Dataset Information

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

ABSTRACT:

Background

While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood.

Methods

Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy.

Findings

376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.

SUBMITTER: Ximenes RAA

PROVIDER: S-EPMC7971861 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

Ximenes Ricardo Arraes de Alencar RAA Miranda-Filho Demócrito de Barros DB Montarroyos Ulisses Ramos UR Martelli Celina Maria Turchi CMT Araújo Thalia Velho Barreto de TVB Brickley Elizabeth E Albuquerque Maria de Fátima Pessoa Militão de MFPM Souza Wayner Vieira WV Ventura Liana O LO Ventura Camila V CV Gois Adriana L AL Leal Mariana C MC Oliveira Danielle Maria da Silva DMDS Eickmann Sophie Helena SH Carvalho Maria Durce C G MDCG Silva Paula F S da PFSD Rocha Maria Angela Wanderley MAW Ramos Regina Coeli Ferreira RCF Brandão-Filho Sinval Pinto SP Cordeiro Marli Tenorio MT Bezerra Luciana Caroline Albuquerque LCA Dimech George G Valongueiro Sandra S Pires Pedro P Castanha Priscila Mayrelle da Silva PMDS Dhalia Rafael R Marques-Júnior Ernesto Torres Azevedo ETA Rodrigues Laura C LC

PLoS neglected tropical diseases 20210308 3

<h4>Background</h4>While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood.<h4>Methods</h4>Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZI ...[more]

PMID: 33684110

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Project description:ImportanceCongenital Zika virus infection causes a spectrum of adverse birth outcomes, including severe birth defects of the central nervous system. The association of prenatal ultrasonographic findings with adverse neonatal outcomes, beyond structural anomalies such as microcephaly, has not been described to date.ObjectiveTo determine whether prenatal ultrasonographic examination results are associated with abnormal neonatal outcomes in Zika virus-affected pregnancies.Design, setting, and participantsA prospective cohort study conducted at a single regional referral center in Rio de Janeiro, Brazil, from September 1, 2015, to May 31, 2016, among 92 pregnant women diagnosed during pregnancy with Zika virus infection by reverse-transcription polymerase chain reaction, who underwent subsequent prenatal ultrasonographic and neonatal evaluation.ExposuresPrenatal ultrasonography.Main outcomes and measuresThe primary outcome measure was composite adverse neonatal outcome (perinatal death, abnormal finding on neonatal examination, or abnormal finding on postnatal neuroimaging). Secondary outcomes include association of specific findings with neonatal outcomes.ResultsOf 92 mother-neonate dyads (mean [SD] maternal age, 29.4 [6.3] years), 55 (60%) had normal results and 37 (40%) had abnormal results on prenatal ultrasonographic examinations. The median gestational age at delivery was 38.6 weeks (interquartile range, 37.9-39.3). Of the 45 neonates with composite adverse outcome, 23 (51%) had normal results on prenatal ultrasonography. Eleven pregnant women (12%) had a Zika virus-associated finding that was associated with an abnormal result on neonatal examination (adjusted odds ratio [aOR], 11.6; 95% CI, 1.8-72.8), abnormal result on postnatal neuroimaging (aOR, 6.7; 95% CI, 1.1-38.9), and composite adverse neonatal outcome (aOR, 27.2; 95% CI, 2.5-296.6). Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities (aOR, 12.8; 95% CI, 2.6-63.2), postnatal neuroimaging abnormalities (aOR, 8.8; 95% CI, 1.7-45.9), and composite adverse neonatal outcome (aOR, 20.5; 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings on prenatal ultrasonography had a sensitivity of 48.9% (95% CI, 33.7%-64.2%) and a specificity of 68.1% (95% CI, 52.9%-80.1%) for association with composite adverse neonatal outcomes. For a Zika virus-associated abnormal result on prenatal ultrasonography, the sensitivity was lower (22.2%; 95% CI, 11.2%-37.1%) but the specificity was higher (97.9%; 95% CI, 88.7%-99.9%).Conclusions and relevanceAbnormal results on prenatal ultrasonography were associated with adverse outcomes in congenital Zika infection. The absence of abnormal findings on prenatal ultrasonography was not associated with a normal neonatal outcome. Comprehensive evaluation is recommended for all neonates with prenatal Zika virus exposure.

Project description:ObjectivesTo estimate the rates of maternal-fetal transmission of Zika virus, adverse fetal/neonatal outcomes, and subsequent rates of asymptomatic/symptomatic congenital Zika virus infections up to the first week of life.DesignCohort study with prospective data collection and subsequent review of fetal/neonatal outcomes.SettingsReferral centre for prenatal diagnosis of the French Guiana Western Hospital.ParticipantsPregnant women at any stage of pregnancy with a laboratory confirmed symptomatic or asymptomatic Zika virus infection during the epidemic period in western French Guiana. The cohort enrolled 300 participants and prospectively followed their 305 fetuses/newborns.Main outcome measuresRate of maternal-fetal transmission of Zika virus (amniotic fluid, fetal and neonatal blood, urine, cerebrospinal fluid, and placentas); clinical, biological, and radiological outcomes (blindly reviewed); and adverse outcomes defined as moderate signs potentially related to congenital Zika syndrome (CZS), severe complications compatible with CZS, or fetal loss. Associations between a laboratory confirmed congenital Zika virus infection and adverse fetal/neonatal outcomes were evaluated.ResultsMaternal-fetal transmission was documented in 26% (76/291) of fetuses/newborns with complete data. Among the Zika virus positive fetuses/newborns, 45% (34/76) presented with no signs/complications at birth, 20% (15/76) with moderate signs potentially related to CZS, 21% (16/76) with severe complications compatible with CZS, and 14% (11/76) with fetal loss. Compared with the Zika virus positive fetuses/neonates, those that were identified as negative for Zika virus (215/291) were less likely to present with severe complications (5%; 10/215) or fetal loss (0.5%; 1/215; relative risk 6.9, 95% confidence interval 3.6 to 13.3). Association between a positive Zika virus test and any adverse fetal/neonatal outcome was also significant (relative risk 4.4, 2.9 to 6.6). The population attributable fraction estimates that a confirmed congenital Zika virus infection contributes to 47% of adverse outcomes and 61% of severe adverse outcomes observed.ConclusionIn cases of a known maternal Zika virus infection, approximately a quarter of fetuses will become congenitally infected, of which a third will have severe complications at birth or fetal loss. The burden of CZS might be lower than initially described in South America and may not differ from other congenital infections.

Project description:Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016-23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2-22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0-52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.

Project description:BackgroundTo compare risk of neonatal morbidities between women with and without documented disability and to evaluate mediation of these associations by pre-term birth and caesarean delivery.MethodsUsing data from the Consortium on Safe Labor (2002-2008; n = 223 385), we evaluated risk of 22 neonatal outcomes among singleton deliveries using ICD-9 codes to define physical (n = 1733), sensory (n = 250) and intellectual disability (n = 91). Adjusted relative risk (aRR) was estimated for each outcome among each category of disability, and among women with any disability using Poisson regression models with robust variance. Causal mediation methods evaluated pre-term birth and caesarean delivery as mediators.ResultsCompared with no disability, neonates of women with any disability had higher risk of nearly all neonatal outcomes, including pre-term birth (aRR = 1.77; 95% CI 1.62-1.94), small for gestational age (SGA) (aRR = 1.25; CI 1.11-1.41), neonatal intensive care unit (NICU) admission (aRR = 1.70; CI 1.54-1.87), seizures (aRR = 2.81; CI 1.54-5.14), cardiomyopathy (aRR = 4.92; CI 1.15-20.95), respiratory morbidities (aRR ranged from 1.33-2.08) and death (aRR = 2.31; CI 1.38-3.87). Women with disabilities were more likely to have a maternal indication for pre-term delivery, including pre-pregnancy diabetes (aRR = 3.80; CI 2.84-5.08), chronic hypertension (aRR = 1.46; CI 0.95-2.25) and severe pre-eclampsia/eclampsia (aRR = 1.47; CI 1.19-1.81). Increased risk varied but was generally consistent across all disability categories. Most outcomes were partially mediated by pre-term birth, except SGA, and heightened risk remained for NICU admissions, respiratory distress syndrome, anaemia and a composite of any adverse outcome (aRR = 1.21; CI 1.10-1.32).ConclusionNeonates of women with disabilities were at higher risk of a broad range of adverse neonatal outcomes, including death. Risks were not fully explained by pre-term birth.

Dataset Information

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

Background

Methods

Findings

Publications

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

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