Placental 11β-HSD2 Activity, Early Postnatal Clinical Course, and Adrenal Function in Extremely Low Birth Weight Infants

Abstract

ABSTRACT:The placental enzyme 11␤-hydroxysteroid dehydrogenase-2 (11␤-HSD2) transforms maternal cortisol to inactive cortisone. Fetal glucocorticoid excess due to reduced 11␤-HSD2 activity could make small preterm infants susceptible to early adrenal insufficiency when the maternal cortisol source is no longer sustained. We assessed whether placental 11␤-HSD2 activity is related to early adrenal insufficiency and postnatal clinical course in extremely low birth weight (Ͻ1000 g) infants. Mean gestational age of the 44 infants was 26.6 wk (range, 23.7-32.0), birth weight was 747 g (440 -981), and relative birth weight was Ϫ1.9 SD (Ϫ4.9 to 1.0). We determined placental 11␤-HSD2 activity, baseline, and ACTHstimulated cortisol and assessed illness severity by the Score of Neonatal Acute Physiology (SNAP). One standard deviation decrease in placental 11␤-HSD2 activity corresponded to a 1.85 (95% CI 0.55 to 3.14; p ϭ 0.006) unit increase in SNAP score and 2.9 mm Hg decrease in minimum mean arterial pressure (95% CI 0.3 to 5.6 mm Hg; p ϭ 0.03). Placental 11␤-HSD2 activity was not associated with cortisol concentrations, although the confidence interval of the ACTH-stimulated cortisol was close to zero: 1 SD increase corresponded to 17% (Ϫ18% to 49%) increase in ACTH-stimulated cortisol. Moreover, a 1 SD decrease in enzyme activity was associated with a hazard ratio for postnatal glucocorticoid treatment of 1.63 (95% CI 1.00 to 2.65); p ϭ 0.05. In ELBW infants, lower placental 11␤-HSD2 activity is associated with more severe early postnatal illness and hypotension. Although an association with baseline or ACTH-stimulated cortisol was not seen, possible relationships with other components of the hypothalamic-pituitary-adrenal axis remain to be determined. (Pediatr Res 59: 575-578, 2006)

Biological Roles of Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11B1), HSD11B2, and Glucocorticoid Receptor (NR3C1) in Sheep Conceptus Elongation1

“…Similarly, Hsd11b2 null mice give birth to lower weight pups compared to wildtype littermates [78]. A study of extremely small birth weight infants (born weighing under 1 kg) also found a correlation between placental HSD11B2 activity and birth weight [79]. Additional studies reported an association between elevated cortisol concentrations in maternal urine and decreased birth weight, consistent with decreased placental cortisol metabolism [80].…”

Sex-specific alterations in placental 11β-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone

“…For infants born Ͻ 72 h after maternal antenatal glucocorticoid exposure, 11␤HSD2 activity was a significant predictor of neonatal physiological stability as measured by the CRIBII physiological score and mean arterial pressure in females only. Low placental 11BHSD2 activity has previously been shown to be associated with a more severe immediate clinical course, as measured by the Score for Neonatal Acute Physiology (SNAP), and a higher incidence of hypotension in infants born prematurely (15). However, SNAP is calculated from data during the first 24 h after birth, unlike CRIBII, which is calculated at 1 h of age, allowing potential treatment bias to influence the relationship with placental 11␤HSD2 activity.…”

Endostatin Concentration in Cord Plasma Predicts the Development of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

“…We assessed the acute effects of antenatal betamethasone on endostatin concentrations by categorizing the subjects into 3 groups according to the time between the last administered betamethasone dose and birth: (1) 0 to 12 hours; (2) 12 to 72 hours; and (3) Ͼ72 hours or no betamethasone. 19 Chorionamnionitis was defined as clinical signs and either leukocytosis (whole blood leukocytes Ͼ 14 ϫ 10 9 /L) or C-reactive protein concentration in plasma of Ͼ50 mg/L. Patent ductus arteriosus was diagnosed with cardiac ultrasound postnatally.…”