Abstract
BackgroundUntil recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes.MethodsAt research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained.DiscussionWith the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure.Trial registrationNCT02856984. Registered August 5, 2016. Retrospectively registered.
Highlights
MethodsAt research sites in Zika virus (ZIKV) endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age
Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting
The results of this study showed a strong association between microcephaly and laboratory confirmed Zika virus infection (Odds Ratio: 73.1; 95% CI 13·0–∞), after adjusting for confounders, and none of the other risk factors studied, including use of the larvicide, pyriproxyfen, nor vaccine administration during pregnancy, was associated with microcephaly in multivariable analyses [13]
Summary
Study design This prospective, international, multisite cohort Zika in Infants and Pregnancy (ZIP) study will recruit up to 10, 000 pregnant women from ZIKV-endemic regions and follow them longitudinally throughout pregnancy, delivery, and 6 weeks postpartum. Women testing positive for ZIKV will be scheduled for two additional clinic visits within 2 weeks for collection of additional blood, urine, saliva, vaginal fluid samples and a fetal ultrasound, per country and local guidelines. Sample size calculations for primary objectives The power of the study to detect a difference was estimated by simulation, using the prevalence of ZIKV infection and adverse fetal outcome (Table 3 and Table 4) These power simulations are based on Fisher’s Exact Tests. The site record maintenance will be compliant with ICH E6 section 4.9 and regulatory and institutional requirements for the protection of participant confidentiality
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