According to these criteria, causality is cstab lished when either criteria 1, 3, and 4 rare ex posure rare defect or criteria and(epidemiologic approach) fulfilled. first criterion states that a proven exposure to an agent must occur at a critical time during prena tal development. The severe microcephaly and other brain anomalies that have been obsered many infants are consistent with an infection occurring in the first or early second trimester of pregnancy. Several case reports and studies have shown that women who had fetuses or in fants with congenital brain anomalies that were believed, on the basis of the mother's symptoms or laboratory confirmation, to be due virus infection were infected in the first or early second trimester of pregnancy, as determined either according to the timing of the symptoms or according to the timing of travel to an area where Zika virus is endemic 1420 An analysis of the timing of laboratory confirmed Zika virus transmission in certain states in Brazil and of the increase in the cases of microcephaly identi fied the first trimester as the critical time period for infection.' Zika virus infections that occur later in pregnancy have been associated with poor intrauterine growth, fetal death, or in some pregnancies, defects on prenatal imaging that have not yet been confirmed postnatally because the pregnancies are ongoing u We conclude that Shepard's first criterion has been met.