Urinary Excretion of Vitamin K Metabolites in Term and Preterm Infants: Relationship to Vitamin K Status and Prophylaxis

Abstract

ABSTRACT:Little is known about the metabolic turnover and excretion of vitamin K in healthy newborn infants and the metabolic consequences of prophylactic regimens designed to protect against vitamin K deficiency bleeding (VKDB). We measured the excretion of two urinary metabolites (Յ24 h) of vitamin K (5C-and 7C-aglycones) in term infants before (n ϭ 11) and after (n ϭ 5) a 1000 g i.m. dose of vitamin K 1 (K 1 ) and in preterm infants after 200 g i.m. (n ϭ 4), 500 g i.m. (n ϭ 4), or 200 g i.v. (n ϭ 5). In preterm infants, we also measured serum K 1 , vitamin K 1 2,3-epoxide, and PIVKA-II at 5 d postpartum. Before prophylaxis, the rate of 5C-and 7C-aglycone excretion was 25 times lower than adults, reflecting low vitamin K stores at birth. After prophylaxis, the excretion rate correlated to K 1 dose (r ϭ 0.6) but was two orders of magnitude lower than that in adults, probably reflecting the immaturity of neonatal catabolism. All term and 10 of 13 preterm infants mainly excreted 5C-aglycone. We present evidence that increased excretion of the 7C-aglycone was associated with metabolic overload because of the exposure to high-tissue K 1 concentrations. Measurement of the 5C-and 7C-aglycones may facilitate longitudinal studies of vitamin K status in neonates and aid the development of improved prophylactic regimens. (Pediatr Res 68: 508-512, 2010)

Vitamin K metabolism: Current knowledge and future research

“…The rate of 5C‐ and 7C‐metabolite excretion by term infants pre‐K 1 prophylaxis is far lower than in healthy young adults (25‐fold) or in adults fed with a K 1 ‐restricted diet of 11 μg/day for 15 days (14‐fold) . This finding is in keeping with the notion that infants are born with vitamin K insufficiency as evidenced by low K 1 and K 2 concentrations in plasma and liver tissue of foetuses and neonates .…”

“…Harrington et al. determined that in term infants only 0.03% of a parenterally administered K 1 dose was excreted as urinary metabolites within the first 24 h post‐prophylaxis . Compared to Shearer's data from adults where 14–20% of an IV dose was excreted within the first 24 h , it appears the rate of K 1 clearance in neonates is significantly slower.…”

“…As in healthy adults, the 5C‐metabolite is the predominant metabolite excreted by term infants and the majority of preterm infants pre‐ and post‐vitamin K prophylaxis. However, exposure to a large pharmacological dose of vitamin K to protect against vitamin K deficiency bleeding can disturb the normal pattern of metabolite excretion .…”

Vitamin K plasma levels determination in human health

“…Harrington et al tested this analytic approach in young adults [39] and studied its clinical significance in the pediatric population [40]. Urinary excretion of 7C-aglycone and 5C-aglycone, vitamin K metabolites common to both phylloquinone and the menaquinone series, were assessed following restriction or supplementation with phylloquinone.…”

“…Infants mainly excreted 5C-aglycone, while increased excretion of the 7C-aglycone was associated with metabolic overload because of the exposure to high-tissue phylloquinone concentrations. Measurement of the 5C-and 7C-aglycones was therefore proposed as a good approach to study vitamin K status in neonates and as an aid the development of improved prophylactic regimens [40]. Urinary vitamin K metabolites have not been studied in CKD patients, but deterioration of renal function might interfere with the reliability of this marker of vitamin K status.…”