scholarly journals 1874. Comparison of the Risk of Birth Defects in Live Births From Pregnant Women Infected and Not Infected by Zika Virus in Guadeloupe, 2016–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S47-S47
Author(s):  
Anna Louise Funk ◽  
Bruno Hoen ◽  
Benoit Tressières ◽  
Ingrid Vingadassalom ◽  
Eustase Janky ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnant Women ◽  
Birth Defects ◽  
Zika Virus ◽  
Growth Curves ◽  
Neurological Complications ◽  
In Utero ◽  
Control Group ◽  
Zikv Infection ◽  
Neurological Abnormalities

Abstract Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was estimated at 7% among fetuses/infants in a cohort of 546 women who developed a symptomatic RT-PCR confirmed ZIKV infection during pregnancy (NEJM 2018;378:985–94). There was no concomitant prospective cohort of pregnant women without ZIKV infection to use as a control group. Methods In Guadeloupe, one of the 3 FTAs that participated in the FTA cohort study, pregnant women were recruited at the time of delivery and tested for ZIKV infection. Women who had a confirmed negative IgG serology test for ZIKV at delivery and no other positive ZIKV test during pregnancy were considered to be ZIKV noninfected. Information on the course of the pregnancy was collected retrospectively and outcomes of live born infants of ZIKV noninfected women were analyzed, using the same definition criteria as those used for the FTA cohort study. Pregnancy outcomes were compared with those of the 241 ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA cohort. Results Of the 490 live born infants without in-utero exposure to ZIKV, 42 infants (8.6%) had neurological abnormalities that were described as “potentially linked to ZIKV infection”; all but one of these were microcephaly without any other brain or clinical abnormalities. The proportion of such abnormalities was not statistically different from that observed in the 241 live born infants with ZIKV exposure (6.6%, P = 0.36). When re-considering the combined 8 fetuses and 241 infants of women with confirmed ZIKV infection in Guadeloupe from the FTA cohort, only two (0.8%) live born infants and three (1.2%) medically aborted fetuses had birth defects that could still be linked to ZIKV infection. Conclusion Isolated anthropometric and other mild neurological abnormalities had the same prevalence among live born infants with and without in utero ZIKV exposure. The high prevalence of isolated microcephaly among ZIKV noninfected women in our study population suggests that the sensitive definition for microcephaly, using a −2 SD cut-off with international growth curves, may lead to an overestimate of the rate of neurological complications of ZIKV infection during pregnancy. Disclosures All Authors: No reported Disclosures.

scholarly journals 1873. Pregnancy and Birth Outcomes Among Colombian Women with Zika Virus Disease in 3 Surveillance Sites, Proyecto Vigilancia de Embarazadas con Zika

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S47-S47
Author(s):  
Margaret (Peggy) Honein ◽  
Marcela Mercado ◽  
Suzanne Gilboa ◽  
Diana Valencia ◽  
Marcela Daza ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Birth Defects ◽  
Symptom Onset ◽  
Zika Virus ◽  
Surveillance System ◽  
National Surveillance ◽  
Second Trimester ◽  
Zikv Infection ◽  
Igm Antibodies ◽  
Laboratory Evidence

Abstract Background Proyecto Vigilancia de Embarazadas con Zika (VEZ) was an intensified surveillance system built upon existing national surveillance of pregnant women with symptoms of Zika virus (ZIKV) disease and conducted in three Colombian cities with a high prevalence of Zika. This analysis of data from VEZ estimates the risk of Zika-associated birth defects among pregnant women with symptoms of ZIKV disease, and among a subset with laboratory evidence of possible ZIKV infection during pregnancy. Methods During April–November 2016, pregnant women were enrolled if they were reported to the surveillance system (Sivigila) or visited participating clinics with symptoms of ZIKV disease. Maternal and pediatric data were abstracted from prenatal care, ultrasound, and delivery records, as well as from pediatric or specialist visit records. Available maternal and infant specimens were tested for the presence of ZIKV RNA and/or anti-ZIKV immunoglobulin (IgM) antibodies. Results Of 1,223 women enrolled, 47.8% and 34.3% reported first or second trimester symptom onset, respectively. Of 381 pregnancies with maternal and/or infant specimens tested, 108 (29%) had laboratory evidence of possible ZIKV infection during pregnancy; half of these (53.3%) were positive for ZIKV RNA only, 37.4% for IgM antibodies only, and 9.3% for both. Of 1,190 of pregnancies with known outcome, 63 (5%) had Zika-associated brain or eye defects; among the subset with any laboratory evidence, 12 (11%) had Zika-associated brain or eye defects. The prevalence of Zika-associated brain or eye defects was 5.9% (35/593) and 4.5% (19/423) among pregnancies with symptom onset in the first and second trimester, respectively. Conclusion Among pregnant women with symptoms of ZIKV disease enrolled during the height of the ZIKV epidemic in Colombia, prevalence of any Zika-associated brain or eye defect was 5%, with a higher prevalence among those with laboratory evidence of possible ZIKV infection. Rapid enhancements to Colombia’s national surveillance enabled the estimation of the risk of birth defects associated with ZIKV disease in pregnancy. Disclosures All Authors: No reported Disclosures.

scholarly journals Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016

2021 ◽  
Vol 15 (3) ◽  
pp. e0009048
Author(s):  
Anna L. Funk ◽  
Bruno Hoen ◽  
Ingrid Vingdassalom ◽  
Catherine Ryan ◽  
Philippe Kadhel ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Birth Defects ◽  
Zika Virus ◽  
Prospective Cohort ◽  
Trial Registration ◽  
Rt Pcr ◽  
Zikv Infection ◽  
Live Births ◽  
Outbreak Period ◽  
Neurological Conditions

Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV. Methods In Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort. Results Of 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2–11.4) had mild abnormalities that have been described as ‘potentially linked to ZIKV infection’; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8–10.6). Conclusions Isolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as ‘potentially linked to ZIKV’ in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4–4.1). Trial registration ClinicalTrials.gov (NCT02916732)

scholarly journals Persistence of Zika virus RNA in the epididymis of the male reproductive tract

2020 ◽  
Author(s):  
Megan B. Vogt ◽  
Francesca Frere ◽  
Seth A. Hawks ◽  
Claudia E. Perez ◽  
Sheryl Coutermarsh-Ott ◽  
...  
Keyword(s):  
Birth Defects ◽  
Persistent Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Infectious Virus ◽  
Sexual Transmission ◽  
In Utero ◽  
Zikv Infection ◽  
Male Reproductive Tract ◽  
Health Decisions

ABSTRACTZika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects. This in utero transmission can occurs following ZIKV infection during pregnancy via sexual transmission or mosquito bite. Infected men may shed ZIKV RNA in semen for over six months post symptom onset, indicating that ZIKV may persistently infect the male reproductive tract (MRT). However, the site of persistent infection in the MRT and whether ZIKV can recrudesce in the MRT is unknown. We hypothesized that if ZIKV establishes a persistent infection in the MRT, then immunosuppressant treatment should stimulate ZIKV replication. We tested this hypothesis in a wild-type mouse model of ZIKV sexual transmission. Male mice were infected with ZIKV and immunosuppressed when they no longer shed infectious virus in their ejaculates. After immunosuppression, ejaculates and MRT tissues were monitored for infectious virus and ZIKV RNA. Our results show that ZIKV recrudescence did not occur following immunosuppression, as we did not detect significant levels of infectious virus in ejaculates or MRT tissues following immunosuppression. We did detect ZIKV RNA in the epididymides of mice treated with the immunosuppressant cyclophosphamide. Further analysis revealed that this ZIKV RNA was contained within the lumen of the epididymis. Our findings suggest that ZIKV persistently infects the epididymis within the male reproductive tract. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.ImportanceZika virus (ZIKV) is an emerging mosquito-transmitted virus that typically causes mild and self-limiting febrile illness in humans; however, during the recent epidemic of ZIKV in the Americas, severe birth defects, such as microcephaly and club foot, were reported in infants born to ZIKV infected mothers. Additionally, sexual transmission has been identified as a secondary method of ZIKV transmission. Since ZIKV can be isolated from semen of infected men long after initial infection, it is imperative to understand the mechanism(s) of ZIKV infection of the male reproductive tract to prevent sexual transmission and ZIKV-associated birth defects. The significance of our research is in identifying a site of persistent ZIKV infection in the male reproductive tract and in assessing the likelihood that a persistently infected individual will begin shedding infectious virus in semen again. This information will enhance our understanding of ZIKV sexual transmission and inform health decisions regarding ZIKV risks.

scholarly journals Molecular Responses to the Zika Virus in Mosquitoes

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 49 ◽  
Author(s):  
Catalina Alfonso-Parra ◽  
Frank Avila
Keyword(s):  
Aedes Aegypti ◽  
Aedes Albopictus ◽  
Birth Defects ◽  
Molecular Interactions ◽  
Zika Virus ◽  
Neurological Complications ◽  
Mosquito Vector ◽  
Zikv Infection ◽  
Molecular Responses ◽  
The Pacific

The Zika virus (ZIKV), originally discovered in 1947, did not become a major concern until the virus swept across the Pacific and into the Americas in the last decade, bringing with it news of neurological complications and birth defects in ZIKV affected areas. This prompted researchers to dissect the molecular interactions between ZIKV and the mosquito vector in an attempt to better understand not only the changes that occur upon infection, but to also identify molecules that may potentially enhance or suppress a mosquito’s ability to become infected and/or transmit the virus. Here, we review what is currently known regarding ZIKV-mosquito molecular interactions, focusing on ZIKV infection of Aedes aegypti and Aedes albopictus, the primary species implicated in transmitting ZIKV during the recent outbreaks.

scholarly journals Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

2021 ◽  
Author(s):  
Raissa Rilo Christoff ◽  
Jefferson H. Quintanilha ◽  
Raiane O Ferreira ◽  
Jessica C. C. G. Ferreira ◽  
Daniel Menezes Guimaraes ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Axon Guidance ◽  
Birth Defects ◽  
Zika Virus ◽  
In Utero ◽  
Mouse Embryos ◽  
Rna Seq ◽  
Zikv Infection ◽  
Density Reduction ◽  
Congenital Zika Syndrome

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with Brazilian ZIKV and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.

scholarly journals In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rebecca Grant ◽  
Olivier Fléchelles ◽  
Benoît Tressières ◽  
Mama Dialo ◽  
Narcisse Elenga ◽  
...  
Keyword(s):  
Cohort Study ◽  
Zika Virus ◽  
Population Based ◽  
In Utero ◽  
Fine Motor ◽  
Neurodevelopmental Outcomes ◽  
Zikv Infection ◽  
Five Dimensions ◽  
Ultrasound Findings ◽  
The Impact

Abstract Background In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. Methods We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother’s pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development—communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. Results Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference − 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. Conclusion In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. Trial registration ClinicalTrials.gov, NCT02810210. Registered 20 June 2016.

scholarly journals Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Genetic Variants ◽  
Educational Level ◽  
Congenital Anomalies ◽  
Family Income ◽  
First Trimester ◽  
In Utero ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

scholarly journals Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1427
Author(s):  
Paula Sobral da Silva ◽  
Sophie Eickmann ◽  
Ricardo Ximenes ◽  
Celina Martelli ◽  
Elizabeth Brickley ◽  
...  
Keyword(s):  
Neurological Examination ◽  
Zika Virus ◽  
Control Group ◽  
P Value ◽  
Zikv Infection ◽  
Clinical Neurological Examination ◽  
Cognitive Delay ◽  
Increased Risk ◽  
Neurodevelopmental Impairment ◽  
The Impact

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

scholarly journals Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dong Wang ◽  
Caixia Liu ◽  
Xinyu Liu ◽  
Ying Zhang ◽  
Yu Wang
Keyword(s):  
Diabetes Mellitus ◽  
Cohort Study ◽  
Pregnant Women ◽  
Gestational Age ◽  
Speckle Tracking ◽  
Control Group ◽  
Second Trimester ◽  
Cardiac Morphology ◽  
Sphericity Index ◽  
And Function

Abstract Background Due to metabolic changes in the second trimester and the increasing number of pregnant women with obesity and advanced maternal age, the incidence of gestational diabetes mellitus (GDM) remains high. This study aimed to evaluate the effects of GDM on fetal cardiac morphology and function, and to determine whether these changes increase with increasing estimated fetal weight (EFW). Methods Fifty-eight women with GDM (GDM group) and 58 women with a healthy pregnancy (control group) were included in this prospective observational cohort study. Each group included subgroups of 31 pregnant women with a gestational age between 24+0 weeks and 27+6 weeks as well as 27 pregnant women with a gestational age between 28+0 weeks and 40+0 weeks. For all fetuses, a cine of 2–3 s in the four-chamber view was obtained, and online speckle-tracking analysis was performed using the GE Automatic Fetal Heart Assessment Tool (fetal HQ; General Electric Healthcare Ultrasound, Zipf, Austria) to measure the global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), 24-segment sphericity index (SI), and 24-segment end-diastolic diameter of the left ventricle (LV) and right ventricle (RV). Data were analyzed using the independent t-test and Wilcoxon rank-sum test, as applicable. Results The GDM group (mean HbA1c value was 5.3 ± 0.57 mmol/L) showed a lower GSI value than the control group (1.21 vs. 1.27, P = 0.000), which indicated a rounder shape of the heart. In addition, fetuses in the GDM group demonstrated significant impairment in cardiac function compared to those in the control group (LV-GLS: -18.26% vs. -22.70%, RV-GLS: -18.52% vs. -22.74%, LV-FAC: 35.30% vs. 42.36%, RV-FAC: 30.89% vs. 36.80%; P = 0.000 for all). Subgroup analyses according to gestational age (24+0–27+6 weeks and 28+0–40+0 weeks) showed that the statistical differences were retained between the GDM and control groups in each subgroup. Conclusions Fetuses of women with GDM present with signs of biventricular systolic dysfunction according to deformation analysis using fetal HQ. Additionally, the heart had a rounder shape in the GDM group than in the control group. This study showed that fetal HQ can be used to assess fetal cardiac morphology and function easily and quickly, and the effects of GDM on fetal cardiac morphology and function appeared from the second trimester. Thus, whether earlier and stricter clinical intervention was necessary remained to be further studied. Furthermore, future studies will need to supplement the effects of blood glucose levels on GLS, FAC, GSI, and 24-segment SI. Additionally, the long-term follow-up after birth should also be improved to observe the influence of changes in the indicators on the prognosis.

scholarly journals Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vertical Transmission ◽  
Birth Defects ◽  
Asian American ◽  
Zika Virus ◽  
French Polynesia ◽  
Transmission Model ◽  
Foreseeable Future ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

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