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 EFFECT OF VITAMIN K ADMINISTRATION ON ACARBOXY PROTHROMBIN (PIVKA-II) LEVELS IN NEWBORNS Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less. Fungal colonization in the very low birth weight infant. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. Early high-dose phenobarbital treatment for prevention of hypoxic-ischemic brain damage in very low birth weight infants. The combined antenatal corticosteroids and vitamin K therapy for preventing periventricular-intraventricular hemorrhage in premature newborns less than 35 weeks gestation. Early vs delayed vitamin A supplementation in very-low-birth-weight infants. A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants Vaginal Misoprostol Compared With Oral Misoprostol in Termination of Second‐Trimester Pregnancy Vitamin A supplementation of South African children with severe diarrhea: optimum timing for improving biochemical and clinical recovery and subsequent vitamin A status Prospective Randomized Trial of Early Versus Late Enteral Iron Supplementation in Infants With a Birth Weight of Less Than 1301 Grams
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 PIVKA-II ( protein induced by vitamin K absence or antagonist-II ) was measured in two groups of newborns , one group being given 5 mg vitamin K at birth and the other untreated . The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group . When vitamin K was administered to newborn babies whose normotest levels were less than 30 % , it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K , as monitored by the normotest . Thus PIVKA-II levels might be more useful than a coagulation test , since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity . The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding A r and omized , double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage ( ICH )  was performed . One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight ( 501 to 750 g and 751 to 1000 g ) and r and omized to treatment or control . The treatment group received intramuscular injections of vitamin E ( dl-alpha-tocopherol ) on days 1 , 2 , 4 , and 6 of life . The control group received intramuscular injections of placebo on the same schedule . All neonates initially received oral vitamin E ( 100 mg/kg/day dl-alpha-tocopheryl acetate ) , which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1 , 5 to 7 , and 12 to 14 . Hemorrhage was defined as mild if less than or equal to grade II ICH , or severe if grade III or IV . No significant differences in neonatal or total hospital mortality between groups were found . However , all ICH , as well as severe ICH , were significantly less in the vitamin E-treated 501 to 750-g subgroup ( all ICH : 60 % vs 29 % ; severe ICH : 32 % vs 4 % ) . When survivors were analyzed separately , a significant decrease in severe ICH was seen in the vitamin E-treated neonates ( 25 % vs 5 % ) . Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild in duration at injection sites , no deleterious side effects of treatment were identified . Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 In the neonate , fungal infections result in significant morbidity and mortality . For very low birth weight ( less than 1,500 g ) infants , we prospect ively determined the fungal colonization rate to be 26.7 % . In one third of infants with fungal colonies , mucocutaneous c and idiasis developed , and in 7.7 % , systemic disease developed . Two thirds of the infants had colonies in the first week of life . This colonization was probably acquired during labor and delivery , because those infants who had colonization were more often delivered vaginally than by cesarean section . Early colonization , commonly from the gastrointestinal or respiratory tract , featured C and ida albicans and C and ida tropicalis . Late colonization , occurring after 2 weeks of life ( 15.0 % of patients ) , was more likely to be cutaneous and was associated with either C and ida parapsilosis or such poor growth that the organism could not be identified . Infants with colonization only rarely had budding yeasts ( 6.1 % ) , whereas more than half of the infants with either a urinalysis showing budding yeasts or a urine culture growing fungi had invasive disease . Fungal contamination was not found on either thoracotomy tubes or catheter tips . In the low birth weight infant , fungal colonization represents a significant risk factor for cutaneous or systemic c and idiasis in these infants CONTEXT Sepsis is a common and severe complication in premature neonates , particularly those with very low birth weight ( VLBW ) ( < 1500 g ) . Whether lactoferrin , a mammalian milk glycoprotein involved in innate immune host defenses , can reduce the incidence of sepsis is unknown . In animal models , the probiotic Lactobacillus rhamnosus GG ( LGG ) enhances the activity of lactoferrin but has not been studied in human infants . OBJECTIVE To establish whether bovine lactoferrin ( BLF ) , alone or in combination with LGG , reduces the incidence of late-onset sepsis in VLBW neonates . DESIGN , SETTING , AND PATIENTS Prospect i ve , multicenter , double-blind , placebo-controlled , r and omized trial conducted in 11 Italian tertiary neonatal intensive care units . Patients were 472 VLBW infants enrolled from October 1 , 2007 , through July 31 , 2008 , and assessed until discharge for development of sepsis . INTERVENTION Infants were r and omly assigned to receive orally administered BLF ( 100 mg/d ) alone ( n = 153 ) , BLF plus LGG ( 6 x 10(9 ) colony-forming units/d ) ( n = 151 ) , or placebo ( n = 168 ) from birth until day 30 of life ( day 45 for neonates < 1000 g at birth ) . MAIN OUTCOME MEASURE First episode of late-onset sepsis , ie , sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid . RESULTS Demographic , clinical , and management characteristics of the 3 groups were similar , including type of feeding and intake of maternal milk . Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups ( 9/153 [ 5.9 % ] and 7/151 [ 4.6 % ] , respectively ) than in the control group receiving placebo ( 29/168 [ 17.3 % ] ) ( risk ratio , 0.34 ; 95 % confidence interval , 0.17 - 0.70 ; P = .002 for BLF vs control and risk ratio , 0.27 ; 95 % confidence interval , 0.12 - 0.60 ; P < .001 for BLF plus LGG vs control ) . The decrease occurred for both bacterial and fungal sepsis . No adverse effects or intolerances to treatment occurred . CONCLUSION Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53107700 BACKGROUND Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants . The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials . METHODS We performed a multicenter , blinded , r and omized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth . The mean birth weight was 770 g in the vitamin A group and 769 g in the control group , and the respective gestational ages were 26.8 and 26.7 weeks . RESULTS By 36 weeks ' postmenstrual age , 59 of the 405 infants ( 15 percent ) in the vitamin A group and 55 of the 402 infants ( 14 percent ) in the control group had died . The primary outcome - death or chronic lung disease at 36 weeks ' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group ( 55 percent vs. 62 percent ; relative risk , 0.89 ; 95 percent confidence interval , 0.80 to 0.99 ) . Overall , 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements . The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar . The proportion of infants with serum retinol values below 20 microg per deciliter ( 0.70 micromol per liter ) was lower in the vitamin A group than in the control group ( 25 percent vs. 54 percent , P<0.001 ) . CONCLUSIONS Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants In a r and omized prospect i ve trial , we studied the effect of early high-dose phenobarbital treatment on the early ( intraventricular hemorrhage ) and late ( neurodevelopmental abnormalities ) manifestations of hypoxic-ischemic encephalopathy in preterm infants weighing 1500 g or less at birth . The first intravenous dose of 15 mg/kg was given at a mean age of 110 minutes , followed by 15 mg/kg after 4 hours and then by 5 mg/kg at 24-hour intervals for 5 days . The overall incidence of intraventricular hemorrhage was 32 % in treated and 46 % in control infants , a nonsignificant difference . An ultrasound brain scan at 9 months old revealed no significant difference in the incidence of ventricular dilatation between treated ( 19 % ) and control ( 29 % ) infants . At 27 months , a similar incidence of mild ( 10 % ) and severe ( 10 % ) neurodevelopmental h and icaps was found in both treated and control groups . Since beneficial effects could not be documented by any of the criteria used , we conclude that routine administration of phenobarbital to low birth weight infants is not justified We prospect ively evaluated whether combined antenatal corticosteroid and vitamin K administration have any benefit , over and above that of corticosteroid or vitamin K used alone , in reducing the frequency and the degree of PIVH in premature newborns less than 35 weeks ' gestation . All of these 280 pregnant women were r and omly allocated into five groups according to the in-patient sequence . Group A ( vitamin K1 group ) including 38 pregnant women ( 40 newborns ) received antenatal intramuscular or intravenously injection of vitamin K1 10 mg per day for 2 - 7 days . Group B ( single dose corticosteroid group ) including 57 pregnant women ( 63 newborns ) received antenatal intramuscular or intravenously injection of dexamethasone 10 mg per day for 1 day . Group C ( two dose corticosteroid group ) including 62 pregnant women ( 70 newborns ) received antenatal intramuscular or intravenously injection of dexamethasone 10 mg per day for 2 days . Group D ( combined using dexamethasone and vitamin K1 ) including 41 pregnant women ( 44 newborns ) received dexamethasone 10 mg per day for 1 day and vitamin K110 mg per day for 2 - 7 days . Control group , including 82 pregnant women ( 87 newborns ) were received neither dexamethasone nor vitamin K1 injection . The results showed PIVH was diagnosed in 17 of 40 ( 42.5 % ) in Group A , 34 of 63 ( 54.0 % ) in Group B , 36 of 70 ( 51.4 % ) in Group C , 14 of 44 ( 31.8 % ) in Group D , and 57 of 87 ( 65.2 % ) in control infants ( p = 0.004 ) . More infants in the control group had grade III or IV intracranial hemorrhage after birth ( p = 0.049 ) . After antenatal supplement of dexamethasone and vitamin K1 , both the total incidence of PIVH and the frequency of severe PIVH decreased significantly . The total and severe incidence of PIVH in Group B ( single doses dexamethasone ) and Group C ( two courses dexamethasone ) there were no significant difference . It showed that after antenatal supplement of dexamethasone and vitamin K1 , both the total incidence of PIVH and the frequency of severe PIVH decreased significantly , and combined antenatal corticosteroid and vitamin K administration have much benefit , over and above that of corticosteroid or vitamin K used alone The purpose of this trial was to test the hypothesis that vitamin A adequacy may decrease the incidence of  bronchopulmonary dysplasia ( BPD ) in very-low-birth-weight infants .  Serum vitamin A levels were measured and the effects of two regimens of vitamin A supplementation on the incidence of BPD were compared . There were 24 infants in each of two groups with a mean birth weight less than 1000 g , a mean gestational age of 27 weeks , and similar sexual and racial mixes . In group I ,  vitamin A levels  were measured after 1 week of parenteral nutrition and , if low , the infant was given a 2000-IU supplement intramuscularly three times a week , beginning on the 10th to 14th day of life . In group II , the same supplementation was begun on the second to fourth day of life . In both groups , when enteral feedings reached 60 kcal/kg per day , 2500 IU/d vitamin A was given orally . The incidence of oxygen support at 28 days was similar in both groups , although in group II there was a trend toward less vigorous ventilatory support . chi 2 analysis showed that a significantly smaller proportion of infants in group II had BPD at 36 weeks ' gestational age than in group I. Length of neonatal intensive care unit stay was significantly reduced from 81 to 60 days . We conclude that vitamin A supplementation should be administered early to small , premature infants who are at risk for BPD and that monitoring of plasma levels is essential OBJECTIVE To compare a new oral preparation of vitamin K1 ( Konakion MM ) containing lecithin and glycocholic acid with a st and ard intramuscular ( IM ) preparation during the first 8 weeks of life in exclusively breast fed infants . METHODS Infants were r and omised at birth to the IM group ( 1 mg vitamin K )  or the oral group  ( 2 mg given at birth and repeated at 7 and 30 days of life ) . Prothrombin time ( INR ) , plasma vitamin K1 , and PIVKA II ( undercarboxylated prothrombin ) were monitored at 14 , 30 , and 56 days of age . RESULTS Seventy nine infants were r and omised to the oral group and 77 to the IM group . Sixty seven infants in each group completed eight weeks of the study . Prothrombin times did not differ between the two groups . Mean ( SD ) plasma vitamin K1values ( in ng/ml ) decreased in both groups over time , but were higher in the oral group at 14 and 56 days : 2.0 ( 1.6 ) v 1.3 ( 1.1 ) at 14 days ; 0.5 ( 0.3 ) v 0.5 ( 0.7 ) at 30 days ; and 0.5 ( 0.8 ) v 0.2 ( 0.2 ) at 56 days of life . PIVKA II was raised ( ⩾ 0.1 AU/ml ) in cord blood in 47 % of the infants . By 14 days , only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood . At 30 days , there were no raised PIVKA II values . At 56 days , there were no raised PIVKA II values in the oral group , although three infants in the IM group had raised values . CONCLUSIONS Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured . Through the first 8 weeks of life , multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation Objective To compare the efficacy of vaginal with oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone . Methods Women requesting termination of secondtrimester pregnancy were r and omized into two groups . Thirty-six to 48 hours after oral administration of 200 mg of mifepristone , women were given either oral or vaginal misoprostol 200 μg every 3 hours for a maximum of five doses in the first 24 hours . Women receiving oral misoprostol also were given a vaginal placebo ( vitamin B6 ) , whereas those receiving vaginal misoprostol were given an oral placebo . If they failed to abort , a second course was given by the same route . Results The median induction-abortion interval in the vaginal group ( 9 hours ) was significantly shorter than that in the oral group ( 13 hours ) . The percentage of women aborting within 24 hours in the vaginal group ( 90 % ) was significantly higher than that in the oral group ( 69 % ) . The median amount of misoprostol  used in the vaginal group ( 600 μg ) also was significantly less than that in the oral group ( 1000 μg ) . There was no significant difference in the incidence of side effects between the two groups except for fatigue and breast tenderness , which were more common in the oral group . Seventy-six percent of the women preferred the oral route , and 24.5 % of the women preferred the vaginal route . Conclusion Vaginal misoprostol is more effective than oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone , but more women preferred the oral route Background . Vitamin A has well‐recognized benefits for prevention of diarrhea , but the impact of therapeutic doses given during diarrhea on biochemical and clinical outcomes is less clear . We investigated these potential therapeutic benefits within a study of the optimum time for vitamin A supplementation to promote vitamin A status . Methods . Young children with severe diarrhea were r and omized to receive 60 mg of retinol as retinyl palmitate during acute diarrhea or once symptoms had resolved , usually after 5 to 8 days . Either during acute diarrhea or after its resolution , children not receiving vitamin A were given identical placebo . On Days 0 and 3 we measured urinary neopterin , plasma retinol and acute phase proteins and intestinal permeability by the lactulose/mannitol test . Eight weeks after discharge children returned to hospital for a modified dose response test of vitamin A stores . Results . Most children presented with  watery diarrhea and grossly abnormal intestinal permeability and immune activation markers . At 8 weeks plasma retinol concentrations of children receiving vitamin A during acute diarrhea , compared with those receiving it in early convalescence [ 0.67 ( 95 % confidence interval , 0.58 to 0.76 ) & mgr;mol/l vs. 0.68 ( 95 % confidence interval , 0.59 to 0.79 ) & mgr;mol/l ] , and the proportion of children with deficient vitamin A stores ( 7 of 34 vs. 8 of 34 ) did not differ . Clinical features , lactulose/mannitol tests and urinary neopterin concentrations on Day 3 also did not differ significantly when vitamin A was given early or late . Conclusions . Even when it was given during severe diarrhea , a large dose of vitamin A improved vitamin A stores in a population in whom vitamin A deficiency is a public health problem . Vitamin A did not significantly improve early clinical or biochemical recovery from severe diarrhea Objectives . To examine whether early enteral iron supplementation ( EI ) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency ( ID ) in infants with a birth weight of < 1301 g. Methods . Infants were r and omly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of > 100 mL/kg/day were tolerated ( EI ) or at 61 days of life ( late enteral iron supplementation [ LI ] ) . Nutritional iron status was assessed : 1 ) at birth , 2 ) at 61 days of life , 3 ) when the infants reached a weight of 1.6 times birth weight , and 4 ) before blood was transfused at a hematocrit of < .25 . ID was defined by any one of the following criteria : ferritin , < 12 μg/L ; transferrin saturation , < 17 % ; or increase of absolute reticulocyte counts by > 50 % one week after the onset of enteral iron supplementation . Restrictive red cell transfusion guidelines were followed and all transfusions were documented . Erythropoietin was not administered . The primary outcome variables were : 1 ) ferritin at 61 days and 2 ) the number of infants with ID . Results . Ferritin at 61 days was not different between the groups . Infants in the LI group were more often iron-deficient ( 26/65 vs 10/68 ) and received more blood transfusions after day 14 of life . No adverse effects of EI were noted . Conclusions . EI is feasible and probably safe in infants with birth weight < 1301 g. EI may reduce the incidence of ID and the number of late blood transfusions . ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia . preterm infant , iron supplementation , iron deficiency , blood transfusion
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 ?