Diminished 11β-Hydroxysteroid Dehydrogenase Type 2 Activity Is Associated With Decreased Weight and Weight Gain Across the First Year of Life

Abstract

Context: Low birth weight is associated with adverse metabolic outcome in adulthood. Exposure to glucocorticoid (GC) excess in utero is associated with decreased birth weight, but the prospective longitudinal relationship between GC metabolism and growth has not been examined. Objective: We have hypothesized that changes in GC metabolism leading to increased availability may impair growth. Design: This was a prospective, longitudinal study with clinical measurements and 24-hour urinary steroid metabolite analysis at 1, 4, 12, 26, and 52 weeks after delivery in mothers and their babies. Setting: The study was conducted with observations and samples collected in the volunteers' own homes. Participants: Healthy mothers and newborn babies/infants participated in the study. Interventions: There were no interventions. Main outcome measures: Urinary steroid metabolite excretion quantified by gas chromatography/mass spectroscopy across the first year of life in relation to change in weight was measured. Results: The total production of the GC metabolites quantified increased across the first year of life. Markers of 11β-hydroxysteroid dehydrogenase type 1 activity increased from the age of 3 months as did those of 5α-reductase activity. After correcting for confounding variables, low markers of 11β-hydroxysteroid dehydrogenase type 2 activity was associated with reduced absolute weight and decreased weight gain over the first year of life. In the mothers, 5α-reductase activity was low at birth and progressively increased to normal over the first 6 months postpartum. Conclusions: Increased GC exposure as a consequence of reduced 11β-hydroxysteroid dehydrogenase type 2 activity is likely to be a critical determinant of growth in early life. This not only highlights the central role of GCs and their metabolism, but also emphasizes the need for detailed longitudinal analyses.