Zika Virus Detection in Amniotic Fluid and Zika-Associated Birth Defects

Abstract Background Zika virus (ZIKV) infection during pregnancy can cause serious birth defects, including brain and eye abnormalities. The clinical importance of detection of ZIKV ribonucleic acid (RNA) in amniotic fluid is unknown. Objectives To describe patterns of ZIKV RNA testing of amniotic fluid relative to other clinical specimens and to examine the association between ZIKV detection in amniotic fluid and Zika-associated birth defects. Our null hypothesis was that ZIKV detection in amniotic fluid was not associated with Zika-associated birth defects. Study Design We conducted a retrospective cohort analysis of women with amniotic fluid specimens submitted to Colombia’s National Institute of Health as part of national ZIKV surveillance from January 2016 to January 2017. Specimens (maternal serum, amniotic fluid, cord blood, umbilical cord tissue, and placental tissue) were tested for the presence of ZIKV RNA using a singleplex or multiplex real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay. Birth defect information was abstracted from maternal prenatal and infant birth records and reviewed by expert clinicians. Chi-square and Fisher’s exact tests were used to compare the frequency of Zika-associated birth defects (defined as brain abnormalities [with or without microcephaly, but excluding neural tube defects and their associated findings] or eye abnormalities) by frequency of detection of ZIKV RNA in amniotic fluid. Results Our analysis included 128 women with amniotic fluid specimens. Seventy-five women (58%) had prenatally-collected amniotic fluid, 42 (33%) at delivery, and 11 (9%) had missing collection dates. Ninety-one women had both amniotic fluid and other clinical specimens submitted for testing, allowing for comparison across specimen types. Of those 91 women, 68 had evidence of ZIKV infection based on detection of ZIKV RNA (ZIKV+) in > 1 specimen. Testing of amniotic fluid collected prenatally or at delivery identified 39 (57%) of these ZIKV infections (15 [22%] identified only in amniotic fluid), and 29 (43%) infections were identified in other specimen types and not amniotic fluid. Among women included in the analysis, 89 had pregnancy outcome information available, allowing for assessment of the presence of Zika-associated birth defects. Zika-associated birth defects were significantly (p Conclusions Testing of amniotic fluid provided additional evidence for maternal diagnosis of ZIKV infection. Zika-associated birth defects were more common among women with ZIKV RNA detected in prenatal amniotic fluid specimens than women with no laboratory evidence of ZIKV infection, but similar to women with ZIKV RNA detected in other, non-amniotic fluid specimen types.