Contrasting effects of intrauterine growth retardation and premature delivery on adult cortisol secretion and metabolism in man

OBJECTIVE Among babies born at term, intrauterine growth retardation (IUGR) predicts adult hypertension and hyperglycaemia. This might be due to elevated circulating glucocorticoids in adulthood, as described in animal models and in several cohorts of men who were low birthweight at term. Recently, we found that premature low birthweight babies also have adult cardiovascular risk factors, irrespective of IUGR. We have now investigated cortisol secretion in this group. DESIGN PATIENTS AND MEASUREMENTS We studied 29 women and 23 men aged 22-25 years who had been recruited at birth as either normal term (mean birthweight 3.1 kg, gestation 39 weeks), premature appropriate for gestational age (AGA; 1.7 kg, 32 weeks), or premature IUGR (1.7 kg, 35 weeks) babies. Body composition was measured by dual-energy X-ray absorptiometry (DEXA); plasma was obtained at 0900 h after overnight fast; and cortisol metabolites were measured in a 24-h urine sample by gas chromatography/mass spectrometry (GCMS). RESULTS Cortisol metabolites were different in men and women, so results were analysed separately. Among women, adult body composition did not differ between groups. Plasma cortisol was not different, but total urinary cortisol metabolite excretion was lower in AGA (3.29 +/- 1.91 mg/day, n = 7, P < 0.02) than in either normals (6.77 +/- 4.10, n = 14) or IUGR (9.47 +/- 8.84, n = 8). Relative excretion of cortisol and cortisone metabolites was not different. Statistically significant differences in cortisol parameters between groups were not seen in men. CONCLUSIONS Premature AGA baby girls have lower cortisol secretion in adulthood but normal plasma cortisol, suggesting impaired metabolic clearance of cortisol. By contrast, premature IUGR babies maintain normal cortisol secretion as adults, suggesting that IUGR, rather than premature delivery, is responsible for programmed activation of the hypothalamic-pituitary-adrenal (HPA) axis. The ability to detect such dramatic differences in a small study suggests that programming has a potent influence on adult cortisol secretion.