Early Human Development 142 (2020) 104942

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Early Human Development

journal homepage: www.elsevier.com/locate/earlhumdev

Movement analysis in early infancy: Towards a motion biomarker of age T

a,b,⁎ b c b d c c
V. Marchi , V. Belmonti , F. Cecchi , M. Coluccini , P. Ghirri , A. Grassi , A.M. Sabatini ,
A. Guzzettab,e
a
Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
b
Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, Pisa, Italy
c
The BioRobotics Institute and the Department of Excellence in Robotics & AI, Scuola Superiore Sant'Anna, Pisa, Italy
d
Department of Maternal and Child Health, Division of Neonatology and Neonatal Intensive Care Unit, Santa Chiara Hospital, University of Pisa, Pisa, Italy
e
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

A R T I C LE I N FO A B S T R A C T

Keywords: Background: Early motor development is characterized by progressive changes in general movements paralleled
Spontaneous motor activity by a gradual organization of the four limbs' repertoire towards the midline, as shown by computerised movement
Early motor development analysis.
Computerised motor analysis Aims: Our aim was to test the performance of quantitative computerised kinematic indexes as predictors of post-
Infant kinematic
term age in an independent cohort of typically developing subjects at fidgety age, tested cross-sectionally.
Subjects: We selected twelve low risk term infants, who were video recorded between 9 and 20 weeks (fidgety
age) during one spontaneous movements session.
Study design: We correlated post-term age with I)indexes of coordination including interlimb correlation of
velocity and position, II)indexes of distance, including interlimb and limb-to- ground, both expressed as linear
distance and as probability of midline limbs position III)indexes of global movement quality by calculating
Hjorth's activity, mobility and complexity parameters. All indexes were calculated for both upper and lower
limbs.
Results: Significant positive correlations were found between post-term age and indexes of distance, and prob-
ability of occurrence of upper-limb antigravity patterns, and with both indexes of global movement quality. By
combining linear and non-linear parameters related to the upper limb kinematics, we determined individual
post-term age with a mean error of < 1 week (5.2 days). No correlations were found between age and indexes of
coordination.
Conclusions: Quantitative computerised analysis of upper-limb movements is a promising predictor of post-term
age in typically developing subjects at fidgety age.

1. Introduction 2 months post-term and normal fidgety movements from 2 to 5 months

The interest towards the early epochs of human development is
increasing across scientific disciplines. Starting in utero, sensorimotor
behaviour develops from self-organizing, spontaneously- generated
activity and, through recurrence of actions and paired reactions to
sensory stimulation, eventually drives the emergence of intentionality
[1]. Spontaneous motor activity, also referred to as General Movements
(GMs), is endogenously generated by central pattern generators and can
be therefore considered as the overt manifestation of the integrated
activity of cortical, subcortical and cerebellar networks [2,3]. The ab-
sence of typical GM patterns (i.e. normal writhing movements until
post-term) is an early neurologic biomarker of an abnormal neuromotor
outcome, and in particular, cerebral palsy [4,5].
The GM assessment is ideal for implementation as a clinical
screening instrument, as it is a tool evaluating an on-off phenomenon,
i.e. the presence/absence of the pattern [5]. It is less precise in cap-
turing the fine maturational changes occurring during the first
5 months of development, which consist of the maturation of motor
patterns of increasing complexity that emerge alongside GMs. Typi-
cally, after birth, the lower limbs are the first to be lifted and then
organized towards the midline (foot-foot contact and exploration),
while the antigravity activity of the upper limbs appears later, with

Abbreviations: GMs, general movements; PTA, post-term age; LH, left hand; RH, right hand; LF, left foot; RF, right foot
⁎
Corresponding author at: IRCCS Fondazione Stella Maris, Viale del Tirreno, 331, 56128 Calambrone (Pisa), Italy.
E-mail address: vmarchi@fsm.unipi.it (V. Marchi).

https://doi.org/10.1016/j.earlhumdev.2019.104942
Received 1 August 2019; Received in revised form 14 December 2019; Accepted 15 December 2019
0378-3782/ © 2019 Published by Elsevier B.V.
V. Marchi, et al.
swipes and oscillations. Subsequently, upper limb movements are pro-
gressively organized towards the midline and stabilized to ensure hand-
to-hand and hand-to-mouth exploration, while gaze is progressively
coordinated to monitor the ongoing action. When GMs disappear, after
the end of the 5th month, the motor repertoire appears more mature
and goal-directed movements become more consistent and accurate
[6–8].
A growing body of literature has focused on the assessment of the
additional motor repertoire co-occurring with fidgety GMs as an in-
dicator of atypical development. It has been shown that, even in pre-
sence of normal fidgety movements, an abnormal or poor motor re-
pertoire is predictive of minor neurological dysfunctions and correlates
with suboptimal cognitive and/or language skills at school age
[7,9,10]. Similar to the assessment of GMs, however, the assessment of
the additional motor repertoire is typically based on visual pattern re-
cognition and qualitative judgements, and therefore examiner-depen-
dent. 3D motion tracking has been recently proposed for an objective
analysis of early motor repertoire, providing several quantitative de-
scriptors of the ongoing complex dynamics of motor development along
the fidgety period. This reinforces the interest towards the global motor
repertoire as a marker of typical and atypical neurodevelopment
[11–15].
The pioneering work of Meinecke et al. in 2006 [11], combined
with the analysis conducted by Disselhorst-Klug et al. [12], introduced
a model based on 8 parameters related to feet velocities and accelera-
tions across longitudinal recordings. It revealed good sensitivity in
differentiating typical infants from infants at neurodevelopmental risk,
thus moving the focus from the fingerprint of fidgety to a broader
concept of typical vs atypical limb kinematics. More recently, attention
was shifted from absolute limb kinematics to dynamics of relative
metrics such as inter-limb distances or limb height from the ground.
Kanemaru et al. [13] explored the interlimb coordination in typi-
cally developing infants between the 2nd and the 4th month of age.
They found different maturational dynamics in legs and arms which are
consistent with observational studies that showed a stabilization of leg
posture and movements at the beginning of fidgety age, yet increasingly
higher variability of the arm movements along the whole period. These
maturational aspects were also targeted by the recent work of Miya-
gashima et al. [15] who focused on the organization of the motor re-
pertoire expressed as inter-leg and inter-arm distances and mean height
from the ground, in full term and preterm infants in the first 3 months
of post-term life. They showed a progressive enrichment of antigravity
limb movements along development in both term infants and preterm
infants with normal GMs. However, preterm infants with pathological
GMs showed an abnormal antigravity limbs repertoire, particularly
after the 2nd month of corrected age, i.e. the beginning of the fidgety
period.
Altogether, these recent studies support the application of quanti-
tative indexes of motor repertoire to characterize movement repertoire
maturation in typical infants. Indeed, quantitative indexes of motor
repertoire were shown to have a developmental trajectory in the same
infant (i.e. longitudinally), but little is known on the validity of these
measures in predicting individual absolute age (i.e. cross-sectionally).
Sensitive cross-sectional indexes of age in typically developing infants
should they be identified, as they would be ideal early biomarkers of
neurodevelopment, potentially apt to identify atypical trajectories in
infants at risk.
The general aim of this study was to test the performance of
quantitative kinematic indexes as predictors of post-term age (PTA), in
an independent cohort of typically developing subjects at fidgety age. In
order to determine the best predictors of post-term age, a set of quan-
titative motor indexes for both upper and lower limbs derived from
three different approaches were tested within a regression model.
To this aim, we tested indexes of coordination in terms of interlimb
correlation of velocity and position, as identified by Kanemaru et al.
[13] - analysis 1. Indexes of distance in terms of distance inter-limb and
2
Early Human Development 142 (2020) 104942
from the ground, as assessed by Myagashima et al. [15], were also
considered - analysis 2. Within this analysis, we also considered infant's
motor repertoire as the behavioural result of a probabilistic process, by
which specific motor patterns emerge from the ongoing interaction of
several neural and non-neural systems [16,17]. In this perspective, we
tested the hypothesis that the probability of limbs location at any time
in a mature posture increases with age, by calculating probability in-
dexes of minimal distance and maximal height between hands and feet.
Finally, we considered indexes of global movement quality in terms of
the change through development from a diffuse, uncoordinated motor
activity of all limbs to increasingly selective and coordinated patterns
[8,13] - analysis 3. We thus tested the performance of non-linear
methods to predict infant's age, by calculating Hjorth's activity, mobi-
lity and complexity parameters, which proved effective in extracting
recurrent features from biological signals [18].
2. Methods
This work is part of a larger project started in 2015 and studying the
kinematics of infant motricity in term and preterm infants born at the
Santa Chiara University Hospital in Pisa (Regional Pediatric Ethical
Committee approval, protocol number: AGMA2015, and renewed in
November 2017). For the purposes of this study, we included twelve
consecutive infants from the larger project cohort, fulfilling the fol-
lowing inclusion criteria: i) a gestational age of 35 weeks or above; ii) at
least one recording between 9 and 20 weeks corrected for term birth
(i.e. 40 weeks and 0 days); iii) no signs or history of complications
during pregnancy, at delivery or postnatally; iv) Apgar score at 5 min
above 8, birth weight and head circumference above the 10th centile
and umbilical cord Ph within the normal range.
2.1. Recording protocol
The recording set up was prepared at the Movement Analysis
Laboratory of the IRCCS Stella Maris Institute of Pisa; all the recordings
were performed by M.C. GMs recordings were acquired in agreement
with the standard protocol according to the GMs Trust [19]: sponta-
neous motility was recorded for at least 3 min with the baby lying su-
pine, during active wakefulness and minimizing environmental inter-
ferences. If the baby got fussy, the recording was interrupted and re-
started when the infant calmed. Within the same session, each infant
was recorded three consecutive times, in order to test the stability of the
kinematic parameters across different recordings. Parents were asked to
attend the entire session.
2.2. Motion analysis system
The kinematics of the lower and the upper limb were assessed using
an optoelectronic motion analysis system (SMART-D, BtS, Italy),
equipped with ten infrared camera operating at 200 fps.
Six small reflective markers (diameter of 1 cm) were fixed with
medical grade tape on the dorsal surface of each hand and of each foot,
on the glabella (the glabella is the space between the eyebrows and
above the nose), and on the pubic symphysis in order to reconstruct the
movement of the hands and the feet, of the head and the trunk. The 3D
coordinates of the markers were extracted and exported in Matlab (The
MathWorks, Natick, MA, USA) using the Visual 3D software (C-motion,
USA).
A video was synchronously recorded for the qualitative scoring of
movement patterns.
2.3. Data processing
3D marker trajectories (position signals), were made available from
the optoelectronic motion analysis system for further processing using
custom analysis software written in MATLAB (The MathWorks, Natick,
V. Marchi, et al. Early Human Development 142 (2020) 104942

MA, USA). Raw position signals were checked in each spatial co-
ordinate for the presence of gaps due to marker occlusions. Gaps
lasting < 500 ms were filled using the MATLAB function fillgaps with
the default settings. Custom functions were written to isolate fragments
of position signals that (a) were gap-free after gap filling, (b) lasted
60 s, (c) existed for both hands and feet simultaneously in all spatial
coordinates (position epochs). In one case, we were unable to get three
gap-free 1-min position epochs (one for each trial performed for each
infant). These constraints reduced the dataset to N = 8 infants. The
position epochs were filtered using a forward-backward second-order
low-pass Butterworth filter (cut-off frequency: 10 Hz). Velocity epochs
were then computed using the Continuous Wavelet Transform (CWT)
through Gaussian wavelet Gauss1 at scale a = 0.09 [20]. CWT differ-
entiation was iterated two additional times, to get acceleration and jerk
epochs.
2.4. Quantitative movement analysis
Signal time series of limb movements were processed according to
three different analysis, as per the aims of the study.
2.4.3. Analysis 3. Indexes of global movement quality
In the aim of describing the increase in complexity in pattern of
general motricity, we decided to introduce a non-linear measure in the
analysis of the times-series for the moving limbs by estimating the
Hjorth parameters. Velocity, acceleration and jerk epochs were used to
compute the Hjorth's activity, mobility, and complexity, respectively
[18]. The computation was based on using a sliding window of width
1 s (overlapping: 50%). The first and the last windows were discarded
to remove transient effects due to filtering and CWT differentiation. The
Hjorth parameters of velocity signals were computed and averaged
across windows, spatial components and body side for hands and feet,
separately. According to the paradigm proposed by Hjorth, activity (A)
provides a measure of the squared standard deviation of velocity, ex-
pressed in m/s; the mobility (M) provides a measure of the slope, that is
the acceleration, with reference to the standard deviation of velocity,
expressed in Hz; complexity (C), that is dimensionless, quantifies any
deviation from the sine shape, knowing that the complexity of a pure
sine wave corresponds to unity [18]. The spontaneous movements of
each infant were thus assessed using the Hjorth parameters of the ve-
locity of hands (Ah, Mh, Ch) and feet (Af, Mf, Cf).

2.5. Statistical analysis

2.4.1. Analysis 1. Indexes of coordination
In order to measure indexes of limb coordination we adapted the The statistical analyses were performed on the calculated de-
paradigm of Kanemaru et al. by determining the first canonical corre- scriptors using the IBM SPSS statistic package, version 23.
lations between the RH (right hand) and LH (left hand) positions, ch and Kinematic parameters were calculated separately for hands and feet,
between the RF (right foot) and LF (left foot) positions, cf, together with and respectively correlated against age at recording, counted as post-
the respective angles between the first canonical vectors, ah and af [13]. term age, and expressed in days. Correlations were calculated using
The 3D tangential velocities of both hands and feet were also computed. Pearson index. Regarding canonical correlation between limb position
The Pearson's correlation coefficients between LH and RH tangential and velocities, we used Fischer's Z-score for comparing correlation
velocities, rh and between LF and RF tangential velocities, rf were de- coefficients with age [13].
termined [13]. In our analysis, ch and cf were denoted as limb position The following parameters of analysis, namely complexity and lift-
correlations and rh and rf as limb velocity correlations. Correlations limb probabilities, were entered in a multiple linear regression model
were then expressed as the Fisher's Z score for comparing the correla- equation to predict the post-term age; models were attempted for hands
tion coefficients of age and upper and lower limbs combination, as and feet data, separately.
proposed by Kanemaru et al.
3. Results
2.4.2. Analysis 2. Indexes of distance
The distances between right- and left-hand markers, and the right- Details on the population are reported in Table 1. Median gesta-
and left-foot markers were calculated to determine to what extent they tional age at birth was 39 weeks (range: 36–41). Median age at re-
could approximate infants' hands or feet. The height displacements cording was 152/7 weeks post-term (range between 92/7 to 202/7 weeks
relative to the surface were calculated to examine to what extent the post-term age). As exposed in the methods section, four subjects have
infants could raise and hold their hands or feet against gravity. The 5th- been excluded due to quality constraints adopted for the data analysis.
percentile (minimal distance) of the relative distance between limbs In details, subject n. 2 was excluded as he was attempting to roll on his
was determined as well as the 95th-percentile (maximal height) of the bask to the prone position during all the recording, thus the signal was
limb height from the ground [15]. frequently masked by the other limbs and interrupted by the mother
As explained in the introduction section, development could be seen arms to keep him lying supine. Subject n. 3 cried for the most part of the
as the behavioural result of a stochastic process, with the emergence recording and thus masking the appearance of general movements. The
and progressive stabilization of specific motor patterns, that could be
therefore best assessed by the probability of finding the limbs at any Table 1
Characteristics of the sample.
time in a mature posture (e.g. the hands reaching to the midline or in an
antigravity posture). The parameters Pch (close-hands probability) and Subject Sex Age at Age at Postnatal age Postterm age Analysis
Pcf (close-feet probability) were thus computed as the proportions of the birth birth at recording at recording
(weeks) (days) (days) (days)
position epoch duration when the distance between the LH and RH (LF
and RF) positions, respectively, were less than a specified threshold, L 1 F 37 1/7 260 104 84 X
(L = 0.25 m). Pch and Pcf assess to what extent, and with which relative 2 M 39 1/7 274 148 142 Excluded
frequency, infants could approximate their hands and feet, respectively 3 F 38 4/7 270 75 65 Excluded
4 M 40 280 110 110 Excluded
[15]. We also computed the parameters Plh (lift-hands probability) and
5 M 35 5/7 250 100 70 X
Plf (lift-feet probability) as the proportion of the position epoch dura- 6 M 35 5/7 250 100 70 X
tion when the minimum height from the table of both hands and feet, 7 M 39 273 115 108 X
respectively, were higher than a specified threshold, H (H = 0.10 m). 8 M 39 5/7 278 116 114 Excluded
Plh and Plf assess to what extent, and with which relative frequency, 9 F 39 6/7 279 143 142 X
10 M 41 1/7 288 118 126 X
infants could raise and hold their hands and feet against gravity, re-
11 M 39 273 139 132 X
spectively [15]. In our dataset, Pch and Pcf were denoted as close-limb 12 M 40 280 71 71 X
probabilities and Plh and Plf as lift-limb probabilities.

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V. Marchi, et al. Early Human Development 142 (2020) 104942

Table 2 3.1.3. Indexes of global movement quality

Correlation results of limbs movements parameters with postmenstrual age (a.) We found that Hjorth parameters of the upper limb were sig-
and motor optimality scores (b.), respectively. Panel a reports the Pearson's nificantly correlated with post-term age (PTA): hands mobility nega-
correlation coefficient between each parameter considered to assess the spon- tively correlated with the increasing age (r = −0.78, p = 0.05; see
taneous movements and the post-term age (AGE). Scatterplots of the significant
Fig. 2), as well as age was in positive correlation with hands complexity
correlations were displayed in Fig. 1.
(r = 0.79, p = 0.05; see Fig. 2). None of the feet parameters as well as
AGE hands activity correlated with post-term age.
We also found that mobility and complexity were in mutual nega-
Hands Feet
tive correlation both for hands (r = −0.92, p < 0.005) and for feet
Indexes of coordination (r = −0.96, p < 0.001); interestingly hands activity positively cor-
Limb position canonical correlation (Zscore) 0,50 0,52 related with feet activity (r = 0.89, p < 0.005) as well as hands
Angle between first canonical vectors limb 0,41 0,34 mobility positively correlated with feet mobility (r = 0.73, p < 0.05)
Limb velocity correlation (Zscore) 0,41 0,33
but no relations there was between arm and feet complexity. Moreover,
Indexes of distance hands mobility negatively correlated with feet complexity (r = −0.82,
Limb distance (< 5° centile) –,88** −0,41
p < 0,01).
Limb lift (> 95° centile) ,84** ,76*
Close-limb probability ,80* 0,49
Lift-limb probability ,85** 0,66 3.1.4. Model of post-term age prediction
Indexes of global movement quality
The following parameters were considered for the model develop-
Activity −0,00 0,07 ment: limb complexity and lift-limb probability (see Fig. 3). They were
Mobility –,78* −0,43 entered in a multiple linear regression for predicting the PTA. While we
Complexity ,79* 0,64 failed to develop a model using feet data, the regression model was
successfully validated in the case of hands data, using hands complexity
Significant results were marked with * for p < 0.05 and with ** for p < 0.01.
and lift-hand probability as predictors for the PTA.
A multiple regression was run to predict PTA from hands complexity
recordings of subjects n. 4 and n. 8 were discarded as the signal was not
and lift-hands probability. The multiple regression model statistically
continuous enough from all the four limbs: subject n. 8 removed one of
significantly predicted PTA, F (2, 5) = 117.3, p < 0.0001, adj.
the markers during the recording during the movements and n. 4 was
R2 = 0.97. Regression coefficients and standard errors can be found in
frequently touched by the caregiver during the recording, thus masking
Table 3. The Root Mean Squared Error was 5.2 days.
the markers.
The quality of general movements, as assessed according to the
4. Discussion
standard methodological principles of the Prechtl's method [19], was
normal in all infants (i.e. normal Fidgety GMs). A summary of results is
The present study has shown that the quantitative, computerised
reported in Table 2 (see also Fig. 1 and Fig. 2).
analysis of limb movements in the fidgety period, and in particular of
the upper limbs, reliably estimates post-term age (PTA) in typically
3.1. Correlation of post-term age with quantitative parameters developing infants. More specifically, by combining linear and non-
linear parameters related to the upper limb kinematics, it was possible
3.1.1. Indexes of coordination to determine individual PTA with a mean error of < 1 week (5.2 days)
No significant linear correlation was found between the increasing in a cross-sectional cohort of infants aged 9 to 20 weeks PTA. This re-
age and the canonical correlation between limb position, the angle gression model was obtained by combining the significant correlation
between canonical vectors of limbs movements and the correlation of analyses of the upper limbs. In detail, all indexes of distance were
limb velocities. significantly correlated with PTA. Older babies were more likely to
have hand lifted from the ground and closer to each other, as de-
termined both with absolute distance and probability measures. Also,
3.1.2. Indexes of distance PTA significantly correlated with indexes of global movement quality,
We found significant correlations between the post-term age and the with a positive correlation with Hjorth's complexity index (i.e. higher
distance between hands, both expressed as minimum distance between complexity for older babies) and negative with Hjorth's mobility index
hands (r = −0.88, p < 0.005; see Fig. 2) and as the probability to put (i.e. higher mobility for younger babies), both of which are non-linear
the hand in contact (r = −0.80, p < 0.05; see Fig. 2). Post-term age descriptors of upper-limb dynamics. No correlations were found with
correlated significantly with antigravity movements of the upper limb, indexes of coordination.
both expressed as the maximal height from the ground (r = −0.84, The strength of the model lays on the combination of linear and
p < 0.01; see Fig. 2) reached along the recorded GMs session, as well non-linear parameters, which seem to be more powerful in capturing
as the probability to find the hands lifted (r = −0.85, p < 0.01; see the complexity of the motor phenomena occurring between 9 and
Fig. 2). Antigravity movements of lower limbs, as expressed by the 20 weeks PT in typical development. Motor development at this age is
maximal height reached by feet (r = 0.76, p < 0.05) also presented a the product of several concurrent processes, among which the gradual
positive correlation with post-menstrual age; none of the other features emergence of additional motor repertoire and the changes of GMs
for the lower limbs correlated with age. patterns are the most prominent and visually recognisable. Qualitative
When tested against each other, we found a significant correlation observations support the hypothesis that changes of motor repertoire
between hand-to-hand distance and antigravity movements of the along the so-called fidgety age, follow an order that seems stable in its
upper-limb, as revealed by the strong correlation between the minimum pattern and pace across different subjects. This is mostly reflected by
distance and the maximal height of the moving hands (r = −0.89, the maturational trend of upper limb movement repertoire with stabi-
p < 0.005; see also Fig. 1) as well as the correlation between the lization of antigravity movements and enrichment of the patterns of
probabilities to find the hands close and lifted (r = 0.89, p < 0.005). exploration of the body and close environment. Our findings both
No significant mutual correlation was found between distances and support the centrality of upper limb kinematics at this age, and the
antigravity movements of feet but we outlined a significant correlation necessity of a multi-faceted approach to capture the complexity of this
between the probabilities to find both feet and hands lifted (r = 0.76, maturation process.
p < 0.05). Further, our findings of a significant correlation between linear

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V. Marchi, et al. Early Human Development 142 (2020) 104942

Fig. 1. Graphical representation of bivariate probabilities density function (PDF) of the hands distance from the midline (horizontal line, in meters) and the hands'
height from the ground (vertical line, in meters). Probability densities have been represented as a logarithmic colour map (in decibel), where blue is the lowest and
yellow is the highest probability to find one hand of the subject in that position. A graph has been displayed for each subject and the age of the subject (in days) has
been reported on the top (only one of the 3 subjects aged around 70 days has been displayed). The higher is the age, the higher is the probability (and thus the time
spent) to find the two hands lifted and in contact on the midline. (For interpretation of the references to colour in this figure legend, the reader is referred to the web
version of this article.)

indexes of distance and PTA are consistent with Myagashima et al. [15]
who reported that infants with normal GMs present a significant in-
crement of antigravity motor patterns from the 2nd to the 3rd month of
age, with no difference between typical term infants and preterm in-
fants showing normal GMs. In the present study, we have extracted the
same parameters as those that were studied by Myagashima et al. [15]
in a cohort of older subjects, and exploited their potential as indicators
of infant maturation, demonstrating that they can be used cross-sec-
tionally to blindly estimate post-term age. Moreover, in addition to
linear indexes of limb distance, we have shown a significant correlation
with increasing PTA of the probability to find hand lifted from the
ground and closer to each other. It is of interest that the probability of
the hands location close to each other correlated significantly with the
probability to find them lifted, as the higher was the maximal height of
the hands, the lower was the minimum distance between them. Com-
pared to linear indexes, this approach allows for controlling for the limb
size as possible confounder.
An essential contribution to the model was provided by non-linear
parameters, which have proven valuable in increasing its accuracy.
Hjorth's parameters are global descriptors of time series derived from
biological signals, combining variations of amplitude and frequency
across time. Though originally designed for EEG, they have been

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V. Marchi, et al. Early Human Development 142 (2020) 104942

Fig. 2. Scatter plots report the post-term age (expressed in days) of the tested infants against (a) the hands mobility and complexity; (b) linear parameters of
antigravity movements: the maximal height of hands and minimal distance between hands (m); c) probabilities to lift the hands or put the hands in contact (%).

Fig. 3. A. Recording set-up, implying 8 surrounding infrared cameras and reflective markers on the extremities and axial body (white dots); upper limbs have been
marked in bigger circles. B Correlation results of hands movements features with postmenstrual age; the table reports the Pearson's correlation coefficient between
each parameter considered to assess the spontaneous movements and the PTA. Lift-hands probability and arm complexity entered in a multiple linear regression
model as combination of predictors for PTA; C. the predicted age by the model is displayed against the actual PTA in the scatterplot (the Root Mean Squared Error
was 5.2 days).

Table 3 the variance in frequency, the higher is mobility, 18. The observed
Summary of multiple linear regression. reduction in mobility with age in our cohort can be interpreted as the
Variable B SEB β
result of a reduction of oscillating limb movements and progressive
stabilization of limb trajectories. Complexity reflects the regularity of
Intercept −225.223 37.511**** the oscillation where the minimum value of complexity describes a pure
Complexity +248.361 31.185**** 0.552 sine function, and any increase in complexity reflects deviations from
Lift-hands probability 0000.806 00.087**** 0.644
its regularity (e.g. showing pauses and bursts with a distinct start and
Note. ***p < 0.001; ****p < 0.0005; B = unstandardized regression coef- end 18). The observed increase in complexity with age in our cohort can
ficient; SEB = standard error of coefficient; β = standardized coefficient. be explained by limb trajectories gradually losing their early character
of continuous oscillations and evolving into more discrete movements.
successfully employed to describe kinematic time series in the present While the upper limbs showed a clear developmental pattern during
study. In particular, two of Hjorth's parameters, mobility and com- fidgety age, the same did not apply to the lower limbs. As expected, a
plexity, have been found to correlate linearly with PTA. Mobility de- gradual increase with age of the maximal height from the ground was
scribes the variance in frequency of an oscillating signal – the higher is observed in the lower limbs, however no significant correlations with
any of the other parameters were found. These results are consistent

6
V. Marchi, et al.
with the previous observation of a different timing for legs and arms in
developing the motor repertoire [13]. Indeed, movements of the lower
limbs towards the midline are typically described as very early emer-
gent and preceding those of the upper limbs [21,22], which can explain
why foot-foot distance is no longer a relevant maturational index
during the fidgety period, contrarily to the hand-hand distance. Inter-
estingly, Galloway et al. [23] also reported that reaching movements
emerge earlier in the feet than in the hands. Consistent findings were
recently documented by Kanemaru et al. in 2012 [13], who studied
longitudinally a small group of infants. Using kinematics, they docu-
mented the emergence of a selective motor coordination between legs
at earlier ages, as compared to coordination between arms, and inter-
preted this maturational trend as parallel trajectory of development to
the emergence of functionally dissociated movements during goal-di-
rected behaviors.
A possible interpretation of these findings could lay in the different
tasks that upper and lower limbs have to accomplish across motor de-
velopment, as the lower limbs show a limited repertoire of functional
synergies compared to the variety of patterns and trajectories exhibited
by the upper limbs [23–25]. The fact that our study did not show a
significant correlation with PTA utilizing the parameters used by Ka-
nemaru, may be related to design difference, and specifically that we
assessed infants cross-sectionally (as opposed to longitudinally), thus
suggesting a high level of inter-subject variability.
Some important limitations of our study need to be acknowledged.
First, it has an explorative and pilot nature as we included only a small
group of typical subjects that have been studied with single recordings.
This may limit the significance of our results, and thus imply the need
to test the protocol with a larger sample of typically developing infants,
as well as to extend the observations to populations of infants at risk for
neurodevelopmental disorders. Moreover, in the present analysis we
adopted hardcoded thresholds to determine the distance between hands
and feet from the ground. However, a possible improvement to refine
the analysis would be not only by using indexes of probability but also
by normalizing by the length of the limbs.
Another potential limit of the study is the use of a high precision
optoeletronic system that requires fixed recording set-up that may be
difficult to adapt to large populations and clinical settings [26].
Indeed, recent advances in infant kinematics may overcome some of
these limitations, as the outlined parameters could be tested and
adapted to sensor-free kinematic systems. In this respect, the RGB-D
cameras systems seem to be promising in this field [27]. These sensor-
free cameras combining colour and depth recordings for full-body 3D
motion analysis can be used in combination with pose-estimation
models that automatically extract a skeleton model tracking the body
movement, resulting in being highly suitable for infant monitoring
[28]. A possible application of the results of this study could therefore
be the adoption of our kinematic parameters as post-hoc features for
colour-depth frames recordings that could lead to development of a
system suitable for studying larger cohorts of infants, and adapted to
routine monitoring of babies at neurodevelopmental risk.
In conclusion, and in line with previous studies, we showed that
during fidgety age computerised analysis of upper-limb movements
holds great promises for estimating the typical progression of neuro-
motor development, by combining linear measures of antigravity
movement repertoire and non-linear features of global movement pat-
tern. Indexes of lower limb motor repertoire seem to be less informative
about maturation at this age, as a good stability in the pattern has been
reached, but it cannot be excluded that lower-limb analysis might be
more relevant at younger ages.
Author contributions
VM participated to the design and conducted the study, participated
in the motor analysis, drafted and revised the manuscript, and she is
also the corresponding author of this publication. AngGr and FC
7
Early Human Development 142 (2020) 104942
contributed conception and design of the study, contacted families and
participated to the data collection. MC collected and organized the
motor recordings database. AMS and VM performed the data analysis
and the statistical analysis, contributed in the interpretation of results
and reviewed and revised the manuscript. And Gu, VB and PG parti-
cipated to the study design, supervised data collection, contributed to
data interpretation, and reviewed and revised the manuscript. All au-
thors contributed to manuscript revision, read and approved the sub-
mitted version.
Fundings
The present study was financed by project grants from the American
Academy for Cerebral Palsy and Developmental Medicine and The
Cerebral Palsy Alliance Research Foundation. Moreover, this work has
been partially supported by a grant from the IRCCS Stella Maris
Foundation (Ricerca Corrente, and the 5 × 1000 voluntary contribu-
tions, Ministry of Health, Italy).
Declaration of competing interest
The authors declare that the research was conducted in the absence
of any commercial or financial relationships that could be construed as
a potential conflict of interest.
Acknowledgments
The authors are grateful to all the families and infants who took part
in the study and the nurses, therapists, physicians at the Division of
Neonatology and Neonatal Intensive Care Unit, Santa Chiara Hospital,
University of Pisa who helped in facilitating the recruitment.
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