Clinical Importance of Placental Testing among Suspected Cases of Congenital Zika Syndrome

Abstract

Contemporaneous Zika virus (ZIKV) strains can cause congenital Zika syndrome (CZS). Current ZIKV clinical laboratory testing strategies are limited and include IgM serology (which may wane 12 weeks after initial exposure) and nucleic acid testing (NAT) of maternal serum, urine, and placenta for (+) strand ZIKV RNA (which is often transient). The objectives of this study were to determine if use of additional molecular tools, such as quantitative PCR and microscopy, would add to the diagnostic value of current standard placental ZIKV testing in cases with maternal endemic exposure and indeterminate testing. ZIKV RNA was quantified from dissected sections of placental villi, chorioamnion sections, and full cross-sections of umbilical cord in all cases examined. Quantitation with high-resolution automated electrophoresis determined relative amounts of precisely verified ZIKV (74-nt amplicons). In order to localize and visualize stable and actively replicating placental ZIKV in situ, labeling of flaviviridae glycoprotein, RNA ISH against both (+) and (–) ZIKV-specific ssRNA strands, and independent histologic examination for significant pathologic changes were employed. We demonstrate that the use of these molecular tools added to the diagnostic value of placental ZIKV testing among suspected cases of congenital Zika syndrome with poorly ascribed maternal endemic exposure.

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

“…Traveller/non-traveller populations: In this update, we found further evidence that congenital abnormalities occurred in infants born to women travellers returning from ZIKV-affected areas and women remaining in those areas. In total, 25 publications report on 272 congenital abnormalities due to ZIKV infection in travellers 27, 29, 30, 32, 34, 36, 38, 42, 45, 56, 58, 61, 89, 94, 98, 109, 117, 122, 123, 137, 140, 151, 153, 166, 173 , with 109 publications reporting congenital abnormalities due to ZIKV in 2652 non travellers 24– 26, 28, 31, 33, 35, 37, 39– 41, 43, 44, 46– 48, 50, 51, 54, 57, 60, 62– 79, 81, 83– 85, 87, 88, 90– 93, 95– 97, 100, 101, 104– 106, 110– 113, 115, 116, 118, 119, 121, 124– 135, 142– 147, 149, 152, 154, 156– 164, 167, 168, 171, 172, 175– 180, 182, …”

Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life

“…classified as uninfected had undetectable viremia and immune response at birth. To increase the sensitivity of neonatal testing, we included positive RT-PCR on placental samples in the definition of laboratory-confirmed congenital ZIKV infections 23 . However, we did not observe contradictory results in cases of infected placentas, as all also had a positive IgM and/or RT-PCR in fetal/neonatal samples.…”

“…Details of maternal, fetal, and neonatal testing are available in our previous studies 4,11 . Placentas were sampled and tested according to the method described in our dedicated study, which also corresponds to what was proposed by Seferovic and colleagues 23,27 .…”

The impact of tobacco chemicals and nicotine on placental development

“…Specific changes have been documented in the placenta with exposures during pregnancy. The placenta is a portal and reservoir for a number of congenital viruses which do not result in evident gross placental inflammation, such as we and others demonstrated with Zika virus . Maternal obesity, gestational diabetes, and alcohol consumption are associated with highly predictive changes in the placenta.…”

“…The placenta is a portal and reservoir for a number of congenital viruses which do not result in evident gross placental inflammation, such as we and others demonstrated with Zika virus. [36][37][38] Maternal obesity, 39,40 gestational diabetes, 41 and alcohol consumption 42,43 are associated with highly predictive changes in the placenta. Levels of polycyclic aromatic hydrocarbons, a carcinogenic and toxic component of tobacco smoke, have been measured from the placenta in a study of preterm birth.…”