Zika in Infants and Pregnancy (ZIP)

NCT02856984 | Completed DMC

• 1 other identifier: GN ZIKA
• Study Type: observational
• Target: 6,461
• Locations: 6 countries
• Sites: 10

Brief Summary

The overall objective of this multisite, multicountry Zika in Infants and Pregnancy (ZIP) study is to assess the strength of the association between Zika virus infection (ZIKV) during pregnancy and adverse maternal/fetal outcomes and the risk of vertical transmission. The study will prospectively enroll a cohort of pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test. The study will follow these women through their pregnancy to identify for clinical evidence of acute ZIKV, while controlling for potential confounders. Outcomes in the women, the developing fetus, and infants will be assessed. All protocol-specified data will be recorded and entered in a central data management system for the purposes of analysis of composite data from the study.

Conditions

Zika Virus Disease (Disorder)

Keywords

Pregnancy; Infant

Outcome Measures

Primary Outcomes (16)

• Incidence of congenital malformations for ZIKV infected participants

  To measure the incidence of congenital malformations in fetuses/infants.

  Time of birth of infant

• Incidence of congenital malformations for ZIKV infected participants

  To measure the incidence of congenital malformations in fetuses/infants.

  3 months of age

• Incidence of congenital malformations for ZIKV infected participants

  To measure the incidence of congenital malformations in fetuses/infants.

  6 months of age

• Incidence of congenital malformations for ZIKV infected participants

  To measure the incidence of congenital malformations in fetuses/infants.

  12 months of age

• Incidence of adverse fetal outcomes for ZIKV infected participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  Time of birth of infant

• Incidence of adverse fetal outcomes for ZIKV infected participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  3 months of age

• Incidence of adverse fetal outcomes for ZIKV infected participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  6 months of age

• Incidence of adverse fetal outcomes for ZIKV infected participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  12 months of age

• Incidence of congenital malformations for ZIKV symptomatic participants

  To measure the incidence of congenital malformations in fetuses/infants.

  Time of birth of infant

• Incidence of congenital malformations for ZIKV symptomatic participants

  To measure the incidence of congenital malformations in fetuses/infants.

  3 months of age

• Incidence of congenital malformations for ZIKV symptomatic participants

  To measure the incidence of congenital malformations in fetuses/infants.

  6 months of age

• Incidence of congenital malformations for ZIKV symptomatic participants

  To measure the incidence of congenital malformations in fetuses/infants.

  12 months of age

• Incidence of adverse fetal outcomes for ZIKV symptomatic participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  Time of birth of infant

• Incidence of adverse fetal outcomes for ZIKV symptomatic participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  3 months of age

• Incidence of adverse fetal outcomes for ZIKV symptomatic participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  6 months of age

• Incidence of adverse fetal outcomes for ZIKV symptomatic participants

  To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.

  12 months of age

Study Arms (2)

ZIKV infected women

The study will prospectively enroll pregnant women up to 17 weeks and 6 days gestation and follow them through their pregnancy for clinical evidence of acute ZIKV infection while controlling for potential confounders. All pregnant women will be followed throughout the pregnancy, delivery, and 6 weeks postpartum. Outcomes in women, the developing fetus, and infants will be assessed.

Control (uninfected women)

The women who remain uninfected will serve as the internal comparison group. The infants who remain uninfected at delivery and throughout the follow-up period will serve as the internal comparison group.

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will recruit up to 10,000 pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test from ZIKV-endemic regions and follow them longitudinally to study the impact of incident ZIKV during pregnancy on maternal, fetal, and newborn outcomes. Researchers will identify cases of incident ZIKV among pregnant women by monitoring for symptoms of Zika-like illness and performing serial laboratory sampling for diagnosis of seroconversion and viral shedding. After delivery, infants born with evidence of ZIKV or born to mothers diagnosed with incident virus infection will be followed in a prospective longitudinal cohort for at least 1 year. In addition, a control group of infants born to mothers without evidence of ZIKV during pregnancy will be followed.

You may qualify if:

• Informed consent
• Age \>15 years
• Assent and consent as required per local country regulations
• Confirmation of pregnancy by beta human chorionic gonadotropin (hCG) measurement in blood/urine or ultrasound confirmation of pregnancy with fetal heart tones present
• Pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test.

You may not qualify if:

• Women who cannot adhere to proposed testing schedule
• Pregnant women enrolled in other research including other ZIKV research
• All infants born to women enrolled in the observational cohort are eligible for enrollment
• Mother or custodial parent does not consent to have child participate
• Infants born to mothers that are not part of the ZIP cohort study

Sponsors & Collaborators

• RTI International: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute of Environmental Health Sciences (NIEHS): collaborator
• Oswaldo Cruz Foundation: collaborator

Study Sites (10)

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS; Rue Waldemar Falcao

Salvador, Estado de Bahia, 40296-710, Brazil

Location

Departamento de Medicina Tropical da Universidade Federal de Pernambuco-UFPE

Recife, Pernambuco, CEP: 50670-901, Brazil

Location

Instituto Fernandes Figueira - FIOCRUZ

Rio de Janeiro, Rio de Janeiro, 22250-020, Brazil

Location

Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - Monte Alegre

Ribeirão Preto, São Paulo, 14049-900, Brazil

Location

Centro Medico Imbanaco

Cali, Colombia

Location

Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP)

Guatemala City, Guatemala

Location

MINSA Central

Managua, 16064, Nicaragua

Location

Universidad Peruana

Lima, Peru

Location

University of Puerto Rico Medical Sciences Campus

San Juan, 00921, Puerto Rico

Location

University of Puerto Rico - Recinto de Río Piedras

San Juan, 00936, Puerto Rico

Location

Related Publications (28)

• WHO statement on the first meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations; 1 February 2016. Available at http://www.who.int/ mediacentre/news/statements/2016/1st-emergency-committee-zika/en/

  BACKGROUND

• Petersen EE, Staples JE, Meaney-Delman D, Fischer M, Ellington SR, Callaghan WM, Jamieson DJ. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3. doi: 10.15585/mmwr.mm6502e1.

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• Powles R, Smith C, Milan S, Treleaven J, Millar J, McElwain T, Gordon-Smith E, Milliken S, Tiley C. Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial. Lancet. 1990 Dec 8;336(8728):1417-20. doi: 10.1016/0140-6736(90)93111-2.

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• CDC. Chikungunya virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/chikungunya/hc/clinicalevaluation.html

  BACKGROUND

• Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. Geneva: World Health Organization; 2009. Available from http://www.ncbi.nlm.nih.gov/books/NBK143157/

  PMID: 23762963 BACKGROUND

• CDC Zika Virus; Areas with Zika http://www.cdc.gov/zika/geo/index.html

  BACKGROUND

• Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7. doi: 10.1002/uog.15831. No abstract available.

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• CDC. West Nile virus: insect repellent use & safety. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/westnile/faq/repellent.html.

  BACKGROUND

• CDC. Zika virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/zika/index.html

  BACKGROUND

• Oduyebo T, Petersen EE, Rasmussen SA, Mead PS, Meaney-Delman D, Renquist CM, Ellington SR, Fischer M, Staples JE, Powers AM, Villanueva J, Galang RR, Dieke A, Munoz JL, Honein MA, Jamieson DJ. Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):122-7. doi: 10.15585/mmwr.mm6505e2.

  PMID: 26866840 BACKGROUND

• Babaliche P, Doshi D. Catching Dengue Early: Clinical Features and Laboratory Markers of Dengue Virus Infection. J Assoc Physicians India. 2015 May;63(5):38-41.

  PMID: 26591143 BACKGROUND

• Wahala WM, Silva AM. The human antibody response to dengue virus infection. Viruses. 2011 Dec;3(12):2374-95. doi: 10.3390/v3122374. Epub 2011 Nov 25.

  PMID: 22355444 BACKGROUND

• Gibney KB, Edupuganti S, Panella AJ, Kosoy OI, Delorey MJ, Lanciotti RS, Mulligan MJ, Fischer M, Staples JE. Detection of anti-yellow fever virus immunoglobulin m antibodies at 3-4 years following yellow fever vaccination. Am J Trop Med Hyg. 2012 Dec;87(6):1112-5. doi: 10.4269/ajtmh.2012.12-0182. Epub 2012 Oct 29.

  PMID: 23109371 BACKGROUND

• Roehrig JT, Nash D, Maldin B, Labowitz A, Martin DA, Lanciotti RS, Campbell GL. Persistence of virus-reactive serum immunoglobulin m antibody in confirmed west nile virus encephalitis cases. Emerg Infect Dis. 2003 Mar;9(3):376-9. doi: 10.3201/eid0903.020531.

  PMID: 12643836 BACKGROUND

• http://www.salud.gov.pr/Estadisticas-Registros-y-Publicaciones/Informes %20Arbovirales/Reporte%20ArboV%20semana%204-2016.pdf

  BACKGROUND

• Chervenak FA, Jeanty P, Cantraine F, Chitkara U, Venus I, Berkowitz RL, Hobbins JC. The diagnosis of fetal microcephaly. Am J Obstet Gynecol. 1984 Jul 1;149(5):512-7. doi: 10.1016/0002-9378(84)90027-9.

  PMID: 6742021 BACKGROUND

• Chervenak FA, Rosenberg J, Brightman RC, Chitkara U, Jeanty P. A prospective study of the accuracy of ultrasound in predicting fetal microcephaly. Obstet Gynecol. 1987 Jun;69(6):908-10.

  PMID: 3554067 BACKGROUND

• Kurtz AB, Wapner RJ, Rubin CS, Cole-Beuglet C, Ross RD, Goldberg BB. Ultrasound criteria for in utero diagnosis of microcephaly. J Clin Ultrasound. 1980 Feb;8(1):11-6. doi: 10.1002/jcu.1870080104.

  PMID: 6766470 BACKGROUND

• Hutchon DJ. Fetal ultrasound biometry: 1. Head reference values. Br J Obstet Gynaecol. 1999 Aug;106(8):875-6. doi: 10.1111/j.1471-0528.1999.tb08417.x. No abstract available.

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• Berger I. Prenatal microcephaly: can we be more accurate? J Child Neurol. 2009 Jan;24(1):97-100. doi: 10.1177/0883073808321045.

  PMID: 19168823 BACKGROUND

• Julie A Boom; Microcephaly in infants and children: Etiology and evaluation UpToDate http://www.uptodate.com/contents/microcephaly-in-infants-and-children- etiology-and-evaluation?source=machineLearning&search=microcephaly+in +pregnacy&selectedTitle=2~130§ionRank=3&anchor=H55603463#H55603463 Accessed on February 16, 2016

  BACKGROUND

• Tolmie JL, McNay M, Stephenson JB, Doyle D, Connor JM. Microcephaly: genetic counselling and antenatal diagnosis after the birth of an affected child. Am J Med Genet. 1987 Jul;27(3):583-94. doi: 10.1002/ajmg.1320270311.

  PMID: 3307411 BACKGROUND

• Atkinson B, Hearn P, Afrough B, Lumley S, Carter D, Aarons EJ, Simpson AJ, Brooks TJ, Hewson R. Detection of Zika Virus in Semen. Emerg Infect Dis. 2016 May;22(5):940. doi: 10.3201/eid2205.160107. No abstract available.

  PMID: 27088817 BACKGROUND

• Medscape Medical News; FDA Issues Guidance to Protect Blood Supply From Zika Virus http://www.medscape.com/viewarticle/858976? nlid=100283_3901&src=wnl_newsalrt_160216_MSCPEDIT&uac=17333MK&impID=993653&faf=1

  BACKGROUND

• Sarno M, Sacramento GA, Khouri R, do Rosario MS, Costa F, Archanjo G, Santos LA, Nery N Jr, Vasilakis N, Ko AI, de Almeida AR. Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise. PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517. doi: 10.1371/journal.pntd.0004517. eCollection 2016 Feb.

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• Brasil P, Pereira JP Jr, Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, Zin AA, Horovitz D, Daltro P, Boechat M, Raja Gabaglia C, Carvalho de Sequeira P, Pilotto JH, Medialdea-Carrera R, Cotrim da Cunha D, Abreu de Carvalho LM, Pone M, Machado Siqueira A, Calvet GA, Rodrigues Baiao AE, Neves ES, Nassar de Carvalho PR, Hasue RH, Marschik PB, Einspieler C, Janzen C, Cherry JD, Bispo de Filippis AM, Nielsen-Saines K. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med. 2016 Dec 15;375(24):2321-2334. doi: 10.1056/NEJMoa1602412. Epub 2016 Mar 4.

  PMID: 26943629 BACKGROUND

• Lebov JF, Nason M, Stolka KB, Ximenes R, Mussi-Pinhata MM, Moye J, Zorrilla CD, Velez Vega CM, Cordero JF, Scalabrin DMF, Ko AI, Moreira MEL, Galvao LA, Britt W, Marques ETA, Balmaseda A, Harris E, Arias JF, Schultz-Cherry S, Garces AL, Krebs NF, Ochoa TJ, Ugarte-Gil CA, Fogleman E, Gabriel E, Welton M, Irizarry CM, de Moura Negrini SB, Coutinho CM, de Barros Miranda-Filho D, Montarroyos UR, Cordeiro MT, Gajewski A, Osorio JE, Figueroa L. Zika in Infants and Pregnancy (ZIP) study: results from a prospective international cohort study of prenatal Zika virus infection and adverse fetal and infant outcomes. BMC Pregnancy Childbirth. 2025 Aug 30;25(1):903. doi: 10.1186/s12884-025-07774-y.

  PMID: 40885911 DERIVED

• Lebov JF, Arias JF, Balmaseda A, Britt W, Cordero JF, Galvao LA, Garces AL, Hambidge KM, Harris E, Ko A, Krebs N, Marques ETA, Martinez AM, McClure E, Miranda-Filho DB, Moreira MEL, Mussi-Pinhata MM, Ochoa TJ, Osorio JE, Scalabrin DMF, Schultz-Cherry S, Seage GR 3rd, Stolka K, Ugarte-Gil CA, Vega CMV, Welton M, Ximenes R, Zorrilla C. International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol. BMC Pregnancy Childbirth. 2019 Aug 7;19(1):282. doi: 10.1186/s12884-019-2430-4.

  PMID: 31391005 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

maternal samples from urine, blood, genital secretions, saliva, and breast milk, and when available amniotic fluid and tissue; infant urine, blood, and saliva

MeSH Terms

Conditions

Zika Virus Infection

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Study Officials

• Ricardo Ximenes, MD

  Departamento de Medicina Tropical da Universidade Federal de Pernambuco-UFPE

  PRINCIPAL INVESTIGATOR

• William Britt, MD

  University of Alabama Birmingham School of Medicine

  PRINCIPAL INVESTIGATOR

• Marisa Mussi, MD

  Ribeirão Preto Medical School, University of São Paulo

  PRINCIPAL INVESTIGATOR

• Albert Ko, MD

  Yale University, Laboratory of Epidemiology and Public Health

  PRINCIPAL INVESTIGATOR

• Deolinda Scalabrin

  Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS

  PRINCIPAL INVESTIGATOR

• Marisa Elisabeth Lopes

  Instituto Fernandes Figueira - FIOCRUZ

  PRINCIPAL INVESTIGATOR

• Ana Garces, MD

  Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP)

  PRINCIPAL INVESTIGATOR

• Jose Cordero, MD

  University of Georgia

  PRINCIPAL INVESTIGATOR

• Carmen Milagros Velez Vega, PhD

  University of Puerto Rico

  PRINCIPAL INVESTIGATOR

• George Seage, MD

  Harvard University School of Public Health

  PRINCIPAL INVESTIGATOR

• Carmen Zorilla, MD

  University of Puerto Rico

  PRINCIPAL INVESTIGATOR

• Eva Harris, PhD

  University of Californina Berkeley

  PRINCIPAL INVESTIGATOR

• Angel Balmaseda

  MINSA Central

  PRINCIPAL INVESTIGATOR

• Juan F Arias, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

• Jill Lebov, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Teresa Ochoa Woodell, PhD

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: August 5, 2016
• Study Start: June 1, 2016
• Primary Completion: May 5, 2020
• Study Completion: May 5, 2020
• Last Updated: August 19, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: IPD Sharing Time Frame: March 2022

Locations

CO (1); BR (4); PR (2); GU (1); PE (1); NI (1)