Two recent studies, including one published today in Pediatrics, show that exposure to the Zika virus (ZIKV) in utero can have affect children's development later in childhood, with today's study showing the finding holds true even when the children are born without signs of congenital Zika syndrome (CZS).
The study in Pediatrics is based on outcomes seen in Brazil among mother-infant pairs from 2018 to 2022. The children were assessed for early (congenital anomalies) and long-term adverse outcomes (neurodevelopmental delay), and the study included children with and without CZS, which is a group of birth defects associated with the disease.
Researchers enrolled 148 mother-child pairs, including 79 Zika-exposed in pregnancy and 69 controls. Children were assessed at ages 2 through 5. Overall, 40 (27.4%) had at least one adverse outcome, including 30 of 77 (39.0%) in the exposed group and 10 of 69 (14.5%) in the control group.
"Children who were ZIKV exposed in utero had 2.7 times the risk of adverse outcomes compared with children who were not classified as having ZIKV exposure in utero," the authors wrote.
Among the Zika-exposed children, 13 had congenital anomalies associated with CZS; notably, all had microcephaly, which means smaller-than-normal brains and heads. Three of the 13 also had hydrocephalus. The overall incidence of congenital anomalies in Zika-exposed children was 16.5 cases per 100 children.
Worse outcomes with exposure in first trimester
In children both with and without CZS in the exposed group, worse outcomes were seen if exposure occurred in the first trimester of pregnancy.
"Children who were ZIKV exposed during the first trimester had 11.2 times the chance of adverse early outcomes compared with children who were exposed in third trimester," the authors said. "For long-term outcomes, children who were ZIKV exposed in the first trimester had 2.8 times the chance of having adverse late outcomes compared with children exposed in the third trimester."
Exposed children without CZS were more likely to show cognitive delays, rather than gross or fine-motor delays.
Though the study was conducted with participants who knew their Zika status in pregnancy through testing, the authors said their findings highlight an important feature of Zika virus infection: In adults, including pregnant women, many infections are asymptomatic.
Clinical manifestations in children can surface later, potentially leading to numerous undetected cases.
"Clinical manifestations in children can surface later, potentially leading to numerous undetected cases," they wrote. "This underscores the complexities in identifying asymptomatic cases, which may result in underestimating the total number of cases."
CZS linked to early childhood hospitalizations
The second study, published last week in the International Journal of Infectious Diseases, shows that children with CZS will have more frequent hospitalizations in early childhood than peers without CZS.
The study, also conducted in Brazil, compared almost 1,894 children with CZS to 2.6 million without. The authors estimated hospitalization rates, causes, and length of stay for the two groups using medical records.
Compared to the group without the syndrome, the children with CZS had a higher incidence of preterm birth (19.5% vs. 10.3%) and of being small for gestational age (36.3% vs. 7.6%), the authors said.
In total 66.5% of children with CZS had at least one hospital admission in early childhood compared to 20.8% without. Hospital visits were twice as long in the CZS group, with an average stay of 10 days versus 5 days.
"The present study found that live-born children with Congenital Zika Syndrome have persistently higher rates of hospitalization compared to those without the syndrome during their first 4 years of life," the authors concluded. "These findings highlight the substantial disease burden and associated healthcare costs for affected children, carrying important implications for families, healthcare providers, and policymakers, particularly in regions where Zika virus is endemic."