Objective. To determine the safety and efficacy of monthly prophylaxis with respiratory syncytial virus immune globulin, intravenous (RSV-IGIV) for reduction of the incidence of RSV-associated hospitalization.
Methods. A randomized, double-blind, placebo-controlled clinical trial was conducted at 54 centers in the United States during the 1994 to 1995 RSV season. A total of 510 children with bronchopulmonary dysplasia and/or a history of prematurity were randomized to receive either 750 mg/kg RSV-IGIV (n = 250) or placebo (1% albumin; n = 260) intravenously every 30 days. Randomized groups were well balanced at entry for demographics, RSV risk factors, and birth characteristics. Children were monitored for adverse events and for RSV-associated hospitalization from randomization through 30 days after the last infusion visit; serious adverse events were monitored for an additional 30 days. For children hospitalized with RSV, data were collected regarding the total days of RSV stay, total days of increased oxygen requirement, total days with a moderate or severe lower respiratory tract illness, and frequency and duration of intensive care unit stay and mechanical ventilation. Ninety-five percent of participants completed the protocol and 85% received a complete course of infusions.
Results. The incidence of RSV hospitalization was reduced by 41% in children receiving RSV-IGIV prophylaxis; 35 (13.5%) of the children in the placebo group were hospitalized for RSV, compared with 20 (8.0%) RSV-IGIV recipients. RSV-IGIV recipients had a 53% reduction in the total number of RSV hospital days per 100 children, a 60% reduction in the number of RSV days with increased oxygen requirement, and a 54% reduction in the number of RSV hospital days with a moderate or severe lower respiratory tract illness. In addition, children receiving RSV-IGIV had a 38% reduction in hospitalization for respiratory illness of any cause and a 46% reduction in total hospital days for respiratory illness per 100 children. RSV-IGIV was safe and well tolerated, with a safety profile similar to other IGIV preparations. Between 1% to 3% of children had medically significant adverse events related to RSV-IGIV administration.
Conclusions. Monthly administration of 750 mg/kg of RSV-IGIV was safe and well tolerated and was effective in reducing the incidence and total days of both RSV hospitalization and overall respiratory hospitalization in infants with a history of prematurity or bronchopulmonary dysplasia or both.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infancy and childhood.1-4 Approximately 50% of infants and young children become infected with RSV each winter season, and it has been estimated that RSV causes more than 90 000 hospitalizations and 4500 deaths annually.2,5,6 Children with underlying bronchopulmonary dysplasia (BPD), prematurity, immunodeficiency, or congenital heart disease (CHD) are known to be at high risk for severe RSV illness.7-10
Studies performed in cotton rats suggested that passive immunization with antibody enriched for RSV neutralizing activity may be a useful method for prevention of RSV.11 The development of methods for production of an intravenous immune globulin for human use (respiratory syncytial virus immune globulin, intravenous [RSV-IGIV; RespiGam]) that is enriched for neutralizing antibody to RSV has paved the way for clinical evaluation of this approach.12RSV-IGIV is approximately sixfold enriched for neutralizing antibodies (compared with commercially available intravenous immune globulin) and is tenfold more potent in reducing pulmonary titers of RSV in cotton rats.13 RSV-IGIV has been shown to neutralize a wide variety of subtype A and B strains of RSV in vitro.13 A previous clinical trial of RSV-IGIV prophylaxis in high-risk infants (ie, prematurity, BPD, CHD) suggested that monthly administration of 750 mg/kg may be associated with a reduction in severity of RSV illness and reduction in the rate of RSV hospitalization.14 The current study (PREVENT) was designed as a pivotal trial to determine the safety and efficacy of RSV-IGIV prophylaxis for reducing the rate of RSV hospitalization among children with BPD and/or a history of prematurity.
PREVENT was a centrally randomized, double-blind, placebo-controlled clinical trial, conducted at 54 centers in the United States. Children were eligible if 1) they were 24 months old or younger and had BPD and a requirement for supplemental oxygen within the past 6 months, or 2) they were less than 6 months old and were premature at birth (35 weeks gestation or less). BPD was diagnosed clinically by a qualified physician, ie, neonatologist or pulmonologist. Patients were excluded if they required hospitalization at the time of randomization (unless discharge was anticipated within 30 days); were mechanically ventilated; had a life expectancy of less than 6 months; had active or recent RSV infection; had known immunoglobulin A deficiency; known immunodeficiency; had a previous reaction to blood products, albumin, or immune globulin (intravenous) [IGIV]; had been treated with IGIV or any other immunoglobulin product within the previous 2 months; or had known renal impairment (creatinine >2.5 mg/dL).
Randomization occurred between November 15, 1994 and December 22, 1994, on the day that a child received his/her first infusion. After randomization, children received either RSV-IGIV (750 mg/kg; 15 mL/kg) or placebo (1% albumin; 15 mL/kg) every 30 days through April 15, 1995. Study drug was administered by intravenous infusion at a rate of 1.5 mL/kg/hour for the first 15 minutes, 3 mL/kg/hour from 15 to 30 minutes and then at 6 mL/kg/hour until the end of the infusion.
Patients were followed for safety and efficacy endpoints regardless of whether they were actively receiving infusions. All hospitalizations were identified through 30 days after the last scheduled infusion visit. Children were considered to have reached the primary endpoint (RSV hospitalization) if they were hospitalized for a respiratory illness and had RSV antigen detected in respiratory secretions within 48 hours of hospitalization. RSV antigen testing was performed using commercially available reagents in each center's clinical laboratory.
The lower respiratory infection/illness (LRI) score was used to describe the investigator's evaluation of a child's respiratory status. At each visit and daily during hospitalization for any cause, the LRI score was recorded as follows: 0 = no respiratory illness/infection; 1 = upper respiratory tract illness/infection; 2 = mild LRI; 3 = moderate LRI; 4 = severe LRI; 5 = mechanical ventilation. Children who acquired nosocomial RSV (RSV antigen positive while in the hospital for other reasons) were also considered to have reached the primary endpoint if they had a LRI score of 3 or greater and 1 higher than their score at the last pre-illness visit.
Children who met the primary endpoint were monitored during hospitalization for the total number of RSV hospital days, the total number of RSV hospital days with an increased (above prehospitalization level) supplemental oxygen requirement, total number of RSV days with LRI score of 3 or greater, and frequency and total days of intensive care unit (ICU) stay and mechanical ventilation.
Children were monitored during each infusion and adverse event information was collected throughout the study period (through 30 days after the last infusion visit). Serious adverse events were recorded for an additional 30 days. Adverse events were defined as any change in the child's condition from entry. Each event was assessed in a blinded manner by the investigator with regard to severity (using standard toxicity tables) and potential relationship to the study drug. Treatment groups were compared for adverse events by evaluating the number of children in each group who reported at least one event by body system and the distribution of severity of these events.
All randomized patients were included in the analysis of efficacy and safety. Statistical comparison of treatment groups was performed using the uncorrected χ2 test or Fisher's exact test (when the number of patient in a group was <5) for categorical variables and the Wilcoxon rank sum test for continuous variables. For the primary endpoint (RSV hospitalization) logistic regression analysis was also performed using predefined variables (gender, age more than or less than 6 months, and entry inclusion category). For analyses using total days, data were transformed and reported as days per 100 children (number of days divided by the number of children × 100).
Characteristics of the Randomized Patients at Entry
A total of 510 children were randomized; 250 to RSV-IGIV and 260 to placebo. The mean number of patients per site was 9.4 (range 2–21). All 510 randomized children were considered eligible and all were included in the analysis. Two BPD patients had minor protocol deviations with respect to inclusion criteria. Both had a confirmed diagnosis of BPD (including past oxygen requirement) but did not appear to require supplemental oxygen within the 6 months before randomization. Demographics, RSV-risk factors and other characteristics were well balanced between the two groups at the time of randomization (Table 1). Overall, 97% of the children had a history of prematurity; approximately 60% were enrolled under the BPD criteria.
Compliance With the Protocol, Infusions, and
Ninety-four percent of children in the placebo group and 95% in the RSV-IGIV group completed the protocol (through 30 days after the last infusion visit). The number of children who exited the study before the end of the follow-up period and without having an RSV hospitalization was small and balanced between the two groups; 10 children (3.8%) in the placebo group and 9 (3.6%) in the RSV-IGIV group. Approximately 85% of children in each group received either four or five infusions (the maximum defined in the protocol). More than 75% of each dose was administered for 83.5% of children in the control group and 81.2% in the RSV-IGIV group.
Primary Efficacy Analyses
RSV-IGIV prophylaxis was associated with a 41% reduction in the incidence of RSV hospitalization and a 53% reduction in the total days of RSV hospitalization. Thirty-five children (13.5%) in the placebo group, compared with 20 (8.0%) in the RSV-IGIV group met protocol criteria for RSV hospitalization (P = .047). The total number of RSV hospital days per 100 children for placebo and RSV-IGIV recipients was 129 and 60, respectively (P = .045). The distribution of total hospital days is shown in Fig 1. The most notable effect on hospital stay was in reduction of prolonged hospitalizations.
During each RSV hospital day, children were assessed to determine the severity of their RSV illness (Fig 2). Children randomized to receive RSV-IGIV prophylaxis had a 60% reduction in the total days of RSV hospitalization requiring increased supplemental oxygen; 85 days per 100 children for placebo and 34 for RSV-IGIV (P = .007). In addition, children in the RSV-IGIV group had a 54% reduction in RSV hospital days in which the investigator classified patients' respiratory illness as moderate or greater severity (LRI score ≥3); 106 days per 100 children for placebo and 49 days for RSV-IGIV (P = .049). These differences were not influenced by ribavirin use, which was balanced between the two groups (7 of 20 [35%] in the RSV-IGIV group and 10 of 35 [29%] in the placebo group, P = .62).
The frequency of total days of ICU or mechanical ventilation for RSV was not significantly different between the two treatment groups. ICU care for RSV was required by 12 children (4.6%) in the placebo group (50 days per 100 children) and 8 (3.2%) in the RSV-IGIV group (28 days per 100 children); 5 children in each group required mechanical ventilation for RSV.
Analyses were performed to assess the effect of RSV-IGIV prophylaxis on the incidence of overall respiratory hospitalizations and on the total number of respiratory hospital days. Sixty-nine children (27%) in the placebo group were hospitalized for respiratory illnesses compared with 41 children (16%) in the RSV-IGIV group (P = .005). Respiratory illness days accounted for 77% of the total number of hospital days for study participants. Placebo recipients were hospitalized for a total of 317 days per 100 children for respiratory illnesses, compared with 170 days for children receiving RSV-IGIV prophylaxis (P = .005).
The trial was not designed nor powered to detect differences in RSV hospitalization rates in subgroups of children. Logistic regression analysis demonstrated no evidence of interaction between treatment and 1) gender, 2) categorical age under or over 6 months, or 3) entry inclusion category. Thus, there was no statistical evidence that the pattern of treatment effect in groups defined by these prospectively defined variables was different from the effect observed for the randomized groups as a whole. Fewer RSV hospitalizations were observed in the RSV-IGIV group than the placebo group in each of these subgroups, with reductions ranging from 17% to 58% (Table2). The largest reductions were observed in children older than 6 months, all of whom had BPD, and the smallest were seen in children less than 6 months old. The latter group, however, had a low incidence of RSV hospitalization in the control group (8.6%), which limited the ability to quantify the magnitude of the treatment effect in this age subgroup. Logistic regression using age as a continuous variable did not demonstrate a significant interaction between age and treatment. Subgroup analyses using age under and over 3 months and weight as a surrogate for young age were also performed (Table 2). Children with entry weight below the median (4.3 kg) who received monthly RSV-IGIV prophylaxis had a 49% observed reduction in RSV hospitalization as compared with a 34% reduction in children with weight greater than the median.
Fluid Volume Complications
Children in both treatment groups tolerated the 15 mL/kg of fluid volume well. In 1.8% of children, at least one infusion was interrupted or the rate was slowed because of a problem with fluid volume. Overall, 8.4% of children (1% premature and 13% BPD) received new or extra diuretics around the time of (24 hours before to 48 hours after) at least one infusion, although the reason for diuretic use was not specified (eg, prophylaxis for fluid overload, treatment of fluid overload, or adjustment of the child's dose for management of the underlying lung disease).
The number of children reporting at least one adverse event was balanced between the two treatment groups, as was the distribution of severity of these events. RSV-IGIV recipients had fewer rashes and other skin abnormalities (38% vs 48%) and otitis media (27% vs 43%), compared with placebo recipients. Slightly more children in the RSV-IGIV group (6% vs 3%) reported adverse events in the nervous system category. However, these events were primarily preexisting complications of prematurity that were identified during the study. Three children in the RSV-IGIV group had mild mononuclear cell cerebrospinal fluid pleocytosis (20 cells or less); one had a presumptive diagnosis of enteroviral meningitis (enterovirus cultured from nasopharynx), one was treated for herpes simplex and improved, and one was found as part of an evaluation for possible sepsis.
Fever that was judged to be related to study drug by the blinded investigator was reported in 6% of children in the RSV-IGIV group and 2% in the placebo group. Three children in the placebo group and eight in the RSV-IGIV group had an adverse event of greater than moderate severity that was judged by the blinded investigator as potentially related to study drug (Table 3). For two of these patients in the RSV-IGIV group an alternative diagnosis was made subsequently. Five of these RSV-IGIV patients had respiratory tract adverse events and one patient had fever.
Adverse events judged potentially related to study drug were the reason for an incomplete or prolonged infusion for two patients (1%) in the placebo group and eight patients (3.2%) in the RSV-IGIV group. Six of eight RSV-IGIV patients with incomplete or prolonged infusions were included among patients previously reported in Table 3 as having at least moderate adverse events related to RSV-IGIV. Among the eight RSV-IGIV patients, RSV-IGIV prophylaxis was permanently discontinued in three cases.
Seven children died during the period from randomization through 60 days after the last infusion visit (two placebo and five RSV-IGIV;P = .28). All of the deaths were due to complications of prematurity and/or underlying chronic illness. None of the deaths was considered by the blinded investigator to be related to study drug administration or to RSV infection.
In this study, infants and children at high risk for severe RSV disease (by virtue of BPD and/or a history of premature birth) who received monthly RSV-IGIV prophylaxis had a significant reduction in the incidence (41%) and total days (53%) of RSV hospitalization compared with placebo recipients. In addition, RSV-IGIV prophylaxis was associated with reduction of the total RSV hospital days with increased oxygen requirement and with a LRI of more than moderate severity. Thus, RSV-IGIV is the first agent with proven benefit in prevention of RSV disease. Administration of RSV-IGIV was safe and well tolerated, with a safety profile similar to other commercially available IGIVs.15-18 Based on these data, the Food and Drug Administration has recently approved RSV-IGIV for prevention of serious RSV disease in children less than 24 months old with BPD or a history of prematurity (≤35 weeks gestation).
Respiratory illnesses represent the most common cause for hospitalization for children with BPD and/or prematurity.7,8 In the PREVENT trial, children in the control group were hospitalized for a total of 1074 days for all reasons and respiratory illnesses accounted for 77% of their total hospital days. Prophylaxis with RSV-IGIV was associated with a significant reduction in hospitalization for both RSV and other respiratory illnesses. The mechanism by which RSV-IGIV results in reduction in non-RSV respiratory hospitalization is not known. It may be, in part, a secondary result of prevention of the late sequelae of RSV infection (eg, wheezing, pulmonary function abnormalities) which result in additional hospitalization, the result of a reduction of respiratory disease other than RSV as a consequence of protection provided by antibodies to other infectious agents found in RSV-IGIV, or possibly the result of immunomodulatory effects of high-dose IVIG which could theoretically result in better lung function. A correlate of the reduction of overall respiratory illness is the 38% reduction observed in otitis media (P < .001), a finding previously reported in RSV-IGIV studies.19 This study suggests that RSV-IGIV has a major impact on overall respiratory hospitalization in addition to its specific effect on RSV hospitalization.
Risk factors for serious RSV infection include: 1) young age (under 1 year, especially under 6 months); 2) underlying medical problems, eg, prematurity, lung disease, CHD, other major congenital anomalies, immunodeficiency; and 3) hospitalization during RSV season, ie, nosocomial RSV.2 In addition, low levels of transplacentally acquired RSV antibody have been reported as another important risk factor.4,20 Previous experience with children at risk for severe RSV as a result of BPD or prematurity suggests that 20% or more will be hospitalized for RSV.7,14 The observed rate of RSV hospitalization in the control group in PREVENT was lower than anticipated (13.5% for the group as a whole) primarily because of a low rate (8.6%) for children under 6 months old. The reason for this low rate in the youngest children in this study is not certain. However, it appears that the youngest participants were “protected” from exposure to both RSV and non-RSV respiratory pathogens as evidenced by a low rate of non-RSV hospitalizations and a low rate of RSV infection as determined by serology and/or antigen detection. This is likely the result of the extensive education that parents received as part of the study recruitment and follow-up. In a controlled study of RSV-IGIV in children with CHD (Cardiac Study) conducted over three successive RSV seasons, the RSV hospitalization rate in control infants under 6 months old was 24%21 and in a previously published study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) in premature, BPD or CHD patients, 22% of control children less than 6 months old were hospitalized for RSV.14
The PREVENT trial was not designed nor powered to detect statistically significant differences in subgroups of children. Nevertheless, reduction in RSV hospitalization was observed in each subgroup of children analyzed (ie, categorical age less than or more than 6 months at entry, gender, and inclusion diagnostic category) and logistic regression using age as either a categorical (less than or more than than 6 months) or continuous variable did not demonstrate a significant interaction between age and treatment. The effect of RSV-IGIV in children ≤6 months old (at entry) has been assessed using data from two other controlled studies of RSV-IGIV (NIAID, Cardiac) described in the preceding paragraph in which comparable data regarding RSV hospitalization were collected.14,21 In each study the incidence of hospitalization was significantly reduced in these younger children.
Complications of RSV-IGIV prophylaxis were limited to those related to fluid volume and those anticipated as complications of IVIG. Prophylaxis with RSV-IGIV requires monthly administration of a fluid volume of 15 mL/kg. Complications related to fluid volume were uncommon, occurred primarily in patients with underlying BPD, and were manageable with modifications of the infusion rate and/or use of diuretics. The safety profile of RSV-IGIV was found to be similar to other commercially available intravenous immunoglobulin products.15-18
Since its discovery in the 1950s, RSV has been recognized as the leading cause of lower respiratory tract disease in infants and young children. Despite intensive efforts over the past 40 years, attempts at development of effective methods for the prevention of serious RSV illness have been unsuccessful. Data from the PREVENT study demonstrates that RSV-IGIV (750 mg/kg) is safe and effective when given monthly by intravenous infusion for prophylaxis for serious lower respiratory tract infection caused by RSV in children under 24 months old with BPD or a history of premature birth (≤35 weeks gestation).
This clinical trial has established the safety and efficacy of RespiGam. For the pediatric community, the availability of this new preventive tool raises natural questions about its optimal utilization. In clinical practice, choosing patients for prophylaxis will be based on assessment of the risk of serious RSV (eg, gestational age, underlying disease, chronological age, etc) as well as the risk:benefit and cost of RespiGam. Evaluation of risk of serious RSV can only be made based on the collective medical literature. Results from this and other studies of RespiGam provide a basis for risk:benefit assessment. Data is just now emerging regarding the cost:effectiveness of RespiGam prophylaxis and suggest that it compares favorably with many other standard medical interventions.22 Because RespiGam prophylaxis has now been shown to be associated with reduction of overall respiratory hospitalizations and otitis media, these factors will have to be included in future cost:benefit assessments.
We would like to thank Terri Mancusi, Bobbi Tuten, and Lori Ovington for their invaluable assistance in preparation of this study report and all of the families and children who participated in this trial.
The PREVENT Study Group consists of: Edward Connor, MD, Franklin Top, MD, Andrew Kramer, PhD, Miriam Schneider, Joni Love, RN, David Carlin, PhD, MedImmune, Inc, Gaithersburg, MD; George Siber, MD, Jeanne Leszczynski, DrPH, James McIver, PhD, Massachusetts Public Health Biologics Laboratory, Boston, MA; Val Hemming, MD, Sally Henson, Uniformed Services Health University, Bethesda, MD; Susan Spruill, MS, Christine Colven, Pharmaceutical Product Development, Wilmington, NC; Janet Wittes, PhD, Statistics Collaborative, Washington, DC; Dharmapuri Vidyasagar, MD, C. Lucy Park, MD, University of Illinois at Chicago, Chicago, IL; John F. Modlin, MD, Torunn Rhodes, MD, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Arun K. Pramanik, MD, Sue Jue, MD, Ed Gustavson, MD, Martic Smith, RN, Louisiana State University Medical Center, Shreveport, LA; Gerard P. Rabalais, MD, Sofia Franco, MD Shirley Wilkerson MD, Karen Bibb, MD, Kosair Children's Hospital, Louisville, KY; Major Bruce E. Pichoff, II, MD, Richard Blaszak, MD, Shon Remich, MD, Matthew Rettke, MD, William Beaumont Army Medical Center, El Paso, TX; Leonard E. Weisman, MD, Meghan C. McDonald, MD, Karen E. Johnson, MD, Karen Adams, RN, Baylor College of Medicine, Houston, TX; Stephen A. Chartrand, MD, Mark C. Wilson, MD, Creighton School of Medicine, Omaha, NE; Gregory J. Redding, MD, Dennis Mayock, MD, Heather J. S. Hanna, RN, University of Washington School of Medicine, Seattle, WA; David K. Stevenson, MD, Ronald L. Ariagno, MD, Marian M. Adams, MD, Siv Modler, BS, Packard Children's Hospital at Stanford, Palo Alto, CA; K. N. Siva Subramanian, MD, Yolande A. Smith, MD, Deborah A. Hoy, MD, Ildiko Kunos, MD, Pamela Angelus, RN, Georgetown University Medical Center, Washington, DC; Ram Yogev, MD, Melissa Davis, RN, Dietra D. Millard, MD, Children's Memorial Hospital, Chicago, IL; Jean J. Steichen, MD, Tari Gratton, PA, Children's Hospital Medical Center, Cincinnati, OH; Judy Bernbaum, MD, Beverly Banks, MD, Sharon Zirin, R.N, Jane Fricko, RN, Linda Corcoran, RN, Children's Hospital of Philadelphia, Philadelphia, PA; Cynthia T. Barrett, MD, Nancy L. Pusser, MD, E. Richard Stiehm, MD, UCLA School of Medicine, Los Angeles, CA; Ellen R. Cooper, MD, Alan Fujii, MD, Boston City Hospital, Boston, MA; Laurence B. Givner, MD, T. Michael O'Shea, MD, Beth Norman, RN, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC; Terese L. Jennings, MD, Robert E. Kimura, MD, Ushanalini Vasan, MD, Amy Hennessy, RN, Rush Presbyterian Medical College, Chicago, IL; Andrea Kovacs, MD, Robert deLemos, MD, Margaret Khoury, MD, LAC & USC Medical Center, CA Women's & Children's Hospital, LA; Sharon A. Nachman, MD, State University of New York, Stony Brook, NY; Paul E. Stobie, MD, Judy Coggins, RN, Kathy M. Perea, RN, Presbyterian Hospital, Albuquerque, NM; Stephen C. Aronoff, MD, Susan Lynch, MD, Mark Polak, MD, Linda S. Baer, RN, West Virginia University Health Sciences Center, Morgantown, WV; Caroline B. Hall, MD, Christine Long, MPH, University of Rochester Medical Center, Rochester, NY; Richard Inwood, MD, Excelsis Antonio, MD, Bellipady C. Rai, MD, Madhu Goyal, MD, Lorraine E. Solecki, BSN, Newark Beth Israel Medical Center, Newark, NJ; Martha L. Lepow, MD, Michael Horgan, MD, Holly Swanson, MD, Albany Medical College, Albany, NY; Roy C. Maynard, MD, David Brasel, MD, Kathy Werner, BSN, Children's Health Care Hospital, Minneapolis, MN; David G. Oelberg, MD, Eastern Virginia Medical School, Children's Hospital of the King's Daughter, Norfolk, VA; Pablo J. Sanchez, MD, R. Sue Broyles, MD, Fiker Zeray, RN University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Elaine S. Barefield, MD, Monica V. Collins, RN, MEd, University of Alabama at Birmingham, Birmingham, AL; Shobhana A. Desai, MD, Thomas E. Wiswell, MD, James E. Cullen, RN, BSN, Jefferson Medical College, Philadelphia, PA; William C. Gruber, MD, Thomas A. Hazinski, MD, Jane Baker, RN, Stefanie Freeman, RN, MSN, Odessa Settles, RN, MP, Vanderbilt University Medical Center, Nashville, TN; Jeffrey S. Gerdes, MD, Reyin Lien, MD, Jean Ann Cieplinski, RN, Pennsylvania Hospital, Philadelphia, PA; J.Owen Hendley, MD, Robert J. Boyle, MD, Melinda Robinson, RN, University of Virginia Health Sciences Center, Charlottesville, VA; Kathleen D. Pfeffer, MD, Dale Robertson, MD, Chris Portelli, RN, University of Utah Medical Center, Salt Lake City, UT; Evan A. Steinberg, MD, Grace Fabillar, RN, Deidre Bloom, MD, Sam Zinner, MD, Kaiser Foundation Hospital, Los Angeles, CA; Robert C. Welliver, MD, Debra A. Tristram, MD, Cynthia Shuff, RN, Kathy Alessi, RN Children's Hospital of Buffalo, Buffalo, NY; Richard Lemen, MD, Leslie Barton, MD, Nahid Maleniazi, RN, University of Arizona Health Sciences Center, Tucson, AZ; Michael J. Romano, MD, Kathy Goei, RN, MSN, San Antonio Pediatric Pulmonary & Critical Care Associates, San Antonio, TX; Jeffrey W. Stolz, MD, MPH, Harvard Medical School, Boston, MA; Ronald B. Turner, MD, Medical University of South Carolina, Charleston, SC; Ellen R. Wald, MD, Marian Michaels, MD, MPH, Michael Green, MD, MPH, Karen Smail, RN, MSN, CRNP, Children's Hospital of Pittsburgh, Pittsburgh, PA; Andrew M. Davey, MD, David G. Rupar, MD, Hortense Turner, RN, MSN, Carolinas Medical Center, Charlotte, NC; Penelope H. Dennehy, MD, Rhode Island Hospital, Providence, RI; Donald M. Null, Jr, MD, Allegheny General Hospital, Pittsburgh, PA; Juan A. Dumois, MD, Glenda Taaffe, RN, All Children's Hospital, St. Petersburg, FL; Karen Hardy, MD, Julie Bushnell, PNP, Kayla Harvey, PNP, California Pacific Medical Center, San Francisco, CA; Brian P. O'Sullivan, MD, Rhoda Spaulding, MSN, FNP, University of Massachusetts Medical Center, Worcester, MA; Peter D. Reuman, MD, MPH, Ira Gessner, MD, Connie Nixon, RN, University of Florida, Gainesville, FL; Mary L. Kumar, MD, Candice E. Johnson, MD, PhD, Marc Collin, MD, MetroHealth Medical Center, Cleveland, OH; Susan Sniderman, MD, Nancy Newton, RN, BSN, Jean Millar, RN, BSN, Kimberly Champawat, RN, BSN, University of California-San Francisco, San Francisco, CA; Russell B. Van Dyke, MD, Benjamin Estrada, MD, Tulane University School of Medicine, New Orleans, LA; Jill E. Baley, MD, Robert Hostoffer, MD, Susan W. Aucott, MD, Avroy A. Fanaroff, MB, BCh, Rainbow Babies and Children's Hospital, Cleveland, OH; Stephen C. Eppes, MD, Judith A. Childs, PhD, RN, Alfred I. duPont Institute, Wilmington, DE; Joseph Marc Majure, MD, Duke University Medical Center, Durham, NC; Mark M. Shelton MD, Donald K. Murphey, MD, Mary L. Jackson, RN, Cook-Fort Worth Children's Medical Center, Fort Worth, TX.
- Received May 28, 1996.
- Accepted August 21, 1996.
- Address correspondence to: Edward Connor, MD, MedImmune, Inc, 35 W Watkins Mill Rd, Gaithersburg, MD 20878.
↵* The members of the PREVENT Study Group are listed on pages 98 and 99 in the Appendix.
- RSV =
- respiratory syncytial virus •
- BPD =
- bronchopulmonary dysplasia •
- CHD =
- congenital heart disease •
- RSV-IGIV =
- respiratory syncytial virus immune globulin, intravenous •
- LRI =
- lower respiratory infection/illness •
- ICU =
- intensive care unit
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- Copyright © 1997 American Academy of Pediatrics