Preterm infants who are exclusively breastmilk fed are at high risk of developing biochemical vitamin K deficiency in early infancy, according to a prospective, observational study of 45 infants. This may be prevented with routine, post-discharge, oral vitamin K1 supplementation that provides intakes comparable to those from formula, according to researchers who published their findings in the Journal of Thrombosis and Haemostasis.
“Without sufficient, ongoing dietary vitamin K intake during infancy, our data suggest the majority of exclusively breastfed preterm babies will develop biochemical evidence of vitamin K deficiency by two to three months corrected age,” explained corresponding author Paul Clarke, MD, a consultant neonatologist at Norfolk and Norwich University Hospital and honorary professor at the University of East Anglia in England.
Breastmilk has a low vitamin K content, and cases of late vitamin K deficiency bleeding are reported most frequently in infants who are exclusively breastmilk fed – including preterm infants, despite parenteral vitamin K1 being given at birth as bleeding prophylaxis.
Dr. Clarke noted that most centers in the U.K., U.S., and Canada do not routinely provide preterm babies with supplemented vitamin K at the point of discharge home from the neonatal intensive care unit (NICU).
“Vitamin K is essential for proper production and functioning of several important proteins in the human body,” Dr. Clarke said. “Our study looked at two of these vitamin K dependent proteins (prothrombin and osteocalcin) and measured undercarboxylated forms of these proteins to assess the vitamin K status of this hemostatic protein and this bone protein, respectively.”
Researchers assessed the prevalence of functional vitamin K insufficiency in preterm infants in four U.K. neonatal units. Functional vitamin K insufficiency was based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively.
Between January 2016 and April 2018, blood samples and dietary history were collected before hospital discharge in 45 babies born at 33 weeks or less gestation and after discharge at two to three months’ corrected age in 37 of the babies. Serum vitamin K1, PIVKA-II, and GluOC as a percentage of the sum of GluOC plus GlaOC (%GluOC) were measured.
After discharge, breastmilk-fed babies had significantly lower serum vitamin K1 (0.15 vs. 1.81 μg/L) and higher PIVKA-II (0.10 vs. 0.02 AU/mL) than those receiving formula or a mixed diet. Bone carboxylation efficiency was especially sensitive to vitamin K1 intakes with mean %GluOC values of 63.6% and 8.1% for breastmilk-fed babies and those receiving a formula or a mixed diet, respectively. Pre-discharge, one of 45 breastmilk-fed infants (2%) was vitamin K insufficient. After discharge, eight of 12 exclusively breastmilk-fed babies (67%) were vitamin K insufficient compared with one of 25 babies that received formula or a mixed diet (4%).
Limitations of the study included that it was relatively small and observational, using proxy biochemical markers of vitamin K deficiency rather than clinical outcomes.
“My hope is that routine vitamin K1 supplementation will be offered to all predominantly breastmilk-fed babies at the point of discharge from the NICU and continued daily for the first few months or until weaned, for as long as breastfed,” Dr. Clarke said. “This will abolish the subclinical deficiency (in the same way that the K supplements added to the formula milks abolish it) and will stop babies from becoming biochemically deficient in this important vitamin.”
He added, “This will help reduce the very rare but still real chance for a later catastrophic brain hemorrhage occurring in preterm infants in the first few months after discharge from NICU.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Clarke P, Shearer MJ, Card DJ, et al. Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth [published online ahead of print, 2022 Sep 10]. J Thromb Haemost. 2022;10.1111/jth.15874.
