children

Article
Early Physiotherapy Intervention Program for Preterm Infants
and Parents: A Randomized, Single-Blind Clinical Trial
Mirari Ochandorena-Acha 1,2 , Marc Terradas-Monllor 1,3, * , Laura López Sala 2 ,
Maria Engracia Cazorla Sánchez 2 , Montserrat Fornaguera Marti 2 , Isabel Muñoz Pérez 2 , Thais Agut-Quijano 2 ,
Martín Iriondo 2 and Joan Carles Casas-Baroy 1

1 Research Group on Methodology, Methods, Models and Outcomes of Health and Social Sciences (M3 O),
Faculty of Health Sciences and Welfare, Centre for Health and Social Care Research (CESS),
University of Vic-Central University of Catalonia (UVIC-UCC), C.Sagrada Família, 7,
08500 Vic, Barcelona, Spain; [email protected] (M.O.-A.); [email protected] (J.C.C.-B.)
2 Sant Joan de Deu Barcelona Children’s Hospital, Passeig de Sant Joan de Déu, 2,
08950 Esplugues de Llobregat, Barcelona, Spain; [email protected] (L.L.S.);
[email protected] (M.E.C.S.); [email protected] (M.F.M.);
[email protected] (I.M.P.); [email protected] (T.A.-Q.); [email protected] (M.I.)
3 Pain Medicine Section, Anaesthesiology Department, Hospital Clínic de Barcelona,
08036 Barcelona, Catalonia, Spain
* Correspondence: [email protected]

Abstract: Background: The early developmental interventions might be designed with a preventative
approach to improving the development of at-risk preterm infants. The present study aimed to
evaluate the effectiveness of an early physiotherapy intervention on preterm infants’ motor and global
Citation: Ochandorena-Acha, M.; development, and on parents’ stress index. Methods: 48 infants were enrolled and randomized into
Terradas-Monllor, M.; López Sala, L.; two groups. Infants allocated to the intervention group received an early physiotherapy intervention,
Cazorla Sánchez, M.E.; Fornaguera based on parental education sessions and tactile and kinesthetic stimulation during the NICU period,
Marti, M.; Muñoz Pérez, I.; as well as a home-based activity program. The intervention commenced after 32 weeks post-menstrual
Agut-Quijano, T.; Iriondo, M.;
age and ended at 2 months corrected age. Infants allocated to the control group received the usual
Casas-Baroy, J.C. Early Physiotherapy
care based on the NIDCAP-care. Results: No differences were found between groups on the Alberta
Intervention Program for Preterm
Infant Motor Scale at 2- or 8-months corrected age. Infants in the intervention group showed more
Infants and Parents: A Randomized,
optimal fine motor, problem-solving, personal-social, and communication development at 1 month
Single-Blind Clinical Trial. Children
2022, 9, 895. https://doi.org/
corrected age. Conclusions: The results showed no effect on the early physiotherapy intervention.
10.3390/children9060895 Results might be related to the dose or intensity of the intervention, but also to the poor parental
compliance. ClinicalTrials.gov NCT03313427.
Academic Editor: Vasanth Kumar

Received: 28 April 2022 Keywords: neonates; parent training; motor development; quantitative methods
Accepted: 13 June 2022
Published: 15 June 2022

Publisher’s Note: MDPI stays neutral

1. Introduction
with regard to jurisdictional claims in
published maps and institutional affil- The knowledge of early human brain development has evidenced that the high de-
iations. velopmental activity in the brain during the second half of gestation induces an increased
vulnerability in infants born preterm [1,2]. Consequently, within their immaturity con-
dition, preterm infants usually show a delay in their motor development. Compared to
infants born at term age, premature infants often present lower muscle tone, less movement
Copyright: © 2022 by the authors. variability, and higher behavioral complexity. These characteristics compromise their pos-
Licensee MDPI, Basel, Switzerland. tural control, which is necessary to gain stability, orientation, and spatial organization [3–5].
This article is an open access article For example, when preterm infants attempt to lift their legs, they are often unable to keep
distributed under the terms and
the limbs off the support surface. In addition, when they succeed in raising their legs,
conditions of the Creative Commons
they frequently roll to the side, demonstrating an inability to turn their head from side to
Attribution (CC BY) license (https://
side or lift one leg at a time [6,7]. Although these motor alterations are sometimes subtle,
creativecommons.org/licenses/by/
they might contribute to delays in other domains such as cognitive development, and
4.0/).

Children 2022, 9, 895. https://doi.org/10.3390/children9060895 https://www.mdpi.com/journal/children

Children 2022, 9, 895 2 of 18

later, academic performance [7,8]. Furthermore, the motor experiences contribute to the
infants’ attempts and motivation to explore the environment. Their motor ability allows
them to receive and interpret relevant information, as well as to communicate and interact
physically with people and objects, and solve problems [8,9].
As a consequence of an unexpected delivery or the admission to the Neonatal Intensive
Care Unit (NICU) [10], preterm infants’ parents usually experience high levels of anxiety,
stress, or depression, and that, in turn, might influence children’s development [11,12].
Therefore, the infants’ and families’ quality of life might also be affected [7,8]. Previous
research has shown that parents’ involvement in early interventions enables them to better
understand their child’s development and learn how to support their child. Moreover, when
parents provide hands-on programs, they experience a sense of autonomy, empowerment,
and stronger bonding with their infant [12–16]. This large body of research has provided
valuable information when designing and administrating developmental programs to
enhance preterm infants’ development and improve their parents’ mental health [17,18].
Early developmental interventions are undertaken to improve brain connections
during critical periods of infants’ central nervous system development [17]. Although
some early interventions are provided only during the NICU period or at home [19,20],
it seems that the duration is not long enough to offset the adverse outcomes of preterm
birth [12,17]. Consequently, previous research concluded that interventions that commence
at the NICU and continue after discharge are the most recommended for families. Further-
more, these interventions have been shown to have a more significant effect on infants’
outcomes [12,17,18,21].
NICU multidisciplinary teams are typically involved in assessing infants born preterm
and are encouraged to provide early developmental interventions to the infants and their
parents. Within the scope of physiotherapy, preventative, developmental interventions are
targeted to at-risk preterm infants—without risk factors for adverse neurological outcomes
in the perinatal period, such as intraventricular hemorrhage, periventricular leukoma-
lacia, sensory abnormalities, specific motor abnormalities, or chromosomal abnormali-
ties [10,12,17,21–23]. Preventative early interventions usually involve parents and aim
to enhance the parent–infant relationship, improve parent coping and the home environ-
ment through parental education, and promote infants’ stimulation and autonomy [21].
Although many types of research have been conducted on early preventative and devel-
opmental interventions [24–32], there is a shortage of high-level evidence-based research
within the scope of physiotherapy.
This research aimed to evaluate the effectiveness of a preventative early physiotherapy
intervention to improve at-risk preterm infants’ motor development at 2- and 8-months cor-
rected age. The study also aimed to evaluate the intervention’s effectiveness in enhancing
the global development of infants born preterm at 1 month corrected age and its post-
intervention effects in decreasing parents’ stress. This study will consider post-intervention
at infants’ 1- and 2-months corrected age, and short-term at 8 months corrected age [33].
The present study might contribute new knowledge to the physiotherapy field as part
of the NICU multidisciplinary team involved in preterm infants and their parents’ care.
We hypothesized that infants who receive early physiotherapy intervention show more
significant motor performance improvements at 2- and 8-months corrected age compared
to the infants in the control group. We also hypothesized that the intervention positively
affects infants’ global development at 1 month corrected age and parents’ post-intervention
stress level.

2. Materials and Methods

2.1. Study Design
A randomized, single-blind clinical trial was conducted at the *** Hospital (***), a
level-III hospital with NICU facilities. The study results have been reported according to
the CONSORT 2010 Statement [34]. Ethical permission was obtained from the relevant
Clinical Research Ethical Committee of *** (***). The protocol accepted by the Ethical
Children 2022, 9, 895 3 of 18

Committee is registered at ClinicalTrials.gov (NCT***). All parents provided informed

written consent. The study has been conducted according to Good Clinical Practice and
Declaration of Helsinki principles [35].

2.2. Participants
Participants’ recruitment took place between December 2017 and December 2018.
Preterm infants born between 28 + 0 and 34 + 0 (weeks + days) of gestational age and
whose parents stayed at the hospital for more than 6 h a day and who were able to speak
and understand Spanish were eligible for the study. Exclusion criteria were preterm
triplets, major central nervous system injury (grade III/IV intraventricular hemorrhage or
periventricular leukomalacia), severe musculoskeletal or congenital abnormalities, bron-
chopulmonary dysplasia, major surgery, severe sepsis or necrotizing enterocolitis during
the neonatal period, hearing impairment or retinopathy of prematurity, and infants born of
mothers with a documented history of social problems or mental illness.

2.3. Sample Size

The sample size was calculated based on the primary outcome, the Alberta Infant Mo-
tor Scale (AIMS) [36]. A difference of 1.2 SD between groups was considered to be clinically
significant [37]. Assuming a 10% drop-out rate, 24 infants in each group were required to
ensure a statistical power of 80% chance of detecting this difference at a significance level
of 0.05 (α) [38].

2.4. Randomization and Masking

Selected participants were recruited by a physical therapist (PT) after 32 + 0 weeks
post-menstrual age (PMA) and only if the preterm children were medically stable (no need
for invasive mechanical ventilation and no active sepsis). In the case of infants born after
32 weeks PMA, the recruitment took place 2–3 days after birth, when the infants were also
medically stable.
The random assignment of each preterm infant with his/her parents was stratified
according to the gestational age at birth (between 28 + 0 and 31 + 6 and between 32 + 0
and 34 + 0 gestational age) to ensure comparability among groups. The stratification was
accomplished using two computer-generated lists at a 1:1 ratio. Twins were assigned to
the same group. The allocation was made through sealed opaque envelopes (identified
according to stratification group and numbered consecutively), which were opened by the
first author before parents were given oral and written information. Parents who agreed to
participate in the study and signed informed consent were included in the study.
Due to the nature of the intervention, neither the PTs conducting the intervention nor
the participants (parents) were blinded to the group allocation. Both the PTs administering
the postintervention assessments and nurses at the neonatal unit were blinded to the
participants’ assigned group. The regular (non-researcher) nursing staff and PTs at the
hospital were not taught about the experimental intervention, and they did not change
their procedures or support provided to parents during the intervention period.

2.5. Intervention
Standard care. The hospital provides the Newborn Individualized Developmental
Care and Assessment Program (NIDCAP), which is based on the concept of newborn or
infant competence and focuses on respecting the individuality of the very tiny human
being and his or her family. The NIDCAP incorporates some principles of developmental
care, such as positioning and the use of incubator covers to shield infants. Additionally,
the hospital encourages breastfeeding and parents’ involvement during a child’s daily care
and provides support to the families during the NICU stay through a multidisciplinary
team, which consists of neonatologists, nurses, psychologists, social workers, and physio-
therapists. The usual physiotherapy care offered during the NICU stay includes at least
one visit to guide parents during the daily activities in the neonatal unit. Before hospital
Children 2022, 9, 895 4 of 18

discharge, parents are also invited to a session called “going home”, where a nurse and a
physiotherapist give specific reminders of the basics of infant care at home (breastmilk
storage and formula feeding, kangaroo care at home, baby massage, and guidance about
positioning, feeding, and sleeping at home). After hospital discharge, if the infant is consid-
ered high-risk, sporadic sessions with a PT for individual assistance are arranged. In those
cases, the number and type of activities were recorded.
Early physiotherapy intervention program. In addition to standard care, the inter-
vention group received the early physiotherapy intervention program during the NICU stay
and after hospital discharge. The intervention is based on traditional developmental care
programs to improve preterm infants’ development outcomes [22,39], and it was designed
with a preventative approach. It aimed to improve preterm infants’ motor development,
enhance the parent–infant relationship, and teach parents about preterm infants’ cues and
management strategies (see Figure 1).

Figure 1. Example of the intervention protocol for a preterm infant born at 31 weeks of gestational
age. The protocol was adapted depending on the infant’s gestational weeks at birth. PI: preterm
infant; TKS: tactile-kinesthetic stimulation.

Intervention at the NICU: The intervention commenced after the infant’s 32 weeks
PMA and before term-equivalent age, during the NICU stay, once the preterm infant was
medically stable. In the case of infants born after 32 weeks PMA, the intervention started
4–5 days after birth.
Firstly, parents received a total of six education sessions for 2–3 weeks. Each session
lasted 1 h, and approximately two sessions were held each week. The education sessions
consisted of teaching parents to understand their infants’ communication cues, recognize
signs of distress, and how to respond sensitively to them. The sessions were divided
into different topics. In the first session, the therapist explained the characteristics and
necessities of the preterm infant regarding light, noise, positioning (in prone, supine, and
lateral), and touch, and she also described infants’ cues and distress signs and how to
respond sensitively to them. In the second session, the therapist taught parents how to
perform the tactile and kinesthetic stimulation and involved them actively to perform
it themselves. The subsequent two sessions focused on understanding and identifying
infants’ cues during daily activities, such as bathing, diaper changing, and feeding, and
learning how to interact sensitively with the infant and incorporate some recommendations
during these activities to enhance infants’ development. In the last two sessions, the PT
explained the typical development of the preterm infant, the recommended toys to enrich
their development, and different positions to stimulate and play with the baby, promoting
antigravity skills and facilitating hands to the midline and toy manipulation. Although
Children 2022, 9, 895 5 of 18

the program can involve the whole family, the mother and the father were the principal
recipients of the intervention.
At the same time, during the second education session, parents were asked to carry
out the tactile and kinesthetic stimulation. The protocol was inspired by Fucile and Gisel’s
(2010) tactile/kinesthetic sensorimotor stimulation model. Each stimulation consisted of
10 min of slow tactile stimulation of the baby, applying moderate pressure stroking with
both hands. During the tactile stimulation, the baby was placed in the prone position.
After that, 5 min of kinesthetic stimulation was provided, performing passive movements
in the infant’s hip, knee, ankle, shoulder, elbow, and wrist. The infant was placed in a
supine position for this stimulation, either in the crib or on the parent’s lap. Parents were
encouraged to provide preterm baby stimulation sessions twice a day, at least 30 min after
feeding and 2 h after the previous one, for ten days in a 15-days period. If the infant showed
any sign of stress or an adverse behavior (e.g., an increase in tone, hiccupping, fluctuating
behavior state), parents were asked to stop the stimulation to calm the infant, or the session
was terminated. During the NICU intervention, parental compliance was registered by
the physiotherapist.
Intervention at home: After hospital discharge, the program continued at the family
home, from term-equivalent age until 2 months corrected age. During this period, the
physiotherapist presented to parents a program of activities for the child, involving them
actively in the intervention. The activity program was designed to be included in the
family’s routine by providing opportunities to experience different positions and move-
ments appropriate for the infants’ development. The PT proposed varying degrees of
activities (by focusing on toys or the parents’ face) in different positions to encourage
the infants’ movements to bring the head and extremities toward the midline, improve
head and postural control, promote antigravity skills, and facilitate toy manipulation. A
maximum of four activities was given at each appointment. Activities such as holding the
infant while gently encouraging them to bring his or her hands to their midline, prone play
(tummy time), and placing small toys on infants’ hands to promote object exploration were
included. The PT provided a demonstration to explain to parents how to complete each
activity with their infant. Parents were encouraged to carry out the activities for 15–20 min,
2 times per day (with a separation of 4–5 h between), 5 days per week. With the home
program, a daily diary was given to parents to document if they accomplished each activity
and the time performed every day. The families received one or two visits per month by
the PT (in total, a maximum of four visits at home) to progress with the program, answer
questions, and explain the importance of promoting infants’ development. Each home visit
lasted approximately 1 h. Additionally, during the home program, parents received a short
telephone message weekly to encourage them to continue completing the activities. Parents
were also asked to keep the activities diary during the intervention at home.
Participants received written materials with pictures summarizing each educational
session and describing the stimulation procedure and the home activity program to develop
them with their infant at home and increase their accomplishment and adherence to
the program.

2.6. Measures
After enrolment, perinatal, demographic, and clinical data were collected through
infants’ medical notes and parental interviews. Recorded data included the following:
gender, birth weight, head circumference at birth, gestational age, twin birth, small for
gestational age (SGA), mode of delivery, assisted reproduction, mother age and educational
attainment, father age and educational attainment, length of hospitalization, weight and
head circumference at hospital discharge, and medical interventions during the neonatal
period (oxygen and antibiotic use).
The primary outcome measure consisted of the Spanish version of the Alberta Infant
Motor Scale [36]. It is a standardized and discriminative scale for gross motor development
and assesses infants’ motor abilities, quality of posture, and movement in four positions:
Children 2022, 9, 895 6 of 18

prone, supine, sitting, and standing. The four positional scores are calculated to determine
infants’ total AIMS score [36,40]. The evaluations were performed at 2- and 8-months
corrected age. Assessments were scheduled at the hospital and performed by four indepen-
dent and experienced PTs. The assessors were blinded regarding group assignments. All
examinations were video-recorded and regularly reviewed to maintain consistent scoring.
Additionally, to ensure that the four examiners’ administration and scoring of the AIMS
were consistent, before commencing the study they practiced assessing some preterm
infants independently at 2 and 8 corrected months. If there were disagreements, they
reviewed the AIMS manual to resolve the doubts and reach an agreement.
The secondary outcome measures consisted of global development and the parental
stress index. The first one was the Spanish version of the Ages and Stages Questionnaires
Third Edition (ASQ-3) [41,42]. It is a child developmental progress screening questionnaire
based on milestones that should be achieved between 0- and 66-months old. The ASQ-3
was designed to monitor a child’s development in five domains: gross motor, fine motor,
problem-solving, communication, and personal-social. Each area has six items; each
scored on a 3-point scale of 10, 5, or 0. The scores are summed to give scores for each
subscale between 0 and 60 points. A higher score indicates better development [43–45].
The assessments were made at the infant’s 1- and 8-months corrected age. The 2 months
age-specific sheet for children between 1 month 0 days to 2 months 30 days was used at
1 month corrected age. The 8 months age-specific sheet for children between 7 months
0 days to 8 months 30 days was used at 8 months corrected age. The questionnaires were
completed by parents through a telephone call from a blinded researcher. Research shows
that the ASQ has been successfully used for follow-up and assessment of premature and at-
risk infants and children [46,47] and also that parents accurately report skills their children
can perform and rarely misrepresent their children’s developmental acumen [44].
Furthermore, the Spanish version of the Parenting Stress Index-Short Form (PSI-SF)
was used to assess the parental stress index [48,49]. This tool measures the feelings of
stress a person experiences regarding his or her role as a parent. It is a self-report measure
comprising 36 items in its short version to which parents must respond on a 5-point Likert-
type scale. The PSI-SF consists of three subscales of 12 items each: the Parental Distress
subscale determines distress experienced by parents in exercising the parental role; the
Parent–Child Dysfunctional Interaction subscale focuses on perceptions that parents have
as to what extent their child meets expectations or not, and the degree of reinforcement
their child provides them; and, the Difficult Child subscale assesses how parents perceive
the ease or difficulty of controlling their children in terms of their behavioral traits. From
the sum of these three subscales, a final overall score is obtained called Total Stress [48–50].
The assessments were made at the infant’s 3 months corrected age, and aimed to assess
the parents’ post-intervention stress index. The questionnaire was completed by parents
through a telephone call from a blinded researcher. The researcher asked them to write
down the 5 answer options to facilitate the task of answering to mothers.
Parental compliance was defined as the number of activities performed by parents
and the time spent on the home program. The parents were asked to document in a daily
diary the time and activities accomplished in each phase of the home program. When
assessing the parents’ compliance, executed activities, minutes, and days of the home
program were calculated from the daily diaries and categorized as “good compliance”
or “poor compliance”. Compliance was rated good when parents provided at least the
recommended dose (5 days per week, at least 2 activities of the program), and poor if they
did not accomplish the proposed dose.
At 8 months corrected age, parents were asked about additional physiotherapy inter-
ventions received between 2- and 8-months corrected age. This information was used to
analyze whether there were differences between groups regarding additional physiotherapy
interventions received during this period.
Children 2022, 9, 895 7 of 18

2.7. Statistical Analysis

All data were analyzed using the Statistical Package for the Social Science (SPSS
Version 26; SPSS, Inc, Chicago, IL, USA). Categorical variables were compared by Fisher’s
exact test and chi-squared test. Shapiro–Wilk’s test verified the normality of distribution.
The Student’s t-test for independent samples was used for normally distributed data
and the non-parametric Mann–Whitney test for non-normal distributed data. Bonferroni
correction was performed for every hypothesis related to the primary outcome measure. A
level of significance of 0.05 was used for all the statistical tests.
Baseline statistics for perinatal, demographic, and clinical characteristics were per-
formed to test a priori baseline differences between the two groups. After that, to verify the
effect of the early physiotherapy intervention program versus standard care, differences
between groups were calculated in primary (AIMS total and subdomains) and secondary
(ASQ-3 domains and PSI-SF) outcome measures. Additionally, the effect size was computed
using Cohen’s d or the r test, depending on whether the data showed normal or non-normal
distribution, respectively [51–53]. The between-groups effect size was calculated for AIMS,
ASQ-3, and PSI-SF. Commonly used criteria specify that a Cohen’s d value below 0.2 is
regarded as no effect, a value of 0.2 as a small effect, a value of 0.5 as a medium-sized, a
value above 0.8 as a large effect, and above 1.3 as a very large effect [51]. The effect size for
the r test was calculated using the following formula: r = √Z , where N is the total of the
N
samples. The values of r were considered small when they were higher than 0.1, medium
when higher than 0.3, and large when higher than 0.5 [53].
Additionally, The ASQ-3 scores were categorized for each domain as “high-risk devel-
opment”, “need for follow-up”, and “correct development”, following the standard criteria.
These results were analyzed through the chi-squared linear trend.
Through longitudinal analyses, changes in primary and secondary outcome measures
were calculated between the first and the second assessments. Multivariate tests were used.
Finally, infants’ primary and secondary outcome measures were analyzed regarding
parental compliance within the intervention group. The parental stress index was also
analyzed regarding their compliance. After dichotomizing parental compliance as “high
compliance” and “poor compliance”, differences between groups were calculated, as well
as the effect size.

3. Results
Initially, 69 preterm infants were assessed for eligibility. A total of 21 children were
then excluded because they did not meet the inclusion criteria (n = 15), or parents declined
to participate in the study (n = 6). The remaining 48 children were recruited and randomized
into intervention (n = 24) and control group (n = 24). The recruitment was considered to
have ended when all the sample size was gathered.
One infant in the control group passed away after hospital discharge, leaving 23 infants
to complete the first assessment at 1 month corrected age. Furthermore, 1 infant from the
control group was not available for the evaluation at 2 months corrected age, resulting in
22 infants with the post-intervention assessment. During the follow-up, 1 infant was lost
due to parents’ lack of availability, leaving 21 infants in the control group for the mid-term
analyses (8 months corrected age). In the intervention group, three children withdrew
before completing the intervention. After performing all the assessments, one infant in the
intervention group was excluded from all analyses (genetic mutation diagnosed). A total
of 20 infants in the intervention group were analyzed at all the assessment measures (see
Figure 2).
The baseline characteristics of infants and their parents are reported in Tables 1 and 2.
No statistically significant differences were found between the two groups at baseline
(p-value > 0.05).
Children 2022, 9, 895 8 of 18

Figure 2. Flow-chart. * Mothers.

Table 1. Sociodemographic and baseline characteristics of infants in the control group (CG), and
intervention group (IG).

Children Characteristics IG (n = 24) CG (n = 24) p-Value

Gestational age at birth, M (SD) (weeks) 31.84 (1.82) 32.05 (1.59) 0.675 a
Prematurity classification, n (%)
Moderate premature 32 < 34 13 (48.1) 14 (51.9) 0.771 c
Very premature 28 < 32 11 (52.4) 10 (47.6)
Children 2022, 9, 895 9 of 18

Table 1. Cont.

Children Characteristics IG (n = 24) CG (n = 24) p-Value

Intrauterine growth restriction, n (%) 4 (16.7) 6 (25.0) 0.724 b
Birth weight, M (DE) (g) 1462.46 (437.27) 1590.79 (331.21) 0.258 a
Cranial circumference at birth, M (SD) (cm) 27.75 (2.61) 28.48 (1.51) 0.247 a
Gender, n (%)
Girls 12 (50.0) 8 (33.3) 0.242 c
Boys 12 (50.0) 16 (66.7)
Twins, n (%) 8 (33.3) 8 (33.3) 1.000 c
Cesarean birth, n (%) 14 (58.3) 12 (50.0) 0.562 c
Assisted reproduction, n (%) 9 (37.5) 5 (20.8) 0.204 c
Antibiotic therapy, n (%)
Yes 10 (41.7) 8 (33.3) 0.551 c
No 14 (58.3) 16 (66.7)
Oxygen therapy, n (%)
Yes 4 (16.7) 4 (16.7) 1.000 b
No 20 (83.3) 20 (83.3)
Jaundice with phototherapy, n (%)
Yes 17 (70.8) 17 (70.8) 1.000 c
No 7 (29.2) 7 (29.2)
Caffeine, n (%)
Yes 13 (54.2) 14 (58.3) 0.771 c
No 11 (45.8) 10 (41.7)
Hospital admission days, M (SD) 37.00 (19.12) 32.25 (17.04) 0.368 a
Weight at hospital discharge, M (SD) (g) 2086.67 (283.05) 2096.46 (236.83) 0.897 a
Cranial circumference at discharge, M (SD) (cm) 32.42 (3.91) 31.38 (1.24) 0.224 a
a Student’s t-test. b Fisher’s exact test. c Pearson’s chi-squared test.

Table 2. Sociodemographic and baseline characteristics of the mothers and fathers of the intervention
group (IG) and control group (CG).

Mother Characteristics IG (n = 20) CG (n = 20) p-Value

Age, M (DE) (years) 33.80 (5.95) 32.20 (6.26) 0.413 a
Education level, n (%)
Primary 1 (5.0) 2 (10.0) 0.160 b
High school 2 (10.0) 7 (35.0)
Medium 11 (55.0) 6 (30.0)
Undergraduate 6 (30.0) 5 (25.0)
Father characteristics IG (n = 20) CG (n = 19) p value
Age, M (DE) (years) 33.40 (4.83) 33.74 (7.24) 0.866 a
Education level, n (%)
Primary 0 (0.0) 1 (5.3) 0.259 b
High school 3 (15.0) 3 (15.8)
Medium 11 (55.0) 12 (63.2)
Undergraduate 6 (30.0) 3 (15.8)
a Student’s t-test. b Linear chi-squared test.

The early physiotherapy intervention at the neonatal unit commenced and finished at
a mean age of 35- and 36-weeks PMA, respectively. At the beginning of the intervention,
the minimum age was 32 weeks PMA, and the maximum age at the end of the intervention
was 39 weeks PMA. Parents of infants allocated to the intervention group received a mean
of five education sessions, each of 45 min approximately. All the infants received the
recommended dose of tactile and kinesthetic stimulation, starting after the second parent
education session. Infants received a mean of 17.94 ± 4.05 min of stimulation per day, in
one or two sessions, during at least 10 days in a 15-day period. No parent reported stress
signs or adverse behaviors in their infants during the stimulation.
After hospital discharge, at 40 weeks PMA, all the infants allocated in the intervention
group started the home program. They received a mean of three sessions with the PT,
Children 2022, 9, 895 10 of 18

each of 45 min approximately. The program lasted 2 months in all cases. The first phase
commenced at 40 weeks PMA until 1 month corrected age, and the second phase started
at 1 month corrected age until 2 months corrected age. Although both parents were
invited to perform the intervention, the mothers were the ones who performed almost all
the interventions.

3.1. Primary Outcome Measure (AIMS)

Infants’ gross motor development was assessed after the intervention period, at
2 months corrected age, and at 8 months corrected age. As shown in Table 3, there were
no statistically significant differences between both groups in mean AIMS total or four
positional scores in either of the assessments nor within the two groups from the first to
the second assessments. The effect size in AIMS total score at 2 months corrected age was
small (r: −0.277).
The longitudinal analysis did not show statistically significant differences between the
two groups from 2 months to 8 months corrected age in any AIMS positional scores or the
total score.

3.2. Secondary Outcome Measures

ASQ-3. After the first phase of the home program was completed, at 1 month cor-
rected age, infants’ global development was assessed for the first time. When comparing
the mean differences in all subscales of the ASQ-3, fine motor, problem-solving, communi-
cation, and personal-social domains showed statistically significant differences between
groups (p-value < 0.05) (see Table 3). Gross motor development did not differ statistically
between groups. The differences in fine motor (r: −0.641), problem-solving (r: −0.416),
and communication (r: −0.418) development showed a large effect size between groups at
1 month corrected age (see Table 3).
At the second assessment, at infants’ 8 months corrected age, there were no statistically
significant differences between both groups in the five domains of the ASQ-3, and neither
were in the categorizations of global development (see Table 3).
Global development was categorized as high-risk of development delay, the need
for follow-up, or correct development. As shown in Table 4, there were statistically sig-
nificant differences between groups in fine motor, problem-solving, and communication
domain categorizations.
Children 2022, 9, 895 11 of 18

Table 3. Alberta Infant Motor Scale (AIMS) at 2- and 8-months corrected age, and Ages and Stages Questionnaire—Version 3 (ASQ-3) at 1- and 8-months of corrected
age in the intervention group (IG) and control group (CG).

2 Months Corrected Age 8 Months Corrected Age

AIMS
Z Mann Z Mann
IG (n = 20) CG (n = 22) p-Value a Effect Size b IG (n = 20) CG (n = 21) p-Value a Effect Size b
Whitney Whitney
Prone, M (SD) 2.30 (1.13) 2.73 (0.99) 0.121 −1.550 −0.239 12.30 (4.04) 12.33 (3.53) 0.875 −0.157 −0.025
Supine, M (SD) 3.15 (0.37) 3.36 (0.58) 0.190 −1.310 −0.202 7.30 (1.42) 7.29 (1.42) 0.989 −0.013 −0.002
Sitting, M (SD) 1.05 (0.22) 1.05 (0.38) 0.980 −0.025 −0.004 7.55 (2.95) 8.76 (2.05) 0.230 −1.201 −0.188
Standing positions, M (SD) 1.25 (0.64) 1.55 (0.60) 0.118 −1.563 −0.241 3.10 (0.97) 3.67 (1.02) 0.063 −2.921 −0.456
Total score, M (SD) 7.80 (1.20) 8.55 (1.50) 0.073 −1.793 −0.277 30.25 (7.15) 32.10 (6.83) 0.396 −1.045 −0.163
1 Month Corrected Age 8 Months Corrected Age
ASQ-3
Z Mann Z Mann
IG (n = 20) CG (n = 23) pValue a Effect Size b IG (n = 20) CG (n = 23) pValue a Effect Size b
Whitney Whitney
Gross Motor, M (SD) 50.00 (5.85) 49.13 (7.18) 0.830 −0.215 −0.033 38.25 (14.63) 41.09 (13.73) 0.532 −0.625 −0.095
Fine Motor, M (SD) 53.50 (5.16) 42.17 (8.64) 0.000 −4.202 −0.641 55.50 (6.05) 54.78 (5.93) 0.517 −0.648 −0.099
Problem Solving, M (SD) 49.25 (7.83) 37.39 (14.91) 0.006 −2.725 −0.416 52.50 (7.69) 55.00 (5.22) 0.351 −0.932 −0.142
Personal-Social, M (SD) 46.25 (5.10) 41.96 (6.70) 0.049 −1.972 −0.301 47.00 (11.17) 50.87 (8.61) 0.263 −1.120 −0.171
Communication, M (SD) 38.00 (12.61) 26.52 (13.52) 0.006 −2.740 −0.418 51.00 (9.40) 51.30 (7.10) 0.870 −0.163 0.025
a Mann-Whitney U test. b Mann Whitney size effect: <0.1 negligible; 0.1–0.3 small effect; 0.3–0.5 medium; >0.5 large effect.
Children 2022, 9, 895 12 of 18

Table 4. Results of Ages and Stages Questionnaire—version 3 (ASQ-3) at 1 month corrected age.

ASQ-3 at 1 Month
IG (n = 20) CG (n = 23) p-Value a
Corrected Age
Gross Motor, n (%)
High-risk 2 (10.0) 4 (17.4)
0.588
Follow-up 4 (20.0) 4 (17.4)
Correct 14 (70.0) 15 (65.2)
Fine Motor, n (%)
High-risk 0 (0) 4 (17.4)
0.003
Follow-up 1 (5.0) 7 (30.4)
Correct 19 (95.0) 12 (52.2)
Problem Solving, n (%)
High-risk 0 (0) 6 (26.1)
0.004
Follow-up 1 (5.0) 4 (17.4)
Correct 19 (95.0) 13 (56.5)
Personal-Social, n (%)
High-risk 0 (0) 2 (8.7)
0.079
Follow-up 5 (25.0) 9 (39.1)
Correct 15 (75.0) 12 (52.2)
Communication, n (%)
High-risk 2 (10.0) 9 (39.1)
0.003
Follow-up 6 (30.0) 10 (43.5)
Correct 12 (60.0) 4 (17.4)
a Linear chi-squared test.

PSI-SF. The parental post-intervention stress index was assessed at 3 months corrected
age. Mothers were the principal recipients, so 19 mothers in the control group and 16 in
the intervention group were assessed with the PSI-SF. As shown in Table 5, there were no
statistically significant differences between both groups in mean SPI-SF total or the three
subdomain scores.

Table 5. Results of parenting Stress Index (PSI-SF) post-intervention in the intervention group (IG),
and control group (CG).

Parenting Stress Index

IG (n = 16) CG (n = 19) p-Value a Size Effect b
(PSI-SF)
Parental Distress, M (SD) 26.38 (10.51) 27.05 (8.46) 0.834 0.07
Parent–Child Dysfunctional
19.69 (5.63) 18.84 (4.63) 0.629 0.16
Interaction, M (SD)
Difficult Child, M (SD) 21.75 (7.79) 21.21 (5.35) 0.810 0.08
Total Stress, M (SD) 68.31 (21.94) 67.11 (16.24) 0.853 0.06
a Student’s t-test. b Cohen’s d: 0.20: small effect; 0.50: medium size; 0.8: large effect; >1.3: very large.

Parental compliance. The daily diary of the home program was completed by 12 (75%)
mothers in the intervention group. Four mothers (25%) did not complete the diary correctly,
so they were excluded from the analyses. Five (41.67%) mothers demonstrated good
compliance, and seven (58.33%) had poor compliance. The results found an association
between parents’ compliance and infants’ development. Infants of mothers with good
compliance showed higher scores on the first assessments of AIMS or ASQ-3 compared with
those with poor compliance. However, there were no statistically significant differences.
The between-groups effect size was medium for total AIMS score at 2 months corrected age
(r: 0.43; p-value 0.121), for prone (r: 0.39; p-value 0.152) and supine (r: 0.45; p-value 0.232)
positions. Communication development at 1 month corrected age by ASQ-3 showed a large
size effect (r: 0.64; p-value 0.014) and personal-social development displayed a medium
size effect (r: 0.42; p-value 0.121). Gross and fine motor development by ASQ-3 showed a
medium size effect (r: 0.41, p-value 0.152 and r: 0.30, p-value 0.336).
Children 2022, 9, 895 13 of 18

Mothers with good compliance had lower scores in all domains of the PSI-SF. Parental
distress score was statistically lower in mothers who showed good compliance than mothers
with poor compliance (p-value 0.013), with a very large size effect (Cohen’s d: 1.76). The
total stress score was not statistically different depending on parental compliance (p-value
0.073), but it showed a very large size effect (Cohen’s d: 4.39).
Regarding additional physiotherapy interventions received between 2- and 8- months
corrected age, ten infants (50%) in the intervention group and eight (34.8%) in the control
group were given other interventions. There were no statistically significant differences
between groups in the proportion of additional physiotherapy interventions received. No
more information was asked about the kind of intervention received or the dose.

4. Discussion
Most of the early interventions provided to preterm infants aim to prevent infants’
neurodevelopment delays in the short- and long-term. In this framework, the main goal
of the early physiotherapy intervention was to prevent preterm infants’ motor and global
developmental delay and decrease the parental stress index. Results achieved in post-
intervention and short-term assessments suggest that the intervention provided, from the
neonatal period until 2 months corrected age, may not affect the overall gross motor devel-
opment of infants born preterm or the parental stress index. Nevertheless, the intervention
might improve infants’ fine motor, communication, problem-solving, and personal-social
development at post-intervention follow-up. Furthermore, although mothers showed
poor compliance with the home program, the results might suggest that preterm infants’
development at 1- and 2- months corrected age and mothers’ stress index could be related
to good parental compliance.
A recent systematic review [18], evaluating neonatal therapies for preterm infants,
found that the daily parent-delivered motor intervention improves infants’ motor and
cognitive outcomes in the short- and possibly in long term. This approach includes teaching
a parent to provide postural support and opportunities for movement with assistance
during a parent–infant interaction. Likewise, interventions starting during the NICU
period and continuing beyond the neonatal period have the strongest effect on infants’
long-term motor development [17,21,22]. Although the early physiotherapy intervention
described in the present study follows the recommendation by Khurana et al., (2020), our
findings were not consistent with a more optimal gross motor development at 2- and
8-months corrected age. A recently published randomized controlled trial concluded that
parent-administered individualized early motor intervention programs in the NICU could
substantially affect motor development in infants born preterm if the intervention dosage
is at least as high as 222 min [54]. Another piece of research published in 2001 analyzed
the effectiveness of a physiotherapy program on at-risk preterm infants. The program was
performed from 40 weeks PMA until 4 months corrected age, and the results showed more
significant improvements in infants’ motor development after receiving the physiotherapy
program [32]. Therefore, the short dose or intensity of the early physiotherapy intervention
described in the present study might be one of the reasons for the lack of group differences
in preterm infants’ motor development [22,29,32,55]. It is well known that early intervention
results in brain structure reorganization, and hence, improved outcomes [17], and it has
also been well considered that increased intervention dosage might be attributed to those
changes in the central nervous system [54,56,57].
As the present intervention targeted preterm infants and their parents, those played a
significant role in carrying out the program. In fact, the primary caregivers, in all cases the
mothers, were actively involved in the intervention: they received information regarding
their infants’ development and the aims for each activity; and were also taught to enhance
their infants’ development. Therefore, the program’s effectiveness relied partially on the
mothers’ understanding and compliance [22,31,58]. The present study followed strategies
known to be helpful to increase parents’ compliance and adherence, such as including
the exercises into daily routines, providing written instructions, and demonstrating the
Children 2022, 9, 895 14 of 18

activities with the child [59–62]. Nevertheless, mothers showed poor compliance with
the home program. Similarly, a recently published study assessing the feasibility of a
novel physiotherapy intervention for preterm infants incorporating participation goals and
telehealth delivery showed that parental adherence to dose was lower than expected as
infants attended an average of half of the prescribed session dose. The authors reported
that paternal mental health was the most common reason for non-attendance [63]. An-
other research suggested that parental adherence depends on factors such as self-efficacy,
perception of barriers and ability to perform the program [59]. Those aspects were not
considered during the development of the present project, and it might have influenced
the results related to parental compliance and, consequently, the effectiveness of the early
physiotherapy intervention. Therefore, future research should consider these findings
and study the importance of assisting parents in achieving good compliance during the
home programs.
The present study showed that mothers with good compliance with the home program
had lower stress levels in the parental distress area, which is determined by the experience of
the parental role [49,50,64]. Although parenting stress is known to be closely correlated with
children’s behavioral development [65], the evidence suggests that parents’ involvement in
the early intervention reinforces parents’ role and decreases their stress index [10,15,66,67].
A recently published qualitative study concluded that parents’ involvement in infants’
care is associated with increased empowerment. Those parents also develop more coping
strategies to deal with prematurity and challenges in the parenting role [16]. Similarly,
a randomized controlled trial studied whether early intervention focused on sensitizing
affected the parenting stress among mothers and fathers of preterm infants. The authors
found that this kind of intervention reduces maternal stress and positively influences
mothers’ perceptions of their children’s adaptability and happiness [65]. On the contrary,
it might also be suggested that less stressed mothers were more able to comply with
the proposed program, and thus produced better outcomes for the infants’ development
and mothers’ stress index. However, more research is needed in this aspect to study
these hypotheses.
Regarding the infants’ motor and global development, there is abundant evidence
supporting that certain brain circuits’ structures can change in response to environmen-
tal stimuli [68,69]. In fact, the brain’s structural-developmental processes result from
a continuous interaction between experience, activity, environment, and genes [2]. For
instance, postural control demands, which are usually presented to infants by their care-
givers, are also crucial when structuring the central nervous system [3]. The present
study showed higher percentages of the correct development of communication, problem-
solving, personal-social, and fine motor skills in the intervention group compared to the
control group. Furthermore, infants of parents that showed good compliance to the early
physiotherapy intervention displayed more optimal gross motor and global development.
Therefore, our results might suggest that infants who received the recommended dose
of the home program could show more positive gross motor and global development.
However, these results should be interpreted prudently as no statistical adjustments were
performed for the secondary outcomes.
A strength of this research is that the early physiotherapy intervention was designed
according to the latest recommendations: it started during the highly neuroplastic period in
the NICU and continued in the infant’s first months of life, and it encouraged early parental
engagement and focused on providing movement opportunities to the infant born preterm.
Moreover, all the included infants were born preterm and did not have any brain injury
during the neonatal period or later, which reduced the heterogeneity of the participants.
However, several limitations should be considered. Firstly, the possible interpretations
might be hard to justify due to the lack of pre-intervention assessments related to infants’
gross motor or global development and parental stress index. While it is true that there are
no data to ensure the probable effect of the early physiotherapy intervention program, it is
reasonable to say that infants started from a similar situation because all the assessed param-
Children 2022, 9, 895 15 of 18

eters at baseline—factors that could influence infants’ neurodevelopment [70]—showed

there were no differences between groups. For that reason, the results suggest that dis-
played differences could be a consequence of the intervention. Secondly, in the present
study, researchers could not control the criteria for deciding whether or not a child received
additional therapy between 2- and 8-months corrected age. Consequently, infants could
have received additional interventions based on different criteria, which could have bi-
ased these results. Furthermore, the hospital’s protocols and logistics were unavoidable
barriers when we proposed administering a different assessment tool and follow-up time
points. Hence, it was impossible to use other assessment tools that are more sensitive for
the preterm infants population, such as the TIMP. Another weakness was that relevant
adjustments were only carried out with the primary outcome (the AIMS), and the results
related to the secondary outcomes must be interpreted prudently. Multiplicity refers to
the potential inflation of the type I error rate as a result of multiple testing. So, further
confirmatory studies are needed to support the findings on the infants’ global development
and parents’ stress index. Moreover, a multiple linear regression analysis between sociode-
mographic variables, parental involvement in the intervention group, and infants’ gross
motor development in the post-intervention assessment could not be performed due to the
limited sample size. Future research should include a larger sample size to be able to build
more powerful statistic models. Regarding parental compliance, it was assessed only at the
end of the home program by a non-standardized tool. Thus, more research is worthwhile
looking at the parent diaries as the home program intervention is provided to encourage
higher parental compliance, if necessary, for example, by increasing the frequency of visits.
Moreover, further investigation is needed to establish standardized and validated parental
compliance recording tools. Finally, the present study included infants of parents that were
in the NICU for 6 or more hours a day. This must be considered when interpreting the
results. While it is essential to engage parents in early intervention, it is also important to
consider that those who are unable to be present might be the ones that need to be targeted
because they might benefit from the intervention and the education demonstrating better
intervention effects. Therefore, future research should take this consideration into account.

5. Conclusions
The results of this RCT suggest that the early physiotherapy intervention was not
effective on preterm infants’ motor or global outcomes nor on parental stress index. These
results might be related to the dose or intensity of the intervention, but also to poor parental
compliance. Furthermore, there is the possibility that parental higher compliance impacted
on mother’s stress index positively, as mothers with high compliance showed a lower stress
index. Further research should consider these findings.

Author Contributions: Conceptualization, M.O.-A., L.L.S., M.E.C.S. and M.T.-M.; methodology,

M.O.-A., M.T.-M., M.I. and J.C.C.-B.; formal analysis, M.O.-A., M.T.-M. and J.C.C.-B.; investigation,
M.O.-A., L.L.S., M.E.C.S., M.F.M., I.M.P. and T.A.-Q.; resources, M.O.-A.; data curation, M.O.-A., L.L.S.,
M.E.C.S., M.F.M., I.M.P. and T.A.-Q.; writing—original draft preparation, M.O.-A., M.T.-M., J.C.C.-B.
and M.I.; writing—review and editing, M.O.-A., M.T.-M., L.L.S., M.E.C.S., M.F.M., I.M.P., T.A.-Q.,
M.I. and J.C.C.-B.; visualization, M.T.-M.; supervision, M.O.-A. and M.T.-M.; project administration,
M.O.-A.; funding acquisition, M.O.-A. All authors have read and agreed to the published version of
the manuscript.
Funding: This research was funded by the Catalan Board of Physical Therapist, grant number
R2/2018.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki, and approved by the Ethics Committee of Fundació Sant Joan de Déu in Barcelona
(protocol code PIC-139-17 on 26 October 2017).
Informed Consent Statement: Informed consent was obtained from all parents involved in the study.
Data Availability Statement: Not applicable.
Children 2022, 9, 895 16 of 18

Acknowledgments: The authors acknowledge and thank all the families and preterm infants and
all the staff from the NICU at the Sant Joan de Déu Barcelona Children’s Hospital. The authors
also acknowledge the Research Group Methodology, Methods, Models and Outcomes of Health
and Social Sciences (M3 O), the University of Vic—Central University of Catalunya for their support,
and the Catalan Board of Physical Therapist for funding. The sincerest acknowledgement for Gunn
Kristin Øberg.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Mottahedin, A.; Ardalan, M.; Chumak, T.; Riebe, I.; Ek, J.; Mallard, C. Effect of Neuroinflammation on Synaptic Organization and
Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders. Front. Cell. Neurosci.
2017, 11, 190. [CrossRef] [PubMed]
2. Hadders-Algra, M. Early Human Brain Development: Starring the Subplate. Neurosci. Biobehav. Rev. 2018, 92, 276–290. [CrossRef]
[PubMed]
3. Valentini, N.C.; Pereira, K.R.G.; Chiquetti, E.M.D.S.; Formiga, C.K.M.R.; Linhares, M.B.M. Motor Trajectories of Preterm and
Full-Term Infants in the First Year of Life. Pediatr. Int. 2019, 61, 967–977. [CrossRef] [PubMed]
4. Albuquerque, P.L.D.; Lemos, A.; Guerra, M.Q.D.F.; Eickmann, S.H. Accuracy of the Alberta Infant Motor Scale (AIMS) to Detect
Developmental Delay of Gross Motor Skills in Preterm Infants: A Systematic Review. Dev. Neurorehabilit. 2015, 18, 15–21.
[CrossRef] [PubMed]
5. van Haastert, I.C.; de Vries, L.S.; Helders, P.J.M.; Jongmans, M.J. Early Gross Motor Development of Preterm Infants According to
the Alberta Infant Motor Scale. J. Pediatr. 2006, 149, 617–622. [CrossRef] [PubMed]
6. Dusing, S.C.; Kyvelidou, A.; Mercer, V.S.; Stergiou, N. Infants Born Preterm Exhibit Different Patterns of Center-of-Pressure
Movement Than Infants Born at Full Term. Phys. Ther. 2009, 89, 1354–1362. [CrossRef]
7. Baumann, N.; Bartmann, P.; Wolke, D. Health-Related Quality of Life into Adulthood after Very Preterm Birth. Pediatrics 2016,
137, e20153148. [CrossRef]
8. Lobo, M.A.; Harbourne, R.T.; Dusing, S.C.; McCoy, S.W. Grounding Early Intervention: Physical Therapy Cannot Just Be About
Motor Skills Anymore. Phys. Ther. 2013, 93, 94–103. [CrossRef]
9. Dusing, S.C.; Tripathi, T.; Marcinowski, E.C.; Thacker, L.R.; Brown, L.F.; Hendricks-muñoz, K.D. Supporting Play Exploration
and Early Developmental Intervention versus Usual Care to Enhance Development Outcomes during the Transition from the
Neonatal Intensive Care Unit to Home: A Pilot Randomized Controlled Trial. BMC Pediatr. 2018, 18, 46. [CrossRef]
10. Puthussery, S.; Chutiyami, M.; Tseng, P.; Kilby, L.; Kapadia, J. Effectiveness of Early Intervention Programs for Parents of Preterm
Infants: A Meta-Review of Systematic Reviews. BMC Pediatr. 2018, 18, 223. [CrossRef]
11. Muller-Nix, C.; Forcada-Guex, M.; Pierrehumbert, B.; Jaunin, L.; Borghini, A.; Nasermet, F. Prematurity, Maternal Stress and
Mother-Child Interactions. Early Hum. Dev. 2004, 79, 145–158. [CrossRef] [PubMed]
12. Benzies, K.M.; Magill-Evans, J.E.; Hayden, K.A.; Ballantyne, M. Key Components of Early Intervention Programs for Preterm
Infants and Their Parents: A Systematic Review and Meta-Analysis. BMC Pregnancy Childbirth 2013, 13, S10. [CrossRef] [PubMed]
13. Håkstad, R.B.; Obstfelder, A.; Øberg, G.K. Parents’ Perceptions of Primary Health Care Physiotherapy with Preterm Infants:
Normalization, Clarity, and Trust. Qual. Health Res. 2016, 26, 1341–1350. [CrossRef] [PubMed]
14. Al Maghaireh, D.F.; Abdullah, K.L.; Chan, C.M.; Piaw, C.Y.; Al Kawafha, M.M. Systematic Review of Qualitative Studies Exploring
Parental Experiences in the Neonatal Intensive Care Unit. J. Clin. Nurs. 2016, 25, 2745–2756. [CrossRef] [PubMed]
15. Øberg, G.K.; Ustad, T.; Jørgensen, L.; Kaaresen, P.I.; Labori, C.; Girolami, G.L. Parents’ Perceptions of Administering a Motor
Intervention with Their Preterm Infant in the NICU. Eur. J. Physiother. 2018, 21, 134–141. [CrossRef]
16. Ochandorena-Acha, M.; Noell-Boix, R.; Yildirim, M.; Iriondo-Sanz, M.; Troyano-Martos, M.J.; Casas-Baroy, J.C. Experiences and
Coping Strategies of Preterm Infants’ Parents and Parental Competences after Early Physiotherapy Intervention: Qualitative
Study. Physiother. Theory Pract. 2020, 1–14. [CrossRef]
17. Spittle, A.; Treyvaud, K.; Hons, B. The Role of Early Developmental Intervention to Influence Neurobehavioral Outcomes of
Children Born Preterm. Semin. Perinatol. 2016, 40, 542–548. [CrossRef]
18. Khurana, S.; Kane, A.E.; Brown, S.E.; Tarver, T.; Dusing, S.C. Effect of Neonatal Therapy on the Motor, Cognitive, and Behavioral
Development of Infants Born Preterm: A Systematic Review. Dev. Med. Child Neurol. 2020, 62, 684–692. [CrossRef]
19. Schwarz, D.F.; O’Sullivan, A.L.; Guinn, J.; Mautone, J.A.; Carlson, E.C.; Zhao, H.; Zhang, X.; Esposito, T.L.; Askew, M.; Radcliffe, J.
Promoting Early Intervention Referral Through a Randomized Controlled Home-Visiting Program. J. Early Interv. 2012, 34, 20–39.
[CrossRef]
20. Spittle, A.J.; Anderson, P.J.; Lee, K.J.; Ferretti, C.; Eeles, A.; Orton, J.; Boyd, R.N.; Inder, T.; Doyle, L.W. Preventive Care at Home
for Very Preterm Infants Improves Infant and Caregiver Outcomes at 2 Years. Pediatrics 2010, 126, e171–e178. [CrossRef]
21. Hughes, A.J.; Redsell, S.A.; Glazebrook, C. Motor Development Interventions for Preterm Infants: A Systematic Review and
Meta-Analysis. Pediatrics 2016, 138, e20160147. [CrossRef] [PubMed]
Children 2022, 9, 895 17 of 18

22. Spittle, A.; Orton, J.; Anderson, P.; Boyd, R.; Doyle, L.W. Early Developmental Intervention Programmes Post-Hospital Discharge
to Prevent Motor and Cognitive Impairments in Preterm Infants. Cochrane Database Syst. Rev. 2015, 11, CD005495. [CrossRef]
[PubMed]
23. Guralnick, M.J. Preventive Interventions for Preterm Children: Effectiveness and Developmental Mechanisms. J. Dev. Behav.
Pediatr. 2012, 33, 352–364. [CrossRef] [PubMed]
24. Procianoy, R.S.; Mendes, E.W.; Silveira, R.C. Massage Therapy Improves Neurodevelopment Outcome at Two Years Corrected
Age for Very Low Birth Weight Infants. Early Hum. Dev. 2010, 86, 7–11. [CrossRef] [PubMed]
25. Nordhov, S.M.; Ronning, J.A.; Dahl, L.B.; Ulvund, S.E.; Tunby, J.; Kaaresen, P.I. Early Intervention Improves Cognitive Outcomes
for Preterm Infants: Randomized Controlled Trial. Pediatrics 2010, 126, e1088-94. [CrossRef] [PubMed]
26. Kynø, N.M.; Ravn, I.H.; Lindemann, R.; Fagerland, M.W.; Smeby, N.A.; Torgersen, A.M. Effect of an Early Intervention Programme
on Development of Moderate and Late Preterm Infants at 36 Months: A Randomized Controlled Study. Infant Behav. Dev. 2012,
35, 916–926. [CrossRef]
27. Kanagasabai, P.S.; Mohan, D.; Lewis, L.E.; Kamath, A.; Rao, B.K. Effect of Multisensory Stimulation on Neuromotor Development
in Preterm Infants. Indian J. Pediatr. 2013, 80, 460–464. [CrossRef]
28. Fucile, S.; Gisel, E.G. Sensorimotor Interventions Improve Growth and Motor Function in Preterm Infants. Neonatal Netw. 2010,
29, 359–366. [CrossRef]
29. Ustad, T.; Evensen, K.A.I.; Campbell, S.K.; Girolami, G.L.; Helbostad, J.; Jorgensen, L.; Kaaresen, P.I.; Oberg, G.K. Early
Parent-Administered Physical Therapy for Preterm Infants: A Randomized Controlled Trial. Pediatrics 2016, 138, e20160271.
[CrossRef]
30. Wu, Y.-C.; Leng, C.-H.; Hsieh, W.-S.; Hsu, C.-H.; Chen, W.J.; Gau, S.S.-F.; Chiu, N.-C.; Yang, M.-C.; Fang, L.-J.; Hsu, H.-C.; et al. A
Randomized Controlled Trial of Clinic-Based and Home-Based Interventinos in Comparison with Usual Care for Preterm Infants:
Effects and Mediators. Res. Dev. Disabil. 2014, 35, 2384–2393. [CrossRef]
31. Cameron, E.C.; Maehle, V.; Reid, J. The Effects of an Early Physical Therapy Intervention for Very Preterm, Very Low Birth Weight
Infants: A Randomized Controlled Clinical Trial. Pediatr. Phys. Ther. 2005, 17, 107–119. [CrossRef] [PubMed]
32. Lekskulchai, R.; Cole, J. Effect of a Developmental Program on Motor Performance in Infants Born Preterm. Aust. J. Physiother.
2001, 47, 169–176. [CrossRef]
33. Jeong, J.; Pitchik, H.O.; Fink, G. Short-Term, Medium-Term and Long-Term Effects of Early Parenting Interventions in Low-and
Middle-Income Countries: A Systematic Review. BMJ Glob. Health 2021, 6, e004067. [CrossRef]
34. Schulz, K.F.; Altman, D.G.; Moher, D.; CONSORT Group. CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel
Group Randomised Trials. BMJ 2010, 340, 698–702. [CrossRef] [PubMed]
35. World Medical Association (WMA). WMA Declaration Of Helsinki—Ethical Principles for Scientic Requirements and Research Protocols;
World Medical Association: Ferney-Voltaire, France, 2013; pp. 29–32.
36. Morales-Monforte, E.; Bagur-Calafat, C.; Suc-Lerin, N.; Fornaguera-Martí, M.; Cazorla-Sánchez, E.; Girabent-Farrés, M. The
Spanish Version of the Alberta Infant Motor Scale: Validity and Reliability Analysis. Dev. Neurorehabilit. 2017, 20, 76–82. [CrossRef]
37. Heathcock, J.C.; Lobo, M.; Galloway, J.C. Movement Training Advances the Emergence of Reaching in Infants Born at Less than
33 Weeks of Gestational Age: A Randomized Clinical Trial. Phys. Ther. 2008, 88, 310–322. [CrossRef]
38. Marrugat, J.; Vila, J.; Pavesi, M.; Sanz, F. Estimation of the Sample Size in Clinical and Epidemiological Investigations. Med. Clin.
1998, 111, 267–276.
39. Vanderveen, J.; Bassler, D.; Robertson, C.; Kirpalani, H. Early Interventions Involving Parents to Improve Neurodevelopmental
Outcomes of Premature Infants: A Meta-Analysis. J. Perinatol. 2009, 29, 343–351. [CrossRef]
40. de Albuquerque, P.L.; de Farias Guerra, M.Q.; de Carvalho Lima, M.; Eickmann, S.H. Concurrent Validity of the Alberta Infant
Motor Scale to Detect Delayed Gross Motor Development in Preterm Infants: A Comparative Study with the Bayley III. Dev.
Neurorehabilit. 2017, 21, 408–414. [CrossRef]
41. Sarmiento Camposa, J.A.; Squires, J.; Ponte, J. Universal Developmental Screening: Preliminary Studies in Galicia, Spain. Early
Child Dev. Care 2011, 181, 475–485. [CrossRef]
42. van Heerden, A.; Hsiao, C.; Matafwali, B.; Louw, J.; Richter, L. Support for the Feasibility of the Ages and Stages Questionnaire as
a Developmental Screening Tool: A Cross-Sectional Study of South African and Zambian Children Aged 2–60 Months. BMC
Pediatr. 2017, 17, 55. [CrossRef] [PubMed]
43. Agarwal, P.K.; Shi, L.; Daniel, L.M.; Yang, P.H.; Khoo, P.C.; Quek, B.H.; Zheng, Q.; Rajadurai, V.S. Prospective Evaluation of
the Ages and Stages Questionnaire 3rd Edition in Very-Low-Birthweight Infants. Dev. Med. Child Neurol. 2017, 59, 484–489.
[CrossRef] [PubMed]
44. Squires, J.; Bricker, D.; Potter, L.W. Revision of a Parent-Completed Developmental Screening Tool: Ages and Stages Question-
naires. J. Pediatr. Psychol. 1997, 22, 313–328. [CrossRef] [PubMed]
45. Otalvaro, A.M.R.; Grañana, N.; Gaeto, N.; Torres, M.D.L.Á.; Zamblera, M.N.; Vasconez, M.A.; Squires, J. ASQ-3: Validation of the
Ages and Stages Questionnaire for the Detection of Neurodevelopmental Disorders in Argentine Children. Arch. Argent. Pediatr.
2018, 116, 7–13. [CrossRef]
46. Schonhaut, L.; Armijo, I.; Schonstedt, M.; Alvarez, J.; Cordero, M. Validity of the Ages and Stages Questionnaires in Term and
Preterm Infants. Pediatrics 2013, 131, e1468–e1474. [CrossRef]
Children 2022, 9, 895 18 of 18

47. Singh, A.; Yeh, C.J.; Boone Blanchard, S. Ages and Stages Questionnaire: A Global Screening Scale. Boletín Médico Hosp. Infant.
México 2017, 74, 5–12. [CrossRef]
48. Pérez-Padilla, J.; Menéndez, S.; Lozano, O. Validity of the Parenting Stress Index Short Form in a Sample of At-Risk Mothers. Eval.
Rev. 2015, 39, 428–446. [CrossRef]
49. Díaz-Herrero, Á.; López-Pina, J.A.; Pérez-López, J.; de la Nuez, A.G.B.; Martínez-Fuentes, M.T. Validity of the Parenting Stress
Index-Short Form in a Sample of Spanish Fathers. Span. J. Psychol. 2011, 14, 990–997. [CrossRef]
50. Díaz-Herrero, Á.; Brito de la Nuez, A.G.; López Pina, J.A.; Pérez-López, J.; Martínez-Fuentes, M.T. Estructura Factorial y
Consistencia Interna de La Versión Española Del Parenting Stress Index-Short Form. Psicothema 2010, 22, 1033–1038.
51. Barton, B.; Peat, J. Medical Statistics. A Guide to SPSS, Data Analysis and Critical Appraisal; John Wiley & Sons: Hoboken, NJ,
USA, 2014.
52. Cohen, J. The Earth Is Round! Am. Psychol. 1994, 49, 997–1003. [CrossRef]
53. Field, A. Discovering Statistics Using SPSS, 2nd ed.; Sage Publications: London, UK, 2005; ISBN 0-7619-4452-4.
54. Øberg, G.K.; Girolami, G.L.; Campbell, S.K.; Ustad, T.; Heuch, I.; Jacobsen, B.K.; Kaaresen, P.I.; Aulie, V.S.; Jørgensen, L. Effects of
a Parent-Administered Exercise Program in the Neonatal Intensive Care Unit: Dose Does Matter—A Randomized Controlled
Trial. Phys. Ther. 2020, 100, 860–869. [CrossRef] [PubMed]
55. Spittle, A.J.; Treyvaud, K.; Lee, K.J.; Anderson, P.J.; Doyle, L.W. The Role of Social Risk in an Early Preventative Care Programme
for Infants Born Very Preterm: A Randomized Controlled Trial. Dev. Med. Child Neurol. 2018, 60, 54–62. [CrossRef] [PubMed]
56. Ismail, F.Y.; Fatemi, A.; Johnston, M.V. Cerebral Plasticity: Windows of Opportunity in the Developing Brain. Eur. J. Paediatr.
Neurol. 2017, 21, 23–48. [CrossRef] [PubMed]
57. Belsky, J.; de Haan, M. Annual Research Review: Parenting and Children’s Brain Development: The End of the Beginning. J. Child
Psychol. Psychiatry Allied Discip. 2011, 52, 409–428. [CrossRef] [PubMed]
58. Orton, J.; Spittle, A.; Doyle, L.; Anderson, P.; Boyd, R. Do Early Intervention Programmes Improve Cognitive and Motor Outcomes
for Preterm Infants after Discharge? A Systematic Review. Dev. Med. Child Neurol. 2009, 51, 851–859. [CrossRef] [PubMed]
59. Medina-Mirapeix, F.; Lillo-Navarro, C.; Montilla-Herrador, J.; Gacto-Sánchez, M.; Franco-Sierra, M.A.; Escolar-Reina, P. Predictors
of Parents’ Adherence to Home Exercise Programs for Children with Developmental Disabilities, Regarding Both Exercise
Frequency and Duration: A Survey Design. Eur. J. Phys. Rehabil. Med. 2017, 53, 545–555. [CrossRef]
60. Santer, M.; Ring, N.; Yardley, L.; Geraghty, A.W.A.; Wyke, S. Treatment Non-Adherence in Pediatric Long-Term Medical
Conditions: Systematic Review and Synthesis of Qualitative Studies of Caregivers’ Views. BMC Pediatr. 2014, 14, 63. [CrossRef]
61. McConnell, D.; Parakkal, M.; Savage, A.; Rempel, G. Parent-Mediated Intervention: Adherence and Adverse Effects. Disabil.
Rehabil. 2015, 37, 864–872. [CrossRef]
62. Lillo-Navarro, C.; Medina-Mirapeix, F.; Escolar-Reina, P.; Montilla-Herrador, J.; Gomez-Arnaldos, F.; Oliveira-Sousa, S.L. Parents
of Children with Physical Disabilities Perceive That Characteristics of Home Exercise Programs and Physiotherapists’ Teaching
Styles Influence Adherence: A Qualitative Study. J. Physiother. 2015, 61, 81–86. [CrossRef]
63. Mobbs, C.; Spittle, A.; Johnston, L. PreEMPT (Preterm Infant Early Intervention for Movement and Participation Trial): Feasibility
Outcomes of a Randomised Controlled Trial. Early Hum. Dev. 2022, 166, 105551. [CrossRef]
64. Roué, J.M.; Kuhn, P.; Maestro, M.L.; Maastrup, R.A.; Mitanchez, D.; Westrup, B.; Sizun, J. Eight Principles for Patient-Centred and
Family-Centred Care for Newborns in the Neonatal Intensive Care Unit. Arch. Dis. Child. -Fetal Neonatal Ed. 2017, 102, F364–F368.
[CrossRef] [PubMed]
65. Landsem, I.P.; Handegård, B.H.; Tunby, J.; Ulvund, S.E.; Rønning, J.A. Early Intervention Program Reduces Stress in Parents of
Preterms during Childhood, a Randomized Controlled Trial. Trials 2014, 15, 387. [CrossRef] [PubMed]
66. Kaaresen, P.I.; Ronning, J.A.; Ulvund, S.E.; Dahl, L.B.; Rønning, J.A.; Ulvund, S.E.; Dahl, L.B. A Randomized, Controlled Trial of
the Effectiveness of an Early-Intervention Program in Reducing Parenting Stress After Preterm Birth. Pediatrics 2006, 118, e9–e19.
[CrossRef] [PubMed]
67. Newnham, C.A.; Milgrom, J.; Skouteris, H. Effectiveness of a Modified Mother-Infant Transaction Program on Outcomes for
Preterm Infants from 3 to 24 Months of Age. Infant Behav. Dev. 2009, 32, 17–26. [CrossRef] [PubMed]
68. Johnston, M.V. Plasticity in the Developing Brain: Implications for Rehabilitation. Dev. Disabil. Res. Rev. 2009, 15, 94–101.
[CrossRef]
69. Chen, R.; Cohen, L.G.; Hallett, M. Nervous System Reorganization Following Injury. Neuroscience 2002, 111, 761–773. [CrossRef]
70. Duncan, A.F.; Matthews, M.A. Neurodevelopmental Outcomes in Early Childhood. Clin. Perinatol. 2018, 45, 377–392. [CrossRef]