This study investigates the association between Zika virus (ZIKV) infection and microcephaly in French Polynesia from October 2013 to April 2014, the largest documented outbreak prior to the current outbreak in the Americas. The researchers used retrospective data on ZIKV infections, microcephaly cases, and serological prevalence to estimate the risk of microcephaly associated with ZIKV infection during pregnancy. They developed mathematical models to predict the temporal trends in microcephaly under different scenarios of the 'period of risk' for ZIKV infection. The findings suggest that the risk of microcephaly increases significantly if a woman is infected with ZIKV during the first trimester of pregnancy, with an estimated risk of 95 per 10,000 women infected. The study provides strong statistical evidence for the association between ZIKV and microcephaly, emphasizing the need for fetal monitoring, vector control, and informed guidance for pregnant women in affected areas.This study investigates the association between Zika virus (ZIKV) infection and microcephaly in French Polynesia from October 2013 to April 2014, the largest documented outbreak prior to the current outbreak in the Americas. The researchers used retrospective data on ZIKV infections, microcephaly cases, and serological prevalence to estimate the risk of microcephaly associated with ZIKV infection during pregnancy. They developed mathematical models to predict the temporal trends in microcephaly under different scenarios of the 'period of risk' for ZIKV infection. The findings suggest that the risk of microcephaly increases significantly if a woman is infected with ZIKV during the first trimester of pregnancy, with an estimated risk of 95 per 10,000 women infected. The study provides strong statistical evidence for the association between ZIKV and microcephaly, emphasizing the need for fetal monitoring, vector control, and informed guidance for pregnant women in affected areas.