Zika virus (ZIKV) is a neurotropic arbovirus almost exclusively transmitted by the bite of Aedes species mosquitoes [1].
An outbreak of ZIKV infection was first confirmed in Northeast of Brazil, early 2015. The prevalence of microcephaly in 15 states of Brazil with laboratory-confirmed ZIKV transmission significantly exceeded that in four states without confirmed ZIKV transmission [2].
Pomar et al. conducted a prospective study in 2016 in French Guiana that included 301 pregnant women with biological confirmation of ZIKV infection and 399 pregnant women who were negative for ZIKV infection. The number of fetuses with central nervous system involvement was higher in the infected group (9.0% vs 4.3%) [3].
A prospective study was conducted in 2016 in French overseas territories. It included women whose pregnancies overlapped with the 2016 Zika epidemic in Guadeloupe, Martinique and French Guiana. Babies born to mothers enrolled in this study were included in a prospective cohort following these babies from birth to 24 months.
The neurodevelopment in children exposed and non exposed in utero with ZIKV from 0 to 24 months was assessed longitudinally during medical visits at the age of 2, 4, 9, 18, and 24 months old, in accordance with the officially recommended routine health screenings of infants in France.
The study enrolled a number of 1180 newborns. Among these babies, 576 were excluded. Ultimately, the analysis was performed on 604 apparently healthy newborns at birth for whom ZIKV infection status in mother is known. Among them, 461 babies were exposed to ZIKV in utero and 143 were unexposed (Fig. 1).
Fig. 1.
Flow-chart.
The study shows better skills for naming image and reaching and grasping objects at 24 months in exposed children (Table 1). Other skills such as pincer grasp, giving back objects, putting cube in a box, sitting without support and eating by himself with a spoon were also better among exposed children, but not persistent at 24 months old.
Table 1.
Neurodevelopemental milestones in children from 0 to 24 months.
| Characteristics | Consultation at 2 months |
Consultation at 4 months |
Consultation at 9 months |
Consultation at 18 months |
Consultation at 24 months |
|||||
|---|---|---|---|---|---|---|---|---|---|---|
| Exposed | Not Exposed | Exposed | Not Exposed | Exposed | Not Exposed | Exposed | Not Exposed | Exposed | Not Exposed | |
| n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | |
| N | 375 | 103 | 372 | 95 | 341 | 84 | 287 | 39 | 296 | 104 |
| Reflex smile | 346 (99.1) | 99 (99.0) | 362 (100.0) | 92 (100.0) | 320 (100.0) | 78 (100.0) | 285 (100.0) | 39 (100.0) | 292 (99.3) | 104 (100.0) |
| Vocalizations | 348 (98.9) | 86 (98.9) | 311 (100.0) | 67 (100.0) | 284 (99.6) | 39 (100.0) | 290 (99.0) | 104 (100.0) | ||
| Laugh | 328 (95.6) | 83 (96.5) | 306 (100.0) | 64 (100.0) | 285 (100.0) | 39 (100.0) | 293 (100.0) | 104 (100.0) | ||
| Raises head on belly | 327 (98.8) | 97 (98.0) | 355 (99.2) | 93 (100.0) | 318 (100.0) | 80 (100.0) | 285 (100.0) | 39 (100.0) | 294 (100.0) | 104 (100.0) |
| Pass arms forward on belly | 93 (66.0) | 32 (84.2)b | 290 (96.3) | 89 (100.0) | 282 (98.9) | 69 (100.0) | 285 (100.0) | 39 (100.0) | 294 (100.0) | 104 (100.0) |
| Throwing objects | 181 (96.3) | 25 (100.0) | 281 (99.3) | 38 (100.0) | 289 (99.7) | 104 (100.0) | ||||
| embed shapes | 196 (72.1) | 29 (82.9) | 254 (91.0) | 85 (89.5) | ||||||
| Holding a pencil and scrible | 287 (99.3) | 104 (100.0) | ||||||||
| Sits without support | 307 (97.2) | 77 (100.0) | 284 (99.6) | 39 (100.0) | 294 (100.0) | 104 (100.0) | ||||
| moves crawling | 62 (37.3) | 11 (36.7) | 251 (95.1) | 53 (98.1) | 281 (98.9) | 39 (100.0) | 270 (93.1) | 104 (100.0) a | ||
| Walks | 292 (99.3) | 104 (100.0) | ||||||||
| Goes up and down the stairs | 286 (97.6) | 102 (98.1) | ||||||||
| Reacts to his first name | 110 (65.9) | 19 (79.2) | 319 (99.4) | 75 (98.7) | 283 (100.0) | 38 (100.0) | 293 (99.7) | 104 (100.0) | ||
| Repeats a word | 50 (26.3) | 10 (38.5) | 255 (90.4) | 36 (97.3) | 282 (95.9) | 95 (91.3) | ||||
| Understands simple order | 125 (69.8) | 26 (100.0)c | 277 (98.6) | 38 (100.0) | 292 (99.3) | 103 (100.0) | ||||
| Names an image | 266 (91.7) | 79 (76.7)d | ||||||||
| Asks going to the bathroom | 168 (58.9) | 53 (51.0) | ||||||||
| Opens hands | 116 (89.9) | 22 (91.7) | 231 (99.6) | 54 (100.0) | 265 (100.0) | 51 (100.0) | 284 (100.0) | 39 (100.0) | 293 (99.7) | 104 (100.0) |
| Plays with hands | 99 (77.3) | 23 (95.8)- | 347 (99.1) | 87 (100.0) | 306 (100.0) | 66 (100.0) | 284 (100.0) | 39 (100.0) | 286 (97.3) | 104 (100.0) |
| Catchs an object when in touch | 79 (68.1) | 22 (95.7)b | 326 (97.3) | 83 (98.8) | 306 (100.0) | 66 (100.0) | 284 (100.0) | 39 (100.0) | 273 (92.9) | 104 (100.0)b |
| Catchs an object on his own | 143 (80.8) | 24 (80.0) | 211 (98.6) | 40 (100.0) | 281 (99.3) | 39 (100.0) | 294 (100.0) | 104 (100.0) | ||
| Kept seated hols his head | 98 (81.0) | 5 (21.7)⁎⁎⁎ | 336 (98.5) | 85 (100.0) | 304 (100.0) | 67 (100.0) | 284 (100.0) | 39 (100.0) | 294 (100.0) | 104 (100.0) |
| Thumb index pliers | 184 (68.9) | 54 (93.1)d | 280 (98.9) | 38 (100.0) | 289 (98.3) | 103 (99.0) | ||||
| Gives objects | 114 (62.0) | 26 (92.9)c | 282 (100.0) | 37 (100.0) | 292 (99.3) | 103 (100.0) | ||||
| Imitates gesture | 281 (99.6) | 38 (100.0) | 289 (98.3) | 103 (99.0) | ||||||
| Puts cube in box | 38 (23.9) | 16 (64.0)d | 261 (94.2) | 36 (97.3) | 287 (98.6) | 102 (99.0) | ||||
| Sits with support | 107 (62.2) | 10 (34.5)c | 298 (99.0) | 74 (100.0) | 284 (100.0) | 39 (100.0) | 292 (100.0) | 104 (100.0) | ||
| Crawls on all fours | 233 (88.6) | 50 (94.3) | 282 (98.9) | 39 (100.0) | 278 (95.5) | 104 (100.0)+ | ||||
| Runs | 39 (18.3) | 8 (25.0) | 281 (98.6) | 39 (100.0) | 290 (99.0) | 104 (100.0) | ||||
| stretches out his arms to be carried | 184 (97.4) | 25 (96.2) | 282 (100.0) | 38 (100.0) | 291 (100.0) | 103 (100.0) | ||||
| Repeats a syllab | 284 (89.9) | 68 (95.8) | 277 (97.9) | 37 (100.0) | 292 (99.3) | 100 (97.1) | ||||
| Coupled words | 139 (51.7) | 15 (40.5) | 258 (87.2) | 85 (83.3) | ||||||
| Designates objects by sounds/gestures | 254 (93.0) | 34 (94.4) | 280 (94.9) | 95 (93.1) | ||||||
| Dressing aid | 265 (94.6) | 36 (97.3) | 290 (98.6) | 100 (99.0) | ||||||
| Eats on his own with a spoon | 13 (7.4) | 7 (28.0)c | 192 (69.1) | 33 (89.2)* | 272 (92.5) | 99 (98.0)a | ||||
p-value <0.1.
p-value < 0.05.
p-value < 0.01.
p-value < 0.001.
Einspieler et al. conducted a cohort study in Brazil. They enrolled in the study 444 infants, including 111 children prenatally exposed to a maternal illness with rash and 333 children without any prenatal exposure to maternal illness. This study showed that 82.1% of ZIKV-exposed infants without congenital microcephaly were healthy at the age of 12 months [4].
Blackmond et al. included mother-child pairs during a period of active ZIKV transmission (April 2016–March 2017) and prospectively followed up children to 30 months. A total of 131 normocephalic ZIKV: exposed (n = 68) and unexposed (n = 63) children were assessed between 22 and 30 months of age. They showed that overall neurodevelopment was unaffected among these children born with normal head circumference [5].
Further studies would be necessary to assess if the minimal differences found in the neurodevelopment of children in the present study persist in their outcome beyond 24 months.
Acknowledgments
Author contributions
The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
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