Encontro Regional: Fortalecimento da Atenção Básica na articulação das Redes de Atenção à Saúde no contexto da Síndrome Congênita Associada à Infecção pelo Vírus Zika
O documento discute:
1) Avanços no conhecimento sobre o vírus Zika e suas consequências feitos por pesquisadores brasileiros.
2) Os principais tópicos abordados são as peculiaridades e complicações da microcefalia por Zika congênita, o que se sabe sobre outras manifestações do espectro da síndrome de Zika congênita, e os esforços de pesquisa em Recife para compreender melhor a síndrome.
3) Estudos em Recife mostram que a síndrome de Zika congênita pode incluir micro
Semelhante a Encontro Regional: Fortalecimento da Atenção Básica na articulação das Redes de Atenção à Saúde no contexto da Síndrome Congênita Associada à Infecção pelo Vírus Zika
Semelhante a Encontro Regional: Fortalecimento da Atenção Básica na articulação das Redes de Atenção à Saúde no contexto da Síndrome Congênita Associada à Infecção pelo Vírus Zika (20)
aula de codigo de etica dos profissionais da enfermagem
Encontro Regional: Fortalecimento da Atenção Básica na articulação das Redes de Atenção à Saúde no contexto da Síndrome Congênita Associada à Infecção pelo Vírus Zika
1. Encontro Regional: Fortalecimento da Atenção Básica na
articulação das Redes de Atenção à Saúde no contexto da
Síndrome Congênita Associada à Infecção pelo Vírus Zika
Avanços no conhecimento sobre o vírus
Zika e suas consequências: a contribuição
dos pesquisadores brasileiros
Demócrito de Barros Miranda Filho
Universidade de Pernambuco
Microcephaly Epidemic Research Group
2. Financiadores de nossas Pesquisas
ZikaPLAN has received funding from the
European Union’s Horizon 2020 research
and innovation programme under grant
agreement No 734584.
3. Tópicos:
• Microcefalia por Zika congenital – peculiaridades e complicações
• O que sabemos sobre o resto do espectro até agora?
• O que estamos fazendo em Recife para compreender melhor a SZC
3
4. Tópicos:
• Microcefalia por Zika congenital – peculiaridades e complicações
• O que sabemos sobre o resto do espectro até agora?
• O que estamos fazendo em Recife para compreender melhor a SZC
4
5. Emerging Infectious Diseases • www.cdc.gov/eid • Vol.
22, No.11, Nov 2016
Microcephaly – first descriptions
Emerging Infectious Diseases • Vol. 22, Number 6, Jun
2016
6. • 85% RN a termo
• Calcificações, ventriculomegalia
• Desordens da migração neuronal
(lisencephaly)
• Anormalidades visuais e auditivas
MERG. Emerg Infect Dis. 2016 Jun
http://dx.doi.org/10.32032/eid2206.160062
67%
Severe macular neuroretinal atrophy in an infant with microcephaly
7. Gestational age at birth, n = 47
Preterm 4 (8.5)
Term 41 (87.2)
Postterm 2 (4.3)
Head circumference z-score at birth,* n = 45
≥ –2 6 (13.3)
Microcephaly, < –2 10 (22.2)
Severe microcephaly, < –3 29 (64.5)
Signs and symptoms, n = 48
Irritability 41 (85.4)
Pyramidal/extrapyramidal syndrome 27 (56.3)
Epileptic seizures 24 (50.0)
Dysphagia 7 (14.6)
Congenital clubfoot 5 (10.4)
Arthrogryposis 5 (10.4)
Cleft lip/cleft palate 1 (2.1)
Cranial computed tomography imaging findings, n = 48
Calcifications in the brain parenchyma 44 (91.7)
Malformation of cortical development 42 (87.5)
Ventriculomegaly 37 (77.1)
White matter attenuation 15 (31.3)
Brain stem and cerebellum hypoplasia 6 (12.5)
Emerging Infectious Diseases •ww.cdc.gov/eid• Vol. 22, No.11, Nov 2016
Moura da Silva et al.
Clinical characteristics of probable congenital Zika
virus syndrome in infants from birth to 1–8 months
of age, Sao Luis, Brazil, 2015–2016
Microcefalia
8. • hipoplasia com sinal do duplo-anel
• palidez
Anormalidades do segment posterior – envolvimento da retina e nervo optico:
• perda de reflexo foveal
• Pigmentação leve a grosseira
Ophthalmological findings in infants with microcephaly and presumable intra-uterus ZikV infection
Ventura CV et al.
Arq Bras Oftalmol. 2016;79(1):1-3http
• áreas circulares de atrofia coriorretiniana
9.
10. 16/70 crianças (22.8%) falharam no primeiro BERA de triagem em pelo menos uma
orelha e 8 falharam no segundo teste
7 (10%) tiveram diagnóstico confirmado de comprometimento auditivo com o BERA de
frequência específica
• 2 tinham perda auditiva condutiva (não foram considerados como perda associada à
a infecção pelo ZikV)
• 5/70 (6%)* com perda sensorioneural (bilateral em 3 e unilateral em 2)
*Uma criança com perda bilateral profunda havia sido tratada com amicacina (ototoxicidade) para sepsis, antes do primeiro
teste de triagem
Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus
Infection — Brazil, November 2015–May 2016
Mariana C Leal; Lilian F Muniz; Tamires SA Ferreira; Cristiane M Santos; Luciana C Almeida; Vanessa Van der Linden; Regina CF Ramos; Laura C
Rodrigues; Silvio S Caldas Neto
MMWR / August 30, 2016 / Vol. 65
11. Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital
Zika Virus Infection, Brazil, 2015
Mariana C. Leal, Vanessa van der Linden, Thiago P. Bezerra, Luciana de Valois, Adriana C.G. Borges,
Margarida M.C. Antunes, Kátia G. Brandt, Catharina X. Moura, Laura C. Rodrigues, Coeli R. Ximenes
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 8, August 2017
• dysphagia
intense irritability
respiratory infection
12. Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital Zika
Virus Infection, Brazil, 2015
Mariana C. Leal, Vanessa van der Linden, Thiago P. Bezerra, Luciana de Valois, Adriana C.G. Borges, Margarida M.C.
Antunes, Kátia G. Brandt, Catharina X. Moura, Laura C. Rodrigues, Coeli R. Ximenes
B) Imagem da avaliação
endoscópica de fibra óptica com
um atraso no início da deglutição;
o líquido tingido espessado é
visível na supraglote.
C) Aspiração silenciosa,
conforme indicado por um
score de Rosenbek de 8
(mais grave).
A) Imagem de deglutição
videofluoroscópica que mostra
uma visão lateral da criança com
derramamento prematuro de
alimento líquido (com contraste) na
faringe antes do desencadeamento
do reflexo de deglutição.
13. Vanessa Van der Linden et al.
Spine and brain MRI of baby with arthrogryposis
A) notável redução da espessura da medula
espinhal (setas curtas) e mega cisterna
magna (seta longa).
B) redução das raízes ventrais do cone
medular (setas longas) em comparação com
raízes dorsais (setas curtas).
C) hipotrofia do corpo caloso (seta branca
longa), cisterna magna aumentada (seta
preta longa), quarto ventrículo alargado (seta
preta curta) e hipoplasia da ponte (seta
branca curta).
D) paquigiria em lobos frontais (setas pretas)
e grande ventriculomegalia, principalmente
na parte posterior dos ventrículos laterais.
E e F), algumas pequenas calcificações
distróficas hipointensas (setas brancas) na
junção entre a substância branca cortical e
subcortical (E) e no mesencéfalo (F).
14.
15. • epilepsia
• grave retardo do desenvolvimento
Microcefalia - Seguimento
Achados no EEG, n = 27
Atividade anormal sem descargas
epileptiformes
13 (48.1)
Descargas epileptiformes focais 8 (29.6)
Descargas epileptiformes multifocais 6 (22.2)
Emerging Infectious Diseases •ww.cdc.gov/eid• Vol. 22, No.11, Nov 2016
Moura da Silva et al. EEG (n = 37)
Idade: 1 a 5 meses (média = 2.6)
Principais anormalidades de base:
Baixa voltagem difusa: 7
Assimetrias: 6
Modified hypsarrhythmia with/without burst–suppression: 11
Anormalidades interictais em 23 (62%)
Frontal focal: 8 ou Occipital: 2
Ondas tipo “Spikes/sharp” ou “spikes sharp” multifocais: 13
Convulsões eletroencefalográficas sem manifestação clínica:
4 (padrão pseudo-rítmico focal)
Outros achados: ondas lentas focais de alta amplitude em
regiões frontal (n = 3) ou occipital (n = 1).
Clinical Neurophysiology 128 (2017) 204–214
intensa irritabilidade
16. Emerging Infectious Diseases
• www.cdc.gov/eid • Vol. 22, No.11, Nov 2016
• Z-score do PC −5.45 aos 4 meses de idade
• Z-score de peso dentro da normalidade (−1.44)
• Z-score de altura alterado (−2.21) mas não tanto
17. 109 crianças reavaliadas ao menos uma vez após o nascimento*
• 73 microcefalia grave (-3SD)
• 23 microcefalia moderada (-2SD)
• 13 PC normal ano nascer
Achados n (%)
Irritabilidae: No 52 (47.7)
Yes 57 (52.3)
Hiperexcitabilidade: No 43 (39.8)
Yes 65 (60.2)
Epilepsia: No 37 (33.9)
Yes 72 (66.1)
Deficit auditivo: No 92 (92.9)
Yes 6 (6.1)
Ao menos 1 achado ocular: No 53 (57)
Yes 40 (43)
Interacção com o olhar (>6 meses): No 60 (57.1)
Yes 45 (42.9)
Controle cervical (>6 meses): No 85 (81.7)
Yes 19 (18.3)
Sorriso social (>6 meses): No 71 (68.9)
Yes 32 (31.1)
*Van der Linden et al. 2017 ainda não publicado
desproporção craniofacial : 99 (91%)
disfagia: 103 (94.5%), pico em torno dos 2-6 m
18. 105 com exames de imagem do SNC:
• 42% com hypoplasia do tronco/cerebelo
• 29 crianças investigadas com novo exame de imagem: 10 (34.5%) tinham
hidrocefalia
109 crianças reavaliadas ao menos uma vez após o nascimento*
*Van der Linden et al. 2017 ainda não publicado
20. Tópicos:
• Microcefalia por Zika congenital – peculiaridades e complicações
• O que sabemos sobre o resto do espectro até agora?
• O que estamos fazendo em Recife para compreender melhor a SZC
20
21. microcefalia
normais ao nascer
calcificações
intracranianas
sem microcefalia
natimortos abortos
normais ao nascer
com manifestações
que surgem nos
primeiros anos de vida
epilepsia
déficit visual
déficit auditivo
retardo mental
dificuldade de aprendizado
autismo?
TDAH?
endocrinopatias?
transtornos psiquiátricos?
SZC
Microcefalia ... E o que mais?
retardo do crescimento intrauterino
artrogripose
26. Características dos neonatos
Casos
N=91
Controles
N=173
P-value
Microcefalia grave (mean - < 3 SD) 29% -
Baixo peso ao nascer (<2500gr) 77% 8% <0.001
Pequeno para a idade gestacional* 76% 5% <0.001
Imagem de crânio anormal
37% -
*Também descrito por:
Brasil P. et al. NEJM. 375;24, Dec15, 2016
Cugola FR. et al. Nature. May11, 2016
Prospective case control study to investigate the association between microcephaly and ZIKV
infection during pregnancy Araujo TVB et al (MERG). Sent to publication
27. microcephaly
normal ao nascer
natimorto
aborto
manifestations oculares
tardias?
epilepsia
comprometimento visual
dificuldades de aprendizado?
autismo?
transtorno de déficit de atenção
doenças endócrinas?
desordens psiquiátricas?
artrogripose
CZS
Microcephaly ... And what else?
crescimento intrauterin retardado
retardo do
desenvolvimento
calcificações
intracranianas sem
microcefalia
avaliação auditiva
anormal
Quas o risco para
essas manifestações?
28. Overall adverse pregnancy outcomes*: 58/125 (46.4) x 7/ 61 (11.5) p<0.001
117 live infants (ZIKV+ women): 42% with grossly abnormal clinical or brain imaging findings or both.
•small for gestational age: 9% x 5% p=0.06
•cerebral calcifications and atrophy, ventricular
enlargement, hypoplasia of cerebral structures,
parenchymal brain hemorrhages
•abnormal funduscopic examinations, strabismus,
abnormal hearing assessments
•abnormal nonspecific MRI findings - cortical dysfunction
•31 of the 49 infants (63%) had grossly abnormal results
on neurologic examinations (hyperreflexia, irritability,
hyper/hypotonicity, dysphagia, seizures)
•fetal distress
•need critical care assistance
Microcephaly: 4/117 (3.4%)
29. Tópicos:
• Microcefalia por Zika congenital – peculiaridades e complicações
• O que sabemos sobre o resto do espectro até agora?
• O que estamos fazendo em Recife para compreender melhor a SZC
29
30. SÍNDROME DE ZIKA CONGÊNITA: ESTUDO CLÍNICO
EPIDEMIOLÓGICO A PARTIR DE COORTES POPULACIONAIS E EM
SERVIÇOS DE SAÚDE ENVOLVENDO GESTANTES E CRIANÇAS
Ricardo Arraes de Alencar Ximenes
Demócrito de Barros Miranda Filho
31. GESTANTES
SEM
EXANTEMA
Periodicamen
te desde o
primeiro
trimestre
RT-PCR and/or
IgM (MAC-ELISA)
SEROCONVERSÃO
SEM
SEROCONVERSÃO
TORCH NEGATIVO
SEM RASH COM RASH
GESTANTES
COM
EXANTEMA
ZIKA
CONFIRMADO
RT-PCR e IgM
(MAC-ELISA
PCR e IgM
NEGATIVOS
PCR ou IgM
POSITIVOS
NEGATIVO POSITIVO
TORCH, CHIKV,
DENV
ZIKA
PROVÁVEL
*Protocol harmonization meeting of Brazilian and Latin American researchers with the support of OPAS/WHO was held in Recife, Brazil, March 2016
GRUPO DE
COMPARAÇÃO
Coortes de gestantes*
ZIKA
CONFIRMADO
ZIKA
CONFIRMADO
PP: Ricardo Ximenes
32. 1. Microcefalia
2. Outras anormalidades
3. Aparentemente
normal ao nascer
4. Filhos de mulher não
infecteda
crianças acompanhadas desde o início da epidemia; do estudo caso
controle; e nascidas de gestantes infectadas (coorte de gestantes)
da coorte de gestantes e do estudo caso controle
Coorte
de crianças
Da descrição da microcefalia ao
espectro complete da SZC ao
Nascimento e depois
Coorte de gestantes
com exantema
PP: Demócrito Miranda
33. Principais desfechos: evolução do perímetro cefálico, distúrbios clínicos e neurológicos,
neurodesenvolvimento, epilepsia, deficiência visual e auditiva, letalidade.
3 exposed group
1 not exposed group
12o mês
18o mês
3o mês
12o mês
18o mês
24o mês
24o mês
36o mês
36o mês
48o mês
48o mês
6o mês
Coorte
de crianças
Da descrição da microcefalia ao
espectro complete da SZC ao
Nascimento e depois
Coorte de gestantes
com exantema
PP: Demócrito Miranda
1. Microcefalia
2. Outras anormalidades
3. Aparentemente
normal ao nascer
4. Filhos de mulher não
infecteda
crianças acompanhadas desde o início da epidemia; do estudo caso
controle; e nascidas de gestantes infectadas (coorte de gestantes)
da coorte de gestantes e do estudo caso controle
6o mês
34. HUOC-UPE HAM-SES
FAV
HC-UFPE
IMIP
Formulário
DIP e neuro
Dados
específicos
Form. comum
Fiocruz
PLATAFORMA DE
DADOS
Gerenciamento
Identificação
Formulário
DIP e neuro
Dados
específicos
Form. comum
Identificação
Formulário
neurodesenvolv.
Dados específicos
Form comum
Identificação
Formulário
oftalmologia
Dados específicos
Form. comum
Identificação
Formulário
ORL e disfagia
Dados específicos
Form comum
Identificação
AACD
Formulário
DIP e neuro
Dados
específicos
Form. comum
Identificação
Coorte única?
Compartilhamento parcial
de dados?
PLATAFORMA DE DADOS Fluxo de avaliação e
seguimento das crianças
na coorte e dinâmica da
coleta e gerenciamento
de dados na plataforma
Estrutura:
• Formulário comum
• Formulários específicos
• Entrada de dados em cada local
• Diferentes níveis de acesso
35. 35
Outros projetos em andamento:
• Para estimar o impacto social e econômicos de ter uma criança com SZC na
vida das mulheres e da família (subsistência, ocupação, saúde mental,
necessidades do serviço de saúde) e para os serviços públicos:
Avaliação qualitativa do impacto nas famílias afetadas;
Avaliação econômica do impacto para famílias e serviços públicos.
36. Conclusões
36
• As consequências da microcefalia são graves e a evolução é muito ruim. O
resto do iceberg e o risco para SZC ainda são desconhecidos
• A proporção de assintomáticos ao nascimento que evoluem para sintomáticos
também ainda é desconhecida
• Não há tratamento adequado, apenas de reabilitação
• A literatura atual sobre o SZC deve ser interpretada com cautela dado o
predomínio de casos graves - uma definição ampla deve ser incorporada
• Um acompanhamento completo e avaliação rotineira do desenvolvimento é
essencial para ajudar a identificar os resultados futuros e encaminhar ao
suporte apropriado
I will start showing our funders. Here, I would like to emphasize European Union and the ZikaPlan consortium in which we have been working together with many European institutions and researchers. And this is the official photo of our kick off meeting in Recife last year.
This is one of the largest case series published so far, and shows the main features and peculiarities observed in 104 infants initially seen in Pernambuco. And this other is a smaller series from São Luis, capital of Maranhão, another State from Northeast of Brazil, published a bit later, whose findings are very similar of ours. In these photographs microcephaly and craniofacial disproportion are easily noticeable. And are also easily identifiable the gross calcifications, ventriculomegaly and the severe loss of brain parenchyma.
This table summarizes the main findings, and I would like to draw attention that eighty-five percent of newborns were term, sixty seven percent of them had severe microcephaly (probably because these were the more typical cases and easily identifiable). Calcifications, ventriculomegaly, neuronal migration disorders and abnormal vision and hearing were also found.
This is the first case report and image published of the ocular CZS involvement
The frequencies in the cohort of São Luis are very similar of ours. Other findings are irritability, pyramidal/extrapyramidal syndromes and epilepsy, observed later, also in our cases
The most common ophthalmological findings are the posterior segment abnormalities with involvement of retina and optic nerve, manifested as hypoplasia, pallor, foveal reflex loss. Pigment mottling and chorioretinal atrophy signs have been also described.
This article shows the diversity of configurations of calcifications seen on the CT scan, as well as several other findings.
We can observe different patterns of calcifications, atrophies and others abnormalities.
Hearing loss in infants with microcephaly was detected between 0 and 10 months of age. From sixteen infants that failed the first screening auditory brainstem response test (ABR), 8 failed the second test, and 7 had confirmed diagnosis of hearing impairment with frequency-specific ABR. Two were not considered to be related to ZikV infection because they had conductive hearing loss. If one infant with bilateral profound sensorineural hearing loss who had been treated with amikacin (a known ototoxic drug) before the hearing testing is excluded, the proportion of infants with sensorineural hearing loss was about 6%.
We still do not know if the damage responsible for any hearing loss is cochlear or retrocochlear (nerve or cortical)
This table shows nine very well studied infants with dysphagia. Here, I would like to emphasise these four with respiratory infection and/or hospitalization in four cases, and the need of feeding interventions for all of them. Dysphagia generally appears after the third month of life and have been associated with intense irritability and respiratory infection.
Eight of the 9 infants had loss of pharyngeal and laryngeal sensitivity leading to delays in initiation of semiautomatic swallowing phase. This delay is associated with increased risk of aspiration before swallowing. These images illustrate the evaluation.
Here a videofluoroscopic swallowing image showing an infant with premature spillage of liquid food (with contrast).
This image shows a fiberoptic endoscopic evaluation of a delay in initiation of swallowing (thickened died liquid is visible on the supraglottis).
And here we can see silent aspiration. A score of 1 in Rosenbek scale indicates absence of aspiration or penetration of material in the airways. A score of 8 indicates the most severe condition, clinically referred as silent aspiration.
Here there is a small series of 7 babies with arthrogryposis. I would like just to point out this case with an extensive atrophy of the spinal cord.
Other findings in this series are these four cases of babies small for gestational age and one without microcephaly or craniofacial disproportion
During the follow up of microcephaly cases we also found: epilepsy and severe developmental delay. These have been frequent complications among these children. This article of our group, describe electroencephalographic patterns in thirty-seven infants investigated in their first 5 months of live. The group of Maranhão also describe abnormal findings in all twenty-seven infants followed to age 1–8 months who did electroencephalography.
These nice graphics are also from the group of Maranhão, and show weight, length, and head circumference z-scores at birth and each postnatal visit up to 8 months of age. As we can see, the head circumference z-score decreased and the growth retardation of head circumference is easily noticeable
These data are from an article that we are finishing, about the evolution of one hundred nine infants that have been followed up since the beginning of the epidemic. All infants were revaluated by the neurologist at least once after birth. The mean age of the infants in the most recent evaluation was 10 months. Seventy-three of them had severe microcephaly, twenty-three had moderate microcephaly and thirteen had normal head circumference. Dysphagia, reported by parent or guardian, has been observed in almost ninety-five percent of infants, generally after the third month of life. Ninety-one percent had craniofacial disproportion and sixteen-point-five percent were small for gestational age at birth.
We had access to one hundred five central nervous system imaging made shortly after birth and all of them had alterations.
It is important to point that:
Forty-two percent of the images show cerebellum/brainstem hypoplasia, suggesting more severe compromising.
And twenty-nine children were investigated with new skull imaging for several reasons, ten had hydrocephalus and seven had an uncertain diagnosis
Based in these initial description, Cindy Moore and colleagues, appropriately describes here what seems most characteristic for a syndromic diagnosis of congenital Zika infection. But, as we know, this is only the tip of the iceberg
Here we have a small series with twelve cases of postnatal microcephaly. This is new in relation to CZS, but it is not at all surprising in the case of what we've been already observed in terms of severity of central nervous system involvement.
I emphasize here these 2 cases in which there was practically no growth of the head circumference in 1 year and the intense fall of standard deviation of the growth curve. And in these other 2 cases, marked in blue, the fact that there is no craniofacial disproportion
This is the first case report of ocular findings in a baby without microcephaly, here we can see a chorioretinal scar on the macular region.
This is the same previous case, without microcephaly but with other findings, as spasms and cerebral calcifications, compounding a series that reports optical coherence tomography - OCT findings in macular lesions of babies with CZS. This is the chorioretinal scar in the fovea. The OCT image has discontinuation of the ellipsoid zone and irregular retinal pigment epithelial contour.
The use of OCT technology showed severe involvement of the neurosensory retina. Although are not unique to CZS, these findings confirm the primary involvement of the retina in infants with CZS. They indicate severe visual impairment in newborns.
This analysis included 91 neonates with microcephaly, as cases, and one hundred-seventy-three neonates without microcephaly, as controls. Here, I will only point to the significant higher proportion of cases that were born with low birthweight and were small for gestational age, and we must consider these findings as part of the spectrum.
This was also described by Patricia Brasil, in the Cohort of Rio de Janeiro, and has been reproduced in animal models as in this case, for example.
…At last, part of the spectrum has been known. On the other hand, we still do not know the risk for these manifestations.
I believe that the full spectrum of the congenital zika syndrome will only be properly investigated in the context of clinical - epidemiological research, particularly cohort studies.
Children whose mothers were exposed in any gestational week had abnormal findings.
Cerebral calcifications and atrophy, ventricular enlargement, hypoplasia of cerebral structures, parenchymal brain hemorrhages, abnormal funduscopic examinations and hearing assessments, abnormal nonspecific MRI findings suggesting cortical dysfunction, hyper or hipotonicity, clonus, hyperreflexia, abnormal movements, spasticity, contractures, seizures, and fetal distress were also described
The next figures summarize the studies, which are underway in Recife and in various parts of the world, that should contribute to a more complete knowledge of CZS. We have two cohorts of pregnant women ongoing in Recife, whose PI is the professor Ricardo Ximenes, here present.
The first one, in partnership and support by NIH, incorporates Zika testing during antenatal care, and will provide information on risk and spectrum of CZS by gestational age in women who had asymptomatic as well as symptomatic Zika during pregnancy.
In the second, women who are identified because they have a rash diagnosed as Zika during pregnancy, will produce the same information by gestational age in women who had symptomatic Zika, including miscarriages and stillbirths. This cohort is part of the ZikaPLAN partnership.
All the neonates will be investigated for outcomes at birth and in the first four years of life, and I am the responsible for this follow up.
Examination of the babies in both cohorts will provide information on the risk and spectrum of CZS diagnosable at birth and after birth, by gestational age at infection.
The four groups of children who compose our cohort have been constructed with participants from various sources. There are cases that have been followed since the beginning of the epidemic, children from the case control study and from the cohort of pregnant women. These are the points in time to reassess the babies, and these are the main outcomes to be investigated.
It will be possible estimate risk for each manifestation by gestational week of infection.
Finally, I would like to show our research group, our partner institutions and say thank you very much for your attention.