Cortisol–cortisone ratios in small for gestational age (SGA) children without postnatal catch‐up growth

Abstract

Low birthweight is a risk factor for metabolic and cardiovascular disorders in later adult life. Changes in the activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and the consequent disequilibrium between cortisol (F) and cortisone (E) are thought to be a key mechanism for these effects. We investigated whether prenatal programming leads to alterations in F/E ratios on a systemic level. In a cross-sectional, retrospective study we analysed sera of 132 children born small for gestational age (SGA) (aged 2-13 years) with persistent short stature [< -2 standard deviation score (SDS)] and of 25 children born appropriate for gestational age (AGA) (aged 4-11 years) with normal body height. Thirty-one per cent of the SGA and 44% of the AGA children were born preterm. Serum E and F concentrations were measured using tandem mass spectrometry. To exclude species-specific effects, we studied the 11beta-HSD system by measuring the ratio of corticosterone (B) to dehydrocorticosterone (11OH-B) in rats that were born SGA after protein restriction of the female dams during pregnancy. F, E and the F/E ratio in serum did not differ in these children when comparing SGA to children who were born AGA and had normal height. The concentrations were independent of weight and length SDS at birth as well as gestational age. In rats born SGA, the B/11OH-B ratio was not different to that in normal control animals at 6, 11 and 15 weeks of life. We found no alterations in systemic cortisol-cortisone conversion either in short children born SGA or in SGA rats. However, local modifications of the 11beta-HSD system may be possible.