Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

Abstract

The third trimester of pregnancy represents a sensitive phase for infant brain plasticity when a series of fast-developing cellular events (synaptogenesis, neuronal migration, and myelination) regulates the development of neural circuits. Throughout this dynamic period of growth and development, the human brain is susceptible to stress. Preterm infants are born with an immature brain and are, while admitted to the neonatal intensive care unit, precociously exposed to stressful procedures. Postnatal stress may contribute to altered programming of the brain, including key systems such as the hypothalamic–pituitary–adrenal axis and the autonomic nervous system. These neurobiological systems are promising markers for the etiology of several affective and social psychopathologies. As preterm birth interferes with early development of stress-regulatory systems, early interventions might strengthen resilience factors and might help reduce the detrimental effects of chronic stress exposure. Here we will review the impact of stress following premature birth on the programming of neurobiological systems and discuss possible stress-related neural circuits and pathways involved in resilience and vulnerability. Finally, we discuss opportunities for early intervention and future studies.

Effects of a tripartite intervention on biological stress in preterm infants during heel pricks for newborn screening: A randomized controlled trial

“…Studies that examined NNS + tucking found preterm infants experienced relief only for mild‐ or short‐term pain (Cignacco et al, 2012; Liaw, Yang, Wang, et al, 2012). However, heel‐stick procedures are both intrusive and painful to preterm infants (Lammertink et al, 2021) requiring the infant's heel to be held and squeezed for 2–3 min to collect 5–6 microtubes of blood. The design of modulating the infant's behavioral state and providing NNS and tucking was based on the findings of Yin et al (2015) who demonstrated that BSM was effective at reducing the trauma of a painful procedure.…”

“…Procedural pain from diagnostics in the NICU, such as heel pricks, ventilation, and venous blood sampling, and non‐painful experiences, which include cluster caregiving, position change, administration of medicine, weighing, and tube removal, also cause disequilibrium in preterm infants (Liaw, Yang, Hua, et al, 2012; Newnham et al, 2009). For preterm infants in the NICU, there are three main sources of stress: physical stress, which includes repetitive procedural pain from a heel prick; environmental stress, such as noise, light, and caregiving events; and maternal stress, such as long periods of separation from the mother (Lammertink et al, 2021). Therefore, for the purposes of this study, we have defined stress related to painful procedures as procedural pain‐related stress.…”

Potential Psychological and Biological Mechanisms Underlying the Effectiveness of Neonatal Music Therapy during Kangaroo Mother Care for Preterm Infants and Their Parents

“…Following preterm delivery, the environmental situation changes significantly from the intrauterine environment to the extrauterine environment. The hospitalization and pain-related events due to medical procedures (acute procedural, and acute prolonged) expose the child to several sources of stress, such as environmental stress, as well as atypical maternal care [23]. Environmental stress is linked to noncyclical and bright light exposure, loud noises (many times exceeding the recommended sound level of 45 dB), gravitational forces, frequent handling, or cool and dry temperature.…”

“…Among the risk factors for adrenal insufficiency are gestational age below 30 weeks, early postnatal age, perinatal stress (linked with the stressful situations and postnatal illness), and duration of corticosteroid use [24]. Lammertink and colleagues [23] suggest that the impact of prematurity provides long-lasting changes in HPA-functioning, while the timing of the stressor plays a fundamental role to the type and magnitude of the stress-responses in preterm babies, as well as that it might contribute to a differential impact and reaction (as hypo-or hyper-reactivity).…”

Consequences of Prematurity on Cortisol Regulation and Adjustment Difficulties: A 9-Year Longitudinal Study

“…Moreover, during the neonatal period, neuronal pathways are immature and are therefore particularly vulnerable [ 37 ]. Exposition to stress and multisensory dystimulation during this period can induce long term impacts on developmental outcomes, including brain development, stress regulation system and adjustment problems [ 29 , 38 , 39 ].…”