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.

Low birth weight predicts higher blood pressure but not dermal capillary density in two populations.

The association between low birth weight and high blood pressure is well established, but underlying mechanisms remain undefined. Vascular rarefaction, which may elevate peripheral vascular resistance, has been observed in capillaries of young men at risk for hypertension and men who had low birth weight. We looked for evidence that capillary rarefaction explains the association of low birth weight with high blood pressure in two cohorts. Participants in study 1 included 107 healthy boys aged 6 to 16 years recruited at random from a single school. Study 2 included 61 members of a cohort recruited at birth and studied at age 24 years. Measurements included indices of current size, blood pressure by automated sphygmomanometer, and dermal capillary density by video capillaroscopy of dorsal index finger skin after 10 minutes of venous occlusion. Lower birth weight predicted higher systolic blood pressure in both studies: in study 1, 3.57 mm Hg/kg birth weight (after adjustment for current height, 95% confidence interval 0.38 to 6.75, P<0.05); in study 2, 122+/-12 mm Hg in low birth weight (<2 kg) versus 115+/-9 in controls (P<0.05). Dermal capillary density was not associated in either group with birth weight or systolic blood pressure. We have found no evidence in these 2 cohorts that reduced capillary density explains the associations between lower birth weight and higher blood pressure.