Original ArticleRise in Late Onset Vitamin K Deficiency Bleeding in Young Infants Because of Omission or Refusal of Prophylaxis at Birth
Introduction
Vitamin K deficiency bleeding (VKDB), formerly known as hemorrhagic disease of the newborn, is an acquired coagulopathy in infants because of an inability to activate the vitamin K–dependent coagulation factors (II, VII, IX, and X) because of a relative deficiency in available vitamin K. VKDB manifestations range from mild “warning bleeds” (epistaxis, umbilical stump, or gastrointestinal bleeding) to severe (intracranial hemorrhage [ICH]). VKDB can be classified by the age of onset: early (<24 hours after birth), classical (2-14 days), and late (2-12 weeks). Newborn infants are at risk for VKDB for the following reasons: (1) reduced bioavailability because of poor placental transfer of vitamin K and the relatively short half-life of the K1 liver stores; (2) reduced vitamin K content in breast milk compared with fortified cow's milk–based formula; and (3) reduced production of vitamin K because of immature or altered gut flora. Because dietary intake is an infant's main source of vitamin K, exclusively breastfed infants have a higher risk for VKDB than formula-fed infants. In infants, the plasma concentrations of all vitamin K–dependent clotting factors are 40-60% of the adult values and slowly rise during infancy but can take up to 90 days to completely normalize even with adequate vitamin K stores.1
VKDB was first described by Townsend in 1894.2 In a definitive study published in 1944, prophylactic vitamin K given at birth was shown to reduce VKDB-associated death by greater than fivefold in the first 2 weeks of life.3 With evidence mounting over the next two decades, the American Academy of Pediatrics4 issued a statement in 1961 recommending that a single dose of vitamin K be given to all neonates shortly after birth, either 0.5-1 mg intramuscular (IM) or 1-2 mg oral. In the era of prophylaxis, VKDB has become rare, with most reported cases being classical or late onset and occurring in infants who either did not receive adequate vitamin K prophylaxis at birth and are exclusively breastfed or who had an undiagnosed malabsorptive or hepatobiliary disorder. Early VKDB is mainly because of the effect of maternal medications and can be effectively prevented by vitamin K at birth; when no prophylaxis is given, rate of early VKDB is 6-12%.5 Without prophylaxis, the incidence of classical VKDB is as high as 1.7% of live births6, whereas the incidence of late VKDB ranges from 4.4 to 7.2 per 100,000 live births.7 When IM vitamin K prophylaxis is given at birth, the rate of late VKDB ranges from 0.24 to 3.2 cases per 100,000 live births.8, 9, 10, 11, 12 ICH occurs frequently in cases of late VKDB and can lead to significant morbidity and mortality. In a pooled analysis of 131 cases, 63% of late VKDB presented with ICH, with 14% mortality and 40% long-term neurological morbidity among surviving infants.13
As part of a Centers for Disease Control investigation that followed a recent rise in the number of infants presenting with VKDB, we determined that 28% (61 of 218) of the parents of children born at local private birthing centers in Tennessee refused vitamin K prophylaxis.7 Over an eight month period after improvement in our education of parents of the risks of declining vitamin K prophylaxis, we demonstrated that 3.4% (104 of 3080) of local parents (Vanderbilt University Medical Center) declined oral or IM vitamin K prophylaxis. There is concern regarding an apparent rise in the rate of parental decline of vitamin K prophylaxis in the middle Tennessee area. However, no state or national mechanism exists to track decline rates at this time. We sought to describe encountered cases of late VKDB in an effort to educate health care providers on the variable presentation of this potentially life-threatening disorder.
Section snippets
Patients
We present five cases of late VKDB occurring at a single tertiary care children's hospital between February and September 2013 and two additional infants noted to have laboratories consistent with severe vitamin K deficiency but no bleeding (one asymptomatic infant evaluated as twin had ICH related to VKDB and one infant with acholic stools undergoing liver disorder evaluation). The details of these children are described with approval by the institutional review board at Vanderbilt University.
Discussion
These cases represent a substantial increase in the number of infants diagnosed with late onset VKDB in our region. We conducted a review of Tennessee hospital discharge data, searching for International Classification of Diseases-9 codes related to vitamin K deficiency and VKDB, and found six probable cases in 2007 (one with ICH), two cases in 2008, zero case in 2009, three cases in 2010, and one case in 2011; however, on further review, none of these met criteria for classical or late VKDB.
Conclusions
It is critical for health care providers to continue to advocate for the use of IM vitamin K prophylaxis at birth. There is concern regarding an apparent rise in the rate of parental decline of vitamin K prophylaxis in the middle Tennessee area. However, there is no state or national mechanism to track decline rates. We were able to establish a rise in the rate of VKDB in newborns in the middle Tennessee area in part because of collaboration with the CDC. The authors feel that education of
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Cited by (92)
Neonatal Bleeding and Thrombotic Disorders
2023, Avery's Diseases of the NewbornCare of the Newborn
2023, Avery's Diseases of the NewbornHemorrhagic Disease of the Newborn: A Case Series Illustrating Preventable Harm: Hemorrhagic disease of the newborn
2023, Journal of Pediatric Health CareVitamin K in human health and metabolism: A nutri-genomics review
2022, Trends in Food Science and TechnologyPlanned home birth and absence of vitamin K prophylaxis
2021, Anales de PediatriaLate vitamin K deficiency bleeding in infants: five-year prospective study
2021, Jornal de PediatriaCitation Excerpt :However, Ozdemir et al.12 demonstrated that subdural hemorrhage was the most common type of ICH reported, followed by intracerebral and subarachnoid hemorrhages, while Martín-López et al.30 mentioned that the majority of the patients (75%) showed ICH at more than one site. Late VKDB subtypes were associated with severe life-threatening bleeding, mainly ICH, which resulted in low hemoglobin level and anemia among our studied infants, which is similar to the findings reported by others.18,21,25,26 Throughout the follow-up period, we observed that VKDB subtypes were associated with morbidity and lethality among studied patients, and the outcome of patients did not have a statistically significant difference between the subtypes of VKDB.