title: Pain-related stress in the Neonatal Intensive Care Unit and salivary cortisol reactivity to socio-emotional stress in 3-month-old very preterm infants.
abstract: Very preterm (VPT) infants are hospitalized in the Neonatal Intensive Care Unit (NICU) and exposed to varying levels of skin-breaking procedures (pain-related stress), even in absence of severe clinical conditions. Repeated and prolonged pain exposure may alter hypothalamic-pituitary-adrenal (HPA) axis reactivity in VPT infants. During the post-discharge period, altered HPA axis reactivity has been documented in response to non-social stressors, using salivary cortisol as a biomarker. However, little is known about the effects of NICU pain-related stress on subsequent HPA axis reactivity to socio-emotional stress in infants. We examined the relationship between pain-related stress in NICU and HPA axis reactivity (i.e., salivary cortisol reactivity) to an age-appropriate socio-emotional condition in 37 healthy VPT infants compared to 53 full-term (FT) controls. The number of skin-breaking procedures was obtained across NICU stay for VPT infants. At 3 months (corrected age for prematurity), all infants participated in the maternal Face-to-Face Still-Face (FFSF) procedure, in order to assess HPA axis reactivity to socio-emotional stress (i.e., maternal unresponsiveness). VPT infants exhibited a blunted salivary cortisol reactivity, which was associated with the amount of skin-breaking procedures during NICU: greater pain-related stress predicted lower salivary cortisol reactivity, adjusting for neonatal confounders. These findings further advance our knowledge of how early exposure to pain-related stress in NICU contributes to the programming of an altered HPA axis reactivity to socio-emotional stress in 3-month-old VPT infants, even in the absence of major perinatal complications.
authors.affiliation: 0-3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy. Electronic address: livio.provenzi@bp.lnf.it.
authors.forename: Livio
authors.initials: L
authors.lastname: Provenzi
authors.affiliation: 0-3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Giusti
authors.affiliation: NICU, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: 0-3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Hilarj
authors.initials: H
authors.lastname: Tasca
authors.affiliation: Biology Laboratory, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Bioinformatic Lab, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Menozzi
authors.affiliation: NICU, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.affiliation: Pediatric Unit, Fatebenefratelli Sacra Famiglia Hospital, Erba, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Morandi
authors.affiliation: Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
authors.affiliation: 0-3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Montirosso
mesh_terms: D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D007223:Infant; D062071:Infant, Extremely Premature; D007363:Intensive Care Units, Neonatal; D008297:Male; D010146:Pain / Q000150:complications*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D006854:Hydrocortisone
keywords: Cortisol; Hypothalamic-pituitary-adrenal axis; Still-Face; Stress; Very preterm infants