International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol

Abstract

Background Until 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. Methods At 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. Discussion With 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 registration NCT02856984 . Registered August 5, 2016. Retrospectively registered.

Cognitive Development of Infants Exposed to the Zika Virus in Puerto Rico

“…The study prospectively enrolled a cohort of pregnant women during their first and early second trimester of pregnancy and followed them through their pregnancies to identify ZIKV through blood testing. 21,22…”

Patient characteristics and pregnancy outcomes among Zika‐infected pregnant women: Epidemiologic surveillance data from two cities in Colombia, 2015–2016

“…Unfortunately, access to data on the occurrence of congenital malformation was restricted; we were therefore unable to include these data in this analysis, but we hope that it will be published in additional studies conducted by other investigators in the country . Our focus was on observing pregnancy outcomes and on describing the quality of demographic surveillance system data.…”

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG–PC): A Cohort Profile

“…The children classified according to their exposure status and clinical characteristics (see Section 2 . Aims and Objectives) were grouped according to the source of the recruitment and referred to as the Outpatient Group (OG) (composed of children classified as i and ii), the Microcephaly Case–Control Study (MCCS) (composed by children classified as i and iv) [ 4 , 5 ], the MERG Pregnant Women with Rash Cohort (MERG–PWC) (composed by children classified as iii and iv) [ 9 ] and the Control Group (CG) (composed by children classified as iv) [ 10 ]. The recruitment for each group is described below.…”