PEDIATRICS Vol. 121 No. 2 February 2008, pp. 289-296 (doi:10.1542/10.1542/peds.2007-1103)
ARTICLE |
Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants Exposed Prenatally to Dexamethasone Versus Betamethasone
a Division of Neonatal-Perinatal Medicine, Emory University School of Medicine, Atlanta, Georgia
b MidAtlantic Neonatology Associates, Morristown, New Jersey
c Research Triangle Institute, Research Triangle Park, North Carolina
d National Institute of Child Health and Human Development, Washington, DC
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ABSTRACT |
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OBJECTIVE. We compared the development of adverse neurodevelopmental outcomes at corrected ages of 18 to 22 months for extremely low birth weight infants exposed prenatally to dexamethasone, betamethasone, or no steroid.
METHODS. Study infants were extremely low birth weight (401–1000 g) infants who were in the care of National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 2002, and April 30, 2003; they were assessed neurodevelopmentally at corrected ages of 18 to 22 months. Outcomes were defined as Bayley Scales of Infant Development-II Mental Development Index of <70, Bayley Scales of Infant Development-II Psychomotor Development Index of <70, bilateral blindness, bilateral hearing aid use, cerebral palsy, and neurodevelopmental impairment. Neurodevelopmental impairment was defined as 
1 of the aforementioned outcomes.
RESULTS. A total of 1124 infants met entry criteria. There were no statistically significant associations between prenatal dexamethasone exposure and any follow-up outcome, compared with no prenatal steroid exposure. Prenatal betamethasone exposure was associated with reduced risks of hearing impairment and neurodevelopmental impairment and with increased likelihood of unimpaired status, compared with no prenatal steroid exposure. Compared with betamethasone, dexamethasone was associated with a trend for increased risk of Psychomotor Development Index of <70, increased risk of hearing impairment, and decreased likelihood of unimpaired status.
CONCLUSIONS. Prenatal betamethasone exposure was associated with increased likelihood of unimpaired neurodevelopmental status and reduced risk of hearing impairment at corrected ages of 18 to 22 months among extremely low birth weight infants, compared with prenatal dexamethasone exposure or no prenatal steroid exposure. Pending a randomized, clinical trial, it may be in the best interests of infants to receive betamethasone, rather than dexamethasone, when possible.
Key Words: prenatal glucocorticoid treatment • dexamethasone • betamethasone • extremely low birth weight • neurodevelopmental outcome
Abbreviations: BSID-II—Bayley Scales of Infant Development-II • CP—cerebral palsy • ELBW—extremely low birth weight • MDI—Mental Development Index • NICHD—National Institute of Child Health and Human Development • NDI—neurodevelopmental impairment • PDI—Psychomotor Development Index • PVL—periventricular leukomalacia • PDA—patent ductus arteriosus • CLD—chronic lung disease • ROP—retinopathy of prematurity • OR—odds ratio • CI—confidence interval • EGA—estimated gestational age • IVH—intraventricular hemorrhage
First introduced by Liggins and Howie1 in 1972, prenatal steroid therapy has been associated with reduced risk of respiratory distress syndrome, intraventricular hemorrhage (IVH), and overall neonatal death.1–6 In 1994, the National Institutes of Health and the American College of Obstetricians and Gynecologists issued a consensus statement advocating the use of prenatal steroid treatment before the imminent delivery of pregnancies at gestational ages of 24 to 34 weeks, for the induction of fetal maturity.4 Dexamethasone and betamethasone are the only 2 fluorinated steroids used for such purposes, with individual use being dependent on commercial availability, institutional formulary listing, and provider preference.
Although no randomized, controlled trial has directly compared the outcomes associated with prenatal treatment with dexamethasone versus betamethasone, animal and human studies have raised concerns that prenatal dexamethasone treatment may be associated with increased risk of adverse neonatal neurologic outcomes.7–9 We reported previously that prenatal betamethasone treatment was associated with reduced risk of neonatal death, compared with prenatal dexamethasone treatment or no prenatal corticosteroid exposure, in a cohort of very low birth weight infants (401–1500 g) registered in the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.10 However, little is known regarding possible differences between the 2 steroids with respect to long-term neurodevelopmental outcomes. Using registry data from the NICHD Neonatal Research Network, the current study was designed to compare neurodevelopmental outcomes at corrected gestational ages of 18 to 22 months among extremely low birth weight (ELBW) infants exposed to prenatal dexamethasone or betamethasone treatment.
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METHODS |
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Study Design
The study population for this historical cohort study consisted of ELBW infants (weighing 401–1000 g at birth) born at NICHD Neonatal Research Network centers.11 The Neonatal Research Network has monitored the use of prenatal steroid therapy since 2002. The primary predictor variable was exposure to dexamethasone or betamethasone; neonates with no prenatal steroid exposure served as a reference group. The primary outcome variables were cerebral palsy (CP), Bayley Scales of Infant Development-II (BSID-II) Mental Development Index (MDI) of <70, BSID-II Psychomotor Development Index (PDI) of <70, blindness, hearing impairment, neurodevelopmental impairment (NDI), and unimpaired neurodevelopmental status at corrected gestational age of 18 to 22 months.
Subjects
Infants with birth weights between 401 g and 1000 g who were born at NICHD Neonatal Research Network centers between January 1, 2002, and April 30, 2003, and underwent neurodevelopmental assessments at corrected ages of 18 to 22 months in the Neonatal Research Network were included in this study. Subjects were excluded if they had a congenital anomaly, chromosomal anomaly, inborn error of metabolism, or exposure to both dexamethasone and betamethasone. Outborn infants were excluded, because prenatal corticosteroid exposure at referring hospitals could not be ascertained reliably by the registry. Estimated gestational age (EGA) was determined through best obstetric estimates from the last menstrual period, standard obstetric parameters, and prenatal ultrasonographic findings.
Exposure Definition
Prenatal steroid exposure was defined as maternal receipt of either dexamethasone or betamethasone during the admission for delivery. A complete course of dexamethasone was defined as four 6-mg intramuscular doses of a commercially obtained product (GensiaSicor Pharmaceuticals, Irvine, CA; American Regent Laboratories, Shirley, NY; American Pharmaceutical Partners, Schaumburg, IL; or Baxter, Deerfield, IL), administered with 12-hour intervals. A complete course of betamethasone was defined as two 12-mg intramuscular doses of a commercially obtained product (Schering-Plough, Kenilworth, NJ), administered with a 24-hour interval.
Outcome Definitions
CP was defined as a nonprogressive central nervous system disorder characterized by abnormal muscle tone in 1 extremity and abnormal control of movement or posture. Moderate or severe CP was defined as being nonambulatory or requiring an assistive device for walking. Hearing impairment was defined as the use of hearing aids in both ears. Blindness was defined as no useful vision in either eye (ie, bilateral visual acuity of 20/200 or less). NDI was defined as the presence of 1 of the following: CP, MDI of <70, PDI of <70, hearing impairment, or blindness. Unimpaired status was defined as the absence of CP, deafness, and blindness, MDI of 85, and PDI of 85.
Statistical Analyses
Continuous variables were summarized with arithmetic means and SDs and were compared by using unadjusted linear models for posthoc testing according to steroid group, with an 
of .05. Unconditional multivariate logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for outcomes among steroid exposure groups, adjusting for mode of delivery (vaginal versus cesarean), maternal educational level, gender, EGA, small-for-gestational age status, race, multiple gestation, severe IVH (grade III or IV), periventricular leukomalacia (PVL), early-onset or late-onset sepsis, treated patent ductus arteriosus (PDA), postnatal steroid exposure, chronic lung disease (CLD), and mother living with the infant at corrected age of 18 to 22 months. Covariates were defined as follows: severe IVH was defined as grade III or IV IVH, as classified by Papile et al;12 PVL or cystic cerebral parenchymal lesions were diagnosed at corrected age of 
36 weeks by pediatric radiologists using cranial sonography, during the NICU hospitalization; early-onset sepsis was defined as positive blood culture results within the first 72 hours of life; late-onset sepsis was defined as positive blood culture results after the first 72 hours of life; treated PDA was defined as a PDA that was closed through either surgical or medical intervention; CLD was defined as supplemental oxygen use at corrected age of 36 weeks or supplemental oxygen use at hospital discharge, whichever occurred first; and postnatally administered steroids were defined as steroids that were administered in the NICU for management of CLD. These covariates were selected on the basis of their importance to the modeled associations and the plausibility of their association with study outcomes; birth weight was not included in the models because of the high degree of collinearity between EGA and birth weight. The model for hearing impairment excluded maternal education and maternal cohabitation, given the lack of biological correlation between these covariates and the outcome. Severe retinopathy of prematurity (ROP) was defined as stage III disease, plus disease, threshold disease, or disease that required ophthalmologic intervention.
For all tests, statistical significance was established at P < .05. All statistical analyses were performed by using SAS 9 software (SAS Institute, Cary, NC).
Sample Size Calculation
The study cohort was drawn from an original population defined by the sample size calculated to detect a hypothesized difference in PVL rates associated with dexamethasone versus betamethasone therapy, compared with no prenatal corticosteroid exposure, among very low birth weight infants, as described previously.10
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RESULTS |
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Study Groups
Between January 1, 2002, and April 30, 2003, a total of 2455 ELBW infants (401–1000 g at birth) were registered in the NICHD Neonatal Research Network database, of whom 1262 were eligible for follow-up evaluations at corrected ages of 18 to 22 months. Of this surviving cohort, 107 were lost to follow-up monitoring; of the remaining 1155 ELBW infants who were evaluated at corrected ages of 18 to 22 months, 1124 had complete follow-up data. Of this final cohort, 408 had been exposed to dexamethasone, 563 had been exposed to betamethasone, and 153 had experienced no prenatal steroid exposure. Among ELBW infants who survived to corrected ages of 18 to 22 months, complete data were obtained for 89% of the total cohort, for 88% of infants exposed to dexamethasone, for 89% of infants exposed to betamethasone, and for 91% of infants not exposed prenatally to steroids.
Baseline Maternal and Neonatal Characteristics
Maternal characteristics of the study cohort are shown in Table 1. In crude comparative analyses, there were statistically significant differences among the 3 groups with respect to race, maternal education, and maternal cohabitation with the infant at corrected age of 18 to 22 months. Mothers who received dexamethasone or betamethasone treatment were more likely to be white, compared with those who did not receive prenatal corticosteroid treatment. Those who received betamethasone treatment were more likely to have completed high school and to be living with the infant at corrected age of 18 to 22 months than were those who did not receive prenatal steroid treatment. In addition, mothers who received betamethasone treatment were more likely to be white and to have completed high school than were those who received dexamethasone treatment.
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Neonatal characteristics of surviving ELBW infants are shown in Table 2. In unadjusted comparisons, the 3 study groups were comparable with respect to gender, birth weight, small-for-gestational age status, mode of delivery, receipt of surfactant, PDA necessitating treatment, postnatal steroid exposure, severe ROP, severe IVH, PVL, and CLD. There were, however, statistically significant differences in multiple-gestation status, EGA at birth, and neonatal sepsis incidence. Infants exposed to either dexamethasone or betamethasone were more likely to be the product of a multiple-gestation pregnancy, compared with infants with no prenatal steroid exposure. Infants with dexamethasone exposure were also statistically more likely to have been born at a younger EGA, compared with those with either betamethasone or no prenatal steroid exposure, although this difference was likely not clinically significant (on average, all of the subjects were born at an EGA of 26.0–26.5 weeks). Infants with betamethasone exposure were less likely to have early-onset sepsis than were those with dexamethasone exposure. Receipt of betamethasone was also crudely associated with a lower risk of late-onset sepsis, compared with dexamethasone exposure or no prenatal steroid exposure.
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Neurodevelopmental Outcomes at Corrected Ages of 18 to 22 Months
The neurodevelopmental outcomes at corrected ages of 18 to 22 months for ELBW infants with prenatal exposure to dexamethasone, betamethasone, or no steroid are presented in Table 3. Overall, 11.7% of infants developed CP, with 6.1% having moderate/severe CP; 21% had a PDI of <70. There were no crude differences among the 3 study groups with respect to risk of CP or PDI of <70. Thirty-two percent of the cohort had a MDI of <70, with betamethasone being crudely associated with a reduced risk of MDI of <70, compared with no prenatal steroid treatment. Overall, there was a low incidence of hearing impairment, with 2.1% of the cohort requiring hearing aids bilaterally; in crude analyses, infants with betamethasone exposure had a lower risk of hearing impairment than did those with either dexamethasone or no prenatal steroid exposure. There was no difference in the rates of blindness among the 3 groups, with an overall rate of 0.9% in the study population. The risk of NDI was 38%, with betamethasone being crudely associated with a lower risk for this outcome, compared with either dexamethasone or no prenatal steroid exposure. Overall, 32% of the cohort was neurodevelopmentally unimpaired at corrected age of 18 to 22 months; betamethasone was crudely associated with an increased likelihood of unimpaired status, compared with either dexamethasone or no prenatal steroid exposure.
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Multivariate Analyses of Neurodevelopmental Outcomes
In multivariate regression analyses comparing the risks of neurodevelopmental outcomes according to steroid exposure groups, there were no statistically significant differences among the 3 groups with respect to risk of CP or moderate/severe CP (Table 4). However, there was a trend toward a reduced risk of PDI of <70 associated with betamethasone, compared with dexamethasone (OR: 1.40; 95% CI: 0.96–2.04). There were no statistically significant differences in risk of MDI of <70 among the 3 study groups. The incidence of blindness in the study cohort was so low that meaningful statistical comparisons were not possible with the multivariate models; therefore, only blindness results from the crude model without covariates are presented in this study. Betamethasone was associated with a reduced risk of hearing impairment, compared with no prenatal steroid exposure (OR: 0.22; 95% CI: 0.06–0.82), whereas dexamethasone was associated with an increased risk, compared with betamethasone (OR: 3.90; 95% CI: 1.31–11.65). The risk of NDI was decreased with betamethasone but not dexamethasone, compared with no prenatal steroid exposure (OR: 0.63; 95% CI: 0.41–0.97). When hearing impairment was taken out of the composite NDI score, however, the association between betamethasone exposure and decreased risk of NDI was not statistically significant (OR: 0.69; 95% CI: 0.45–1.06). However, neurodevelopmentally unimpaired status was still statistically associated with betamethasone exposure, compared with no prenatal steroid exposure, regardless of whether hearing status was included in the definition (OR: 2.42; 95% CI: 1.49–3.91) or not (OR: 2.28; 95% CI: 1.42–3.68). It is important to note that unimpaired status is not a reciprocal of NDI, differing in the use of MDI and PDI scores of
85 for the former and MDI and PDI scores of <70 for the latter.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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This is the largest study to date that has studied the possible differences in association of prenatal dexamethasone and betamethasone exposure with long-term neurodevelopmental outcomes. We reported previously that betamethasone exposure but not dexamethasone exposure, compared with no prenatal steroid exposure, was associated with decreased risk of neonatal death at 28 days of life,10 consistent with the findings of the Cochrane meta-analysis by Crowley6 and the study by Jobe and Soll.13 Although multiple studies have documented the association of both dexamethasone and betamethasone exposure with decreased risks of IVH and severe IVH,2,3,7,10 there have been concerns regarding an increased risk of PVL associated with dexamethasone versus betamethasone exposure.7 However, in a previous study with the overall cohort from which the current study was drawn, we found no difference in the risks of cystic PVL associated with prenatal steroid exposures, compared either with each other or with the absence of prenatal steroid exposure.10
The current study found that betamethasone exposure was associated with increased likelihood of a neurodevelopmentally unimpaired status among ELBW infants at corrected age of 18 to 22 months, compared with dexamethasone exposure or no prenatal steroid exposure. Although betamethasone exposure was also associated with decreased risk of NDI, compared with dexamethasone exposure or no prenatal steroid exposure, this association became nonsignificant when hearing impairment was removed from the NDI definition. This is of importance because hearing deficit was the only individual component of NDI that had statistically significantly different associations among the 3 steroid exposure groups; when dexamethasone was compared with betamethasone, there were no differences in individual risks of CP, MDI of <70, blindness, or NDI in the study population, although there was a strong trend toward increased risk of PDI of <70 with dexamethasone exposure, compared with betamethasone exposure. Therefore, the difference in NDI risks associated with betamethasone exposure, dexamethasone exposure, and no prenatal steroid exposure is likely attributable in large part to the difference in hearing deficit risks in this study population. However, the likelihood of neurodevelopmentally unimpaired status with betamethasone treatment remained statistically significant even after the removal of hearing deficit from the outcome definition. It should be noted that the difference between the definition of NDI and that of unimpaired status is that NDI measured severe cognitive and psychomotor delay (BSID-II scores of <70), whereas unimpaired status assessed for BSID-II scores of 85.
The decreased risk of hearing impairment associated with betamethasone exposure, compared with dexamethasone exposure or no prenatal steroid exposure, was unexpected; it was expected that, if different risks existed between the steroid groups, they would be with respect to psychomotor development.14–18 However, given the relative rarity of this outcome, the analytical model for hearing impairment was statistically limited, and the possibility of a type I error cannot be excluded. It may be that other confounders that were unaccounted for in the model, such as different usage patterns of ototoxic medications among the 3 steroid groups, contributed to this finding. This particular association between prenatal steroid exposure and hearing impairment warrants further investigation.
Evidence that dexamethasone may be neurologically detrimental, compared with betamethasone, has been previously reported in animal and human studies. Rayburn et al8 reported that mice exposed to dexamethasone had decreased neurobehavioral functionality with regard to anxiety and memory, compared with mice given betamethasone. Several human studies similarly found associations of postnatal dexamethasone exposure with increased risks of long-term adverse neurodevelopmental and motor development.14–16,18,19 Conversely, Karemaker et al17 reported recently that, in a cohort of premature infants of EGA of <32 weeks at birth, those with prenatal betamethasone exposure had no differences in behavioral or neuromotor outcomes at 7 to 10 years of age, compared with premature infants without prenatal steroid exposure. LeFlore et al20 reported that their cohort of ELBW infants exposed to prenatal dexamethasone did not have any significant differences in BSID-II scores, compared with ELBW infants with no prenatal exposure. Similarly, follow-up reports from the prenatal steroid trials of the 1970s and 1980s all reported no differences in neurodevelopmental or psychological outcomes at childhood to adult ages for premature infants with prenatal betamethasone exposure, compared with no prenatal corticosteroid exposure.21–23 The US Antenatal Steroid Trial monitored its cohort of preterm infants exposed to prenatal dexamethasone through childhood and reported no statistically significant neurodevelopmental differences, compared with infants with no prenatal steroid exposure.24 The current study differs from the other follow-up studies with respect to the use of statistical modeling that adjusted for multiple covariates and a large sample size and theoretically might have been able to more clearly identify subtle differences in neurodevelopmental outcomes between prenatal dexamethasone exposure, prenatal betamethasone exposure, and no prenatal steroid exposure. Indeed, the results of our study suggest that, if there is any lasting difference in neurodevelopmental outcomes associated with dexamethasone versus betamethasone, it is subtle (ie, the difference in the risk of unimpaired status but not that of NDI was statistically significant). This speculation is supported by the findings of Spinillo et al,9 who reported trends of increased risks for adverse neurodevelopmental outcomes associated with dexamethasone versus betamethasone, which became statistically significant when multiple prenatal courses were used.
Our study did not find different risks of blindness associated with either steroid, compared with each other or with no prenatal steroid exposure. Previous studies suggested that prenatal steroid exposure may decrease the risk of ROP,25–29 possibly because of glucocorticoid-mediated acceleration of retinal vascular maturation and inhibition of tumor necrosis factor- production, a key factor in inflammatory and angiogenic mechanisms.29 In our previous neonatal outcome study of this cohort, there were no statistical differences in the risks of ROP or severe ROP associated with either dexamethasone or betamethasone, compared with no prenatal steroid exposure or with each other. The current study had a very low rate of blindness, however, and the possibility of a type II error cannot be ruled out.
Caution must be used when interpreting associations from this observational study. The theoretical reasons for the increased risks of adverse outcomes with dexamethasone versus betamethasone are unclear. It is not likely that they have differing genomic effects, given that dexamethasone and betamethasone differ only in the orientation of the methyl group at position 16 (in the -configuration in dexamethasone and in the β-configuration in betamethasone). However, there may be significant nongenomic differences between the 2 steroids. Buttgereit et al30 reported that dexamethasone was 5 times more potent than betamethasone in inhibiting thymocyte respiration in an in vitro study. There may also be nongenomic differences in membrane receptor interactions, including the expression of glutamate receptors and ion transport channels.31–33 Furthermore, potential different cardiovascular and hormonal effects of dexamethasone and betamethasone were not investigated directly in the current study and might have effects of significant magnitude on the long-term neurodevelopmental outcomes observed. In addition, because 27 of the 971 infants with prenatal steroid exposure received >1 course of prenatal steroid treatment, we were unable to perform meaningful analyses with respect to steroid course, although this is an area of ongoing concern regarding fetal and neonatal effects.
In the current study, certain statistical limitations must also be considered. The current sample size was determined prehoc, because the study cohort was drawn from an original population defined by a sample size calculation for detection of different PVL rates.10 Particularly because no sample size calculations were performed for the current study, type II errors cannot be excluded. In addition, retrospective multivariate analyses, such as the ones performed here, can adjust only for known measurable covariates of the outcomes of interest. It should be noted that the current study used logistic modeling primarily to control for confounding and not to create a predictive model for neurodevelopmental outcomes associated with prenatal steroid exposure. That is, the modeling strategy used in the current study was designed to investigate etiologic and not predictive associations. To elucidate more fully predictive or causative associations between prenatal steroid exposure and neonatal or neurodevelopmental outcomes, a randomized, clinical trial comparing dexamethasone and betamethasone should be performed.
Finally, the concerning racial disparity in prenatal steroid exposure profiles, with white mothers being more likely to receive betamethasone or either steroid than nonwhite mothers, should be noted. Although there are certainly many social and demographic factors that influence this observation, it warrants further study. Of note, we were unable to analyze the time intervals between admission and delivery (which might influence this observation) because the Neonatal Research Network does not routinely collect these data.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The current study suggests that prenatal betamethasone exposure increases the likelihood of unimpaired neurodevelopmental status in ELBW infants, compared with infants with prenatal dexamethasone exposure or no prenatal steroid exposure. Furthermore, although results were not statistically significant, there were consistent trends of improved motor outcomes at corrected ages of 18 to 22 months associated with prenatal betamethasone exposure, compared with prenatal dexamethasone exposure, among ELBW infants. Finally, there was a statistically significant reduction in the risk of hearing impairment associated with prenatal betamethasone exposure, compared with prenatal dexamethasone exposure or no prenatal steroid exposure, of unclear cause. In the absence of a randomized, clinical trial evaluating the possible different fetal and neonatal effects of prenatal dexamethasone and betamethasone exposure and on the basis of the findings of the current study and other studies, it may be in the best interest of neonates to receive prenatal betamethasone treatment, rather than prenatal dexamethasone treatment, when the option is available.
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ACKNOWLEDGMENTS |
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This work was conducted for and supported by the NICHD (Bethesda, MD).
Members of the NICHD Neonatal Research Network (1996–2007) were as follows: Steering Committee chairman, Alan H. Jobe, MD, PhD; University of California, San Diego (grant U10 HD40461), Neil N. Finer, MD, Maynard Rasmussen, MD, Wade Rich; Case Western Reserve University (grant U10 HD21364), Michele Walsh, MD, Avroy A. Fanaroff, MB, BCh, Nancy Newman, RN; University of Cincinnati (grant U10 HD27853), Edward F. Donovan, MD, Vivek Narendran, MD, MRCP, Cathy Grisby, RN; Duke University (grant U10 HD40492), Ronald N. Goldberg, MD, Michael Cotten, MD, Kathy Auten, RN; Emory University (grant U10 HD27851), Barbara J. Stoll, MD, Ellen Hale, RN; Indiana University (grant U10 HD27856), James A. Lemons, MD, Brenda Poindexter, MD, Lucy Miller, RN; University of Miami (grant U10 HD21373), Shahnaz Duara, MD, Emmalee S. Bandstra, MD, Ruth Everett, RN; NICHD, Rosemary D. Higgins, MD, James Hansen, MD; Research Triangle Institute (grant U10 HD36790), W. Kenneth Poole, PhD, Betty Hastings, Carolyn M. Petrie, MS; University of Rochester (grant U10 HD40521), Dale L. Phelps, MD, Ronnie Guillet, MD, PhD, Linda Reubens, RN; Stanford University (grant U10 HD27880), David K. Stevenson, MD, Krisa Van Meurs, MD, Bethany Ball, BS; University of Texas Health Science Center at Houston (grant U10 HD21373), Jon E. Tyson, MD, MPH, Kathleen Kennedy, MD, MPH, Georgia McDavid, RN; University of Texas Southwestern Medical Center (grant U10 HD40689), Abbot R. Laptook, MD, Walid Salhab, MD, Gay Hensley, RN; Wake Forest University, T. Michael O'Shea, MD, Robert Dillard, MD, Nancy Peters, RN; Wayne State University (grant U10 HD21385), Seetha Shankaran, MD, Ganesh Konduri, MD, Geraldine Muran, RN; Women and Infants Hospital (grant U10 HD27904), William Oh, MD, Barbara Stonestreet, MD, Angelita Hensman, RN; Yale University (grant U10 HD27871), Richard A. Ehrenkranz, MD, Patricia Gettner, RN; University of Alabama at Birmingham (grant U10 HD34216), Waldemar A. Carlo, MD, Namasivayam Ambalavanan, MD, Monica V. Collins, RN.
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FOOTNOTES |
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Accepted Jul 23, 2007.
Address correspondence to Ben H. Lee, MD, MPH, MSCR, MidAtlantic Neonatology Associates, 100 Madison Ave, Box 85, Morristown, NJ 07960. E-mail: ben.lee{at}atlantichealth.org
The authors have indicated they have no financial relationships relevant to this article to disclose.
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