Adverse neurologic outcomes associated with maternal Zika virus infection

1. Infants born to symptomatic Zika-positive mothers demonstrated higher rates of fetal death, fetal growth restriction and central nervous system abnormalities.

2. Zika-positive pregnant women were more likely to present with maculopapular pruritic rash and conjunctival injection compared to Zika-negative pregnant women.

Evidence Rating Level: 2 (Good)

Study Rundown: Zika virus (ZIKV) is a flavivirus that uses the Aedes aegypti mosquito as a vector. Clinical signs and symptoms of Zika virus include fever with maculopapular pruritic rash, arthralgias and nonpurulent conjunctivitis. In this prospective cohort study that spanned between September 2015 and May 2016, researchers assessed whether symptomatic ZIKV-positive pregnant women had abnormal pregnancy outcomes compared to similarly symptomatic but ZIKV-negative pregnant women in Brazil. Overall, adverse outcomes in newborns occurred at a significantly greater rate in symptomatic ZIKV-positive mothers compared to ZIKV-negative mothers. While there was no significant difference in fetal death rate between groups, infants born to ZIKV-positive mothers had higher rates of abnormal findings on clinical exam, brain imaging or both. This study is limited by clinical and imaging data that reflects individual assessment with knowledge of ZIKV infection status.

Click to read the study, published today in NEJM

Relevant Reading: Neurologic syndrome, congenital malformations and Zika virus infection: Implications for public health in the Americas

In-Depth [prospective cohort]: Researchers enrolled 345 pregnant women between September 2015 and May 2016. Women were included if they had experienced a rash within the previous 5 days of enrolment. Of these women, 53% (182) were ZIKV-positive by testing blood, urine or both. For this study, 134 ZIKV-positive women and 73 ZIKV-negative women were included. Of the ZIKV-positive and negative participants, 94% and 83.5% had known and available pregnancy outcomes. ZIKV infection occurred anywhere between 6-39 weeks. Conjunctival injection occurred in 58% and 52% of ZIKV-positive and –negative women, respectively (p = 0.03). Fatigue and malaise occurred in 52% and 75% of ZIKV-positive and negative women, respectively (p = 0.002). Among ZIKV-pregnancies, there were 5 miscarriages, 2 losses and 2 still births. Of the live births of ZIKV-positive and –negative mothers, 49 out of 117 (42%) versus 3 out of 57 (5%) had abnormalities on clinical exam, imaging or both (p < 0.001). With regards to specific newborn outcomes, 9% vs. 5.3% were small for gestational age for ZIKV-positive and –negative mothers, respectively (p = 0.006). Four infants in the ZIKV-positive were born with microcephaly. There was no significant difference in fetal loss for ZIKV-positive and –negative mothers (7.2% versus 6.6%; p = 1.0). Of note, chikungunya infection was more common in the ZIKV-negative versus –positive mothers (42% versus 43%; p < 0.001). Overall adverse outcomes occurred in 46% of newborns of ZIKV-positive women compared to 11.5% among of ZIKV-negative women (p < 0.001).

Image: PD

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