Vitamin K prophylaxis and late vitamin K deficiency bleeding in infants: Fifth nationwide survey in Japan

Background: In 1980, the first nationwide survey on late vitamin K deficiency bleeding (VKDB) in infants was conducted in Japan, and it was followed by the second, third and fourth nationwide surveys in 1985, 1988 and 1991, respectively. The fifth nationwide survey was designed to ascertain the epidemiology of late VKDB between January 1999 and December 2004. Patients and methods: Questionnaires were sent to 2161 hospitals in Japan that employed members of the Japan Pediatric Society in March 2005. Responses were received from 1373 hospitals, for a response rate of 63.5%. Results: The total number of reported cases was 71, including 21 idiopathic type and 16 secondary type. The incidence of late VKDB was estimated to be 1.9 cases per 100 000 births (95% confidence interval: 1.2–3.0) during this survey period. In 34 cases, the presence or absence of any underlying disease was not clarified. A total of 67/71 infants were entirely breast‐fed. Intracranial hemorrhaging was observed in 26 (63.4%) out of 41 infants whose bleeding sites were described in the questionnaires. In 63 cases (88.7%) of late VKDB found in the present survey, however, vitamin K had been given at least once either during or after the neonatal period. Conclusions: A reevaluation of the current prophylaxis strategy for late VKDB in infants is necessary.     

Oral vitamin K1 prophylaxis for newborns with a new mixed-micellar preparation of phylloquinone: 3 years experience in Switzerland

In 1995, a new water-soluble mixed-micellar analogue of vitamin K₁ (Konakion MM paediatric) was introduced in Switzerland to replace the formerly used fat-soluble Konakion drops for the prevention of vitamin K₁-deficiency-bleeding (VKDB) in infants. According to the new guidelines, an oral dose of 2 mg is given after birth and again on the 4th day of life. We examined the compliance with these guidelines and the impact on the incidence of VKDB. To assess compliance, questionnaires were sent to all hospitals with delivery services 6 months after the introduction of the new guidelines. Using the database of the Swiss Paediatric Surveillance Unit (SPSU) which records rare paediatric diseases, we assessed the incidence of VKDB in Switzerland between July 1995 and June 1998. In addition, we determined the precise circumstances under which the episodes of VKDB occurred. More than 99% of infants received vitamin K₁ prophylaxis. Since July 1995, 93% of newborns have received prophylaxis according to the new guidelines; the remaining infants were given fat-soluble Konakion drops or parenteral vitamin K₁. Within 3 years, one case of classical and 12 cases of late-onset VKDB (11 confirmed, 1 probable) were reported to the SPSU. Of the 11 confirmed late-onset cases, 7 received the recommended prophylaxis, whereas 3 had not and 1 had been given fat-soluble Konakion drops. All confirmed cases of late-onset VKDB occurred in fully breast-fed infants and 8 of 11 had hepatobiliary disease. Conclusion With the introduction of two oral doses of a mixed-micellar vitamin K₁ preparation administered in the 1st week of life, the incidence of late vitamin K₁-deficiency-bleeding has decreased from 7.2:100 000 between 1986–1987 to 2.8:100 000 between 1995 and 1998. This regimen may be suitable for prophylaxis of vitamin K₁-deficiency-bleeding, however, it does not fully protect infants with cholestatic disease from late-onset bleeding. If oral prophylaxis is considered for these infants, vitamin K₁ has to be administered repeatedly to all infants during the breast feeding period. Received: 13 October 1998 / Accepted in revised form: 5 January 1999     

Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric Surveillance Unit Surveys, 1993 94 and 2001-02

Objective

To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988–90 survey (VKDB‐90).

Design

Two 2‐year surveys conducted during 1993–4 (VKDB‐94) and 2001–02 (VKDB‐02).

Setting

Data collected from all consultant paediatricians in Great Britain and Ireland.

Patients

All infants presenting with bleeding resulting from vitamin K (VK) deficiency.

Main outcome measures

Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features.

Results

Compared with previous studies, VKDB‐02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long‐term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast‐fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB‐90, 10 of 32 in VKDB‐94 and 4 (because of parental refusal) of 7 in VKDB‐02. Seven received one oral dose of VK in VKDB‐90, 16 in VKDB‐94 and none in VKDB‐02. Underlying liver disease was found in six cases in VKDB‐90, 12 in VKDB‐94 and one in VKDB‐02.

Conclusions

In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast‐fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.     

Prevention of vitamin K deficiency bleeding with oral mixed micellar phylloquinone: results of a 6-year surveillance in Switzerland

In 1995, a new form of vitamin K prophylaxis with two oral doses of 2 mg mixed micellar phylloquinone (Konakion MM) on the 1st and 4th day of life was introduced in Switzerland. It was hoped that this new galenic preparation of phylloquinone would protect infants with insufficient or absent bile acid excretion from late vitamin K deficiency bleeding (VKDB). Subsequently, the occurrence of VKDB was monitored prospectively between July 1, 1995 and June 30, 2001 with the help of the Swiss Paediatric Surveillance Unit (SPSU). Over a period of 6 years (475,000 deliveries), there were no cases of early (<24 h of age), one case of classical (2–7 days of life), and 18 cases of late (1–12 weeks) VKDB fulfilling standard case definitions. In 13/18 patients with late VKDB there was pre-existing liver disease and in 4/18 patients, parents had refused prophylaxis. The incidence of late VKDB for infants with completed Konakion MM prophylaxis was 2.31/100,000 (95% CI: 1.16–4.14) and for the entire population 3.79/100,000 (95% CI: 2.24–5.98). There was only one case of late VKDB after complete prophylaxis in an infant without underlying liver disease. Conclusion: two oral doses of 2 mg of a mixed micellar vitamin K preparation failed to abolish VKDB. The recommendations for vitamin K prophylaxis in Switzerland have therefore been changed to include a third dose at 4 weeks of age. Starting on January 1, 2004, the incidence of vitamin K deficiency bleeding will again be monitored prospectively by the Swiss Paediatric Surveillance Unit.Abbreviations CI confidence interval - SPSU Swiss Paediatric Surveillance Unit - VKDB vitamin K deficiency bleeding     

Neonatal vitamin K prophylaxis in Denmark: three years' experience with oral administration during the first three months of life compared with one oral administration at birth

A Danish surveillance group established after the introduction of oral vitamin K prophylaxis monitored Danish cases with late onset vitamin K deficiency bleeding by regular questionnaires to all paediatric departments. Six cases were reported, one of whom died and three are severely handicapped. All cases occurred among an estimated 134,500 infants given a single oral 1 mg vitamin K' dose at birth. No cases have been reported so far during the existent regimen: 2 mg at birth and 1 mg weekly orally administered vitamin K during the first 3 months of life, given to at least 163,000 infants. The present study is concordant with the only other study on weekly peroral prophylaxis published. We consider the mentioned weekly regimen safe and appropriate.     

Incidence of late vitamin K deficiency bleeding in newborns in the Netherlands in 2005: evaluation of the current guideline

Vitamin K prophylaxis is recommended to prevent the hazard of haemorrhage caused by vitamin K deficiency in newborns. The present Dutch guideline recommends 1 mg of vitamin K₁ orally at birth, followed by a daily dose of 25 μg of vitamin K₁ from 1 to 13 weeks of age for breastfed infants. Since the introduction of this prophylaxis, the incidence of vitamin K deficiency bleeding (VKDB) has decreased; however, late VKDB is still reported. From 1 January to 31 December 2005, a nationwide active surveillance was performed by the Netherlands Paediatric Surveillance Unit (NSCK) to study the current incidence and aetiology of late VKDB in infants. Six cases could be validated as late VKDB: all were breastfed, one fatal idiopathic intracranial haemorrhage at the age of 5 weeks and five bleedings secondary to an underlying cholestatic liver disease between the age of 3 and 7 weeks. The total incidence of late VKDB and idiopathic late VKDB was calculated to be 3.2 (95% CI: 1.2–6.9) and 0.5 (95% CI: 0–2.9) per 100,000 live births, respectively. With the current Dutch guideline, idiopathic late VKDB is rare but late VKDB secondary to cholestasis still occurs in breastfed infants. Doubling the daily dose of vitamin K₁ to 50 μg, as is comparable to formula-feeding, may possibly prevent VKDB in this group. Further research, however, is needed to prove this hypothesis.     

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1

Abstract: The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K₁ prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K₁, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K₁. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K₁ were to have a longer duration of effect than intravenous vitamin K₁. This may be because intramuscular vitamin K₁ acts as a depot preparation. The findings suggest that intravenous vitamin K₁ is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K₁ should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.     

Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric Surveillance Unit Surveys, 1993 94 and 2001-02.

OBJECTIVE: To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988-90 survey (VKDB-90). DESIGN: Two 2-year surveys conducted during 1993-4 (VKDB-94) and 2001-02 (VKDB-02). SETTING: Data collected from all consultant paediatricians in Great Britain and Ireland. PATIENTS: All infants presenting with bleeding resulting from vitamin K (VK) deficiency. MAIN OUTCOME MEASURES: Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features. RESULTS: Compared with previous studies, VKDB-02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long-term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast-fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB-90, 10 of 32 in VKDB-94 and 4 (because of parental refusal) of 7 in VKDB-02. Seven received one oral dose of VK in VKDB-90, 16 in VKDB-94 and none in VKDB-02. Underlying liver disease was found in six cases in VKDB-90, 12 in VKDB-94 and one in VKDB-02. CONCLUSIONS: In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast-fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.     

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

Aim: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at 1 wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. Results: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1.17-3.13, p = 0.006).

Conclusion: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.     

Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K

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 Netherlands and Switzerland 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 Netherlands); (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) (Switzerland). 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 Netherlands; (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 Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0–0.7) in The Netherlands; (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 Switzerland. 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. Received: 12 April 1996 / Accepted: 21 July 1996     

Vitamin K concentrations in the maternal milk of Japanese women

Aim: To determine the concentration of vitamin K including K1 (phylloquinone) and K2 (menaquinone-n; MK-n) in the maternal milk of Japanese women. Methods: We collected human milk samples from more than 4000 mothers living throughout Japan from December 1998 to September 1999, and analysed the contents of vitamin K1 and K2 in 834 of the samples. We defined as group A the 555 samples among them that met the following conditions: breast milk of mothers who were under 40 y old, not in the habit of smoking and/or using vitamin supplements, and whose babies showed no symptoms of atopy and whose birthweights were 2.5 kg or more. Vitamins extracted from the enzymatic hydrolysates of the human milk were purified with a Sep-Pak Plus silica cartridge, and then measured by a method based on high-performance liquid chromatography (HPLC) combined with coulometric reduction and fluorometric detection. Results: The mean concentration of vitamin K (K1 + K2) of mothers of group A and all groups were 0.434 ± 0.293 and 0.517 ± 1.521 μg/100 ml (average ± SD), respectively, and menaquinones containing 4, 6 and 7 isoprenoid residues could be detected in the milk samples. Vitamins K1 and MK-4 were found to be predominant in the milk samples, and the concentration of MK-4 in colostrum was higher than that of MK-4 in mature milk. We also found that the MK-7 concentration in the milk of mothers living in eastern Japan was higher than that of mothers living in western Japan.

Conclusion: The different features of vitamin K1 and MK-7 concentrations in the milk of Japanese women may be due to differences in dietary foods.     

Vitamin K prophylaxis: Leaving the old route for the new one?

Oral or parenteral administration of vitamin K is the accepted practice for prevention of early vitamin K deficiency bleeding (VKDB) in the newborn. However, vitamin K prophylaxis in the newborn continues to be a worldwide health concern, particularly in breastfed infants. This paper reviews the current status of the use of vitamin K for the prevention of early and late VKDB.     

Vitamin K status of lactating mothers and their infants

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 μg kg⁻¹ d⁻¹) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.     

Prevention of vitamin K deficiency bleeding with three oral mixed micellar phylloquinone doses: results of a 6-year (2005–2011) surveillance in Switzerland

In 2003, the Swiss guidelines to prevent vitamin K deficiency bleeding (VKDB) were adapted. As two oral doses (2 mg, hour/day 4) of mixed micellar VK preparation had failed to abolish late VKDB, a third dose (week 4) was introduced. This report summarizes the new guidelines acceptance by Swiss pediatricians and the results of a prospective 6-year surveillance to study their influence on the incidence of VKDB. The new guidelines acceptance by Swiss pediatricians was evaluated by a questionnaire sent to all pediatricians of the Swiss Society of Paediatrics. With the help of the Swiss Paediatric Surveillance Unit, the incidence of VKDB was monitored prospectively from July 1, 2005 until June 30, 2011. Over a 6-year period (458,184 live births), there was one case of early and four cases of late VKDB. Overall incidence was 1.09/10⁵ (95 % confidence intervals (CI) 0.4–2.6). Late VKDB incidence was 0.87/10⁵ (95 % CI 0.24–2.24). All four infants with late VKDB had an undiagnosed cholestasis at the time of bleeding; parents of 3/4 had refused VK prophylaxis, and in 1/4, the third VK dose had been forgotten. Compared with historical control who had received only two oral doses of mixed micellar VK (18 cases for 475,372 live births), the incidence of late VKDB was significantly lower with three oral doses (Chi²,Yates correction, P?=?0.007). Conclusion VKDB prophylaxis with 3?×?2 mg oral doses of mixed micellar VK seems to prevent adequately infants from VKDB. The main risk factors for VKDB in breast-fed infants are parental VK prophylaxis refusal or an unknown cholestasis.     

New Zealand surveillance of neonatal vitamin K deficiency bleeding (VKDB): 1998-2008

Aim: To undertake surveillance of vitamin K deficiency bleeding (VKDB) from 1998, through the transition to a new single licensed vitamin K preparation in 2001, to 2008. Methods: VKDB was listed with other rare conditions on the card sent monthly to registered specialist paediatricians by the New Zealand Paediatric Surveillance Unit with a request to indicate whether or not a case had been seen in the previous month. Those notifying a case were sent a two‐page questionnaire. The main outcome measures were incidence of VKDB of early (first day of life), classic (days 2–7) and late‐onset (day 8 to 6 months) type; related morbidity and mortality; receipt of vitamin K; and predisposing factors. Results: Response rate of return of surveillance cards was high, averaging 94.5%. There were 35 notifications of which 23 were valid cases. Seventeen cases met criteria for confirmed VKDB, two for ‘probable’ and four for ‘possible’. There were eight confirmed classic cases with an overall incidence of 1.24 (95% confidence interval 0.54–2.45) per 100 000 births; none had received vitamin K prophylaxis, seven were fully breastfed and all fully recovered. There were nine confirmed late‐onset cases with an overall incidence of 1.40 (95% confidence interval 0.64–2.65) per 100 000 births; eight had received no vitamin K, eight were fully breastfed, six had liver disease, four suffered an intracranial haemorrhage and one died. Conclusions: In New Zealand, VKDB is virtually confined to fully breastfed infants not given vitamin K at birth. Late‐onset cases were frequently associated with liver disease.     

Can 3 oral 2 mg doses of vitamin K effectively prevent late vitamin K deficiency bleeding?

A 1 mg dose of vitamin K given intramuscularly at birth prevents almost all cases of late VKDB, whereas even two oral doses of 1 mg vitamin K given in the first week and a third given in week 5 to 6 are less effective. Is efficacy improved by increasing the dose to 3 2 2 mg? For active surveillance of VKDB, monthly postcards which include a nothing-to-report option, were sent to all heads of pediatric hospitals in Germany from January 1995 to December 1998. All reports were validated according to a standard case definition for late VKDB by means of a questionnaire. The incidence of VKDB with three oral doses of 2 mg vitamin K is compared to previously published rates for VKDB on 3 oral 1 mg oral doses, which had been ascertained with the same surveillance scheme. The number of cases of VKDB (excluding the failure-of-management cases) in children aged 8 days to 12 completed weeks during the 4 year period was 23. 14 had intracranial hemorrhage, 22 had been exclusively breastfed, and in 20 cholestasis was detected after the bleeding episode. 14/23 had been given all recommended 2 mg doses for vitamin K prophylaxis. Until 1996 all had been given the cremophor vitamin K preparation, whereas in 1997 to 1998 two children with late VKBD had received the new mixed micellar (MM) preparation, first licensed in July 1996. The incidence of VKBD per 100,000 live births during the 1995 to 1998 period was 0.72, including children given no vitamin K prophylaxis, and 0.44 for children who had received all age-related recommended vitamin K doses. These incidence rates are significantly lower than those previously published for the 3 2 1 mg dose regimen in Germany (1.8 cases of late VKDB per 100,000 live births in children who had received all recommended vitamin K doses). Not all cases of late VKDB, however, are prevented by the 3 2 2 mg dose regimen, even if the new mixed micellar preparation is given instead of the cremophor preparation.     

Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding

OBJECTIVE: To determine whether the use of mixed micellar vitamin K improves the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule. DESIGN: Nationwide active surveillance for vitamin K deficiency bleeding (VKDB) complemented with two surveys on the use of the mixed micellar preparation in hospitals and by paediatricians. SETTING AND PATIENTS: Infants in Germany in 1997-2000. INTERVENTION: Prophylaxis with three oral doses of 2 mg mixed micellar vitamin K. MAIN OUTCOME MEASURE: Confirmed VKDB between day 8 and week 12 and no condition requiring specific vitamin K supplementation known before the onset of bleeding. RESULTS: Twenty nine reports met the case definition: seven had not received any vitamin K prophylaxis; for three, vitamin K prophylaxis was unknown; two had insufficient vitamin K prophylaxis for their age; 17 had been given the recommended doses. The mixed micellar preparation had been given to seven, other preparations to nine, and one had been given both. These cases did not differ with respect to the site of bleeding and cholestasis detected at bleeding. Estimates of the use of the mixed micellar preparation in birth hospitals and by paediatricians yielded 1 817 769 newborns exposed to the mixed micellar preparation and 1 320 926 newborns exposed to other preparations. The rate of late VKDB was 0.44/100 000 (95% confidence interval (CI) 0.19 to 0.87) in children given mixed micellar vitamin K compared with 0.76/100 000 (95% CI 0.36 to 1.39) in children given other preparations. CONCLUSION: Mixed micellar vitamin K did not significantly improve the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule.     

Vitamin K,an update for the paediatrician

Introduction  This review summarizes current knowledge on vitamin K for the paediatrician. Vitamin K is a fat-soluble vitamin, present in plants as phylloquinone and produced by bacteria as menaquinone. It is acting as a co-factor for γ-glutamyl carboxylase. This enzyme is responsible for post-translational modification of some glutamate side chains to γ-carboxyglutamate. The majority of γ-carboxylated proteins function in blood coagulation; others play a role in calcium homeostasis. Data  Newborn babies are at particular risk of vitamin K deficiency, as placental transfer is limited and human milk is a poor source. Vitamin K prophylaxis at birth effectively prevents vitamin K deficiency bleeding (VKDB), formerly known as “haemorrhagic disease of the newborn”. Recent epidemiological studies provide data on the effectiveness of different administration routes and dosing schemes. Infants of mothers taking drugs that inhibit vitamin K are at risk of early VKDB and should receive 1 mg intramuscular (IM) as soon as possible after birth. Classic VKDB is prevented by intramuscular as well as by oral administration of 1 mg vitamin K. In exclusively breast-fed infants, single IM administration at birth is also effectively preventing (rare) late VKDB but single oral administration is not. If given orally, prophylaxis should be continued by either weekly administration of 1 mg till 12 weeks or repeating 2 mg at weeks 1 and 4. Daily administration of 25 μg offers insufficient protection. The only infants not fully protected in this way are those with yet unrecognised liver disease. Conclusions  Further work is needed before firm recommendations can be made regarding dose in preterm infants and in patients with fat malabsorption/cholestasis or regarding the role of vitamin K in the prevention of osteoporosis.     

Mother-infant skin-to-skin contact after delivery results in early recognition of own mother's milk odour

Aim: To determine the effects of mother-infant skin-to-skin contact immediately after birth on infant recognition of their own mother's milk odour and breastfeeding duration until 1 y of age. Methods: Sixty healthy, full-term neonates were randomly assigned to group A with skin-to-skin contact and group B without. One and 4 d after birth, infant responses to the following odour stimuli were observed: own mother's milk, another mother's milk, formula, orange juice and distilled water. Infant facial action was videotaped and the frequency of mouthing movements was evaluated for each stimulus. Nutritional assessment, focused particularly on breastfeeding, was performed every 3 mo on participating infants. Statistical analysis comparing the frequency of mouthing movements with the aforementioned five different odour exposures was performed by ANOVA with Fisher's PLSD. Kaplan-Meier analysis with a log-rank test was used to compare breastfeeding rates between groups. Results: Infants in both groups responded differently to mother's milk odour (either their own or another mother's milk) compared to the other stimuli on days 1 and 4. However, infants in group A demonstrated a larger difference in mouthing movements between their own and another mother's milk odour at 4 d of age (2.6 ± 1.6) compared to infants in group B (0.9 ± 2.0, p = 0.01). Infants in group A were breastfed an average of 1.9 mo longer than the others.

Conclusion: Our study provides evidence that mother-infant skin-to-skin contact for more than 50 min immediately after birth results in enhanced infant recognition of their own mother's milk odour and longer breastfeeding duration.     

Late vitamin K deficiency bleeding in infants: five-year prospective study

ObjectiveTo study the presenting clinical and demographic features, risk factors, and outcome of infants with late vitamin K deficiency bleeding.MethodsOver a 5-year study period, the presenting clinical features and outcome of all 47 infants observed aged less than 6 months, who were diagnosed with late-onset primary and secondary VKDB by detailed history, physical examination, and laboratory findings were evaluated. Confirmed primary late VKDB was diagnosed when no cause other than breastfeeding could be found, while in the secondary subtype additional risk factors compromising the vitamin K effect were diagnosed.ResultsSecondary late VKDB (83%, 39 patients) was more common than the primary subtype. The mean age of patients was 10.50 ± 5.75 and 9.74 ± 6.04 weeks in primary and secondary VKDB subtypes, respectively, and the age of infants did not have a significant difference (p > 0.05). The male to female ratio was 2.13:1. The residency, place and mode of delivery, gestational age, and types of feeding of patients did not have a significant difference between VKDB subtypes. The skin and gastrointestinal tract (GIT) (40.4%) followed by intracranial hemorrhage (ICH) (32%), were common sites of bleeding. Neurological complications were seen in 21% of patients; however, lethality was 23%, and the outcome of patients did not have a significant difference (p > 0.05) between VKDB subtypes.ConclusionSecondary late VKDB is more common than the primary subtypes, and late VKDB is still a serious disease in developing countries, including Iraq, when vitamin K prophylaxis isn’t routinely used at birth.