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  • Systematic Review
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Gestational age and the risk of allergic diseases: a systematic review and meta-analysis

Pediatric Research (2025)Cite this article

Abstract

Background

The perinatal period has been postulated to be a window of opportunities in preventing atopic disorders. Accumulating studies suggested that an association exists between gestational age (GA) and allergic diseases.

Methods

The meta-analysis of observational studies was conducted through a search of relevant literature until 31 December 2023 from PubMed, Embase, and Web of Science databases. Subgroup analyses and sensitivity analyses were performed to test the robustness and consistency of the observed associations.

Results

Thirty observational studies comprising 5,410,969 participants were included in the meta-analysis. The pooled estimates (odds ratio [OR]) of atopic dermatitis (AD) risk for early preterm, preterm and post-term birth were 0.75 (95% confidence interval [CI]: 0.68–0.82), 0.86 (95% CI: 0.81–0.93), 1.08 (95% CI: 1.03–1.14), respectively. Additionally, early preterm birth was suggestively associated with reduced risk of allergic rhinitis (AR) (OR: 0.84, 95% CI: 0.73–0.97).

Conclusion

Our study demonstrated that early preterm and preterm births were associated with a reduced risk of AD, while post-term birth was linked to an increased risk, with early preterm birth also suggestively associated with a reduced risk of AR.

Impact

  • This large-scale meta-analysis demonstrates that early preterm and preterm births are associated with a significantly reduced risk of atopic dermatitis (AD), while post-term birth is linked to an increased risk.

  • Early preterm birth is also suggestively associated with a lower risk of allergic rhinitis (AR), highlighting the nuanced role of gestational age in the development of allergic diseases.

  • These findings underscore the importance of the perinatal period as a critical window for allergy risk stratification and early prevention strategies in pediatric populations.

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Fig. 1: Flowchart of study inclusion and exclusion.
Fig. 2: Forest plots of gestational age and allergic diseases.

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Data availability

The datasets used and/or analyzed during the current study are publicly available and accessible.

References

  1. Shin, Y. H. et al. Global, regional, and national burden of allergic disorders and their risk factors in 204 countries and territories, from 1990 to 2019: A systematic analysis for the Global Burden of Disease Study 2019. Allergy 78, 2232–2254 (2023).

    Article  PubMed  CAS  Google Scholar 

  2. Barker, D. J. The origins of the developmental origins theory. J. Intern Med 261, 412–417 (2007).

    Article  PubMed  CAS  Google Scholar 

  3. Siltanen, M., Kajosaari, M., Pohjavuori, M. & Savilahti, E. Prematurity at birth reduces the long-term risk of atopy. J. Allergy Clin. Immunol. 107, 229–234 (2001).

    Article  PubMed  CAS  Google Scholar 

  4. Siltanen, M. et al. Preterm birth reduces the incidence of atopy in adulthood. J. Allergy Clin. Immunol. 127, 935–942 (2011).

    Article  PubMed  Google Scholar 

  5. Korhonen, P. et al. Asthma and atopic dermatitis after early-, late-, and post-term birth. Pediatr. Pulmonol. 53, 269–277 (2018).

    Article  PubMed  Google Scholar 

  6. Haataja, P. et al. Asthma and atopic dermatitis in children born moderately and late preterm. Eur. J. Pediatr. 175, 799–808 (2016).

    Article  PubMed  CAS  Google Scholar 

  7. Mitselou, N. et al. Preterm birth reduces the risk of IgE sensitization up to early adulthood: A population-based birth cohort study. Allergy 77, 1570–1582 (2022).

    Article  PubMed  CAS  Google Scholar 

  8. Liberati, A. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Stang, A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur. J. Epidemiol. 25, 603–605 (2010).

    Article  PubMed  Google Scholar 

  10. Higgins, J. P., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ 327, 557–560 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chen, B. & Benedetti, A. Quantifying heterogeneity in individual participant data meta-analysis with binary outcomes. Syst. Rev. 6, 243 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yuan, S. et al. Homocysteine, folate, and nonalcoholic fatty liver disease: a systematic review with meta-analysis and Mendelian randomization investigation. Am. J. Clin. Nutr. 116, 1595–1609 (2022).

    Article  PubMed  CAS  Google Scholar 

  13. Hamling, J., Lee, P., Weitkunat, R. & Ambuhl, M. Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat. Med 27, 954–970 (2008).

    Article  PubMed  Google Scholar 

  14. Begg, C. B. & Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088–1101 (1994).

    Article  PubMed  CAS  Google Scholar 

  15. Olesen, A. B., Ellingsen, A. R., Olesen, H., Juul, S. & Thestrup-Pedersen, K. Atopic dermatitis and birth factors: historical follow up by record linkage. BMJ 314, 1003–1008 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Steffensen, F. H. et al. Low birth weight and preterm delivery as risk factors for asthma and atopic dermatitis in young adult males. Epidemiology 11, 185–188 (2000).

    Article  PubMed  CAS  Google Scholar 

  17. Katz, K. A., Pocock, S. J. & Strachan, D. P. Neonatal head circumference, neonatal weight, and risk of hayfever, asthma and eczema in a large cohort of adolescents from Sheffield, England. Clin. Exp. Allergy 33, 737–745 (2003).

    Article  PubMed  CAS  Google Scholar 

  18. Kerkhof, M. et al. Risk factors for atopic dermatitis in infants at high risk of allergy: the PIAMA study. Clin. Exp. Allergy 33, 1336–1341 (2003).

    Article  PubMed  CAS  Google Scholar 

  19. Mai, X. M. et al. Asthma, lung function and allergy in 12-year-old children with very low birth weight: a prospective study. Pediatr. Allergy Immunol. 14, 184–192 (2003).

    Article  PubMed  Google Scholar 

  20. Bernsen, R. M., de Jongste, J. C., Koes, B. W., Aardoom, H. A. & van der Wouden, J. C. Perinatal characteristics and obstetric complications as risk factors for asthma, allergy and eczema at the age of 6 years. Clin. Exp. Allergy 35, 1135–1140 (2005).

    Article  PubMed  CAS  Google Scholar 

  21. Linneberg, A., Simonsen, J. B., Petersen, J., Stensballe, L. G. & Benn, C. S. Differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology. J. Allergy Clin. Immunol. 117, 184–189 (2006).

    Article  PubMed  Google Scholar 

  22. Mallen, C. D., Mottram, S., Wynne-Jones, G. & Thomas, E. Birth-related exposures and asthma and allergy in adulthood: a population-based cross-sectional study of young adults in North Staffordshire. J. Asthma 45, 309–312 (2008).

    Article  PubMed  Google Scholar 

  23. Govaere, E. et al. The prevalence, characteristics of and risk factors for eczema in Belgian schoolchildren. Pediatr. Dermatol 26, 129–138 (2009).

    Article  PubMed  Google Scholar 

  24. Kumar, R. et al. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood. J. Allergy Clin. Immunol. 124, 1031–8.e1-4 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Kvenshagen, B., Jacobsen, M. & Halvorsen, R. Atopic dermatitis in premature and term children. Arch. Dis. Child 94, 202–205 (2009).

    Article  PubMed  CAS  Google Scholar 

  26. Lundholm, C., Ortqvist, A. K., Lichtenstein, P., Cnattingius, S. & Almqvist, C. Impaired fetal growth decreases the risk of childhood atopic eczema: a Swedish twin study. Clin. Exp. Allergy 40, 1044–1053 (2010).

    Article  PubMed  CAS  Google Scholar 

  27. Sonnenschein-van der Voort, A. M. et al. Fetal and infant growth and asthma symptoms in preschool children: the Generation R Study. Am. J. Respir. Crit. Care Med 185, 731–737 (2012).

    Article  PubMed  Google Scholar 

  28. Barbarot, S. et al. Lower risk of atopic dermatitis among infants born extremely preterm compared with higher gestational age. Br. J. Dermatol 169, 1257–1264 (2013).

    Article  PubMed  CAS  Google Scholar 

  29. Miyake, Y. & Tanaka, K. Lack of relationship between birth conditions and allergic disorders in Japanese children aged 3 years. J. Asthma 50, 555–559 (2013).

    Article  PubMed  Google Scholar 

  30. Tronnes, H., Wilcox, A. J., Lie, R. T., Markestad, T. & Moster, D. The association of preterm birth with severe asthma and atopic dermatitis: a national cohort study. Pediatr. Allergy Immunol. 24, 782–787 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Vrijlandt, E. J., Kerstjens, J. M., Duiverman, E. J., Bos, A. F. & Reijneveld, S. A. Moderately preterm children have more respiratory problems during their first 5 years of life than children born full term. Am. J. Respir. Crit. Care Med 187, 1234–1240 (2013).

    Article  PubMed  Google Scholar 

  32. Egeberg, A., Andersen, Y. M., Gislason, G., Skov, L. & Thyssen, J. P. Neonatal risk factors of atopic dermatitis in Denmark - Results from a nationwide register-based study. Pediatr. Allergy Immunol. 27, 368–374 (2016).

    Article  PubMed  Google Scholar 

  33. Yrjana, J. M. S., Koski, T., Torola, H., Valkama, M. & Kulmala, P. Very early introduction of semisolid foods in preterm infants does not increase food allergies or atopic dermatitis. Ann. Allergy Asthma Immunol. 121, 353–359 (2018).

    Article  PubMed  Google Scholar 

  34. Morata-Alba, J., Romero-Rubio, M. T., Castillo-Corullon, S. & Escribano-Montaner, A. Respiratory morbidity, atopy and asthma at school age in preterm infants aged 32-35 weeks. Eur. J. Pediatr. 178, 973–982 (2019).

    Article  PubMed  Google Scholar 

  35. Monir, R. L., Schoch, J. J., Garvan, C. W., Neu, J. & Lemas, D. J. Association between atopic dermatitis and race from infancy to early childhood: a retrospective cohort study. Int J. Dermatol 61, 727–732 (2022).

    Article  PubMed  Google Scholar 

  36. Gerner, T. et al. Differences in Occurrence, Risk Factors and Severity of Early-onset Atopic Dermatitis among Preterm and Term Children. Acta Derm. Venereol. 102, adv00737 (2022).

    Article  PubMed  CAS  Google Scholar 

  37. Braback, L. & Hedberg, A. Perinatal risk factors for atopic disease in conscripts. Clin. Exp. Allergy 28, 936–942 (1998).

    Article  PubMed  CAS  Google Scholar 

  38. Bager, P., Melbye, M., Rostgaard, K., Benn, C. S. & Westergaard, T. Mode of delivery and risk of allergic rhinitis and asthma. J. Allergy Clin. Immunol. 111, 51–56 (2003).

    Article  PubMed  Google Scholar 

  39. Crump, C., Sundquist, K., Sundquist, J. & Winkleby, M. A. Gestational age at birth and risk of allergic rhinitis in young adulthood. J. Allergy Clin. Immunol. 127, 1173–1179 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mitselou, N. et al. Adverse pregnancy outcomes and risk of later allergic rhinitis-Nationwide Swedish cohort study. Pediatr. Allergy Immunol. 31, 471–479 (2020).

    Article  PubMed  Google Scholar 

  41. Li, Y. et al. Pre- and Postnatal Risk Factors in Relation to Allergic Rhinitis in School-Aged Children in China. Plos One 10, e0114022 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Loid, P. et al. A persistently high body mass index increases the risk of atopic asthma at school age. Acta Paediatr. 104, 707–712 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Zhu, T., Zhao, J., Qu, Y., Zhang, L. & Mu, D. Association of very preterm birth with decreased risk of eczema: A systematic review and meta-analysis. J. Am. Acad. Dermatol 78, 1142–1148 (2018).

    Article  PubMed  Google Scholar 

  44. Herberth, G. et al. Maternal immune status in pregnancy is related to offspring’s immune responses and atopy risk. Allergy 66, 1065–1074 (2011).

    Article  PubMed  CAS  Google Scholar 

  45. Strachan, D. P. Hay fever, hygiene, and household size. BMJ 299, 1259–1260 (1989).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Halling, A. S. et al. Skin TARC/CCL17 increase precedes the development of childhood atopic dermatitis. J. Allergy Clin. Immunol. 151, 1550–1557 (2023).

    Article  PubMed  CAS  Google Scholar 

  47. Garn, H. & Renz, H. Epidemiological and immunological evidence for the hygiene hypothesis. Immunobiology 212, 441–452 (2007).

    Article  PubMed  CAS  Google Scholar 

  48. Mitselou, N. et al. Cesarean delivery, preterm birth, and risk of food allergy: Nationwide Swedish cohort study of more than 1 million children. J. Allergy Clin. Immunol. 142, 1510–1514 (2018).

    Article  PubMed  Google Scholar 

  49. Pekkanen, J., Xu, B. & Jarvelin, M. R. Gestational age and occurrence of atopy at age 31-a prospective birth cohort study in Finland. Clin. Exp. Allergy 31, 95–102 (2001).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors sincerely thank the researchers and participants of the original articles for their collection and management of data resources.

Funding

This work was supported by grants from the National Natural Science Foundation of China (82204843), the Medical and Health Science and Technology Program of Zhejiang Province (2023KY845), the Traditional Chinese Medicine Science and Technology Program of Zhejiang Province (2023ZR084), Youth Talent Support Program of Zhejiang Provincial Science and Technology Association (2024-HT-334), and Natural Science Youth Exploration Program of Zhejiang Chinese Medicine University (2023JKZKTS12).

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Author notes

  1. These authors contributed equally: Xuanli Zhao, Ke Liu.

Authors and Affiliations

  1. School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China

    Xuanli Zhao, Ke Liu, Jiaxin Chen, Xinzhe Jing, Jiayu Li, Xiaohui Sun, Yingying Mao & Ding Ye

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  1. Xuanli Zhao
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Contributions

XZ, KL, DY, JC, and XJ were responsible for the statistical analysis. YM, JL, and XS contributed to the conceptualization and methodology. XZ, KL, DY, and YM were responsible for writing, reviewing, and editing the subsequent and final drafts of the manuscript. All authors had full access to the study data and held final responsibility for the decision to submit the manuscript for publication.

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Correspondence to Yingying Mao or Ding Ye.

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This study is based on secondary analyses of previously published individual participant data (IPD). All original studies included had been independently registered and received ethics approval in accordance with the regulations of their respective countries and institutions.

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Zhao, X., Liu, K., Chen, J. et al. Gestational age and the risk of allergic diseases: a systematic review and meta-analysis. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04439-6

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