Congenital Zika syndrome: association between the gestational trimester of maternal infection, severity of brain computed tomography findings and microcephaly at birth

Abstract

This study analyzed possible associations between the trimester of maternal Zika virus infection (ZIKV) in pregnancy, severity of brain computed tomography (CT) findings and the presence of microcephaly at birth in children with Congenital Zika Syndrome (CZS). It was an analytical study in a cohort of children with CZS. Symptoms of maternal infection were dichotomized into the 1st trimester of pregnancy and other trimesters. Head circumference (HC) at birth was used to calculate the z-score. Mild microcephaly was defined as HC between 2 and ≥3 standard deviations (SD) below the mean for each gestational age and sex, and severe microcephaly when HC <3 SD below average. Brain CT images were evaluated by two radiologists and classified, according to the severity, into mild, moderate and severe. Fisher's exact, Mann-Whitney and Kruskal-Wallis tests were used to verify the associations between variables. In 108 children, maternal infection in the 1st trimester of pregnancy was associated with more severe brain CT abnormalities (p=0.038), greater severity of microcephaly at birth (p=0.013) and lower HC z-scores at birth (p=0.021). The severity of brain CT lesions was also associated with lower HC z-scores at birth (p<0.001). Maternal ZIKV infection during the first trimester of pregnancy proved to be an important risk factor for a more severe spectrum of CZS, as it is associated with more severe brain CT abnormalities and, consequently, with lower HC z-scores at birth.

Figure 1. Classification of the severity of brain CTlesions : A) axial section showing sparse calcifications in the cerebral parenchyma, alteration classified as mild, with no signs of volumetric reduction of the brain or malformation of cortical development; B) axial section showing malformation of diffuse cortical development, alteration classified as moderate, in addition to sparse calcifications and moderate reduction in brain volume; C) axial section showing severe brain atrophy (severe alteration), cerebral calcifications and severe ex-vacuum ventriculomegaly.