the lower end of the current reference range is set too low OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P < .001 ) . Compared with controls , children receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency Summary Background Vitamin D has a role in regulating immune function , and its deficiency is a suggested risk factor for childhood pneumonia . Our aim was to assess whether oral supplementation of vitamin D3 ( cholecalciferol ) will reduce the incidence and severity of pneumonia in a high-risk infant population . Methods We did a r and omised placebo-controlled trial to compare oral 100 000 IU ( 2·5 mg ) vitamin D3 with placebo given to children aged 1–11 months in Kabul , Afghanistan . R and omisation was by use of a computer-generated list . Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months . Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically . Our primary outcome was the first or only episode of radiologically confirmed pneumonia . Our analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00548379 . Findings 1524 children were assigned to receive vitamin D3 and 1522 placebo .  There was no significant difference between the incidence of first or only pneumonia between the vitamin D ( 0·145 per child per year , 95 % CI 0·129–0·164 ) and the placebo group ( 0.137 , 0·121–0·155 ) ; the incidence rate ratio was 1·06 ( 95 % CI 0·89–1·27 ) . From 652 children during five separate periods of testing serum calcifediol , only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group — a toxic level . Interpretations Quarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting . Funding Wellcome Trust and British Council BACKGROUND Respiratory syncytial virus ( RSV ) is a common cause of severe lower respiratory tract infection in infants . Only a proportion of children infected with RSV require hospitalization . Because known risk factors for severe disease , such as premature birth , can not fully explain differences in disease severity , genetic factors have been implicated . METHODS To study the complexity of RSV susceptibility and to identify the genes and biological pathways involved in its development , we performed a genetic association study involving 470 children hospitalized for RSV bronchiolitis , their parents , and 1008 r and om , population controls . We analyzed 384 single-nucleotide polymorphisms ( SNPs ) in 220 c and i date genes involved in airway mucosal responses , innate immunity , chemotaxis , adaptive immunity , and allergic asthma . RESULTS SNPs in the innate immune genes VDR ( rs10735810 ; P=.0017 ) , JUN ( rs11688 ; P=.0093 ) , IFNA5 ( rs10757212 ; P=.0093 ) , and NOS2 ( rs1060826 ; P=.0031 ) demonstrated the strongest association with bronchiolitis . Apart from association at the allele level , these 4 SNPs also demonstrated association at the genotype level ( P=.0056 , P=.0285 , P=.0372 , and P=.0117 for the SNPs in VDR , JUN , IFNA5 , and NOS2 , respectively ) . The role of innate immunity as a process was reinforced by association of the whole group of innate immune SNPs when the global test for groups of genes was applied ( P=.046 ) . CONCLUSION SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis OBJECTIVES To determine whether ( i ) supplementation of oral 100,000 iu of vitamin D(3 ) ( cholecalciferol ) along with antibiotics will reduce the duration of illness in children with pneumonia ; ( ii ) supplementation will reduce the risk of repeat episodes . METHODS Double-blind individually r and omised placebo-controlled trial in an inner-city hospital in Kabul , of 453 children aged 1 - 36 months , diagnosed with non-severe or severe pneumonia at the outpatient clinic . Children with rickets , other concurrent severe diseases , very severe pneumonia or wheeze , were excluded . Children were given vitamin D(3 ) or placebo drops additional to routine pneumonia treatment . RESULTS Two hundred and twenty-four children received vitamin D(3 ; ) and 229 received placebo .  There was no significant difference in the mean number of days to recovery between the vitamin D(3 ) ( 4.74 days ; SD 2.22 ) and placebo arms ( 4.98 days ; SD 2.89 ; P = 0.17 ) . The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention ( 92/204 ; 45 % ) than the placebo group [ 122/211 ; ( 58 % ; relative risk 0.78 ; 95 % CI 0.64 , 0.94 ; P = 0.01 ] . Children in the vitamin D(3 ) group survived longer without experiencing a repeat episode ( 72 days vs. 59 days ; HR 0.71 ; 95 % CI 0.53 - 0.95 ; P = 0.02 ) . CONCLUSION A single high-dose oral vitamin D(3 ) supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia Two hundred and fifty children with clinical , biochemical and radiological evidence of vitamin-D-deficiency rickets were studied over a period of 5 years . Their ages ranged from 1 month to 2 years . Breastfed infants formed 63 % of total cases . Intramuscular therapy with vitamin D in a dose of 600,000 IU , deep intramuscular , proved to be safe and effective . In contrast , oral vitamin D did not provide such satisfactory results , presumably owing to poor patient/parental compliance . This report reveals that vitamin-D-deficieny rickets is common in Kuwait in spite of abundant sunlight all through the year because children are wrapped up and kept indoors . Insufficient intake of vitamin D is another important factor in the pathogenesis of vitamin-D-deficiency rickets in Kuwait BACKGROUND The association of rickets and vitamin D deficiency ( VDD ) with pneumonia is well documented , but not with its outcomes . OBJECTIVES To investigate whether rickets and VDD predict the outcomes in very severe pneumonia ( VSP ) . DESIGN A prospect i ve cohort study conducted at Al-Sabeen hospital in Sana'a , Yemen . A total of 152 children aged 2 - 59 months with WHO-defined VSP were enrolled , managed , and followed for up to 30 days . Treatment outcome was either successful or failure ( antibiotic modification for clinical worsening , death , relapse after 10-day antibiotics , or development of complications ) . Serum vitamin D ( 25OHD )  was measured in 79 cases . A concentration of < or=30 nmol/L defines VDD . MAIN OUTCOME MEASURES Association of rickets with treatment outcome ; and VDD with the circulating neutrophils ( PMNs ) , and oxygen saturation% ( SpO(2)% ) , respectively . RESULTS Treatment failure occurred in 24 ( 15.8 % ) , all aged 2 - 12 months , and 21 ( 87.5 % ) were rachitic . Of the 79 subset , 29 had VDD of which 23 ( 79.3 % ) had rickets . Treatment failure was significantly higher in the rachitic compared to non-rachitic [ 20.6 % ( 21/102 ) vs. 6 % ( 3/50 ) ; OR 1.38 ( 95 % CI 1.13 - 1.69 ) , P = 0.031 ] . In multivariate regression , rickets significantly predict a reduced successful treatment compared with non-rachitic [ 79.4 % ( 81/102 ) vs. 94 % ( 47/50 ) ; Adjusted OR 0.41 ( 95 % CI 0.20 - 0.85 ) ; P = 0.02 ] . VDD was strongly associated with reduced PMNs% [ Mean ( SD ) 37 ( 17 ) vs. 47 ( 17 ) ; Adjusted OR 0.71 ( 95 % CI 0.53 - 0.95 ) , P = 0.02 ] , and reduced SpO(2)% [ Mean ( SD ) 85.9 ( 7.9 ) vs. 89.8 ( 7.1 ) ; OR 0.96 ( 95 % CI 0.93 - 0.99 ) , P = 0.021 ] . CONCLUSIONS In VSP , rickets was significantly associated with treatment outcome and VDD significantly predict both reduced circulating PMNs , and Day-5 hypoxemia ( SpO(2)% , < 88 % ) BACKGROUND : Respiratory syncytial virus ( RSV ) is the most important pathogen causing severe lower respiratory tract infection ( LRTI ) in infants . Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI . OBJECTIVE : To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI . DESIGN : A prospect i ve birth cohort study was performed in healthy term neonates . Concentrations of 25-hydroxyvitamin D ( 25-OHD ) in cord blood plasma were related to RSV LRTI in the first year of life , defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen . RESULTS : The study population included 156 neonates . Eighteen ( 12 % ) developed RSV LRTI . The mean plasma 25-OHD concentration was 82 nmol/L. Overall , 27 % of neonates had 25-OHD concentrations < 50 nmol/L , 27 % had 50 - 74 nmol/L and only 46 % had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy . Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not ( 65 nmol/L versus 84 nmol/L , P = .009 ) . Neonates born with 25-OHD concentrations < 50 nmol/L had a sixfold ( 95 % confidence interval : 1.6 - 24.9 ; P = .01 ) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥75 nmol/L. CONCLUSIONS : Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life . Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy Objective To determine the role of oral vitamin D supplementation for resolution of severe pneumonia in under-five children . Design R and omized , double blind , placebo-controlled trial . Setting In patients from a tertiary care hospital . Participants Two hundred children [ mean ( SD ) age : 13.9 ( 11.7 ) months ; boys : 120 ] between 2 months to 5 years with severe pneumonia . Pneumonia was diagnosed in the presence of fever , cough , tachypnea ( as per WHO cut-offs ) and crepitations . Children with pneumonia and chest indrawing or at least one of the danger sign ( inability to feed , lethargy , cyanosis ) were diagnosed as having severe pneumonia . The two groups were comparable for baseline characteristics including age , anthropometry , socio-demographic profile , and clinical and laboratory parameters . InterventionOral vitamin D ( 1000 IU for < 1 year and 2000 IU for > 1 year ) ( n=100 ) or placebo ( lactose ) ( n=100 ) once a day for 5 days , from enrolment . Both the groups received antibiotics as per the Indian Academy of Pediatrics guidelines , and supportive care ( oxygen , intravenous fluids and monitoring ) . Outcome variables Primary : time to resolution of severe pneumonia . Secondary : duration of hospitalization and time to resolution of tachypnea , chest retractions and inability to feed . Results Median duration ( SE , 95 % CI ) of resolution of severe pneumonia was similar in the two groups [ vitamin D : 72 ( 3.7 , 64.7–79.3 ) hours ; placebo : 64 ( 4.5 , 55.2–72.8 ) hours ] . Duration of hospitalization and time to resolution of tachypnea , chest retractions , and inability to feed were also comparable between the two groups . ConclusionS hort-term supplementation with oral vitamin D ( 1000–2000 IU per day for 5 days ) has no beneficial effect on resolution of severe pneumonia in under-five children . Further studies need to be conducted with higher dose of Vitamin D or longer duration of supplementation to corroborate these findings
target: Children with LRTI were found to have significantly lower mean vitamin D levels as compared to controls There was likewise a correlation between vitamin D levels and incidence and severity of LRTI .
background: Studies related to vitamin D deficiency and lower respiratory tract infections ( LRTI ) in children have inconsistent findings .
  The objective of this systematic review was to assess the prevalence of vitamin D deficiency in children with LRTI , and to evaluate the correlation between vitamin D levels and the incidence and severity of LRTI .