Cytokines in Blood of Pregnant Women with Zika May Help Develop Prenatal Screening for Zika-Related Birth Defects

Investigators from the University of Southern California (USC) say they have discovered biomarkers in the blood of pregnant women infected with Zika that are associated with severe fetal abnormalities, a finding that could lead to the development of a prenatal screening for microcephaly and other birth defects.

The US Centers for Disease Control and Prevention (CDC) reported 2493 cases of pregnant women with laboratory evidence of Zika virus infection from 2015 through October 16, 2018, in the United States and the District of Columbia, and 4914 such cases in US territories. These have resulted in 116 liveborn infants with Zika-associated birth defects and 9 pregnancy losses. Pregnant women can become infected with Zika through the bite of a mosquito carrying the virus as well as from sexual transmission from an infected partner. Microcephaly, a birth defect marked by smaller than normal head and brain size, is the most common abnormality in infants born to mothers infected with Zika during pregnancy. Congenital Zika syndrome is marked by severe microcephaly, brain damage and decreased brain tissue, damage to the back of the eye, limited range of motion in joints, and muscle changes that restrict a baby’s motion.

Zika virus infection during pregnancy increases the chances of having babies born with these issues; however, not all pregnant women infected with the Zika virus will have a baby born with a birth defect. To this end, a multi-institutional team led by USC investigators explored the association between Zika virus infection and congenital birth defects to understand the varying rate of fetal abnormalities.

For the study, the team analyzed the immune systems of both healthy and Zika-infected pregnant women using blood samples taken during the first, second and third trimesters of pregnancy.

Blood samples from 30 pregnant Zika-infected women and 30 healthy pregnant women from Rio de Janeiro, Brazil, along with 14 healthy pregnant women from Los Angeles were used for the study. After analyzing 69 different cytokines in the blood, the team found that 16 cytokines were associated with congenital defects.

Although the study team has yet to determine if these cytokines cause birth defects, the findings could help researchers develop a prenatal screening for birth defects in Zika-infected mothers.

In an interview with Contagion®, study first author Suan-Sin Foo, PhD, USC, explained that a screening could be helpful to expectant mothers, particularly those exposed to Zika during the first or second trimester of pregnancy, when the risk of birth defects is highest.

“Elevated expressions of these biomarkers can be detected in blood specimens of Zika-positive pregnant women from all stages of pregnancy,” Dr. Foo explained. “However, higher expressions of these biomarkers are present in Zika-positive pregnancies associated with fetal abnormalities when compared to Zika-positive pregnancy with normal outcomes.”

Before an accurate prenatal screening can become available, Dr. Foo says they will need to conduct extensive studies to evaluate the biological roles of these biomarkers during Zika-positive pregnancies and also confirm the expression of these biomarkers in a larger pool of Zika-positive pregnancies that are associated with abnormal fetal outcomes.

“We will definitely be performing more thorough studies experimentally using whole blood infection model and subsequently Zika mouse model to dissect the biological role of these elevated biomarkers in contributing to Zika virus-induced fetal abnormalities,” said Dr. Foo.

Pregnant women who may become exposed to the Zika virus are encouraged to take steps to avoid mosquito bites and avoid sex with a Zika-infected partner. The CDC recommends preventing pregnancy for women living in Zika-affected areas or with Zika-infected partners.