Evaluating the safety profile of poliomyelitis vaccines: insights from post-marketing surveillance

Abstract

Poliomyelitis (POLIO) vaccines are widely used because of their high clinical effectiveness and minimal side effects.However, as post-marketing surveillance data have been collected, several serious adverse events (SAEs) linked to poliomyelitis vaccination have been reported.Currently, there is a lack of quantitative studies using real-world data, and detailed information about these adverse events is scarce.To fill this gap, adverse event signals associated with the poliomyelitis vaccine were extracted and analyzed using U.S. data.The Vaccine Adverse Event Reporting System (VAERS) serves as an important resource for post-marketing vaccine safety surveillance.Various statistical methods, such as the reporting odds ratio (ROR), the Proportional Reporting Ratio (PRR) approach, and the Bayesian Confidence Propagation Neural Network (BCPNN), were utilized to identify adverse event signals linked to poliomyelitis vaccination.Positive signals corresponding to designated medical events (DMEs) were identified for in-depth comparison and analysis.An analysis of 60,710 adverse events related to the poliomyelitis vaccine revealed 342 positive signals across 25 System Organ Classifications, with the most frequent being General disorders and administration site conditions.Three potential positive new signals consistent with Preferred Terms (PTs) were identified in DME: Erythema multiforme, Dermatitis exfoliative and Anaphylactoid reaction. This study identified disproportionality signals for erythema multiforme, exfoliative dermatitis, and anaphylactoid reaction in VAERS reports following poliomyelitis vaccination. These findings represent statistical reporting associations rather than evidence of causality and should be interpreted as hypothesis-generating signals requiring confirmation in well-designed epidemiological studies. Prompt clinical evaluation is recommended if severe or persistent symptoms occur.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12985-026-03244-9.

Introduction

Poliomyelitis (commonly known as polio) is a highly infectious disease caused by the poliovirus, primarily affecting children. In 1988, the World Health Assembly set a goal to eliminate polio by 2000 by halting the spread of all three wild poliovirus types. This decision followed the success of developed countries and regional efforts in the Americas in eliminating indigenous wild polioviruses through high immunization coverage [1–3]. Globally, the epidemiological characteristics of polio have changed significantly with the widespread use of vaccination. Since the introduction of the poliomyelitis vaccine, the number of polio cases worldwide has decreased dramatically, and many countries have achieved polio eradication. However, some adverse events (AEs) may still occur during vaccination, which need to be monitored and evaluated through the Vaccine AE Reporting System (VAERS).

The VAERS serves as a national vaccine safety surveillance mechanism jointly administered by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). Its primary objective is to identify vaccine safety signals and generate hypotheses through the collection and analysis of reports concerning AEs post-vaccination. Despite the limitations inherent in VAERS due to its passive surveillance nature, it remains a crucial component in the assessment of vaccine safety [4]. VAERS plays a crucial role in monitoring and analyzing AEs, helping identify potential safety issues and providing scientific evidence for vaccination policy development [2]. This study utilizes the proportion imbalance method with the VAERS database to analyze AE signals related to the Poliomyelitis (POLIO) vaccine.The objective is to evaluate the poliomyelitis vaccine’s safety and provide a basis for vaccination practices.

Materials and methods

Data acquisition and management

This study used data from the VAERS, a U.S. database created in 1990 and overseen by the CDC and FDA to track vaccine safety [5]. VAERS identifies new or rare AEs, monitors increases in known events, assesses patient risk factors, and evaluates the safety of new vaccines [6]. It records symptoms using MedDRA preferred term (PT) codes, with each VAERS ID listing up to five symptoms [7]. Our study analyzed all vaccine AEs reported in the United States from 1990 to January 30, 2025, using the VAERS database. We excluded foreign entries and removed duplicate reports and those missing essential information like age and gender to maintain data quality. Duplicate reports were identified and removed based on VAERS identification numbers, and reports with missing key demographic variables were excluded from the analysis. All data processing and statistical analyses were conducted using R software (version 4.4.2). After data cleaning, reports were included only when “VAX_NAME” was recorded as “POLIO VIRUS” and vaccine type was recorded as “POLIO.” Reports listing one or more co-administered vaccines were excluded from the primary analysis. This restriction was applied to reduce attributional ambiguity and to limit confounding from adverse events potentially associated with concurrently administered vaccines. Therefore, the analytic dataset represented reports of poliomyelitis vaccine administration without documented co-administered vaccines, rather than all real-world poliomyelitis vaccination encounters. All other eligible adverse-event reports in the database were used as the reference group for disproportionality comparisons. The study utilized MedDRA version 26.1 to encode each AE’s PT and associate them with their corresponding System Organ Classes (SOCs). To concentrate on vaccine-related ADRs and eliminate irrelevant reports, certain SOCs, such as product issues and social circumstances, were excluded. The flowchart of data cleaning is shown in Fig. 1. To explore potential heterogeneity between poliovirus vaccine formulations, additional formulation-stratified disproportionality analyses were conducted separately for inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV), according to the vaccine formulation recorded in the VAERS vaccine file. Signal detection criteria were identical to those used in the primary analysis. The formulation-specific results are presented in Supplementary Tables S1 and S2.

Fig. 1.

Flowchart of screening and classification of poliovirus vaccine-related adverse event reports from the US VAERS database

Descriptive analysis

Descriptive statistics categorized AE reports for the poliomyelitis vaccine based on gender, age, dosage, onset time, reporting year, and outcome.Annually, serious adverse events (SAEs) such as death, permanent disability, life-threatening conditions, hospitalization, prolonged hospital stays, congenital anomalies, or birth defects were analyzed.

Statistical analysis

Disproportionality analysis is widely used for adverse drug reaction signal detection in spontaneous reporting databases. It compares the reporting frequency of a specific vaccine–event pair with the corresponding background reporting frequency. The two-by-two contingency table is presented in Table 1, in which a represents reports containing both the target vaccine and target adverse event, whereas b, c, and d represent the remaining report categories.

Table 1.

Two-by-two contingency table for measure of disproportionality

	Number of target adverse event reports	Number of other adverse event reports	Total
Target drug	A	B	A+B
Other drugs	C	D	C+D
Total	A+C	B+D	A+B+C+D

This study applied three complementary disproportionality methods—the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN)—according to established pharmacovigilance criteria [8–10]. A signal was considered positive only when all three algorithms met their predefined thresholds. For the ROR and PRR methods, a minimum of three reports was required for each vaccine–event pair (N ≥ 3). Higher ROR, PRR, and IC-2SD values indicated stronger disproportionality signals; detailed algorithms and thresholds are provided in Table 2.

Table 2.

Signal detection primarily utilizes three key algorithms

Algorithms	Equation	Criteria
ROR	ROR = ad/b/c	lower limit of 95% CI > 1, N ≥ 3
	95%CI = eln(ROR)±1.96(1/a+1/b+1/c+1/d)^0.5
PRR	PRR = a(c + d)/c/(a + b)	PRR ≥ 2, χ2 ≥ 4, N ≥ 3
	χ2=[(ad-bc)^2](a + b+c + d)/[(a + b)(c + d)(a + c)(b + d)]
BCPNN	IC=log2a(a + b+c + d)(a + c)(a + b)	IC025 > 0
	95%CI = E(IC) ± 2 V(IC)^0.5

Equation: a, number of reports containing both the target drug and target adverse drug reaction; b, number of reports containing other adverse drug reaction of the target drug; c, number of reports containing the target adverse drug reaction of other drugs; d, number of reports containing other drugs and other adverse drug reactions.95%CI refers to the 95% confidence interval; N denotes the number of reports; χ² represents the chi-squared statistic; IC stands for the information component; IC025 is the lower limit of the 95% confidence interval for the IC; E(IC) indicates the expected value of the IC; V(IC) signifies the variance of the IC

Because these measures are derived from reporting frequencies rather than verified incidence data, positive findings were interpreted as statistical reporting associations requiring further evaluation, rather than evidence of increased absolute risk or causal associations. Adverse events were analyzed at the MedDRA Preferred Term (PT) level and subsequently summarized by System Organ Class (SOC). PT-level signals were not considered mutually independent because related PTs may represent overlapping manifestations, coding variation, or different descriptions of a common underlying event. In addition, estimates for rare events with limited report counts may remain unstable despite the use of multiple algorithms and the minimum case threshold; therefore, such signals were interpreted cautiously as hypothesis-generating findings.

Designated medical events (DME) list screening

In 2016, the EU established a list of 62 PTs classified as ‘inherently serious’ and frequently associated with medicine.According to the EMA [11]. the list serves to prioritize AEs in signal detection, functioning as a ‘safety net’ to prevent overlooked signals.This study assesses serious safety events associated with the poliomyelitis vaccine by identifying significant signals through the DME list and conducting a detailed analysis using relevant SOCs.

Results

Descriptive overview of cases

This study retrieved a total of 60,710 AE reports associated with poliomyelitis vaccination from the VAERS database (Table 3). A slight male predominance was noted among these reported cases, and pediatric populations comprised the majority of reports: infants (≤ 1 year) and children aged 2–12 years together accounted for over 80% of all cases. AE onset was predominantly reported on the day of vaccination or within 30 days after vaccination. However, the reported temporal proximity should not be interpreted as evidence of causality because VAERS data do not permit assessment of background incidence, confounding factors, or alternative explanations for the reported events. Serious outcomes, including hospitalization, life-threatening events, and death, were reported in only a small subset of cases, whereas a considerable proportion of reports lacked complete classification of clinical outcomes.

Table 3.

Characteristics of AE reports associated with poliomyelitis vaccine from VEARS between 1990.1.1–2025.1.30

Characteristics		N	Proportion (%)
Total		60,710	100%
Gender	Male	31,481	51.9%
	Female	28,593	47.1%
	Unknown	636	1.0%
Age(year)	<=1	23,428	38.6%
	> 1, < 2	7163	11.8%
	≥ 2, < 12	26,561	43.8%
	≥ 12, < 22	1969	3.2%
	≥ 22, < 42	799	1.3%
	≥ 42, < 62	594	1.0%
	≥ 62, < 120	196	0.3%
Administration dose	1	11,882	19.6%
	2	9300	15.3%
	3	10,503	17.3%
	4	18,109	29.8%
	5	2256	3.7%
	6	134	0.2%
	7+	37	0.1%
	Unknown	8489	14.0%
Outcome	Died	1388	2.3%
	Life threatening	1117	1.8%
	Emergency room	24,355	40.1%
	Hospitalized	5398	8.9%
	Prolonged hospitalization	297	0.5%
	Disability	937	1.5%
	Emergency room/department or urgent care	303	0.5%
	healthcare professional office/clinic visit	653	1.1%
	Unknown	26,262	43.3%
Onset time(day)	0	25,682	42.3%
	> 0, < 30	29,633	48.8%
	≥ 30, < 60	434	0.7%
	≥ 60, < 90	135	0.2%
	≥ 90, < 120	77	0.1%
	≥ 120	1101	1.8%
	Unknown	3648	6.0%

AE refers to an adverse event, POLIO stands for Poliomyelitis Vaccine, and VAERS is the vaccine adverse event reporting system.

The temporal distribution of reported AEs and SAEs from 1990 to 2025 is presented in Fig. 2, which identifies three distinct phases. The first phase (1990–2003) was characterized by relatively high and fluctuating reporting volumes, during which SAEs consistently accounted for 15%–40% of all reports; this period coincided with large-scale poliomyelitis eradication campaigns. The second phase (2004–2020) saw a marked decline in reporting rates, a trend temporally aligned with the transition from oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) formulations and the sustained control of poliomyelitis. A modest uptick in reporting was observed between 2021 and 2024, driven primarily by non-serious AEs; this pattern potentially reflects post-pandemic immunization catch-up initiatives. Notably, the proportion of SAEs remained relatively stable across all study periods.

Fig. 2.

Yearly frequencies of overall poliomyelitis vaccine AEs and SAEs reports

Among AEs with ≥ 1,000 reported occurrences (Table 4), General disorders and administration site conditions was the most frequently reported SOC, followed by Skin and subcutaneous tissue disorders and Nervous system disorders. The most commonly documented PTs included pyrexia, injection site reactions, rash, convulsion, and somnolence—symptoms consistent with expected post-vaccination reactions. While these frequency-based findings provide a comprehensive overview of the AE reporting landscape for polio vaccination, they do not inherently indicate disproportionate safety signals; such signals were further investigated through disproportionality analyses.

Table 4.

Distribution of adverse events in reports with sample sizes of 1000 or more

SOC	PT (n ≥ 1000)
General disorders and administration site conditions(83943)	Pyrexia(16636), Injection Site Erythema(9078), Injection Site Oedema(5813), Crying(4760), Screaming(4747), Injection Site Swelling(4622), Injection Site Hypersensitivity(4316), Injection Site Warmth(3478), Injection Site Pain(3381), Injection Site Induration(2244), Feeling Hot(2091), Injection Site Mass(2021), Pain(2019), Swelling(1730), Oedema(1674), Oedema Peripheral(1585), Injection Site Reaction(1509), No Adverse Event(1119)
Skin and subcutaneous tissue disorders(23465)	Rash(4678), Erythema(4562), Urticaria(3521), Pruritus(2596), Rash Maculo-Papular(1095)
Nervous system disorders(20608)	Convulsion(3478), Somnolence(2117), Hypotonia(1825), Stupor(1668), Tremor(1350)
Psychiatric disorders(10577)	Agitation(5925), Irritability(1454)
Gastrointestinal disorders(8695)	Vomiting(3766), Diarrhoea(1442)
Infections and infestations(8515)	Cellulitis(1565), Infection(1466)
Vascular disorders(6563)	Vasodilatation(2279), Pallor(2244), Cyanosis(1230)
Respiratory, thoracic and mediastinal disorders(6444)	Dyspnoea(1114), Apnoea(1064), Cough(1016)
Metabolism and nutrition disorders(2706)	Anorexia(1441)

AE refers to an adverse event, PT denotes the preferred term, and SOC stands for system organ classification

Disproportionality analysis

Disproportionality analysis using ROR, PRR, and BCPNN, with signals defined by concordance across all three methods, identified 342 signal-positive MedDRA PTs spanning 25 SOCs. These PT-level signals represent reported clinical terms and may include overlapping or closely related manifestations; therefore, they should not be interpreted as 342 independent clinical conditions (Figs. 3 and 4). Signal-positive SOCs were broadly distributed across multiple physiological systems, most prominently involving Nervous system disorders, General disorders and administration site conditions, Skin and subcutaneous tissue disorders, Infections and infestations, and Psychiatric disorders. Formulation-stratified analyses showed partially overlapping but distinct reporting patterns for IPV and OPV. A total of 255 signal-positive PTs were identified for IPV and 164 for OPV, of which 74 PTs were shared between formulations (Supplementary Tables S1 and S2). Sudden infant death syndrome was detected in both analyses, with higher disproportionality estimates in OPV reports than in IPV reports (OPV: ROR 70.84, 95% CI 63.50–79.04; IPV: ROR 21.60, 95% CI 18.93–24.65). Erythema multiforme was also detected for both IPV and OPV. In contrast, dermatitis exfoliative and anaphylactoid reaction were detected as positive signals only in the OPV-stratified analysis. These formulation-specific findings indicate heterogeneity in reporting patterns; however, they do not provide direct evidence of differences in incidence or causal risk between vaccine formulations.

Fig. 3.

poliomyelitis vaccine AE SOC positive signals

Fig. 4.

The positive signaling for adverse events related to the poliomyelitis vaccine includes specific Preferred Terms (PT) within the System Organ Class (SOC)

At the SOC level, Nervous system disorders exhibited the greatest diversity of signal-positive PTs, followed by General disorders and administration site conditions and Infections and infestations, indicating a wide range of neurologic and systemic events demonstrating disproportionate reporting. Importantly, the distribution of signal-positive PTs across SOCs did not consistently parallel overall reporting frequency, underscoring the distinction between commonly reported AEs and disproportionate safety signals.

At the PT level, while frequently reported events such as pyrexia, injection site erythema, agitation, and rash were among the signal-positive terms, the strongest disproportionality signals were observed for several less frequent but clinically significant events. These included Stupor (ROR = 64.17; PRR = 63.63; IC = 4.94; χ² = 48,765.39), Sudden infant death syndrome (ROR = 60.34; PRR = 60.11; IC = 4.90; χ² = 21,178.50), screaming (ROR = 58.26; PRR = 56.86; IC = 4.86; χ² = 130,939.74), and vomiting neonatal (ROR = 57.37; PRR = 57.37; IC = 4.87; χ² = 55.39).

These PTs demonstrated elevated disproportionality estimates across all three algorithms. However, particularly for events with lower absolute reporting frequencies, these estimates may be sensitive to sparse-data effects and reporting-related biases. They should therefore be interpreted as exploratory signals of potential interest that warrant further clinical and epidemiological evaluation.

DME list screening results

Among the detected signals, Erythema multiforme, Dermatitis exfoliative, and Anaphylactoid reaction were identified as potential new signals related to the DME (Table 5).

Table 5.

DME screening results for poliomyelitis vaccine. DME designated medical events

PT	N	ROR	PRR	χ2	IC025
Skin and subcutaneous tissue disorders
Erythema multiforme	189	3.60 (3.11–4.17)	3.60	333.65	1.57
Dermatitis exfoliative	34	9.52 (6.62–13.68)	9.52	222.24	2.53
Immune system disorders
Anaphylactoid reaction	37	2.81 (2.02–3.91)	2.81	41.06	0.97

Discussion

This study evaluated the post-licensure safety profile of the poliomyelitis (POLIO) vaccine using disproportionality analysis of the VAERS database combined with Designated Medical Event (DME) screening. A total of 342 positive signals across 25 SOCs were identified, encompassing both common, expected post-vaccination reactions and rarer outcomes of potential clinical significance. While most detected signals were consistent with established safety profiles, several findings warrant further discussion within a pharmacovigilance framework.

Among the identified signals, Sudden Infant Death Syndrome (SIDS) exhibited one of the highest RORs. Given the severity of this outcome, careful interpretation is required. SIDS predominantly occurs during infancy, which temporally overlaps with routine poliomyelitis immunization schedules and may contribute to elevated disproportionality estimates in passive surveillance systems. Importantly, disproportionality signals reflect reporting associations rather than causal relationships, and current epidemiological evidence does not support a causal link between routine childhood immunization and SIDS. Accordingly, this signal should be regarded as hypothesis-generating and warrants further evaluation using controlled epidemiological studies.

In addition to SIDS, erythema multiforme was identified as a potential new signal through DME screening. Although this immune-mediated dermatological condition has been infrequently reported following vaccination and reports specifically associated with the poliomyelitis vaccine remain limited, its detection in this analysis underscores the utility of disproportionality-based approaches for identifying rare but potentially clinically relevant AEs, which are discussed in further detail below.

The potential DME signals identified in this study should be interpreted within a hypothesis-generating pharmacovigilance framework [12]. Although biological mechanisms can be considered for contextual interpretation, the present VAERS-based analysis cannot establish that poliomyelitis vaccination caused any of the identified events. The available reports lack detailed clinical adjudication, laboratory testing, pathological confirmation, information on concurrent infections or medications, and product-specific data required to evaluate causality or define an underlying mechanism [13, 14].

Erythema multiforme is an acute immune-mediated mucocutaneous reaction characterized by target-like lesions and, in some cases, mucosal involvement [15]. It is most commonly associated with infections, particularly herpes simplex virus, although medications and vaccinations have also been reported as potential temporal triggers [16]. Available immunopathological evidence suggests that cytotoxic T-cell activity and inflammatory cytokine pathways may contribute to keratinocyte injury in erythema multiforme. Thus, it is biologically plausible that immune stimulation following vaccination could temporally coincide with erythema multiforme in susceptible individuals. However, this theoretical explanation should not be interpreted as evidence that poliomyelitis vaccination directly induces erythema multiforme. In the present study, no information was available regarding preceding infection, medication exposure, lesion biopsy, viral testing, immunological markers, or recurrence after re-exposure. Therefore, alternative explanations cannot be excluded.

Exfoliative dermatitis is a clinically heterogeneous inflammatory skin syndrome characterized by diffuse erythema, scaling, and desquamation [17]. It may occur in association with medications, infections, pre-existing inflammatory dermatoses, malignancy, or other systemic conditions [18]. Although immune dysregulation and T-cell-mediated inflammatory pathways may contribute to some forms of erythrodermic skin disease, the pathophysiology of exfoliative dermatitis is not uniform [19]. The disproportionality signal observed in this study does not provide sufficient evidence to identify a poliomyelitis-vaccine-specific biological mechanism. In particular, VAERS reports do not allow confirmation of the diagnosis, evaluation of disease severity, assessment of pre-existing skin disease, or exclusion of competing etiologies. Accordingly, exfoliative dermatitis should be regarded as an exploratory signal requiring continued monitoring and further clinical investigation.

Anaphylactoid reaction is a MedDRA-coded term describing an acute hypersensitivity-like clinical presentation [20]. Such reactions may involve several mechanisms, including classical IgE-mediated hypersensitivity, non-IgE-mediated mast-cell activation, complement-related pathways, or host-specific susceptibility to vaccine antigens, excipients, or residual substances. Certain inactivated poliovirus vaccine formulations contain residual substances that may theoretically contribute to allergic reactions in sensitized individuals. However, the present study could not determine the vaccine formulation, lot-specific composition, route of administration, timing of symptom onset, serum tryptase level, allergy-testing results, or other clinical features required to distinguish IgE-mediated anaphylaxis from non-IgE-mediated reactions. Therefore, the identified anaphylactoid reaction signal should be interpreted as a statistical reporting association of potential clinical interest rather than evidence of a confirmed vaccine-induced immunological mechanism.

Overall, these biological considerations provide a rationale for further investigation but do not establish causality. Future studies should use clinically adjudicated case series, active surveillance systems, linked immunization-healthcare databases, and mechanistic investigations to evaluate the potential role of vaccine formulation, host susceptibility, concurrent infections, and alternative etiologies in these reported events.

Anaphylactoid reactions, which are clinically similar to anaphylaxis but do not involve an IgE-mediated immune response, can occur as AEs following immunisation, including with vaccines such as the poliomyelitis vaccine. These reactions are characterized by symptoms such as urticaria, angioedema, respiratory distress, and hypotension, and they require prompt medical attention to prevent severe outcomes. The rarity of these events makes them difficult to detect in prelicensure vaccine trials, as they often rely on passive reporting schemes that may not capture all instances of such reactions.

Researchers in the UK and Ireland carried out a study to determine the frequency and clinical characteristics of anaphylaxis as a side effect of vaccination using prospective active monitoring. The study, examining children under 16, concluded that anaphylaxis is an uncommon AE post-immunisation. Notably, no cases were linked to vaccines administered in the routine infant and preschool immunisation programme, despite over 5.5 million vaccines being administered during the study period.The incidence rates for vaccines like the single component measles vaccine and the bivalent human papilloma virus vaccine were calculated, underscoring the infrequency of these occurrences [16].

While the study did not specifically address the poliomyelitis vaccine, it underscores the importance of monitoring and reporting AEs following immunisation to ensure vaccine safety. Healthcare providers should be prepared to promptly manage anaphylactoid reactions, particularly in patients with a history of allergies. This vigilance helps maintain public confidence in vaccination programs and ensures the continued success of immunisation efforts in preventing infectious diseases.

Limitation

This study has several limitations inherent to analyses based on the Vaccine Adverse Event Reporting System (VAERS). First, VAERS is a passive spontaneous reporting system and is susceptible to underreporting, incomplete information, diagnostic uncertainty, coding errors, and reporting-related biases. Mild or transient events may be less likely to be reported, whereas serious, unusual, temporally proximate, or highly publicized events may be preferentially submitted. Stimulated reporting and notoriety bias related to media coverage, public concern, regulatory communications, or increased clinical awareness may further alter reporting patterns independently of a true change in event occurrence. Therefore, the reporting frequencies observed in VAERS may not reflect the true incidence of adverse events following poliomyelitis vaccination. Second, although duplicate reports were removed using VAERS identification numbers, residual duplication cannot be completely excluded because the same clinical episode may be reported by different sources and assigned different identifiers. In addition, VAERS reports often lack sufficient information to verify diagnoses, evaluate event severity, assess medical history or concomitant medications, and exclude alternative etiologies. The exclusion of reports with missing demographic information may also have introduced selection bias if excluded reports differed systematically from retained reports. Third, the primary analysis excluded reports involving co-administered vaccines to reduce attributional ambiguity. However, poliovirus vaccines are commonly administered with other routine childhood vaccines, and this restriction may reduce the representativeness of the analytic population. Individuals receiving poliomyelitis vaccine without documented co-administration may differ from those receiving routine combination immunization with respect to age, vaccination setting, clinical characteristics, and reporting behavior. Conversely, including co-administered vaccine reports would increase representativeness but would make vaccine-specific attribution uncertain. Accordingly, the observed signals may not be directly generalizable to the broader population receiving poliovirus vaccines within routine multi-vaccine immunization schedules. Fourth, disproportionality analyses are influenced by the structure of the reporting database. Frequently reported events may obscure signals associated with less frequently reported reactions, whereas rare events may yield high ROR, PRR, or BCPNN estimates because of sparse-data effects, small cell counts, and random variation. Although a minimum of three reports was required for each vaccine–event pair and signals were defined by concordance across ROR, PRR, and BCPNN, these criteria do not fully eliminate instability or false-positive findings for rare events. Similarly, the absence of a signal does not exclude the possibility of masking by more frequently reported events. Finally, adverse events were analyzed at the MedDRA Preferred Term level. Multiple related PTs may reflect overlapping manifestations of a common clinical condition, coding variation, or several symptoms recorded within the same report. Therefore, the number of signal-positive PTs should not be interpreted as the number of independent clinical syndromes or distinct safety concerns. Future studies could complement PT-level analyses with clinically informed aggregation using higher MedDRA hierarchy levels, Standardised MedDRA Queries, or related event groupings. Because VAERS does not provide reliable vaccine-exposure denominators or an unvaccinated comparison group, this study cannot estimate incidence, absolute risk, relative risk, or causality. The identified ROR, PRR, and BCPNN findings should therefore be interpreted as statistical reporting associations and hypothesis-generating signals that require confirmation through active surveillance, linked healthcare databases, and well-designed epidemiological studies.

Conclusion

This study evaluated the post-marketing safety profile of poliomyelitis vaccines using VAERS-based disproportionality analysis and identified 342 signal-positive adverse-event terms across multiple System Organ Classes. Most signals involved general, neurological, and dermatological manifestations and were broadly consistent with the established safety profile of poliomyelitis vaccines. Several signals, including sudden infant death syndrome (SIDS), showed elevated disproportionality estimates; however, these findings require particularly cautious interpretation because temporal coincidence with routine infant immunization, confounding, and reporting bias may influence passive-surveillance data. The present findings do not establish a causal association between poliomyelitis vaccination and SIDS.

Potential signals for erythema multiforme, exfoliative dermatitis, and anaphylactoid reaction were also identified. These uncommon events should be regarded as statistical reporting associations of potential clinical interest rather than evidence of increased incidence, excess risk, or causal effects. The findings should also be interpreted in the context of the restriction to reports without documented co-administered vaccines and may not fully reflect the reporting profile of poliomyelitis vaccination within routine multi-vaccine schedules. Overall, the results support the established safety profile of poliomyelitis vaccines while highlighting rare events that may warrant continued pharmacovigilance and confirmation through active surveillance and well-designed epidemiological studies.

Abbreviatons

POLIO

Poliomyelitis

SAEs

Serious Adverse Events

VAERS

Vaccine Adverse Event Reporting System

ROR

Reporting Odds Ratio

PRR

Proportional Reporting Ratio

BCPNN

Bayesian Confidence Propagation Neural Network

DMEs

Designated Medical Events

PT

Preferred Term

SOCs

System Organ Classifications

CDC

Centers for Disease Control and Prevention

FDA

Food and Drug Administration

AEs

Adverse Events

ADR

Adverse Drug Reaction

IPV

Inactivated Poliovirus Vaccine

OPV

Oral Poliovirus Vaccine

EM

Erythema Multiforme

CI

Confidence Interval

IC

Information Component

SIDS

Sudden Infant Death Syndrome

EMA

European Medicines Agency

Author contributions

Conceptualization, Gang Qiu; methodology, Xiao-Dong Ma and Feng-Feng Fu; writing—original draft preparation, Gang Qiu; writing—review and editing, Xiao-Dong Ma and Feng-Feng Fu. All authors were involved in executing the research and in the composition of this manuscript.

Funding

Not applicable.

Data availability

The data and materials are derived from the Vaccine Adverse Event Reporting System (VAERS) and are publicly available through the VAERS request form.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

This manuscript has not been published or presented elsewhere in part or in entirety, and is not under consideration by another journal. All the authors have approved the manuscript and agree with submission to your esteemed journal.

Competing interests

The authors declare no competing interests.