Fetal and neonatal outcomes after Zika virus infection during pregnancy: A systematic review

Dr Clare Whitehead1, Dr Laura Erdman2, Dr Lauren Ramsay3, Mr Justin Boyle4, Dr Raphael Ximenes3, Ms Joanne Bielecki3, Ms Panashe Tombindo3, Mr Ryan O'Reilly4, Dr Carsten Krueger2, Dr Shannon Willmott2, Dr Rafael Neves Miranda3, Dr Shaun Morris2, Dr Kellie Murphy1, Dr Beate Sander3
1Mount Sinai Hospital, Toronto, ON, Canada. 2Hospital for Sick Children, Toronto, ON, Canada. 3THETA, University of Toronto, Toronto, ON, Canada. 4University of Toronto, Toronto, ON, Canada


Objective:  A systematic review of the current literature to determine the fetal and neonatal outcomes of pregnancies infected with Zika virus (ZIKV). Methods: We conducted a systematic review following PRISMA guidelines and Cochrane systematic review methodology. MEDLINE, Embase, PubMed, CINAHL, LILACS, and WHO's ICTRP clinical trials registries database were searched using terms “Zika virus” and “Zika infection”. Editorials, letters, news articles, and experimental animal studies were excluded. Case reports or series with less than 10 cases were excluded. Two independent reviewers conducted title/abstract screening, full text screening, and data extraction using a pre-specified form. Conflicts were resolved by consensus or consultation with a third reviewer. JBI tools were used to assess quality. Results: The initial search (up to 30/04/2018) identified 7394 references, of which 69 studies met inclusion criteria (92,882 cases of possible ZIKV in pregnancy). There were 47 case series, 7 case-control, 9 cohort and 6 cross-sectional studies. Studies were predominately from Brazil (45), the USA (11) and Colombia (5). There was wide variation in diagnostic criteria for ZIKV exposure due to local availability of serological testing and pre/postnatal neuroimaging. 6.5% (258/3772) of exposed fetuses developed birth defects consistent with ZIKV. Anomalies were most common after first trimester exposure (8.5% vs. 6.3% vs 5.2% per trimester). Microcephaly and intracranial abnormalities predominated, but extracranial CNS, cardiac and growth abnormalities were also frequently present in affected fetuses/infants. The effect of timing of exposure, maternal symptoms, testing approaches and infant follow up duration were analyzed individually. Final analysis will include all publications to 31/12/2018. Conclusion: ZIKV infection during pregnancy leads to intracranial and extracranial abnormalities in affected fetuses and infants. Understanding the nature, timing and frequency of these abnormalities will allow development of screening, diagnostic and clinical guidelines for ZIKV.