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Born from pre-eclamptic pregnancies predisposes infants to altered cortisol metabolism in the first postnatal year

Fiona Broughton Pipkin¹, Hiten D Mistry¹, Chandrima Roy¹

¹Department of Obstetrics and GynaecologySchool of Medicine, University of Nottingham, Nottingham, NG5 1PB, UKDepartment of NephrologyHypertension and Clinical Pharmacology, Clinical Research, University of Bern, 3010 Berne, SwitzerlandLeicester Royal InfirmaryLeicester, LE1 5WW, UK.

Endocrine Connections

|September 18, 2015

Insights

Infants born to mothers with pre-eclampsia show altered cortisol metabolism, with higher enzyme activity at 3 months and increased cortisol excretion at 12 months, suggesting developmental impacts.

Area of Science:

Endocrinology
Developmental Biology
Perinatal Medicine

Background:

Pre-eclampsia disrupts fetal development, potentially affecting the pituitary-adrenal axis and leading to metabolic syndrome.
Altered glucocorticoid exposure in utero may have long-term consequences for infant health.

Purpose of the Study:

To investigate differences in cortisol metabolism in infants born to pre-eclamptic versus normotensive mothers.
To assess the impact of maternal pre-eclampsia on infant cortisol metabolite profiles and enzyme activities at 3 and 12 months of age.

Main Methods:

Collected 24-hour urine samples from infants at 3 and 12 months postpartum.
Analyzed cortisol metabolites and apparent enzyme activities using gas chromatography-mass spectrometry.
Compared metabolite excretion and enzyme activities between infants from pre-eclamptic and normotensive pregnancies.

Main Results:

Cortisol metabolite excretion (THS, THF, pregnandiol) increased from 3 to 12 months in both groups; THF also increased in the pre-eclamptic group.
Infants exposed to pre-eclampsia exhibited higher 17α-hydroxylase and 11β-HSD activities at 3 months and increased 11β-hydroxylase activity at 12 months.
Enzyme activity patterns differed between groups, with infants of pre-eclamptic mothers showing distinct adjustments in cortisol metabolism.

Conclusions:

Infants born from pre-eclamptic pregnancies display altered cortisol metabolism, with specific enzyme activities showing significant differences compared to controls.
Increased 11β-hydroxylase activity in infants of pre-eclamptic mothers may compensate for altered cortisol degradation and substrate availability.
These findings highlight potential long-term endocrine programming effects of pre-eclampsia on fetal development.

Read full analysis

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.

Keywords:

infants pre-eclampsia steroid hormones urine

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