Wu Y-C, Hsieh W-S, Hsu C-H, Chang J-H, Chou H-C, Hsu H-C, Chiu N-C, Lee W-T, Chen W-J, Ho Y-W, Jeng S-F. Intervention effects on emotion regulation in preterm infants with very low birth weight: A randomize controlled trial. Res Dev Disabil 2016; 48: 1-12. PMID: 26524725
Tara FitzGerald, BPhys (Hons)
School of Physiotherapy, The University of Melbourne and Murdoch Childrens Research Institute, VIC, Australia
TYPE OF INVESTIGATION
In preterm infants with birthweight < 1500g, does a comprehensive home or clinic based child, parent and dyad focused intervention program delivered until 12 months corrected age, affect stress reactivity and emotional regulation at toddler age compared with standard care?
- Design: Multicentre randomised control trial (RCT) with parallel-group study
- Allocation: The infants were assigned to one of three groups using computer-generated random sequencing with stratification by gestational age (GA) and hospital. Allocation was concealed from parents, clinical and research staff.
- Blinding: The experimenters and coders involved in the testing procedure were blinded to the participant’s group allocation.
- Follow-up period: Follow-up assessments were completed at 12, 18 and 24 months corrected age (CA).
- Setting: Three hospitals in Taiwan (National Taiwan University-Hospital, Mackay Memorial Hospital, and Branch for Women and Children at Taipei City Hospital).
- Patients: Singleton infants, or the first child of a multiple birth, weighing < 1500g (VLBW), < 37 weeks’ GA, and born or admitted to any participating hospital within 7 days of birth were eligible for recruitment. Infants who were medically unstable at 36 weeks’ post-menstrual age (PMA), discharged from hospital ≥ 44 weeks’ PMA, had congenital anomalies, or developed severe neonatal diseases were excluded. Wu and colleagues included 62 healthy term born infants at 12, 18 and 24 months of age to act as a reference group. The term infants did not participate in the intervention.
- Intervention: VLBW infants and their families were randomised to receive a home-based intervention program (HBIP), a clinic-based intervention program (CBIP), or a usual care program (UCP). The HBIP group consisted of 63 infants, and a further 58 were allocated to the CBIP, and 58 to the UCP.
- The participants in the HBIP and CBIP groups received 5 in-hospital sessions, and 8 sessions post discharge. The sessions were scheduled at 36-38 weeks’ PMA, 40 weeks’ PMA, 1,2,4,6,9 and 12 months CA. The HBIP and CBIP involved child, parent and dyad targeted services aimed at supporting modification of the neonatal intensive care and home environment. The HBIP and CBIP also included parental education regarding developmental skills (milestones, age appropriate toys and activities to facilitate development), baby massage, and parent-infant interaction activities. Post discharge, these 30-40 minute sessions were completed at home (HBIP) or in a clinic setting (CBIP).
- The participants allocated to the UCP group received standard child-focused developmental care comprised of 5 in-hospital and 8 follow-up clinic sessions.
- Primary outcome:
- The primary outcomes were stress reactivity, advanced regulatory strategies and primitive behaviour in response to stress at 12, 18 and 24 months CA. Primary outcomes were measured during a toy-behind barrier procedure. Participants played with a toy for 90 seconds, after which the toy was removed and placed behind a transparent barrier to induce stress for a further 90 seconds. Stress reactivity was characterised by negative vocalisation, and primitive behaviour was measured by duration of avoidance. Advanced regulatory strategies included distraction, self-soothing and communication behaviours.
- Secondary outcomes:
- Cognitive and language performance, and maternal interaction quality at 12 months CA were secondary outcomes of this study. Cognitive and language ability was measured using the Bayley Scales of Infant Development, 3rd Edition (Bayley-III), while the quality of maternal interaction (duration of high quality maternal responsiveness) was measured during a free play procedure. These secondary measures were later used as covariates for primary outcomes. The emotional reactivity and regulation of the full term reference group at 12, 18 and 24 months of age were also analysed.
- Primary outcome:
- Analysis and Sample Size: Birth and demographic factors were compared across the three intervention groups using analysis of variance and chi-squared tests as appropriate. The authors completed various regression analyses in their statistical methods. Univariate regression was used to compare infant and maternal factors. Stress reactivity and self-regulation behaviour of the preterm groups at all three time points were also assessed using a multivariate regression model. Predictors in this model were group allocation, age and the group x rou interaction, with unbalanced infant and maternal factors added as covariates. In addition, the stress reactivity and self-regulation of full term infants from 12 to 24 months corrected age were analysed using univariate regression analysis in which age was treated as a predictor. The sample size used in this study was not statistically calculated.
- Patient follow-up: Of 357 VLBW infants assessed for eligibility, 146 did not meet inclusion criteria, leaving 211 infants to be randomised. Of these infants, 29 were early drop-outs and data from 4 participants were used for pilot testing, leaving 178 VLBW participants (84% of eligible infants recruited). The number of VLBW participants assessed at 12, 18 and 24 months CA and the follow up rates at each time point are presented in the Table 1.
TABLE 1: VLBW infants assessed and follow up rates at each time point.
|Age||HBIP (63)||CBIP (57)||UCP (58)||Follow up (%)|
|12 months CA||43||47||44||64|
|18 months CA||41||46||39||60|
|24 months CA||46||43||42||62|
Term born infants (n=62) were identified for assessment, however only 52 infants entered the study (84% of assessed infants recruited). At 12 months of age, 46 (88%) were assessed, 41 (79%) were seen at 18 months, and 38 (73%) were assessed for emotion regulation 24 months of age.
The authors found no age, group, or group x age interaction effect for stress reactivity across VLBW groups, despite adjustment for high quality maternal responsiveness. Two advanced regulatory strategies showed an age effect only (duration of re-orientation and self-comforting), but no group, or group x age interaction effects (Table 2). Duration of communication had no significant group, age, or group x age interaction effect.
Duration of avoidance showed a significant effect of CBIP group only (Table 2). Infants in this group showed shorter duration of avoidance when compared with UCP group infants from 12 to 24 months CA. Duration of orientation to the toy showed a significant effect of age, and group, with the HBIP participants showing a shorter duration of toy orientation when compared with UCP group infants from 12 to 24 months CA.
TABLE 2: Effect of group, age and age x group interaction on the advanced regulatory strategies and primitive behaviour in response to stress of VLBW participants
|Regulatory Strategy||Group Effect||Age Effect||Group x Age Effect|
|Duration of re-orientation||X||0.06 [0 -0.13] p= 0.04||X|
|Self-comforting||X||0.06 [0.01-0.12], p= 0.02||X|
|Duration of communication||X||X||X|
|Duration of avoidance||CBIP:
-0.84 [-1.57 to -0.10], p = 0.03
|Duration of orientation to toy||HBIP:
-1.60 [-3.07 to -0.13], p = 0.03
|-0.06 [-0.12 to -0.01], p= 0.03||X|
Data presented as adjusted b, [95% Confidence Interval]. X indicates no intervention effect. HBIP; home based intervention program, CBIP; clinic based intervention program.
Bayley-III cognitive and language performance did not differ between HBIP, CBIP and UCP groups at 12 months corrected age (Table 3). The proportion of high quality maternal responsiveness is also shown in Table 3, and was slightly higher in the CBIP group compared to the UCP group.
A significant age effect was found for stress reactivity and all regulatory behaviours in full term infants; decrease in reactivity (b [95% confidence interval (CI)] -0.04 [- 0.07 to -0.01], p < 0.01), duration of avoidance (-0.03 [ -0.06 to -0.01], p = 0.02), orientation to toy (-0.09 [ -0.15 to -0.03], p < 0.01), increased duration of reorientation (0.11 [0.05 to 0.17], p < 0.01), communication (0.17 [0.10 to 0.25], p < 0.01) and self-comforting (0.14 [0.08–0.19], p < 0.01).
TABLE 3: Bayley-III performance of VLBW and term born participants and quality of maternal interaction.
|Bayley-III||HBIP (49)||CBIP (52)||UCP (48)||Term (51)|
|Cognitive composite score (points)||103.1 (9.8)||103.0 (9.3)||101.1 (12.3)||108.1 (7.5)|
|Bayley-III Language composite score (points)||
|Maternal Responsiveness||CBIP Dyads (50)||HBIP Dyads (63)||UCP Dyads (45)||Term Dyads (46)|
|High quality maternal interaction (%)||0.51 (0.28)*||0.46 (0.29)||0.41 (0.27)||0.70 (0.20)|
Data presented as mean (SD), numbers in parentheses are the numbers of participants assessed. Age is corrected for prematurity for VLBW participants. * marginal difference between the CBIP and UCP groups, b=0.10, p =0.07. HBIP; home based intervention program, CBIP; clinic based intervention program, UCP; usual care program.
The authors state that the HBIP and CBIP resulted in decreased primitive behaviour in response to stress for VLBW preterm born toddlers, concluding that comprehensive interventions involving environmental modification, dyadic interaction, parental support and child development were effective in this study. The authors advocate for clinic and home based early intervention settings to enrich the developmental experience of preterm infants in both familiar and novel environments.
Infants born preterm are at higher risk of adverse developmental outcomes compared with term born infants, including attentional difficulties (1), reduced cognitive performance and behavioural impairments at school age (2), and motor impairment from infancy to adolescence (3). Early intervention programs positively affect cognitive and motor outcomes in infancy, with persisting cognitive benefits at pre-school age (4). However, Wu and colleagues highlight that studies investigating the efficacy of early intervention programs for emotion regulation in preterm infants at toddler age are lacking, and Taiwanese services for VLBW preterm infants are largely limited to in-hospital child centred design (5).
This multicentre RCT suggests that a comprehensive clinic or home based child, parent and dyad focused early intervention program improved emotion regulation for VLBW preterm infants in Taiwan. However, the authors found no stress reactivity benefits, or enhanced regulatory strategies for either intervention group which only partly supports this conclusion. Furthermore, cognitive and language performance at 12 months CA did not differ between groups, although statistical significance is not presented in this paper.
The authors identify several pertinent limitations of their study. Of particular interest is the demographic characteristics of VLBW families, with 73% having high maternal education level, and moderate to high socio-economic status (SES). Social and environmental factors play an important role in the developmental outcome of preterm infants (6, 7), therefore this factor may affect the representativeness of the study population. The laboratory setting for outcome assessment, and the length of follow up should be considered in future study design.
Participant follow up is another important consideration, with low follow up rates introducing potential bias and possibly affecting the statistical power of this study. Furthermore, at each time point a proportion of infants were not assessed due to seating difficulty. For VLBW infants, this was reported 42 times, with an additional 8 term born toddlers at 24 months unable to be seated. The birth and demographic characteristics of these infants were comparable with assessed infants, however it is possible that non-participants may have had underlying behavioural or motor difficulties. Exclusion of these infants from assessment further limits the representativeness of the VLBW population in this study.
This RCT contributes to the field by exploring the important area of emotion regulation and behaviour after a comprehensive child, parent and dyad focused early intervention program in Taiwan. Future research should include high risk preterm populations to identify the efficacy of intervention programs for those infants who are likely to benefit most (4). The financial feasibility of the home and clinic based interventions detailed by Wu and colleagues would be a valuable area of further study to guide future design of early intervention programs. As both clinic and home based settings were found to be beneficial for reducing stress evoked primitive behaviour when compared to usual care, the parental mental health, wellbeing and engagement in each program could also be a valuable method of evaluating each setting.
- Anderson PJ, De Luca CR, Hutchinson E, Spencer-Smith MM, Roberts G, Doyle LW. Attention problems in a representative sample of extremely preterm/extremely low birth weight children. Developmental Neuropsychology. 2011;36(1):57-73.
- Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand K. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. Jama. 2002;288(6):728-37.
- de Kieviet JF, Piek JP, Aarnoudse-Moens CS, Oosterlaan J. Motor development in very preterm and very low-birth-weight children from birth to adolescence: a meta-analysis. JAMA: Journal of the American Medical Association. 2009;302(20):2235-42 8p.
- Spittle A, Orton J, Anderson PJ, Boyd R, Doyle LW. Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants. The Cochrane Library. 2015.
- Wu Y-C, Hsieh W-S, Hsu C-H, Chang J-H, Chou H-C, Hsu H-C, et al. Intervention effects on emotion regulation in preterm infants with very low birth weight: A randomize controlled trial. Research in developmental disabilities. 2016;48:1-12.
- Treyvaud K, Anderson VA, Howard K, Bear M, Hunt RW, Doyle LW, et al. Parenting behavior is associated with the early neurobehavioral development of very preterm children. Pediatrics. 2009;123(2):555-61.
- Miceli PJ, Goeke-Morey MC, Whitman TL, Kolberg KS, Miller-Loncar C, White RD. Brief report: birth status, medical complications, and social environment: individual differences in development of preterm, very low birth weight infants. Journal of pediatric psychology. 2000;25(5):353-8.