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

Stephanie Ardell; Martin Offringa; Colleen Ovelman; Roger Soll

doi:10.1002/14651858.CD008342.pub2

Profilaktyczna podaż witaminy K w zapobieganiu krwawieniom z niedoboru witaminy K u wcześniaków

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Referencias

References to studies included in this review

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Clarke P, Mitchell SJ, Shearer MJ. Total and differential phylloquinone (Vitamin K1) intakes of preterm infants from all sources during the neonatal period. Nutrients 2015;7(10):8308‐20. [DOI: 10.3390/nu7105393; PUBMED: 26426042]

Clarke P, Mitchell SJ, Sundaram S, Win T, Roeves D, Shearer MJ. Vitamin K prophylaxis in preterm infants: evidence for current dose recommendations. Pediatric Academic Societies Annual Meeting; 2005 May 14‐17; Washington DC. Washington DC: Pediatric Academic Societies, 2005; Vol. 57:1321.

Google Scholar

Clarke P, Mitchell SJ, Wynn R, Sundaram S, Sharma V, Gardener E, et al. Vitamin K status in preterm Infants: a randomised controlled trial to compare three regimes of prophylaxis. Pediatric Academic Society Abstract Archive 2002‐2015. 2004; Vol. 2520.

Google Scholar

Clarke P, Mitchell SJ, Wynn R, Sundaram S, Sharma V, Gardener E, et al. Vitamin K status in preterm infants: a randomised controlled trial to compare three regimes of prophylaxis. Eastern Society for Pediatric Research Abstracts. 2004; Vol. 54:473.

Google Scholar

Clarke P, Mitchell SJ, Wynn R, Sundaram S, Speed V, Gardener E, et al. Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics 2006;118(6):e1657‐66.

Clarke PA. Comparison of vitamin K status in preterm infants following intravenous or intramuscular prophylaxis and the effects of feeding with preterm formula or fortified human milk [PhD thesis]. Manchester: University of Manchester, 2008.

References to studies excluded from this review

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Costakos DT, Greer FR, Love LA, Dahlen LR, Suttie JW. Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg. American Journal of Perinatology 2003;20(8):485‐90.

Kumar D, Greer FR, Super DM, Suttie JW, Moore JJ. Vitamin K status of premature infants: implications for current recommendations. Pediatrics 2001;108(5):1117‐22. [PUBMED: 11694690]

Ogata T, Motohara K, Endo F, Kondo Y, Ikeda T, Kudo Y, et al. Vitamin K effect in low birth weight infants. Pediatrics 1988;81(3):423‐7. [PUBMED: 3344186]

Rossi R, Albrecht O, Pollmann H, Jorch G, Harms E. Effect of a reduced vitamin K supplementation on prothrombin time in prematures and high‐risk neonates. Acta Paediatrica 1996;85(6):747‐9.

Seydewitz HH, Witt I, Pringsheim W, Kunzer W. The influence of vitamin K administration on the levels of prothrombin and acarboxy‐prothrombin in premature and small‐for‐date newborns during the first day of life; 3rd Congress on Thrombosis and Hemostasis, 1984 February 15‐18; Berne. Blut 1984;49(2):137‐8.

Google Scholar

Vakrilova L, Slŭncheva B, Mladenova A. The effects of intramuscular and oral prophylaxis with vitamin K on the coagulation status of low‐weight newborn infants [Bulgarian]. Akusherstvo i Ginekologiia (Sofiia) 1995;34(1):12‐4.

Google Scholar

Additional references

Ir a:

estudios incluidos
estudios excluidos
otras versiones publicadas

Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the healthy premature infant. Blood 1988;72(5):1651‐7.

Bovill EG, Soll RF, Lynch M, Bhushan F, Landesman M, Freije M, et al. Vitamin K1 metabolism and the production of des‐carboxy prothrombin and protein C in the term and premature neonate. Blood 1993;81(1):77‐83.

Clarke P, Mitchell S. Vitamin K prophylaxis in preterm infants: current practices. Journal of Thrombosis and Haemostasis 2003;1(2):384‐6.

Clarke P, Mitchell SJ, Sundaram S, Sharma V, Wynn R, Shearer M. Vitamin K status of preterm infants with a prolonged prothrombin time. Acta Paediatrica 2005;94(12):1822‐4.

Clarke P. Vitamin K prophylaxis for preterm infants. Early Human Development 2010;86(Supplement 1):17‐20.

American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. Pediatrics 2003;112(1 Pt 1):191‐2.

PubMed

Crowther CA, Crosby DD, Henderson‐Smart DJ. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD000229.pub2]

Dickson RC, Stubbs TM, Lazarchick J. Antenatal vitamin K therapy in the low‐birth‐weight infant. American Journal of Obstetrics and Gynecology 1994;170(1 Pt 1):85‐90.

McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed 5 December 2016. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015.

Greer FR, Marshall SP, Severson RR, Smith DA, Shearer MJ, Pace DG, et al. A new mixed micellar preparation for oral vitamin K prophylaxis: randomized controlled comparison with an intramuscular formulation in breast fed infants. Archives of Disease in Childhood 1998;79(4):300‐5.

Greer FR. Vitamin K the basics ‐ what's new?. Early Human Development 2010;86(Suppl 1):43‐7.

Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Kurata M, IIdaka T, Yamasaki N, Sasyama Y, Hamada Y. Battery of tests profiling abnormalities of Vitamin K‐dependent coagulation factors in drug‐toxicity studies in rats. Experimental Animals 2005;54(2):189‐92.

Liu J, Wang Q, Zhao JH, Chen YH, Qin GL. The combined antenatal corticosteroids and vitamin K therapy to prevent periventricular‐intraventricular hemorrhage in premature newborns less than 35 weeks gestational age. Journal of Tropical Pediatrics 2006;52(5):355‐9.

Morales WJ, Angel JL, O'Brien WF, Knuppel RA, Marsalisi F. The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage. American Journal of Obstetrics and Gynecology 1988;159(3):774‐9.

O’Shaughnessy D, Allen C, Woodcock T, Pearce K, Harvey J, Shearer M. Echis time, under‐carboxylated prothrombin and vitamin K status in intensive care patients. Clinical and Laboratory Haematology 2003;25(6):397‐404.

Puckett RM, Offringa M. Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database of Systematic Reviews 2000, Issue 4. [DOI: 10.1002/14651858.CD002776]

Pilcher E, Pilcher L. The neonatal coagulation system and the vitamin K deficiency bleeding ‐ a mini review. Wiener Medizinische Wochenschrift 2008;158(13‐4):385‐95.

Pomerance JJ, Teal JG, Gogolok JF, Brown S, Stewart ME. Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage. Obstetrics and Gynecology 1987;70(2):235‐41.

Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE Working Group. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations. Updated October 2013. Available from https://gdt.gradepro.org/app/handbook/handbook.html. (accessed 01 September 2017).

Solano C, Cobcroft RG, Scott DC. Prediction of vitamin K response using the Echis time and Echis‐prothrombin time ratio. Thrombosis and Haemostasis 1990;64(3):353‐7.

Van Winckel M, De Bruyne R, Van De Velde S, Van Bierveliet S. Vitamin K, an update for the pediatrician. European Journal of Pediatrics 2009;168(2):127‐34.

Yang YM, Simon N, Maertens P, Brigham S, Liu P. Maternal‐fetal transport of Vitamin K1 and its effects on coagulation in premature infants. Journal of Pediatrics 1989;115(6):1009‐13.

Zipursky A. Prevention of vitamin K deficiency in newborns. British Journal of Haematology 1999;106(1):256.

References to other published versions of this review

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Ardell S, Offringa M, Soll R. Prophylactic vitamin K for the prevention of vitamin K deficiency bleeding in preterm neonates. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD008342]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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Clarke 2006

Methods	Randomized controlled trial (RCT) Computer generated allocation sequence using variable block sizes of 6 and 12 Blinding of treatment assignment: treatment allocation was sealed in sequentially numbered opaque envelopes that were opened at the central coordinating unit Stratified by gestational period (< 28 weeks; 28 to 31 + 6 weeks) Blinding of treatment: unclear Blinding of outcome measurement: unclear Completeness of follow‐up: 82% of enrolled infants were analyzed
Participants	Eligible infants were < 32 weeks' gestational age. Exclusion criteria included fetal intracranial hemorrhage, maternal antiplatelet antibody, maternal drug treatment with known vitamin K antagonists, major congenital anomalies, and marked bruising at birth. During the study period the study authors identified 152 eligible infants, of whom 98 were randomized.
Interventions	Eligible infants were randomly assigned to receive 1 of 3 regimens of vitamin K prophylaxis (0.5 mg IM, 0.2 mg IM, 0.2 mg IV). For the purpose of this comparison, we compared both groups that received IM vitamin K to the single group that received IV vitamin K (the 0.2 mg IM (N = 32) dose to the 0.2 mg IV dose (N = 29) as well as the 0.5 mg IM dose (N = 29) to the 0.2 mg IV dose (N = 29)). The vitamin K preparation used was Konakion Neonatal (Roche Ltd, Basel, Switzerland) which has phytomenadione (2 mg/mL) solubilized in Cremophor EL. The allocated vitamin K regimen was prescribed by the attending physician and given either by medical or nursing staff as soon as possible after admission. One rescue dose of vitamin K 0.2 mg IM was given to any infant who, at any time, had an abnormal coagulation test (prolonged prothrombin time beyond the 95 percentile preterm reference for age) or clinical signs of bleeding.
Outcomes	Outcomes measured included serum vitamin K₁ levels, vitamin Vitamin K₁ 2,3‐epoxide (K10) and PIVKA II. vitamin K₁ and K₁O were measured using high performance liquid chromatography on day 5 and day 25 of life. vitamin K₁ levels in the enrolled infants were compared to levels in adults (0.17 to 0.68 ng/mL, if fasting, 0.15 to 1.55 ng/mL in non‐fasting). There are no adult reference values for K₁O because it is not a normal metabolite of healthy adults. PIVKA II levels were evaluated on cord blood samples and serum samples on day 5 and day 25 of life. PIVKA II was measured using enzyme‐linked immunosorbent assay using a conformation specific monoclonal antibody that selectively binds under‐carboxylated species of prothrombin. PIVKA II levels < 1 arbitrary units/mL were considered clinically insignificant. Secondary outcome measures were PT and factor II (FII) concentrations measured on citrated plasma on day 5 and at full feeds. PT was measured using a semi‐automated coagulation analyzer. At day 5 there were 90 valid samples and at day 25 there were 80 valid samples for all 3 treatment groups.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	RCT. Computer generated allocation sequence using variable block sizes of 6 and 12
Allocation concealment (selection bias)	Unclear risk	Blinding of treatment assignment: treatment allocation was sealed in sequentially numbered opaque envelopes that were opened at the central coordinating unit. Stratified by gestational period (< 28 weeks; 28 to 31 + 6 weeks)
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Blinding of treatment: unclear
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding of outcome measurement: unclear
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 82% of enrolled infants were analyzed
Selective reporting (reporting bias)	Low risk	No study protocol available, but all clinically relevant outcomes are reported and it is unlikely that any selective reporting bias occurred.
Other bias	Low risk	There are no concerns regarding other potential sources of bias.

Abbreviations: IM: intramuscular; IV: intravenous; PIVKA: plasma protein‐induced in vitamin K absence; RCT: randomized controlled trial.

Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Costakos 2003	Costakos 2003 studied infants 22 to 32 weeks' gestational age born to mothers who wished to breast feed. Group 1 received 1 mg of vitamin K and Group 2 received 0.5 mg of vitamin K. During the time period of the study 81 infants of 22 to 32 weeks' gestation were admitted to the NICU. Treatment assignment was based on physician choice (non‐random assignment). The more immature and lowest birth weight infants tended to get the lower dose of vitamin K.
Kumar 2001	Kumar 2001 assessed vitamin K status in preterm infants (≤ 36 weeks' gestation) by measuring plasma vitamin K and plasma protein‐induced in vitamin K absence (PIVKA II) from birth until 40 weeks' postconceptional age. Preterm infants were divided at birth into groups by gestational age (group 1, ≤ 28 weeks; group 2, 29 to 32 weeks; group 3, 33 to 36 weeks). Supplemental vitamin K (1 mg IM) was administered at birth followed by 60 µg/day (weight < 1000 g) or 130 µg/day (weight ≥ 1000 g) via total parenteral nutrition. After hyperalimentation, most received vitamin K‐fortified enteral feedings with the remainder receiving unfortified breast milk. Blood was obtained for PIVKA II in cord blood and for PIVKA II and vitamin K at 2 weeks and 6 weeks after birth and at 40 weeks postconception.
Ogata 1988	Ogata 1988 measured Factor II coagulant antigen (FII‐AG), the protein induced by vitamin K absence or antagonist II (PIVKA‐II), and coagulant activity (Normotest) in low birth weight infants. Infants whose Normotest levels were less than 30% at 1 day (group A) received vitamin K2, and the others whose Normotest levels were greater than 30% at 1 day (group B) were not treated.
Rossi 1996	Rossi 1996 studied infants that were 27 to 42 weeks' gestation at birth. The population included preterm infants and high risk term infants (unclear what deemed the term infants high risk). Non‐randomized report of biochemical markers after recommended dosing changes in preterm infants.
Seydewitz 1984	Seydewitz 1984 studied infants that were preterm or small‐for‐date, or both. Data on only the preterm infants included in the study were unavailable. Infants were randomized into 2 groups: 1 group received 1 mg IM vitamin K after a first plasma sample was obtained; the second group received 1 mg IM vitamin K after a second plasma sample was obtained (time between the first sampling and second sampling was 4 hours in 1 series and 24 hours in another series).
Vakrilova 1995	Vakrilova 1995 conducted a prospective study of newborn infants with birth weight below 2500 g comparing the effect of IM vitamin K to oral vitamin K for preventing hemorrhagic disease of the newborn. Additional comparison group included healthy term infants who had not received vitamin K. Treatment assignment unclear.

Abbreviations: IM: intramuscular; PIVKA: plasma protein‐induced in vitamin K absence.

Data and analyses

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Comparison 1. Intravenous versus intramuscular vitamin K

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bleeding complications Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 1 Bleeding complications.
1.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	7.0 [0.38, 129.11]
1.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.20, 3.27]
1.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.38, 6.46]
2 Intraventricular hemorrhage > Grade II Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.2 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 2 Intraventricular hemorrhage > Grade II.
2.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.19, 20.72]
2.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.13, 3.96]
2.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.20, 5.31]
3 Presence of PIVKA II at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 3 Presence of PIVKA II at day 5.
3.1 0.2 mg IV versus 0.2 mg IM	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.52 [0.37, 6.23]
3.2 0.2 mg IV versus 0.5 mg IM	1	57	Risk Ratio (M‐H, Fixed, 95% CI)	2.07 [0.41, 10.43]
3.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	89	Risk Ratio (M‐H, Fixed, 95% CI)	1.74 [0.51, 6.00]
4 Presence of PIVKA II at day 25 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.4 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 4 Presence of PIVKA II at day 25.
4.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.07, 16.36]
4.2 0.2 mg IV versus 0.5 mg IM	1	51	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.07, 15.74]
4.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	78	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.10, 11.15]
5 Prolonged PT at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 5 Prolonged PT at day 5.
5.1 0.2 mg IV versus 0.2 mg IM	1	63	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.24, 1.76]
5.2 0.2 mg IV versus 0.5 mg IM	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.30, 2.90]
5.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	92	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.30, 1.93]
6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.6 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5).
6.1 0.2 mg IV versus 0.2 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	9.9 [0.56, 176.29]
6.2 0.2 mg IV versus 0.5 mg IM	1	58	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.19, 1.74]
6.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.38, 3.78]
7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25).
7.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.82]
7.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.11]
7.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.01, 3.23]
8 Necrotizing enterocolitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.8 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 8 Necrotizing enterocolitis.
8.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.15, 6.57]
8.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.16, 7.10]
8.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.20, 5.31]
9 Sepsis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 9 Sepsis.
9.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.28, 3.58]
9.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.26, 2.86]
9.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.31, 2.72]
10 Mortality (all infants) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.10 Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 10 Mortality (all infants).
10.1 0.2 mg IV versus 0.2 mg IM	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.56, 3.14]
10.2 0.2 mg IV versus 0.5 mg IM	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	2.82 [0.84, 9.46]
10.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	98	Risk Ratio (M‐H, Fixed, 95% CI)	1.77 [0.80, 3.93]

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Comparison 2. Vitamin K dosage

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bleeding complications Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 Vitamin K dosage, Outcome 1 Bleeding complications.
1.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.11]
2 Intraventricular hemorrhage > Grade II Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 Vitamin K dosage, Outcome 2 Intraventricular hemorrhage > Grade II.
2.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.04, 3.24]
3 Presence of PIVKA II at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.3 Comparison 2 Vitamin K dosage, Outcome 3 Presence of PIVKA II at day 5.
3.1 0.2 mg IM versus 0.5 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	1.36 [0.24, 7.57]
4 Presence of PIVKA II at day 25 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.4 Comparison 2 Vitamin K dosage, Outcome 4 Presence of PIVKA II at day 25.
4.1 0.2 mg IM versus 0.5 mg IM	1	53	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.06, 14.60]
5 Prolonged PT at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.5 Comparison 2 Vitamin K dosage, Outcome 5 Prolonged PT at day 5.
5.1 0.2 mg IM versus 0.5 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.53, 3.93]
6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.6 Comparison 2 Vitamin K dosage, Outcome 6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5).
6.1 0.2 mg IM versus 0.5 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	0.06 [0.00, 1.02]
7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.7 Comparison 2 Vitamin K dosage, Outcome 7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25).
7.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.03, 2.25]
8 Necrotizing enterocolitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.8 Comparison 2 Vitamin K dosage, Outcome 8 Necrotizing enterocolitis.
8.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.16, 7.10]
9 Sepsis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.9 Comparison 2 Vitamin K dosage, Outcome 9 Sepsis.
9.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.26, 2.86]
10 Mortality (all infants) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.10 Comparison 2 Vitamin K dosage, Outcome 10 Mortality (all infants).
10.1 0.2 mg IM versus 0.5 mg IM	1	65	Risk Ratio (M‐H, Fixed, 95% CI)	2.13 [0.60, 7.51]

Figure 1

PRISMA flow diagram

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Figure 2

Forest plot of comparison: 1 Intravenous versus intramuscular vitamin K, outcome: 1.3 Presence of PIVKA II at day 5.

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Figure 3

Forest plot of comparison: 2 Vitamin K dosage, outcome: 2.3 Presence of PIVKA II at day 5.

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Analysis 1.1

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 1 Bleeding complications.

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Analysis 1.2

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 2 Intraventricular hemorrhage > Grade II.

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Analysis 1.3

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 3 Presence of PIVKA II at day 5.

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Analysis 1.4

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 4 Presence of PIVKA II at day 25.

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Analysis 1.5

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 5 Prolonged PT at day 5.

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Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 6 Vitamin K1 epoxide detected (≥ 10 ng/mL on day 5).

Analysis 1.6

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5).

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Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 7 Vitamin K1 epoxide detected (≥ 0.3 ng/mL on day 25).

Analysis 1.7

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25).

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Analysis 1.8

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 8 Necrotizing enterocolitis.

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Analysis 1.9

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 9 Sepsis.

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Analysis 1.10

Comparison 1 Intravenous versus intramuscular vitamin K, Outcome 10 Mortality (all infants).

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Analysis 2.1

Comparison 2 Vitamin K dosage, Outcome 1 Bleeding complications.

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Analysis 2.2

Comparison 2 Vitamin K dosage, Outcome 2 Intraventricular hemorrhage > Grade II.

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Analysis 2.3

Comparison 2 Vitamin K dosage, Outcome 3 Presence of PIVKA II at day 5.

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Analysis 2.4

Comparison 2 Vitamin K dosage, Outcome 4 Presence of PIVKA II at day 25.

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Analysis 2.5

Comparison 2 Vitamin K dosage, Outcome 5 Prolonged PT at day 5.

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Comparison 2 Vitamin K dosage, Outcome 6 Vitamin K1 epoxide detected (≥ 10 ng/mL on day 5).

Analysis 2.6

Comparison 2 Vitamin K dosage, Outcome 6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5).

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Comparison 2 Vitamin K dosage, Outcome 7 Vitamin K1 epoxide detected (≥ 0.3 ng/mL on day 25).

Analysis 2.7

Comparison 2 Vitamin K dosage, Outcome 7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25).

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Analysis 2.8

Comparison 2 Vitamin K dosage, Outcome 8 Necrotizing enterocolitis.

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Analysis 2.9

Comparison 2 Vitamin K dosage, Outcome 9 Sepsis.

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Analysis 2.10

Comparison 2 Vitamin K dosage, Outcome 10 Mortality (all infants).

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Summary of findings for the main comparison. Intramuscular vitamin K versus intravenous vitamin K

Intramuscular vitamin K versus intravenous vitamin K
Patient or population: preterm infants Setting: neonatal intensive care units Intervention: prophylactic intravenous (IV) vitamin K Comparison: prophylactic intramuscular (IM) vitamin K
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)
	Risk with prophylactic IV vitamin K treatment	Risk with prophylactic IM vitamin K
Bleeding complications: 0.2 mg IV versus 0.2 mg IM	Study population		RR 7.00 (0.38 to 129.11)	52 (1 RCT)	⊕⊕⊝⊝ low¹
	0 per 1000	0 per 1000 (0 to 0)
Bleeding complications: 0.2 mg IV versus 0.5 mg IM	Study population		RR 0.81 (0.20 to 3.27)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	143 per 1000	116 per 1000 (29 to 467)
Intraventricular hemorrhage > Grade II: 0.2 mg IV versus 0.2 mg IM	Study population		RR 2.00 (0.19 to 20.72)	52 (1 RCT)	⊕⊕⊝⊝ low¹
	38 per 1000	77 per 1000 (7 to 797)
Intraventricular hemorrhage > Grade II: 0.2 mg IV versus 0.5 mg IM	Study population		RR 0.72 (0.13 to 3.96)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	107 per 1000	77 per 1000 (14 to 424)
Presence of PIVKA II at day 5: 0.2 mg IV versus 0.2 mg IM	Study population		RR 1.52 (0.37 to 6.23)	60 (1 RCT)	⊕⊕⊝⊝ low¹
	94 per 1000	143 per 1000 (35 to 584)
Presence of PIVKA II at day 5: 0.2 mg IV versus 0.5 mg IM	Study population		RR 2.07 (0.41 to 10.43)	57 (1 RCT)	⊕⊕⊝⊝ low¹
	69 per 1000	143 per 1000 (28 to 719)
Presence of PIVKA II at day 25: 0.2 mg IV versus 0.2 mg IM	Study population		RR 1.08 (0.07 to 16.36)	52 (1 RCT)	⊕⊕⊝⊝ low¹
	37 per 1000	40 per 1000 (3 to 606)
Presence of PIVKA II at day 25 ‐ 0.2 mg IV versus 0.5 mg IM	Study population		RR 1.04 (0.07 to 15.74)	51 (1 RCT)	⊕⊕⊝⊝ low¹
	38 per 1000	40 per 1000 (3 to 605)
Necrotizing enterocolitis ‐ 0.2 mg IV versus 0.2 mg IM	Study population		RR 1.00 (0.15 to 6.57)	52 (1 RCT)	⊕⊕⊝⊝ low¹
	77 per 1000	77 per 1000 (12 to 505)
Necrotizing enterocolitis: 0.2 mg IV versus 0.5 mg IM	Study population		RR 1.08 (0.16 to 7.10)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	71 per 1000	77 per 1000 (11 to 507)
Sepsis: 0.2 mg IV versus 0.2 mg IM	Study population		RR 1.00 (0.28 to 3.58)	52 (1 RCT)	⊕⊕⊝⊝ low¹
	154 per 1000	154 per 1000 (43 to 551)
Sepsis: 0.2 mg IV versus 0.5 mg IM	Study population		RR 0.86 (0.26 to 2.86)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	179 per 1000	154 per 1000 (46 to 511)
Mortality (all infants): 0.2 mg IV versus 0.2 mg IM	Study population		RR 1.32 (0.56 to 3.14)	67 (1 RCT)	⊕⊕⊝⊝ low¹
	206 per 1000	272 per 1000 (115 to 646)
Mortality (all infants): 0.2 mg IV versus 0.5 mg IM	Study population		RR 2.82 (0.84 to 9.46)	64 (1 RCT)	⊕⊕⊝⊝ low¹
	97 per 1000	273 per 1000 (81 to 915)
The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations:* CI: confidence interval; intravenous: IV; intramuscular: IM; RR: risk ratio; OR: odds ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹We downgraded by two levels due to the small sample size from one included trial.

Summary of findings for the main comparison. Intramuscular vitamin K versus intravenous vitamin K

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Summary of findings 2. Higher dose vitamin K compared to lower dose vitamin K for preterm infants

Higher dose vitamin K compared to lower dose vitamin K for preterm infants
Patient or population: preterm infants Setting: neonatal intensive care unit Intervention: higher dose intramuscular (IM) vitamin K Comparison: lower dose IM vitamin K
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with lower dose vitamin K	Risk with higher dose vitamin K
Bleeding complications: 0.2 mg IM versus 0.5 mg IM	Study population		RR 0.12 (0.01 to 2.11)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	143 per 1000	17 per 1000 (1 to 301)
Intraventricular hemorrhage > Grade II: 0.2 mg IM versus 0.5 mg IM	Study population		RR 0.36 (0.04 to 3.24)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	107 per 1000	39 per 1000 (4 to 347)
Presence of PIVKA II at day 5: 0.2 mg IM versus 0.5 mg IM	Study population		RR 1.36 (0.24 to 7.57)	61 (1 RCT)	⊕⊕⊝⊝ low¹
	69 per 1000	94 per 1000 (17 to 522)
Presence of PIVKA II at day 25: 0.2 mg IM versus 0.5 mg IM	Study population		RR 0.96 (0.06 to 14.60)	53 (1 RCT)	⊕⊕⊝⊝ low¹
	38 per 1000	37 per 1000 (2 to 562)
Necrotizing enterocolitis: 0.2 mg IM versus 0.5 mg IM	Study population		RR 1.08 (0.16 to 7.10)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	71 per 1000	77 per 1000 (11 to 507)
Sepsis: 0.2 mg IM versus 0.5 mg IM	Study population		RR 0.86 (0.26 to 2.86)	54 (1 RCT)	⊕⊕⊝⊝ low¹
	179 per 1000	154 per 1000 (46 to 511)
Mortality (all infants): 0.2 mg IM versus 0.5 mg IM	Study population		RR 2.13 (0.60 to 7.51)	65 (1 RCT)	⊕⊕⊝⊝ low¹
	97 per 1000	206 per 1000 (58 to 727)
The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations:* CI: confidence interval; intravenous: IV; intramuscular: IM; RR: risk ratio; OR: odds ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.
¹We downgraded by two levels due to the small sample size from one included trial.

Summary of findings 2. Higher dose vitamin K compared to lower dose vitamin K for preterm infants

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Comparison 1. Intravenous versus intramuscular vitamin K

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bleeding complications Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	7.0 [0.38, 129.11]
1.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.20, 3.27]
1.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.38, 6.46]
2 Intraventricular hemorrhage > Grade II Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.19, 20.72]
2.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.13, 3.96]
2.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.20, 5.31]
3 Presence of PIVKA II at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 0.2 mg IV versus 0.2 mg IM	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.52 [0.37, 6.23]
3.2 0.2 mg IV versus 0.5 mg IM	1	57	Risk Ratio (M‐H, Fixed, 95% CI)	2.07 [0.41, 10.43]
3.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	89	Risk Ratio (M‐H, Fixed, 95% CI)	1.74 [0.51, 6.00]
4 Presence of PIVKA II at day 25 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.07, 16.36]
4.2 0.2 mg IV versus 0.5 mg IM	1	51	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.07, 15.74]
4.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	78	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.10, 11.15]
5 Prolonged PT at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 0.2 mg IV versus 0.2 mg IM	1	63	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.24, 1.76]
5.2 0.2 mg IV versus 0.5 mg IM	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.30, 2.90]
5.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	92	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.30, 1.93]
6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 0.2 mg IV versus 0.2 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	9.9 [0.56, 176.29]
6.2 0.2 mg IV versus 0.5 mg IM	1	58	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.19, 1.74]
6.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.38, 3.78]
7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.82]
7.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.11]
7.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.01, 3.23]
8 Necrotizing enterocolitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.15, 6.57]
8.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.16, 7.10]
8.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.20, 5.31]
9 Sepsis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 0.2 mg IV versus 0.2 mg IM	1	52	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.28, 3.58]
9.2 0.2 mg IV versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.26, 2.86]
9.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.31, 2.72]
10 Mortality (all infants) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 0.2 mg IV versus 0.2 mg IM	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.56, 3.14]
10.2 0.2 mg IV versus 0.5 mg IM	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	2.82 [0.84, 9.46]
10.3 Any IV Vitamin K (0.2 mg) versus any IM Vitamin K (0.2 mg and 0.5 mg)	1	98	Risk Ratio (M‐H, Fixed, 95% CI)	1.77 [0.80, 3.93]

Comparison 1. Intravenous versus intramuscular vitamin K

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Comparison 2. Vitamin K dosage

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bleeding complications Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.11]
2 Intraventricular hemorrhage > Grade II Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.04, 3.24]
3 Presence of PIVKA II at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 0.2 mg IM versus 0.5 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	1.36 [0.24, 7.57]
4 Presence of PIVKA II at day 25 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 0.2 mg IM versus 0.5 mg IM	1	53	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.06, 14.60]
5 Prolonged PT at day 5 Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 0.2 mg IM versus 0.5 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.53, 3.93]
6 Vitamin K₁ epoxide detected (≥ 10 ng/mL on day 5) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 0.2 mg IM versus 0.5 mg IM	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	0.06 [0.00, 1.02]
7 Vitamin K₁ epoxide detected (≥ 0.3 ng/mL on day 25) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.03, 2.25]
8 Necrotizing enterocolitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.16, 7.10]
9 Sepsis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 0.2 mg IM versus 0.5 mg IM	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.26, 2.86]
10 Mortality (all infants) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 0.2 mg IM versus 0.5 mg IM	1	65	Risk Ratio (M‐H, Fixed, 95% CI)	2.13 [0.60, 7.51]

Comparison 2. Vitamin K dosage

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Referencias

References to studies included in this review

Clarke 2006 {published data only}

References to studies excluded from this review

Costakos 2003 {published data only}

Kumar 2001 {published data only}

Ogata 1988 {published data only}

Rossi 1996 {published data only}

Seydewitz 1984 {published data only}

Vakrilova 1995 {published data only}

Additional references

Andrew 1988

Bovill 1993

Clarke 2003

Clarke 2005

Clarke 2010

Committee on Fetus and Newborn 2003

Crowther 2010

Dickson 1994

GRADEpro GDT 2015 [Computer program]

Greer 1998

Greer 2010

Higgins 2011

Kurata 2005

Liu 2006

Morales 1988

O'Shaughnessy 2005

Offringa 2000

Pilcher 2008

Pomerance 1987

RevMan 2014 [Computer program]

Schünemann 2013

Solano 1990

Van Winckel 2009

Yang 1989

Zipursky 1999

References to other published versions of this review

Ardell 2010

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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