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Panvequio Aizawa CY1, Rodrigues Caron DM1, Françoso Genovesi F1, Brasil P2, Nielsen-Saines K3, Marschik P4,5, Einspieler C4, Hydee Hasue R1
1University of Sao Paulo, Department of Physical Therapy, Communication Sciences and Disorders, and Occupational Therapy, São Paulo, Brazil, 2Fundação Oswaldo Cruz, Laboratório de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil, 3David Geffen UCLA School of Medicine, Division of Pediatric Infectious Diseases, Los Angeles, United States, 4Medical University of Graz, iDN- Interdisciplinary Developmental Neuroscience, Department of Phoniatrics, Graz, Austria, 5Karolinska Institutet, Center of Neurodevelopmental Disorders, Stockholm, Sweden
Background: The infection caused by Zika virus (ZIKV) had huge impact in infants who were born with congenital microcephaly, but it is also necessary to assess the neurodevelopment in infants exposed to ZIKV without microcephaly. A prospective cohort study in Rio de Janeiro (Brazil) of symptomatic pregnant women with RT-PCR (Polimerase Chain Reaction) confirmed ZIKV-infection was established during the ZIKV epidemic (2015-2016) with focus on assessing the neurodevelopment in these infants.
Purpose: To describe global general movements (GMs) at 1 month (writhing movements) and at 3 months postterm age (fidgety movements - FM) together with the age-specific concurrent motor repertoire (detailed GMA); and to correlate them to the time of prenatal exposure to maternal illness with rash and results on RT-PCR.
Methods: Cohort study, with GMs as dependent variable. Study population: 81 infants (55,9% male, 13,6% preterm): 79 infants prenatally exposed to acute maternal illness with rash without congenital microcephaly and 2 with microcephaly were recorded and assessed by GMA at 1 and 3 months postterm age. The ZIKV infection was detected by RT-PCR in urine and blood of mother and baby (ZIKV+). A group with a negative result was also assessed (ZIKV-). Statistical analysis was conducted using chi-squared test to compare ZIKV+ and ZIKV- with GMs and the Mann-Whitney U test to determine whether two independent samples (ZIKV-positive vs. ZIKV-negative) had the same distribution of their continuous variables (detailed GMA). P≤0.05 was considered statistically significant.
Results: Ninety-two percent - 92,3% of ZIKV+ infants (n=24) showed abnormal GMs at 1 month and 20,3% (n=12) at 3 months. This proportion was 85,7% (n=6) and 14,2% (n=2), respectively among ZIKV- infants. There were no statistical differences between ZIKV+ and ZIKV- groups. From 19 ZIKV+ infants classified as Poor Repertoire at 1 month, 26,3% had abnormal or absent FM at 3 months. Most of the sample had normal FM (84% ZIKV+ and 85% ZIKV- infants) at 3 months. The median score of the detailed GMA was 23 (maximum 28) for both groups, for the two microcephalic the scores were 6 and 9. Absent FM occurred in a few infants, but was more often when them were exposed to maternal infection during the first trimester than beyond 12 weeks gestation.
Conclusion(s): There was no difference on the percentage of infants with abnormal GMs between ZIKV+ and ZIKV- groups and neither on scores of detailed GMA. Nevertheless, only ZIKV+ infants had abnormal trajectory of GM, suggesting tendency to alterations in neurodevelopment. Major neurological damage can be found if infection occurred during the first trimester.
Implications: These results show the necessity of following up the ZIKV+ infants. Although a large proportion of ZIKV- exposed infants without microcephaly develop normally, many do not. GMA already seems to be an important tool for early detection of alterations in neurological function. Assessing their neurodevelopmental outcomes is necessary to evaluate and to early provide targeted treatment programs in order to minimize functional deficits.
Keywords: Zika virus, neurodevelopment, general movement assessment
Funding acknowledgements: Our project was supported by the Bill and Melinda Gates Foundation - Grand Challenges Explorations (OPP 1128871).
Purpose: To describe global general movements (GMs) at 1 month (writhing movements) and at 3 months postterm age (fidgety movements - FM) together with the age-specific concurrent motor repertoire (detailed GMA); and to correlate them to the time of prenatal exposure to maternal illness with rash and results on RT-PCR.
Methods: Cohort study, with GMs as dependent variable. Study population: 81 infants (55,9% male, 13,6% preterm): 79 infants prenatally exposed to acute maternal illness with rash without congenital microcephaly and 2 with microcephaly were recorded and assessed by GMA at 1 and 3 months postterm age. The ZIKV infection was detected by RT-PCR in urine and blood of mother and baby (ZIKV+). A group with a negative result was also assessed (ZIKV-). Statistical analysis was conducted using chi-squared test to compare ZIKV+ and ZIKV- with GMs and the Mann-Whitney U test to determine whether two independent samples (ZIKV-positive vs. ZIKV-negative) had the same distribution of their continuous variables (detailed GMA). P≤0.05 was considered statistically significant.
Results: Ninety-two percent - 92,3% of ZIKV+ infants (n=24) showed abnormal GMs at 1 month and 20,3% (n=12) at 3 months. This proportion was 85,7% (n=6) and 14,2% (n=2), respectively among ZIKV- infants. There were no statistical differences between ZIKV+ and ZIKV- groups. From 19 ZIKV+ infants classified as Poor Repertoire at 1 month, 26,3% had abnormal or absent FM at 3 months. Most of the sample had normal FM (84% ZIKV+ and 85% ZIKV- infants) at 3 months. The median score of the detailed GMA was 23 (maximum 28) for both groups, for the two microcephalic the scores were 6 and 9. Absent FM occurred in a few infants, but was more often when them were exposed to maternal infection during the first trimester than beyond 12 weeks gestation.
Conclusion(s): There was no difference on the percentage of infants with abnormal GMs between ZIKV+ and ZIKV- groups and neither on scores of detailed GMA. Nevertheless, only ZIKV+ infants had abnormal trajectory of GM, suggesting tendency to alterations in neurodevelopment. Major neurological damage can be found if infection occurred during the first trimester.
Implications: These results show the necessity of following up the ZIKV+ infants. Although a large proportion of ZIKV- exposed infants without microcephaly develop normally, many do not. GMA already seems to be an important tool for early detection of alterations in neurological function. Assessing their neurodevelopmental outcomes is necessary to evaluate and to early provide targeted treatment programs in order to minimize functional deficits.
Keywords: Zika virus, neurodevelopment, general movement assessment
Funding acknowledgements: Our project was supported by the Bill and Melinda Gates Foundation - Grand Challenges Explorations (OPP 1128871).
Topic: Paediatrics; Neurology
Ethics approval required: Yes
Institution: Faculdade de Medicina da Universidade de São Paulo
Ethics committee: Faculdade de Medicina da Universidade de São Paulo
Ethics number: 55685416.9.0000.0065
All authors, affiliations and abstracts have been published as submitted.
