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2016; 62(2):108-115
CHART 4
Number of studies retrieved by primary
database.
Database
Number of studies
PubMed-Medline
173
Embase
171
Cochrane
0
Inclusion criteria for studies retrieved
Selection of studies, assessment of titles and abstracts ob-
tained from the search strategy in the consulted databas-
es was conducted by two researchers (R.S.S. and W.M.B.)
with skills in the preparation of systematic reviews, both
independent and blinded, strictly observing the inclusion
and exclusion criteria previously established. All poten-
tially relevant studies were identified. Whenever the title
and the summary were not enlightening, researchers
sought the full article.
Study design
Case reports, case series and
guidelines
were included in
the evaluation. Narrative reviews were included in the
reading with the purpose of retrieving reference that could
have been lost in the initial search strategy. Physiological
reports or studies based on animal models, as well as those
unrelated with our P.I.C.O. components, were not includ-
ed. Only articles whose full text was available were includ-
ed in the guideline.
P.I.C.O. components
•
•
Patient:
Pregnant women, patients diagnosed with
Guillain-Barré syndrome, newborns of pregnant wom-
en with a history of Zika virus infection, newborns di-
agnosed with microcephaly during pregnancy. In all
cases, patients with a established or suspected diagno-
sis of Zika virus infection were considered.
•
•
Intervention:
Diagnosis, treatment.
•
•
Comparison.
•
•
Outcome:
Microcephaly, Guillain-Barré syndrome.
Language
We included studies available in Portuguese, English,
French or Spanish.
Studies retrieved
After entering the search strategy in the primary databas-
es (PubMed-Medline, Embase and Cochrane), the assess-
ment of titles and abstracts led to the selection of 288
studies.
Evidence selected
The studies considered for full text reading were assessed
according with set inclusion and exclusion criteria,
P.I.C.O., language and availability of the full text (Fig-
ure 1 – Annex).
1. D
uring
pregnancy
,
what
is
the
association
between
zika
virus
and microcephaly
?
In Brazil, a possible association between Zika virus infec-
tion during pregnancy and microcephaly has been under
investigation since October 2015 when the Ministry of
Health reported an increase in the number of cases of mi-
crocephaly close to 20 times that previously reported (ap-
proximately 0.5 cases for each 10,000 live births) after an
outbreak of this virus.
10,11
(
D
) This report made the Pan
American Health Organization (PAHO) publish a warn-
ing about the increased occurrence of microcephaly in
Brazil.
12
(
D
) In the same year, the PAHO reported viral ge-
nome identification using reverse transcriptase technique
followed by polymerase chain reaction in real time (RT-
-PCR) in amniotic fluid samples from two pregnant wom-
en whose fetuses had microcephaly identified during ul-
trasonography performed during prenatal monitoring.
In addition, Zika virus RNA was identified in various tis-
sues, including the brain, of a child with microcephaly
who died in the immediate neonatal period.
13
(
D
) These
events led to new alerts issued by the Ministry of Health
of Brazil, the European Centre for Disease Prevention
and Control (ECDC), and the US Center for Disease Con-
trol and Prevention (CDC) on a possible association be-
tween microcephaly and the recent outbreak of Zika virus
infection.
14,15
(
D
) The first case of congenital malforma-
tions (microcephaly) found in the European Union and
which is associated with infection by Zika virus during
pregnancy, was published in February 2016.
4
(
C
) The re-
port was that of a case of fetus with microcephaly, whose
mother had Zika virus infection in the first trimester of
pregnancy after a trip to Brazil.
4
(
C
)
The sudden increase in the number of children born
with microcephaly associated with brain damage typical-
ly seen in congenital infections in regions where newly cir-
culating virus outbreak occurred, as well as the identifica-
tion of viral genome in amniotic fluid, are suggestive of a
possible causal relationship. Also, neurotropism of this vi-
rus is known since 1952, found in studies using guinea
pigs.
16
(
C
)
17
(
D
) However, some questions are necessary to
understand and validate the relationship of cause and ef-
fect. The first point refers to the prevalence of the histori-
cal birth of infants with malformations of the central ner-