Immunization Status at the Time of Liver Transplant in Children and Adolescents

Abstract

This study characterizes the percentage of pediatric patients undergoing liver transplant who were up to date for their age on immunizations at the time of transplant and risk factors for underimmunization.

Vaccine-preventable infections are a serious complication following transplant. In a multicenter retrospective cohort study of 6980 pediatric solid organ transplant recipients between 2004 and 2011, 15.6% were hospitalized with a vaccine-preventable infection in the first 5 years after transplant at a rate of up to 87 times higher than in the general pediatric population.¹ Immunizations are a minimally invasive, cost-effective way to reduce the incidence of these infections. We quantified the percentage of patients at Society of Pediatric Liver Transplantation centers who were up to date for their age on immunizations at the time of transplant and determined whether demographic and clinical factors were associated with immunization status at the time of transplant.

Methods

We collected clinical and demographic data on all patients younger than 18 years who underwent a liver transplant between August 2017 and August 2018 at 39 centers in the United States and Canada. Each center used state registries and electronic medical, primary care, and parental records to determine which vaccines had been given by the date of transplant. Patients who underwent transplant for acute liver failure were excluded. Up-to-date immunization status was determined using 3 vaccine schedules: (1) the 7-vaccine benchmark used by the National Immunization Survey (NIS)²; (2) the Centers for Disease Control and Prevention (CDC) immunization schedule for healthy children³; and (3) the 2013 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for Vaccination of the Immunocompromised Host,⁴ which includes recommendations to accelerate measles, mumps, and rubella (MMR); varicella; and human papillomavirus immunizations in transplant candidates (Supplement). Bivariable analysis was performed to explore factors associated with being up to date on immunizations (using CDC guidelines) at the time of transplant. Statistical significance was set at P < .05 by 2-sided tests. Data were analyzed using SAS version 9.4. Participation in the Society of Pediatric Liver Transplantation registry was approved by institutional review or research ethics boards; parents or legal guardians provided written informed consent and patient assent was obtained when appropriate.

Results

Immunization records were available for 281 (93%) of 301 eligible patients. Of these patients, 55% (95% CI, 49%-61%) were up to date on immunizations based on the NIS requirements, 29% (95% CI, 24%-35%) based on the CDC schedule, and 19% (95% CI, 14%-24%) based on the IDSA accelerated schedule. Based on the CDC schedule, the percentage of children up to date (for age) for individual vaccines ranged from 50% for Haemophilus influenzae type b to 94% for meningococcus (Table 1). Of the 199 children not up to date based on the CDC schedule, 51% (95% CI, 44%-58%) were missing at least 4 immunizations. Of the 52 patients aged 6 to 11 months at the time of transplant who were eligible using the IDSA guidelines for accelerated live vaccines, 13 (25%) received MMR vaccinations (95% CI, 14%-39%) and 8 (15%) received varicella vaccinations (95% CI, 7%-28%). There were no demographic or clinical factors significantly associated with underimmunization, including administration by primary care physicians vs other clinicians (Table 2). Only 13 patients (5%) were reported to have had delayed transplant listing to allow for immunization compliance.

Table 1. Percentage of Children and Adolescents Up to Date for Individual Vaccines at the Time of Liver Transplant Based on the Centers for Disease Control and Prevention Schedule.

Immunization	Up-to-Date Patients, % (95% CI)
Hepatitis B	84 (80-88)
Diphtheria, tetanus, and pertussis	68 (62-73)
Hepatitis A	68 (63-74)
Haemophilus influenzae type b	50 (44-56)
Pneumococcus	63 (57-69)
Polio	77 (71-81)
Meningococcus	94 (91-97)
Varicella	88 (84-91)
Measles, mumps, and rubella	89 (85-93)
Human papillomavirus	90 (86-93)

Table 2. Characteristics of Patients Up to Date and Not Up to Date With Immunizations at the Time of Liver Transplant Based on the Centers for Disease Control and Prevention Schedule.

Characteristic	No. (%)		P Valuea
	Patients Not Up to Date (n = 199)	Patients Up to Date (n = 82)
Age, mo			.14
<18	64 (65)	34 (35)
≥18	135 (74)	48 (26)
Sex			.71
Male	102 (72)	40 (28)
Female	97 (70)	42 (30)
Raceb			.92
White	112 (71)	45 (29)
Black	28 (67)	14 (33)
Otherc	35 (73)	13 (27)
Missing	24 (71)	10 (29)
Ethnicityb			.29
Not Hispanic or Latino	147 (69)	66 (31)
Hispanic or Latino	31 (72)	12 (28)
Missing	21 (84)	4 (16)
Insurance			.62
Medicaid/SCHIP	97 (75)	33 (25)
Private insurance	65 (67)	32 (33)
Other	23 (70)	10 (30)
Missing	14 (67)	7 (33)
Diagnosis			.89
Biliary atresia	77 (70)	33 (30)
Nonbiliary atresia	104 (71)	43 (29)
Missing	18 (75)	6 (25)
Patient status			.26
Not hospitalized	127 (75)	42 (25)
Hospitalized, not in the ICU	28 (67)	14 (33)
In the ICU	26 (63)	15 (37)
Missing	18 (62)	11 (38)
Wait-list time, median (IQR), d	85 (34 to 206)	86 (38 to 215)	.64d
Calculated PELD or MELD score at listing, median (IQR)e	9.1 (–0.8 to 18.3)	6.5 (–3.4 to 24.2)	.72d
Transplant center volume			.08
Large (≥10 transplants/y)	172 (73)	64 (27)
Small (<10 transplants/y)	27 (60)	18 (40)
Type of clinician administering vaccine			.67
PCP only	128 (72)	50 (28)
Hepatology, hepatology and PCP, or other	66 (69)	29 (31)
Infectious disease physician involved in transplant evaluation			.62
Yes	90 (70)	39 (30)
No	108 (72)	41 (28)

Abbreviations: ICU, intensive care unit; IQR, interquartile range; MELD, Model for End-Stage Liver Disease; PCP, primary care physician; PELD, Pediatric End-Stage Liver Disease; SCHIP, State Children’s Health Insurance Program.

^aχ² Tests were used for categorical variables and Wilcoxon tests were used for continuous variables due to nonnormality.

^bRace and ethnicity were classified by participants and were included in this study because they have been shown to be factors associated with underimmunization.

^cOther includes 27 patients (9.6%) who identified as Asian, 14 (5.0%) as more than 1 race, 4 (1.4%) as American Indian/Alaska Native, and 3 (1.0%) as other.

^dCalculated via Wilcoxon test.

^eThe PELD and MELD scores are algorithms used to estimate relative disease severity and likely 90-day survival of patients awaiting liver transplant (PELD for patients younger than 12 years and MELD for patients older than 12 years). The PELD score is based on blood tests for bilirubin, albumin, and international normalized ratio and takes into account age younger than 1 year and history of growth failure. The MELD score is based on blood tests for bilirubin, albumin, sodium, and creatinine. Higher scores indicate more critical condition. The PELD algorithm is logarithmic so scores are infinite. The MELD score ranges from 6 to 40.

Discussion

In this high-risk population of pediatric liver transplant recipients with a lifetime of anticipated exposure to immunosuppressive therapy, there were low rates of age-appropriate immunization at the time of transplant. Only 55% of transplant recipients were up to date on the least stringent NIS 7-vaccine series compared with 70% of US children aged 19 to 35 months.⁵ Transplant recipients had lower vaccine rates than the overall population of children aged 19 to 35 months for each of the 7 core vaccines.⁵ Particularly concerning was underutilization of live vaccines in young children, which are not routinely recommended after transplant.^4,6

The study was limited by reliance on individual centers to collect immunization records using state registries and electronic medical, primary care, and parental records. Incomplete records could lead to a falsely increased underimmunization rate; however, included data were the only data available to transplant centers. Cloud-based digital immunization records or a national immunization registry might help overcome data barriers in the future.

Further research is needed to understand barriers to immunization in the pediatric transplant population. Novel tools that provide pretransplant vaccine education and enhance communication between primary care and subspecialty clinicians are needed to increase immunization rates in these high-risk children.

Section Editor: Jody W. Zylke, MD, Deputy Editor.

Supplement.

eFigure. Immunization schedules