Background
Introduction
Why is vitamin K important?
Context
Key questions
Key question 1 | Key question 2 | Key question 3 | |
---|---|---|---|
Participants
| Neonates | ||
Intervention
| Vitamin K supplement | Oral vitamin K supplement | Multiple doses of vitamin K supplement |
Comparison
| Placebo or no vitamin K supplement | Parenteral vitamin K supplement | Single dose of vitamin K |
Outcome
| HDN or VKDB | ||
Adverse effects
| Any adverse effect |
Search methods and selected manuscripts
#4 Search (#1) AND #2 Filters: published in the last 10 years | |
#3 Search (#1) AND #2 | |
#2 Search (haemorrhagic disease of the newborn [Title/Abstract]) OR vitamin K deficiency [Title/Abstract] | |
#1 Search ((newborn*[Title/Abstract]) OR infant*[Title/Abstract]) OR neonat*[Title/Abstract] |
Sources | Final selected manuscripts |
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WHO | • WHO recommendations on newborn health [3] • Pregnancy, childbirth, postpartum and newborn care: a guide for essential practice [4] • Recommendations for management of common childhood conditions: evidence for technical update of pocket book recommendations [5] |
USPSTF | None |
PrevInfad | • 2010 recommendations and supporting document [6] |
NICE | • NICE clinical guideline 2015 – Postnatal care up to 8 weeks after birth [7] |
CDC | • Recommendations [8] |
AAP | |
Cochrane Library | • Ardell 2018 – Prophylactic vitamin K for the prevention of vitamin K deficiency bleeding in preterm neonates (Systematic review) [11] • Puckett 2000 (published before 2010, but supporting evidence used for PrevInfad and WHO recommendations) [12] |
Pubmed | • Sankar 2016 (Systematic review) [2] • Martín-López 2011 (Systematic review) [13] • Löwensteyn 2019 (Cohort study) [14] • Witt 2016 (Cohort study) [15] • Mihatsch 2016 (ESPGHAN position paper with review of the literature and recommendations) [16] • Canadian Agency for Drugs and Technologies in Health 2015 (Review) [17] |
Existing recommendations
Source | Ref | Date | General recommendations for use of prophylactic vitamin K in newborns |
---|---|---|---|
WHO | 2012, updated in 2017 | “All newborns should be given 1 mg of vitamin K intramuscularly (IM) after birth (i.e. after the first hour by which the infant should be in skin-to-skin contact with the mother and breastfeeding should be initiated).” (Strong recommendation, moderate quality evidence) “Neonates requiring surgical procedures, those with birth trauma, preterm newborns, and those exposed in utero to maternal medication known to interfere with vitamin K are at especially high risk of bleeding and must be given vitamin K (1 mg IM).” (Strong recommendation, moderate quality evidence) | |
[4] | 2015 | “Give 1 mg of vitamin K IM to all newborns, one hour after birth” | |
PrevInfad | [6] | 2010 | After birth, prophylactic vitamin K should be administered to prevent HDN (Strong recommendation). After birth, IM administration of 1 mg of vitamin K is recommended to prevent classical HDN (Strong recommendation). After birth, IM administration of 1 mg of vitamin K is recommended to prevent late HDN (Weak recommendation). In case of parents who do not want IM administration, oral administration of 2 mg of vitamin K is recommended followed by 1 mg weekly until 12 weeks of age in totally or partially breastfed infants (Weak recommendation). For preterm babies: • < 32 weeks and > 1000 g: 0.5 mg IM or IV • < 1000 g independently of gestational age: 0.3 mg IM or IV (Weak recommendation) |
NICE | [7] | 2015 | “All parents should be offered vitamin K prophylaxis for their babies to prevent the rare but serious and sometimes fatal disorder of vitamin K deficiency bleeding.” “Vitamin K should be administered as a single dose of 1 mg intramuscularly as this is the most clinically and cost-effective method of administration.” “If parents decline intramuscular vitamin K for their baby, oral vitamin K should be offered as a second-line option. Parents should be advised that oral vitamin K must be given according to the manufacturer’s instructions for clinical efficacy and will require multiple doses.” Note: These recommendations were established in 2006 when the first clinical guideline was published, but updated in 2015. |
CDC | [8] | Updated 2018 | One shot intramuscularly in the thigh just after birth, can be delayed up to 6 h after birth. |
AAP | 2003 (updated 2020) | “Vitamin K1 should be given to all newborns as a single, intramuscular dose of 0.5 to 1 mg.” “Additional research should be conducted on the efficacy, safety, and bioavailability of oral formulations and optimal dosing regimens of vitamin K to prevent late VKDB.” “Health care professionals should promote aware- ness among families of the risks of late VKDB associated with inadequate vitamin K prophylaxis from current oral dosage regimens, particularly for newborns who are breastfed exclusively.” | |
ESPGHAN | [16] | 2016 | “Healthy newborn infants should either receive: (a) 1 mg of Vitamin K1 by IM injection at birth, OR (b) 3 × 2 mg Vitamin K1 orally at birth, at 4 to 6 days and at 4 to 6 weeks, OR (c) 2 mg Vitamin K1 orally at birth, and a weekly dose of 1 mg orally for 3 months.” “The oral route is not appropriate for preterm infants and for newborns who are unwell, have cholestasis or impaired intestinal absorption or are unable to take oral vitamin K, or those whose mothers have taken medications that interfere with vitamin K metabolism.” |
CADTH | [17] | 2015 | “Single intramuscular dose of vitamin K (0.5 mg for birthweight ≤1500 g or 1.0 mg for birthweight ≥1500 g) should be administered to all newborns within the first 6 h after birth.” “If intramuscular vitamin K is refused by parents, an oral dose of 2 mg vitamin K was recommended at the time of first feeding, followed by a second dose at 2 to 4 weeks, and a third dose at 6 to 8 weeks.” |
Existing evidence
Vitamin K versus placebo or no treatment for preventing HDN
IM vitamin K (single dose) versus placebo or no treatment
Oral vitamin K (single dose) versus placebo or no treatment
Oral versus intramuscular vitamin K for preventing HDN
Country | Vitamin K prophylaxis | Incidence of HDN per 100,000 infants, RR (95% CI) |
---|---|---|
Denmark | ||
1994 to June 2000 | 2 mg po at birth, 1 mg po weekly for 3 months | 0.0 (0 to 0.9) |
After June 2000 | 2 mg IM at birth | Not available |
France | 2 mg po weekly for 6 weeks | Not available |
Germany | 2 mg po for 3 doses: days 1, 4–10 and 28–42 | 0.44 (0.2 to 0.9) |
Netherlands | (A) 1 mg po at birth, 25 μg po daily from week 2 to 13 (B) 1 mg po at birth, 150 μg po daily from week 2 to 13 | (A) 3.2 (1.2 to 6.9) Intracranial HDN, general and targeted surveillance (A) 1.6 (0.4 to 5.1) and 3.1 (1.9 to 5.0) (B) 1.3 (0.5 to 3.2) and 1.2 (0.6 to 2.3) |
United Kingdom | 1 mg IM at birth | 0.1 |
2 mg po for 3 doses: day 1, weeks 1 and 4 | 0.43 | |
Spain | 1 mg IM at birth | ‘Almost inexistent’a |
Switzerland | 2 mg po for 3 doses: day 1, day 4, week 4 | 0.0 (0.0 to 0.81)b [16] 1.09 (0.4 to 2.6) [17] |
Single dose of oral versus IM vitamin K
Multiple doses of oral versus single dose of IM vitamin K
Vitamin K prophylaxis for preventing HDN in preterm babies
Adverse effects
Summary of findings
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All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth is effective for preventing classical HDN.
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There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN.
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There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. As such trials are unlikely to be conducted, the efficiency of the different regimens is assessed by national epidemiological surveillance.
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Older trials comparing oral versus intramuscular administration of vitamin K do not report clinical bleeding as outcome but conclude that both routes of administration improve biochemical indices of coagulation status.
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Looking at surveillance data from European countries, it seems that there is no significant difference between the IM and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed.
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The oral route is not appropriate for newborns with biliary atresia.
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Evidence assessing vitamin K prophylaxis in preterm infants is scarce.