ReviewFrontiers in pediatrics2026
Differences in cortisol levels between preterm and term infants: a systematic review and meta-analysis combined with Mendelian randomization study.
Review in Frontiers in pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Background: Preterm infants have an immaturity hypothalamic-pituitary-adrenal (HPA) axis, whether cortisol levels differ from those in term infants remains inconsistent. This study employed a meta-analysis to compare cortisol levels between preterm and term infants (PROSPERO: CRD42024606328, https://www.crd.york.ac.uk/PROSPERO/). We then applied Mendelian randomization (MR) to assess a potential causal relationship, with preterm birth as the exposure and cortisone (a key cortisol precursor) as the outcome. Methods: We systematically searched 10 databases from inception to August 2024 for studies reporting cortisol in preterm and term infants. Subgroup analyses and meta-regression were conducted by the type of specimens, measurement methods, measurement ages, gestational ages, measurement times, and the usage of steroid hormones. Random effects models were used for analysis, and data were reported using 95% confidence intervals. Publication bias was assessed using Eggers test, and a leave-one-out sensitivity analysis was performed. MR analysis was conducted to explore the causal relationship between preterm birth and cortisone. Results: A total of 74 studies were included, consisting of 18 umbilical cord blood (UCB) studies, 28 peripheral blood studies, and 31 saliva studies. Preterm infants had lower cortisol levels in UCB (SMD: -0.45; 95% CI: -0.77 to -0.12, Conclusion: Cortisol levels in preterm infants exhibit a trend of being initially lower, then higher, but finally comparable to those of term infants in the long term. MR supports a causal link between preterm birth and cortisone. These findings may guide the clinical management of preterm infants and individualized glucocorticoid strategies. Future high-quality clinical studies are required to further validate and optimize glucocorticoid protocols. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/. PROSPERO: CRD42024606328.
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