NICHD International Site Development Initiative (NISDI)
Perinatal and LILAC Protocols: A prospective, observational study of HIV-infected pregnant women and HIV-exposed uninfected infants at clinical sites in Latin America and the Caribbean.
Pediatric and PLACES protocols: A prospective, observational study of HIV-exposed and HIV-infected children at clinical sites in Latin America and the Caribbean.
Maternal and Pediatric Infectious Disease Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health, 6100 Executive Blvd., Room 4B11
Bethesda, MD 20892-7510
The Perinatal (2002-2007) and LILAC (2008-2011) protocols enrolled a cohort of subjects who were receiving care at sites in Argentina (2002-2011, Perinatal and LILAC), Brazil (2002-2011, Perinatal and LILAC), Peru (2006-2011, Perinatal and LILAC), Mexico (2002-2007, Perinatal only), Bahamas (2002-2007, Perinatal only) and Jamaica (2006-2007, Perinatal only). This cohort was composed of 1) pregnant women who were diagnosed with HIV infection either prior to or during pregnancy or within 1 month postpartum and 2) their infants (< 12 months of age). On the LILAC protocol, HIV-exposed, uninfected children 6 mo. – 5yrs of age who had available complete antenatal maternal ARV histories and documentation of maternal HIV infection before or during pregnancy or within 1 month postpartum were also eligible for enrollment.
The Pediatric (2002-2007) and PLACES (2008-2011) protocols enrolled a cohort of subjects who were receiving care at sites in Argentina (2002-2007, Pediatric), Brazil (2002-2011, Pediatric and PLACES), Peru (2006-2011, Pediatric and PLACES), Mexico (2002-2011, Pediatric and PLACES), and Jamaica (2006-2007, Pediatric only). This cohort was composed of HIV-infected infants, children and adolescents (< 21 years of age), whose mode of infection could be either vertical (born to HIV-infected mothers) or horizontal (had to have another mode of transmission and/or not be born to an HIV-infected mother). Additionally, children < 12 months old who were born to an HIV-infected woman were also enrolled, regardless of the child's infection status.
Cohort Enrollment Dates:
Enrollment began in the autumn of 2002 and follow up was completed on 30 Nov 2011.
(i) (Perinatal/LILAC) to describe the characteristics of HIV-infected pregnant women and their HIV-exposed, uninfected children receiving care at participating clinical sites in Latin America, including the utilization of efficacious interventions related to decreasing the risk of MTCT (ARV prophylaxis, Caesarean section before labor and before rupture of membranes, complete avoidance of breastfeeding); the use of ARVs or other therapy for the woman’s own health; and rates of MTCT of HIV;
(ii) (Perinatal/LILAC) to characterize adverse events according to receipt of and exposure to ARVs (by HIV-infected women during pregnancy and postpartum and by their HIV-exposed but uninfected children in utero and during the first few weeks of life).
(iii) to describe the characteristics of HIV-infected infants, children and adolescents cared for at clinical sites in Latin America and the Caribbean,
(iv) to describe early and late outcomes related to pediatric HIV disease and ARV therapy and
(v) to describe early and late outcomes related to in utero exposure to ARVs and HIV and to postnatal exposure to ARVs.
Types of Data collected:
Medical history (including diagnoses, hospitalizations, medications and vaccinations), physical examination, laboratory evaluations (including hematology, flow cytometry and standard biochemical assays), growth parameters, morbidity evaluation and mortality status. Virologic assessments were performed in the HIV-infected group. In addition, peripheral blood mononuclear cells and plasma were collected from all subjects (maternal and pediatric) and stored in a central repository for potential future studies. In later years of the study, additional data collected included: antiretroviral adherence; supplemental vitamins and minerals; antiretroviral resistance testing; prechewing and prewarming (LILAC); and nutritional intake at age 6 months (LILAC infants)
Data collection interval
Pediatric/PLACES: Data were collected from participants every six months after enrollment.
Perinatal/LILAC: Women in the Perinatal protocol were enrolled during pregnancy, at 8 weeks gestation or later (including at the time of presentation for delivery). They were followed during pregnancy, with up to three antepartum visits, at delivery and at hospital discharge, and at 6–12 weeks and 6 months postpartum. Children in the Perinatal protocol were enrolled at birth then followed on the same schedule as the women thereafter. HIV-infected women who experienced pregnancy losses continued to be followed. In addition, HIV-infected women were eligible for re-enrollment with subsequent pregnancies during this study. Women in the LILAC protocol were enrolled during pregnancy at 22 weeks of gestation or later. They were followed during pregnancy with up to two antepartum visits, at delivery and hospital discharge, at 6–12 weeks and 6 months postpartum and then every 6 months thereafter up to 5 years post-delivery. HIV-infected pregnant women who experienced pregnancy losses also were followed according. Children of women enrolled in the LILAC protocol were enrolled at birth then followed on the same schedule as the women thereafter. Children enrolled on LILAC between 6 mo. – 5yrs of age were followed every 6 months for up to 5 years.
Data collection methodology (All protocols):
Data were collected prospectively using standardized case report forms (CRFs) specifically designed for this study. Data collectors were doctors and nurses at each participating site who were trained by the coordinating center in the use and appropriate completion of the CRFs.
Data Quality (All protocols):
Each participating clinical site designed quality assurance / quality control methods to meet the needs of their sites. These QA/QC plans were approved by the coordinating center and the sponsoring institution. Additionally the coordinating center performed annual site monitoring visits; at these visits, clinical research associates from the coordinating center selected a number of participants randomly and the CRFs were reviewed against the source documentation (medical charts, laboratory reports, etc). Additionally at the coordinating center, where electronic data entry occurred, there were visual and automated checks of the CRF data; visual checks include review of the CRF image CRF completion errors (e.g. required questions left blank), and automated checks include range and logic checks to ensure data quality. Monthly reports were produced to check for data anomalies and to track enrollment and attrition. Further, data were frozen every six months and the data were reviewed for inconsistencies through examination of reports including descriptive statistics and cross tabulations.
Perinatal/LILAC: HIV infected pregnant woman with gestational age of > 8 weeks (Perinatal Protocol) or > 22 weeks (LILAC Protocol). All infants of enrolled women were eligible for enrollment.
Pediatric/PLACES: Children < 12 months old who were born to an HIV-infected woman (regardless of the child's infection status) and HIV-infected infants, children, and adolescents (< 21 years of age).
For children, parent or guardian signed informed consent was required unless the subject was able to provide his/her own consent because of age or status as an emancipated minor (as defined by the specific country of enrollment). An informed assent document was obtained for children 8 years of age or older.
Number of patients enrolled to date:
Pediatric/PLACES Cohort: In the first version of the protocol a total of 1629 subjects were enrolled in the cohort of whom 735 (45%) were vertically HIV infected, 82 (5%) horizontally HIV infected, 768 (47%) confirmed to be HIV- uninfected and 44 (3%) whose HIV status was indeterminate. With enrollment to the second version of the protocol, a total of 1032 perinatally HIV-infected children have been followed.
Perinatal/LILAC Cohorts: 1548 pregnant women enrolled with their first on-study pregnancies (1174 from the Perinatal protocol and 374 from the LILAC protocol). Overall, most women were enrolled in Brazil and Argentina.
NOTE: All protocols completed enrollment in 2009 and ended follow-up in 2011.
Other Information: Primary collaborators and participating organizations, Funding sources, etc.
Funding Agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Coordinating Center : Westat, Rockville, Maryland
Argentina: Hospital General de Agudos José María Ramos Mejía, Buenos Aires
Bahamas: Princess Margaret Hospital, Nassau
Universidade Federal de Minas Gerais
Universidade de Caxias do Sul/Secretaria Municipal de DST/AIDS de Caxias do Sul-Ambulato’rio Municipal DST/AIDS
Hospital Geral Nova de Iguacu Setor de DST/AIDS
Universidade de Caxias do Sul/Hospital Fêmina
Hospital de Clínicas de Porto Alegre
Irmandade da Santa Casa de Misericordia de Porto Alegre
Hospital das Clínicas da Cauldade de Medicina de Ribeirão Preto
Insituto de Puericultura e Pediatria Martagão Gesteira
Hospital dos Servidores do Estado
Federal University of São Paulo
Insituto de Infectologia Emilio Ribas
Jamaica: University Hospital of the West Indies Comprehensive Health Center
Mexico: Hospital Infantil de México Federico Gómez
Peru: Instituto de Medicina Tropical “Daniel Alcides Carrión”- División de Epidemiología María Castillo Díaz
Funding: NICHD Contracts (#N01-HD-3-3345 and #N01-HD-8-0001).
Publications describing the cohorts:
- International Journal of Epidemiology 2008; 1-8
Cohort Profile: NICHD International Site Development Initiative (NISDI): a prospective, observational study of HIV-exposed and HIV-infected children at clinical sites in Latin American and Caribbean countries
Rohan Hazra, Sonia K. Stoszek, Laura Freimanis Hance, Jorge Pinto, Heloisa Marques, Mario Peixoto, Jorge Alarcon, Marisa Mussi-Pinhata and Leslie Serchuck for the NISDI Pediatric Study Group 2008
- International Journal of Epidemiology 2012; 41: 642-9
Cohort Profile: The NICHD International Site Development Initiative perinatal cohorts (2002-09)
Jennifer S. Read, Geraldo Duarte, Laura Freimanis Hance, Jorge Pinto, Maria I. Gouvea, Rachel A. Cohen, Breno Santos, Elizabete Teles, Regina Succi, Jorge Alarcon, Sonia K. Stoszek and the NISDI Perinatal Study Group
Cohort Management Team:
Eunice Kennedy Shriver National Institute of Child Health and Human Development:
Rohan Hazra MD: Principal Investigator, Pediatric/PLACES
George Siberry MD: Principal Investigator, Perinatal/LILAC