Placental infection by Zika virus in French Guiana

Abstract

Objectives To describe placental findings on prenatal ultrasound and anatomopathological examination in women with Zika virus (ZIKV) infection, and to assess their association with congenital ZIKV infection and severe adverse outcome, defined as fetal loss or congenital Zika syndrome (CZS). Methods This was a prospective study of pregnancies undergoing testing for maternal ZIKV infection at a center in French Guiana during the ZIKV epidemic. In ZIKV‐positive women, congenital infection was defined as either a positive reverse transcription polymerase chain reaction result or identification of ZIKV‐specific immunoglobulin‐M in at least one placental, fetal or neonatal sample. Placental ZIKV‐infection status was classified as non‐exposed (placentae from non‐infected women), exposed (placentae from ZIKV‐infected women without congenital infection) or infected (placentae from ZIKV‐infected women with proven congenital infection). Placentae were assessed by monthly prenatal ultrasound examinations, measuring placental thickness and umbilical artery Doppler parameters, and by anatomopathological examination after live birth or intrauterine death in women with ZIKV infection. The association of placental thickness during pregnancy and anatomopathological findings with the ZIKV status of the placenta was assessed. The association between placental findings and severe adverse outcome (CZS or fetal loss) in the infected group was also assessed. Results Among 291 fetuses/neonates/placentae from women with proven ZIKV infection, congenital infection was confirmed in 76 cases, of which 16 resulted in CZS and 11 resulted in fetal loss. The 215 remaining placentae from ZIKV‐positive women without evidence of congenital ZIKV infection represented the exposed group. A total of 334 placentae from ZIKV‐negative pregnant women represented the non‐exposed control group. Placentomegaly (placental thickness > 40 mm) was observed more frequently in infected placentae (39.5%) than in exposed placentae (17.2%) or controls (7.2%), even when adjusting for gestational age at diagnosis and comorbidities (adjusted hazard ratio (aHR), 2.02 (95% CI, 1.22–3.36) and aHR, 3.23 (95% CI, 1.86–5.61), respectively), and appeared earlier in infected placentae. In the infected group, placentomegaly was observed more frequently in cases of CZS (62.5%) or fetal loss (45.5%) than in those with asymptomatic congenital infection (30.6%) (aHR, 5.43 (95% CI, 2.17–13.56) and aHR, 4.95 (95% CI, 1.65–14.83), respectively). Abnormal umbilical artery Doppler was observed more frequently in cases of congenital infection resulting in fetal loss than in those with asymptomatic congenital infection (30.0% vs 6.1%; adjusted relative risk (aRR), 4.83 (95% CI, 1.09–20.64)). Infected placentae also exhibited a higher risk for any pathological anomaly than did exposed placentae (62.8% vs 21.6%; aRR, 2.60 (95% CI, 1.40–4.83)). Conclusions Early placentomegaly may represent the first sign of congenital infection in ZIKV‐infected women, and should prompt enhanced follo...

Zika Induces Human Placental Damage and Inflammation

“…The main alteration observed in the placentae of the cases studies was the delay in villi maturation, confirmed by other groups ( 17 – 19 ). These histopathological alterations are similar to those described in the placentae from ZIKV + women in French Guiana, such as villitis, intervillositis, calcification, infarct, ischemia, inflammatory infiltrate and fibrin deposits ( 20 – 22 ). Overall, the placental changes discovered in ZIKV infection are non-pathognomonic and often have particular characteristics in different patients.…”

Adequate Placental Sampling for the Diagnosis and Characterization of Placental Infection by Zika Virus

“…Moreover, distinction between low-and high-grade villitis is important because high-grade villitis has significant associations with IUGR, neurodevelopmental impairment, and likelihood of recurrence (Tamblyn et al, 2013;Khong et al, 2016). Interestingly, some groups showed that ZIKV-infected placentas have a higher risk for development of pathological anomalies than non-infected placentas (Pomar et al, 2019). Placentomegaly, umbilical artery Doppler anomaly, fibromuscular hypertrophy, acute chorioamnionitis, funisitis, chronic villitis, fibrosis, and the presence of neutrophils in the intervillous space can be frequently observed in ZIKV-infected placentas (Beaufrère et al, 2019;Pomar et al, 2019).…”

“…Interestingly, some groups showed that ZIKV-infected placentas have a higher risk for development of pathological anomalies than non-infected placentas (Pomar et al, 2019). Placentomegaly, umbilical artery Doppler anomaly, fibromuscular hypertrophy, acute chorioamnionitis, funisitis, chronic villitis, fibrosis, and the presence of neutrophils in the intervillous space can be frequently observed in ZIKV-infected placentas (Beaufrère et al, 2019;Pomar et al, 2019). In fact, it is not totally clear if placental alterations are risk factors for adverse fetal or neonatal outcomes or if they are associated with maternal-fetal transmission of ZIKV, which is estimated between 7 and 26% (Pomar et al, 2019).…”

Insights into the role of placenta thickness as a predictive marker of perinatal outcome

“…Several maternal complications can lead to sonographic abnormalities of PT, including preeclampsia, diabetes mellitus (DM), anemia, cytomegalovirus (CMV) infection, Toxoplasma gondii infection, or syphilis. 31–39 Increased PT may be induced by preeclampsia via reactive changes in placenta villi to ischemia, along with increased secretion of trophoblast-derived proteins in maternal blood, such as human chorionic gonadotropin, activin, and inhibin. 30 Such changes might lead to an antiangiogenic state and reciprocally trigger preeclampsia.…”