Comparative study of oral versus injectable vitamin K in neonates. Safety and feasibility of high-dose administration of nicorandil before reperfusion therapy in acute myocardial infarction Prevention of subclinical vitamin K deficiency based on PIVKA-II levels: oral versus intramuscular route. Vitamin K to Neonates: Peroral versus Intramuscular Administration Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K Effect of oral water soluble vitamin K on PIVKA-II levels in newborns. Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less. Newborn Vitamin A Supplementation Reduced Infant Mortality in Rural Bangladesh
One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn ( HDN ) . The babies were grouped into four categories of 25 each : Group A--1 mg Vitamin K intramuscular ( Menadione sodium disulphite ) at birth ; Group B--0.5 mg Vitamin K intramuscular ; Group C--1 mg Vitamin K orally , and group D -- no Vitamin K. The prothrombin index was estimated in all babies between 36 - 72 hours of age . The results revealed a prothrombin index in Groups A , B , C and D as 94.98 + /- 7.64 % , 95.08 + /- 9.91 % , 92.51 + /- 10.10 % and 80.39 + /- 15.90 % , respectively . The differences between Groups A , B and C were insignificant . However , Group D , prothrombin index was significantly reduced as compared with the other three groups . It is , therefore , concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy The efficacy and safety of high-dose nicor and il therapy in acute myocardial infa rct ion ( AMI ) have not yet been clarified . This is a prospect i ve study including 30 patients who received nicor and il at 0.06 mg/kg/h [ st and ard dose nicor and il ( SDN ) group ] and 32 patients who received a bolus injection of nicor and il 0.2 mg/kg followed by a continuous infusion at 0.2 mg/kg/h [ high-dose nicor and il ( HDN ) group ] . The benefits and adverse events were assessed during acute phase and 12-month follow-up period . There were no significant differences between the groups in blood pressure , heart rate or urine volume 2 , 6 and 24 h after drug administration , although blood pressure decreased during acute phase . The percentages of patients who required dose reduction or discontinuation of nicor and il were 34.4 and 16.7 % in HDN and SDN groups , respectively ( p = 0.11 ) . In HDN group , subgroup analysis revealed that the TIMI frame count ( TFC ) was significantly lower in patients in whom the treatment was started within 12 h compared to those more than 12 h ( 17.0 vs. 21.0 , p = 0.017 ) and in patients with baseline WBC elevation compared to those without it ( 16.5 vs. 22.0 , p = 0.029 ) . A TFC of > 20 was significantly associated with being in HDN group [ odds ratio ( OR ) 0.27 ; 95 % confidence interval , CI 0.07–0.89 ] , onset-to-balloon time ( OR 1.06 ; 95 % CI 1.01–1.16 ) , and ∑creatine kinase ( OR 7.27 ; 95 % CI 1.40–57.83 ) . There were no significant differences in incidences of cardiovascular death , rehospitalization , and target lesion revascularization between the groups . HDN therapy may improve coronary microcirculation in patients with AMI Classical  hemorrhagic disease of newborn ( HDNB )  was first described in 1894(1 ) . Clinical ly manifest classical HDNB is relatively uncommon with incidence of 1 - 2/1000 live births . Exclusively breastfed babies are predisposed to develop HDNB because of absence of bacterial flora in the gut , lack of stores of vitamin K and low vitamin K levels in breastmilk(2,3 ) . In the absence of vitamin K , its precursor non-carboxylated proteins called Proteins Induced in Vitamin K Absence ( PIVKA ) are elevated . Levels of PIVKA-II ( Precursor Protein of Factor II ) are more specific than Pro-thrombin Time ( PT ) because the former does not get elevated in states of decreased synthesis of coagulation factors as occurs in hepatitis(4 ) . The American Academy of Pediatrics ( AAP ) recommends prophylactic administration of intramuscular ( IM ) vitamin K for all newborn babies at birth(5 ) whereas in India , there is lack of consensus and ( IM ) vitamin K is given only to high risk babies in many centers . Intramuscular vitamin K is associated with the potential risks of transmission of viral infections , lymphoreticular malignancies in later childhood and excessive cost . Oral administration of vitamin K is thus preferable because of safety and cost effectiveness . The present study was conducted to look for sub- clinical evidence of  vitamin K deficiency in exclusively breastfed term neonates and evaluate the efficacy of orally and intramuscularly administered water soluble vitamin K in them ABSTRACT . In a r and omized study of 300 infants , the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection . The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint . Prothrombin ( antigen ) and PIVKA II ( acarboxyprothrombin ) were also measured . All infants were observed for events of bleeding until discharge from the hospital , normally on the fifth day . No significant differences between the groups in any of the biochemical markers were observed . The 95 % confidence limits of the differences were very narrow for all factors . No cases of bleeding were observed . We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn Abstract There is consensus that  late vitamin K deficiency bleeding ( VKDB )  should be prevented by vitamin K prophylaxis . One single dose of 1 mg vitamin K1 is effective if given i.m . or s.c . , but not if given orally . Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established . Different oral dose schedules are presently used in different countries . In Australia , Germany , The Netherl and s and Switzerl and active surveillance data on late VKDB were collected in a similar manner and failure rates compared . Identical case definitions were used . There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries : ( 1 ) daily supplementation of low dose vitamin K ( 25 μg ) for breast-fed infants ( The Netherl and s ) ; ( 2 ) 3 × 1 mg orally [ Australia ( January 1993 – March 1994 ) and Germany ( December 1992 – December 1994 ) ] ; ( 3 ) 1 mg vitamin K i.m . ( Australia since March 1994 ) ; and ( 4 ) 2 × 2 mg vitamin K ( new mixed micellar preparation ) ( Switzerl and ) . The respective failure rates per 100,000 live births ( including cases given all recommended doses and those given incomplete prophylaxis ) were for strategy : ( 1 ) 0.2 ( 0–1.3 ) in The Netherl and s ; ( 2 ) 2.3 ( 95 % CI 1.6–3.4 ) in Germany and 2.5 ( 1.1–4.8 ) in Australia ( oral prophylaxis ) ; ( 3 ) Australia ( i.m . prophylaxis ) 0 ( 0–0.9 ) ; and ( 4 ) 3.6 ( 0.7–10.6 ) in Switzerl and . The failure rates for complete prophylaxis only were : strategy ( 1 ) 0 ( 0–0.7 ) in The Netherl and s ; ( 2 ) 1.8 ( 1.1–2.8 ) in Germany and 1.5 ( 0.5–3.6 ) in Australia ; ( 3 ) Australia ( i.m . ) 0 ( 0–0.9 ) ; and ( 4 ) 1.2 ( 0–6.5 ) in Switzerl and . Conclusions The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m . vitamin K prophylaxis . A daily low oral dose of 25 μg vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis . The effectiveness of the “ mixed-micellar ” preparation of vitamin K1 needs further study Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost , pain , anxiety to parents and risk of transmission of infection . Oral route is a better alternative . Oral absorption of vitamin K has been shown to be equally good using special oral preparations . However , this preparation is not available in India . A prospect i ve study was carried out on 51 full term , healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K ( menadione sodium bisulphite ) could be as effective . Fourteen babies received 1 mg vitamin K intramuscularly , 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth .  PIVKA-II levels were measured in cord blood and at 72 - 78 hours of age in all babies as a marker of vitamin K deficiency . The overall PIVKA-II prevalence in cord blood was 64.7 % . At 72 - 78 hours , PIVKA-II was present in 50 % of babies in IM group , 58.3 % of babies in oral group and in 76.9 % of babies in ' no vitamin K ' group ( p > 0.05 ) . The PIVKA-II levels decreased or did not change at 72 - 78 hours in 91.6 % of babies in oral group versus 92.8 % of babies in IM group ( p > 0.05 ) . On the other h and , PIVKA-II levels increased in 30.7 % of babies who did not receive vitamin K as against in 7.8 % of babies receiving vitamin K in either form ( p < 0.05 ) . Hence , vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K ( menadione sodium bisulphite ) given orally to term healthy babies is effective in preventing vitamin K deficiency state BACKGROUND Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease . AIM To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants . METHODS Infants with birth weight < 1000 g were r and omised at birth to receive oral vitamin A supplementation ( 5000 IU/day ) or placebo for 28 days . The primary outcome was oxygen dependency at 28 days of age or death . RESULTS A total of 154 infants were r and omised ; 77 received vitamin A ( median birth weight ( interquartile range ) 806 ( 710–890 ) g ) , and 77 received placebo ( median birth weight ( interquartile range ) 782 ( 662–880 ) g ) . Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth , 12 hours of age , 7 days , or 28 days of life . There were no significant differences in the proportion of infants who survived , required oxygen at 28 days , required oxygen at 36 weeks postmenstrual age , survived without chronic lung disease at 36 weeks , survived without significant retinopathy , or who survived without significant intraventricular haemorrhage . CONCLUSIONS Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease . However , this dose may have been inadequate to achieve optimal serum retinol concentrations OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient We conducted a r and omized , double-blind , controlled trial to determine whether vitamin A supplementation from early postnatal life could reduce the morbidity associated with bronchopulmonary dysplasia in very low birth weight ( VLBW ) neonates . Forty VLBW neonates ( 700 to 1300 g birth weight , 26 to 30 weeks gestational age ) , who were oxygen dependent and required mechanical ventilation for at least 72 hours after birth , were given by the intramuscular route either supplemental vitamin A ( retinyl palmitate 2000 IU ) or 0.9 % saline solution on postnatal day 4 and every other day thereafter for a total of 14 injections over 28 days . The study groups were comparable in gestational maturity , clinical characteristics , initial lung disease , and vitamin A status at entry into the trial . Vitamin A administration result ed in significantly higher mean plasma concentrations of vitamin A and retinol-binding protein in treated infants compared with controls . Bronchopulmonary dysplasia was diagnosed in nine of 20 infants given vitamin A supplement and in 17 of 20 control infants ( P less than 0.008 ) . Four of 19 infants in the vitamin A group and 11 of 20 in the control group required mechanical ventilation on study day 28 ( P less than 0.029 ) . The need for supplemental oxygen , mechanical ventilation , and intensive care was reduced in infants given vitamin A supplement compared with controls . Airway infection and retinopathy of prematurity were less frequent in the vitamin A group . We conclude that vitamin A supplementation at the dosage used in this trial in VLBW neonates not only improves their vitamin A status but also appears to promote regenerative healing from lung injury , as evidence d by a decrease in the morbidity associated with bronchopulmonary dysplasia The incidence of culture-proven neonatal sepsis and necrotizing enterocolitis ( NEC ) in preterm infants maintained at pharmacologic ( mean 5.1 mg/dL + /- 1.45 SD ) serum vitamin E levels for long periods was prospect ively studied as part of a double-masked clinical trial of the effect of prophylactic vitamin E v placebo treatment on the development and course of retinopathy of prematurity ( ROP ) . Within a few days of birth , 914 preterm infants were enrolled in the study ; 545 ( 275 placebo-treated infants , 270 vitamin E-treated infants had birth weight of 1,500 g or less . A significant difference in incidence of neonatal sepsis ( 17 placebo-treated infants , 37 vitamin E-treated infants ) and NEC ( 18 placebo-treated infants , 32 vitamin E-treated infants ) was observed among infants who had been treated for eight or more days and who had developed neither sepsis nor NEC before that time . The association of vitamin E treatment with increased incidence of disease was much higher with sepsis than with NEC . The most likely reason for these observations is a pharmacologic serum vitamin E-related decrease in oxygen-dependent intracellular killing ability which results in a decreased resistance to infection in preterm infants . The data suggest that , if this occurs , it is clinical ly significant only in the more immature infants . In view of the known variability of absorption of oral vitamin E and the association between high serum vitamin E levels and increased incidence of sepsis and late-onset NEC reported here , it can be concluded that serum vitamin E levels must be monitored when supplemental vitamin E is administered to premature infants , especially those with birth weight 1,500 g or less . The risk-benefit ratio of long-term treatment using vitamin E at high serum levels should be clearly assessed OBJECTIVES . We assessed the effect of supplementing newborns with 50000 IU of vitamin A on all-cause infant mortality  through 24 weeks of age . PATIENTS AND METHODS . This was a community-based , double-masked , cluster-r and omized , placebo-controlled trial conducted in 19 unions in rural northwest Bangladesh . The study was nested into and balanced across treatment arms of an ongoing placebo-controlled , weekly maternal vitamin A or β-carotene supplementation trial . Study -defined sectors ( N = 596 ) were evenly r and omized for newborns of participating mothers to receive a single , oral supplement of vitamin A ( 50000 IU ) or placebo as droplets of oil squeezed from a gelatinous capsule . Mothers provided informed consent for newborn participation at ∼28 weeks ' gestation . After birth , typically at home ( where > 90 % of births occurred ) , infants were supplemented and their vital status was followed through 24 weeks of age . The main outcome measure was mortality through 24 weeks of age . RESULTS . We obtained maternal consent to dose 17116 live-born infants ( 99.8 % of all eligible ) among whom 15937 ( 93.1 % ) were visited to be supplemented < 30 days after birth and for whom vital status at 24 weeks of age was known . Dosed infants ( n = 15902 [ 99.8 % ] ) received their study supplement at a median age of 7 hours . Relative to control subjects , the risk of death in vitamin A – supplemented infants was 0.85 , reflecting a 15 % reduction in all-cause mortality . Protective relative risks were indistinguishable by infant gender , gestational age , birth weight , age at dosing , maternal age , parity , or across the 3 treatment arms of the maternal supplementation trial . CONCLUSIONS . Newborn vitamin A dosing improved infant survival through the first 6 months of life in Bangladesh . These results corroborate previous findings from studies in Indonesia and India and provide additional evidence that vitamin A supplementation shortly after birth can reduce infant mortality in South Asia
One dose of vitamin K reduced clinical bleeding at 1 - 7 days , including bleeding after circumcision , and improved biochemical indices of coagulation status .
There was no evidence of a difference between the oral and intramuscular route in effects on biochemical indices of coagulation status .
REVIEW ER 'S CONCLUSIONS A single dose ( 1.0 mg ) of intramuscular vitamin K after birth is effective in the prevention of classic HDN .
Either intramuscular or oral ( 1.0 mg ) vitamin K prophylaxis improves biochemical indices of coagulation status at 1 - 7 days .
Neither intramuscular nor oral vitamin K has been tested in r and omized trials with respect to effect on late HDN .
Oral vitamin K , either single or multiple dose , has not been tested in r and omized trials for its effect on either classic or late HDN
BACKGROUND  Vitamin K deficiency can cause bleeding in an infant in the first weeks of life .
This is known as Hemorrhagic Disease of the Newborn ( HDN ) .
HDN is divided into three categories : early , classic and late HDN .
Early HDN occurs within 24 hours post partum and falls outside the scope of this review .
Classic HDN occurs on days one to seven ; common bleeding sites are gastrointestinal , cutaneous , nasal and from a circumcision .
Late HDN occurs from week 2 - 12 ; the most common bleeding sites are intracranial , cutaneous , and gastrointestinal .
Vitamin K is commonly given prophylactically after birth for the prevention of HDN , but the preferred route is uncertain .
OBJECTIVES To review the evidence from r and omized trials in order to determine the effectiveness of vitamin K prophylaxis in the prevention of classic and late HDN .
Main questions are : Is one dose of vitamin K , given after birth , able to significantly reduce the incidence of classic and late HDN ?
Is there a significant difference between the oral route and the intramuscular route in preventing classic and late HDN ?
Are multiple oral doses of vitamin K , given after birth , able to significantly reduce the incidence of classic and late HDN ?