Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis

Suarez

et al. 2022

IJERPH

During the 2015–2016 Zika Virus (ZIKV) epidemic in Brazil, the geographical distributions of ZIKV infection and microcephaly outbreaks did not align. This raised doubts about the virus as the single cause of the microcephaly outbreak and led to research hypotheses of alternative explanatory factors, such as environmental variables and factors, agrochemical use, or immunizations. We investigated context and the intermediate and structural determinants of health inequalities, as well as social environment factors, to determine their interaction with ZIKV-positive- and ZIKV-negative-related microcephaly. The results revealed the identification of 382 associations among 382 nonredundant variables of Zika surveillance, including multiple determinants of environmental public health factors and variables obtained from 5565 municipalities in Brazil. This study compared those factors and variables directly associated with microcephaly incidence positive to ZIKV and those associated with microcephaly incidence negative to ZIKV, respectively, and mapped them in case and control subnetworks. The subnetworks of factors and variables associated with low birth weight and birthweight where birth incidence served as an additional control were also mapped. Non-significant differences in factors and variables were observed, as were weights of associations between microcephaly incidence, both positive and negative to ZIKV, which revealed diagnostic inaccuracies that translated to the underestimation of the scope of the ZIKV outbreak. A detailed analysis of the patterns of association does not support a finding that vaccinations contributed to microcephaly, but it does raise concerns about the use of agrochemicals as a potential factor in the observed neurotoxicity arising from the presence of heavy metals in the environment and microcephaly not associated with ZIKV. Summary: A comparative network inferential analysis of the patterns of variables and factors associated with Zika virus infections in Brazil during 2015–2016 coinciding with a microcephaly epidemic identified multiple contributing determinants. This study advances our understanding of the cumulative interactive effects of exposures to chemical and non-chemical stressors in the built, natural, physical, and social environments on adverse pregnancy and health outcomes in vulnerable populations.

Section: Resultsmentioning

confidence: 99%

Big Data to Knowledge Analytics Reveals the Zika Virus Epidemic as Only One of Multiple Factors Contributing to a Year-Over-Year 28-Fold Increase in Microcephaly Incidence

Suarez

et al. 2022

IJERPH

The American Journal of Tropical Medicine and Hygiene

“…28 But, maternal ZIKV infection has been associated with several serious fetal and neonatal defects including intracranial calcifications, ventriculomegaly, microcephaly, ocular abnormalities, fetal loss, small for gestational age, low birth weight, and prematurity. 9,28,29 Though several cognitive, sensory, and motor disabilities caused by ZIKV are also seen with other congenital infections, a unique congenital Zika syndrome has been described that includes five features: severe microcephaly, thin cerebral cortices with subcortical calcifications, macular scarring, congenital contractures, and extrapyramidal symptoms with hypertonia. 30 This is probably the first study from India studying the three arboviruses, that is, dengue, chikungunya, and Zika viruses in pregnant women.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Dengue, Chikungunya, and Zika Viruses in Febrile Pregnant Women: An Observational Study at a Tertiary Care Hospital in North India

Gupta

Jain

Venkatesh

et al. 2022

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) are arboviruses that can affect maternal and fetal outcome if acquired during pregnancy. This study was done to estimate the positivity of DENV, CHIKV, and ZIKV in febrile pregnant women attending a tertiary care hospital in north India. Symptomatic pregnant women were tested for these viruses by IgM ELISA and/or by Trioplex real-time polymerase chain reaction. Their symptoms and laboratory parameters were recorded and were followed up till delivery to know their immediate delivery outcome. Of 104 women tested, 50 (48.1%) were positive for viral markers. Of these, evidence of infection by DENV, CHIKV, and both was found in 34 (32.7%), 10 (9.6%), and 6 (5.8%), respectively. ZIKV was not detected in any woman. Maximum DENV positivity occurred in the third trimester of pregnancy and in women residing in urban than rural areas. Chills and rigors, arthralgia, retro-orbital pain, anemia, and vaginal bleeding were more commonly associated with DENV positivity. Backache, arthralgia, jaundice, and vaginal bleeding were more common in CHIKV positives but the difference between positives and nonpositives regarding these symptoms was not statistically significant. Dengue infections were associated with more frequent hospitalizations (OR = 8.38, 95% confidence intervals [CI] = 3.29–21.30) and mortality (OR = 19.0, 95% CI = 1.01–357.10). Hence, to conclude, in India wherever possible, all symptomatic pregnant women should be screened for DENV, CHIKV, and ZIKV as part of sentinel surveillance for ZIKV.

“…The causal connection between ZIKV infection during pregnancy and subsequent birth defects, which are collectively referred to as Congenital Zika Syndrome (CZS), was confirmed with the detection of ZIKV RNA in amniotic fluid of pregnant women carrying children with microcephaly and the isolation of ZIKV from the brain of an infant who died after birth (6,8). Notably, multiple systematic reviews and meta-analyses performed after the end of the epidemic confirmed the association between ZIKV infection during pregnancy and CZS (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 87%

Downregulation of Transcriptional Activity, Increased Inflammation, and Damage in the Placenta Following in utero Zika Virus Infection Is Associated With Adverse Pregnancy Outcomes

et al. 2022

Zika virus (ZIKV) infection during pregnancy causes serious adverse outcomes to the developing fetus, including fetal loss and birth defects known as congenital Zika syndrome (CZS). The mechanism by which ZIKV infection causes these adverse outcomes, and specifically the interplay between the maternal immune response and ZIKV replication has yet to be fully elucidated. Using an immunocompetent mouse model of transplacental ZIKV transmission and adverse pregnancy outcomes, we have previously shown that Asian lineage ZIKV disrupts placental morphology and induces elevated secretion of IL-1β. In the current manuscript, we characterized placental damage and inflammation during in utero African lineage ZIKV infection. Within 48 h after ZIKV infection at embryonic day 10, viral RNA was detected in placentas and fetuses from ZIKA infected dams, which corresponded with placental damage and reduced fetal viability as compared with mock infected dams. Dams infected with ZIKV had reduced proportions of trophoblasts and endothelial cells and disrupted placental morphology compared to mock infected dams. While placental IL-1β was increased in the placenta, but not the spleen, within 3 h post infection, this was not caused by activation of the NLRP3 inflammasome. Using bulk mRNAseq from placentas of ZIKV and mock infected dams, ZIKV infection caused profound downregulation of the transcriptional activity of genes that may underly tissue morphology, neurological development, metabolism, cell signaling and inflammation, illustrating that in utero ZIKV infections causes disruption of pathways associated with CZS in our model.