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PEDIATRICS Vol. 113 No. 6 June 2004, pp. 1559-1566

Fetal Infants: The Fate of 4172 Infants With Birth Weights of 401 to 500 Grams—The Vermont Oxford Network Experience (1996–2000)

Jerold F. Lucey, MD*,{ddagger}, Cherise A. Rowan, MD*, Patricia Shiono, PhD{ddagger}, Andrew R. Wilkinson, MB, ChB§, Sarah Kilpatrick, MD, PhD||, Nathaniel R. Payne, MD, Jeffrey Horbar, MD*,{ddagger}, Joseph Carpenter, MS{ddagger}, Jeannette Rogowski, PhD# and Roger F. Soll, MD*,{ddagger}

* Department of Pediatrics, College of Medicine, University of Vermont, Burlington, Vermont
{ddagger} Vermont Oxford Network, Burlington, Vermont
§ Department of Pediatrics, University of Oxford, Oxford, United Kingdom
|| University of Illinois at Chicago, Chicago, Illinois
Children’s Healthcare, Minneapolis, Minnesota
# RAND, Washington, DC


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 APPENDIX: PARTICIPATING...
 REFERENCES
 
Objective. Improvement in the survival of extremely low birth weight infants requires that we evaluate the limits of our care and assess the impact of treatment on a population of infants who previously rarely survived.

Methods. A review was conducted of demographic and clinical data of infants who had birth weight 401 to 500 g and were entered in the Vermont Oxford Network Database between 1996 and 2000.

Results. A total of 4172 infants who weighed 401–500 g (mean gestational age: 23.3 ± 2.1 weeks) were born at 346 participating centers. Overall, 17% survived until discharge. A total of 2186 (52%) died in the delivery room (DR), and 1986 (48%) were admitted to a neonatal intensive care unit (NICU). Compared with infants who died in the DR, infants who survived the DR and were admitted to the NICU were more likely to be female (58% vs 49%), to be small for gestational age (56% vs 11%), to have received prenatal steroids (61% vs 12%), and to have been delivered by cesarean section (55% vs 5%). Thirty-six percent of NICU admissions survived to discharge. Mean gestational age of the 690 NICU survivors was 25.3 ± 2.0 weeks. These survivors experienced significant morbidity in the NICU.

Conclusions. An appreciable number of these marginally viable fetal infants survive. They experienced a high rate of serious morbidities while in the NICU. There is very little information about long-term outcomes, as the medical and developmental status of few of these infants has been followed carefully. Parents should be made aware of the high incidence of serious problems, and concerted efforts should be made to follow the status of these infants.

Key Words: fetal infants • extremely low birth weight infants • extremely low gestational age infants • neonatal intensive care nursery • neonatal outcomes

Abbreviations: VON, Vermont Oxford Network • NICU, neonatal intensive care unit • DR, delivery room • SGA, small for gestational age • ROP, retinopathy of prematurity

During the past decade, significant improvement in the survival of extremely low birth weight infants has been reported.1–22 These survivors include some of the smallest and most immature infants for whom care has ever been provided. These successes require that we evaluate the limits of our care and assess the impact of treatment on this population of infants who previously rarely survived. The Centers for Disease Control and Prevention national statistics report 5462 liveborn infants in this weight category born in 1996 and 5952 born in 2000.23 There is debate regarding the limits of viability and the ethics of resuscitating these infants because of increasing evidence that these fetal infants face significant neurologic and developmental handicaps as they grow older.24–30

The Vermont Oxford Network (VON) is a voluntary, worldwide collaboration among neonatal intensive care units (NICUs).1 This article provides descriptive information from the VON database about the smallest infants enrolled (401–500 g birth weight) regarding their delivery room (DR) interventions, common treatments, and outcomes from 346 participating NICUs.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 APPENDIX: PARTICIPATING...
 REFERENCES
 
This report is an analysis of the data for all inborn infants who were born between 1996 and 2000 with birth weights between 401 and 500 g in 346 institutions that participate in the VON. Members adhere to uniform definitions included in the VON's Database Manual of Operations. Infants with birth weights of 401 to 500 g have been eligible since 1996 for inclusion in the database if they were liveborn at a member center or were transferred to a member center within the first 28 days after birth. For inclusion in the database, all infants in the weight range who met these criteria were eligible, including those who died in the DR or in another location at the participating hospital before admission to the NICU. For the purposes of this study, only infants who were born at the participating centers are included in the analysis, because the decision of whom to transfer introduces to the study a variety of biases. Data on demographic measures and major birth defects were collected for all eligible infants. Data for other interventions and all morbidity outcome measures were collected for eligible infants who were admitted to the NICU. Mortality was assessed for all infants who were discharged from the hospital or died at the reporting hospital or at the hospital to which they were initially transferred. Infants who were transferred more than once or who were readmitted after transfer were excluded from the mortality analyses, because these data were not available in all years studied. Infants were classified as small for gestational age (SGA) when birth weight was <10% for gestational age using the United States Natality data set specific for race, gender, and type of gestation (single or multiple). Centers that participate in the VON database are responsible for developing and following a data verification plan to ensure that data for all eligible infants are submitted.31 Descriptive data are presented; no statistical comparisons were performed.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 APPENDIX: PARTICIPATING...
 REFERENCES
 
A total of 4172 infants with birth weights of 401 to 500 g were born in VON member hospitals during the period of study 1996–2000 (Fig 1). Among the 4172 study infants, 2186 (52%) died in the DR and 1986 (48%) were admitted to the NICU. Of those infants who were admitted to the NICU, 63% died before discharge home, 35% survived to discharge, and 43 (2%) had unknown survival status. Overall, 690 (17%) survived to discharge from the NICU or initial transfer hospital.


Figure 1
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  		Fig 1. Total number of inborn infants who were born at 401 to 500 g: disposition.

 
The mean gestational age of the population whose survival status is known was 23.2 weeks (±2.1) with a mean birth weight of 457.8 g (±28.8 g; Table 1). Forty-seven percent of the infants were male, and 72% were singletons. Thirty-two percent of the infants were SGA, and 5% of the infants received a diagnosis of having congenital anomalies. Almost all (94%) of the mothers received some prenatal care, and 35% received antenatal steroids. There is no information on the type of steroid used or the amount or duration of administration. Twenty-nine percent of the population was delivered via cesarean section. The 1-minute Apgar score for these infants was commonly low: 79% had a reported score of <4.


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  		TABLE 1. Population Characteristics of All Infants 401 to 500 g at Birth Whose Survival Status is Known (N = 4129)

 
The majority of infants who survived to NICU admission received support in the DR, including supplemental oxygen, bag and mask ventilation, and intubation (Table 2). Those infants who died in the DR were less likely to have received any intervention. DR survival was related to gestational age. Thirty-two percent of infants who were born at 22 to 23 weeks’ gestational age survived the DR, whereas 83% of infants who were born at 24 to 25 weeks’ gestation, 92% of infants who were born at 26 to 27 weeks’ gestation, and 89% of infants who were estimated to be >27 weeks’ gestation survived the DR to NICU admission. In comparing DR survivors with infants who died in the DR, several differences emerge (Table 3). A majority (56%) of DR survivors were assessed to be SGA, whereas only 11% of infants who died in the DR were SGA. Both survivors and DR deaths were likely to have received prenatal care, but the use of antenatal steroids and delivery by cesarean section were different between the groups. Sixty-one percent of infants who survived to NICU admission received antenatal steroids, compared with 12% of infants who died in the DR. A majority (55%) of DR survivors were delivered by cesarean section, whereas only 5% of the infants who ultimately died in the DR were delivered by cesarean section.


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  		TABLE 2. DR Interventions of All Infants 401 to 500 g at Birth

 

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  		TABLE 3. Population Characteristics of DR Survivors Versus DR Deaths

 
Infants who survived to discharge from the NICU were more mature than those who died before discharge (mean gestational age of survivors: 25 vs 24 weeks’ gestation for NICU deaths; Table 4). Sixty-seven percent of survivors to discharge were female, and the survivors were more likely to be SGA (78% vs 44% of NICU deaths). The majority (76%) of survivors to discharge were delivered by cesarean section, whereas more than half of the infants who died in the NICU were delivered vaginally. The survivors were also more likely to have a 1-minute Apgar score >4 (52% vs 34% of NICU deaths).


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  		TABLE 4. Population Characteristics of NICU Survivors Versus NICU Deaths

 
The majority of deaths occurred during the first day of life (Fig 2). Infants who survived to discharge from the NICU had a median length of stay of 116 days, whereas those who died in the NICU had a median length of stay of 3 days. NICU survivors were more likely to receive mechanical ventilation (98% vs 80% of NICU deaths), nasal continuous positive airway pressure (77% vs 8%), and postnatal steroids (82% vs 16%).


Figure 2
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  		Fig 2. Timing of deaths of all infants.

 
Ninety-four percent of infants who survived to discharge from the NICU received a diagnosis of respiratory distress syndrome, and 11% were treated for a pneumothorax (Table 5). Approximately one half of these infants had a patent ductus arteriosus, 65% were treated with indomethacin, and 14% underwent surgical ligation. Infection rates in surviving infants were high. Fifty-three percent of NICU survivors experienced a nosocomial bacterial infection (infection with either a known bacterial pathogen or coagulase-negative staphylococcus): 27% with late bacterial sepsis (an infection with a known bacterial pathogen) and 37% with coagulase-negative staphylococcus sepsis (Table 5). Eleven percent of the NICU survivors had fungal infections, and 9% received a diagnosis of necrotizing enterocolitis. Cranial ultrasound screening was obtained in 98% of all NICU survivors. Twenty-six percent of these infants had a cranial ultrasound abnormality, with 8% receiving a diagnosis of severe intraventricular hemorrhage (grades 3–4). Retinopathy of prematurity (ROP) screening was performed in 97% of survivors, with 89% of the infants receiving a diagnosis of ROP. Severe ROP (stage III to IV) occurred in 40% of the survivors to discharge. Chronic lung disease at 36 weeks’ corrected gestational age was diagnosed in 74% of the infants who survived to discharge from the NICU.


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  		TABLE 5. Outcomes of NICU Survivors

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
APPENDIX: PARTICIPATING...
 REFERENCES
 
An increasing number of infants who are born at what traditionally has been considered the lower threshold of viability are now surviving until hospital discharge. Decision making regarding antenatal interventions, route of delivery, and resuscitation in the DR of these infants is complex and based on numerous variables. In general, fewer infants who are born at 401 to 500 g receive antenatal steroids, cesarean section delivery, or support in the DR than slightly heavier and more mature infants.1 Our data are limited because we have no information about this decision process on the part of the obstetrician, neonatologist, and parents. However, the assumptions made and the subsequent actions performed on the basis of possible prognosis separate the survivors from those infants who died in the DR or in the NICU. For example, 61% of infants who survived to NICU admission received antenatal steroids, whereas only 12% of infants who ultimately died in the DR received this treatment. Delivery by caesarean section was performed in 55% of DR survivors but in only 5% of infants who died in the DR. Seventy-six percent of the infants who survived to discharge from the NICU were delivered by caesarean section, and 76% received antenatal steroids, compared with 44% caesarean section rate of infants who died in the NICU and 53% receiving antenatal steroids. These differences in survival may be attributable to a value judgment on the part of the obstetrician or neonatologist that these particular infants were in better condition and "worth" trying to save. Our study cannot clarify this question.

The large sample size of the study is a strength that contributes to the generalizability of the findings. The data may be limited by the fact that our information is not population based; rather, it reflects the neonatal intensive care practices and outcomes of a diverse group of hospitals from around the world. This study is based on birth weight rather than on gestational age, and this, too, may be a limitation. Reports on outcomes of extremely low birth weight infants published in the past decade generally have used birth weight stratification to present their data.1–16 In the developed world, however, the use of obstetric ultrasound scanning for dating in the first trimester has become routine practice and is a reliable tool for assessing gestational age.32 In the most recent literature on outcomes of extremely premature infants, it is common practice to present information on morbidity and mortality on the basis of gestational age, especially in light of the differing outcomes that infants may have when gestationally more mature but significantly growth restricted.17–22,33 Infants in this cohort who were assessed to be SGA seem to have a survival advantage. This suggests that in light of the accuracy and universal use (in the developed world) of obstetric ultrasound scans for dating pregnancies, information regarding outcomes and decisions at the threshold of viability should in the future best be made on the basis of gestational age rather than on birth weight.

Neonatal care in the developed world continues to lower the limits of viability in extremely small, extremely premature "fetal infants." The fate of infants who have birth weights 401 to 500 g and are born within the VON is similar to previous reports.1–22 Hack and Fanaroff4 reviewed studies that reported the outcomes of extremely premature infants and found that survival at <500 g ranged from 4% to 18%. DR survivors at birth weights <500 g were usually SGA girls. A geographically based study by Sauve et al8 of 1193 infants who were born with a birth weight of <500 g reported that 45% of the liveborn infants died in the DR and that 25% of the liveborn infants received only compassionate care. Of those who were treated in the NICU, 15% were discharged from the hospital, a majority of whom had significant neurodevelopmental problems on follow-up evaluation at 3 years. El-Metwally et al20 reported on outcomes of 278 infants who were of 22 to 25 weeks’ gestation and born at a single medical center. At 22 weeks’ gestation, 43% of infants were resuscitated; 1 infant survived to discharge from the NICU. Eighty-one percent of infants who were born at 23 weeks’ gestation were resuscitated, and 34% survived to discharge. All infants who were born at 24 to 25 weeks’ gestation were resuscitated; 49% and 76%, respectively, survived to discharge. Lemons et al2 reported results from a multicenter study on low birth weight infants that included data on 195 infants who were <500 g at birth. Sixty percent of these infants were not resuscitated, and 11% of those who received neonatal intensive care survived. The EPICure study provides one of the best estimations of outcomes of extremely premature infants. The study evaluated the outcomes to discharge of 1269 live births at 20 to 25 weeks’ gestation in Ireland and the United Kingdom.19 Of the 811 infants who were admitted to the NICU, 61% died before discharge. Fifty-five percent of these deaths were attributed to withdrawal of active intensive care.

Our data do not include information on long-term follow-up. Other reports show a high incidence of poor neurologic and developmental outcome. Vohr et al26 reported on a large cohort of extremely low birth weight infants, 15 of whom were born <500 g, who were evaluated at 18 months. They found that 43% of the infants with birth weights <500 g had an abnormal neurologic examination, and 29% had cerebral palsy. More than half of the infants who were born at <500 g required early intervention services and occupational and physical therapy at home. Hack and Fanaroff4 reported rates of severe disability that ranged from 18% to 40% for infants who were born at 23 to 25 weeks’ gestation. Wood et al27 reported follow-up data on the EPICure study and showed similar poor neurodevelopmental outcomes, with 23% of infants having severe disability at 30 months’ follow-up and an additional 25% of survivors having some neurodevelopmental disability. A recent comparison of perinatal management strategies in hospitals in the Netherlands and in the United States showed that nearly universal aggressive treatment of infants who were born at 23 to 26 weeks’ gestation in New Jersey was associated with 24 additional survivors per 100 live births and 7 additional cases of disabling cerebral palsy per 100 live births, with a cost of 1372 additional ventilator days per 100 live births.25

In 1995, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists composed a joint statement entitled "Perinatal Care at the Threshold of Viability."34,35 The statement emphasizes the need to inform parents of survival rates and outcomes of infants who are born extremely prematurely and to clarify the risks and benefits of different approaches to treatment. It stresses the importance of keeping parents aware throughout the infant’s course of the potential complications of prolonged intensive care treatment. Currently, we all are engaged in a large uncontrolled experiment. The effectiveness of the neonatal intensive care technology at the extreme limits of birth weight or gestational age is essentially unknown. There are no randomized, clinical trials on any of the interventions (eg, surfactant, mechanical ventilation) currently in use for infants at this birth weight.36–39 The debate regarding who is too small and too immature to live will probably never end. This study provides prospectively gathered information on the largest cohort of infants who weighed <500 g published to date. This information is not encouraging, suggesting that the vast majority of these infants die and that surviving infants have serious complications. Our understanding of the impact of these "fetal infants" must be improved by obtaining more information regarding long-term follow-up. In the future, sufficient resources need to be allocated to carry out improved follow-up studies across a large number of intensive care units.


   APPENDIX: PARTICIPATING HOSPITALS IN THE VON
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 APPENDIX: PARTICIPATING...
REFERENCES
 
Abington Memorial Hospital, Abington, PA; Adventist Center for Children, Rockville, MD; Advocate Lutheran General Hospital, Park Ridge, IL; Aiiku Hospital, Tokyo, Japan; Al Corniche, Abu Dhabi, United Arab Emirates; Albany Medical Center, Albany, NY; All Saints Episcopal Hospital, Ft Worth, TX; Alta Bates 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 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-NYU Medical Center, New York, NY; Beth Israel Deaconess Medical Center, Boston, MA; Bethesda Memorial Hospital, Boynton Beach, FL; Blank Children’s Hospital, Des Moines, IA; Brandon Regional Hospital, Brandon, FL; Brookdale Hospital Medical Center, Brooklyn, NY; The Brooklyn Hospital Center, Brooklyn, NY; Broward General Medical Center, Ft Lauderdale, FL; Bryn Mawr Hospital, Bryn Mawr, PA; C.R.C.H, Roanoke, VA; CA Pacific Medical Center, San Francisco, CA; Cape Fear Valley Medical Center, Fayetteville, NC; Cardinal Glennon Children’s Hospital, St Louis, MO; CARElina Neonatology-Wake Medical, Raleigh, NC; Carle Foundation Hospital, Urbana, IL; 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 at Cooper U. Medical Center, Camden, NJ; 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 Wisconsin, Milwaukee, WI; Children’s Hospital-Lee Memorial, Ft Myers, FL; Children’s Hospitals & Clinics, Minneapolis, MN; Children’s Hospitals and Clinics, St Paul, MN; CHKD/Sentara Norfolk, Norfolk, VA; CHOA/Brackenridge Campus, Austin, TX; CHOI at OSF St Francis Medical Center, Peoria, IL; Christ Hospital & Medical Center, Oak Lawn, IL; Christchurch Women’s Hospital, Christchurch, New Zealand; Christiana Care Health Services, Newark, DE; Christus Santa Rosa Healthcare, San Antonio, TX; Citrus Valley-Queen of the Valley Campus, W Covina, CA; City Avenue/Allegheny University Hospital, Philadelphia, PA; Columbia East Ridge Hospital, Chattanooga, TN; Columbia Hospital for Women, Washington, DC; Columbia Medical Center of Plano TX, Dallas, TX; Columbia Women’s Hospital, Indianapolis, IN; Columbus Regional Medical Center, Columbus, GA; Community Medical Center, Missoula, MT; Connecticut Children’s Medical Center, Hartford, CT; Cook Children’s Medical Center, Ft Worth, TX; Coral Springs Medical Center, Coral Springs, FL; Crozer-Chester Medical Center, Upland, PA; Dameron Hospital, Stockton, CA; Danbury Hospital, Danbury, CT; Danube Hospital-SMZ-Ost, Vienna, Austria; Dartmouth-Hitchcock Medical Center, Lebanon, NH; Deaconess Medical Center, Spokane, WA; DeVos Children’s/Spectrum Health, Grand Rapids, MI; Doctor’s Medical Center, Modesto, CA; Eastern Maine Medical Center, Bangor, ME; Encino Tarzana Regional Medical Center, Tarzana, CA; Evanston Hospital, Evanston, IL; Exempla St Joseph Hospital, Denver, CO; Fairview University Medical Center, Minneapolis, MN; Fernando Fonseca Hospital, Lisbon, Portugal; Fitzgerald Mercy Medical Center, Darby, PA; Florida Hospital, Orlando, FL; Flushing Hospital & Medical Center, Flushing, NY; 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 & Health System, Joplin, MO; Gazi University Hospital, Ankara, Turkey; Geisinger Medical Center, Danville, PA; Glendale Memorial Hospital & Health Center, Glendale, CA; Good Samaritan HCA, San Jose, CA; Good Samaritan Hospital, Los Angeles, CA; Good Samaritan Hospital, West Palm Beach, FL; Good Samaritan Hospital, Cincinnati, OH; Grant Medical Center, Columbus, OH; Greater Baltimore Medical Center, Baltimore, MD; Gundersen Lutheran, LaCrosse, WI; Hackensack University Medical Center, Hackensack, NJ; Hahnemann University Hospital, Philadelphia, PA; Harbor UCLA Medical Center, Torrance, CA; Harris Methodist, Ft Worth, TX; Hennepin County Medical Center, Minneapolis, MN; Henrico Doctor’s Hospital, Richmond, VA; Henry Ford Hospital, Detroit, MI; Holy Cross Hospital, Silver Spring, MD; Hospital Auxilio Mutuo, San Juan, Puerto Rico; Hospital de S. Joao, Gaia, Portugal; Hospital for Children, Helsinki, Finland; Hospital of University of Pennsylvania, Philadelphia, PA; Houston NW Medical Center, Houston, TX; Howard County General Hospital, Columbia, MD; Huntington Memorial Hospital, Pasadena, CA; Huntsville Hospital, Huntsville, AL; Hurley Medical Center, Flint, MI; ICP-Milan, Milan, Italy; Illinois Masonic Medical Center, Chicago, IL; Inova Alexandria Hospital, Alexandria, VA; Inova Fairfax Hospital for Children, Falls Church, VA; IWK Health Centre, Halifax, Nova Scotia, Canada; Jackson-Madison County General Hospital, Jackson, TN; Joe DiMaggio Children’s Hospital, Hollywood, FL; John Peter Smith Hospital, Ft Worth, TX; K.K. Women’s & Children’s Hospital, Singapore; Kaiser Foundation, Bellflower, CA; Kaiser Foundation, Fontana, CA; Kaiser Foundation, Los Angeles, CA; Kaiser Foundation-Orange County, Anaheim, CA; Kaiser Foundation-Panorama City, CA; Kaiser Foundation-Riverside Medical Center, Riverside, CA; Kaiser Foundation, San Diego, CA; Kaiser Foundation-West Los Angeles, Los Angeles, CA; Kaiser Foundation, Woodland Hills, CA; Kaiser Permanente, Baldwin Park, CA; Kaiser Permanente-Harbor City, Harbor City, CA; Kinderklinik Glanzing im Wilhelminenspital, Vienna, Austria; Kinderklinik Graz, Graz, Austria; Kosair Children’s Hospital, Louisville, KY; LDS Hospital, Salt Lake City, UT; Legacy Emanuel Children’s Hospital, Portland, OR; Lehigh Valley Hospital, Allentown, PA; Lenox Hill Hospital, New York, NY; Little Company of Mary Hospital, Torrance, CA; Loma Linda University Children’s, Loma Linda, CA; Loyola University Medical Center, Maywood, IL; LPCH-Stanford University, Palo Alto, CA; Maimonides Medical Center, Brooklyn, NY; Maternidade Dr Alfredo Da Costa, Lisbon, Portugal; McKay-Dee Hospital Center, Ogden, UT; McLeod Regional Medical Center, Florence, SC; Mease Hospital, Dunedin, FL; Medical City, Dallas, TX; Medical College of Georgia, Augusta, GA; Medical College of PA, Philadelphia, PA; Medical University of South Carolina, Charleston, SC; Memorial Hermann Southwest, Houston, TX; Memorial Hospital, South Bend, IN; Memorial Hospital, Gulfport, MS; Memorial Hospital West, Pembroke Pines, FL; Memorial Medical Center, New Orleans, LA; Mercer Medical Center, Trenton, NJ; Mercy Children’s Hospital, Toledo, OH; Mercy Health Center, Oklahoma City, OK; Mercy Hospital & Medical Center, Chicago, IL; Mercy Hospital of Pittsburgh, Pittsburgh, PA; Mercy Hospital South, Charlotte, NC; 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; MHUMC, Savannah, GA; Miami Valley Hospital, Dayton, OH; Midwest Neoped Associates, Oak Brook, IL; Miller Children’s Hospital, Long Beach, CA; Milton S. Hershey Medical Center, Hershey, PA; Mission St Joseph’s Hospital, Asheville, NC; Monash Medical Centre, Victoria, Australia; Monmouth Medical Center, Long Branch, NJ; Morristown Memorial Hospital, Morristown, NJ; Mt Sinai Hospital, Toronto, Ontario, Canada; Mt Sinai Hospital Medical Center, Chicago, IL; Munson Medical Center, Traverse City, MI; National Naval Medical Center, Bethesda, MD; Naval Medical Center, San Diego, CA; Neonatologiezentrum-LKH, Salzburg, Austria; Neonatology Associates, Kingsport, TN; New Hanover Regional Medical Center, Wilmington, NC; New York Presbyterian Hospital, New York, NY; Newark Beth Israel Medical Center, Newark, NJ; Newborn Specialists of Tulsa, Tulsa, OK; North Memorial Medical Center, Robbinsdale, MN; North Oaks Medical Center, Hammond, LA; North Shore U. Hospital Manhasset, Manhasset, NY; Northbay Medical Center, Fairfield, CA; Northridge Hospital, Northridge, CA; Northside Hospital, Atlanta, GA; Northwestern Memorial, Chicago, IL; Norton Suburban Hospital, Louisville, KY; Novor. Dd. NsP., Nove Zamky, Slovakia; Oakwood Hospital & Medical Center, Dearborn, MI; OH-CHEO, Ottawa, Ontario, Canada; Oregon Health & Sciences University, Portland, OR; Osaka City General Hospital, Osaka, Japan; P.C.M.H., Greenville, NC; Parkview Hospital, Ft Wayne, IN; Pennsylvania Hospital, Philadelphia, PA; Phoenix Children’s Hospital, Phoenix, AZ; Pinnacle/Harrisburg Campus, Harrisburg, PA; Presbyterian Hospital, Albuquerque, NM; Presbyterian Hospital of Dallas, Dallas, TX; Presbyterian-St Luke’s Medical Center, Denver, CO; Promina Gwinnett Health, Lawrenceville, GA; Provena Covenant Medical Center, Urbana, IL; Providence St Joseph Medical Center, Burbank, CA; Providence St Vincent Medical Center, Portland, OR; Queen Mary Hospital, Hong Kong, China; Royal Hobart Hospital, Hobart, Tasmania, Australia; Rainbow Babies & Children’s Hospital, Cleveland, OH; Reading Hospital & Medical Center, Reading, PA; Regional Medical Center at Memphis, Memphis, TN; Riverside Methodist Hospital, Columbus, OH; Rockford Memorial Hospital, Rockford, IL; Rogue Valley Medical Center, Medford, OR; Rose Medical Center, Denver, CO; Rotunda Hospital, Dublin, Ireland; Royal Victoria Hospital, Montreal, Quebec, Canada; Sacred Heart Health System, Pensacola, FL; Sacred Heart Medical Center, Eugene, OR; Sacred Heart Medical Center, Spokane, WA; San Francisco General Hospital, San Francisco, CA; Scott & White Hospital, Temple, TX; Seton Medical Center, Austin, TX; Sharp Mary Birch Hospital for Women, San Diego, CA; Sheridan Children’s, Plantation, FL; Sinai Hospital of Baltimore, Baltimore, MD; Sioux Valley Children’s Hospital, Sioux Falls, SD; Sisters of Charity, Staten Island, NY; South Fulton Medical Center, East Point, GA; Southern Regional Medical Center, Riverdale, GA; Sparrow Hospital, Lansing, MI; St Agnes Hospital, Baltimore, MD; St Barnabas Medical Center, Livingston, NJ; 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 Elizabeth’s Medical Center, Boston, MA; St Francis Hospital, Hartford, CT; St Francis Hospital, Tulsa, OK; St Francis Medical Center, Lynwood, CA; St John Hospital & Medical Center, Detroit, MI; St John’s Hospital, Springfield, IL; St John’s Mercy Medical Center, St Louis, MO; St John’s Regional Medical Center, Oxnard, CA; St Joseph Hospital & Medical Center, Paterson, NJ; St Joseph Hospital/TX, Houston, TX; St Joseph Hospital-Marshfield Clinic, Marshfield, WI; St Joseph Mercy Oakland, Pontiac, MI; St Joseph’s Health Center, Syracuse, NY; St Joseph’s Hospital, Milwaukee, WI; St Joseph’s Hospital & Medical Center, Phoenix, AZ; St Luke’s Hospital, Kansas City, MO; St Luke’s Hospital, Bethlehem, PA; St Luke’s Hospital, Racine, WI; St Luke’s Regional Medical Center, Boise, ID; St Mary Medical Center, Long Beach, CA; St Mary’s Hospital, Milwaukee, WI; St Mary’s Hospital & Medical Center, Grand Junction, CO; St Mary’s Hospital Medical Center, Madison, WI; St Mary’s Hospital, West Palm Beach, FL; St Mary’s Medical Center, Duluth, MN; St Paul Medical Center, Dallas, TX; St Peter’s Hospital, Albany, NY; St Peter’s Medical Center, New Brunswick, NJ; St Vincent Hospital, Indianapolis, IN; St Vincent Hospital, Green Bay, WI; St Vincent Hospital & Health Center, Billings, MT; Stamford Hospital, Stamford, CT; Sunnybrook & Women’s College Health Science, Toronto, Ontario, 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; Tacoma General Hospital, Tacoma, WA; 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; Tokyo Women’s Medical College, Tokyo, Japan; 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; U. Mass Memorial Health Care, Worcester, MA; U. of TN Medical Center, Knoxville, TN; UC Irvine Medical Center, Orange, CA; UCDMC, Sacramento, CA; UCHSC, Denver, CO; UCSD Medical Center, San Diego, CA; UCSF Medical Center, San Francisco, CA; University Hospital, Zurich, Switzerland; University Hospital Motol, Prague, Czech Republic; University Hospital Vienna-AKH, Vienna, Austria; 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 Kentucky Children’s Hospital, Lexington, KY; University of Louisville Hospital, Louisville, KY; University of Michigan-Holden NICU, Ann Arbor, MI; University of Washington Medical Center, Seattle, WA; UPMC Lee Regional, Johnstown, PA; Utah Valley Regional Medical Center, Provo, UT; Vassar Brothers Hospital, Poughkeepsie, NY; Ventura County Medical Center, Ventura, CA; Via Christi-St Francis Campus, Wichita, KS; Virginia Beach General Hospital, Virginia Beach, VA; VT Children’s at Fletcher-Allen Health Care, Burlington, VT; Waikato Hospital, Hamilton, New Zealand; Waukesha Memorial Hospital, Waukesha, WI; Weiler Hospital-Montefiore, Bronx, NY; Wellstar Cobb Hospital, Kennesaw, GA; Wellstar Kennestone Hospital, Marietta, GA; Wesley Medical Center, Wichita, KS; Western Medical Center, Santa Ana, CA; Western Pennsylvania Hospital, Pittsburgh, PA; Willis-Knighton South, Shreveport, LA; Woman’s Hospital, Baton Rouge, LA; Women’s & Children’s Hospital, Lafayette, LA; Women’s Hospital of Greensboro, Greensboro, NC; 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.


   ACKNOWLEDGMENTS
 
Sponsored by the Vermont Oxford Network (Burlington, VT).


   FOOTNOTES
 
Received for publication Oct 31, 2003; Accepted Feb 3, 2004.

Address correspondence to Jerold F. Lucey, MD, University of Vermont College of Medicine, D201 Given, 89 Beaumont Ave, Burlington, VT 05405-0068. E-mail: jerold.lucey{at}uvm.edu


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 APPENDIX: PARTICIPATING...
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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics



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