The study results demonstrate an association between the degree of neurological impairment, as indicated by GMFCS level, and gross motor performance in children with CZS, as previously described in the CP literature [8, 12, 18–20]. As described in CP studies [15, 21], children with severe impairment (GMFCS levels IV and V) also had severe impairment of gross motor function, with a low mean GMFM score. Severely impaired children in our study were unable to achieve more advanced postures (such as sitting, crawling and walking), with some only reaching head control in the sitting posture when supported by the therapist. Also of note, despite neuromotor impairments, some children with milder forms of CZS, especially regarding muscle tone, were able to reach gait and other more elaborate functions in orthostatic posture, such as leaping and kicking a ball.
Using the GMFCS tool, 88% of children were classified in levels IV or V, indicating a more severe motor impairment and the need for assistance for performance of daily tasks. Such impairment was similar to that described in other case series of CZS [22, 23]. In a study with 77 children with CZS, Ventura et al (2019) [22] observed that 97.4% (n = 75) had severe functional impairment (GMFCS IV and V) and only 2.6% (n = 2) had mild functional impairment (GMFCS I); however, the inclusion of children with arthrogryposis may have increased the frequency of serious abnormalities. Carvalho et al (2019) [23] evaluated 69 children with CZS, of whom 4 had arthrogryposis, and observed that only 7% (n = 5) were classified as GMFCS I to III and 93% (n = 64) were classified as GMFCS IV or V. The present study did not include children with arthrogryposis in order to avoid interference in GMFM scoring. The literature has already described the association between congenital orthopedic abnormalities and worse neurological outcome [24–26].
Children with CZS and muscle tone, sensory (visual and/or auditory) or orthopedic (hip dislocation and/or arthrogryposis) abnormalities have greater limitations in performance of daily tasks and are restricted in their ability to participate in age-appropriate activities. This can be further compounded by limited resources restricting access to medication, physical therapy or assistive technology [8]. Ferreira et al (2018) [7] described a variety of structural and functional deficiencies in children with CZS, such as dysphagia, cognitive and language disorders, altered muscle tone, decreased control of voluntary movements and decreased joint mobility. These deficiencies deeply impacted performance of daily activities, as fine motor development was not age-appropriate in more than 90% of the children, who were also unable to walk. Another study by Alves et al (2017) [19] analyzed 24 children with CZS and identified hyperreflexia in 100% of the sample, increased muscle tone in 95% and clonus in 77%. No child was able to stand or walk even with support, which denotes a significant motor delay. The present study results have demonstrated similar findings.
In the current study, the mean GMFM score was 11.5 (range: 3.7–90.3). Furthermore, there was an inverse association between GMFCS groups and GMFM scores, indicating the higher the level of GMFCS (greater functional impairment), the lower the GMFM score. Melo et al (2019) [18] analyzed a group of children with CZS between 5 to 29 months of age and showed a mean GMFM score of 6.5 (range: 2-82.9), which is lower than that observed in this study.
GMFM and GMFCS are promising tools for improving understanding of limitations and prognosis of children with CZS. They serve as a guide for tailoring care and informing health care and educational policies and priorities [10, 12]. The poor motor prognosis of the study sample raises concerns about prospects for the group’s full participation in the daily activities of society without substantial long-term support.
We used the GMFM-88 instead of the reduced version of the scale, GMFM-66, since the full version is more sensitive for detection of alterations in dimensions A and B [27]. Younger and/or severely affected children are mostly able to reach developmental milestones in the first two dimensions; the research sample was evaluated at a young age (mean of 13.9 months) and was mostly considered severely impaired. Therefore, GMFM-88 appears to be an appropriate tool to evaluate gross motor function in children with CZS.
As seen in Table 2, the group with severe impairment according to GMGCS levels, scored only in the first two dimensions (A) lying and rolling and (B) sitting, which demonstrates that they had a worse prognosis, with difficulties in performing simple tasks independently. Children in the group with moderate impairment managed to remain seated without support from the upper limb and even had some skills in dimension C (crawling and kneeling). These children have the ability to perform postural shifts with greater independence, but they may present postural compensations, like to sit with lumbar hyperkiohosis [23, 28]. Children in the group with mild impairment managed to score in all dimensions, and some of them were already walking. These results are expected, especially those in the severe group, and have been observed in other studies of children with CZS [6, 8, 22].
The presence of microcephaly at birth is another important factor for the impact of ZIKV congenital infection on neurological development [3, 6, 19, 29, 30]. Gordon-Lipkin et al (2017) [31] have demonstrated that congenital microcephaly is associated with gross motor development abnormalities in 65% of cases. Microcephaly in CZS is caused by a disruptive process [7, 13]. Severe microcephaly is caused by brain growth arrest, mainly affecting the frontal, temporal and parietal lobes [7, 32]. There is a close relationship between neuromotor development delay and the degree of microcephaly, as the impaired head growth is indicative of the extent of brain damage [2, 8, 33]. The study results corroborate these findings, since severe microcephaly was more frequent in the group of children classified as severely impaired by GMFCS.
It is important that longitudinal cohort studies evaluating sensorineural development use standardized scales. A recent study in the northeastern region of Brazil was the first to analyze motor development of children with CZS over time; this study reported advances in motor development in the first 18 months of age. However, at 24 months of age, most children had reached 90% of their final motor abilities [22].
Although the present study was cross-sectional, prospective studies of children with CZS are essential for the understanding of the natural history of congenital ZIKV infection, motor development of affected children, and their functional impairments. Although exclusion of children with arthrogryposis can be considered a study limitation in the present study, their inclusion would have negatively impacted gross motor development results in CZS.
In conclusion, low mean GMFM scores in this population, where most children were classified as GMFCS IV and V, demonstrate the severe functional impairment and poor prognosis of children born with CZS. Our results highlight the pressing need for implementation of early stimulation programs, with inclusive public health and educational policies, in order to reduce the disease burden and enable improved motor and sensory development of affected children.