22 - Association of female sex with refusal of newborn vitamin K and hepatitis B vaccine administration

Publication Number: 2019.22

Sarah A. Coggins, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Dustin D. Flannery, Children's Hospital of Philadelphia, Wynnewood, PA, United States; Karen M. Puopolo, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Sagori Mukhopadhyay, Childrens Hospital of Philadelphia, Philadelphia, PA, United States

Background: Medical misinformation is contributing to increasing parental hesitancy towards evidence-based standards of pediatric care. Rising refusal of newborn intramuscular vitamin K prophylaxis (VK) and hepatitis B vaccine (HBVx) is an emerging public health threat.

Objective: To determine factors associated with refusal of newborn Vitamin K and hepatitis B vaccine administration.

Design/Methods: Retrospective cohort study of all live births 1/1/2018 - 8/31/2025 at 3 centers of the University of Pennsylvania health system. Infants were excluded if born ≤34 weeks' gestation, or if they transferred or died before discharge. Maternal and infant demographic and medication administration data for the birth admission were abstracted from the electronic medical record. We used multivariable logistic regression to estimate the association between demographic/clinical variables with receipt of VK and HBVx, and the Jonckheere-Terpstra test to analyze trend by birth year.

Results: Among 88,255 infants, 704 (0.8%) were not administered VK and 8,527 (9.7%) did not receive HBVx. VK refusal was associated with female infant sex, maternal Black race and non-Hispanic ethnicity, vaginal delivery, and year of birth (Table 1). Female sex was significantly associated with 2.1-fold higher adjusted odds of VK refusal (95% CI 1.76, 2.41) compared to male sex. Absolute rates of VK refusal per 1000 live births rose significantly between 2018-2025 among both female and male infants (p < 0.001), increasing from 9.6 to 19.4 per 1000 female infants, and from 4.0 to 9.3 per 1000 male infants (Figure 1). HBVx refusal was associated with similar variables as VK refusal (Table 2). Female sex was significantly associated with HBVx refusal (aOR 1.07, 95% CI 1.02, 1.11) compared to male sex. Absolute rates of HBVx refusal rose between 2018-2025 among both female and male infants (p < 0.001), increasing from 86.4 to 164.2 per 1000 female infants, and from 77.9 to 152.6 per 1000 male infants (Figure). Male circumcision rates ranged 72-77% over the study period.

Conclusion(s): Female sex was associated with significantly higher odds of newborn VK and HBVx refusal, with substantial female sex-discordance in rates of VK compared to HBVx refusal. VK refusal rates doubled between 2018-2025 among both sexes, but female infants accounted for two-thirds of all infants not administered VK. These data suggest that parental decision-making for VK acceptance may be driven less by perceived safety and more by social mores (e.g., desire for male circumcision). Innovative strategies are required to reduce disparity in VK acceptance among female infants.

Table 1: Study Cohort Demographics and Multivariable Modeling of Factors Associated with Vitamin K Refusal
Footnotes: Univariate analyses performed using the Chi-square or Fisher's exact test for categorical data, and the Wilcoxon rank-sum test for continuous data. Multivariable logistic regression for odds of vitamin K refusal adjusted for infant sex, GA, maternal race and ethnicity, year of birth, and birth hospital. *Among infants with and without vitamin K administration, data were missing in the following: maternal ethnicity 6 (0.9%) and 620 (0.7%), birth hospital 0 (0%) and 53 (0.1%), respectively. Missing data accounting for >1% of a variable are shown in the table.

Table 2: Study Cohort Demographics and Multivariable Modeling of Factors Associated with Hepatitis B Vaccine Refusal
Footnotes: Univariate analyses performed using the Chi-square or Fisher's exact test for categorical data, and the Wilcoxon rank-sum test for continuous data. Multivariable logistic regression for odds of hepatitis B vaccine refusal adjusted for infant sex, GA, maternal race and ethnicity, year of birth, and birth hospital. *Among infants with and without Hepatitis B vaccine administration, data were missing in the following: maternal ethnicity 73 (0.9%) and 553 (0.7%), birth hospital 10 (0.1%), 53 (0.1%), respectively. Missing data accounting for >1% of a variable are shown in the table.

Sex-Specific Rates of Vitamin K and Hepatitis B Vaccine Refusal, 2018-2025