ABSTRACT
- Objective: Examine coagulation outcomes of Vitamin K intervention (via injection) within infants diagnosed with vitamin k deficiency bleeding (VKDB).
- Design: A systematic literature review of studies published from 2012 to 2015 concerning vitamin K deficiency bleeding in infants and the prophylaxis of vitamin k injections related to coagulation meters.
- Results: Of the 4 citations identified and included, the most common outcome was a significant impact on vitamin k deficiency bleeding in newborns with vitamin k intervention at birth. Neonates that received vitamin K injection at birth did not experience vitamin k deficiency bleeding. Neonates who did not receive vitamin k prophylaxis at birth had high rates of vitamin K deficiency bleeding and received vitamin k as a treatment to bleeding.
- Discussion: Findings determines consistency that vitamin k deficiency bleeding can be prevented by the use of vitamin k injection at 0.5-1.0mg at birth.
- Conclusion and Implications: Studies determine that hemorrhagic disorders are the most frequent bleeding disorder among newborns without vit k injection. More research can be done in developed countries as opposed to third world countries.
- Key Words: Vitamin K, Infant hemorrhagic disorders, vitamin k deficiency bleeding, infant deaths.
INTRODUCTION
Vitamin K plays a key role in many components of blood coagulation in humans. At birth, infants only have around 50% of proper coagulation factors making hemorrhage or bleeding high risk for infants.1Vitamin K deficiency bleeding is a very concerning cause of death in early infancy and neonates. While this is the case, it has also been determined to be completely preventable by proper prophylaxis at birth.3 It is routine for neonates to receive a vitamin K injection at birth dosed at 0.5-1.0 mg soon after delivery.1,2 This practice has been the means of preventing infant hemorrhagic disorders which are associated with high mortality rates and often long-term neurological disorders.2 Developed countries have routine practice of administering vitamin k at birth while third world countries often do not, and have significant cases of infant bleeding. This review is aimed at looking at the evidence behind vitamin k prophylaxis at birth, the impact on infant hemorrhagic conditions, and the comparison between infants who have not received this preventative treatment at birth. The questions aimed to be answered is: In newborn infants less than a year old with vitamin k deficiency bleeding, how does 0.5-1mg vitamin K injection at birth within 6 hours compared to no supplementation, impact the coagulation factor during infancy?
METHODS
Databases Used: Pubmed, CINAHL
Key Search Terms
| Search terms related to the POPULATION | Search terms related to the INTERVENTION | Search terms related to the ALTERNATIVE or COMPARISON | Search terms related to OUTCOMES or EFFECTS |
| Infant (MeSH) Vitamin K Deficiency Bleeding (MeSH) Newborn Nutrition Disorders (MeSH) | Vit K (MeSH) Vit K Injection @ birth
Vit K IV |
VKDB (MeSH) No Vit k supplementation Breast Milk/Formula Vit K | Coagulation Factor (MeSH) Infant Bleeding Blood Clotting |
Inclusion Criteria
| Inclusion Criteria | |
| Age | <12 months old |
| Other Demographics | |
| Setting | Hospital/Place of birth |
| Health Status | Otherwise Healthy Newborn |
| Problem/Condition | Vit K deficiency bleeding |
| Study Design Preferences | Primary research articles |
| Size of Study Groups: | 10n n= study groups |
| Study Drop Out Rate: | 10% |
| Year Range | 2012-2022 |
| Authorship | Most recent review for authors on multiple articles |
| Language
Indicate if limited to articles in English |
English only |
| Article Citation | Reason(s) for Inclusion |
| Hutton ARJ, Quinn HL, McCague PJ, et al. Transdermal delivery of vitamin K using dissolving microneedles for the prevention of vitamin K deficiency bleeding. Int J Pharm. 2018;541(1-2):56-63. doi:10.1016/j.ijpharm.2018.02.031 | Newer research, inclusion of vkdb and vit k injection. |
| Araki S, Shirahata A. Vitamin K Deficiency Bleeding in Infancy. Nutrients. 2020;12(3):780. Published 2020 Mar 16. doi:10.3390/nu12030780 | Considers multiple factors inducing VKDB in infants, includes prevention |
| Hasbaoui BE, Karboubi L, Benjelloun BS. Newborn haemorrhagic disorders: about 30 cases. Pan Afr Med J. 2017;28:150. Published 2017 Oct 18. doi:10.11604/pamj.2017.28.150.13159 | Examines varying haemorrhagic disorders from the lens of vit k issues. Includes important coagulation information. |
| Santorino D, Siedner MJ, Mwanga-Amumpaire J, Shearer MJ, Harrington DJ, Wariyar U. Prevalence and Predictors of Functional Vitamin K Insufficiency in Mothers and Newborns in Uganda. Nutrients. 2015;7(10):8545-8552. doi:http://dx.doi.org/10.3390/nu7105408. | Includes vkdb across varying circumstances and examines coagulation |
Exclusion Criteria
| Exclusion Criteria Template | List Your Criteria Here |
| Age | >12 months |
| Other Demographics | |
| Setting | n/a |
| Health Status | Bleeding conditions that do not include vit K |
| Problem/Condition | Conditions unrelated to vit k |
| Study Design Preferences | SYstematic reviews/analysis |
| Size of Study Groups:
Typically, <10 per comparison group |
<10/ comparison group |
| Study Drop Out Rate:
Typically, you want to exclude if dropout rate is >20% |
>20% |
| Year Range | 0-1 year |
| Authorship | multiple articles from the same author |
| Language | English |
| Article Citation | Reason(s) for Exclusion |
| Ardell S, Offringa M, Ovelman C, Soll R. Prophylactic vitamin K for the prevention of vitamin K deficiency bleeding in preterm neonates. Cochrane Database Syst Rev. 2018;2(2):CD008342. Published 2018 Feb 5. doi:10.1002/14651858.CD008342.pub2 | Population is for preterm infants instead of term infants |
| Tie JK, Carneiro JD, Jin DY, Martinhago CD, Vermeer C, Stafford DW. Characterization of vitamin K-dependent carboxylase mutations that cause bleeding and nonbleeding disorders. Blood. 2016;127(15):1847-1855. doi:10.1182/blood-2015-10-677633
|
Discusses mutations which are not included in my research question
|
| Ng E, Loewy AD. Guidelines for vitamin K prophylaxis in newborns. Paediatric & Child Health (1205-7088). 2018;23(6):394-402. Doi: 10.1093/pch/pxy082 | Did not include any coagulation information |
RESULTS
| Author, Year,
Study Design, Country, Funding Source |
Quality Grade
(+, -, Ø) |
Study Purpose –
Should be a single objective statement in one to two sentences. |
Study Population
(Demographics) |
Intervention and Setting | Outcome Data | Conclusions/ Results – Should be a single conclusion statement in one to two sentences. |
| Santorino, Data; Siedner, Mark J; Mwanga-Amumpaire, Juliet; Shearer, Martin J; Harrington, Dominic J; et al.
2015
Retrospective cohort research
Funding: Mbarara University of Science and Technology, The German Academic Exchange Service and the Centre for Haemostasis and Thrombosis, St. Thomas’ Hospital, London |
+ | To determine the prevalence of vitamin k insufficiency in mothers and newborns in Uganda and the association of increased risk of bleeding | 141 mother-baby pairs over a period of 4 months. Median maternal age was 25 yrs. Median birth weight was 3.2kg. Spontaneous vaginal delivery accounted for 75% of deliveries with cesarean deliveries and one vacuum delivery accounting for the rest.
|
Mothers and babies in the peripartum ward at MRRH.
Women with self-reported liver disease, visible jaundice or taking warfarin were excluded We used questionnaires to collect socio-demographic data. Assessed maternal diet using a 22-item non-validated, and non-quantitative food frequency questionnaire to determine intake frequency of VK rich food. |
VK insufficiency defined by a detectable PIVKA-II of ě0.2 AU/mL was present in 33% (47/141) of mothers and 66% (93/141) of babies . Highly elevated, concentrations of PIVKA-II (ě5.0 AU/mL) indicative of likely abnormal coagulation were found in 22% (31/141) of newborns but in none of their mothers. No newborn babies had detectable postpartum bleeding before hospital discharge. However, all newborn babies received intramuscular vitamin K within one hour of delivery during the period of the study irrespective of study enrolment status.
|
Functional VK insufficiency evidenced by raised PIVKA-II is common among mothers and newborn babies in southwestern Uganda. Worryingly, 22% of babies had highly elevated PIVKA-II concentrations that are likely to be associated with an increased risk of bleeding.
|
|
Brahim El Hasbaoui,1,& Lamia Karboubi,1 et Badr Sououd Benjelloun1
2017
Randomized control study
Funding: Unknown
|
+ | Describe the epidemiological, diagnostic, and common causes of new-born hemorrhagic syndrome in pediatric emergency medical department of the Rabat Children’s Hospital.
|
30 cases of newborn hemorrhagic syndromes on 594 hospitalizations (5.05%). The sex-ratio (M/F) was 1.5. None of them received vitamin K after birth and all were breastfed. Mean gestational age of 38 weeks. Mean birth weight of 2700g.
|
Setting: Rabat Children’s Hospital.
Intervention: The detailed history included the mother’s general health and medical condition prior to delivery, the place of birth, and whether vitamin K was given at birth. Laboratory studies included complete blood count, partial thromboplastin time (PTT), prothrombin time (PT), and liver function tests. Vitamin K-dependent factor activities were performed when possible. After blood had been drawn for the baseline evaluation, vitamin K (l-2mg) was given intravenously. In babies with severe anaemia packed red blood cells and fresh frozen plasma were given. Cranial ultrasonography and computed tomography (CT) were performed in all babies for the diagnosis and the evaluation of intracranial bleeding.
|
. Vitamin K dependent factor activities (factors II, VII, IX and X) measured in three infants were decreased. Cranial and abdominal ultrasounds were normal in all our cases. The most common cause of bleeding was Haemorrhagic disease of the newborn, a disease resulting from a deficiency in Vitamin K and Vitamin K-dependent cofactors, it was seen in twenty-four babies (80%), followed by Disseminated intravascular coagulation (DIC) in three cases (10%), esophagitis in two cases and isolated thrombocytopenia in one cases
|
Most reports of late HDN have been in babies born at home and not given vitamin K prophylaxis.
|
| Shigeo Iijima,1 Toru Baba,1 Daizo Ueno,1 and Akira Ohishi1
Japan
2014
Funding: unknown |
+ | Establish reference intervals (RIs) of POC capillary puncture INR for a coagulation screening test in healthy term neonates and to evaluate factors that correlate with INR.
|
488 healthy term neonates
They were born at full term (37–41 weeks of gestation) with normal birth weight (2500–3999 g), and all of them were given 2 mg of vitamin K syrup (Menatetrenone Kaytwo Syrup, Eisai Co., Ltd., Tokyo, Japan) orally 6–12 h after birth.
|
Setting: Hamamastu University Hospital
Intervention: The coagulation screening test consisted of PT using a portable coagulometer, CoaguChek XS, and the INR was calculated. A single heel prick was performed and the first drop of capillary blood (at least 8 μL) obtained was then applied to the test strip, which was already inserted into the CoaguChek XS device. Next, a whole blood sample (approximately 40 μL) was collected into a heparinized capillary tube for measurement of serum bilirubin and hematocrit values. Finally, another whole blood sample (at most 200 μL) for mass-screening was collected
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Spearman correlation coefficient was 0.967 (p < 0.001). In addition, individual differences between laboratory INR and CoaguChek INR values were less than 0.1 in 11 cases (61%) and less than 0.15 in 17 cases (94%).
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In this study, we reported the RIs (0.90–1.30) for CoaguChek XS INR in healthy term neonates. In case an INR value exceeds 1.30, frequent (daily or weekly) oral vitamin K administration and follow-up CoaguChek XS INR evaluations should be recommended.
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Doniyorjon Tursunov,1,2 Yoshitoku Yoshida,1 Keneshbek Yrysov,1 Dilmurad Sabirov,2 Khilola Alimova,2Eiko Yamamoto,1 Joshua A. Reyer,1 and Nobuyuki Hamajima1
2018
Uzbekistan
Funding: unknown |
+ | Illustrate the costs of treatment of VKDB patients and prophylaxis in Tashkent Uzbekistan, based on hospital records and vital statistics on birth.
|
202 VKDB newborns were found in Tashkent among 42,225 live births; 151 patients had intracranial hemorrhage and another 51 patients had bleeding in different sites (post injection, intestine and nose).. All 100 patients had brain hematoma and considerable degree of bleeding in the brain. One non-operated patient out of the 100 patients died soon after arriving at hospital.
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Based on medical reports, patients’ expenses for tests (laboratory and imaging), medications, operations, and anesthesia were calculated from the first day in hospital until discharge. Medical service expenses documented on patient medical reports were calculated based on the prices fixed by the RRCEM in 2014.
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The incidence rate was 478 per 100,000 live births (95% CI, 415 to 548 per 100,000). The largest number of infants (92.0%) were breast-fed, only 2 babies were bottle-fed, and remaining 6 newborns was mixed (breast-fed and bottle-fed).
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The estimated treatment expenses for all 202 patients were about 172 million SOM (64,600 USD), while the prophylaxis cost for all newborns in Tashkent was estimated to be about 139 million SOM (52,000 USD). The total cost of prophylaxis was 81.0% of the cost for diagnosis and treatment of VKDB.
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DISCUSSION
Vitamin K deficiency bleeding in infancy is not as common as it used to be but is still an ongoing serious condition that occurs during the neonatal period. The cause of this condition often varies but are often correlated with the intravascular coagulation that is thus coincided with the lack of vitamin k present in newborn infants. Exclusively breastfed infants are at higher risk for VKDB due to the low amount of vitamin K present in breastmilk, making it even more imperative to have some kind of vitamin K intervention at birth. The most common vitamin K administration is via intramuscular injection of between 0.5-1mg of vitamin K at birth within the first hour. Higher instances of VKDB occurs among newborns that are not given vitamin K at birth, especially among the population in other countries where the vitamin k injection is not widely available. Vitamin K is thus considered a key component of coagulation to prevent VKDB in infancy.
There are a few strengths associated with this review. Between all research included in this review, the correlations stayed consistent and drew the same conclusions. Across all the research, vitamin k deficiency bleeding can be prevented by vitamin k prophylaxis at birth. Limitations, however, did include the questionnaires that were used by the studies that included questionnaires that were variable between studies, thus possibly leading to incongruences between research studies using questionnaires. With this understanding, there could be a need in the future accurate and standardized dietary records. Additionally, there is some lack of previous research in neonatal populations making it difficult to have data to formulate new research.
Gaps in research included knowledge gaps present among the mothers and populations among studies conducted in third world countries. There were no definitive determinations made regarding coagulation and vitamin k in relation to the prevention of VKDB.
CONCLUSION
Vitamin K intramuscular injection at birth within 6 hours has a direct impact on the coagulation factors in infancy, thus preventing vitamin K deficiency. Higher rates of VKDB occurs among populations where vitamin K injection is not available or declined at birth.
REFERENCES
- Hasbaoui BE, Karboubi L, Benjelloun BS. Newborn haemorrhagic disorders: about 30 cases. Pan Afr Med J. 2017;28:150. Published 2017 Oct 18. doi:10.11604/pamj.2017.28.150.13159
- Iijima S, Baba T, Ueno D, Ohishi A. International normalized ratio testing with point-of-care coagulometer in healthy term neonates. BMC Pediatr. 2014;14:179. Published 2014 Jul 9. doi:10.1186/1471-2431-14-179
- Tursunov D, Yoshida Y, Yrysov K, et al. Estimated costs for treatment and prophylaxis of newborn vitamin K deficiency bleeding in Tashkent, Uzbekistan. Nagoya J Med Sci. 2018;80(1):11-20. doi:10.18999/nagjms.80.1.11
- Santorino D, Siedner MJ, Mwanga-Amumpaire J, Shearer MJ, Harrington DJ, Wariyar U. Prevalence and Predictors of Functional Vitamin K Insufficiency in Mothers and Newborns in Uganda. Nutrients. 2015;7(10):8545-8552. Published 2015 Oct 16. doi:10.3390/nu7105408