1. In a randomized controlled trial comparing prophylactic vitamin K doses in 75 very preterm or very low birthweight infants, those receiving 1 mg intramuscular vitamin K at birth had significantly lower rates of vitamin K deficiency 28 days than those receiving 0.3 mg.

2. No significant difference was found in rates of specific bleeding complications or mortality based on prophylactic vitamin K dosage.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Vitamin K prophylaxis is routinely given at birth to prevent vitamin K deficiency, which can cause serious bleeding complications. In the United States, recommended intramuscular vitamin K dosages vary based on several factors, with doses of 0.3-0.5 mg/kg for infants weighing less than 1,000 grams and 0.5-1.0 mg total for other newborns. This small randomized trial was conducted in India to compare dosages of 0.3, 0.5, and 1 mg in very preterm or very low birth weight infants. The primary outcome was serum level of protein induced in vitamin K absence II (PIVKA-II), an assay for vitamin K deficiency, at days 5 and 28. Among 75 infants randomized, PIVKA-II levels did not significantly differ at 5 days, but at 28 days median levels were significantly lower, indicating higher vitamin K levels, in the 1-mg group than in the 0.3-mg group. Peak bilirubin levels and phototherapy duration were significantly higher in the 1-mg group, but there were no significant differences in rates of intraventricular hemorrhage, pulmonary hemorrhage, or mortality between groups. The small size, use of an indirect assay for vitamin K levels, and the small number of bleeding complications in this study population limit interpretation of the clinical significance of different doses. Baseline risk for vitamin K deficiency is also higher in India than in high-income countries due to lower prevalence of milk fortification, among other factors; concern for excessive vitamin K levels after higher dosing in the US preterm population may be warranted. Still, this randomized trial supports a benefit for relatively high doses of vitamin K prophylaxis even in very small preterm neonates.

Click to read the study in the Journal of Pediatrics

Relevant Reading: Vitamin K and the newborn infant

In-Depth [randomized controlled trial]: Infants who were born very preterm, defined as 32 weeks gestation or earlier, and/or very low birth weight, defined as 1,500 grams or less, at a single tertiary center in India were randomized to the three dosage groups at birth. Infants were randomized in blocks of 3-6. The trial was non-blinded. The p-value for the difference in median PIVKA-II levels between the 1-mg and 0.3-mg groups was 0.004. At day 28, 100% of infants in the 1-mg group, 91.3% of infants in the 0.5-mg group, and 72.7% of infants in the 0.3-mg group had sufficient vitamin K levels based on the PIVKA-II assay (p = 0.019). Median peak bilirubin levels were 10.45 mg/dL in the 1-mg group compared to 8.10 in the 0.3-mg group (p = 0.001). Only 4 of the 75 total infants had periventricular or intraventricular hemorrhage, and 3 had pulmonary hemorrhage.

Image: PD

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