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Published on: August 25, 2014
Differences in cortisol levels between preterm and term infants: a systematic review and meta-analysis combined with
Yun Li1,2, Xiaohui Liang2, Limin Cao2
1Department of Neonatal Intensive Care Unit (NICU), Shanxi Children's Hospital(Maternal and Child Health Hospital of Shanxi Province, Maternity Hospital of Shanxi Province), Taiyuan, China.
Insights
Cortisol levels are initially lower in preterm infants compared to term infants, but increase over time. Mendelian randomization suggests a causal link between preterm birth and cortisone, impacting infant health.
Area of Science:
- Neonatal Physiology
- Endocrinology
- Perinatal Medicine
Background:
- Preterm infants exhibit hypothalamic-pituitary-adrenal (HPA) axis immaturity, but cortisol level differences compared to term infants are unclear.
- Existing research presents inconsistent findings regarding cortisol levels in preterm versus term infants.
Purpose of the Study:
- To compare cortisol levels between preterm and term infants using meta-analysis.
- To investigate the potential causal relationship between preterm birth and cortisone levels via Mendelian randomization.
Main Methods:
- Systematic literature search across 10 databases up to August 2024.
- Meta-analysis of 74 studies, including subgroup and meta-regression analyses.
- Mendelian randomization (MR) analysis with preterm birth as exposure and cortisone as outcome.
Main Results:
- Preterm infants showed lower cortisol in umbilical cord blood and early peripheral blood, but higher levels after two weeks.
- Salivary cortisol levels did not significantly differ between groups.
- MR analysis revealed a negative causal association between preterm birth and cortisone (β = -0.011, P = 0.035).
Conclusions:
- Cortisol levels in preterm infants follow a dynamic pattern: initially lower, then higher, and eventually comparable to term infants.
- Mendelian randomization supports a causal relationship between preterm birth and cortisone.
- Findings may inform clinical management and individualized glucocorticoid strategies for preterm infants.
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, P < 0.05) and the peripheral blood on the first day after birth (SMD: -0.46; -0.91 to -0.02, P < 0.05). Peripheral blood cortisol levels became higher in preterms after two weeks. Salivary cortisol did not differ. MR indicated a negative causal association between preterm birth and cortisone (β = -0.011, P = 0.035).
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.
