Research in Developmental Disabilities 48 (2016) 253–261

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Research in Developmental Disabilities

Early motor development of children with a congenital

cytomegalovirus infection
Alexandra De Kegel a,b,1, Leen Maes c,1,*, Ingeborg Dhooge b,d,
Helen van Hoecke b,d, Els De Leenheer b,d, Hilde Van Waelvelde a
a
Faculty of Medicine and Health Sciences, Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Ghent, Belgium
b
Department of Otorhinolaryngology, University Hospital Ghent, Ghent, Belgium
c
Faculty of Medicine and Health Sciences, Department of Speech, Language and Hearing Sciences, Ghent University, Ghent, Belgium
d
Faculty of Medicine and Health Sciences, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium

A R T I C L E I N F O A B S T R A C T

Article history: Background: Congenital cytomegalovirus (cCMV) infection is the most important etiology
Received 8 June 2015 of non-hereditary childhood hearing loss and an important cause of neurodevelopmental
Received in revised form 22 October 2015 delay. The current study aimed to investigate the early motor development of
Accepted 16 November 2015
symptomatic and asymptomatic cCMV infected children with and without sensorineural
Available online 7 December 2015
hearing loss (SNHL).
Methods: Sixty-four children with a cCMV infection, without cerebral palsy, were
Keywords:
compared to a control group of 107 normal hearing children. They were assessed around
Congenital cytomegalovirus infection
Gross motor development the ages of 6, 12, and 24 months with the Peabody Developmental Motor Scales-2 (PDMS-
Symptomatic 2), Alberta Infant Motor Scales (AIMS), and Ghent Developmental Balance Test (GDBT). The
Asymptomatic cCMV infected children were subdivided into a symptomatic (n = 26) and asymptomatic
Sensorineural hearing loss cCMV group (n = 38) but also into a cCMV group with SNHL (n = 19) and without SNHL
(n = 45).
Results: Symptomatic cCMV infected children and cCMV infected children with SNHL
performed significantly weaker for all gross motor outcome measures.
Conclusion: A congenital CMV infection is a risk factor for a delay in the early motor
development. Follow-up will be necessary to gain insight into the exact cause of this motor
delay and to define the predictive value of early motor assessment of cCMV infected
children.
ß 2015 Elsevier Ltd. All rights reserved.

1. What this paper adds

The presence of severe motor deficits, such as cerebral palsy, are well documented in children with a congenital CMV
infection. However, less is known about the prevalence of mild motor disorders in these children. The current study
addresses this topic with special focus on the differences in motor performance between symptomatic and asymptomatic
cCMV infected children and between children with and without sensorineural hearing loss. Moreover, a longitudinal design
is applied to investigate the deterioration of the motor performance.

* Corresponding author at: Department of Speech, Language and Hearing Sciences (2P1), Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
E-mail address: LeenK.Maes@UGent.be (L. Maes).
1
These authors share first authorship.

http://dx.doi.org/10.1016/j.ridd.2015.11.014
0891-4222/ß 2015 Elsevier Ltd. All rights reserved.
254 A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261

The results of this study are of clinical value for everyone working with cCMV infected children with or without a hearing
loss. It is clear that the group of symptomatic cCMV infected children and the group of cCMV infected children with SNHL,
have risks for motor deficits. Longitudinal follow-up shows a deterioration of the gross motor performance in all cCMV
infected children from 6 months toward the age of 2 years and indicates an effect of a SNHL on the motor performance with
especially a deterioration toward the age of 1 year. A trend of recovery toward the age of 2 years could be established.
However, longer follow-up will be necessary in the future to find out if the children can catch up their gross motor delay at a
later age. Evaluation of motor and vestibular functioning seems to be informative and could help in the future to find
explanations for the affected gross motor development in cCMV infected children.

2. Introduction

Cytomegalovirus is the most common congenital infection worldwide. In developed countries, the average prevalence of
congenital cytomegalovirus (cCMV) infection is 0.58–0.70% (Dollard, Grosse, & Ross, 2007; Goderis et al., 2014; Kenneson &
Cannon, 2007). Following the systematic vaccination for Rubella, it is the most common non-genetic cause of childhood
sensorineural hearing loss and an important cause of neurodevelopmental delay (Dollard et al., 2007; Fowler & Boppana,
2006; Goderis et al., 2014). Of all children born with cCMV, 90% will be asymptomatic at birth. These children do not have
clinical findings at birth, although 7–21% may develop late sequels (Dahle et al., 2000; Dollard et al., 2007). The remaining
10% life born children with cCMV have clinically apparent symptoms at birth (Cheeran, Lokensgard, & Schleiss, 2009). These
symptomatic children present with severe (neurological) symptoms in variable grades. Their prognosis is much worse than
asymptomatic newborns, with a mortality up to 30% (Jones, 2003). Jaundice, petechial rash and hepatosplenomegaly are the
most common symptoms. Intrauterine growth retardation, microcephaly, and chorioretinitis are also described (Nassetta,
Kimberlin, & Whitley, 2009). Important long-term sequels associated with cCMV include sensorineural hearing loss (SNHL),
visual deficits, convulsions, and psychomotor and mental retardation (Cheeran et al., 2009). These symptoms appear with a
delayed onset in 20–30% of all cCMV infected children and can be progressive up to years after birth (Lombardi, Garofoli, &
Stronati, 2010).
The risk of developing a SNHL is more prominent in the symptomatic group with percentages of 30–65%, although the
asymptomatic group will eventually develop hearing loss in 7–15% of cases (Dahle et al., 2000; Pass, Fowler, Boppana, Britt, &
Stagno, 2006; Williamson et al., 1982; Williamson, Demmler, Percy, & Catlin, 1992). Longitudinal audiologic follow-up of
children with cCMV infection is necessary because of the possible delayed onset and progressive character of the hearing
disorders (Dahle et al., 2000; Fowler et al., 1997). The delayed onset of hearing loss in some patients suggests persistence of
the virus and/or inflammation in the inner ear and/or auditory pathways (Sugiura et al., 2003).
The neurological sequels of a cCMV infection are focused mainly on the cognitive development (Damato & Winnen, 2002;
Ornoy & Diav-Citrin, 2006). The presence of severe motor deficits, like cerebral palsy, in those children are also well
documented (Noyola et al., 2001; Pass et al., 2006; Ramsay, Miller, & Peckham, 1991). However, less is known about the
prevalence of mild motor disorders in asymptomatic as well as in symptomatic cCMV infected children. A limited number of
studies (Gan, Tung, Tang, & Wang, 2008; Temple, Pass, & Boll, 2000) found no significant influence on the psychomotor
behavior in asymptomatic cCMV infected children. However, less is known about the differences in motor performance
between asymptomatic and symptomatic cCMV infected children without cerebral palsy or severe mental retardation.
As the group of cCMV infected children has a great risk for SNHL and a higher risk for concomitant vestibular deficits
(Zagolski, 2008), it could be expected that this group has greater risks for balance deficits (De Kegel, Maes, Baetens, Dhooge, &
Van Waelvelde, 2012; Maes, De Kegel, Van Waelvelde, & Dhooge, 2014a).
Therefore, it was decided to start a longitudinal follow-up study of infants with a cCMV infection from the age of 6 months
until 2 years to gain insight in the early motor development of symptomatic as well as asymptomatic cCMV infected children
with and without SNHL.

3. Materials and methods

This follow-up study started in January 2011 wherein 64 children (30 boys and 34 girls) diagnosed with a cCMV infection
were included. Not all cCMV infected children were tested at all testing times because of intercurrent disease or familial
reasons. Moreover, there were three time-points at which a child could be included in the study. An overview of the number
of children assessed at the different testing times is presented in Fig. 1. Forty-six children entered the study at the first time-
point of 6 months. Eighteen children were enrolled at 12 or 24 months in the study because the diagnosis of cCMV was
detected at a later age. Thirty-four children discontinued the follow-up before the third time-point. Consequently,
16 children were assessed at all testing times, 21 were assessed at 2 testing times, and 27 were assessed once.
All children were recruited from the CMV registry at the Department of Otorhinolaryngology of the Ghent University
Hospital. The children were subdivided into a symptomatic cCMV group (n = 26) and an asymptomatic cCMV group (n = 38).
The symptomatic cCMV infected infants that enrolled in this study had apparent clinical manifestations at birth, such as
hearing impairment, petechiae, jaundice, hepatosplenomegaly or microcephaly, whereas the asymptomatic cCMV infected
children exhibited none of these clinical manifestations at birth. Consequently, inclusion criteria for the asymptomatic
children at birth were based on known seroconversion of the mother during pregnancy. Detection of asymptomatic children
at a later age, was mostly because of delayed onset hearing loss. In this latter case the diagnosis of cCMV was made
[(Fig._1)TD$IG] A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261 255

T1: Test moment at the age of 6 months (n=46)

Disconnued further follow-up (n=15)

New enrollment in the study at T2 (n=10)

T2: Test moment at the age of 12 months (n=41)

(31 follow-ups from T1 and 10 new enrollments)

Disconnued further follow-up (n=19)

New enrollment in the study at T3 (n=8)

T2: Test moment at the age of 24 months (n=30)

(22 follow-ups from T1 & T2 and 8 new enrollments)

Analysis(n=64)
New enrollments at T1 (46) + T2 (10) + T3 (8)

Fig. 1. Flow-chart presenting the number of children that were assessed at the different testing times.

retrospectively by polymerase chain reaction (PCR)-based assay using dried blood spots taken within the first days after
birth, whereas cCMV detection at birth was made by CMV isolation in neonatal urine. Exclusion criteria were gestational age
of less than 37 weeks, periventricular leucomalacia or microcephalia diagnosed by means of magnetic resonance imaging
(MRI), clinical features suggesting cerebral palsy or intellectual disability diagnosed by a pediatric neurologist, orthopedic
dysfunctions or vision problems that could not be corrected.
Fourteen out of 26 (53.8%) of the symptomatic cCMV group and 5 out of 38 (13.2%) of the asymptomatic cCMV group had a
SNHL of more than 40 dB nHL in one or both ears from birth on or developed a SNHL during this follow-up period of 2 years.
Consequently, the cCMV group was also subdivided into a cCMV group with SNHL (n = 19) and a cCMV group without SNHL
(n = 45). The characteristics of the hearing impairment in both groups of cCMV infected children are described in Table 1.
Twenty-two out of 26 of the symptomatic cCMV group had received an intravenous or oral ganciclovir treatment for
6 weeks during the first months of their life. None of the asymptomatic cCMV group received this treatment. Neuroimaging
by means of MRI was done in all symptomatic cCMV infected children in the first months of life and showed some
abnormalities like multifocal leuko-encephalitis or white matter hyperintensities in eight children of this group.

Table 1
Characteristics of the hearing impairment in the symptomatic cCMV and asymptomatic cCMV group.

Symptomatic cCMV group (n = 26) Asymptomatic cCMV group (n = 38)

Number (%) of children with SNHL n = 14 (53.8%) n = 5 (13.2%)

Onset
Congenital n = 13 (50%) n = 0 (0%)
Delayed onset n = 1 (3.8%) n = 5 (13.2%)
Progression
Stable n = 4 (15.4%) n = 0 (0%)
Progressive n = 10 (38.5%) n = 5 (13.2%)
Side
Unilateral n = 7 (26.9%) n = 2 (5.3%)
Bilateral n = 7 (26.9%) n = 3 (7.9%)
Mean PTA (SD)[Min; Max]
Left ear 74.6 (48.5) [20; 120] 94.0 (45.5) [15; 120]
Right ear 83.2 (37.5) [20; 120] 94.0 (45.5) [15; 120]
CI
Unilateral CI n = 2 (7.7%) n = 0 (0.0%)
Bilateral CI n = 4 (15.4%) n = 3 (7.9%)
No CI n = 8 (30.7%) n = 2 (5.3%)
Mean age at implantation (SD)[Min; Max]expressed in months
CI 1 12.9 (8.2) [7.2; 28.8] 24.3 (9.1) [18.7; 34.9]
CI 2 17.2 (7.1) [10.0; 26.8] 30.7 (20.2) [18.7; 54.0]

cCMV, congenital cytomegalovirus; n, number; SNHL, sensorineural hearing loss; PTA, pure tone average; SD, standard deviation; Min, minimum; Max,
maximum; CI, cochlear implant.
256 A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261

Table 2
Characteristics for gender and age at the different test moments in the symptomatic cCMV group, the asymptomatic cCMV group, the control group, the
cCMV group with SNHL, and the cCMV group without SNHL.

Mean (SD) [Min–Max] Symptomatic cCMV Asymptomatic cCMV Control group cCMV group with cCMV group without
group (n = 26) group (n = 38) (n = 107) SNHL (n = 19) SNHL (n = 45)

Gender
Girl n = 14 n = 20 n = 53 n=9 n = 20
Boy n = 12 n = 18 n = 54 n = 10 n = 25

Age T1expressed in months n = 18 n = 28 n = 35 n=9 n = 37

6.5 (1.2) [4.2–9.1] 6.8 (0.9) [6.0–8.8] 6.8 (1.5) [4.1–10.4] 6.4 (1.1) [4.2–7.9] 6.8 (1.0) [4.8–9.1]

Age T2expressed in months n = 16 n = 25 n = 37 n = 14 n = 27

13.8 (1.9) [11.0–17.7] 13.4 (2.2) [10.4–18.3] 13.4 (2.4) [10.3–19.2] 14.9 (2.4) [11.0–18.3] 12.9 (1.4) [10.4–15.9]

Age T3expressed in months n = 13 n = 17 n = 28 n = 13 n = 17

25.9 (3.9) [20.0–33.4] 25.6 (2.9) [19.3–33.4] 25.3 (2.1) [20.9–29.8] 26.5 (4.2) [20.0–33.4] 25.0 (2.4) [19.3–29.6]

cCMV, congenital cytomegalovirus; SNHL, sensorineural hearing loss; n, number; SD, standard deviation; Min, minimum; Max, maximum; T1, test moment
1; T2, test moment 2; T3, test moment 3.

The cCMV infected children were compared to a cross-sectional control group of 107 typically developing children,
recruited by different public day care centers. All children were assessed around the ages of 6 (T1), 12 (T2), and 24 (T3)
months with the Peabody Developmental Motor Scales-second edition (PDMS-2), the Alberta Infant Motor Scales (AIMS),
and the Ghent Developmental Balance Test (GDBT) in a randomized order. Table 2 presents the number of participants, the
gender distribution and the age of the participants at the different testing times in the symptomatic and asymptomatic cCMV
group, the cCMV group with and without SNHL, and in the control group.
By means of the PDMS-2 (Folio & Fewel, 2000), the early motor milestones and fundamental motor skills were assessed at
the different testing times. The items of the PDMS-2 are categorized into six skill categories. The Gross Motor Scale contains
the categories: reflexes (<1 year), stationary, locomotion and object manipulation (>1 year). The Fine Motor Scale contains
the categories grasping and visual–motor integration. For each item in the test, performance criteria are specified and scored
on a three-point scale, from 0 to 2. The raw scores were transformed into standardized scores, percentiles, and motor
quotients (mean = 100; standard deviation = 15) for the Gross Motor Scale (GMQ), the Fine Motor Scale (FMQ) as well as for
the Total Scale based on the USA standardization sample. An MQ of 75 corresponds with a percentile score 5 and can be
classified as a ‘weak’ performance. The PDMS-2 evidences a high degree of reliability and validity (Folio & Fewel, 2000; van
Hartingsveldt, Cup, & Oostendorp, 2005; Van Waelvelde, Peersman, Lenoir, & Engelsman, 2007; Wang, Liao, & Hsieh, 2006).
The AIMS (Piper & Darrah, 1994) is an observational measure that examines the gross motor movement repertoire of
children from birth to walking, wherefore norm references are available until the age of 18 months. Consequently, this test
could only be evaluated at T1 and T2. The 58 items of the AIMS were scored in four different positions (prone, supine, sitting
and standing) with specific criteria (weight bearing, posture and antigravity movements) regarding the quality of
movements. Each item was scored as either ‘observed’ (1 point) or ‘not observed’ (0). Raw scores for each of the positions and
a total raw score was derived. The latter was converted to an age-corrected z-score based on a Belgian standardization group
because the original norm reference values of the AIMS are not representative for the Belgian population anymore (De Kegel
et al., 2013). A z-score  2 corresponds with a percentile score 5 and can be classified as a ‘weak’ performance. High inter-
rater and test–retest reliability and concurrent validity are reported (Blanchard, Neilan, Busanich, Garavuso, & Klimas, 2004;
Jeng, Yau, Chen, & Hsiao, 2000; Piper & Darrah, 1994; Snyder, Eason, Philibert, Ridgway, & McCaughey, 2008).
The GDBT (De Kegel & Van Waelvelde, 2009) aims specifically to evaluate balance in children from the moment of
independent walking until the age of 5 years and therefore this test could only be evaluated at T3. The test consists of
35 balance items in a developmental order. Each item can be scored on a three-point scale, from 0 to 2. The raw score was
converted to an age-corrected z-score based on the Belgian standardization group. A z-score  2 corresponds with a
percentile score 5 and can be classified as a ‘weak’ performance. The GDBT is a reliable and valid clinical assessment tool
(De Kegel, Baetens, et al., 2012).
All assessments were performed in a quiet room with the children awake and alert. The time of testing was 30–60 min,
depending on the age of the child. The study was approved by the Ethical Committee of Ghent University Hospital and
informed consent forms were obtained from the children’s parents.

3.1. Statistical analysis

All statistical analyses were performed using SPSS 22.0 (SPSS Software, SPSS, Chicago, IL). The Kolmogorov–Smirnov test
and Q-Q plots were used to check normality assumptions. Four dependent variables were considered: PDMS-2 Gross and
Fine motor Quotient (GMQ and FMQ) (at T1, T2 and T3), AIMS z-score (AIMSz) (at T1 and T2), and GDBT z-score (GDBTz)
(at T3).
At first the performance on the four dependent variables at the different testing times were compared using univariate
analysis of variance (ANOVA) between the symptomatic cCMV group, the asymptomatic cCMV group, and the control group
 A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261 257

but also between the cCMV group with SNHL, the cCMV group without SNHL, and the control group. Alpha was set at
0.05. Post hoc comparisons were performed using the Fisher’s least significant difference (LSD) test.
Finally, group differences in PDMS-2 GMQ, PDMS-2 FMQ, and AIMSz were analyzed using Linear Mixed Model (LMM)
analysis for repeated measures, with as well ‘symptoms at birth’ (symptomatic cCMV group versus asymptomatic cCMV
group) as ‘SNHL’ (cCMV group with SNHL versus cCMV group without SNHL) as a between-subjects factor, and ‘test time’ (T1,
T2, and/or T3) as a fixed factor. Alpha was set at 0.05. Subsequent planned contrasts (Bonferroni corrected with the alpha
level for statistical significance set at 0.008, i.e., 0.05/6 comparisons for PDMS-2 data and 0.012, i.e., 0.05/4 for AIMSz) were
performed to compare the motor performance over time within and between children from the different groups.

4. Results

Analysis of variance compared the motor performance between the symptomatic, asymptomatic cCMV, and control
group and revealed significant differences between groups for PDMS-2 GMQ at T1, T2 and T3, for AIMS-z at T1 and T2 and for
GDBTz at T3 and for PDMS-2 FMQ only at T1 (Fig. 2). Post hoc tests indicated that the symptomatic cCMV group performed
significantly weaker than the control group with p-values <0.001 for all gross motor outcome measures at T1, T2 and T3
assessments, but also weaker than the asymptomatic cCMV group for PDMS-2 GMQ at T1 (p = 0.001) and T2 (p = 0.005), for
AIMSz at T1 (p = 0.012) and T2 (p < 0.001), and for GDBTz at T3 (p = 0.002). The asymptomatic cCMV group performed not
significantly weaker than the control group for all gross motor outcome measures except for PDMS-2 GMQ at T2 (p = 0.029)
and at T3 (p < 0.001).
Fig. 3 presents the comparison of the motor performance between the cCMV group with SNHL, cCMV group without
SNHL, and the control group. Significant differences were shown for PDMS-2 GMQ at T1, T2 and T3, for PDMS-2 FMQ at T2, for
AIMSz at T1 and T2 and for GDBTz at T3. Post hoc tests indicated that the cCMV group with SNHL performed significantly
weaker than the control group with p-values <0.001 for all gross outcome measures and performed also weaker than the
cCMV group without SNHL with p-values 0.013, except for PDMS-2 GMQ at T3. The cCMV group without SNHL performed
not significantly different from the control group except for the PDMS-2 GMQ at T3 (p = 0.001) and the GDBTz at T1
(p = 0.040) where the cCMV group without SNHL performed weaker than the control group.
Summarized, the lowest gross motor performance was found in the symptomatic cCMV group with SNHL, and this group
also demonstrated the highest amount of children that scored at or under percentile 5 for their gross motor development
(PDMS-2 GMQ 75 or AIMSz/GDBTz < 2).
Mean AIMSz, PDMS-2 GMQ, and PDMS-2 FMQ distributed over the different testing times in the symptomatic and
asymptomatic cCMV group are presented in Fig. 4 and in the cCMV group with and without SNHL in Fig. 5.
LMM analysis for repeated measures of PDMS-2 GMQ scores, revealed a significant effect for ‘test time’ (T1, T2, T3)
(p < 0.001), a significant effect for ‘SNHL’ (cCMV group with SNHL versus cCMV group without SNHL) (p = 0.002) but not for
‘symptoms at birth’ (symptomatic cCMV group versus asymptomatic cCMV group) (p = 0.198), and no significant
interactions between ‘SNHL’ and ‘test time’ (p = 0.059) and between ‘symptoms at birth’ and ‘test time’ (p = 0.509). Contrasts
indicated that both groups showed a deterioration in PDMS-2 GMQ between T1 and T2 (p = 0.003), and between T1 and T3
[(Fig._2)TD$IG]
(p < 0.001) but not between T2 and T3 (p = 0.038). The cCMV group with SNHL showed a greater deterioration in PDMS-2

Fig. 2. Comparison of the motor performance (mean values and 95% confidence intervals) between the symptomatic cCMV group, the asymptomatic cCMV
group, and the control group.
[(Fig._3)TD$IG]
258 A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261

Fig. 3. Comparison of the motor performance (mean values and 95% confidence intervals) between the cCMV group with sensorineural hearing loss (SNHL),
the cCMV group without SNHL, and the control group.

GMQ at T2 than the cCMV group without SNHL (p < 0.001). However, contrasts indicated a trend toward recovery at T3
(p = 0.110).
The LMM for PDMS-2 FMQ showed a significant effect for ‘SNHL’ (p = 0.024) but no significant effects for ‘symptoms at
birth,’ ‘test time,’ as well as for the interactions between those factors.
For AIMSz, LMM pointed out a significant effect for ‘symptoms at birth’ (p = 0.001) and for ‘SNHL’ (p < 0.001), no
[(Fig._4)TD$IG]
significant effects for ‘test time’ (T1, T2) and for the interaction between ‘symptoms at birth’ and ‘test time’ but a significant

Fig. 4. Distribution of the mean AIMSz, PDMS-2 GMQ, and PDMS-2 FMQ over time in the symptomatic and asymptomatic cCMV group.
[(Fig._5)TD$IG] A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261 259

Fig. 5. Distribution of the mean AIMSz, PDMS-2 GMQ, and PDMS-2 FMQ over time in the cCMV group with SNHL and in the cCMV group without SNHL.

effect for the interaction between ‘SNHL’ and ‘test time’ (p = 0.015). Contrasts indicated that the cCMV group with SNHL
performed significantly weaker than the cCMV group without SNHL at T2 (p < 0.001) and the symptomatic cCMV group
performed also significantly weaker than the asymptomatic cCMV group (p < 0.001) at T2.

5. Discussion

The current study established that a congenital CMV infection is a risk factor for a delay in the early motor development.
The group of symptomatic cCMV infected children and the group of cCMV infected children with SNHL, with no suspicious
signs for cerebral palsy, have the greatest risk for a gross motor developmental delay. Both groups performed significantly
weaker for all gross motor outcome measures when compared to a control group, and this was visible at 6 and 12 months as
well as at 2 years of age, but they performed also weaker than the asymptomatic cCMV group, respectively, the cCMV group
without SNHL. Asymptomatic cCMV children still have a raised risk for motor delay, but it seems that this is mainly related to
the development of SNHL.
The fact that the symptomatic cCMV group performed significantly weaker than the asymptomatic cCMV group
confirmed the findings of previous research (Jones, 2003; Noyola et al., 2001) that showed that the neurodevelopmental
outcome is worse in symptomatic cCMV infected children in comparison to asymptomatic newborns.
The fact that the hearing impaired group performed significantly weaker, can probably be explained by the fact that
children with SNHL (Arnvig, 1955; Brookhouser, Cyr, & Beauchaine, 1982; De Kegel, Maes, et al., 2012; Maes, De Kegel, Van
Waelvelde, & Dhooge, 2014b; O’Reilly et al., 2010; Selz, Girardi, Konrad, & Hughes, 1996; Shinjo, Jin, & Kaga, 2007; Tribukait,
Brantberg, & Bergenius, 2004; Zhou, Kenna, Stevens, & Licameli, 2009) and specifically those with CMV induced hearing loss
(Strauss, 1990; Zagolski, 2008) have a higher risk for vestibular dysfunctions which can have a significant impact on balance
and gross motor performance (De Kegel, Baetens, et al., 2012; Maes et al., 2014a). Potassium homeostasis dysregulation
related to dark-cell infection by CMV is the main mechanism for the prevalence of vestibular dysfunctions (Cheeran et al.,
2009; Teissier et al., 2011). Zagolski (2008) observed in a group of symptomatic as well as asymptomatic cCMV infected
children that a vestibular dysfunction was even more frequently detected than a SNHL. More recently, Bernard, Wiener-
Vacher, Van Den Abbeele, and Teissier (2015) demonstrated that vestibular disorders are frequent and severe in children
congenitally infected with CMV and that these vestibular disorders were significantly associated with hearing disorders.
Therefore, it is of the utmost importance that symptomatic cCMV infected children but also asymptomatic cCMV infected
children with late onset hearing loss, should be assessed regularly by motor and vestibular testing so that rehabilitation, if
necessary, can be started as early as possible to improve the motor performance and the child’s quality of life.
260 A. De Kegel et al. / Research in Developmental Disabilities 48 (2016) 253–261

The current study seems to confirm the findings of Shan, Wang, and Fu (2009) and Temple et al. (2000) that found no
significant influence on the psychomotor performance in asymptomatic cCMV infected children. The asymptomatic cCMV
infected children without SNHL from the current study performed not significantly weaker than the control group of
typically developing children, except for PDMS-2 GMQ at T2 and T3. This last finding however suggests that although they
started at a normal level, they showed a deterioration and therefore longer follow-up is necessary in the future to trace if
these children catch up their delay or if the gap with the control group will enlarge. Also, the fact that the LMM analysis
showed a significant deterioration in the PDMS-2 GMQ from T1 to T3 in all groups support the suggestion that longer follow-
up is necessary.
The LMM analyses showed that although the symptomatic cCMV infected children performed weaker than the
asymptomatic cCMV infected children, there were no significant differences in the course between both groups. The LMM
analyses showed however a significant effect of a SNHL on the development in the PDMS-2 GMQ whereby the cCMV group
with SNHL showed a greater deterioration in PDMS-2 GMQ from T1 to T2 than the cCMV group without SNHL, but toward T3
a trend to recovery could be shown. The same tendency of a greater deterioration could be shown in the development of the
AIMS z-score from T1 to T2 whereby those with SNHL showed a deterioration in contrast to those without SNHL showing an
amelioration. Unfortunately, the AIMS could not be tested anymore at T3 because it fell beyond the reach of the test. Possible
explanations for these findings can be the fact that the hearing loss of a large number (15 out of 19) of the cCMV infected
children with SNHL, was progressive so maybe the vestibular dysfunction is fluctuating or progressive as well. Additionally, a
large number (9 out of 19) of this group received one or two cochlear implants during the follow-up period. Because one of
our recent studies proved that the trajectory of gross motor development can be changed in children with a hearing loss
following a cochlear implantation, it could declare the current findings (De Kegel, Maes, Van Waelvelde, & Dhooge, 2015).
However, the current findings suggest that the vestibular function and the motor performance must be studied further in the
future.
Some important limitations of the current study must be pointed out. The first one is the mixed longitudinal–cross-
sectional design because a lot of patients enrolled at a later age in the study or discontinued follow-up. The most frequent
reason for a late enrolment was a late diagnosis of cCMV because of a late onset SNHL and the most frequent reason for
discontinuing follow-up was the feeling of the parents that their child developed well and needed no follow-up anymore.
This could have biased the results somehow in the direction of having more children with poor motor development in this
study compared to the complete cCMV population. A second important limitation is the fact that the children of the current
study were only assessed by motor testing and not by vestibular testing.

6. Conclusion

The reported results of this study are of clinical value for everyone working with cCMV infected children with or without a
hearing loss. It is clear that the group of symptomatic cCMV infected children and the group of cCMV infected children with
SNHL, have risks for motor deficits. Longitudinal follow-up showed a deterioration of the gross motor performance in all
cCMV infected children from 6 months toward the age of 2 years and showed an effect of a SNHL on the motor performance
with especially a deterioration toward the age of 1 year. A trend of recovery toward the age of 2 years could be established.
However, longer follow-up will be necessary in the future to find out if the children can catch up their gross motor delay at a
later age. Evaluation of motor and vestibular functioning testing seems to be informative and could help in the future to find
explanations for the affected gross motor development in cCMV infected children.

7. Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgements

The authors would like to thank all the parents and the children that participated in this study, Dr Julie Goderis, Dr Birgit
Philips, Dr Freya Swinnen, and Mieke Vercruysse from the ENT-department of the University Hospital of Ghent, as well as
Lotte Rombaut, Stephen Vlaeminck, Sandrien Van Vooren, Saartje Vanaudenaerde, Stefanie Vanhecke, Jolien Baelde, Vicky
Defever, Marieke Sucaet, Valentine Tahon, Hanne Maertens, and Rob Van Hooreweder for their assistance in collecting data.

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