Published online November 13, 2006
PEDIATRICS Vol. 118 No. 6 December 2006, pp. e1657-e1666 (doi:10.1542/peds.2005-2742)
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ARTICLE

Vitamin K Prophylaxis for Preterm Infants: A Randomized, Controlled Trial of 3 Regimens

Paul Clarke, MB ChB, FRCPCH, MRCP (UK)a, Simon J. Mitchell, MD, FRCPCH, MRCPb, Robert Wynn, MD, MRCP, MRCPathc, Shanmuga Sundaram, MBBS, MRCPCHd, Valerie Speed, BEd RGN, RSCNe, Elizabeth Gardener, MScf, Donna Roevesg and Martin J. Shearer, PhD, MRCPathg

a Neonatal Unit
f Research and Development Directorate, Hope Hospital, Salford, United Kingdom
b Neonatal Medical Unit, St Mary’s Hospital, Manchester, United Kingdom
c Department of Paediatric Haematology, Royal Manchester Children’s Hospital, Manchester, United Kingdom
d Neonatal Unit, Royal Bolton Hospital, Bolton, United Kingdom
e Neonatal Unit, Billinge Hospital, Wigan, United Kingdom
g Centre for Haemostasis and Thrombosis, St Thomas’s Hospital, London, United Kingdom

OBJECTIVE. Preterm infants may be at particular risk from either inadequate or excessive vitamin K prophylaxis. Our goal was to assess vitamin K status and metabolism in preterm infants after 3 regimens of prophylaxis.

METHODS. Infants <32 weeks’ gestation were randomized to receive 0.5 mg (control) or 0.2 mg of vitamin K1 intramuscularly or 0.2 mg intravenously after delivery. Primary outcome measures were serum vitamin K1, its epoxide metabolite (vitamin K1 2,3-epoxide), and undercarboxylated prothrombin assessed at birth, 5 days, and after 2 weeks of full enteral feeds. Secondary outcome measures included prothrombin time and factor II concentrations.

RESULTS. On day 5, serum vitamin K1 concentrations in the 3 groups ranged widely (2.9–388.0 ng/mL) but were consistently higher than the adult range (0.15–1.55 ng/mL). Presence of vitamin K1 2,3-epoxide on day 5 was strongly associated with higher vitamin K1 bolus doses. Vitamin K1 2,3-epoxide was detected in 7 of 29 and 4 of 29 infants from the groups that received 0.5 mg intramuscularly and 0.2 mg intravenously, respectively, but in none of 32 infants from group that received 0.2 mg intramuscularly. After 2 weeks of full enteral feeding, serum vitamin K1 was lower in the infants who received 0.2 mg intravenously compared with the infants in the control group. Three infants from the 0.2-mg groups had undetectable serum vitamin K1 as early as the third postnatal week but without any evidence of even mild functional deficiency, as shown by their normal undercarboxylated prothrombin concentrations.

CONCLUSIONS. Vitamin K1 prophylaxis with 0.2 mg administered intramuscularly maintained adequate vitamin K status of preterm infants until a median age of 25 postnatal days and did not cause early vitamin K1 2,3-epoxide accumulation. In contrast, 0.2 mg administered intravenously and 0.5 mg administered intramuscularly led to vitamin K1 2,3-epoxide accumulation, possibly indicating overload of the immature liver. To protect against late vitamin K1 deficiency bleeding, breastfed preterm infants given a 0.2-mg dose of prophylaxis should receive additional supplementation when feeding has been established.


Key Words: vitamin deficiency • preterm • prophylaxis • vitamin K • phytomenadione

Abbreviations: VKDB—vitamin K deficiency bleeding • IM—intramuscular • IV—intravenous • PIVKA-II—undercarboxylated prothrombin • PT—prothrombin time • K1O—vitamin K1 2,3-epoxide • AU—arbitrary units • FII—factor II (prothrombin) • TPN—total parenteral nutrition • IQR—interquartile range • VKOR—vitamin K epoxide reductase


Accepted Jun 20, 2006.


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