Beyond coverage: can vaccination reduce child mortality despite structural inequality? A global ecological analysis of routine childhood immunization (2010–2023)

  1. Valeria Rios Montoya
  2. Arlet Yelisse Suarez Alarcon
  3. Shamira Perez Castillo
  4. Trilce Zamudio Raez
  5. Antonio M. Quispe

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Abstract

Routine childhood immunization is still a critical topic for global public health, since it prevents an estimated 3.5 to 5 million deaths annually. However, its access remains uneven, especially in low-income countries, where structural inequalities limit the reach of immunization programs, and the Covid-19 pandemic disrupted routine services, worsening the existing disparities. This ecological study (2010-2023) examined associations between vaccine coverage and infant mortality using the WHO/UNICEF data for six childhood vaccines: BCG, DTP3, HepB3, Hib3, MCV2, and Pol3. Countries were stratified by income level using the World Bank World Development Indicators. Associations between vaccine coverage and infant mortality were evaluated using multivariable linear regression models adjusted for national income level. In addition, non-linear relationships and rank-based associations were explored using LOESS smoothing and Spearman correlation analyses. Results showed higher coverage and lower mortality in high-income countries; meanwhile, low-income countries faced both reduced coverage and higher mortality rates. A significant decline in coverage occurred in 2020, with only partial recovery by 2023. After adjusting for income, most vaccine coverage indicators lost statistical significance in relation to infant mortality. These findings highlight that income-related structural inequities determine immunization coverage and preventable child mortality, emphasizing the need for policies that simultaneously expand vaccine access, reduce structural barriers, and strengthen health systems.

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  1. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/18840808.

    This review is the result of a virtual, collaborative Live Review discussion organized by one of PREreview 2025 Champions on February 20, 2026. The discussion was joined by 5 people: 2 facilitators and 3 live review participants. The authors of this review have dedicated additional asynchronous time over the course of 10 days to help compose this final report using the notes from the Live Review. Special thanks to all participants who contributed to the discussion and made it possible to provide feedback on this preprint.

    Summary

    The main goal of this study was to examine the associations between vaccine coverage and infant mortality using WHO and UNICEF data for six childhood vaccines: BCG, DTP3, HepB3, Hib3, MCV2, and Pol3. The data covered the years 2010–2023, and countries were stratified based on income level using the World Bank World Development Indicators.

    This study is important because routine childhood immunization is still a critical public health strategy since it prevents an estimated 3.5 to 5 million deaths annually. However, according to this study, access to childhood immunization programmes is unequal, especially in low-income countries due to structural inequalities. The results show that high-income countries tend to have higher vaccine coverage and lower infant mortality rate, while low-income countries have lower coverage and higher mortality. However, after adjusting for income level, the study found no significant difference in the impact of vaccine coverage indicators on infant mortality.

    An interesting aspect of the study is its focus on the association between income levels, structural inequalities, vaccine coverage and infant mortality. It exposes how socioeconomic factors affect vaccine outcomes across countries.

    A weakness of the study lies in the fact that it is ecological in design. As a result, it can not determine the exact cause or explain how other factors (such as family education level, location i.e. urban, rural, and access to healthcare systems) influence vaccine coverage and infant mortality rates at the individual level. It only highlights the general impact of income levels and structural inequalities at the population level in the countries under study.

    List of major concerns and feedback

    • In Line 188, please justify the reason for classifying high-income countries as the reference category. As there's a level of dislike for childhood vaccination in some high-income countries due to misinformation and distrust.

    • In Table 2, the "Reference: High income " does not have any data, making the interpretation difficult. How were the CIs and P-values for other categories calculated, if there was no numerical value to be compared with in the reference?

    • The main figures 1-3, are not embedded in the main text of the manuscript, making interpretation of results to be difficult for readers.

    • The figures at the bottom of the manuscript are not numbered and can't be correlated with the main text.

    • The supporting information (Lines 487-532) only contains the titles of tables, figures, and datasets. There's no visual representation for them. The authors should include the complete supporting information.

    • While the manuscript text may support the data in Table 1, corrections or revisions need to be made to the data in Table 2. In addition, other figures though clearly represented, do not have numbered labels. Table 2 should be carefully cross-checked to ensure accuracy while the figures should be clearly numbered for proper identification.

    • It seems the data presented in Table 2 shows the different VCIs almost in the same range across the different income levels of classification. How then is the mortality rate widely different? Whereas, in the manuscript, VCI is reported to be low in low-income countries while the mortality there is high and vice versa, the table seems to say otherwise - showing VCI almost the same, but with a reduced mortality rate. The authors need to clarify this discrepancy and report their exact P-values to show whether the differences are statistically significant.

    • In the"Study Population" section (line 123), the manuscript states that "all countries with available country-level data" were included. Whereas, in line 130-133 it indicates that certain countries were excluded based on missing data. Please, clarify. From which database was the "country level data on routine vaccination, mortality" gotten from? Add a reference. Also, the inclusion criteria isn't detailed enough - only about one was included.

    List of minor concerns and feedback

    • The included countries ought to be listed so that the accuracy of their classification into low-, middle-, and high-income groups can be validated. In addition the number of countries within each income category is not stated. A supplementary table may be provided listing all included countries along with their income category based on the World Bank criteria. This would improve transparency and allow readers to assess the validity of the classification.

    Details for reproducibility and validation of the study

    • The study is partially reproducible because access to some raw data and sources were provided (https://doi.org/10.6084/m9.figshare.30958886). However, key information missing from Table 2 and the supporting information makes them lack sufficient details to allow independent reproduction and validation of the findings.

    Limitations and ethics discussed

    • Lines 348-357 of the manuscript appropriately discussed the study's limitations.

    • Ethics was adequately followed. The study utilized data from open sources and de-identified personal information to minimise ethical concerns.

    Additional comments

    • The manuscript is generally well structured; although revisions should be made in line with the comments above before publication.

    Concluding remarks

    We thank the authors of the preprint for posting their work openly for feedback. Many thanks also to all participants of the Live Review call for their time and for engaging in the lively discussion that generated this review.

    Toba Olatoye was a facilitator of this call and a PREreview champion.

    Competing interests

    The authors declare that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The authors declare that they did not use generative AI to come up with new ideas for their review.

  2. Version published to 10.64898/2025.12.31.25343235 on medRxiv