BACKGROUND. Postnatal corticosteroids were widely used in the 1990s in an attempt to reduce the incidence of bronchopulmonary dysplasia. However, high rates of short-term adverse effects and impaired neurodevelopmental outcomes were seen. In early 2002, a joint statement of the American Academy of Pediatrics and Canadian Paediatric Society called for limitation in the use of postnatal corticosteroids. The impact of this statement is not known.
OBJECTIVES. The purpose of this work was to determine the frequency of postnatal corticosteroid use and mortality and morbidities over time, particularly before and after the joint statement.
DESIGN/METHODS. We conducted a retrospective analysis of cohort data within 3 large network registries (the National Institute of Child Health and Development Neonatal Research Network [18 centers], the Vermont Oxford Network [444 centers], and the Canadian Neonatal Network [10 centers]) for the following 3 periods: prestatement (2001), statement (2002), and poststatement (2003) of very low birth-weight infants (501–1500 g). The National Institute of Child Health and Development Neonatal Research Network and the Vermont Oxford Network were also analyzed for longer-term trends from 1990 to 2003. Postnatal corticosteroid use, mortality at discharge, and neonatal morbidities (bronchopulmonary dysplasia at 36 weeks, late-onset infection >72 hours of age, necrotizing enterocolitis treated with surgery, and length of stay) between periods were compared.
RESULTS. Mean birth weight (range: 1022–1060 g), postmenstrual age (28 weeks), and gender (51% male) were similar between the networks. Race differed with more black infants in the National Institute of Child Health and Development Neonatal Research Network than the Vermont Oxford Network (38% vs 24%). Antenatal steroid use was similar (range: 61%–75%). Postnatal corticosteroid use rose from 1990 (8%–16%), peaked in 1996–1998 (24%–28%), and began to decline in 1999. Use in 2003 was significantly less than in 2001. Mortality and major morbidities were similar.
CONCLUSIONS. Postnatal corticosteroid use had decreased significantly in 3 large neonatal networks before the joint statement with further decreases after the statement with no apparent impact on mortality and short-term morbidity. Despite substantial decreases, ∼8% of very low birth-weight infants continue to be treated with postnatal corticosteroid.
In the 1990s, neonatologists embraced the use of postnatal steroids (PNSs) in infants with bronchopulmonary dysplasia (BPD) when small trials suggested that use could enhance the ability to extubate infants.1 By the mid-1990s, publications documented that ≤50% of all very low birth weight (VLBW; <1500 g) infants were exposed to ≥1 dose of PNS.
Subsequently larger studies and studies that included longer term outcomes demonstrated that PNS use was associated with substantial short- and long-term complications.2–4 These complications included hyperglycemia, hypertension, increased risk of infection, increased rates of intestinal perforation, adrenal suppression, and reduced growth. Of more concern, neurodevelopmental impairment was seen, although some feel that this may be limited to longer courses at higher doses. Randomized, controlled trials to date have failed to show benefit.5,6 In 1998, metanalyses demonstrated the substantial detrimental effects of PNS exposure.7–10 In 2002, the American Academy of Pediatrics and the Canadian Paediatric Society published a combined statement calling for limitation of the use of PNS.11,12 The statement was based on a synopsis of 5 Cochrane reviews, 7 systematic reviews published in paper journals, and additional trials completed since the reviews were published. The impact of this statement is not known. We conducted a retrospective cohort study of prospectively collected data of PNS use among 3 large neonatal networks to determine changes in PNS use over time with particular focus on the time period surrounding the joint American Academy of Pediatrics and Canadian Paediatric Society statement.
All of the inborn neonates born between January 1, 2000, and December 31, 2003, weighing 501 to 1500 g, and enrolled in the databases of 3 large neonatal networks were included (the National Institute of Child Health and Development Neonatal Research Network [NICHD NRN], the Vermont Oxford Network [VON], and the Canadian Neonatal Network [CNN]). In addition, the trend in PNS use from 1990 to 2004 was examined in the NICHD NRN and the VON. The VON includes VLBW infants in its database if they are transferred within 28 days of birth, and the NRN includes those transferred within 7 days of birth. The networks participating were the NICHD NRN (16 NICUs), the VON (410 NICUs), and the CNN (10 NICUs). The number of participating units varied over the study period in each of the networks, with the most change seen in the VON (2001: n = 378; 2002: n = 408, 2004: n = 444). Definitions were scrutinized to ensure similar applications across the networks. Data on demographic characteristics, PNS use, and common neonatal morbidities were described by year. In all 3 of the registries, PNS exposure was coded as yes versus no. No data were available on timing, type, or dose of exposure. Data were available for 1990–2004 in NICHD NRN and VON and for 2001–2003 in the CNN. Length of stay was calculated for all of the infants admitted to the NICU until final discharge to home or chronic care. BPD was defined in this study as oxygen exposure >21% at 36 weeks' corrected age. Infants transferred or discharged before 36 weeks were handled differently by the 3 networks. In the NICHD NRN and CNN infants discharged or transferred on oxygen/respiratory support were assigned the outcome BPD, if no additional information was available. In the VON, neonates were assigned the outcome BPD according to an algorithm based on gestational age at transfer. Those <32 weeks' postmenstrual age who were transferred on oxygen were coded as unknown, and those transferred without oxygen were coded as no BPD. Those >32 weeks' postmenstrual age at the time of transfer with an oxygen requirement were assigned the outcome BPD. In the NICHD NRN and CNN late-onset sepsis was defined as any organism obtained on blood culture at >72 hours of age associated with clinical signs of infection. For VON, only blood culture organisms on a predefined list of pathogens or coagulase negative staphylococcus together with clinical signs of infection and antibiotic treatment for >5 days were counted. Surgery for necrotizing enterocolitis included both laparotomy and drain placement.
Sample Size and Statistical Analyses
Because of confidentiality agreements with existing network members, each network completed analyses of their own data, and results were combined for presentation. Thus, statistical analyses of intranetwork differences could not be performed. Based on a 25% rate of PNS exposure and an annual sample of 35000 among all 3 of the networks, the available sample had 90% power to detect a ≥2% absolute reduction in PNS use (2-sided α = .05). To determine the significance of change in steroid use over time and changes in other outcome variables, proc genmod (SAS 9, SAS Institute, Cary, NC) was used adjusting for intraclass correlation within hospital. Publication of anonymous aggregate results was approved by local institutional review boards (NICHD NRN and CNN) and by the institutional review board governing the VON registry.
Birth weight, gestational age, and gender were similar between the 3 networks (Table 1). Racial distribution differed between the networks with more black infants in the NICHD NRN. Use of antenatal steroids was slightly less frequent in the CNN.
PNS use in the NICHD NRN and the VON is shown in Fig 1. Use increased throughout the 1990s, peaked at ∼25% of all VLBW infants in 1996–1998, and began to decline in 1999 in advance of publication of the joint statement in 2002. The decline continued at the same rate before and after the joint statement. In all 3 of the networks, PNS use in 2003 was significantly less than in 2001 (P < .01) although the reduction in use in the CNN was of a larger magnitude. The NICHD NRN reduced use from 13.1 to 7.9% (P < .0001), VON from 17.7 to 9.9% (P < .001), and CNN from 23.6% to 2.6% (P < .001; Table 2). Over the same time period that PNS reduced, neonatal mortality and major short-term morbidities, including BPD, remained relatively unchanged between 2001 and 2003 (Table 2).
The characteristics of the neonates treated with PNS changed overtime. In the NICHD NRN, the birth weight and gestational age of infants treated with PNS declined significantly between 1990 and 2003 (mean birth weight: 836 ± 211 g vs 811 ± 225 g; P < .0001; gestational age: 27.2 ± 1.8 weeks vs 25.6 ± 2.0 weeks; P < .0001). Similar declines were seen in the VON (mean birth weight: 885 ± 225 g vs 821 ± 220 g; gestational age: 26 ± 2 weeks vs 25 ± 2 weeks). Other measures of severity of illness are not available in these databases.
PNS use peaked in 1996–1998 with ∼25% of all VLBW neonates treated with PNS; use then declined throughout the study period. The decline in use was parallel in all of the networks. The decline in PNS use began before the release of the joint statement in 2002 and continued to decline after release of the statement. Despite the significant decrease, ∼8% of neonates continued to be treated with PNS in 2004. It is reassuring to note in this large cohort that there has been little impact on short-term morbidities of VLBW neonates, including BPD. It will be important to assess the impact of reduced PNS use on later neurodevelopment. Doyle et al13 have suggested in a metaregression of randomized trials that neonates with an estimated risk of BPD >50% benefit from treatment with PNS. More detailed studies are needed on subgroups to ensure that the group of highest risk neonates are not disadvantaged by declining PNS use. In addition, more data are needed to determine whether intravenous dexamethasone use has been replaced with other steroid types or routes.
Our retrospective observational study has important limitations that must be recognized. Our study provides estimates of prevalence of PNS during the periods studied. Associations with outcomes are noted, but observational studies cannot assign causality. Historical cohort studies are inevitably confounded by changes in practices and therapies over time. Data on important ventilatory and treatment variables are limited in these databases and, thus, could not be used to control for severity of illness. Finally, no data are available on dose, duration, or timing of PNS exposure.
The forces leading to the decrease in PNS use are unknown but seem to antedate the release of the consensus statement. We speculate that one of the modulating forces was increasing awareness by neonatologists of the potential deleterious effects of PNS together with the release of the Cochrane metanalyses of the impact of PNS use by Halliday and Ehrenkranz8 in 1999 and other systematic reviews/studies published outside of the Cochrane Library.2,6,9,10,14 The timing of the peak use and first year of reduced use points to the publication of the multicenter trials of Yeh et al3 and O'Shea et al2 as instrumental in influencing practice. Shinwell et al15 noted a similar reduction in PNS use in Israel between 1993–1994 and 2001 from 22% to 6%. It is encouraging to see such a rapid dissemination of information and incorporation into practice. Other authors have cited longer times to diffusion of new treatments.16
In the 1990s, PNS for prevention and treatment of BPD was commonly used. PNS use has decreased significantly in 3 large neonatal networks before the joint statement with further decreases after the statement with no apparent impact on mortality and short-term morbidity. Despite substantial decreases in use, ∼8% of VLBW infants continue to be treated with PNS. Additional work is needed in high-risk subgroups to ensure that declining use does not adversely impact such patients.
Members of the NICHD Neonatal Research Network include: Case Western Reserve University, Cleveland, OH (U10 HD21364); University of Cincinnati, Cincinnati, OH (U10 HD27853); Emory University, Atlanta, GA (U10 HD27851); Indiana University, Indianapolis, IN (U10 HD27856); University of Miami, Miami, FL (U10 HD21397); Research Triangle Institute, Research Triangle, NC (U01 HD36790); Stanford University, Stanford, CA (U10 HD27880); University of Texas Health Science Center at Houston, Houston, TX (U10 HD21373); Wayne State University, Detroit, MI (U10 HD21385); Women and Infants Hospital, Providence, RI (U10 HD27904); Yale University, New Haven, CT (U10 HD27871); and University of Alabama at Birmingham, Birmingham, AL (U10 HD34216).
Members of the CNN include: Janeway Hospital, St John's, Newfoundland; St Boniface Hospital, Winnipeg, Manitoba; St Joseph's Health Centre, London, Ontario; Mt. Sinai Hospital, Toronto, Ontario; Royal Alexandra Hospital, Edmonton, Alberta; Royal University Hospital, Saskatoon, Saskatchewan; Winnipeg Health Sciences Centre, Winnipeg, Manitoba; Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia; Victoria General Hospital, Victoria, British Columbia; and Children's Hospital of Eastern Ontario, Ottawa, Ontario.
Members of the VON include: Abington Memorial Hospital, Abington, PA; Advocate Lutheran General Hospital, Park Ridge, IL; Affinity NICU-St Elizabeth Hospital, Appleton, WI; Akron Children's Hospital, Akron, OH; Al Corniche Hospital, Abu Dhabi, United Arab Emerates; Albany Medical Center, Albany, NY; Albert Einstein Medical Center, Philadelphia, PA; Alegent Health Bergen Mercy Medical Center, Omaha, NE; All Saints Episcopal Hospital, Fort Worth, TX; All Saints Healthcare-St Luke's Hospital, Racine, WI; Alta Bates Summit Medical Center, Berkeley, CA; Anne Arundel Medical Center, Annapolis, MD; Antelope Valley Hospital, Lancaster, CA; Arnot Ogden Medical Center, Elmira, NY; Aultman Hospital, Canton, OH; Aurora Sinai Medical Center, Milwaukee, WI; Avera McKennan, Sioux Falls, SD; Ball Memorial Hospital, Muncie, IN; Baptist Children's Hospital, Miami, FL; Baptist Healthcare System, San Antonio, TX; Baptist Medical Center, Montgomery, AL; Baptist Memorial Hospital for Women, Memphis, TN; Baptist St Anthony's Health System, Amarillo, TX; Barbara Bush Children's at Maine Medical, Portland, ME; Baylor University Medical Center, Dallas, TX; Baystate Medical Center, Springfield, MA; Bellevue Hospital, New York, NY; Benefis Healthcare, Great Falls, MT; Beth Israel Deaconess Medical Center, Boston, MA; Blank Children's Hospital, Des Moines, IA; Bon Secours Richmond Health System, Richmond, VA; Brandon Regional Hospital, Brandon, FL; Brenner Children's Hospital at WFUBMC, Winston-Salem, NC; Brigham and Women's Hospital, Boston, MA; Brookdale Hospital Medical Center, Brooklyn, NY; Brooklyn Hospital Center, Brooklyn, NY; Broward General Medical Center, Fort Lauderdale, FL; Bryn Mawr Hospital, Bryn Mawr, PA; CA Hospital Medical Center, Los Angeles, CA; CA Pacific Medical Center, San Francisco, CA; CHOA/Brackenridge Campus, Austin, TX; CHOC at Mission, Mission Viejo, CA; CHOI at OSF St Francis Medical Center, Peoria, IL; CHOP Neonatology at Chester County Hospital, West Chester, PA; Cape Fear Valley Medical Center, Fayetteville, NC; Capital Health System, Trenton, NJ; Cardinal Glennon Children's Hospital, St Louis, MO; Caritas St Elizabeth's Medical Center, Boston, MA; Carle Foundation Hospital, Urbana, IL; Carolinas Medical Center, Charlotte, NC; Cedars-Sinai Medical Center, Los Angeles, CA; Centennial Medical Center, Nashville, TN; Central Dupage Hospital, Winfield, IL; Central Mississippi Medical Center, Jackson, MS; Charite-Mitte, Berlin, Germany; Charleston Area Medical Center, Charleston, WV; Children's Health Care of Atlanta-Egleston, Atlanta, GA; Children's Hospital and Research Center at Oakland, Oakland, CA; Children's Hospital-Columbus, Columbus, OH; Children's Hospital-Omaha, Omaha, NE; Children's Hospital Central CA, Madera, CA; Childrens Hospital Los Angeles, Los Angeles, CA; Children's Hospital Medical Center, Cincinnati, Cincinnati, OH; Children's Hospital at Bronson, Kalamazoo, MI; Children's Hospital at Providence Alaska, Anchorage, AK; Children's Hospital of Greenville, Greenville, SC; Children's Hospital of Iowa, Iowa City, IA; Children's Hospital of Orange County, Orange, CA; Children's Hospital of SW Florida-Lee Memorial, Ft Myers, FL; Children's Hospital of WI-Fox Valley, Neenah, WI; Children's Hospital of Wisconsin, Milwaukee, WI; Children's Hospital-San Diego, San Diego, CA; Children's Hospitals and Clinics, Minneapolis, MN; Children's Hospitals and Clinics, St Paul, MN; Children's Medical Center-Dayton, Dayton, OH; Children's Mercy Hospital, Kansas City, MO; Children's at Cooper University Medical Center, Camden, NJ; Christ Hospital and Medical Center, Oak Lawn, IL; Christiana Care Health Services, Newark, DE; Christus Santa Rosa Healthcare, San Antonio, TX; Citrus Valley-Queen of the Valley Campus, W Covina, CA; Cleveland Clinic Foundation, Cleveland, OH; Columbia Hospital for Women-DC, Washington, DC; Columbia St Mary's Hospital, Milwaukee, WI; Columbia University Medical Center, New York, NY; Columbus Regional Medical Center, Columbus, GA; Community Medical Center, Missoula, MT; Conemaugh Memorial Medical Center, Johnstown, PA; Connecticut Children's Medical Center, Hartford, CT; Cook Children's Medical Center, Fort Worth, TX; Coombe Women's Hospital, Dublin, Ireland; Crawford Long Hospital, Atlanta, GA; Creighton University Medical Center, Omaha, NE; Crozer-Chester Medical Center, Upland, PA; Danbury Hospital, Danbury, CT; Danube Hospital-SMZ-Ost, Vienna, Austria; Dartmouth-Hitchcock Medical Center, Lebanon, NH; DeVos Children's/Spectrum Health, Grand Rapids, MI; Deaconess Medical Center, Spokane, WA; Desert Regional Medical Center, Palm Springs, CA; Doctor's Hospital West, Columbus, OH; Doctor's Medical Center, Modesto, CA; Driscoll Children's Hospital, Corpus Christi, TX; Dupont Hospital, Fort Wayne, IN; EBZ LKA Salzburg, Salzburg, Austria; Earl K. Long Medical Center, Baton Rouge, LA; East Tennessee Children's Hospital, Knoxville, TN; Eastern Maine Medical Center, Bangor, ME; Edward Hospital and Health Services, Naperville, IL; Elliot Hospital, Manchester, NH; Encino Tarzana Regional Medical Center; Tarzana, CA; Evanston Hospital, Evanston, IL; Exempla St Joseph Hospital, Denver, CO; Fairview Hospital, Cleveland, OH; Fernando Fonseca Hospital, Lisbon, Portugal; Fitzgerald Mercy Medical Center, Darby, PA; Florida Hospital Orlando, Orlando, FL; Forrest General Hospital, Hattiesburg, MS; Forsyth Memorial Hospital, Winston-Salem, NC; Forum Health-Tod Children's, Youngstown, OH; Frankford Torresdale Hospital, Philadelphia, PA; Freeman Hospital and Health System, Joplin, MO; Garfield Medical Center, Monterey Park, CA; Gazi University Hospital, Ankara, Turkey; Geisinger Medical Center, Danville, PA; Genesis Medical Center, Davenport, Iowa; Glendale Memorial Hospital and Health Center, Glendale, CA; Good Samaritan HCA, San Jose, CA; Good Samaritan Hospital, Cincinnati, OH; Good Samaritan Hospital, Los Angeles, CA; Grady Memorial Hospital, Atlanta, GA; Grant Medical Center, Columbus, OH; Greater Baltimore Medical Center, Baltimore, MD; Greater Lafayette Health Services, Lafayette, IN; Grossmont Hospital Women's Health Center, La Mesa, CA; Gundersen Lutheran, LaCrosse, WI; Gwinnett Health System, Lawrenceville, GA; Hackensack University Medical Center, Hackensack, NJ; Hahnemann University Hospital, Philadelphia, PA; Harbor UCLA Medical Center, Torrance, CA; Harris Methodist Fort Worth Hospital, Fort Worth, TX; Hennepin County Medical Center, Minneapolis, MN; Henrico Doctor's Hospital, Richmond, VA; Henry Ford Hospital, Detroit, MI; Hoag Memorial Hospital Presbyterian, Newport Beach, CA; Holy Cross Hospital, Silver Spring, MD; Hospital Sant Joan de Deu, Barcelona, Spain; Hospital de Cruces, Barakaldo, Spain; Hospital de S. Joao, Porto, Portugal; Hospital de Santa Maria, Lisbon, Portugal; Hospital for Children, Helsinki, Finland; Hospital of University of Pennsylvania, Philadelphia, PA; Howard County General Hospital, Columbia, MD; Huntington Memorial Hospital, Pasadena, CA; Huntsville Hospital, Huntsville, AL; Hurley Medical Center, Flint, MI; IWK Health Centre, Halifax, Canada; Illinois Masonic Medical Center, Chicago, IL; Inova Fairfax Hospital for Children, Falls Church, VA; Jackson-Madison County General Hospital, Jackson, TN; Jacobi Medical Center, Bronx, NY; Janeway Children's Hospital Centre, St John, Canada; Joe DiMaggio Children's Hospital, Hollywood, FL; John Peter Smith Hospital, Fort Worth, TX; John Radcliffe Hospital, Oxford, United Kingdom; K.K. Women's and Children's Hospital, Singapore, Singapore; Kadlec Medical Center NICU, Richland, WA; Kaiser Foundation Hospital-South Bay, Harbor City, CA; Kaiser Foundation-Bellflower, Bellflower, CA; Kaiser Foundation-Fontana, Fontana, CA; Kaiser Foundation-Los Angeles, Los Angeles, CA; Kaiser Foundation-Orange County, Anaheim, CA; Kaiser Foundation-Panorama City, Panorama City, CA; Kaiser Foundation-Riverside Medical Center, Riverside, CA; Kaiser Foundation-San Diego, San Diego, CA; Kaiser Foundation-Walnut Creek, Walnut Creek, CA; Kaiser Foundation-West Los Angeles, Los Angeles, CA; Kaiser Foundation-Woodland Hills, Woodland Hills, CA; Kaiser Hayward Medical Center, Hayward, CA; Kaiser Permanente-Baldwin Park, Baldwin Park, CA; Kaiser Permanente-Sacramento, Sacramento, CA; Kaiser Permanente-Santa Clara, Santa Clara, CA; Kaiser San Francisco, San Francisco, CA; Kinderklinik Glanzing im Wilhelminenspital, Vienna, Austria; Kinderklinik Graz, Graz, Austria; Kings County Hospital Center, Brooklyn, NY; LDS Hospital, Salt Lake City, UT; LPCH-Stanford University, Palo Alto, CA; Lafayette General Medical Center, Lafayette, LA; Lancaster General Hospital, Lancaster, PA; Landeskinderklinik Linz, Linz, Austria; Landeskrankenhaus, Academic Teaching Hospital, Feldkirch, Austria; Lankenau Hospital, Bryn Mawr, PA; Laranjeiras Perinatal Clinic, Rio de Janeiro, Brazil; Legacy Emanuel Children's Hospital, Portland, OR; Lehigh Valley Hospital, Allentown, PA; Lenox Hill Hospital, New York, NY; Limerick Regional Maternity Hospital-St Munchin's, Limerick, Ireland; Little Company of Mary Hospital, Torrance, CA; Loma Linda University Children's, Loma Linda, CA; Loyola University Medical Center, Maywood, IL; Lutheran Hospital of Indiana, Fort Wayne, IN; MHUMC-Savannah, Savannah, GA; Macedonio Melloni Maternity Hospital, Milan, Italy; Magee-Womens Hospital, Pittsburgh, PA; Maimonides Medical Center, Brooklyn, NY; Maternidade Dr Alfredo Da Costa, Lisbon, Portugal; McKay-Dee Hospital Center, Ogden, UT; McLeod Regional Medical Center, Florence, SC; Medcenter One Health Systems, Bismarck, ND; Medical Center of LA-New Orleans, New Orleans, LA; Medical City, Dallas, TX; Medical College of Georgia, Augusta, GA; Medical University of South Carolina, Charleston, SC; Memorial Hermann Southwest, Houston, TX; Memorial Hospital, South Bend, IN; Memorial Hospital at Gulfport, Gulfport, MS; Memorial Medical Center, New Orleans, LA; Mercy Children's Hospital, Toledo, OH; Mercy Health Center, Oklahoma City, OK; Mercy Hospital and Medical Center, Chicago, IL; Mercy Hospital of Pittsburgh, Pittsburgh, PA; Mercy Medical Center, Canton, OH; Mercy Medical Center-Des Moines, Des Moines, IA; Mercy San Juan Hospital, Carmichael, CA; Meridia Hillcrest Hospital, Mayfield Heights, OH; Meritcare Children's Hospital, Fargo, ND; Methodist Children's Hospital, San Antonio, TX; Methodist Hospital of Indiana, Indianapolis, IN; Methodist Hospitals, Inc, Gary, IN; Miami Children's Hospital, Miami, FL; Miami Valley Hospital, Dayton, OH; Miller Children's Hospital, Long Beach, CA; Milton S. Hershey Medical Center, Hershey, PA; Mission Hospitals, Asheville, NC; Mississippi Baptist Health Systems, Jackson, MS; Monmouth Medical Center, Long Branch, NJ; Morristown Memorial Hospital, Morristown, NJ; Morton Plant Mease, Safety Harbor, FL; Mt Carmel Health Systems, Columbus, OH; Mt. Sinai Hospital, Toronto, Canada; Mt Sinai Hospital Medical Center, Chicago, IL; Munson Medical Center, Traverse City, MI; NICU Ospedale S. Anna-Como, Como, Italy; National Maternity Hospital, Dublin, Ireland; National Naval Medical Center, Bethesda, MD; Naval Medical Center Portsmouth, Portsmouth, VA; Naval Medical Center-San Diego, San Diego, CA; Nebraska Medical Center, Omaha, NE; Neonatologia-Trento/Ospedale S. Chiara, Trento, Italy; Neonatologie Zentralklinikum St Polten, St Polten, Austria; Neonatology-Saudi Aramco, Dhahran, Saudi Arabia; Neonatology Associates-Wellmont Holston Med Center, Kingsport, TN; New Hanover Regional Medical Center, Wilmington, NC; Newark Beth Israel Medical Center, Newark, NJ; Newborn Specialists of Tulsa, Tulsa, OK; North Memorial Medical Center, Robbinsdale, MN; North Mississippi Medical Center, Tupelo, MS; North Oaks Medical Center, Hammond, LA; Northbay Medical Center, Fairfield, CA; Northridge Hospital, Northridge, CA; Northside Hospital, Atlanta, GA; Northwest Medical Center, Margate, FL; Northwestern Memorial, Chicago, IL; Norton Suburban Hospital, Louisville, KY; Novor. dd. NsP., Nove Zamky, Slovakia; O.U. Health Sciences Center, Oklahoma City, OK; OH-CHEO, Ottawa, Canada; Oakwood Hospital and Medical Center, Dearborn, MI; Ochsner Clinic Foundation, New Orleans, LA; Oregon Health and Sciences University, Portland, OR; Ospedale di Lecco, Lecco, Italy; Ospedale Maggiore Policlinico, Mangiagalli Regina, Milan, Italy; Oulu University Hospital, Oulu, Finland; Our Lady of Lourdes Hospital, Drogheda, Ireland; Overland Park Regional Medical Staff, Overland Park, KS; PCMH, Greenville, NC; Palomar Medical Center NICU, Escondido, CA; Panorama Medi-Clinic, Panorama, South Africa, Parkridge East Hospital, Chattanooga, TN; Parkview Hospital, Fort Wayne, IN; Pennsylvania Hospital, Philadelphia, PA; Phoenix Children's Hospital, Phoenix, AZ; Piedmont Hospital, Atlanta, GA; Pomona Valley Hospital Medical Center, Pomona, CA; Poudre Valley Health System, Fort Collins, CO; Presbyterian Hospital, Albuquerque, NM; Presbyterian Hospital of Dallas, Dallas, TX; Presbyterian Intercommunity Hospital, Whittier, CA; Presbyterian-St Luke's Medical Center, Denver, CO; Primary Children's Medical Center, Salt Lake City, UT; Provena Covenant Medical, Center, Urbana, IL; Providence Hospital and Medical Center, Southfield, MI; Providence St Joseph Medical Center/CA, Burbank, CA; Providence St Vincent Medical Center, Portland, OR; Queen Mary Hospital, Hong Kong, China; Rainbow Babies and Children's Hospital, Cleveland, OH; Reading Hospital and Medical Center, Reading, PA; Redlands Community Hospital, Redlands, CA; Regional Medical Center at Memphis, Memphis, TN; River Oaks Health System, Jackson, MS; Riverside Community Hospital, Riverside, CA; Riverside Methodist Hospital, Columbus, OH; Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia; Robert Wood Johnson University Hospital, New Brunswick, NJ; Rockford Memorial Hospital, Rockford, IL; Rogue Valley Medical Center, Medford, OR; Rose Medical Center, Denver, CO; Rotunda Hospital, Dublin, Ireland; Royal Victoria Hospital, Montreal, Canada; Rush-Copley Medical Center, Aurora, IL; Sacred Heart Health System, Pensacola, FL; Sacred Heart Medical Center, Spokane, WA; Sacred Heart Medical Center, Eugene, OR; Salinas Valley Memorial Hospital, Salinas, CA; San Francisco General Hospital, San Francisco, CA; Sandton Medi-Clinic, Bryanston, South Africa; Scott and White Hospital, Temple, TX; Scottsdale Healthcare-Quality, Scottsdale, AZ; Seton Medical Center, Austin, TX; Shady Grove Adventist Hospital, Rockville, MD; Sharp Mary Birch Hospital for Women, San Diego, CA; Sheridan Children's/Plantation Hospital, Plantation, FL; Sinai Hospital of Baltimore, Baltimore, MD; Sioux Valley Children's Hospital, Sioux Falls, SD; Sisters of Charity, Staten Island, NY; Sligo General Hospital, Sligo, Ireland; South Fulton Medical Center, East Point, GA; South Miami Hospital, Miami, FL; Southern Regional Medical Center, Riverdale, GA; Southmead Hospital, Bristol, United Kingdom; Sparrow Hospital, Lansing, MI; St Agnes Hospital, Baltimore, MD; St Barnabas Medical Center, Livingston, NJ; St Charles Medical Center, Bend, OR; St Cloud Hospital, St Cloud, MN; St David's Medical Center, Austin, TX; St Elizabeth Hospital Center, Youngstown, OH; St Elizabeth Regional Medical Center, Lincoln, NE; St Francis Hospital, Tulsa, OK; St Francis Hospital, Hartford, CT; St Francis Medical Center, Lynwood, CA; St Francis Medical Center, Cape Girardeau, MO; St John Detroit Riverview Hospital, Detroit, MI; St John Hospital and Medical Center, Detroit, MI; St John's Hospital, Springfield, IL; St John's Hospital, Santa Monica, CA; St John's Mercy Medical Center, St Louis, MO; St Joseph Hospital and Medical Center, Paterson, NJ; St Joseph Hospital-Marshfield Clinic, Marshfield, WI; St Joseph Hospital/TX, Houston, TX; St Joseph Mercy Hospital, Ann Arbor, MI; St Joseph Mercy Oakland, Pontiac, MI; St Joseph's Children's Hospital of Tampa, Tampa, FL; St Joseph's Health Center, Syracuse, NY; St Joseph's Hospital, Milwaukee, WI; St Joseph's Hospital and Medical Center, Phoenix, AZ; St Luke's Hospital, Bethlehem, PA; St Luke's Hospital, Kansas City, MO; St Luke's Regional Medical Center, Boise, ID; St Mary Medical Center, Long Beach, CA; St Mary's Hospital and Medical Center, Grand Junction, CO; St Mary's Hospital Medical Center, Madison, WI; St Mary's Medical Center, Evansville, IN; St Mary's Medical Center-Duluth, Duluth, MN; St Mary's Mercy Medical Center, Grand Rapids, MI; St Mary's Regional Medical Center, Reno, NV; St Michaels Hospital, Bristol, United Kingdom; St Peter's Hospital, Albany, NY; St Peter's Medical Center, New Brunswick, NJ; St Rita's Medical Center, Lima, OH; St Vincent Hospital, Green Bay, WI; St Vincent Hospital and Health Center, Billings, MT; St Vincent Hospital-Manhattan, New York, NY; St Vincent Women's Hospital, Indianapolis, IN; St Vincent Women's Hospital, Indianapolis, IN; Stamford Hospital, Stamford, CT; Staten Island University Hospital, Staten Island, NY; Summa Health System, Akron, OH; Sunnybrook and Women's College Health Science, Toronto, Canada; Sunrise Children's Hospital, Las Vegas, NV; Sutter Memorial Hospital, Sacramento, CA; Swedish American Hospital, Rockford, IL; Swedish Medical Center, Englewood, CO; T.C. Thompson Children's Hospital, Chattanooga, TN; Tampere University Hospital, Tampere, Finland; Temple University Hospital, Philadelphia, PA; Texas Tech U. Health Science Center, Amarillo, TX; Thomas Jefferson University Hospital, Philadelphia, PA; Tisch Hospital-NYU Medical Center, New York, NY; Toledo Children's Hospital, Toledo, OH; Truman Medical Center, Kansas City, MO; Tufts-New England Medical Center, Boston, MA; Tulane Medical Center, New Orleans, LA; Turku University Hospital, Turku, Finland; University of Massachusetts Memorial Health Care, Worcester, MA; University of Tennessee Medical Center at Knoxville, Knoxville, TN; University of California Irvine Medical Center, Orange, CA; UCDMC, Sacramento, Sacramento, CA; UCHSC, Denver, CO; UCSD Medical Center, San Diego, CA; UCSF Medical Center, San Francisco, CA; UPMC Lee Regional, Johnstown, PA; Unified Maternity and Neonatal Services Cork, Cork, Ireland; Unita di Terapia Intensiva Neonatale, Ferrara, Italy; University Children's Hospital NICU, Greifswald, Germany; University College Hospital Galway, Galway, Ireland; University Hospital-Zurich, Zurich, Switzerland; University Hospital Motol, Prague, Czech Republic; University Hospital NICU-Cincinnati, Cincinnati, OH; University Hospital UMDNJ, Newark, NJ; University Hospital Vienna-AKH, Vienna, Austria; University Hospital of Brooklyn, Brooklyn, NY; University Kebangsaan Malaysia, Kuala Lumpur, Malaysia; University Klinik F. Kinder, Innsbruck, Austria; University Medical Center, Las Vegas, NV; University of Chicago, Chicago, IL; University of Illinois at Chicago, Chicago, IL; University of Kansas Hospital Authority, Kansas City, KS; University of Kentucky Children's Hospital, Lexington, KY; University of Louisville Hospital, Louisville, KY; University of Michigan-Holden NICU, Ann Arbor, MI; University of Minnesota Medical Center, Minneapolis, MN; University of Puerto Rico Hospital NICU, San Juan, PR; University of Utah Health Sciences Center, Salt Lake City, UT; University of Washington Medical Center, Seattle, WA; Utah Valley Regional Medical Center, Provo, UT; VT Children's at Fletcher-Allen Health Care, Burlington, VT; Valley Presbyterian Hospital, Van Nuys, CA; Vassar Brothers Hospital, Poughkeepsie, NY; Ventura County Medical Center, Ventura, CA; Via Christi-St Joseph Campus, Wichita, KS; Virtua Hospital Systems, Voorhees, NJ; WAKEMED Faculty Physicians-Wake Medical Center, Raleigh, NC; Waikato Hospital, Hamilton, New Zealand; Waterford Regional Hospital, Waterford, Ireland; Waukesha Memorial Hospital, Waukesha, WI; Weiler Hospital-Montefiore, Bronx, NY; Wellstar Cobb Hospital, Austell, GA; Wellstar Kennestone Hospital, Marietta, GA; Wesley Medical Center, Wichita, KS; West Virginia University School of Medicine, Morgantown, WV; Western Medical Center, Santa Ana, CA; Western Pennsylvania Hospital, Pittsburgh, PA; Willis-Knighton South, Shreveport, LA; Winchester Medical Center, Winchester, VA; Winnicott Infant Unit-St Mary's Hospital, London, United Kingdom; Winthrop University Hospital, Mineola, NY; Woman's Hospital, Baton Rouge, LA; Women and Children's Hospital, Lake Charles, Lake Charles, LA; Women's and Children's Hospital, Lafayette, LA; Women's Hospital of Greensboro, Greensboro, NC; Woodhull Medical Center, Brooklyn, NY; Wyckoff Heights Medical Center, Brooklyn, NY; Yakima Valley Memorial Hospital, Yakima, WA; Yale-New Haven Children's Hospital, New Haven, CT; York Hospital, York, PA; and ZOL St Jan, Genk, Belgium.
- Accepted June 8, 2006.
- Address correspondence to Michele C. Walsh, MD, Rainbow Babies & Children’s Hospital, 11100 Euclid Ave, Cleveland, OH 44106. E-mail:
↵1 Financial Disclosure: Dr Horbar is the chief scientific officer and Dr Carpenter is the chief statistician for the Vermont Oxford Network.
- ↵O'Shea TM, Kothadia KJ, Klinepeter KL, et al. Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age. Pediatrics.1999;104 :15– 21
- ↵Yeh TF, Lin YJ, Hsieh WS, et al. Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial. Pediatrics.1997;100(4) . Available at: www.pediatrics.org/cgi/content/full/100/4/e3
- ↵Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics.1998;101(5) . Available at: www.pediatrics.org/cgi/content/full/101/5/e7
- ↵Halliday HL, Ehrenkranz RA. Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev.2003;(1) :CD001146
- ↵Halliday HL, Ehrenkrantz RA, Doyle LW. Moderately early (7–14 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cohchrane Database Syst Rev.2003;(1) :CD001144
- ↵Halliday HL, Ehrenkrantz RA, Doyle LW. Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants. Cohchrane Database Syst Rev.2003;(1) :CD001145
- ↵American Academy of Pediatrics, Canadian Paediatric Society. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Pediatrics.2002;109 :330– 338
- ↵Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair J. Impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: Effect modification by risk for chronic lung disease. Pediatrics.2005;115 :655– 661
- Copyright © 2006 by the American Academy of Pediatrics