Vitamin K dosing needs boost in deficient Dutch infants

Last Updated: 2016-04-28

By David Douglas

NEW YORK (Reuters Health) - Despite a recent increase, the recommended Dutch regimen to prevent vitamin K deficiency bleeding (VKDB) in breastfed infants is still inadequate, according to Dutch and Danish researchers.

As Dr. Henkjan J. Verkade told Reuters Health by email, in unrecognized cholestasis "neither of two prophylactic regimens used in the Netherlands the last 25 years based on daily vitamin K supplementation to breastfed infants is sufficiently protective."

"In a previous study (published in Pediatrics in 2008)," he added, "we showed that the regimen of daily 25 mcg supplementation was not effective. The present study indicates that increasing the daily dosage six-fold is still not sufficient."

In an April 28 online paper in Pediatrics, Dr. Verkade, of University Medical Center Groningen, and colleagues note that given the high incidence of VKDB in infants with unrecognized cholestasis, many countries have introduced vitamin K supplementation. The optimal dose is unclear. However, the incidence of VKDB per 100,000 in the Netherlands is 3.2. In Denmark it's close to none.

Data from biliary atresia registries from 1991 to 2011, showed 45 of 55 (82%) of Dutch infants given 25 mcg developed VKDB. The dose was raised to 150 mcg in March of 2011, but between then and 2015, nine of 11 such infants (still 82%) developed VKDB. In Denmark, where the regimen is a single intramuscular dose of 2 mg vitamin K at birth, between 2000 and 2014 there were 25 cases but only one infant developed VKDB.

Given these findings, continued Dr. Verkade, "We feel that the national prophylactic regimen in our country should be adapted toward either a single intramuscular injection at birth or, although probably slightly less efficient, to an oral administration at birth of 1 or 2 mg, followed by regular administrations during the first three months of large oral dosages (1-2 mg)."

In fact, he continued, "We have contacted the Dutch Society of Pediatrics who has supported our conclusion that the presently used regimen is insufficiently protective. The Dutch Society of Pediatrics has decided to request that the Dutch Minister of Health consider this new information with regard to ensuring that a new/adapted prophylactic regimen does sufficiently protect breastfed infants against vitamin K deficiency bleeding."

Commenting on the findings by email, Dr. Benjamin L. Shneider of Baylor College of Medicine, Houston, Texas, told Reuters Health that the article "provides dramatic evidence of the potentially devastating consequences of vitamin K deficiency in the newborn liver disease, biliary atresia. This disease is associated with profound cholestasis and associated low intestinal luminal concentrations of bile acids. Those luminal bile acids are critical for enteral absorption of fat-soluble vitamins."

Dr. Shneider, who is chief of pediatric gastroenterology, Hepatology, and nutrition at Texas Children's Hospital, added, "A number of studies have shown that infants with cholestasis have significant problems with fat-soluble vitamin deficiency -- in this study an oral regimen of vitamin K prophylaxis was remarkably ineffective in infants with cholestasis. In fact, 82% of the infants developed vitamin K dependent bleeding. Newborn intramuscular vitamin K administration, which is recommended by the American Academy of Pediatrics, was highly effective in preventing this potentially devastating complication."

"These findings," he concluded, "confirm the importance of early identification of neonatal cholestasis, with subsequent prompt attention to both diagnosis and treatment. The results of the current analysis are difficult to extrapolate to the vast majority of infants who do not have cholestasis, and as such, caution is warranted in using this information to make a cost-effectiveness and public policy decision."

The authors reported no funding or disclosures.

SOURCE: http://bit.ly/1NXDBu3

Pediatrics 2016.