Multisensory early intervention can improve visual function in preterm infants at term equivalent age

March 20, 2021


Fontana C, De Carli A, Ricci D, Dessimone F, Passera S, Pesenti N, Bonzini vM, Bassi L, Squarcina L, Cinnate C, Mosca F, Fumagalli M. Effects of Early Intervention on Visual Function in Preterm Infants: A Randomized Controlled Trial. Front Pediatr 2020; 8:291: 1-9. PMID: 32582595


Rochelle Lester, Physiotherapist
The Women’s Hospital




For preterm infants born between 25 and 29 weeks gestational age (P), does a multisensory early intervention program (I) compared with routine care (C), improve visual function as measured by the Ricci neonatal visual examination (O) when assessed at term equivalent age (T)?


  • Design: Randomised Controlled Trial
  • Allocation: Concealed envelopes; computer generated randomization
  • Blinding: assessor was blinded to group allocation
  • Follow-up period: preterm to term equivalent age (TEA)
  • Setting: Neonatal Intensive Care Unit, Milan, Italy
  • Patients:
    • Neonates born between 25+0 and 29+6 weeks’ gestation
    • Recruited after the first week of life once clinically stable.
    • Exclusion criteria:
      • mothers < 18 years or those who had obvious cognitive impairment, drug addiction or psychiatric disorders or did not have good comprehension of Italian
      • single parent families
      • neonates who developed retinopathy of prematurity >stage 2 or with extensive non-cystic white matter damage on their term equivalent brain MRI were not included in the visual function analysis.
  • Intervention: multisensory stimulation which included infant massage and visual interaction. The intervention was implemented by parents following training which focused on understanding infant behaviour and promoting joint interactions.
    • Parental training commenced 1 week after birth or when the infant was clinically stable. Twice daily infant massage commenced 3 weeks after parents had received initial training.  Daily visual interaction activities were commenced at 34+0 weeks gestational age and continued until term equivalent age.
  • Outcomes: visual function at term equivalent age using the Ricci neonatal visual examination
  • Analysis and Sample Size: a sample size of 70 infants was selected to provide 80% power to detect a difference equal to 30% or more in visual performance between the intervention and control groups, accounting for 15% drop out. Differences between groups were compared using Fisher’s exact test with sensitivity analysis conducted using logistic regression models to control for confounders (alpha = 0.05).
  • Patient follow-up: 57/70 (81% included in analysis)


70 eligible infants were recruited for the study.  13 were excluded according to the study protocol and the remaining 57 were assessed at term equivalent age. Of those, 27 infants were randomized to intervention and 30 to standard care. The visual component of the intervention commenced 3 weeks after parents received initial training, at a mean age of 32.1 weeks gestational age (GA).  Infants in the intervention group demonstrated more mature visual performance than those in the control group.

Neonatal Visual assessment Intervention group (n-27) Control Group


Multivariate odds ratio (95% confidence interval) P-value
Mean gestational age at birth (standard deviation) 28.4 (0.9) 27.8 (1.3)
Spontaneous ocular motility (mainly conjugated) 26 (96.3%) 21 (70%) 13.7 (2.1-279) 0.013
Occular movements with target (mainly conjugated) 23 (85.2%) 16 (53.3%) 5.9 (1.6-26.3) 0.012
Vertical tracking (complete) 27 (100%) 29 (96.7%) ** 1
Tracking in an arc (complete) 27 (100%) 24 (80%) ** 0.025
Stripes discrimination (7-8 cards) 21 (77.8%) 10 (33.3%) 7.5 (2.3-28.0) 0.001
Attention at distance ≥70cm 20 (74.1%) 6 (20%) 14.9 (4.1-67.4) <0.001

Note: results reflect the number in each group that achieved the highest possible score for each visual assessment category.
**odds ration unable to be calculated


All infants in both groups achieved stable visual fixation and were able to track a horizontal target and a coloured target. There was no significant difference between the groups for vertical tracking


A multisensory early intervention program of infant massage and early visual interaction provided by parents in the NICU can positively impact on the visual maturity of preterm infants without major brain lesions at term equivalent age.


The visual system is a complex pathway which incorporates multiple motor, cognitive and perceptual functions.  Suboptimal neonatal visual function has been associated with poorer neurodevelopmental outcome.1 It is well accepted that early experiences in the neonatal intensive care unit (NICU) influences the development of preterm infants2 and that the involvement of parents in the NICU is key to improving infant outcomes.3  While early experience is hypothesized to enhance visual development in preterm infants, limited research exists for specific intervention programs.

Fontana et al. implemented a multisensory early intervention program (behavioural cues, massage and visual training) for preterm infants born between 25+0 and 29+6 weeks gestation. Infants in the intervention group showed more mature visual performance at term equivalent age (TEA) compared with the control group who received standard care. Differences between the groups were noted in attention at distance and stripes discrimination.  Additionally, infants in the intervention group had better occular motility and tracking for an arc, supporting previous research which suggests that the maturation of these subcortically mediated aspects of visual function may be accelerated by early experience.1  Use of a control group allowed the authors to determine the efficacy of the intervention relative to normal maturation over time. Given the multiple interventions employed in this study it is impossible to extrapolate the individual effect of each intervention on outcomes, a point which the authors acknowledge in their discussion. Further research should aim to determine the relative contribution of each intervention.

A strength of this study was that the early, enriched multisensory program commenced early, in the NICU and was provided by parents following a period of training to support them in understanding their infant’s behaviour and developing the parent-infant relationship. The authors highlight the importance of active engagement of parents in the NICU and the potential long term benefits of this to infant brain development. Of note, single parent families were excluded from this study with the rationale for this exclusion criteria not described.  Further discussion of the infants’ tolerance of the intervention and any associated stress responses would be useful, particularly given the potential for early visual stimulation to be inappropriate as the visual system is the last sense to develop.

It will be important to examine the long term outcomes of the infants and parents in this study.  Firstly, to determine whether the differences in vision between groups are maintained beyond TEA and secondly, to determine whether the accelerated visual maturity translates into a functional difference in overall neurodevelopment, for example at 2 years or beyond. Furthermore, the authors acknowledge a systematic review which suggests improved visual outcomes with early visual interventions in infants who are at high risk of cerebral palsy4 and suggest that these children should be included in future studies.  Indeed infants with more severe brain lesions (who were excluded from the present trial) or significant comorbidities such as bronchopulmonary dysplasia or those who have required surgery are known to be at highest risk of developmental delay5 and may therefore benefit more from Fontana et al.’s early intervention program.


  1. Ricci D, Romeo DM, Gallini F, Groppo M, Cesaini L, Pisoni S, et al. Early visual assessment in preterm infants with and without brain lesions: correlation with visual and neurodevelopmental outcomes at 12 months. Early Hum Dev. 2011:87:177-82.
  2. Mooney-Leber SM, Brummelte S. Neonatal pain and reduced maternal care: early-life stressors interacting to impact brain and behavioral development. 2017:342:21-36.
  3. 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. 2009:123(2):555–561.
  4. Chorna OD, Guzzetta A, Maitre NL. Vision assessments and interventions for infants 0-2 years at high risk for cerebral palsy: a systematic review. Pediatr Neurol. 2017:76:3-13.
  5. Cheong JLY, Anderson PJ, Burnett AC, et al. Changing Neurodevelopment at 8 years in Children Born Extremely Preterm Since the 1990s. 2016:139 (6).