Vitamin K to Neonates: Peroral versus Intramuscular Administration Prevention of subclinical vitamin K deficiency based on PIVKA-II levels: oral versus intramuscular route. [Effects of the administration of vitamin K on the activity of Factor II, VII and X in healthy newborns]. Combined Antenatal Vitamin K and Phenobarbital Therapy for Preventing Intracranial Hemorrhage in Newborns Less Than 34 Weeks' Gestation EFFECT OF VITAMIN K ADMINISTRATION ON ACARBOXY PROTHROMBIN (PIVKA-II) LEVELS IN NEWBORNS Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants. Comparative study of oral versus injectable vitamin K in neonates. A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K Vitamin K1 concentration in breast-fed neonates after oral or intramuscular administration of a single dose of a new mixed-micellar preparation of phylloquinone. Does vitamin C and vitamin E supplementation prolong the latency period before delivery following the preterm premature rupture of membranes? A randomized controlled study. Can oral vitamin K before elective surgery substitute for preoperative heparin bridging in patients on vitamin K antagonists? Role of ethamsylate in preventing periventricular-intraventricular hemorrhage in premature infants below 34 weeks of gestation. Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study) 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.
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 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 The study was design ed to know the effect of oral vitamin K ( VK ) treatment , on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II ( PIVCA II ) on full term infants . Seventy healthy newborns were studied and each was r and omly placed in one of two groups : Group A , newborns that received  human milk and milk formula ( mixed feeding ) and group B , newborns that were exclusively breast fed . These groups were also divided in two subgroups : I received 2 mg of VK1 orally and II ( control ) did not receive VK .  Clotting activity of the coagulation factors and PIVCA II was determined from blood plasma obtained immediately after birth and 48 hours after VK administration . Basal activity of the factors analyzed was similar in all groups with values ranging from 25 % to 40 % . After 48 hours a significant increase in all factors studied and a decrease of PIVKA II was observed in those children who received oral VK . The results suggest that oral VK effectively increases VK dependent factors and prevents the risk of hemorrhagic disease in the newborn , with the advantage of being less traumatic and less risky to the infant than intramuscular VK Objective To determine whether maternal antenatal therapy with vitamin K and phenobarbital prevents intracranial hemorrhage in premature newborns . Methods Women at high risk for spontaneous or indicated premature delivery before 34 weeks ' gestation were r and omly assigned to receive either placebo or vitamin K and phenobarbital . All patients received betamethasone and antibiotics and were managed uniformly by a single perinatal group in one hospital . All newborns were managed uniformly in the same nursery by one neonatal group . Two independent interpretations of neonatal head ultrasound examinations were obtained . Results The duration of gestation at study entry and at delivery were similar in the  placebo ( 181 mothers ) and treatment ( 191 ) groups . With the hospital radiology group ( the primary interpreter ) , the incidence rates of severe intracranial hemorrhage ( 8 versus 7 % ) and mild intracranial hemorrhage ( 38 versus 32 % ) were similar for both groups . With the secondary interpreter ( a single pediatric radiologist ) , the incidence rates of severe intracranial hemorrhage ( 9 versus 7 % ) and mild intracranial hemorrhage ( 27 versus 26 % ) were also similar . Neonatal mortality was equivalent in both the placebo and treatment groups ( 8 versus 10 % ) . Conclusion Combined antenatal therapy with vitamin K and phenobarbital does not reduce the frequency or severity of intracranial hemorrhage in premature newborns 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 omised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1 , proteins induced by vitamin K absence ( PIVKA-II ) , and clotting factors . Two groups of about 165 healthy breast fed infants who received at r and om 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age . Although  vitamin K1 concentrations were statistically significantly higher in the intramuscular group , blood coagulability , activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups . At 2 weeks of age  vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable . At 3 months  vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5 % of infants . Therefore , a repeated oral prophylaxis will be necessary to completely prevent ( biochemical ) vitamin K deficiency beyond the age of 1 month 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 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 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 The plasma disposition of a new mixed-micellar preparation ( KONAKION MM , Roche ) of phylloquinone ( vitamin K1 ) has been studied in 25 healthy , fully breast-fed , newborn babies , r and omized to receive a single dose of either 1.5 mg i.m . ( 11 babies ) or 3 mg p.o . ( 14 babies ) . Venous blood sample s were collected at 25 h , 4 days , and 24 days . After p.o . administration , the median plasma phylloquinone concentration increased to 89 ng/ml after 24 h , then decreased to 51 ng/ml after 4 days ; the respective concentrations after i.m . injection were 146 ng/ml and 34 ng/ml . The higher plasma phylloquinone level in the i.m . group after 24 h was not statistically significant compared with that of the p.o . group , but the reversed higher concentration in the p.o . group after 4 days was significant ( p < 0.01 ) . After 24 days the median plasma phylloquinone had decreased to 0.44 ng/ml ( range 0.19 - 1.44 ) and 1.05 ng/ml ( range 0.37 - 1.87 ) in the p.o . and i.m . groups , respectively . There was a significant difference between these plasma concentrations ( p < 0.01 ) . They were within or above the reference adult fasting range ( 0.17 - 0.68 ng/ml ) . The narrow range of plasma concentrations at 24 h and 4 days suggests a greater consistency of absorption from this micellar preparation than from other emulsion-based preparations . Further studies are required to assess the long-term protection of a single oral dose against late hemorrhagic disease of the newborn . Until such time , breast-fed babies given this preparation orally should receive ( an ) additional dose(s ) OBJECTIVE To determine whether maternal vitamin C and vitamin E supplementation after the premature rupture of membranes is associated with an increase in the latency period before delivery . METHODS In the present prospect i ve open r and omized trial , 229 pregnant women with preterm premature rupture of membranes ( PPROM ) at ≥ 24.0 and < 34.0 weeks ' gestation were r and omly assigned to receive either 1,000 mg of vitamin C and 400 IU of vitamin E ( n = 126 ) or a placebo ( n = 123 ) . The primary outcome was the latency period until delivery . Analysis was performed on an intention-to-treat basis . RESULTS No significant differences in demographic or clinical characteristics were observed between the groups . Latency period until delivery was significantly higher in the group that received vitamins compared with the control group ( 11.2 ± 6.3 days versus 6.2 ± 4.0 days ; p < 0.001 ) . Gestational age at delivery was also significantly higher in the vitamin group compared with the control group ( 31.9 ± 2.6 weeks versus 31.0 ± 2.6 weeks ; p = 0.01 ) . No significant differences in adverse maternal outcome ( i.e. , chorioamnionitis or endometritis ) or neonatal outcome ( i.e. , neonatal sepsis , neonatal death , necrotizing enterocolitis , or grade 3 to 4 intraventricular hemorrhage ) were noted between groups . CONCLUSIONS The findings of the present study suggest that the use of vitamins C and E in women with PPROM is associated with a longer latency period before delivery . Moreover , adverse neonatal and maternal outcomes , which are often associated with prolonged latency periods , were similar between the groups BACKGROUND After a vitamin K antagonist ( VKA ) overdose , 1 - 2 mg of oral vitamin K can lower the International Normalized Ratio ( INR ) to the therapeutic range . OBJECTIVE To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to < or = 1.5 before elective surgery . METHODS Patients on long-term VKAs were r and omized either to heparin bridging after the last VKA dose on day -5 before surgery ( group H ) or to VKA treatment until day -2 , followed by 1 mg of oral vitamin K on the day before surgery ( group K ) . Blood clotting variables were assessed on days -5/-2 , 1 and 0 , and postoperatively . If the target INR was not achieved 2 h before incision , surgery was deferred or performed after injection of prothrombin complex concentrate ( PCC ) . RESULTS In 30 of 94 included patients , baseline INR was outside the chosen range ( 18 , INR < 2 ; 12 , INR > 3.5 ) , leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index , VKA treatment duration and indication , scheduled surgery , preoperative and postoperative hemoglobin , and blood loss . The INR was significantly higher in group K on days -1 and 0 than in group H. An INR < or = 1.5 was not achieved in 20 group K patients ( 66 % ) . Surgery was postponed or performed after PCC injection in 12 of these 20 patients . CONCLUSIONS Oral vitamin K ( 1 mg ) can not substitute for heparin bridging before surgery . In addition , one-third of patients on VKAs were exposed to a risk of bleeding ( overdose ) or thrombosis ( underdose ) , thus highlighting the need for new oral anticoagulants OBJECTIVE To determine the role of ethamsylate in prevention of PVH-IVH in premature infants < 34 weeks gestational age . DESIGN Prospect i ve , r and omized , controlled study . METHODS Infants less than 34 weeks gestational age were included in the trial . Neonates with congenital malformations , family history of bleeding disorders and with Apgar scores < 5 at 5 minutes were excluded . Subjects were r and omized into two groups -- Group A infants received intravenous ethamsylate ( 12.5 mg/kg ) six hourly for four days and Group B infants served as a control group . Regular cranial ultrasounds  to detect the presence of PVH-IVH were done between days 3 - 5 , 10 - 14 and 28 - 30 of post natal age , and before hospital discharge in all infants and weekly in infants detected to have PVH-IVH on earlier scans . Various antenatal and postnatal factors known to affect the incidence of PVH-IVH were recorded . RESULTS A total of 192 infants underwent the trial , 93 in Group A and 99 in Group B. Antenatal corticosteroids ( 1 or 2 doses ) were administered to 32 ( 34.4 % ) and 36 ( 36.3 % ) women in Group A and Group B , respectively . None of the mothers received phenobarbitone , vitamin K or indomethacin antenatally and none of the infants received phenobarbitone , vitamin E or indomethacin postnatally during the study period . PVH-IVH was seen in 26 infants in Group A , of which Grade I IVH occurred in 9 , Grade II in 14 , Grade III in 2 and Grade IV in one infant . Twenty-nine infants had PVH-IVH in Group B of which 11 had Grade I , 15 Grade II and 3 Grade III . None of the differences were statistically significant . CONCLUSION Postnatal administration of ethamsylate did not decrease the incidence of PVH-IVH in the study infants BACKGROUND Supplementation of vitamin A in children aged 6 - 59 months improves child survival and is implemented as global policy . Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results . We aim ed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days ( 6 months ) . METHODS We did an individually r and omised , double-blind , placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania . Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam . In Kilombero , Ulanga , and Kilosa districts , women were seen at home as part of the health and demographic surveillance system . Newborn infants were eligible for r and omisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months . We r and omly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth . Infants were r and omly assigned in blocks of 20 , and investigators , participants ' families , and data analysis teams were masked to treatment assignment . We assessed infants on day 1 and day 3 after dosing , as well as at 1 , 3 , 6 , and 12 months after birth . The primary endpoint was mortality at 6 months , assessed by field interviews . The primary analysis included only children who were not lost to follow-up . This trial is registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , number ACTRN12610000636055 . FINDINGS Between Aug 26 , 2010 , and March 3 , 2013 , 31,999 newborn babies were r and omly assigned to receive vitamin A ( n=15,995 ) or placebo ( n=16,004 ; 15,428 and 15,464 included in analysis of mortality at 6 months , respectively ) . We did not find any evidence for a beneficial effect of vitamin A  supplementation on mortality in infants at 6 months ( 26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group ; risk ratio 1·10 , 95 % CI 0·95 - 1·26 ; p=0·193 ) . There was no evidence of a differential effect for vitamin A supplementation on mortality by sex ; risk ratio for mortality at 6 months for boys was 1·08 ( 0·90 - 1·29 ) and for girls was 1·12 ( 0·91 - 1·39 ) . There was also no evidence of adverse effects of supplementation within 3 days of dosing . INTERPRETATION Neonatal vitamin A supplementation did not result in any immediate adverse events , but had no beneficial effect on survival in infants in Tanzania . These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation . FUNDING Bill & Melinda Gates Foundation to WHO Introduction In  vitamin K antagonist (VKA)-treated patients with severe hemorrhage , guidelines recommend prompt VKA reversal with prothrombin complex concentrate ( PCC ) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality . Methods Data from consecutive patients treated with PCC were prospect ively collected in 44 emergency departments .  Type of hemorrhage , coagulation parameters , type of treatment and seven-day mortality mortality were recorded . Guideline -concordant administration of PCC and vitamin K ( GC-PCC-K ) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission . Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage ( ICH ) . Results Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months .  Bleeding was gastrointestinal ( 32 % ) , intracranial ( 32 % ) , muscular ( 13 % ) , and “ other ” ( 23 % ) . In the whole cohort , seven-day mortality was 13 % and 33 % in patients with ICH . GC-PCC-K was performed in 38 % of all patients and 44 % of ICH patients . Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K ( odds ratio ( OR ) = 2.15 ( 1.20 to 3.88 ) ; P = 0.011 ) ; this mortality reduction was also observed when only ICH was considered ( OR = 3.23 ( 1.53 to 6.79 ) ; P = 0.002 ) . Conclusions Guideline -concordant VKA reversal with PCC and vitamin K within eight hours after admission was associated with a significant decrease in seven-day mortality 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
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 ?