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Could cortisol explain the association between birth weight and cardiovascular disease in later life? A meta-analysis

¹ Departments of Clinical Epidemiology, ² Pediatrics and ³ Medical Statistics and Bioinformatics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

(Correspondence should be addressed to F W Dekker; Email: f.w.dekker{at}lumc.nl)

Objective: Studies about the association between birth weight and circulating cortisol level have been published from 1998 onwards. However, their findings were inconsistent. To quantitatively assess the overall association between birth weight and circulating cortisol level, we aimed to perform a meta-analysis of the published literature.

Methods: A literature search was conducted in PubMed, and selected papers were systematically reviewed. A pooled regression coefficient was calculated for the entire group as well as for males and females separately.

Results: Data from 11 study populations were pooled (n = 2301). These populations differed with respect to geographical area, age, sex distribution, inclusion criteria and gestational age. We found a statistically significant inverse association between birth weight and circulating cortisol level: a 1 kg lower birth weight was associated with a 25.3 nmol/l (95% confidence interval (CI): 5.9–44.8) higher cortisol level. Separate results were reported for males and females in six study populations. The association in males was 20.6 nmol/l per kg (95% CI: 4.2–37.0) and in females it was 30.9 nmol/l per kg (95% CI: 7.4–54.4).

Conclusion: Differences between study populations hampered the comparability of the included studies. Although the majority of studies were underpowered, by using a meta-analytic approach we found an inverse association between birth weight and circulating cortisol level. Thus, our findings suggest that there is some evidence for a possible role of the hypothalamus–pituitary–adrenal axis in the epidemiological association between birth weight and cardiovascular disease. However, the strength of the overall association between birth weight and circulating cortisol level was weak.