Cumulative stress in very preterm neonates due to early-life medical interventions in the Neonatal Intensive Care Unit and the moderation of a stress reducing intervention : impact on short- and longer-term neurobehavioral development.

Stravers, C.A. (2016) Cumulative stress in very preterm neonates due to early-life medical interventions in the Neonatal Intensive Care Unit and the moderation of a stress reducing intervention : impact on short- and longer-term neurobehavioral development. thesis, Medicine.

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Abstract

Background During a period of rapid brain development, preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU). Neonatal stress in NICU can be measured by using a tool to assess cumulative stress exposures; the Neonatal Infant Stressor Scale (NISS). Aims To evaluate the relationship in very preterm infants (<30 weeks) between cumulative stress due to medical interventions (measured by the NISS) and neurobehavioral development at term-equivalent age and at 4.5 years of age. Methods This study used existing data from the cohort of infants from the PremieStart randomised controlled trial (RCT) in combination with NISS scores retrospectively collected from medical records. Short-term development of cerebral diameter was assessed by metrics obtained via Magnetic Resonance Imaging (MRI) at 42 weeks full term-equivalent age. Standardised neurodevelopmental examinations at 4.5 years old were used to assess neurobehavioral functioning. Data analyses also assessed whether the ‘PremieStart’ intervention, a Mother-Infant like Transaction Program, acted as a moderator in the relationship between neurobehavioral development and stress exposure represented by the NISS. Results Analyses of MRI brain metrics at term-equivalent age (n=76) revealed that, as hypothesised, exposure to greater cumulative stress in NICU had a negative linear relationship with frontal brain width (bifrontal diameter) representing a decrease of 0.4mm for every additional 100 points on the NISS (B-0.04, p=0.039). PremieStart intervention: However, the PremieStart intervention group (n = 42), showed no significant negative linear relationship (B-0.014, p = 0.549). While premature infants who received no intervention showed a decrease of 1 mm in brain width for each additional 100 NISS points (B -0.105, p=0.006). As predicted, analyses of outcomes at 4.5 years old on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), NEuroPSYchological Assessment (NEPSY) and Child Behavior Checklist (CBCL) found that exposure to greater cumulative stress displayed correlations in the hypothesised directions with almost all of these measures. However, the ΔR2 values attributable to the NISS in all step-wise linear regression models of longer-term outcomes were relatively small, and only a few (performance IQ, processing speed IQ, verbal IQ) approached statistical significance. PremieStart intervention: There was no reliable evidence to suggest that the PremieStart intervention played a significant moderating role in these neurodevelopmental outcomes. Discussion In very preterm infants without major cognitive, motor or sensory impairments, neonatal cumulative stress in NICU appears to result in a significant decrease the frontal brain width. The PremieStart intervention appears to be a moderating protective factor and is able to minimize the decrease in frontal brain width. Our analyses observed many correlations in the hypothesized directions between cumulative stress in NICU, as measured by the NISS, and 4.5 year outcomes on IQ (WPPSI), NEPSY and CBCL. This study failed to detect these effects as statistically significant, partly due to a loss of power due to missing data. Conclusion Our data suggest vulnerability of the immature preterm brain due to stressful exposures in NICU and agree with previous research. In particular, this vulnerability plays a role during physical brain development in the immediate neonatal period. This impact appears to be reduced at the age of 4.5 in terms of neurobehavioral development, perhaps by other environmental influences, which play a role in neurobehavioral development. PremieStart intervention: PremieStart is a protective moderating factor on short-term (term equivalent age) outcome. Preterm infants in the intervention group who had more stress due to medical interventions (NISS) had less brain width loss than the control group. There was no robust evidence that PremieStart functioned as a protective factor for these longer-term neurobehavioral developmental outcomes in very preterm infants. As is well established in the research literature, decreasing GA at birth and severity of medical illness were the strongest determinants of neurobehavioral developmental outcomes.

Item Type:	Thesis (Thesis)
Supervisor name:	Faculty supervisor and Burger, dr. Huib physician epidemiologist and Groningen
Supervisor name:	Milgrom, Prof. Jeannette and Gemmill, dr. Alan W. and Parent-Infant Research Institute (PIRI) and Austin Health Melbourne and Australia
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:03
Last Modified:	25 Jun 2020 11:03
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2339

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