The Brazil Ministry of Health developed a case definition for Zika virus–related microcephaly (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth). A task force and registry were established to investigate Zika virus–related cases of microcephaly and to describe the clinical characteristics of cases. Among the first 35 cases of microcephaly reported to the registry, 74% of mothers reported a rash illness during pregnancy, 71% of infants had severe microcephaly (>3 SD below the mean), approximately half had at least one neurologic abnormality, and among 27 who had neuroimaging studies, all were abnormal. Cerebrospinal fluid from all infants is being tested for Zika virus; results are not currently available.

In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August–October 2015 in eight of Brazil’s 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label.

An outbreak of Zika virus infection was recognized in northeast Brazil in early 2015 (1). In September 2015, health authorities began to receive reports from physicians in this region of an increase in the number of infants born with microcephaly. In October, the MoH confirmed an increase in birth prevalence of microcephaly in northeast Brazil, compared with previously reported estimates (approximately 0.5/10,000 live births), which are based on review of birth certificates and include descriptions of major congenital anomalies. The MoH rapidly established a microcephaly registry in Brazil. On November 17, 2015, the MoH reported the increase in microcephaly cases, and possible association of microcephaly with Zika virus infection during pregnancy on its website;* and the Pan American Health Organization (PAHO) published an alert regarding the increase in occurrence of microcephaly in Brazil (2). In December, PAHO reported the identification of Zika virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in amniotic fluid samples from two pregnant women whose fetuses were found to have microcephaly by prenatal ultrasound, and the identification of Zika virus RNA from multiple body tissues, including the brain, of an infant with microcephaly who died in the immediate neonatal period (3). These events prompted new alerts from the MoH, the European Centre for Disease Prevention and Control (4), and CDC (5) concerning the possible association of microcephaly with the recent outbreak of Zika virus infection.

A comprehensive protocol for notification and investigation of all infants with microcephaly and all women with suspected Zika virus infection during pregnancy was developed by the MoH and implemented nationwide. In addition, the Brazilian Society of Medical Genetics established the Zika Embryopathy Task Force (SBGM–ZETF), which includes clinical geneticists, obstetricians, pediatricians, neurologists, and radiologists, to review all incident cases of microcephaly as well as all infants born to mothers with suspected Zika virus infection during pregnancy. Task force members collect data concerning the pregnancy (including exposure history, symptoms, and laboratory testing), physical examination of the infant, and any additional studies using a standardized spreadsheet. Microcephaly was defined as neonatal head circumference ≥2 SD below the mean for gestational age and sex of the infant at birth. Infection with Zika virus is difficult to confirm retrospectively because serological immunological tests might cross-react with other flaviviruses, especially dengue virus (6). Therefore a mother’s report of a rash illness during pregnancy was used as a proxy indicator of potential Zika virus infection.

Although 37 infants with microcephaly were evaluated, only 35 cases are included in this report. Two infants with microcephaly were excluded from the original cohort of 37 babies: one had autosomal recessive microcephaly with sibship recurrence, and one had cytomegalovirus infection. Overall, 26 (74%) mothers of infants with microcephaly reported a rash during the first (n = 21) or second (5) trimester (Table). Residence in or travel during pregnancy to areas where Zika virus is circulating was confirmed for all mothers, including women without a history of rash. Twenty-five (74%) infants had severe microcephaly (head circumference >3 SD below the mean for gestational age). Computed tomography scans and transfontanellar cranial ultrasounds showed a consistent pattern of widespread brain calcifications, mainly in the periventricular, parenchymal, and thalamic areas, and in the basal ganglia, and was associated in approximately one third of cases with evidence of cell migration abnormalities (e.g., lissencephaly, pachygyria). Ventricular enlargement secondary to cortical/subcortical atrophy was also frequently reported. Excessive and redundant scalp skin, reported in 11 (31%) cases, also suggests acute intrauterine brain injury, indicating and arrest in cerebral growth, but not in growth of scalp skin. Four (11%) infants had arthrogryposis (congenital contractures), indicative of central or peripheral nervous system involvement (7). All 35 infants in the cohort tested negative for syphilis, toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus infections. CSF samples from all infants enrolled in the cohort were sent to a reference laboratory in Brazil for Zika virus testing; the results are not yet available.