Between February and September 2013, four confirmed cases of late vitamin K deficient bleeding were diagnosed at a children's hospital in Nashville, Tennessee. The four infants had laboratory-confirmed coagulopathy. Three of the infants were born at major area hospitals, and one was born at home. The infants all had been healthy and developing normally until experiencing sudden symptomatic bleeding at age 6–15 weeks. Three of the infants had diffuse intracranial hemorrhage, and the fourth had gastrointestinal bleeding. Additionally, asymptomatic laboratory-confirmed coagulopathy was identified in the twin of one of the patients. In each case, the parents had declined intramuscular vitamin K administration at birth. The Tennessee Department of Health initiated a public health investigation of this cluster and requested assistance from the CDC.
All four of the infants survived. The infant with gastrointestinal bleeding recovered fully. The three with intracranial hemorrhage are being followed by neurologists; one has an apparent gross motor deficit. Although deficits have not yet been identified in the other infants, all are currently aged less than one year old, and the neurodevelopmental impact of the hemorrhages might become apparent in the context of further development.
Vitamin K deficiency bleeding (VKDB) is a coagulopathy that develops in infants who do not have sufficient vitamin K stores to support production of clotting factors. In adults, vitamin K is absorbed from food and from vitamin K synthesized by gut bacteria. However, placental transfer in humans is limited; cord blood and infant liver reserve levels of vitamin K are substantially below adult levels. As a result, infants are predisposed to develop VKDB, which is classified as early, classic, and late, according to when it presents.
The late form of VKDB can develop in infants two weeks to six months of age who did not receive the vitamin K injection at birth and do not have enough vitamin K dependent proteins in their bodies to allow normal blood clotting. Untreated, this can cause bleeding in the brain, which may lead to neurological problems and can even be fatal. The risk for developing late VKDB has been estimated at 81 times greater among infants who do not receive a vitamin K injection at birth than in infants who do receive it.
In the United States, administration of intramuscular vitamin K at birth to prevent all forms of VKDB has been standard practice since first recommended by the American Academy of Pediatrics in 1961. Without this prophylaxis, incidence of early and classical VKDB ranges from 0.25% to 1.7% of births; incidence of late VKDB ranges from 4.4 to 7.2 per 100,000 infants.
Parents of the four infants with VKDB were asked why they declined vitamin K prophylaxis for their neonate. Reasons included concern about an increased risk for leukemia when vitamin K is administered, an impression that the injection was unnecessary, and a desire to minimize the newborn's exposure to "toxins." Concern about increased risk for leukemia in those receiving the vitamin K injection was initially generated by a 1992 report associating vitamin K injection and childhood cancer. The finding of an association with either leukemia specifically or general childhood cancer has not been replicated in other studies, but concern persists. In all cases, parental knowledge about the risk for development of late VKDB was either incomplete or absent at the time of declining prophylaxis, with most parents learning about the possibility of late VKDB only after their infants developed the condition.
“Not giving vitamin K at birth is an emerging trend that can have devastating outcomes for infants and their families,” said CDC Director Tom Frieden, M.D., M.P.H. “Ensuring that every newborn receives a vitamin K injection at birth is critical to protect infants.”
Preliminary queries of Tennessee hospital discharge data during 2007 to 2012 revealed no confirmed cases of late vitamin K deficiency bleeding. During this period, 493,259 live births occurred in Tennessee. To assess the proportion of neonates who did not receive a vitamin K injection in 2013, records of a random sample of infants born during January to October 2013 at each of three Nashville area hospitals and at four major Tennessee nonhospital birthing centers were reviewed. At the Nashville hospital with the highest proportion of neonates not administered vitamin K, 3.4% of 3,080 infants discharged from the newborn nursery received no vitamin K injection. In contrast, 28.0% of 218 neonates at birthing centers did not receive vitamin K. Case-finding efforts revealed no additional cases of late VKDB in Tennessee in 2013.
This investigation is ongoing. A case-control study is under way to assess whether any additional risk factors might contribute to the development of late VKDB in children who do not receive vitamin K at birth. Record review at two more Nashville hospitals and one more nonhospital birthing center is in progress, and a survey of all parents identified through these record reviews who declined vitamin K administration for their children is planned to better understand why some parents decline this safe and effective prophylaxis.
See the CDC Announcement
See the CDC Report
See also Medical Law Perspectives, May 2013 Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication
See also Medical Law Perspectives, January 2013 Report: Vaccines: An Ounce of Prevention May Lead to a Pound of Injury