Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm

Abstract

Background: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children.

Methods: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30' later, evening).

Results: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p < 0.01; girls p = 0.04). Cortisol was similar between preterm-born and term-born at study visit; however, preterm-born children showed a blunted morning cortisol. In term-born children, DHEA correlated with BMI (p = 0.04), subscapular, and abdominal skinfold thicknesses (both p < 0.01).

Conclusion: Cortisol and DHEA correlated inversely with early postnatal growth and directly with systolic BP in extremely preterm-born children, suggesting perinatal programming. Blunted morning cortisol may reflect NICU stress, as seen after other adverse childhood experiences (ACEs).

Figure 1:

The relationship of cortisol and DHEA to Z-scores for weight at 36 weeks postmenstrual age in children born extremely preterm (Panels A and B, significant for both cortisol (0.85 (0.75,0.96), p=0.01) and DHEA (0.78 (0.63,0.95), p=0.02) and to systolic blood pressure in children born extremely preterm (—) and in those born at term (––––) (panels C and D), significant for preterm-born (cortisol 1.09 (1.00, 1.18), p=0.04; DHEA 1.24 (1.01, 1.51), p=0.04), but not term-born children (cortisol 1.11 (0.86, 1.43), p=0.39; DHEA 1.12 (0.81, 1.55) p=0.48), possibly due to a smaller sample size.

Figure 2:

Cortisol concentrations during clinic visit (A) and at home (B) for extremely preterm born (—) and term-born children (––––). Preterm-born children had blunted morning cortisol values (1.09 (1.00, 1.18), p=0.02), with geometric mean values 22% lower on awakening and 10% lower at 30 minutes than term-born children.