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Preterm delivery occurs in 7 to 10 percent of all pregnancies and is a major cause of infant mortality and morbidity. In addition, preterm births are associated with more than $2 billion in health care costs annually. Preterm infants account for the majority of all neonatal deaths. Immature infants may have numerous complications including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), sepsis, patent ductus arteriosus (PDA), and retinopathy of prematurity. RDS is often the most acute problem of the very immature infant and, along with IVH, accounts for a significant proportion of neonatal deaths. Although most premature infants survive without major sequelae, some require rehospitalization and special services.
Corticosteroid treatment of pregnant women delivering prematurely was first introduced in 1972 to enhance fetal lung maturity. A recent meta-analysis concluded that corticosteroid administration prior to anticipated preterm delivery is associated with a large reduction in the incidence of early neonatal death, RDS, IVH, and NEC.
Despite evidence of beneficial effects from both experimental models and randomized controlled trials in humans, a minority of women delivering prematurely receive antenatal corticosteroid treatment. In reports from approximately 500 perinatal centers, only 12 to 18 percent of women who deliver preterm infants of 501 to 1,500 grams birthweight are treated with antenatal corticosteroids. Clinicians are not treating many patients who might benefit because of concerns about the efficacy of corticosteroids and the potential complications of treatment in certain conditions. Use of this therapy is further impeded by lack of access to prenatal care and to appropriate delivery services.
To address these issues, the National Institute of Child Health and Human Development, together with the Office of Medical Applications of Research of the National Institutes of Health, convened a Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. The conference was cosponsored by the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research. After a year of study and preparation concluding with a day and a half of presentations by experts in the relevant fields and discussion from the audience, an independent consensus panel composed of representatives from the medical and related scientific disciplines, as well as representatives from the public, considered the evidence and formulated a consensus statement in response to the following key questions:
For what conditions and purposes are antenatal corticosteroids used, and what is the scientific basis for that use?
What are the short-term and long-term benefits of antenatal corticosteroid treatment?
What are the short-term and long-term adverse effects for the infant and mother?
What is the influence of the type of corticosteroid, dosage, timing and circumstances of administration, and associated therapy on treatment outcome?
What are the economic consequences of this treatment?
What are the recommendations for use of antenatal corticosteroids?
What research is needed to guide clinical care?
Animal studies conducted in the 1950's and 1960's showed that the pituitary adrenal system affected differentiation of the intestine and lung. Later studies found physiologic surges in corticosteroids just before term or preterm delivery, and a relationship between fetal cortisol levels at delivery and lung maturity. Since then, randomized controlled trials in women have confirmed the maturational effects of corticosteroids on fetal organ systems such as the cardiovascular, respiratory, nervous, and gastrointestinal systems. As a result, antenatal corticosteroids are now administered for the purpose of hastening maturation of the preterm infant's organs and tissues, thus reducing morbidity and mortality related to prematurity.
The clinical conditions under which antenatal corticosteroid administration has been investigated are those associated with threatened or inevitable preterm delivery. These include (1) preterm labor, which accounts for 30 to 50 percent of all preterm deliveries; (2) preterm premature rupture of membranes, which accounts for 20 to 50 percent of all preterm deliveries; (3) preeclampsia, which is associated with 10 to 25 percent of preterm deliveries; and (4) other conditions, such as diabetes mellitus, third trimester bleeding, fetal distress, or isoimmunization necessitating preterm delivery, which account for up to 10 percent of preterm deliveries. The use of antenatal corticosteroid therapy has been studied in relatively few pregnancies less than 24 weeks' or greater than 34 weeks' gestation.
Additional issues that have been investigated include duration of the "treatment window," the gender and race of the fetus, the relationship of gestational age to the risks and benefits of treatment, and the use of antenatal corticosteroids along with other treatments, such as postnatal pulmonary surfactant and tocolytic administration.
I: Evidence obtained from at least one properly designed randomized controlled trial.
II-1: Evidence obtained from well-designed controlled trials without randomization.
II-2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.
II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940's) could also be regarded as this type of evidence.
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
A: There is good evidence to support use.
B: There is fair evidence to support use.
C: There is inadequate evidence to argue for or against use.
D: There is fair evidence to avoid use.
E: There is good evidence to avoid use.
| Quality of Evidence for Benefit | Strength of Recommendation | ||
|---|---|---|---|
| Interval from Treatment to Delivery | |||
| Gestational Age | |||
| Preterm Premature Rupture of Membranes | I | B | |
| Neonatal Outcomes | |||
| <24 hours | I | B | |
| 24 hours to 7 days | I | A | |
| >7 days | I | C | |
| Delivery at 24-28 weeks | I | A | |
| Delivery at 29-34 weeks | I | A | |
| Delivery at >34 weeks | I | C | |
| Mortality | I | A | |
| Respiratory distress syndrome | I | A | |
| Intraventricular hemorrhage | I | A | |
Antenatal corticosteroid therapy in the preterm fetus in many randomized controlled trials has reduced neonatal mortality and the incidence of the respiratory distress syndrome (RDS). A meta-analysis based on 15 such trials showed a reduction in the incidence of RDS with a typical odds ratio of 0.5 (95% CI 0.4-0.6)1 and a reduction of neonatal mortality with a typical odds ratio of 0.6 (95% CI 0.5-0.8). These data are not only statistically significant, but also clinically compelling. In subgroup analysis these benefits were confirmed regardless of the infant's gender or race.
One recent randomized controlled trial showed a significant reduction in IVH with antenatal corticosteroid treatment. Secondary outcome variables reported in the meta-analysis of randomized controlled trials also showed a significant reduction in the incidence of IVH with an odds ratio of 0.5 (95% CI 0.3-0.9). This reduction in IVH is supported by the results of the observational database, information prospectively collected in five registries involving more than 30,000 low-birthweight infants. Since IVH is an important contributor to mortality and serious long-term neurodevelopmental disability, this reduction is a major benefit.
Improved circulatory stability and reduced requirements for oxygen and ventilatory support were additional benefits identified in randomized controlled trials. Data are conflicting for NEC and PDA. The meta-analysis of the randomized controlled trials revealed a reduction of the incidence of NEC, however, this finding was not corroborated by the observational database. Conversely, the incidence of PDA was not found to be reduced in the meta-analysis, but was significantly reduced in the observational database.
Several studies have followed infants from the randomized trials for as long
as 12 years. The increased survival of treated infants has not resulted in the
appearance of adverse long-term effects.
Short-term adverse effects of antenatal corticosteroid administration of greatest concern in the neonate include infection and adrenal suppression. The evidence presented to date shows no increase in infection in treated infants, no clinically important adrenal suppression, and rapid return of adrenal function when antenatal corticosteroids are discontinued.
Some animal studies have suggested that antenatal corticosteroid treatment might promote maladaptive responses to hypoxia. Other animal studies have shown that corticosteroids in doses similar to those used in humans antenatally provide protection against hypoxic-ischemic brain injury. More data are needed from human studies in this area of research.
Studies initiated in the 1970's, which followed the development of children treated antenatally with corticosteroids up to the age of 12 years, showed no adverse outcomes in the areas of motor skills, language, cognition, memory, concentration or scholastic achievement. The possibility of adverse, long-term neurodevelopmental outcomes has been suggested by studies of corticosteroid administration in animals. These studies were conducted using doses approximately 10 times the doses used in human clinical trials. There does not seem to be an increased risk in children of long-term neurodevelopmental impairment as reflected in any greater prevalence of learning, behavioral, motor, or sensory disturbances. Long-term effects of antenatal corticosteroids on growth and the onset of puberty are not fully known.
Maternal pulmonary edema can occur when antenatal corticosteroids are used in combination with tocolytic agents. This complication is more commonly associated with maternal infection, fluid overload, and multiple gestation. Pulmonary edema has not been reported when antenatal corticosteroids are used alone.
The risk of maternal infection may be increased when corticosteroids are
used in preterm premature rupture of membranes (PPROM), however, the degree of
this effect, if any, is unclear. Furthermore, there is no evidence that
antenatal corticosteroid treatment interferes with the ability to diagnose
maternal infection. When corticosteroids are administered to pregnant diabetic
women, diabetic control may become more difficult and insulin may have to be
adjusted accordingly. Screening for gestational diabetes may similarly be
affected. In serious maternal medical conditions that necessitate premature
delivery, the delay necessary to demonstrate maximal corticosteroid effects for
the fetus may worsen the maternal medical status. A subgroup analysis in the
first randomized trial suggested that antenatal corticosteroid administration
might predispose to fetal death in hypertensive women. Subsequent trials failed
to demonstrate this effect. No long-term maternal adverse effects have been
reported.
Dexamethasone and betamethasone are the preferred corticosteroids for antenatal therapy. These two compounds are identical in biological activity and readily cross the placenta in their biologically active forms. They are devoid of mineralocorticoid activity, relatively weak in immunosuppressive activity, and exert longer duration of action than cortisol and methylprednisolone. They also are the most extensively studied antenatal corticosteroids for accelerating fetal maturation.
Treatment of two doses of 12 mg of betamethasone given intramuscularly 24 hours apart or four doses of 6 mg of dexamethasone given intramuscularly 12 hours apart has been shown to be effective. Although these regimens were arbitrarily selected, subsequently they have been shown to deliver concentrations to the fetus that are comparable to physiologic stress levels of cortisol occurring after birth in untreated premature infants who develop RDS.
These regimens result in an estimated 75 percent occupancy of available corticosteroid receptors, which should provide a near maximal induction of antenatal corticosteroid receptor-mediated response in fetal target tissues. Higher or more frequent doses do not increase the benefits of antenatal corticosteroid therapy and may increase the likelihood of adverse effects.
Strong evidence exists for neonatal benefits from a complete course of antenatal corticosteroids starting at 24 hours and lasting up to 7 days after treatment. Evidence suggests a reduction in mortality, RDS, and IVH even with treatment initiated less than 24 hours prior to delivery. Both clinical and in vitro evidence suggest that the corticosteroid biological effects persist up to 7 days following initial treatment.
Data are inadequate to establish the clinical benefit beyond 7 days after antenatal corticosteroid therapy. The potential benefits or risks of repeated administration after 7 days are unknown. In vitro experiments in human fetal lung explants show that inducible biochemical effects have dissipated by 7 days although structural changes persist.
For infants born at 29 to 34 weeks' gestation, treatment with antenatal corticosteroids clearly reduces the incidence of RDS and overall mortality. While antenatal corticosteroids do not clearly decrease the incidence of RDS in infants born at 24 to 28 weeks' gestation, they reduce its severity. More important, antenatal corticosteroids clearly reduce mortality and the incidence of IVH in this age group. All fetuses between 24 and 34 weeks' gestation threatened with premature delivery are candidates for treatment with antenatal corticosteroids.
In infants born beyond 34 weeks' gestation the risk of neonatal mortality, RDS, and IVH is low. The evidence for significant improvement in outcomes in these infants with antenatal corticosteroid use is limited. Use of corticosteroids in mothers expected to deliver at > 34 weeks is therefore not recommended unless there is evidence of pulmonary immaturity.
There is no convincing evidence from any of the clinical trials that either gender or race of the fetus affects the response to therapy with antenatal corticosteroids.
The use of antenatal corticosteroids to reduce infant morbidity in the presence of PPROM remains controversial. Antenatal corticosteroids reduced the risk of RDS in PPROM in randomized controlled trials, although the magnitude of the reduction was not as great as when the membranes were intact. Strong evidence from observational studies suggests that, even in the presence of PPROM, the incidence of neonatal mortality and IVH is reduced when antenatal corticosteroids are used. Although the risk of neonatal infection associated with antenatal corticosteroid use in the face of PPROM may be increased, the magnitude of the increase is small. Because of the effectiveness of antenatal corticosteroids in reducing mortality and IVH in fetuses of less than 30 to 32 weeks' gestation, antenatal corticosteroid use is appropriate in the absence of chorioamnionitis.
Data are insufficient to assess the effectiveness of antenatal corticosteroid use in certain maternal high-risk conditions such as hypertension and diabetes. In the absence of evidence of adverse effects, it may be reasonable to treat these women as one would others with threatened premature delivery. Similarly, in the presence of high-risk fetal conditions, such as multiple gestation, intrauterine growth retardation, and hydrops, it is reasonable to treat these patients as one would others with threatened premature delivery.
Antenatal administration of corticosteroids acts additively with postnatal administration of surfactant to reduce mortality, RDS, and IVH. Furthermore, surfactant replacement appears to have little or no impact on the incidence of IVH or PDA. For these reasons the decision to use antenatal corticosteroids should not be altered by availability of surfactant replacement therapy.
Thyroid hormones accelerate fetal lung maturation in animal studies. However, T3; and T4; do not cross the placenta. This problem has been circumvented by maternal administration of thyrotropin-releasing hormone (TRH). The combination of TRH plus antenatal corticosteroids was more effective than corticosteroids alone in two randomized studies. Women who received both drugs had infants with fewer adverse outcomes, fewer days on the ventilator, and a lower incidence of BPD. The use of TRH to accelerate fetal pulmonary maturation currently is experimental and randomized studies are in progress.
Beta-mimetic agents such as ritodrine and terbutaline are frequently
administered in an attempt to arrest preterm labor. Women receiving tocolytic
therapy are candidates for antenatal corticosteroids to accelerate fetal
maturation in the face of threatened premature delivery. Several studies have
examined the outcomes of infants born prematurely to mothers who received both
ritodrine and dexamethasone or betamethasone. Although there are flaws in the
design of each of these studies, they all showed a significant decrease in
incidence of RDS. In addition, one study demonstrated a decrease in ventilator
dependency and incidence of PDA. There is evidence that beta-mimetic agents may
be associated with increased risk of IVH. However, the use of antenatal
corticosteroids may reduce this risk.
Neonatal intensive care is expensive, but is more cost-effective in terms of years of life gained than many other accepted medical interventions. Because the costs of caring for infants with RDS are so high, interventions that may reduce its incidence, such as antenatal corticosteroids or prophylactic surfactant, have the potential of producing large cost savings, in addition to improving health.
The net economic consequences include the costs of initial treatment,
changes in treatment made to allow the corticosteroids to work, the costs of any
harmful side effects of treatment, the savings resulting from reduced length of
stay and intensity of treatment, and the long-term costs of the burden of
chronic diseases in surviving infants. Because the direct costs of
corticosteroid treatment are so low and differential extra long-term burden has
not been well quantified, net cost estimates were derived from the balance of
costs of the health outcomes of initial treatment. Costs of infant care are
relatively low for both uncomplicated preterm infants and early neonatal deaths.
For any proposed clinical situation, costs are decreased to the extent that
corticosteroids reduce illness in survivors, and increased for infants that
would have died quickly without them. Data on costs from randomized trials are
scant, but length of stay was reduced by about one-third in
corticosteroid-treated infants in the four trials for which these data were
collected. To estimate costs or savings from increased use, data on efficacy
from all corticosteroid trials can be applied to data on current costs of caring
for infants with and without disease. The resulting calculated base case cost
savings were more than $3,000 per treated neonate. Of the 4,100,000 babies born
in the United States each year, 106,000 weigh less than 2,000 grams at birth.
Currently 15 percent of these babies are treated with corticosteroids. If this
were increased to 60 percent, as observed in some hospitals, a conservative
estimate of the annual savings in health care costs would be $157 million from
the initial hospitalization alone.
The benefits of antenatal administration of corticosteroids to fetuses at risk of preterm delivery vastly outweigh the potential risks. These benefits include not only a reduction in the risk of RDS but also a substantial reduction in mortality and IVH.
All fetuses between 24 and 34 weeks' gestation at risk of preterm delivery should be considered candidates for antenatal treatment with corticosteroids.
The decision to use antenatal corticosteroids should not be altered by fetal race or gender or by the availability of surfactant replacement therapy.
Patients eligible for therapy with tocolytics should also be eligible for treatment with antenatal corticosteroids.
Treatment consists of two doses of 12 mg of betamethasone given intramuscularly 24 hours apart or four doses of 6 mg of dexamethasone given intramuscularly 12 hours apart. Optimal benefit begins 24 hours after initiation of therapy and lasts 7 days.
Because treatment with corticosteroids for less than 24 hours is still associated with significant reductions in neonatal mortality, RDS, and IVH, antenatal corticosteroids should be given unless immediate delivery is anticipated.
In preterm premature rupture of membranes at less than 30 to 32 weeks' gestation in the absence of clinical chorioamnionitis, antenatal corticosteroid use is recommended because of the high risk of IVH at these early gestational ages.
In complicated pregnancies where delivery prior to 34 weeks' gestation is likely, antenatal corticosteroid use is recommended unless there is evidence that corticosteroids will have an adverse effect on the mother or delivery is imminent.
Areas of animal and human research that need to be addressed include the following:
The short- and long-term benefits and risks of repeating administration of antenatal corticosteroids 7 days after the initial course.
Long-term effect of antenatal corticosteroids on cognitive, behavioral, psychological, and physical development of the neonate.
Effects of antenatal corticosteroids on organ maturation.
Effects of antenatal corticosteroids on hypoxic-ischemic insults.
Effects of antenatal corticosteroids on neonatal hemodynamic stability.
Mechanism of antenatal corticosteroid induction of cell and organ maturation at the molecular level.
The interaction of antenatal corticosteroids with other therapies administered during the perinatal period (e.g., the effect of corticosteroids and tocolytics on the incidence of IVH).
Development of alternative therapies to antenatal corticosteroids for fetal maturation.
Systematic study of the diffusion of these scientifically based recommendations into clinical practice.
Antenatal corticosteroid therapy for fetal maturation reduces mortality, respiratory distress syndrome, and intraventricular hemorrhage in preterm infants. These benefits extend to a broad range of gestational ages (24 to 34 weeks) and are not limited by gender or race. Although the beneficial effects of corticosteroids are greatest more than 24 hours after beginning treatment, treatment less than 24 hours in duration also improves outcomes. The benefits of antenatal corticosteroids are additive to those derived from surfactant therapy.
In the presence of preterm premature rupture of the membranes, antenatal corticosteroid therapy reduces the frequency of respiratory distress syndrome, intraventricular hemorrhage, and neonatal death, although to a lesser extent than with intact membranes. Whether this therapy increases either neonatal or maternal infection is unclear. However, the risk of death from prematurity is greater than the risk from infection.
Data from trials with followup of children up to 12 years indicate that antenatal corticosteroid therapy does not adversely affect physical growth or psychomotor development.
Antenatal corticosteroid therapy is indicated for women at risk of premature
delivery with few exceptions and will result in a substantial decrease in
neonatal morbidity and mortality, as well as substantial savings in health care
costs. The use of antenatal corticosteroids for fetal maturation is a rare
example of a technology that yields substantial cost savings in addition to
improving health.
Larry C. Gilstrap, M.D.
Panel and Conference Chairperson
Professor
Department of Obstetrics and Gynecology
University of Texas Southwestern Medical Center
Dallas, Texas
Robert Christensen, M.D.
Professor and Chief
Neonatology/Pediatrics
University of Florida College of Medicine
Gainesville, Florida
William H. Clewell, M.D.
Associate Director
Department of Maternal-Fetal Medicine
Phoenix Perinatal Associates
Phoenix, Arizona
Mary E. D'Alton, M.D.
Chief
Obstetrics and Maternal Fetal Medicine
Department of Obstetrics and Gynecology
New England Medical Center—Tufts University
Boston, Massachusetts
Ezra C. Davidson, Jr., M.D.
Professor and Chairman
Obstetrics and Gynecology
Martin Luther King, Jr./Charles R. Drew University
Los Angeles, California
Marilyn B. Escobedo, M.D.
Professor of Pediatrics
Director
Division of Neonatology
University of Texas Health Sciences Center
San Antonio, Texas
Dwenda K. Gjerdingen, M.D.
Associate Professor
Department of Family Practice and Community Health
University of Minnesota
Saint Paul, Minnesota
Jan Goddard-Finegold, M.D.
Associate Professor
Department of Pediatrics and Pathology
Division of Pediatric Neurology
Baylor College of Medicine
Houston, Texas
Robert L. Goldenberg, M.D.
Director
Center for Obstetric Research
Professor
Department of Obstetrics and Gynecology
University of Alabama at Birmingham-School of Medicine
Birmingham, Alabama
David A. Grimes, M.D.
Professor
Department of Obstetrics and Gynecology
University of California at San Francisco
San Francisco General Hospital
San Francisco, California
Thomas N. Hansen, M.D.
Professor
Department of Pediatrics
Baylor College of Medicine
Houston, Texas
Ralph E. Kauffman, M.D.
Professor
Department of Pediatrics and Pharmacology
Wayne State University
Children's Hospital of Michigan
Detroit, Michigan
Emmett B. Keeler, Ph.D.
Senior Mathematician
Department of Social Policy
RAND
Santa Monica, California
William Oh, M.D.
Professor and Chair
Department of Pediatrics
Brown University School of Medicine
Women and Infants Hospital
Providence, Rhode Island
Elizabeth J. Susman, Ph.D., R.N.
Professor
Biobehavioral Health Program
The Pennsylvania State University
University Park, Pennsylvania
Marlyn G. Vogel, Ed.D.
Psychologist
School District of Hatboro Horsham
Elkins Park, Pennsylvania
Mary Ellen Avery, M.D.
Thomas Morgan Rotch Professor of Pediatrics
Department of Pediatrics
Harvard Medical School
Boston, Massachusetts
"Historic Overview of Antenatal Steroid Use"
Philip L. Ballard, M.D., Ph.D.
Professor of Pediatrics
Director of Neonatal Research
Division of Neonatology
Department of Pediatrics
University of Pennsylvania School of Medicine
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
"Hormone Levels Achieved With Steroid Treatment and Their Relationship to Normal Development"
Roberta A. Ballard, M.D.
Professor of Pediatrics, Obstetrics, and Gynecology
Chief
Division of Neonatology
Department of Pediatrics
University of Pennsylvania School of Medicine
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
"Scientific Basis for Antenatal Steroid Use"
Patricia Crowley, M.R.C.O.G., F.R.C.P.I.
Senior Lecturer
Department of Obstetrics and Gynaecology
Trinity College
Dublin, Ireland
"Update of the Antenatal Steroid Meta-analysis: Current Knowledge and Future Research Needs"
Marilyn B. Escobedo, M.D.
Professor of Pediatrics
Director, Division of Neonatology
University of Texas Health Sciences Center
San Antonio, Texas
"Evidence for Adverse and Beneficial Effects of Antenatal Steroid Use for Fetal Maturation on Perinatal Outcome: Introduction and Definition of the Problem"
Thomas Garite, M.D.
Professor and Chairman
Department of Obstetrics and Gynecology
University of California
Orange, California
"The Use of Corticosteroids for Acceleration of Fetal Pulmonary Maturity in Special Clinical Situations"
Robert L. Goldenberg, M.D.
Director of the Center for Obstetric Research
Professor, Department of Obstetrics and Gynecology
University of Alabama at Birmingham-School of Medicine
Birmingham, Alabama
"Use of Antenatal Steroids in Special Circumstances and Populations: Introduction and Definition of the Problem"
Gary D.V. Hankins, M.D.
Chairman
Department of Obstetrics and Gynecology
Wilford Hall USAF Medical Center (PSO)
San Antonio, Texas
"Adverse Maternal Effects of Combination Steroid and Beta-Mimetic Treatment"
Alan H. Jobe, M.D., Ph.D.
Professor of Pediatrics -- Neonatology
Director
Walter P. Martin Research Center
Harbor-UCLA Medical Center
UCLA School of Medicine
Torrance, California
"Beneficial Interactions of Antenatal Corticosteroids and Postnatal Surfactant"
Ralph E. Kauffman, M.D.
Professor
Department of Pediatrics and Pharmacology
Wayne State University, Children's Hospital of Michigan
Detroit, Michigan
"Pharmacology of Corticosteroids"
Janna G. Koppe, M.D., Ph.D.
Professor of Neonatology
University of Amsterdam
Amsterdam, The Netherlands
"Cognitive, Developmental, and Psychological Effects of Antenatal Steroid Therapy"
James E. Maher, M.D.
Assistant Professor of Obstetrics and Gynecology
Associate Director
Obstetrics and Gynecology Residency Program
University of Florida at Pensacola
Pensacola, Florida
"The Effect of Corticosteroid Therapy in the Very Premature Infant"
Irwin R. Merkatz, M.D.
Professor and Chairman
Department of Obstetrics and Gynecology
Albert Einstein College of Medicine/Montefiore Medical Center
Bronx, New York
"What Is the Evidence for the Effectiveness of Maternal Combination Therapy?"
Seetha Shankaran, M.D.
Director of Neonatal and Perinatal Medicine
Children's Hospital of Michigan
Detroit, Michigan
"Antenatal Steroids To Reduce the Risk of Severe Intracranial Hemorrhage in the Neonate"
Kit N. Simpson, Dr.P.H.
Assistant Professor
Department of Health Policy and Administration
University of North Carolina School of Public Health
Chapel Hill, North Carolina
"Cost Savings From the Use of Antenatal Steroids To Prevent Respiratory Distress Syndrome and Related Conditions in Premature Infants"
John C. Sinclair, M.D.
Professor
Department of Pediatrics and Clinical Epidemiology and
Biostatistics
McMaster University Medical Center
Hamilton, Ontario, Canada
"Discussion of Crowley's Meta-analysis of Randomized Controlled Trials of Antenatal Corticosteroids for Prevention of Respiratory Distress Syndrome"
Theodore A. Slotkin, Ph.D.
Professor
Department of Pharmacology
Duke University Medical Center
Durham, North Carolina
"Adverse Effects of Antenatal Steroids on Nervous System Development: Animal Models"
H. William Taeusch, Jr., M.D.
Chief
Pediatrics
San Francisco General Hospital
Professor and Vice-Chair
Department of Pediatrics
University of California at San Francisco
San Francisco, California
"Infectious Risks for the Newborn Infant After Maternal Antepartum Glucocorticoid Treatment"
Linda L. Wright, M.D.
Special Assistant to the Director
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland
"Evidence from Multicenter Networks on the Current Use and Effectiveness of Antenatal Corticosteroids in Very Low Birthweight Infants"
Duane Alexander, M.D.
Planning Committee Chairperson
Director
National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland
Roberta A. Ballard, M.D.
Professor
Pediatrics, Obstetrics, and Gynecology
Chief
Division of Neonatology
Department of Pediatrics
University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Mary Anne Berberich, Ph.D.
Health Sciences Administrator
Cell and Developmental Biology Branch
Division of Lung Diseases
National Heart, Lung, and Blood Institute
National Institutes of Health
Bethesda, Maryland
Michael Bracken, Ph.D.
Professor and Vice Chairman
Department of Epidemiology and Public Health
Yale University
New Haven, Connecticut
Leslie Cooper, Ph.D.
Nurse Epidemiologist
Division of Extramural Programs
National Institute of Nursing Research
National Institutes of Health
Bethesda, Maryland
Larry Culpepper, M.D., M.P.H.
Research Director
Department of Family Medicine
Brown University Memorial Hospital of Rhode Island
Pawtucket, Rhode Island
Jerry M. Elliott
Program Analyst
Office of Medical Applications of Research
National Institutes of Health
Bethesda, Maryland
John H. Ferguson, M.D.
Director
Office of Medical Applications of Research
National Institutes of Health
Bethesda, Maryland
Frederic Frigoletto, M.D.
Chief
Vincent Memorial Obstetrics Division
Massachusetts General Hospital
Boston, Massachusetts
Dorothy Berlin Gail, Ph.D.
Chief
Cell and Developmental Biology Branch
Division of Lung Diseases
National Heart, Lung, and Blood Institute
National Institutes of Health
Bethesda, Maryland
Larry C. Gilstrap, M.D.
Professor
Department of Obstetrics and Gynecology
University of Texas Southwestern Medical Center
Dallas, Texas
William H. Hall
Director of Communications
Office of Medical Applications of Research
National Institutes of Health
Bethesda, Maryland
Alan H. Jobe, M.D., Ph.D.
Professor of Pediatrics—Neonatology
Director
Walter P. Martin Research Center
Harbor-UCLA Medical Center
UCLA School of Medicine
Torrance, California
M. Douglas Jones, Jr., M.D.
Chairman
Department of Pediatrics
University of Colorado School of Medicine
Pediatrician-in-Chief
The Children's Hospital
Denver, Colorado
Barbara Medoff-Cooper, Ph.D.
Associate Professor
University of Pennsylvania School of Nursing
Philadelphia, Pennsylvania
Gerald B. Merenstein, M.D.
Professor
Department of Pediatrics
University of Colorado School of Medicine/The Children's Hospital
Denver, Colorado
Linda L. Wright, M.D.
Special Assistant to the Director
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland
National Institute of Child Health and Human Development
Duane F. Alexander, M.D.
Director
Office of Medical Applications of Research
John H. Ferguson, M.D. Director
National Heart, Lung, and Blood Institute
Claude Lenfant, M.D. Director
National Institute of Nursing Research
Ada Sue Hinshaw, Ph.D., R.N. Director
A meta-analysis uses quatitative methods to summarize results derived from a systematic review of randomized controlled trials. Results of meta-analyses are customarily reported in terms of odds ratios and 95 percent confidence intervals (CIs). Odds ratios of 1.0 indicate no effect; those below 1.0 imply protective effect; and those above 1.0 an increased risk. Ninety-five percent CIs that exclude 1.0 are considered significant at the p <0.05 level.
