Pain exposure associates with telomere length erosion in very preterm infants

Abstract

Very preterm (VPT) infants (gestational age < 32 weeks) require long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU), even in absence of severe morbidities. During NICU stay, life-saving interventions occur and include invasive and painful skin-breaking procedures (NICU-related stress), which constitute a major early adverse experience for VPT infants. Telomeres are repeat-sequence at the end of chromosomes, which shorten with age and are highly susceptible to life adversities: the exposure to early adverse experiences is associated with shorter telomere length (TL). Nonetheless, previous research did not assess longitudinally the association between NICU-related stress and TL in VPT infants. In the present study, leukocyte TL was assessed from cord blood at birth in 46 VPT infants and in a group of 31 full-term (FT) infants, as well as at NICU discharge in VPTs only. NICU-related stress was measured as the number of skin-breaking procedures occurring throughout the NICU stay. A significant difference emerged for TL between VPT infants and FT counterparts at birth. TL decreased from birth to discharge in VPT infants, although the change was not significant in the group as a whole. The amount of NICU-related stress emerged as the primary predictor of TL erosion in VPT infants, even controlling for neonatal and clinical confounders. Furthermore, VPT infants exposed to high NICU-related stress exhibited a marked and significant decrease in TL, whereas VPT exposed to low NICU-related stress exhibited a non-significant increase. The present study confirms previous evidence of longer telomeres in VPT infants at birth compared to FT controls. Moreover, NICU-related stress emerged as a key regulator of TL erosion from birth to discharge in VPT infants. Future research is warranted to further explore TL erosion in VPT infants and the factors associated with individual differences in NICU-related stress susceptibility at the epigenetic level.

Keywords: Epigenetics; NICU; Preterm infants; Stress; Telomere.