116 - Neonatal Vitamin K Injections and Hyperbilirubinemia: Debunking Misconceptions

Publication Number: 2111.116

Connie Hu, University of California San Diego, San Diego, CA, United States; Zaineb Boulil, Rady Children's Hospital San Diego, San Diego, CA, United States; Eustratia M. Hubbard, UC San Diego School of Medicine, San Diego, CA, United States; Richard Silva, University of California, San Diego School of Medicine, San Diego, CA, United States; Joshua M. Rothman, University of California, San Diego School of Medicine, La Jolla, CA, United States

Background: Intramuscular vitamin K (phytonadione) injections prevent vitamin K deficiency bleeding (VKDB) of the newborn. Although rare, VKDB can cause significant neurological consequences and even death, but is preventable with vitamin K. Some families refuse vitamin K due to beliefs that it can cause hyperbilirubinemia. This originated from studies in the 1950s, where high doses of vitamin K in neonates were observed to have hemolysis, severe hyperbilirubinemia, and even death from kernicterus. No further studies have provided evidence to debunk this misconception.

Objective: The purpose of this study is to identify whether a correlation exists between intramuscular vitamin K and hyperbilirubinemia in the neonatal period.

Design/Methods: This retrospective cohort study evaluated birth hospitalization data from January 1, 2018 to December 31, 2023 of all singleton newborns, gestational age ≥37 weeks, born at two California academic medical centers. Total bilirubin levels were compared based on whether newborns received the 1 mg intramuscular Vitamin K injection. Data extracted from the electronic medical record system was then analyzed with multivariate linear regression models.

Results: A total of 17,618 electronic medical records were evaluated, of which 17,112 (97.1%) received the vitamin K injection. There was no significant association between receipt of vitamin K and bilirubin levels (95% confidence interval [-0.202, 0.285], p value = 0.74). Newborns that received phototherapy had higher bilirubin levels (coefficient = 6.02, p value < 1e-4). Full-term newborns had increased bilirubin levels (coefficient 0.27, p value < 1e-04) compared to late/post-term newborns (coefficient -0.21, p value 0.003). ABO incompatibility was also associated with a modest increase in bilirubin levels (coefficient 0.18, p value 0.002). When IgG positivity was included in the analysis, neither IgG positivity (p value = 0.45) nor ABO incompatibility (p value = 0.06) was significantly associated with higher bilirubin levels. However, when IgG positivity was excluded, both associations become significant (p value = 0.003 and p value = 0.002, respectively), suggesting that IgG positivity acts as a confounder.

Conclusion(s): This study found no association between routine vitamin K administration in newborns and elevated bilirubin levels, regardless of ABO incompatibility or Coombs positivity. As expected, bilirubin levels were higher among newborns who required phototherapy, were full-term compared to late/post-term, and had ABO incompatibility.

Table 1. Bilirubin Multivariate Linear Regression Model
This table shows the relationship between bilirubin and variables including vitamin K, phototherapy, full-term gestation, late/post-term gestation, ABO incompatibility, and IgG positivity. *Gestational age (GA) for full term defined as 39 0/7 to 40 6/7 weeks and late/post term defined as more ≥ 41 0/7 weeks.

Table 2. Bilirubin Multivariate Linear Regression Model (Excluding IgG)
This table shows the relationship between bilirubin and variables including vitamin K, phototherapy, full-term gestation, late/post-term gestation, and ABO incompatibility when IgG positivity is excluded.*Gestational age (GA) for full term defined as 39 0/7 to 40 6/7 weeks and late/post term defined as more ≥ 41 0/7 weeks.