Late-onset vitamin K deficiency bleeding in an extremely preterm infant fed an exclusively human milk-based diet.

All newborns need extra phylloquinone (vitamin K1; K1) to prevent vitamin K deficiency bleeding (VKDB). In preterm babies, the main sources are prophylactic K1 given at birth and parenteral and/or enteral feeding thereafter. Preterm babies are at risk of late-onset VKDB if ongoing K1 supplementation is inadequate. For extremely preterm infants fed an exclusive human milk diet, the low K1 content of human milk may predispose them to vitamin K deficiency. Human milk fortification with either bovine milk-derived fortifier or human milk-based fortifier (HMF) made from pooled donor milk is a widely used strategy to improve the micronutrient and growth status of preterm infants. However, the K1 content of HMF is markedly lower than that of bovine-based preparations. We present an unusual case of late-onset VKDB in an extremely preterm infant who received an exclusive human milk diet and HMF and quantify total K1 intake prior to the bleeding.

Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth.

BACKGROUND: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1 ) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively. PATIENTS/METHODS: Prospective, multicenter, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and after discharge at 2-3 months' corrected age. Outcome measures were serum VK1 , PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants after discharge. RESULTS: After discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 µg/L), higher PIVKA-II (0.10 vs. 0.02 AU/ml) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only one (2%) of 45 breastmilk-fed infants was VK insufficient. After discharge, eight (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only one (4%) of 25 formula/mixed-fed babies. CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk-fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.

Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone.

SCOPE: The mechanism for increased bleeding and decreased vitamin K status accompanying vitamin E supplementation is unknown. We hypothesized that elevated hepatic α-tocopherol (α-T) concentrations may stimulate vitamin K metabolism and excretion. Furthermore, α-T may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4). METHODS AND RESULTS: In order to investigate these hypotheses, rats were fed phylloquinone (PK) or menadione (MN) containing diets (2 µmol/kg) for 2.5 weeks. From day 10, rats were given daily subcutaneous injections of either α-T (100 mg/kg) or vehicle and were sacrificed 24 h after the seventh injection. Irrespective of diet, α-T injections decreased MK-4 concentrations in brain, lung, kidney, and heart; and PK in lung. These decreases were not accompanied by increased excretion of urinary 5C- or 7C-aglycone vitamin K metabolites, however, the urinary α-T metabolite (α-CEHC) increased ≥ 100-fold. Moreover, α-T increases were accompanied by downregulation of hepatic cytochrome P450 expression and modified expression of tissue ATP-binding cassette transporters. CONCLUSION: Thus, in rats, high tissue α-T depleted tissue MK-4 without significantly increasing urinary vitamin K metabolite excretion. Changes in tissue MK-4 and PK levels may be a result of altered regulation of transporters.