Maternal and Neonatal Characteristics Associated with Microcephaly Following Prenatal Zika Virus Infection

Background and Objectives: Prenatal Zika virus (ZIKV) infection can cause varying degrees of brain injury, though it is unclear why some infants are more severely affected than others. We aimed to evaluate how maternal and neonatal factors relate to brain injury in infants prenatally exposed to Zika virus.<br><br>Methods: We performed a secondary analysis of 961 mother-infant dyads across Brazil, Colombia, and Puerto Rico. This analysis was performed using the datasets made available through the Prenatal Infections and Neurodevelopmental Genetics (PING) Consortium. We evaluated trimesters of infection, maternal age, and a harmonized composite socioeconomic-education index. Signs of brain injury were evaluated by neuroimaging or clinical evaluation. Associations were estimated using Generalized Linear Models and logistic mixed-effects models.<br><br>Results: Among 961 ZIKV-exposed mother–infant dyads, 257 infants met criteria for microcephaly-defined severe brain injury. Infants with microcephaly exhibited a higher co-occurrence of structural and clinical neurological findings compared to normocephalic infants, including ventriculomegaly (63.8%), cortical malformation (54.5%), and cortical atrophy (17.1%). Infants with microcephaly were more likely to have reduced median birth weight (2725 g) and length (47.0 cm) compared to normocephalic affected infants. Low maternal socioeconomic-education status was associated with over eight-fold increased odds of microcephaly (OR 8-9; p&lt;0.01). Among exposed cases, 53 infants (20.6%) were normocephalic at birth but developed postnatal microcephaly. Most of these children were in low (39.6%) or intermediate (45.3%) socioeconomic-education households.<br><br>Discussion: Socioeconomic-educational disadvantage emerges as a key predictor of severe ZIKV-related brain injury. Addressing social disparities through targeted public health interventions may reduce brain injury severity and improve outcomes for prenatally infected infants.