Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study.

BACKGROUND/AIM: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens. METHODS: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay. RESULTS: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 µg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations. CONCLUSIONS: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency.

Gastrointestinal bleeding due to idiopathic early onset of vitamin K deficiency bleeding in a girl baby 50 min after birth: a rare case.

BACKGROUND: The incidence of early-onset vitamin K deficiency bleeding (VKDB) in at-risk neonates who did not receive vitamin K supplementation varied from 6 to 12%. This case report aims to show that VKDB can occur abruptly after birth despite vitamin K1 1 mg IM being given immediately after birth. CASE PRESENTATION: A term female baby was born through vaginal delivery of a 28 years old mother, G1P0A0, 39-40 weeks gestation with normal APGAR score, and birth weight was 3445 g, birth length was 52 cm. During pregnancy, the mother did not take any drugs except vitamins. There are no abnormalities on the baby's physical examination. The anus is patent. Immediately after birth, the baby received a vitamin K1 1 mg intramuscularly. Abruptly, 50 min after delivery, there was meconium with lots of fresh blood. Laboratory results showed hemoglobin, 19.6 g/dL; leukocytes, 25,010/uL; platelets, 390,000/uL, with increased PT and aPTT. A peripheral blood smear showed a normal blood morphology. When 7 h old, the baby had much hematochezia. Laboratory results showed decreased hemoglobin to 17.5 g/dL and increased PT, aPTT, and INR. No abnormalities were found on the babygram and abdominal ultrasound. The working diagnosis was gastrointestinal bleeding due to idiopathic early-onset VKDB. The baby received vitamin K1 2 mg IM, Fresh Frozen Plasma, and a Packed Red Cells transfusion. The patient returned home in good clinical condition. CONCLUSION: Vitamin K1 1 mg IM prophylaxis should be given immediately after birth to prevent early-onset VKDB. In addition, pregnant women who receive drugs that interfere with vitamin K metabolism (anti-epileptic drugs, anti-tuberculosis drugs, vitamin K antagonist drugs) should be given prophylactic vitamin K1, 20 mg/d orally, for at least two weeks before the expected time of delivery.

Midwives' Perspectives about Vitamin K Prophylaxis Against Vitamin K Deficiency Bleeding of the Newborn.

BACKGROUND: The American Academy of Pediatrics recommends one intramuscular (IM) vitamin K injection at birth to prevent Vitamin K Deficiency Bleeding of the Newborn (VKDB). Among factors associated with IM vitamin K refusal, investigators have reported an increased frequency of IM vitamin K refusal among parents who select midwife-assisted deliveries. Reasons behind this association are unclear. METHODS: To understand the perspectives of midwives on IM vitamin K prophylaxis and approach to counseling parents using qualitative methodology, we conducted in-depth semi-structured interviews of midwives associated with 3 tertiary academic medical centers and surrounding communities in Connecticut, Iowa and Michigan. We used the grounded theory approach and the constant comparative method until saturation was reached. RESULTS: We interviewed 19 white female midwives from different training pathways. Participants who were Certified Nurse Midwives (CNMs) routinely recommended IM vitamin K prophylaxis and Certified Professional Midwives (CPMs) took a more neutral approach. The following 4 themes emerged: (1) Emphasis on an educational approach to counseling that supports parents' decision-making authority; (2) Low-intervention philosophy in the midwifery model of care attracts certain parents; (3) Need for relationship building between midwives and pediatricians and (4) Opportunities for the future. CONCLUSIONS: Midwives in our study perceived that the midwifery model of care, the focus on physiologic birth and prioritizing parents' decision-making autonomy appears to attract a sub-set of expectant parents with certain belief systems who question interventions such as IM vitamin K prophylaxis. There are opportunities for better collaboration between midwives and pediatricians.

Intracranial Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a Newborn.

We present a case of a 6-week-old infant who presented with seizure-like activity. Workup revealed abnormal coagulation and imaging confirmed intracranial hemorrhage. Parental refusal of vitamin K treatment at birth suggested vitamin K deficiency bleeding (VKDB) in this newborn. Though VKDB is rare in developed countries, rates have been rising which coincides with an increasing trend of parental refusal of vitamin K prophylaxis at birth.

Vitamin K prophylaxis in newborns.

We looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn (HDN).We conducted a literature search up to the 10th of December 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth are effective for preventing classical HDN. There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN. There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. From older trials and surveillance data, it seems that there is no significant difference between the intramuscular and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed. Evidence assessing vitamin K prophylaxis in preterm infants is scarce.

The challenge to define the optimal prophylactic regimen for vitamin K deficiency bleeding in infants.

Infants are at risk of vitamin K deficiency that may lead to vitamin K deficiency bleeding (VKDB). Although many vitamin K prophylactic regimens have been developed throughout the years, still cases of late form VKBD may occur. The introduction of combined prophylactic strategy with prolonged oral prophylaxes after the intramuscular dose at birth has showed a decrease of the late severe VKDB incidence. Nevertheless, there is still lack of consensus about the administration scheme after the first dose at birth. CONCLUSION: Late form VKBD is not eradicated, and the best prophylactic regimen in term and preterm infants is still an open debate.

Intracranial haemorrhage associated with Vitamin K deficiency in Egyptian infants.

AIM: Intracranial haemorrhage (ICH) in infancy is a rare life-threatening event. The aim of this review is to highlight the association of ICH and potentially preventable vitamin K deficiency and to describe risk factors, presentation and outcome. METHODS: Original published data on ICH related to vitamin K deficiency during 2008-2012 were extracted from records of participating centres in Egypt (Cairo and Delta region). Full data on 70 infants (0-24 weeks) have been reported in three publications. RESULTS: The first study involved premature infants where ICH was potentially preventable with administration of parenteral vitamin K prophylactic doses to mothers ahead of imminent preterm delivery. The other 2 studies involved term newborns and infants. ICH due to early or classic vitamin K deficiency was reported in nine patients while 44 were due to late vitamin K deficiency. Main risk factors for late onset were exclusive breastfeeding, persistent diarrhoea and/or prolonged antibiotic therapy. CONCLUSION: Vitamin K deficiency bleeding is a relatively frequent problem underlying ICH in infancy. Prophylactic vitamin K to mothers when anticipating preterm labour or a vitamin K boost in exclusively breast-fed infants with prolonged antibiotic usage and, or, persistent diarrhoea might have an impact on prevention and outcome.

Temporal association between serious bleeding and immunization: vitamin K deficiency as main causative factor.

BACKGROUND: Bleeding as an adverse event following immunization (AEFI) that is rarely reported in children, although it can be a parental concern. Bleeding episodes ranging in severity from mild to severe and defined as any external and/or internal bleeding can be caused by acquired or hereditary disorders. This study analyzes whether bleeding episodes in children that were recorded as AEFIs are causally associated with immunization and elaborates their etiology. METHODS: A cross-sectional study of 388 AEFI cases in children from West Java Provincial Committee in Indonesia confirmed by case findings from 2000 until 2017. RESULTS: Of the total number of cases studied, 55 (14%) involved children aged 5 days to 12 years who presented with bleeding and were referred to a provincial hospital. Analysis revealed that 32 cases were most likely caused by acquired prothrombin complex deficiency (APCD) and 30 of these APCD cases were strongly suspected to be manifestations of vitamin K deficiency bleeding (VKDB). All VKDB subjects were aged 5 days to 3 months without a history of administration of prophylactic vitamin K. When a World Health Organization classification was used, most bleeding cases in this study became coincidental events with a temporal association with immunization. A causality assessment suggested that these cases were causally unrelated. CONCLUSION: Most cases of bleeding reported as an AEFI were found to be VKDB, which is considered a coincidental event following immunization with a temporal association, and an unrelated category based on the results of a causality assessment. Vitamin K should be administered to all newborns as a prophylactic and AEFI surveillance should be improved based on the low numbers of AEFI reported in Indonesia.

Vitamin K Deficiency Bleeding: An Ounce of Prevention.

Vitamin K is a fat-soluble vitamin essential for the formation of factors in the clotting cascade. Newborns are born with insufficient levels of vitamin K, resulting in high risk for vitamin K deficiency bleeding (VKDB). Vitamin K deficiency bleeding can occur in the first week of life ("classic" VKDB) and also between 2 weeks and 3 months of age ("late" VKDB). Vitamin K deficiency bleeding can present as bleeding in the skin or gastrointestinal tract, with as many as half of affected neonates experiencing intracranial bleeding. A single intramuscular injection of vitamin K effectively prevents both classic and late VKDB. Although intramuscular vitamin K is safe and effective, VKDB has reemerged because of decreased utilization. Parents refuse intramuscular vitamin K for a variety of reasons, including a disproven association with childhood cancer, the desire to avoid exposure to additives, and valid concerns about early neonatal pain. Many parents request oral vitamin K, an inferior alternative strategy that requires multiple doses utilizing products not designed for neonatal oral administration. In this setting, health care professionals must understand the epidemiology of VKDB and compassionately counsel parents to assuage concerns. Delivery of intramuscular vitamin K to all newborns remains a public health imperative, benefitting thousands of infants annually.

A potential biotechnological process for the sustainable production of vitamin K1.

The primary objective of this review is to propose an approach for the biosynthesis of phylloquinone (vitamin K1) based upon its known sources, its role in photosynthesis and its biosynthetic pathway. The chemistry, health benefits, market, and industrial production of vitamin K are also summarized. Vitamin K compounds (K vitamers) are required for the normal function of at least 15 proteins involved in diverse physiological processes such as coagulation, tissue mineralization, inflammation, and neuroprotection. Vitamin K is essential for the prevention of Vitamin K Deficiency Bleeding (VKDB), especially in neonates. Increased vitamin K intake may also reduce the severity and/or risk of bone fracture, arterial calcification, inflammatory diseases, and cognitive decline. Consumers are increasingly favoring natural food and therapeutic products. However, the bulk of vitamin K products employed for both human and animal use are chemically synthesized. Biosynthesis of the menaquinones (vitamin K2) has been extensively researched. However, published research on the biotechnological production of phylloquinone is restricted to a handful of available articles and patents. We have found that microalgae are more suitable than plant cell cultures for the biosynthesis of phylloquinone. Many algae are richer in vitamin K1 than terrestrial plants, and algal cells are easier to manipulate. Vitamin K1 can be efficiently recovered from the biomass using supercritical carbon dioxide extraction.

Increasing the dose of oral vitamin K prophylaxis and its effect on bleeding risk.

Vitamin K prophylaxis in infancy aims to prevent life-threatening vitamin K deficiency bleeding (VKDB). The Dutch prophylactic oral daily regimen was increased sixfold from 25 to 150 µg because of a high failure rate. To evaluate the efficacy of this new regimen, incidences of intracranial VKDB under both regimens were compared using both general and targeted surveillance. Late VKDB in the general pediatric population was identified by the Netherlands Pediatric Surveillance Unit, between 1 October 2014 and 31 December 2016. Additionally, infants with intracranial vitamin K deficiency bleeding were identified using the Dutch Pediatric Intensive Care Evaluation registry. The incidence of intracranial VKDB as assessed by general and targeted surveillance decreased from 1.6 per 100,000 (95% CI, 0.4-5.1) to 1.3 per 100,000 (95% CI, 0.5-3.2) and from 3.1 per 100,000 live births (95% CI, 1.9-5.0) to 1.2 per 100,000 live births (95% CI, 0.6-2.3), respectively. Median time between consecutive cases in the latter increased from 24 to 154 days (p < 0.001).Conclusion: A sixfold increase in oral vitamin K prophylaxis was associated with a surprisingly modest reduction in the incidence of intracranial VKDB, indicating that factors other than the dose need addressing to improve efficacy. What is Known: • The efficacy of intramuscular vitamin K prophylaxis is threatened by an increasing number of parents opting out. • Oral prophylaxis represents an attractive and less invasive alternative but is inferior, especially in infants with malabsorption of vitamin K due to cholestasis. What is New: • Increasing the daily oral dose of vitamin K sixfold had a surprisingly modest effect on the incidence of late vitamin K deficiency bleeding. • This finding indicates that factors other than the dose must play an important role.

Spontaneous intracranial haemorrhage in children-intensive care needs and predictors of in-hospital mortality: a 10-year single-centre experience.

PURPOSE: Spontaneous intracranial haemorrhage (SICH) in children, although uncommon, is associated with significant mortality and morbidity. Paediatric data is however limited. MATERIAL AND METHODS: Case records of 105 children with SICH, > 1 month to 12 years, admitted to a tertiary level PICU of a teaching and referral hospital between January 2009 and May 2018 were analysed retrospectively. In-hospital mortality was the primary outcome. Variables between survivors and non-survivors were compared to  determine predictors of mortality. RESULTS: The median (IQR) age of subjects was 6 (2.25, 70) months. Common clinical features were altered sensorium (n = 87, 82.9%), seizures (n = 73, 69.5%), pallor (n = 66, 62.9%) and bulging anterior fontanelle (n = 52, 49.5%). Median (IQR) Glasgow Coma Scale (GCS) at admission was 10 (6, 13) with herniation noted in 27 (25.7%) children. Vitamin K deficiency bleeding (VKDB) and arteriovenous malformation (AVM) were the most common etiology for bleeding among infants and older children respectively. The most common site of bleeding was intracerebral (n = 47, 44.8%) followed by subdural (n = 26; 24.8%). Sixteen (15.2%) children died during hospital stay. On univariate analysis, GCS < 8, Pediatric Risk of Mortality score (PRISM III) > 20, need for intubation, thiopentone coma for refractory intracranial pressure (ICP) and progression to shock and acute kidney injury (AKI) predicted mortality. Seizures were favourably associated with survival. Age, site of bleeding, etiology or type of management for raised ICP (conservative versus decompressive craniectomy) did not affect the outcome. On multivariable analysis, progression to AKI (OR 5.86; 95% CI, 1.53-22.4; p 0.01) predicted poor outcome. Seizures, however, were associated with better odds for survival (OR 0.12; 95% CI, 0.03-0.47; p 0.002). CONCLUSIONS: VKDB and AVM were the common etiologies among infants and older children respectively. Age, site, etiology of bleeding and type of management did not affect outcome. Severe decompensation at presentation, thiopentone for refractory ICP and progression to multiorgan dysfunction determined mortality.

The Presentation of a Fussy Infant With Bruising: Late-Onset Vitamin K Deficiency Bleeding.

Vitamin K plays an integral role in the clotting cascade. Deficiency, specifically in vulnerable neonates with insufficient stores, can lead to spontaneous bleeding and devastating effects. In this case, we report a young infant with late-onset vitamin K deficiency bleeding who did not receive vitamin K prophylaxis after birth. Initially presenting with bruising and fussiness, the patient was later found to have intracerebral hemorrhage with midline shift and uncal herniation. The infant was not a surgical candidate and died shortly thereafter. Laboratory studies confirmed the diagnosis of late-onset vitamin K deficiency bleeding as the cause of hemorrhage and death.

Late-Onset Vitamin K Deficiency Presenting as Scrotal Bruising and Mediastinal Mass.

Although there are several reports of intracranial hemorrhage associated with vitamin K deficient bleeding, there are few reported cases of extracranial manifestations, specifically involving the thymus. Here, we discuss the unique case of a 4-week-old infant presenting with scrotal discoloration, respiratory distress, and widened mediastinum, found to have thymic hemorrhage related to confirmed coagulopathy secondary to late-onset vitamin K deficiency bleeding of the newborn.

[CURRENT APPROACHES TO PREVENTION OF BLEEDINGS, ASSOCIATED WITH VITAMIN K DEFICIENCY IN NEWBORNS AND INFANTS].

In the article intended for neonatologists, general practitioners and family doctors, the main causes of hemostatic disorders that lead to the development of hemorrhagic syndrome in newborns and infants are given. The emphasis is on the different forms of neonatal hemorrhagic disease (HD), which is based on the deficiency of vitamin K1, and therefore the bleeding that is observed in children who are breastfed in the first half of life is mostly associated, namely, with vitamin K deficiency. Risk factors of HD depending from the time of the beginning, of the action of one or another factor. The main clinical manifestations of both early and late forms of HD are described, it is shown which of them are mistakenly diagnosed that lead to the appointment of the wrong treatment. The assessment of the need for prevention of late form of bleeding associated with vitamin K deficiency is carried out by determining the concentration in the blood of a functional coagulation marker - PIVKA II. Modern methods of prevention of late bleeding associated with vitamin K1 deficiency, based on nosological units - chronic cholestasis, cystic fibrosis, are presented. The current recommendations on the use of vitamin K1 in newborns and infants of the American Academy of Pediatrics, the scientific community of Canada, Netherlands, Switzerland, Germany, France, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the World Health Organization, which are clearly followed by the effects of local peculiarities are described and interpreted. on approaches to the prevention of bleeding associated with vitamin K1 deficiency, which affects the choice of a single dose, the duration of the prophylactic course and the route of administration of vitamin in K1 (phytomenadion). The role of parents in the prevention of vitamin K deficiency is emphasized.

Characterization of vitamin K-dependent carboxylase mutations that cause bleeding and nonbleeding disorders.

Vitamin K-dependent coagulation factors deficiency is a bleeding disorder mainly associated with mutations in γ-glutamyl carboxylase (GGCX) that often has fatal outcomes. Some patients with nonbleeding syndromes linked to GGCX mutations, however, show no coagulation abnormalities. The correlation between GGCX genotypes and their clinical phenotypes has been previously unknown. Here we report the identification and characterization of novel GGCX mutations in a patient with both severe cerebral bleeding disorder and comorbid Keutel syndrome, a nonbleeding malady caused by functional defects of matrix γ-carboxyglutamate protein (MGP). To characterize GGCX mutants in a cellular milieu, we established a cell-based assay by stably expressing 2 reporter proteins (a chimeric coagulation factor and MGP) in HEK293 cells. The endogenous GGCX gene in these cells was knocked out by CRISPR-Cas9-mediated genome editing. Our results show that, compared with wild-type GGCX, the patient's GGCX D153G mutant significantly decreased coagulation factor carboxylation and abolished MGP carboxylation at the physiological concentration of vitamin K. Higher vitamin K concentrations can restore up to 60% of coagulation factor carboxylation but do not ameliorate MGP carboxylation. These results are consistent with the clinical results obtained from the patient treated with vitamin K, suggesting that the D153G alteration in GGCX is the causative mutation for both the bleeding and nonbleeding disorders in our patient. These findings provide the first evidence of a GGCX mutation resulting in 2 distinct clinical phenotypes; the established cell-based assay provides a powerful tool for studying the clinical consequences of naturally occurring GGCX mutations in vivo.

Prophylactic vitamin K for the prevention of vitamin K deficiency bleeding in preterm neonates.

BACKGROUND: Vitamin K is necessary for the synthesis of coagulation factors. Term infants, especially those who are exclusively breast fed, are deficient in vitamin K and consequently may have vitamin K deficiency bleeding (VKDB). Preterm infants are potentially at greater risk for VKDB because of delayed feeding and subsequent delay in the colonization of their gastrointestinal system with vitamin K producing microflora, as well as immature hepatic and hemostatic function.  OBJECTIVES: To determine the effect of vitamin K prophylaxis in the prevention of vitamin K deficiency bleeding (VKDB) in preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11), MEDLINE via PubMed (1966 to 5 December 2016), Embase (1980 to 5 December 2016), and CINAHL (1982 to 5 December 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs of any preparation of vitamin K given to preterm infants. DATA COLLECTION AND ANALYSIS: We evaluated potential studies and extracted data in accordance with the recommendations of Cochrane Neonatal. MAIN RESULTS: We did not identify any eligible studies that compared vitamin K to no treatment.One study compared intravenous (IV) to intramuscular (IM) administration of vitamin K and compared various dosages of vitamin K. Three different prophylactic regimes of vitamin K (0.5 mg IM, 0.2 mg vitamin K1, or 0.2 mg IV) were given to infants less than 32 weeks' gestation. Given that only one small study met the inclusion criteria, we assessed the quality of the evidence for the outcomes evaluated as low.Intramuscular versus intravenousThere was no statistically significant difference in vitamin K levels in the 0.2 mg IV group when compared to the infants that received either 0.2 or 0.5 mg vitamin K IM (control) on day 5. By day 25, vitamin K1 levels had declined in all of the groups, but infants who received 0.5 mg vitamin K IM had higher levels of vitamin K1 than either the 0.2 mg IV group or the 0.2 mg IM group.Vitamin K1 2,3-epoxide (vitamin K1O) levels in the infants that received 0.2 mg IV were not statistically different from those in the control group on day 5 or 25 of the study. All of the infants had normal or supraphysiologic levels of vitamin K1 concentrations and either no detectable or insignificant amounts of prothrombin induced by vitamin K absence-II (PIVKA II).Dosage comparisonsDay 5 vitamin K1 levels and vitamin K1O levels were significantly lower in the 0.2 mg IM group when compared to the 0.5 mg IM group. On day 25, vitamin K1O levels and vitamin K1 levels in the 0.2 mg IM group and the 0.5 mg IM group were not significantly different. Presence of PIVKA II proteins in the 0.2 mg IM group versus the 0.5 mg IM group was not significantly different at day 5 or 25 of the study. AUTHORS' CONCLUSIONS: Preterm infants have low levels of vitamin K and develop detectable PIVKA proteins during the first week of life. Despite being at risk for VKDB, there are no studies comparing vitamin K versus non-treatment and few studies that address potential dosing strategies for effective treatment. Dosage studies suggest that we are currently giving doses of vitamin K to preterm infants that lead to supraphysiologic levels. Because of current uncertainty, clinicians will have to extrapolate data from term infants to preterm infants. Since there is no available evidence that vitamin K is harmful or ineffective and since vitamin K is an inexpensive drug, it seems prudent to follow the recommendations of expert bodies and give vitamin K to preterm infants. However, further research on appropriate dose and route of administration is warranted.

Estimated costs for treatment and prophylaxis of newborn vitamin K deficiency bleeding in Tashkent, Uzbekistan.

Vitamin K deficiency bleeding (VKDB) is a preventable cause of infant mortality and long-term morbidity through the world. This study aimed to demonstrate the costs of VKDB treatment estimated from the hospital records in Tashkent, Uzbekistan, as well as the prophylaxis costs for mass vitamin K medication. Subjects were 50 patients with no operation and 50 patients who had received a brain operation, consecutively enrolled from 180 cases diagnosed at Republican Research Center of Emergency Medicine in 2014. In that year, an additional 22 VKDB patients were found in Tashkent; the incidence of VKDB was 478/100,000 among 42,225 newborns. The prophylaxis costs for all newborns in Tashkent were estimated under a plausible condition. The average age at admission was 43.2 days among 100 patients (67 boys and 33 girls) with birth weight from 2,600 g to 3,800 g (3,105 g on average). The great majority of patients (92.0%) were breastfed; 89.5% in boys and 97.0% in girls. Average treatment cost per VKDB patient was 365 USD for the operated and 285 USD for the non-operated. Total expenses of the 202 patients were estimated to be 64,603 USD. A single prophylaxis was estimated to cost 1.24 USD, totaling 52,359 USD for the prophylaxis of 42,225 newborns. Since the reduction of VKDB incidence through prophylaxis is considered to be higher than 78.5% (52,359/64,603), provision of prophylaxis services would reduce the total costs of VKDB treatment in Uzbekistan, where prophylaxis is not provided.

Position Statement: Guidelines for vitamin K prophylaxis in newborns: A joint statement of the Canadian Paediatric Society and the College of Family Physicians of Canada.

Newborns are at risk for vitamin K deficiency bleeding (VKDB) caused by inadequate prenatal storage and deficiency of vitamin K in breast milk. Systematic review of evidence to date suggests that a single intramuscular (IM) injection of vitamin K at birth effectively prevents VKDB. Current scientific data suggest that single or repeated doses of oral (PO) vitamin K are less effective than IM vitamin K in preventing VKDB. The Canadian Paediatric Society and the College of Family Physicians of Canada recommend routine IM administration of a single dose of vitamin K at 0.5 mg to 1.0 mg to all newborns. Administering PO vitamin K (2.0 mg at birth, repeated at 2 to 4 and 6 to 8 weeks of age) should be confined to newborns whose parents decline IM vitamin K. Health care providers should clarify with parents that newborns are at increased risk of VKDB if such a regimen is chosen. Current evidence is insufficient to recommend routine intravenous vitamin K administration to preterm infants undergoing intensive care.Keywords HDNB; Newborn; Prophylaxis; Vitamin K; VKDB.

Parental Refusal of Vitamin K and Neonatal Preventive Services: A Need for Surveillance.

Objectives Vitamin K deficiency bleeding (VKDB) in infants is a coagulopathy preventable with a single dose of injectable vitamin K at birth. The Tennessee Department of Health (TDH) and Centers for Disease Control and Prevention (CDC) investigated vitamin K refusal among parents in 2013 after learning of four cases of VKDB associated with prophylaxis refusal. Methods Chart reviews were conducted at Nashville-area hospitals for 2011-2013 and Tennessee birthing centers for 2013 to identify parents who had refused injectable vitamin K for their infants. Contact information was obtained for parents, and they were surveyed regarding their reasons for refusing. Results At hospitals, 3.0% of infants did not receive injectable vitamin K due to parental refusal in 2013, a frequency higher than in 2011 and 2012. This percentage was much higher at birthing centers, where 31% of infants did not receive injectable vitamin K. The most common responses for refusal were a belief that the injection was unnecessary (53%) and a desire for a natural birthing process (36%). Refusal of other preventive services was common, with 66% of families refusing vitamin K, newborn eye care with erythromycin, and the neonatal dose of hepatitis B vaccine. Conclusions for Practice Refusal of injectable vitamin K was more common among families choosing to give birth at birthing centers than at hospitals, and was related to refusal of other preventive services in our study. Surveillance of vitamin K refusal rates could assist in further understanding this occurrence and tailoring effective strategies for mitigation.