Birth weight and postnatal growth in preterm born children are associated with cortisol in early infancy, but not at age 8 years

Background Preterm birth has been associated with altered hypothalamic-pituitary-adrenal (HPA-) axis activity as well as cardiometabolic diseases and neurodevelopmental impairments later in life. We assessed cortisol from term age to age 8 y in children born preterm, to explore the development of HPA-axis activity in association with intrauterine and early-postnatal growth until 6 mo. corrected age. Methods In 152 children born at a gestational age ≤32 wks. and/or with a birth weight ≤1,500 g, random serum cortisol was assessed at term age (n = 150), 3 mo. (n = 145) and 6 mo. corrected age (n = 144), and age 8 y (n = 59). Salivary cortisol was assessed at age 8 y (n = 75): prior to bedtime, at awakening, 15 min after awakening, and before lunch. Cortisol was analyzed in association with birth weight-standard deviation score (SDS), being born small for gestational age (SGA), and combinations of intrauterine and postnatal growth: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+ or AGA GR−) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA CUG+ or SGA CUG−) at 6 mo. corrected age. Cross-sectional associations at all time points were analyzed using linear regression, and longitudinal associations were analyzed using generalized estimating equations. Results Longitudinally, birth weight-SDS was associated with cortisol (β [95%CI]): lower cortisol over time was seen in infants with a birth weight ≤−2 SDS (−50.69 [−94.27; −7.11], p = 0.02), infants born SGA (−29.70 [−60.58; 1.19], p = 0.06), AGA GR+ infants (−55.10 [−106.02; −4.17], p = 0.03) and SGA CUG− infants (−61.91 [−104.73; −19.10], p = 0.01). In cross-sectional analyses at age 8 y, no associations were found between either serum or salivary cortisol and birth weight-SDS, SGA-status, or growth from birth to 6 mo. corrected age. Conclusion In children born preterm, poor intrauterine and postnatal growth were associated with lower cortisol in early infancy, but not at age 8 y. Even though HPA-axis activity no longer differed between groups at age 8 y, or differences could not be confirmed due to attrition, it is unknown whether the differences found in early infancy could attribute to increased health risks later in life.