Elsevier

Pediatric Neurology

Volume 50, Issue 6, June 2014, Pages 564-568
Pediatric Neurology

Original Article
Rise in Late Onset Vitamin K Deficiency Bleeding in Young Infants Because of Omission or Refusal of Prophylaxis at Birth

https://doi.org/10.1016/j.pediatrneurol.2014.02.013Get rights and content

Abstract

Background

Newborns are at risk for vitamin K deficiency and subsequent bleeding unless supplemented at birth. Vitamin K deficiency bleeding is an acquired coagulopathy in newborn infants because of accumulation of inactive vitamin K–dependent coagulation factors, which leads to an increased bleeding tendency. Supplementation of vitamin K at birth has been recommended in the United States since 1961 and successfully reduced the risk of major bleeding. Refusal or omission of vitamin K prophylaxis is increasing and puts newborn infants at risk for life-threatening bleeding.

Patients

Over an eight month period, we encountered seven infants with confirmed vitamin K deficiency; five of these patients developed vitamin K deficiency bleeding.

Results

The mean age of the seven infants with vitamin K deficiency was 10.3 weeks (range, 7-20 weeks); manifestations ranged from overt bleeding to vomiting, poor feeding, and lethargy. None of the infants had received vitamin K at birth, and all were found to have profound derangement of coagulation parameters, which corrected rapidly with administration of vitamin K in IV or intramuscular form. Four of the seven infants had intracranial hemorrhage; two of these infants required urgent neurosurgical intervention.

Conclusion

Supplementation of vitamin K at birth for all newborns prevents major hemorrhagic complications, such as intracranial bleeding, due to vitamin K deficiency. Parental refusal of vitamin K is increasingly common. It is critical that health care providers and the public be made aware of the varied presentation of this preventable acquired coagulopathy.

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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    Shinji et al. studied the value for prothrombin levels by the CA-1 method in the early neonatal period and then to explore whether the prothrombin levels change with gestational age, birth weight, concurrent diseases, and VK administration. To reduce the incidence of VKDB, oral VK prophylaxis with phytomenadione, or administration of a single intramuscular (IM) dose of 0.5–1 mg at birth is recommended by the World Health Organization (WHO) (Schulte et al., 2014)⁠. VK deficiency can become worse when certain drugs like heparin and carbamazepine are ingested during pregnancy (Davidson et al., 1987; Ross et al., 2012).

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