Microcephaly and Associated Risk Factors in Newborns: A Systematic Review and Meta-Analysis Study

Abstract

Congenital microcephaly is caused by a multitude of drivers affecting maternal–fetal health during pregnancy. It is a rare outcome in high-income industrial countries where microcephaly rates are in the range of 0.3–0.9 per 1000 newborns. Prevalence of microcephaly varies considerably across developing countries and can go as high as 58 cases per 1000 live births in pregnancies exposed to infection by Zika virus (ZIKV). Not only ZIKV-infected pregnancies, but other drivers can modulate the occurrence and severity of this outcome. Here, we sought to test the ZIKV–microcephaly association vs. competing hypotheses using a meta-analysis with 8341 microcephaly cases pooled from 10,250,994 newborns in the Americas, Africa, and Asia. Analysis of risk ratios (RR) showed teratogens the most likely microcephaly-associated risk factor (RR = 3.43; 95%-CI 2.69–4.38; p-value < 0.0001), while the statistical significance of the ZIKV–microcephaly association was marginal (RR = 2.12; 95%-CI 1.01–4.48; p-value = 0.048). Other congenital infections showed strong but variable associations with microcephaly (RR = 15.24; 95%-CI 1.74–133.70; p-value = 0.014). Microcephaly cases were associated with impoverished socioeconomic settings, but this association was statistically non-significant (RR = 2.75; 95%-CI 0.55–13.78; p-value = 0.22). The marginal ZIKV–microcephaly association and statistical significance of the competing hypotheses suggest maternal ZIKV infection might not be a cause of microcephaly alone.

Relação entre alterações congênitas observadas em síndrome de infecção congênita pelo Zika Vírus

“…Entretanto, o Sul representa 14,38% da população brasileira, portanto, apresenta um número de casos, proporcionalmente, menor. Pode-se observar que o vírus da Zika teve, proporcionalmente, grande impacto no Nordeste, em que uma percentagem maior da população é carente e as condições climáticas são mais favoráveis a propagação de vírus transmitidos por mosquitos do que no Sul, proporcionalmente menos afetado, sendo essa região mais rica e menos tropical (Melo et al, 2022). Ademais, a quantidade de notificações reduziu, de maneira geral, ao longo do período em estudo em todas as regiões.…”

Sociodemographic and Clinical Factors for Microcephaly Secondary to Teratogenic Infections in Brazil: An Ecological Study

“…The scientific literature also shows heterogeneity of associated sociodemographic factors [ 46 ], but socioeconomic status is an important determinant influencing these rates. [ 47 ] Poverty-related variables, such as low maternal education, maternal smoking during pregnancy, and preterm and vaginal birth, were generally more strongly associated with microcephaly in Brazil, Canada, and China [ 45 , 48 , 49 ].…”