Title
The impact of cumulative pain/stress on neurobehavioral development of preterm infants in the NICU
Authors
Xiaomei Cong, Jing Wu, Dorothy Vittner, Wanli Xu, Naveed Hussain, Shari Galvin, Megan Fitzsimons, Jacqueline M. McGrath, Wendy A. Henderson
Summary
Introduction
The rate of preterm births is unacceptably high in US. stressful early life experiences in the neonatal intensive care unit (NICU) have ocntinued to be an inherent part of high-tech lifesaving care for these infants, which often involves painful or stressful diagnostic and therapeutic procedures. Within substantial gains in survivals from NICU, there is increased focus on decreasing neurological morbidity and long-term adverse outcomes .
NICU Infant Stressor Scale (NISS) has been successfully utilized to provide a cumulative measure of infant’s exposure to both acute (numbers) and chronic (hours) stressful exposure.
We hypothesized that premature infants subjected to stressful early life experiences would develop an altered neurodevelopmental outcome at 36-37 weeks post-menstrual age (PMA).
purpose of this study:
- describe the cumulative pain/stress of preterm infants during the first 28 days of life in the NICU.
- describe neurobehavioral profile of preterm infants at 36-s7 weeks PMA.
- investigate the relationship of 1 and 2.
Methods
Design
prospective longitudinal study design was used to explore cumulative early life stressors. ????
Participants
stable preterm infants, meet Inclusion and exclusion criteria.
???? The calculation of sample size was based on exploratory nature of the study design.
Outcome measurements and data collection
NISS
Early life stressor were measured daily from NICU enrollment to 4 weeks of hospitalization using the NISS. The acute and chronic NISS scores were calculated over the course of days and weeks, and total scores over 4 weeks were summarized. It is possible that the daily duration of chronic events might be larger than 24 hours.
**Parental Contacts **(duration, minutes) were measured daily by recording in the NICU, including skin-to-skin contact, maternal direct breastfeeding, holding, cuddling, hand swaddling or touch, and talking, singing, or reading, etc.
Neurobehavioral responses
Neurobehavioral responses were measured when the infant reaches 36-37 weeks of PMA or prior to hospital discharge using NNNS, which is designed to examine both neurologic integrity and behavioral functioning of the normal and at-risk infant at 34-48 weeks PMA. three main sections, 115 items which generates 13 summary subscales measureing: habituation, attention, need for handling, quality of movement, self-regulation, nonoptimal reflexes, asymmetric reflexes, arousal, hypertonicity, hypotonicity, excitability, lethargy, and stress/abstinence.
NSTRESS and NHABIT were selected as primary measure for evaluating the relationship. higher NSTRESS score demostrated a more stressful behavioral performance. higher NHABIT indicates a better (more rapid) habituation outcome in response to stimulation.
Additional variables
demographics, severity of illness, feeding type, infection, antibiotics use, probiotics and other medication use.
Data analysis
Exploratory data analysis describes characteristics of each stressor variable’s daily occurrence and its distribution over time, graph + summary statistics (mean + sd).
NSTRESS
A linear regression model was used to assess the relationship between NSTRESS and key summary NISS (mean, minimum, maximum) while controlling for confounding clinical and demographic factors. Residual Diagnosis, White test for equal-variance, Shapiro-Wilk for normality. The variables in the final model were selected using stepwise selection in SAS, VIF to determine evidence of multicollinearity.
Post-hoc power analysis was conducted using Power Analysis and Sample Size Software (PASS-13) based on the method of Cohen.
NHABIT
missing of NHABIT, use logistic regression to compare the missing data group member with their non-missing counterparts to identify missing at random (MAR), use Multiple Imputation (MI) with expectation-maximization (EM) to resolve the missing data problem:
- Impute the missing entries of the incomplete dataset 40 times (how?)
- analysis each of 40 completed datasets using LM
- combine the estimates(coeffs, se, and p-value) using Rubin’s combination Rule.
- for R-square, use transformation to make it asymptotic normal, using Rubin’s Rule, then transform back.
Sensitivity analysis using the pattern-mixture approach to adjust MAR assumption.
Results
majority of infants characteristics, demographic summary,
graph for unweighted daily acute score, and chrnoic score over time.
summary statistics for parent contact
summary statistics for 13 NNNS scores.
NSTRESS
ESS = 40, R2 = 0.59,
daily weighted acute NISS score significant, higher acute score, higher NSTRESS.
daily weighted chronic NISS score significant, more chrnoic pain, higher NSTRESS.
NHABIT
ESS = 40 after MI, R2 = 0.78
daily weightd acute and chrnoic NISS score significant, higher score, lower NHABIT.
daily mean duration of direct breastfeeding and skin-to-skin holding sig, more time, better NHABIT.
Discussion
This is the first study innovatively taken together stressful events and protective experiences of preterm infants during the NICU stay to examine neurobehavioral outcomes.
the weighted NISS score is still considered as an indirect measurement of stress because the stressful level of each events in the NICU is perceived by the halth professionals.
Reference
- Cong X, Wu J, Vittner D, et al. The impact of cumulative pain/stress on neurobehavioral development of preterm infants in the NICU. Early Hum Dev. 2017;108:9–16. doi:10.1016/j.earlhumdev.2017.03.003
- Applied Missing Data Analysis with SPSS and Rstudio. https://bookdown.org/mwheymans/Book_MI/rubins-rules.html
Thoughts
Question:
- How can “causal” conclusion be made?
- Is the way to calculate the total acute/chronic NISS scores for assessing cumulative pain/stress appropriate?
- Acute and Chronic pain/stress are functional?
- NISS and parental contacts are correlated? clustering? more NISS more contacts or more NISS less contacts?
- are NSTRESS and NHABIT pre-specificly selected?
- for the linear model, use Q1, Q3 instead to remove outlier compared to min & max?
- For Fig 1, did the author consider the number of infants recorded for each day?
- preterm and very preterm infants subgroup analysis?
- Why NSTRESS and NHABIT share the same covariates in the final model?