International Effort to Enroll Approximately 10,000 Women
June 21, 2016
The National Institutes of Health and Fundacao Oswaldo Cruz-Fiocruz (Fiocruz), a national scientific research organization linked to the Brazilian Ministry of Health, have begun a multi-country study to evaluate the magnitude of health risks that Zika virus infection poses to pregnant women and their developing fetuses and infants. The study is opening in Puerto Rico and will expand to several locations in Brazil, Colombia and other areas that are experiencing active local transmission of the virus.
Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, although other forms of transmission—notably, mother-to-child and sexual transmission—also occur. Active virus transmission currently is ongoing in 60 countries and territories. The virus has been linked to a spike in cases of microcephaly, a condition in which babies are born with abnormally small heads and possible neurological damage, sparking international concern. In addition to microcephaly, other problems have been detected in pregnancies and among fetuses and infants infected with Zika virus before birth, including miscarriage, stillbirth, absent or poorly developed brain structures, eye defects, hearing deficits, and impaired growth.
The Zika in Infants and Pregnancy (ZIP) study aims to enroll as many as 10,000 pregnant women ages 15 years and older at up to 15 sites. The participants will be in their first trimester of pregnancy and will be followed throughout their pregnancies to determine if they become infected with Zika virus and if so, what outcomes result for both mother and child. The participants’ infants will be carefully followed for at least one year after birth.
The National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Environmental Health Sciences (NIEHS), all part of the NIH, are funding and conducting the study, along with Fiocruz.
“The full scope of the effect of Zika virus in pregnancy has not yet been fully determined,” said NIAID Director Anthony S. Fauci, M.D. “This large prospective study promises to provide important new data that will help guide the medical and public health responses to the Zika virus epidemic.”
“Zika virus has spread rapidly through the Americas,” said NICHD Acting Director Catherine Y. Spong, M.D. “We anticipate that this study will provide important information on the link between Zika infection and pregnancy complications and inform strategies to help safeguard the health of mothers and their newborns.”
“A mother’s environment may be an important part of the Zika virus puzzle,” said NIEHS Director Linda Birnbaum, Ph.D. “We’ve included environmental measures in the study and will also be evaluating nutrition and socio-economic status.”
The researchers plan to compare birth outcomes between mothers who were infected with Zika virus and those who were not, documenting the frequency of miscarriage, preterm birth, microcephaly, malformations of the nervous system, and other complications. The researchers also seek to compare the risk of pregnancy complications among women who have symptoms of Zika virus infection and those who are infected but do not have symptoms. Additionally, the study will evaluate how the timing of infection affects pregnancy outcomes and the role environmental influences, social determinants and other infections, such as dengue virus infection, may play on the health of the study participants and their newborns.
Women participating in the ZIP study will be monitored monthly for the duration of their pregnancies and then six weeks after delivery. They will have a physical examination and be asked to provide blood, urine, saliva and vaginal swab samples at study entry and at each monthly prenatal care visit. If the participants note that they will be receiving an amniocentesis in connection with their clinical care, the research team will arrange with the participant and her obstetrician to obtain a sample of the amniotic fluid to test for Zika infection. The participants will be instructed about the signs and symptoms of acute Zika virus infection and will be asked to notify their clinic immediately if they experience symptoms. Post-delivery, a breast milk sample, if available, will be obtained for Zika testing. Infants whose mothers consent to their participation in the study will be evaluated within 48 hours of birth and again at three, six and 12 months.
“This study, in partnership with NIH, is essential to elucidating the scientific complexity of the Zika virus,” said Fiocruz President Paulo Gadelha. “It will be fundamental to developing prevention and treatment strategies against the disease.”
It is important to note that the ZIP study is a research effort that is distinct from and complementary to public health registries underway in the United States (U.S. Zika Public Health Registry), Puerto Rico (Zika Active Pregnancy Surveillance System), and Colombia (SIVIGILA/Projecto Vez). These registries are population-based and collect observations from medical evaluations and testing with the intent of providing information for public health action.
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NICHD conducts and supports research in the United States and throughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit NICHD’s website.
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Questions & Answers
The Zika in Infants and Pregnancy (ZIP) study is a multi-site, multi-country clinical research study designed to improve our understanding of the health effects of Zika virus infection on pregnant women and their developing fetuses and infants. The study aims to recruit approximately 10,000 pregnant women ages 15 years and older in their first trimester of pregnancy at sites across Latin America and the Caribbean where active, local transmission of Zika virus is occurring.
The study will take place at 15 sites beginning in Puerto Rico and then expanding to locations in Brazil, Colombia, and other countries and territories.
The National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Environmental Health Sciences (NIEHS)—all part of the U.S. National Institutes of Health (NIH)—are funding and conducting the ZIP study. Fundacao Oswaldo Cruz-Fiocruz, a scientific research institution affiliated with the Brazilian Ministry of Health, is partnering with NIH to fund and conduct the study in Brazil.
Overall, this study of pregnant women in Zika-endemic areas will help inform strategies for safeguarding the health of Zika-exposed pregnant women and their newborn infants. The study is designed to discern the risk of adverse outcomes for women infected by the Zika virus during pregnancy, regardless of whether symptoms occur. Researchers also aim to establish the impact that the timing of Zika infection has on pregnancy outcomes and the role, if any, of prior exposures to other pathogens, such as dengue virus, and environmental factors.
Additionally, the study will document the spectrum of pregnancy and neonatal outcomes related to the transmission of Zika virus infection. This includes not only microcephaly (a condition in which babies are born with abnormally small heads and possible neurological damage), but also fetal loss/stillbirth and other serious brain anomalies, such as cerebellar hypoplasia (the infant’s cerebellum is reduced in size but normal in shape). Further, the research aims to improve understanding of Zika-related eye and hearing abnormalities, as well as neurobehavioral effects, such as altered motor function, stiffness, seizures, irritability and incessant crying in affected infants.
Going forward, it is important to characterize the full extent of Zika’s impact on fetal development, so that strategies can be developed to assess and monitor the growth of children exposed to the Zika virus in the womb and to find the optimal methods for treating and caring for these children.
Recruitment will occur through prenatal clinics and other community outreach, depending on the study site, region and country; NIH will work with local groups in the study regions to determine the optimal method for recruitment. Each study site will be responsible for obtaining informed consent and enrolling participants in accordance with local practices and regulations.
The women participants will be monitored monthly for the duration of their pregnancies and then at six weeks after they give birth. They will receive a physical examination and be asked to provide blood, urine, saliva and vaginal swab samples at study entry and at each monthly prenatal care visit. If the participants note that they will be receiving an amniocentesis in connection with their clinical care, the research team will arrange with the participant and her obstetrician to obtain a sample of the amniotic fluid to test for Zika infection. They will be instructed about the signs and symptoms of acute Zika virus infection and will be asked to notify their clinic immediately if they experience symptoms. Post-delivery, a breast milk sample, if available, will be obtained for Zika testing. Infants whose mothers consent to their participation in the study will be evaluated within 48 hours of birth and then again at three, six and 12 months.
The ZIP study is expected to last for at least a year and potentially longer.