PEDIATRICS Vol. 121 No. 1 January 2008, pp. 22-27 (doi:10.1542/10.1542/peds.2007-0381)
ARTICLE |
Use of Medications for Gastroesophageal Reflux at Discharge Among Extremely Low Birth Weight Infants
a Department of Pediatrics, Duke University, Durham, North Carolina
b Research Triangle Institute International, Research Triangle Park, North Carolina
c Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
OBJECTIVES. Our goals were (1) to determine the use of medications to treat gastroesophageal reflux in extremely low birth weight infants (birth weight of <1000 g) at discharge; (2) to identify risk factors associated with the use of medications to treat gastroesophageal reflux at discharge; and (3) to assess the contribution of gastroesophageal reflux medication use at discharge to growth and development at corrected ages of 18 to 22 months.
METHODS. This retrospective cohort analysis included extremely low birth weight infants enrolled at National Institute of Child Health and Human Development Neonatal Research Network Centers between 2002 and 2003 who survived to follow-up evaluations at corrected ages of 18 to 22 months. Analyses were used to identify factors associated with discharge with antireflux medications and poor growth or neurodevelopmental impairment after discharge.
RESULTS. A total of 1598 infants were included in the analyses; 24.8% were discharged from the hospital with medications to treat gastroesophageal reflux. A total of 19.3% of the 1287 infants discharged at postmenstrual age of 
42 weeks were discharged with antireflux medications. For those infants, center, lower gestational age, and race had significant effects on the use of antireflux medications at discharge. A total of 47.6% of the 311 infants discharged at postmenstrual age of >42 weeks were discharged with antireflux medications. For those infants, no tested variables were associated with treatment with antireflux medications at discharge. Use of antireflux medications at discharge was not associated with either poor growth or neurodevelopmental impairment at corrected ages of 18 to 22 months.
CONCLUSIONS. Use of antireflux medications at the time of discharge seems to be common for extremely low birth weight infants, especially those discharged at postmenstrual age of >42 weeks, but does not seem to have effects on growth or development at the time of follow-up evaluations.
Key Words: gastroesophageal reflux • infant • premature • low birth weight • antacid • growth • development
Abbreviations: GER—gastroesophageal reflux • PMA—postmenstrual age • ELBW—extremely low birth weight
Gastroesophageal reflux (GER) occurs commonly in extremely low birth weight (ELBW) infants (birth weight of <1000 g) and often is considered pathologic enough to warrant treatment with medications that have not been proved safe or efficacious for this population. Although information on the best strategies for diagnosis and treatment of GER in premature infants is largely extrapolated from studies of term infants and older children, clinicians continue to make the diagnosis and to initiate treatment in this high-risk population with the intent of improving outcomes.
The effects of GER in premature infants are largely undefined and poorly understood. Cardiorespiratory compromise among premature infants frequently is attributed to GER, although studies have failed to show consistently this association or a benefit of medical treatment.1–4 Reflux-specific behaviors have also been shown to be unreliable indicators of GER in premature infants.5 Despite this uncertainty, GER is a common clinical diagnosis in NICUs and has been associated with longer hospital stays and higher hospital costs.6,7
The medical treatment of premature infants with the presumed diagnosis of GER with antireflux medications, such as H2 receptor blockers and prokinetic agents, is a common occurrence in US NICUs, during hospitalization and at discharge. Although studies have been unable to demonstrate consistently the short-term benefits of antireflux medications in preterm infants, H2 receptor blocker therapy was shown to be used commonly for very low birth weight infants and metoclopramide was reported to be 1 of the 10 medications prescribed most commonly in NICUs.8,9 Data on the effects of antireflux medications on follow-up growth and development are lacking. The objectives of this study were (1) to determine the frequency of use of antireflux medications at hospital discharge among ELBW infants in 16 academic tertiary centers; (2) to identify risk factors associated with being discharged from the hospital with antireflux medications; and (3) to assess the contribution of the clinical diagnosis of GER, defined on the basis of the use of antireflux medications at discharge, to growth and development at corrected ages of 18 to 22 months.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
A retrospective cohort analysis of ELBW infants (birth weight of <1000 g) who were enrolled in the National Institute of Child Health and Human Development Neonatal Research Network generic database between January 1, 2002, and December 31, 2003, and who survived to the 18- to 22-month follow-up visit was performed. The registry included maternal and infant sociodemographic, pregnancy, and clinical data collected by trained research personnel in a standardized manner, providing multicenter baseline and outcome data. The question, "Was the child discharged from the hospital on any of the following medications?" was included on the case report form, with antireflux medications being one of the categories. If the question was answered yes, then the specific medication was recorded. The institutional review boards at all member institutions approved collection of the data.
Antireflux medication use among centers included but was not limited to the H2 receptor blockers ranitidine and famotidine and the prokinetic agent metoclopramide. Infants with chromosomal or congenital anomalies or any abdominal surgery were excluded from this secondary analysis.
Bivariate and multivariate analyses were used to identify demographic factors or morbidities associated with the use of antireflux medications at discharge and poor growth or neurodevelopmental impairment at follow-up evaluation. Poor growth was defined as weight, length, or head circumference below the 10th percentile for corrected age on the 2000 Centers for Disease Control and Prevention growth charts (birth to 36 months) at follow-up evaluation.10 Neurodevelopmental impairment was defined as moderate/severe cerebral palsy, Bayley Scales of Infant Development Mental Developmental Index or Psychomotor Development Index of <70, blindness, or deafness at follow-up evaluation.11 Separate analyses for risk-adjusted odds of the outcomes (use of medications, poor growth, and neurodevelopmental impairment) were conducted for infants discharged from the hospital at postmenstrual age (PMA) of 42 or >42 weeks by using logistic regression models that included demographic factors, perinatal factors, and neonatal morbidities. We chose PMA of 42 weeks as a cutoff value to delineate prolonged hospital stays because this value was used previously for this population and is based on evidence that suggests that the majority of extremely premature infants are discharged from the hospital by this age.12,13 All analyses were conducted by the network data coordinating center at Research Triangle Institute (Research Triangle Park, NC), with SAS 9.1.3 (SAS Institute, Cary, NC).
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Enrollment and Discharge Findings
A total of 3645 ELBW infants were enrolled in the National Institute of Child Health and Human Development Neonatal Network generic database from 2002 to 2003, with 2344 of those infants surviving to discharge and 2303 surviving to the 18- to 22-month follow-up visit. A total of 267 infants were excluded because of congenital anomalies or abdominal surgery. Incomplete discharge information was available for 479 infants. Therefore, data for 1598 infants were included in this study, with complete follow-up data being available for 1433 of those infants. The mean gestational age of all enrolled infants was 26.7 weeks (range: 22–34 weeks), with a mean birth weight of 789 g (range: 410–998 g). A total of 80.5% of the infants (1287 of 1598 infants) were discharged from the hospital at PMA of
42 weeks. A total of 24.8% of all enrolled infants (396 of 1598 infants) were discharged from the hospital with antireflux medications; 19.3% of infants (248 of 1287 infants) discharged before and 47.6% of infants (148 of 311 infants) discharged after PMA of 42 weeks were discharged from the hospital with antireflux medications (Fig 1).
|
Center Variance
Use of antireflux medications at discharge varied widely among the centers in the National Institute of Child Health and Human Development Neonatal Network. The center range for treatment with antireflux medications for infants discharged from the hospital at PMA of
42 weeks was 1.7% to 45.7%. The center range for treatment for infants discharged from the hospital at PMA of >42 weeks was 22.2% to 90% (Fig 2).
|
Factors Associated With Treatment
For infants discharged at PMA of
42 weeks, several variables were associated with use of antireflux medications in bivariate analyses but only center (P <.0001), earlier gestational age (P <.001), and race (P <.03) were associated with medication use at discharge in multivariate analysis. For those discharged at PMA of >42 weeks, the model including center, demographic factors, and morbidities was not predictive of medication use at discharge (Table 1).
|
Antireflux Medications at Discharge and Follow-up Findings
After controlling for demographic and morbidity variables, the clinical diagnosis of GER at discharge, defined as the use of antireflux medications at discharge, was not predictive of poor growth or neurodevelopmental impairment at 18 to 22 months for infants discharged from the hospital before or after PMA of 42 weeks. When components of the composite variable neurodevelopmental impairment were examined, infants discharged at PMA of >42 weeks with antireflux medications were at greater risk for poor cognitive development (P <.05) (Table 2).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
There is currently no standard practice for the diagnosis or treatment of ELBW infants with GER that is thought to be clinically significant. As written, the North American Society for Pediatric Gastroenterology and Nutrition clinical practice guidelines for the evaluation and treatment of infants and children with suspected GER are not intended to be used for neonates <72 hours of age, premature infants, or infants and children with neurologic impairments.14 However, the results of our study show that providers frequently diagnose GER in ELBW infants, perceive it to be problematic, and prescribe antireflux medications. Twenty-five percent of all ELBW infants in this cohort and as many as 90% in some nurseries were discharged from the hospital with these medications.
The frequent use of antireflux medications in this population is concerning, because recent information suggests potential harmful associations between the use of H2 receptor blockers and the development of necrotizing enterocolitis in very low birth weight infants.9 Similarly, antacid use has been shown to increase the risk of infection and feeding intolerance in infants receiving gavage feedings in an intensive care setting.15 Although there may be a role for the use of antacids for convalescing ELBW infants who are at low risk for necrotizing enterocolitis and are learning to feed orally, indications for early empirical use of H2 receptor blockers for ELBW infants are not compelling.
Although antacids may have some potential benefit in preventing or treating acquired esophagitis resulting from long-standing acid reflux, the use of motility agents as a treatment for GER in infants has been supported poorly by the literature. A recent systematic review concluded that current literature is insufficient either to support or to oppose the use of metoclopramide for GER disease in infants.16 Furthermore, multiple adverse effects of metoclopramide use in infants have been reported, including apnea, irritability, and dystonia. Study of the long-term neurologic effects of exposure to metoclopramide during the initial hospitalization of ELBW infants is warranted.
A limitation of this study is the retrospective nature of the data collection, with the possibility of recall bias. The database was also limited by its inability to determine when the medication was first prescribed, the indication for medication use, and the duration of medication usage. Nonetheless, it was shown in previous studies that, with the declining use of cisapride, which was previously the only motility agent approved to treat reflux in infants and is no longer on the market because of the potential for cardiac dysrhythmias, there have been increases in the use of ranitidine and metoclopramide in NICUs since 1998.8 These medications, like so many medications used commonly in NICUs, have not been approved by the Food and Drug Administration for use for this population and are used in an off-label manner because of the perceived safety and potential benefits demonstrated for older populations. Clinicians should be reminded that there is a lack of dosing, safety, and efficacy data for these medications for ELBW infants.
Center variations in the use of GER medications at discharge (2%–90%) were striking, particularly for those being discharged at PMA of >42 weeks. A multicenter survey in the United Kingdom suggested similarly large variations in diagnostic and treatment strategies for GER in the neonatal environment.17 Center variations have been noted for multiple morbidities and treatments for ELBW infants; the variation in reflux treatment at discharge is likely attributable to center therapy bias and the difficulty of diagnosing GER accurately for extremely preterm infants, rather than population differences among centers.18
Current radiographic tools used for neonates, such as upper gastrointestinal radiography, ultrasonography, and radionucleotide studies, are inadequate for diagnosing GER because of the episodic nature of the condition. The current standard diagnostic procedure used to determine GER in older infants and children is 24-hour, continuous pH probe monitoring, to determine the degree of esophageal acid exposure. This is an ineffective tool for premature infants, because of the developmental immaturity of the acid-making parietal cells in the stomach and the buffering effects of frequent or continuous feedings in this population. Indeed, studies using multichannel, intraluminal impedance monitoring in combination with pH monitoring showed that pH monitoring alone underestimated greatly the frequency of reflux episodes in infants, particularly preterm infants.19 Although it is primarily a research tool at the present time, impedance monitoring likely will prove to be a valuable clinical tool for determining accurately whether symptoms correlate with reflux episodes in neonates. Future studies using impedance monitoring likely will also assist in documenting normal values and demonstrating the efficacy of various GER treatment strategies in neonates.
ELBW infants being discharged from the hospital at PMA of >42 weeks were discharged with reflux medications at twice the rate of those being discharged from the hospital earlier (47.6% vs 19.3%). It might be concluded that GER, in addition to many other factors (such as prolonged intubation), interferes with the acquisition of normal feeding patterns and contributes to prolonged hospitalizations. Unexpectedly, this study did not show an association of the use of GER medications at the time of discharge with serious neonatal morbidities known to prolong hospitalization, such as chronic lung disease, severe brain injury (grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia), or history of necrotizing enterocolitis.
Neonatal follow-up providers and gastroenterologists frequently encounter ELBW infants with poor growth after hospital discharge, which is likely attributable, in part, to acquired oral aversions. A significant correlation between postnatal growth and neurodevelopmental outcomes has been shown.20 Clinicians might therefore speculate that clinically significant GER might negatively affect early oral-motor skills and lead to poor growth or neurodevelopmental delays.
Although it was demonstrated that the diagnosis of GER in NICUs was not associated with poor growth during the infants' hospital stay, early feeding experiences may well have an impact on growth and developmental outcomes for the highest-risk infants.6 Feeding disorders in children with conditions such as cerebral palsy and Down syndrome were described in detail previously.21 More recently, it was reported that lack of sufficient early feeding experience may lead to a disorganized sucking pattern and this abnormal feeding performance in the neonatal period may be related to later neurodevelopmental delays.22 Our data did not show a correlation between discharge from the hospital with antireflux medications and poor growth or neurodevelopmental impairment at the 18- to 22-month follow-up visit, with variables for known contributing morbidities being held constant; however, we did observe that those with prolonged hospitalizations who were treated with antireflux medications at discharge were more likely to have lower cognitive scores in developmental testing. If GER contributes to poor early oral-motor skill acquisition, then it may have an adverse affect on early language development, which is an important component of the cognitive testing score at that age.
|
CONCLUSIONS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Clinicians commonly discharge ELBW infants home with medications to treat GER, especially those discharged at PMA of >42 weeks. Our data show that this practice varies widely among centers, which suggests the lack of a valid diagnostic test or treatment guidelines for this population. We did not observe an association between GER medication use and other neonatal morbidities, and we did not find that presumed GER, treated with antireflux medications at discharge, negatively affected outcomes. The lack of certainty in diagnosis and extreme variations in treatment practices demonstrate that identifying valid diagnostic tests and performing randomized, prospective studies of treatment safety and efficacy, before and after discharge, are essential for understanding the clinical significance of GER and optimizing outcomes for ELBW infants.
|
ACKNOWLEDGMENTS |
|---|
Dr Malcolm was funded by a diversity supplement through the National Institute of Child Health and Human Development Cooperative Multicenter Neonatal Research Network (grant 3 U10 HD040492-06S1). National Institute of Child Health and Human Development Neonatal Research Network grants (1996 to 2006) were as follows: Shahnaz Duara, MD (August 2001), and Charles R. Bauer, University of Miami (Miami, FL), grant U10 HD21397; Michele C. Walsh, MD (August 2001), and Avroy A. Fanaroff, MB, BCh, Case Western Reserve University (Cleveland, OH), grant U10 HD21364; Waldemar A. Carlo, MD, University of Alabama at Birmingham (Birmingham, AL), grant U10 HD34216; Kurt Schibler, MD (April 2006), and Edward F. Donovan, MD, University of Cincinnati (Cincinnati, OH), grants U10 HD27853 and M01 RR08084; Richard A. Ehrenkranz, MD, Yale University (New Haven, CT), grants U10 HD27871, M01 RR06022, and M01 RR00125; Neil N. Finer, MD, University of California, San Diego (San Diego, CA), grant U10 HD40461; Ronald N. Goldberg, MD, Duke University (Durham, NC), grants U10 HD40492 and M01 RR000030-45; Sheldon B. Korones, MD, University of Tennessee, Memphis (Memphis, TN), grant U10 HD21415; Pablo Sanchez, MD (April 2006), and Abbot R. Laptook, MD, University of Texas Southwestern Medical Center at Dallas (Dallas, TX), grant U10 HD40689; Brenda Poindexter, MD (April 2006), and James A. Lemons, MD, Indiana University (Indianapolis, IN), grants U10 HD27856 and M01 RR00750; Abbot R. Laptook, MD (April 2006), and William Oh, MD, Women and Infants' Hospital of Rhode Island (Providence, RI), grant U10 HD27904; T. Michael O'Shea, MD, Wake Forest University School of Medicine (Winston-Salem, NC), grant U10 HD40498; Dale L. Phelps, MD, University of Rochester (Rochester, NY), grants U10 HD40521 and 5 M01 RR00044; Abhik Das, PhD (February 2005), and W. Kenneth Poole, PhD, Research Triangle Institute (Research Triangle Park, NC), grant U01 HD36790; Seetha Shankaran, MD, Wayne State University (Detroit, MI), grant U10 HD21385; Ann R. Stark, MD, Harvard University (Boston, MA), grants U10 HD34167, M01 RR02635, M01 RR02172, and M01 RR01032; David K. Stevenson, MD, Stanford University (Stanford, CA), grants U10 HD27880 and M01 RR00070; Barbara J. Stoll, MD, Emory University (Atlanta, GA), grants U10 HD27851 and M01RR 00039; Jon E. Tyson, MD, MPH, University of Texas Health Science Center at Houston (Houston, TX), grant U10 HD 21373; Rosemary D. Higgins, MD, National Institute of Child Health and Human Development (Bethesda, MD).
The following investigators participated in the generic database study: Brown University Women and Infant's Hospital, William Oh, MD, and Angelita Hensman, BSN, RNC; Case Western University, Avroy A. Fanaroff, MD, and Nancy Newman, RN; Duke University, Ronald N. Goldberg, MD, and Kathy Auten; Emory University, Barbara J. Stoll, MD, and Ellen Hale, RN, BS; Indiana University Riley Hospital for Children and Methodist Hospital, James Lemons, MD, Diana Dawn Appel, RN, BSN, and Lucy Miller, RN, BSN; Stanford University, Lucile Salter Packard Children's Hospital, David K. Stevenson, MD, and Bethany Ball, BS, CCRC; University of Alabama at Birmingham University Hospital, Waldemar A. Carlo, MD, Shirley S. Cosby, RN, BSN, and Monica Collins; University of Cincinnati University Hospital, Cincinnati Children's Hospital Medical Center, and Good Samaritan Hospital, Edward Donovan, MD, Marcia Mersmann, RN, Barb Alexander, RN, Jody Shively, RN, and Holly Mincey, RN; University of California, San Diego, Medical Center and Sharp Mary Birch Hospital for Women, Neil N. Finer, MD, Maynard R. Rasmussen, MD, Chris Henderson, CRTT, Clarence Demetrio, RN, and Wade Rich, RRT-NPS; University of Miami, Shahnaz Duara, MD, and Ruth Everett, RN; University of Rochester Golisano Children's Hospital at Strong, Dale L. Phelps, MD, and Linda Reubens, RN; University of Texas-Dallas Parkland, Abbot Laptook, MD, Susie Madison, RN, Gay Hensley, RN, and Nancy Miller, RN; University of Texas-Houston Memorial Hermann Children's Hospital, John Tyson, MD, MPH, and Georgia McDavid, RN; Wake Forest University Baptist Medical Center, Forsyth Medical Center, and Brenner Children's Hospital, T. Michael O'Shea, MD, MPH, and Nancy Peters, RN; Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan, Seetha Shankaran, MD, Rebecca Bara, RN, BSN, and Geraldine Muran, RN, BSN; Yale University New Haven Children's Hospital, Richard A. Ehrenkranz, MD, and Patricia Gettner, RN. The members of the National Institute of Child Health and Human Development Neonatal Research Steering Committee were as follows: Brown University, William Oh, MD; Case Western University, Avroy A. Fanaroff, MD; Duke University, Ronald N. Goldberg, MD; Emory University, Barbara J. Stoll, MD; Indiana University, James A. Lemons, MD; Stanford University, David K. Stevenson, MD; University of Alabama at Birmingham, Waldemar A. Carlo, MD; University of Cincinnati, Edward F. Donovan, MD; University of California, San Diego, Neil N. Finer, MD; University of Miami, Shahnaz Duara, MD; University of Rochester, Dale L. Phelps, MD; University of Texas-Dallas, Abbot R. Laptook, MD; University of Texas-Houston, Jon E. Tyson, MD, MPH; Wake Forest University, T. Michael O'Shea, MD, MPH; Wayne State University, Seetha Shankaran, MD; Yale University, Richard A. Ehrenkranz, MD; University of Cincinnati, Alan Jobe, MD (Chair). Members at the data coordinating center were W. Kenneth Poole, PhD, Betty Hastings, and Carolyn Huitema, MS. Members at the National Institute of Child Health and Human Development were Rosemary D. Higgins, MD, Linda L. Wright, MD, and Elizabeth McClure, MEd.
|
FOOTNOTES |
|---|
Accepted Jul 6, 2007.
Address correspondence to William F. Malcolm, MD, Department of Pediatrics/Neonatology, Box 3179, Duke University Medical Center, Durham, NC 27710. E-mail: malco002{at}mc.duke.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
- Peter CS, Sprodowski N, Bohnhorst B, Silny J, Poets CF. Gastroesophageal reflux and apnea of prematurity: no temporal relationship.
Pediatrics. 2002;109
:8
–11
[Abstract/Free Full Text] - Barrington KJ, Tan K, Rich W. Apnea at discharge and gastro-esophageal reflux in the preterm infant. J Perinatol. 2002;22 :8 –11[CrossRef][Medline]
- Molloy EJ, Di Fiore JM, Martin RJ. Does gastroesophageal reflux cause apnea in preterm infants? Biol Neonate. 2005;87 :254 –261[CrossRef][Web of Science][Medline]
- Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnea in premature infants. J Pediatr. 2001;138 :355 –360[CrossRef][Web of Science][Medline]
- Snel A, Barnett CP, Cresp TL, et al. Behavior and gastroesophageal reflux in the premature neonate. J Pediatr Gastroenterol Nutr. 2000;30 :18 –21[CrossRef][Web of Science][Medline]
- Frakaloss G, Burke G, Sanders MR. Impact of gastroesophageal reflux on growth and hospital stay in premature infants. J Pediatr Gastroenterol Nutr. 1998;26 :146 –150[CrossRef][Web of Science][Medline]
- Ferlauto JJ, Walker MW, Martin MS. Clinically significant gastroesophageal reflux in the at-risk premature neonate: relation to cognitive scores, days in the NICU, and total hospital charges. J Perinatol. 1998;18 :455 –459[Medline]
- Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set.
Pediatrics. 2006;117
:1979
–1987
[Abstract/Free Full Text] - Guillet R, Stoll BJ, Cotten CM, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117(2) . Available at: www.pediatrics.org/cgi/content/full/117/2/e137
- Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States. Adv Data. 2000;(314) :1 –27[Medline]
- Bayley N. Manual for the Bayley Scales of Infant Development. 2nd ed. San Antonio, TX: Psychological Corp; 1993
- Cotten CM, Oh W, McDonald S, et al. Prolonged hospital stay for extremely premature infants: risk factors, center differences, and the impact of mortality on selecting a best-performing center. J Perinatol. 2005;25 :650 –655[CrossRef][Medline]
- Tyson JE, Younes N, Verter J, Wright LL. Viability, morbidity, and resource use among newborns of 501- to 800-g birth weight.
JAMA. 1996;276
:1645
–1651
[Abstract/Free Full Text] - Rudolph CD, Mazur LJ, Liptak GS, et al. Pediatric gastroesophageal reflux clinical practice guidelines. J Pediatr Gastroenterol Nutr. 2001;32(suppl 2) :1 –31
- Mehall JR, Kite CA, Saltzman DA, Wallett T, Jackson RJ, Smith SD. Prospective study of the incidence and complications of bacterial contamination of enteral feeding in neonates. J Pediatr Surg. 2002;37 :1177 –1182[CrossRef][Web of Science][Medline]
- Hibbs AM, Lorch SA. Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review.
Pediatrics. 2006;118
:746
–752
[Abstract/Free Full Text] - Dhillon AS, Ewer AK. Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units. Acta Paediatr. 2004;93 :88 –93[CrossRef][Web of Science][Medline]
- Fanaroff AA, Stoll BJ, Wright LL, et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol. 2007;196 :147.e1 –147.e8
- Wenzl TG, Moroder C, Trachterna M, et al. Esophageal pH monitoring and impedance measurement: a comparison of two diagnostic tests for gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2002;34 :519 –523[CrossRef][Web of Science][Medline]
- Latal-Hajnal B, von Siebenthal K, Kovari H, Bucher HU, Largo RH. Postnatal growth in VLBW infants: significant association with neurodevelopmental outcome. J Pediatr. 2003;143 :163 –170[Web of Science][Medline]
- Reilly S, Skuse D, Poblete X. Prevalence of feeding problems and oral motor dysfunction in children with cerebral palsy: a community survey. J Pediatr. 1996;129 :877 –882[CrossRef][Web of Science][Medline]
- Mizuno K, Ueda A. Neonatal feeding performance as a predictor of neurodevelopmental outcome at 18 months. Dev Med Child Neurol. 2005;47 :299 –304[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
