A retrospective cohort study was conducted at Cincinnati Children’s Hospital Medical Center (CCHMC), a tertiary care center with active pediatric SOT programs. The study included recipients of a first liver, kidney, heart, lung, intestinal, or multi-visceral transplant between January 1, 2018, and December 31, 2024. Demographic and clinical data were extracted from the electronic medical records, including age at first transplant evaluation, listing and transplantation dates, sex, underlying diagnosis, type of transplanted organ, vaccination records, and serologic results. Vaccination records were obtained from patients’ electronic medical records, which are routinely updated with internal and external vaccine records by the infectious diseases clinic during the standard pre-transplant assessment. Patients were excluded if they lacked vaccination records or were not transplanted at CCHMC.

Vaccination status was determined for measles and varicella based on documented vaccination records. Completed vaccination was defined separately for measles and varicella as meeting the following criteria for different age groups:

Pre-transplant vaccine immunogenicity was assessed using commercial chemiluminescent immunoassays (LIAISON, DiaSorin) in routine clinical practice: varicella-zoster virus IgG qualitatively at our institutional laboratory (seropositive >1.0 S/CO) and measles (rubeola) IgG at a reference laboratory (ARUP Laboratories, Salt Lake City, UT; positive ≥16.5 AU/mL, with equivocal results [13.5–16.5 AU/mL] classified as seronegative). Serologic status was analyzed dichotomously (seropositive vs. seronegative); numerical titers were not included. If testing was not performed, immunity status was recorded as unknown.

Descriptive statistics were used to summarize the data. Categorical variables were expressed as counts and percentages, while continuous variables were summarized using medians and interquartile ranges (IQRs). Comparisons between groups were performed using Chi-square or Fisher’s exact test for categorical variables and Mann–Whitney U or Student’s t-test for continuous variables. A two-sided p-value <0.05 was considered statistically significant. Analyses were conducted using IBM SPSS Statistics (Version 30).

This study was approved by the CCHMC Institutional Review Board (IRB ID:2023-0334). Due to the study’s retrospective nature and the use of de-identified data, the requirement for informed consent was waived in accordance with institutional policy.

During the 7-year study period, a total of 457 patients were evaluated for solid organ transplantation at CCHMC. Twenty patients who were not transplanted at CCHMC and 16 patients who had second or subsequent transplantations were excluded from the study, leaving a total of 421 SOT recipients in the analysis (Figure 1). The distribution of the transplants in the study cohort was 38.0% kidney (160/421), 33.5% liver (141/421), 17.1% heart (72/421), 3.8% lung (16/421), 2.6% heart-dual organ (11/421), and 5% abdominal multi-visceral and intestinal transplant (21/421). The number of transplants per organ type for each calendar year is shown in Supplementary Figure S1.

Among 421 patients, 53.7% (226/421) were male. The median age at transplantation was 8 years (range 0.6–38.4 years). Most patients (60.3%, 254/421) were >4 years old, while infants (<12 months) and toddlers (1–<4 years) comprised 13.3% (56/421) and 26.4% (111/421), respectively. Median times between evaluation and listing for transplantation, and between listing and operation were 42 and 114 days, respectively (Table 1).

Vaccination status was assessed for the same cohort of 421 recipients at all three time points (evaluation, listing, and transplantation), reflecting longitudinal follow-up of one population rather than separate groups. As age-based eligibility was reassessed at each milestone, the number of completely vaccinated patients could increase through catch-up vaccination or decrease as patients aged into categories requiring additional doses.

During follow-up, changes in pre-transplant vaccination status were observed in a subset of patients (Figure 2). For varicella, 7.1% (30/421) of patients transitioned from full to incomplete status, most frequently among heart transplant recipients (10/72, 13.9%) and liver transplant recipients (17/141, 12.1%), primarily based on changes in age category. Conversely, 4.8% (20/421) improved from incomplete to complete, primarily among kidney (11/160, 6.9%), liver (5/141, 3.5%), and lung (1/16, 6.3%) candidates, with no improvement observed in heart and heart-dual organ recipients. Similarly, for measles, 8.6% (36/421) transitioned to incomplete vaccination status, with the highest rates among liver (25/141, 17.7%) and heart (10/72, 13.9%) recipients. Improvement occurred in 3.8% (16/421), most commonly among kidney (9/160, 5.6%) and liver (6/141, 4.3%) transplant candidates, while no improvement was noted in lung, heart, or heart-dual organ recipients.

To identify patient characteristics associated with the risk of incomplete vaccination status at the time of transplantation, we compared demographics and clinical factors (Table 3). In this analysis, only cases exceeding the lower age limit of the relevant vaccine were included as vaccine-eligible (384 patients for varicella, and 406 patients for measles vaccination).

The distribution of organ types differed significantly for both varicella and measles (p < 0.05 for both). For varicella, liver and heart candidates were disproportionately represented in the incompletely vaccinated group, accounting for 42.0% (34/81) and 32.1% (26/81) of this cohort, respectively. In contrast, kidney recipients comprised nearly half of the fully vaccinated group (49.8%, 151/303) but only 11.1% (9/81) of the incompletely vaccinated group.

For measles, the disparity between organ groups was even more pronounced. Liver and heart candidates together constituted 83.5% of the incompletely vaccinated cohort (51.6% [47/91] and 31.9% [29/91], respectively). Conversely, kidney recipients accounted for 49.5% (156/315) of fully vaccinated patients but only 4.4% (4/91) of those who were incompletely vaccinated, highlighting a strong association between organ type and the likelihood of completing the recommended measles vaccination series before transplantation. While the lung transplant group had the second-lowest observed rate of complete vaccination (68.8%) for varicella, due to the small number of lung transplants, the difference between their vaccination rates in vaccine-eligible patients was not statistically significant.

Age was also a significant factor; children under 1 year of age at the first evaluation accounted for nearly half of those incompletely vaccinated for varicella (48.1%) and the majority of those incompletely vaccinated for measles (64.8%) at the time of transplantation. Consequently, the median ages at evaluation, listing, and transplant were all significantly lower in the incompletely vaccinated groups (p < 0.001 for all, Table 3). The duration between initial evaluation and listing was significantly shorter for patients in the incompletely vaccinated groups for both varicella (median 28 vs. 58 days; p < 0.001) and measles (median 23 vs. 59 days; p < 0.001). In multivariable analysis (Supplementary Tables S1, S2), non-kidney candidates and younger patients had significantly higher odds of incomplete vaccination (p < 0.05). Conversely, the evaluation-to-listing interval lost significance after adjustment. This suggests organ type captures the clinical urgency driving shorter timelines, while young age remains a distinct, independent barrier. In a sensitivity analysis applying a stricter two-dose definition for the 1–<4 years group, non-kidney organ type and younger age remained independent predictors for both vaccines (Supplementary Tables S3, S4). No significant differences were observed based on sex, year of transplantation, or the duration from listing to transplantation.

Serological tests were not performed on all patients at each assessment point or vaccination. Overall, varicella and measles serology were available for 94.3% (397/421) and 57.9% (244/421) of patients, respectively. To minimize the effect of passive maternal antibodies, all tests from patients under 12 months of age were excluded from comparative analysis. In completely vaccinated recipients, pre-transplant seropositivity was 76.4% (217/284) for varicella and 87.0% (167/192) for measles.

Among 1–<4-year-olds with serology, most had received one dose (74.7% varicella, 81.5% measles). Varicella seropositivity was lower after one than two doses (67.7% [44/65] vs. 95.5% [21/22]; p = 0.010), with 9 of 10 initially seronegative children seroconverting after the second dose; measles was already immunogenic after one dose (95.5% vs. 100%; p = 1.0). Among fully vaccinated older children (≥4 years), differences in seropositivity rates for measles were observed across the organ groups (p = 0.007, Table 4). Post-hoc analysis revealed that the seronegativity rate in kidney recipients (25.4%) was significantly higher than the rates in both liver (0.0%) and heart (5.0%) recipients (p < 0.05). Additionally, older kidney recipients were significantly more likely to be seronegative than their younger counterparts (93.1% vs. 74.6%, p < 0.05). For varicella, a trend toward higher seropositivity was observed in liver recipients (88.9%) compared to kidney (72.9%) and heart (66.7%) recipients; however, this difference was not statistically significant (p = 0.057).

A distinctive strength of our study lies in its organ-specific analysis and longitudinal tracking of vaccination status from initial evaluation to the time of transplantation. While other reports have provided valuable snapshots of incomplete vaccination across SOT populations, our longitudinal analysis, to our knowledge, is the first to document the transition of status systematically. This longitudinal approach revealed that overall vaccine coverage declined during the pre-transplant period, with a notable subset of patients—7.1% for varicella and 8.6% for measles—transitioning from complete to incomplete status rather than progressing toward schedule completion (Figure 2). As status was re-evaluated by age at each milestone, completely vaccinated counts could rise with catch-up vaccination or fall as patients aged into stricter requirements; the net decline thus reflects reclassification rather than loss of previously administered vaccines. The transition in vaccination status was most prominent in liver and heart transplant candidates. These shifts were primarily driven by age-based eligibility changes, highlighting the importance of continued, dynamic assessment of immunization status throughout the waitlist period.

Notably, the lowest vaccination rates in our cohort were observed among infants aged 9 to <12 months. These low rates highlight a critical vulnerability in the youngest candidates, a finding that is strongly corroborated by other research. One study found that a staggering 81% of infants aged 6–11 months with documented vaccination status had not received the first dose of the varicella vaccine prior to transplantation [12]. The same study concluded that this specific age group accounted for nearly half (47%) of missed immunization opportunities for the first vaccine dose. Crucially, our multivariable analysis confirmed that younger age is an independent predictor of incomplete vaccination, distinct from the type of organ transplant. Although our criteria for toddlers (1 to <4 years) required only one dose for 'complete' status, the decline in coverage observed as patients age underscores the difficulty of completing the full two-dose series. This definition did not affect our conclusions on sensitivity analysis, but its serologic impact was vaccine-specific: a single varicella dose was seroprotective in only 67.7% (vs. 95.5% after two doses), whereas one measles dose sufficed (95.5%), supporting prioritization of two-dose varicella completion before transplantation. Nonetheless, where sufficient time exists before transplantation, these candidates should still complete the full two-dose measles schedule recommended by AST IDCOP [2]. Guidelines for transplant candidates suggest accelerating vaccination, including early initiation (MMR from 6 months, varicella from 9 months) and early completion (second dose before age 4). Our data, and those of others, demonstrate that uptake of the early first dose is lagging. Low vaccine uptake in this population is further demonstrated by the European network survey, which found that 39% of transplant programs reported never prescribing an accelerated schedule for live-attenuated vaccines to infants [10].

Specific reasons for incomplete vaccination were not systematically recorded; however, the decline among younger candidates likely reflects urgent transplantation, temporary medical contraindications, and missed opportunities for accelerated dosing. Broader implementation of accelerated schedules, both early initiation and completion, improved documentation and standardized tracking could help clarify these barriers and enhance preparedness.

In contrast to the kidney group, where we saw rates of full vaccination exceeding 94% for both measles and varicella, rates at transplant were considerably lower for liver (66.7% for measles, 75.9% for varicella) and heart recipients (59.7% for measles, 63.9% for varicella). One of the key findings of our study was the unique vulnerability of heart transplant candidates as the existing literature is limited by publication era or study design [1, 13, 14]. In the multicenter observational study from Europe that included 430 pediatric liver transplant recipients, varicella and measles vaccination coverage rates before transplantation were reported as 65.2% and 81.1% respectively [11]. Again, a multicenter cohort of 281 pediatric SOT recipients (96% liver) from the US reported similarly low pre-transplant vaccination rates of 36% for MMR and 34% for varicella [3].

The underlying reason for increased risk in liver and heart candidates appears to be the urgency of their clinical course. The challenge of a shortened timeline is directly supported by the survey of European transplant centers, where “insufficient time before transplant” was cited by 86% of programs as the primary reason for incomplete immunization [10]. In contrast, the relative stability and higher vaccination rates we observed among kidney transplant recipients may reflect their longer and more predictable pre-transplant course afforded by the availability of dialysis. In our analysis, the evaluation-to-listing interval lost significance after adjustment, suggesting organ type effectively proxies for the clinical urgency and limited vaccination window characterizing liver and heart transplantation. Liver candidates lack a comparable bridging therapy, and while pediatric heart candidates may be stabilized with mechanical circulatory support devices, their clinical course often remains urgent. This fundamental difference in pre-transplant management directly impacts the window of opportunity for completing immunization schedules, positioning kidney recipients at a distinct advantage for vaccination administration.

Our cohort’s overall seropositivity rates in completely vaccinated children—76.4% for varicella and 87.0% for measles—appear more favorable but still demonstrate that a significant percentage of children who are up to date on vaccinations lack detectable antibodies. This discordance between vaccination records and humoral immunity is a well-documented challenge in transplant populations with one study of pediatric kidney candidates reporting seropositivity rates were as low as 59.0% for measles and 43.6% for varicella despite being fully vaccinated [15]. Another study found 50% seropositivity among children aged 7 years or older with two documented varicella vaccine doses [1].

This seropositivity gap was influenced by organ type and other clinical factors. In a multicenter study focused on pediatric liver transplant candidates, 53.1% were seropositive for varicella and 62.9% for measles before transplant [11].

In our cohort, older, completely vaccinated kidney recipients showed lower measles seropositivity than other organ groups. Although we did not collect renal-function laboratory values or dialysis data and did not perform any analysis relating these factors to serologic status, prior literature offers a plausible context: chronic kidney disease (CKD) and the uremic state have been associated with immune dysfunction and impaired vaccine responses [16]. Furthermore, factors such as the dialysis modality and a more rapid waning of vaccine-induced antibodies are documented challenges in this population [15, 16]. This observation is not limited to pediatrics, as studies in adult transplant candidates have also found that kidney recipients can be more likely to be seronegative despite vaccination compared to other transplant groups [17]. These mechanisms were not tested here and remain hypotheses for future, appropriately designed studies.

The discrepancy between vaccination history and measurable seropositivity raises critical questions about how best to assess protection before transplant. While national guidelines for the general pediatric population often consider two documented vaccine doses as sufficient evidence of immunity regardless of serology, transplant-specific guidelines recommend a more cautious approach due to the high risks in this population [1, 18]. For instance, the AST IDCOP guidelines recommend considering a third dose of MMR or varicella vaccine for transplant candidates who remain seronegative after completing their initial series [2]. However, the decision to revaccinate based on titers is complex, as serology measures only humoral immunity, and protection may persist through T-cell-mediated responses even with undetectable antibody levels [18, 19]. Ultimately, incorporating serologic screening into pre-transplant evaluations for select patients—especially those in high-risk groups, such as those with CKD—could help mitigate the risk of post-transplant vaccine-preventable diseases. The assessment of cellular immunity—such as Lymphocyte Transformation Testing (LTT)—and benchmarking against antibody persistence for non-live vaccines (e.g., tetanus) in seronegative candidates represent important targets for future research aimed at refining the assessment of pre-transplant vaccination status in children.

This study has some limitations. First, its retrospective design carries an inherent risk of information bias, particularly regarding vaccination histories from outside institutions. However, to mitigate this, our center has a standardized practice of collecting and integrating external vaccine records into the patient’s electronic medical record. Additionally, we could not account for unmeasured confounders, such as socioeconomic factors, parental vaccine hesitancy, or exposure to blood products or intravenous immunoglobulin—which can temporarily defer live viral vaccination. These unmeasured factors may influence vaccine administration. Our dataset did not include renal function laboratory values or dialysis details (duration or modality), and we did not perform any analyses relating these factors to serologic status. The lower seropositivity observed among kidney recipients is therefore a descriptive finding only; the contribution of the uremic state and dialysis-related factors, while biologically plausible and supported by prior literature, could not be evaluated in this study and should be addressed in future work. Another limitation is the incomplete serologic data for measles, available for only 58% of the cohort. Routine institutional screening for measles was implemented only during the final 2 years of the study period. Despite this, the available data still provides valuable insights into seropositivity gaps. Our reliance on serology provides information solely on humoral immunity, although cellular immunity also plays a protective role. Therefore, seronegativity does not definitively equate to a lack of protection. Nevertheless, serologic testing is currently the clinical standard for assessing the risk of vaccine-preventable diseases and guiding clinical decisions, such as the administration of additional vaccine doses. Finally, as a single-center study at a tertiary referral institution, our results—particularly our higher-than-average vaccination rates—may not be fully generalizable to other settings. However, the consistent protocols at a single center allowed for a detailed longitudinal analysis that is a unique strength of this study. Furthermore, the core challenges identified by this study, such as the impact of clinical urgency on vaccination timelines and the presence of organ-specific immunity gaps, are fundamental issues likely applicable to other pediatric transplant centers.

In conclusion, our longitudinal analysis uniquely reveals that the risk for incomplete vaccination is a dynamic process likely reflecting an overlap in system and clinical barriers. Shifts in care from primary to specialty providers, limited time for vaccination in acutely ill children, and variability in infectious disease involvement may contribute. A patient’s vaccination status can change during the pre-transplant period as they age, highlighting the need for continuous monitoring. Early infectious disease consultation and standardized vaccine tracking within transplant workflows could help reduce missed opportunities and improve coverage. We identified infants and those awaiting liver or heart transplantation as the most vulnerable subgroups, where shorter pre-transplant timelines directly correlate with a failure to maintain or complete vaccination schedules. Furthermore, our serologic data confirm that the number of vaccine doses received is not a guarantee for seropositivity. Therefore, these combined challenges underscore the urgent need for proactive, continuous vaccine management, including early implementation of expedited protocols and consideration of serologic screening, to ensure this high-risk population is truly protected.