This final report updates preliminary data on Zika virus infection among pregnant women in Rio de Janeiro. ZIKV infection during pregnancy was associated with fetal death, fetal growth restriction, ...and central nervous system abnormalities.
We have been conducting active surveillance for dengue infection in the general population of Rio de Janeiro since 2007. In 2012, we established a prospective cohort for dengue surveillance in mother–infant pairs within the Manguinhos Rio de Janeiro area. In 2015, we noted an increase in cases of a denguelike illness that was characterized by a descending rash, generally without fever; this increase coincided with a surge in the number of cases of illness characterized by a pruriginous rash in northeastern Brazil.
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In early 2015, most cases were originally reported to surveillance systems as dengue; however, Zika virus (ZIKV) was . . .
IMPORTANCE: Current guidelines recommend screening eye examinations for infants with microcephaly or laboratory-confirmed Zika virus infection but not for all infants potentially exposed to Zika ...virus in utero. OBJECTIVE: To evaluate eye findings in a cohort of infants whose mothers had polymerase chain reaction–confirmed Zika virus infection during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: In this descriptive case series performed from January 2 through October 30, 2016, infants were examined from birth to 1 year of age by a multidisciplinary medical team, including a pediatric ophthalmologist, from Fernandes Figueira Institute, a Ministry of Health referral center for high-risk pregnancies and infectious diseases in children in Rio de Janeiro, Brazil. PARTICIPANTS: Mother-infant pairs from Rio de Janeiro, Brazil, who presented with suspected Zika virus infection during pregnancy were referred to our institution and had serum, urine, amniotic fluid, or placenta samples tested by real-time polymerase chain reaction for Zika virus. MAIN OUTCOMES AND MEASURES: Description of eye findings, presence of microcephaly or other central nervous system abnormalities, and timing of infection in infants with confirmed Zika virus during pregnancy. Eye abnormalities were correlated with central nervous system findings, microcephaly, and the timing of maternal infection. RESULTS: Of the 112 with polymerase chain reaction–confirmed Zika virus infection in maternal specimens, 24 infants (21.4%) examined had eye abnormalities (median age at first eye examination, 31 days; range, 0-305 days). Ten infants (41.7%) with eye abnormalities did not have microcephaly, and 8 (33.3%) did not have any central nervous system findings. Fourteen infants with eye abnormalities (58.3%) were born to women infected in the first trimester, 8 (33.3%) in the second trimester, and 2 (8.3%) in the third trimester. Optic nerve and retinal abnormalities were the most frequent findings. Eye abnormalities were statistically associated with microcephaly (odds ratio OR, 19.1; 95% CI, 6.0-61.0), other central nervous system abnormalities (OR, 4.3; 95% CI, 1.6-11.2), arthrogryposis (OR, 29.0; 95% CI, 3.3-255.8), and maternal trimester of infection (first trimester OR, 5.1; 95% CI, 1.9-13.2; second trimester OR, 0.5; 95% CI, 0.2-1.2; and third trimester OR, 0.3; 95% CI, 0.1-1.2). CONCLUSIONS AND RELEVANCE: Eye abnormalities may be the only initial finding in congenital Zika virus infection. All infants with potential maternal Zika virus exposure at any time during pregnancy should undergo screening eye examinations regardless of the presence or absence of central nervous system abnormalities.
We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015-2016 (refs.
...). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below -2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between -1 and -2 s.d. in any domain (scores <85-70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the
gene. It causes bilateral pediatric cataract and ...hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in
, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis-a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in
was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in
(c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both
and
genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
: media-1vid110.1542/5804915134001PEDS-VA_2018-1104
OBJECTIVES: To characterize ophthalmic manifestations of confirmed or suspected antenatal Zika virus (ZIKV) exposure.
Infants with antenatal ZIKV ...exposure were referred for evaluation during the 2015-2016 Rio de Janeiro outbreak. Mothers with symptomatic ZIKV infection during pregnancy and/or infants with microcephaly or other findings that were suggestive of suspected antenatal exposure were tested with reverse transcriptase polymerase chain reaction (RT-PCR). Complete eye examinations were performed by pediatric ophthalmologists between January 2016 and February 2017. The main outcome measure was eye abnormalities in RT-PCR-positive and suspected (ie, not tested or RT-PCR-negative) antenatal ZIKV cases.
Of 224 infants, 189 had RT-PCR testing performed. Of 189 patients, 156 had positive RT-PCR results in their blood, urine, and/or placenta. Of 224 infants, 90 had central nervous system (CNS) abnormalities, including microcephaly (62 infants). Eye abnormalities were present in 57 of 224 (25.4%) infants. Optic nerve (44 of 57; 77.2%) and retina abnormalities (37 of 57; 64.9%) were the most common. The group with suspected ZIKV infection (68 infants) had proportionally more eye (36.8% vs 20.5%;
= .022) and CNS abnormalities (68.3% vs 28.1%;
= .008), likely because of referral patterns. Eye abnormalities consistent with ZIKV infection were clinically comparable in both RT-PCR-positive and unconfirmed groups, including 4 RT-PCR-positive infants of 5 without any CNS abnormalities.
Similar eye manifestations were identified regardless of laboratory confirmation. Well-appearing infants were also found to have eye abnormalities. Therefore, all infants born after ZIKV outbreaks should be universally screened for eye abnormalities.
Up to 25% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 (
) has the smallest number of reported ...variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G>A/p.Gly156Glu in
in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of
is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G>A/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.
There are limited data on amniocentesis as a diagnostic tool for congenital Zika syndrome. Here we report on a prospective cohort of 16 women with suspected Zika virus infection in a highly endemic ...area, and discuss the role of amniocentesis in the prenatal diagnosis of fetal Zika infection.
Retinopathy of prematurity (ROP) care in Brazil varies in availability of resources and infrastructure. A cross-sectional survey was conducted among ophthalmologists of the Brazilian ROP Group ...(BRA-ROP) to assess the profiles and practices of ophthalmologists involved in ROP care. A total of 78 responses of BRA-ROP participants (79%) were included. Participants were mostly retina experts (64.1%), female (65.4%), and over 40 years of age (60.2%). Eighty-six percent reported following Brazil’s ROP screening criteria. Retinal imaging is available to 16.9% of respondents; fluorescein angiography, to 1.4%. For ROP stage 3 zone II (with plus disease), laser treatment was the preferred treatment (78.9%); for aggressive ROP, anti-VEGF was favored (66.2%). There were significant regional differences in treatment choice. Not all respondents continued to follow treated patients after discharge from the neonatal intensive care unit, highlighting an aspect of ROP care in need of improvement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The goals were to determine optimal screening criteria for retinopathy of prematurity (ROP) in 7 neonatal units in Rio de Janeiro, Brazil, and to explore the workload implications of applying ...different criteria.
Infants with birth weights of < or = 2000 g or gestational age of <37 weeks were examined by 3 ophthalmologists in 7 of the largest units in Rio de Janeiro, during a 34-month period. ROP was classified by using the international classification, and laser treatment was given to infants developing type 1 ROP.
A total of 3437 (87%) of 3953 eligible infants were examined, of whom 124 (3.6% range: 2.1%-7.8%) were treated. Eleven infants were treated for aggressive posterior ROP. Appropriate screening criteria for the 2 NICUs with high survival rates (ie, > or =80% among infants with birth weights of <1500 g) would be < or =1500 g or <32 weeks. For NICUs with low survival rates (ie, <80%), appropriate criteria would be < or =1500 g or < or =35 weeks. UK, US, and previous Brazilian criteria would all miss infants needing treatment.
ROP programs in Brazil should use the wider criteria of < or =1500 g or < or =35 weeks until further evidence-based criteria become available, although this would mean a slight increase in workload across the city, compared with use of the narrower criteria in the better units. Whether survival rates can be used as a proxy to indicate screening criteria requires further investigation.
To report the findings of a cross-sectional study of visual function in infants with confirmed or suspected antenatal Zika virus (ZIKV) infection seen at a single referral center in Rio de Janeiro.
...Infants were examined following the ZIKV outbreak period at Instituto Fernandes Figueira/FIOCRUZ. Visual function was considered abnormal if an infant could not fix and follow a standardized high-contrast target (10 cm) by 3-6 months of age. Visual function and associations with structural eye abnormalities, central nervous system (CNS) abnormalities, microcephaly, and nystagmus were assessed. Sensitivity and specificity of screening criteria for structural eye abnormalities was assessed.
A total of 173 infants met inclusion criteria. Abnormal visual function was found in 52 infants (30.0%) and was significantly associated with eye abnormalities (40/52; OR = 44.2; 95% CI, 16.6-117.6), CNS abnormalities (50/52; OR = 64.0; 95% CI, 14.7-277.6), microcephaly (44/52; OR = 31.5; 95% CI, 12.7-77.8), and nystagmus (26/52; OR = 120.0; 95% CI, 15.6-924.5). Using microcephaly as screening criteria for the detection of eye abnormalities provided a sensitivity of 88.9% (95% CI, 76.0-96.3) and specificity of 82.8% (95% CI, 75.1-88.9). Using both abnormal visual function and microcephaly increased sensitivity to 100% (95% CI, 92.1-100.0) and decreased specificity to 80.5% (95% CI, 72.5-86.9).
Infants with suspected antenatal ZIKV infection and reduced visual function should be referred to an ophthalmologist. Visual function assessments are helpful in screening for antenatal ZIKV exposure in resource-limited settings and can identify infants who may benefit from visual habilitation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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