Abstract

Pre-eclampsia leads to disturbed fetal organ development, including metabolic syndrome, attributed to altered pituitary-adrenal feedback loop. We measured cortisol metabolites in infants born from pre-eclamptic and normotensive women and hypothesised that glucocorticoid exposure would be exaggerated in the former. Twenty-four hour urine was collected from infants at months 3 and 12. Cortisol metabolites and apparent enzyme activities were analysed by gas chromatography-mass spectrometry. From 3 to 12 months, excretion of THS, THF and pregnandiol had risen in both groups; THF also rose in the pre-eclamptic group. No difference was observed with respect to timing of the visit or to hypertensive status for THE or total F metabolites (P>0.05). All apparent enzymes activities, except 17α-hydroxylase, were lower in infants at 12 compared to 3 months in the normotensive group. In the pre-eclamptic group, only 11β-HSD activities were lower at 12 months.17α-hydroxylase and 11β-HSD activities of tetrahydro metabolites were higher in the pre-eclamptic group at 3 months (P<0.05). 11β-hydroxylase activity increased in the pre-eclamptic group at 12 months. Cortisol excretion, determined by increased 11β-hydroxylase, compensates for high 11β-HSD-dependent cortisol degradation at 3 months and at 12 months counterbalances the reduced cortisol substrate availability in infants born from pre-eclamptic mothers.

Highlights

  • The fetal adrenal gland and hypothalamic–pituitary axis (HPA) play important roles during pregnancy

  • Between weeks 32 and 34 of gestation, there is a rapid maturation of the fetal adrenal cortex, allowing development of a variety of mechanisms associated with a successful transition to extrauterine life (1, 2, 3, 4)

  • 4 : 234 growth restriction (IUGR) and premature delivery are due to pre-eclampsia (5), a pregnancy-specific syndrome occurring in w3% of all pregnancies and one of the leading causes of maternal/perinatal mortality and morbidity worldwide (6, 7)

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Summary

Introduction

The fetal adrenal gland and hypothalamic–pituitary axis (HPA) play important roles during pregnancy. Between weeks 32 and 34 of gestation, there is a rapid maturation of the fetal adrenal cortex, allowing development of a variety of mechanisms associated with a successful transition to extrauterine life (1, 2, 3, 4). 4 : 234 growth restriction (IUGR) and premature delivery are due to pre-eclampsia (5), a pregnancy-specific syndrome occurring in w3% of all pregnancies and one of the leading causes of maternal/perinatal mortality and morbidity worldwide (6, 7). Various organ functions in these infants are subject to intrauterine developmental reprogramming (8, 9), with evidence of decreased pituitary adrenal feedback control of glucocorticoid maintenance and an association with metabolic syndrome (10, 11)

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