Plasma lipidome profiling of newborns with antenatal exposure to Zika virus

PLoS Negl Trop Dis. 2021 Apr 30;15(4):e0009388. doi: 10.1371/journal.pntd.0009388. eCollection 2021 Apr.


The 2015-2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil / epidemiology
  • Disease Outbreaks
  • Eye Abnormalities / blood
  • Eye Abnormalities / epidemiology*
  • Eye Abnormalities / virology
  • Female
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / epidemiology
  • Infectious Disease Transmission, Vertical / statistics & numerical data
  • Lipids / blood*
  • Male
  • Microcephaly / blood
  • Microcephaly / epidemiology*
  • Microcephaly / virology
  • Pregnancy
  • Pregnancy Complications, Infectious / virology*
  • Zika Virus / isolation & purification
  • Zika Virus Infection / blood
  • Zika Virus Infection / congenital*
  • Zika Virus Infection / transmission


  • Lipids

Grants and funding

This research was funded by the Coordenação de Vigilância em Saúde e Laboratórios de Referência, Brazilian Ministry of Health (CVSRL-Fiocruz to AMBF), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, grant number E-26/2002.930/2016 to AMBF), Horizon 2020 through ZikaPlan and ZikAction (grant agreement numbers 734584 and 734857), the International Development Research Centre Canada (IDRC, 108411-001 to AMBF), the National Council for Scientific and Technological Development (CNPq, 440685/2016-8 and 443875/2018 to ICS), and the São Paulo Research Foundation (FAPESP, CEPID-Redoxoma 2013/07937–8 to SM). Postdoc fellowships were received from the Coordination for the Improvement of Higher Education Personnel (MYY), IDRC (NRCF) and FAPESP (ABC-F). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.