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Growth in the Neonatal Intensive Care Unit Influences Neurodevelopmental and Growth Outcomes of Extremely Low Birth Weight Infants

^a Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
^b University of Indiana, Indianapolis, Indiana
^c Department of Pediatrics, Brown University, Providence, Rhode Island
^d National Institutes of Child Health and Human Development, Bethesda, Maryland
^e RTI International, Research Triangle Park, North Carolina

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS PARTICIPANTS IN THE NICHD... REFERENCES

 
OBJECTIVES. The objectives of this study were to assess whether (1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age among extremely low birth weight (ELBW) infants and (2) in-hospital growth velocity contributes to these outcomes after controlling for confounding demographic and clinical variables.

METHODS. Infants 501 to 1000 g birth weight from a multicenter cohort study were divided into quartiles of in-hospital growth velocity rates. Variables considered for the logistic-regression models included gender, race, gestational age, small for gestational age, mother’s education, severe intraventricular hemorrhage, periventricular leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late-onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for pulmonary disease, and center.

RESULTS. Of the 600 discharged infants, 495 (83%) were evaluated at 18 to 22 months’ corrected age. As the rate of weight gain increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) <70 and Psychomotor Developmental Index (PDI) <70, abnormal neurologic examination, neurodevelopmental impairment, and need for rehospitalization fell significantly. Similar findings were observed as the rate of head circumference growth increased. The in-hospital rate of growth was associated with the likelihood of anthropometric measurements at 18 months’ corrected age below the 10th percentile values of the Centers for Disease Control and Prevention 2000 growth curve. Logistic-regression analyses, controlling for potential demographic or clinical cofounders, and adjusted for center, identified a significant relationship between growth velocity and the likelihood of cerebral palsy, MDI and PDI scores of <70, and neurodevelopmental impairment.

CONCLUSIONS. These analyses suggest that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.

Key Words: extremely low birth weight infant • growth • neurodevelopmental outcome

Abbreviations: ELBW—extremely low birth weight • MDI—Mental Developmental Index • PDI—Psychomotor Developmental Index • PMA—postmenstrual age • CP—cerebral palsy • NDI—neurodevelopmental impairment • SGA—small for gestational age • NEC—necrotizing enterocolitis • IVH—intraventricular hemorrhage • PVL—periventricular leukomalacia • BPD—bronchopulmonary dysplasia • OR—odds ratio • CI—confidence interval

Postnatal growth failure is the norm for extremely low birth weight (ELBW) infants, especially the sickest infants.^1–4 The NICHD Growth Observational Study¹ demonstrated that, although the rate of weight gain was similar to the reported intrauterine rate of weight gain (15 g/kg per day), once birth weight was regained, most of the infants between 24 to 29 weeks’ gestation did not achieve the median birth weight of the reference fetus of the same postmenstrual age (PMA) at hospital discharge. In fact, at discharge from the NICU or at 36 weeks’ PMA, most were less than the comparable 10th percentile birth weight for completed weeks of gestation according to the reference intrauterine growth data reported by Alexander et al.⁵ Although nonnutritional factors contribute to the development of growth failure, delays in regaining birth weight and low nutrient intakes also play a major role. Compared with fetal nutrient intakes, the early parenteral and enteral nutritional support received by ELBW infants results in substantial protein and energy deficits that persist for weeks and can be directly related to subsequent postnatal growth restriction.^3,4

Numerous studies have demonstrated that inadequate early nutrition exerts an adverse influence on long-term developmental outcome.⁶ Malnutrition at a vulnerable period of brain development has been shown to result in a decreased number of brain cells as well as deficits in behavior, learning, and memory.^7–9 Based on data derived from nutritional studies conducted in rural Guatemala by the Institute of Nutrition of Central America and Panama (INCAP) from 1969 to 1977 and the long-term follow-up studies on statural growth and intellectual and social achievement conducted in 1988–1989, malnutrition is no longer only considered to result in cognitive deficiencies through brain damage.¹⁰ It most likely alters neurodevelopment by interfering with overall health as well as the child’s energy level, rate of motor development, and rate of growth. Extrapolating these concepts to hospitalized ELBW infants suggests that although inadequate nutrition may directly result in brain injury, it may also interfere with overall health by reducing immune competence, resistance to infection, and the energy and nutrients available to support recovery from acute and chronic lung disease and to support an adequate rate of growth and development, let alone catch-up growth, during the hospitalization.

An objective of the Growth Observational Study¹ was to use prospectively collected NICU growth, morbidity, and long-term follow-up data from a large heterogeneous population of ELBW infants to examine the impact of in-hospital growth velocity on outcomes at 18 to 22 months’ corrected age. The study’s primary hypothesis is that the growth status of ELBW infants at NICU discharge, as reflected by growth velocity (grams per kilogram per day for weight gain or centimeters per week for head circumference growth), is associated with neurodevelopmental outcome, growth percentile, and the incidence of rehospitalization at 18 to 22 months’ corrected age.

	MATERIALS AND METHODS

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The study cohort for this report is a subset of the NICHD Neonatal Research Network Growth Observational Study population.¹ Six hundred (86%) of the 695 infants 501 to 1000 g birth weight who participated in that study survived and were discharged from network NICUs. The families of those infants were invited to participate in network ELBW follow-up programs for a comprehensive assessment at 18 to 22 months’ corrected age. Although 495 (83%) of the eligible infants were evaluated, sufficient growth data were only available to calculate growth velocities on 490 infants; early back transfer accounted for the insufficient growth data. In addition, length and head circumference growth data were not available for 1 infant from whom weight gain data were available. The Growth Observational Study was a prospective, cohort study that collected anthropometric data on 1660 infants 501 to 1500 g birth weight.¹ Infants were admitted at 24 hours of age to 1 of the network centers between August 31, 1994, and August 9, 1995, survived at least 168 hours, and were free of major congenital malformations. Body weight was recorded daily for a minimum of 14 days or until birth weight was regained, whichever occurred later, and then weekly. Recumbent length and head circumference were determined weekly. Trained research nurses performed these anthropometric measurements as previously described¹ and abstracted study data, including information about maternal and neonatal demographics, selected morbidities, clinical conditions, and nutritional practices, until discharge, transfer, death, or 120 days after birth, whichever came first, using previously described definitions.^2,11,12

For this report, growth velocity was calculated for the period between the time that the infant regained birth weight and discharge, transfer, age 120 days, or until a body weight of 2000 g was reached, a time point that is referred to as "status."¹ Infants within each 100-g birth weight interval from 501 to 1000 g were then divided into quartiles of in-hospital growth velocity rates. Thus, by design, a similar number of infants from each birth weight interval were assigned to each growth velocity quartile of the follow-up cohort. The birth weight distribution of the study population is displayed in Table 1.

The specific aims of this project are to determine if at 18 to 22 months’ corrected age, compared with infants in the lowest growth velocity quartile: (1) ELBW infants in the highest weight gain quartile have a lower incidence of Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores <70, cerebral palsy (CP), neurodevelopmental impairment (NDI), rehospitalization, and growth (weight, length, and head circumference) below the 10th percentile; (2) ELBW infants in the highest head circumference growth quartile have a lower incidence of MDI and PDI scores <70, CP, and NDI; and (3) that the association between growth velocity and outcome persist after adjusting for demographic and clinical factors that influence outcome. NDI was defined as the presence of any of the following: CP, Bayley MDI <70, Bayley PDI <70, deaf/hearing loss requiring amplification in both ears, or bilaterally blind.

Statistical Analyses
For the purpose of this report, the growth velocity was treated as a 4-level categorical variable that indicated the quartile into which an infant’s growth velocity fell. Neurodevelopmental and growth outcomes and rehospitalization were treated as binary variables. Associations between these variables and growth velocity quartile, maternal and neonatal variables, and in-hospital morbidities were explored. Variables included in these analyses were gender, race, gestational age, small for gestational age (SGA) at birth, mother’s education, age at regaining birth weight, proven necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH) grades 3 and 4, periventricular leukomalacia (PVL), late-onset infection, bronchopulmonary dysplasia ([BPD] oxygen therapy at 36 weeks’ PMA), and postnatal steroid therapy for pulmonary disease. Statistical significance (P < .05) was determined by the Kruskal-Wallis test for continuous variables and by ² (Mantel-Haenszel ² or Pearson ²) or Fisher’s exact tests for categorical variables, as appropriate. Adjusted relationships were evaluated using logistic-regression models to fit the binary outcomes and to identify associations between growth at status and neurodevelopmental and growth outcomes and incidence of rehospitalizations at 18 to 22 months’ corrected age. Covariates included in the models were those variables with P .10 from the bivariate tests. All analyses were adjusted for center. The results were expressed as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were completed at RTI International (Research Triangle Park, NC) by using SAS software (SAS Institute, Inc, Cary, NC).

	RESULTS

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The characteristics of the infants in the follow-up cohort by weight gain quartile are displayed in Table 2. The average daily rate of weight gain between regaining birth weight and discharge increased from 12.0 to 21.2 g/kg per day from quartile 1 to quartile 4. The rate of length and head circumference growth within each of these weight gain quartiles both increased from 0.8 cm per week to 1.1 cm per week between quartile 1 and quartile 4. At status, body weight was significantly lower in quartile 1 than in the other quartiles, whereas length and head circumference measurements were similar. Because both the postnatal and postmenstrual ages at status fell significantly between quartile 1 and quartile 4, the differences in growth velocity are understandable. Although the overall percentages of the demographic characteristics and incidences of the selected morbidities are similar to that previously observed at NICHD Neonatal Research Network Centers during that time period,^2,11,12 they specifically reflect the characteristics of the infants included in the Growth Observational Study¹: 51% were female, 49% non-Hispanic blacks, 33% of their mothers had less than a high school education, 25% had severe IVH, 9% proven NEC, 65% late-onset sepsis (culture-positive plus culture-negative, but treated with antibiotics for 5 days), 40% BPD, and 48% were treated with postnatal steroids for pulmonary disease. However, in contrast to our earlier report, SGA in this study cohort was defined as birth weight <10th percentile for gender according to Alexander et al.⁵ As the rate of weight gain increased between quartile 1 and quartile 4, the incidence of proven NEC, late-onset infection, BPD, and postnatal steroid therapy for pulmonary disease significantly decreased, suggesting that the slowest growth velocity was experienced by the sickest infants. Interestingly, the mean age at regaining birth weight (defined as regaining birth weight and maintaining it for at least 2 days¹) was significantly lower in quartile 1 and significantly fewer infants in quartile 1 regained birth weight after 18 days of age (the mean age at which infants in the entire study population regained birth weight). However, because the length of time between the age that birth weight was regained and status was significantly lower in quartile 4, and because 13 (10%) infants in quartile 1 compared with 1 (0.8%) infant in quartile 4 never lost weight, we believe that differences in severity of illness and fluid management practices provide a probable explanation for this paradoxic observation.

	DISCUSSION

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Dusick et al¹⁵ previously reported on growth outcomes at 18 to 22 months’ corrected age in a cohort of ELBW infants cared for at NICHD Neonatal Research Network Centers in 1993–1994. Forty-six percent of the infants were below the 10th percentile for weight and 43% were below the 10th percentile for length and head circumference at 18 to 22 months’ corrected age. The likelihood of weight, length, and head circumference below the 10th percentile increased as birth weight fell. Additional factors related to poor growth included SGA, severe IVH/PVL, and abnormal swallow and abnormal neurologic examination at 18 to 22 months’ corrected age. The current report demonstrates that, in addition to birth weight, in-hospital growth velocity influenced the likelihood of weight, length, and head circumference measurements below the 10th percentile at 18 to 22 months’ corrected age.

As shown in Table 2, the infants who experienced the slowest growth velocity had the highest incidence of morbidities (proven NEC, late-onset infection, BPD, and postnatal steroid therapy for pulmonary disease) that affect the provision and use of nutritional support and growth potential. We previously reported that infants with major morbidities regained birth weight later and gained weight more slowly than infants without morbidities¹ and suggested that poorly nourished infants who were gaining weight slowly might be more prone to late-onset infection and to severe BPD. Others have suggested that the degree of undernutrition that occurs in many ELBW infants contributes to poor neurocognitive outcomes.¹⁶

The higher incidence of NEC in the infants in quartile 1 compared with the other quartiles (20% versus <7%) may have contributed to the slower rate of weight gain observed in infants in that quartile (Table 2). Others^17,18 have reported slower weight gain during the hospitalization in infants with NEC compared with those without NEC. In addition, growth after discharge seems to be related to the severity of NEC; Walsh¹⁷ reported that approximately one third of the infants with severe NEC had body weights that were >2 standard deviations below the mean at 8 months’ corrected age and head circumferences that were >2 standard deviations below the mean at 20 months’ corrected age. Also, Hintz¹⁹ recently reported that compared with infants without a history of NEC, infants who had NEC managed surgically were significantly more likely to have body weight, length, and head circumference measurements below the 10th percentile at 18 to 22 months’ corrected age; infants who had NEC managed medically had anthropometric measurements that were similar to the infants without a history of NEC. Furthermore, neurodevelopmental impairment has been observed more frequently in infants with severe NEC.^17–21 Because of a lack of significance in the bivariate test results, NEC was not included in either logistic-regression model (Tables 4 and 6) examining the relationship between growth and neurodevelopmental outcome.

Poor nutrition is considered a major contributing factor in the pathogenesis of BPD.²² The logistic-regression analyses demonstrated that BPD or postnatal steroid therapy for pulmonary disease were significantly associated with CP, MDI scores <70, PDI scores <70, and NDI (Tables 4 and 6). Vohr¹³ has previously reported logistic-regression analyses in which both BPD and postnatal steroids for pulmonary disease were significant risk factors associated with the likelihood of neurodevelopmental impairment. Furthermore, postnatal steroid therapy for prevention or treatment of BPD has been shown to reduce the rate of weight gain^23,24 and has been increasingly incriminated as a factor contributing to the development of CP and other neurodevelopmental impairments.^25–29

Previous investigators^30–32 have also reported an association between the severity of neonatal illness and postnatal head growth and have directly correlated head growth with neurodevelopmental outcome. In addition, infants with culture-positive and culture-negative infections are more likely than uninfected infants to have adverse neurodevelopmental outcomes at 18 to 22 months’ corrected age and to have a head circumference <10th percentile at 36 weeks’ postmenstrual age and at 18 to 22 months’ corrected age.³³ Our findings demonstrating an association between the incidence of poor neurodevelopmental outcomes and head circumference measurements below the 10th percentile at 18 to 22 months’ corrected age with the rate of in-hospital head circumference growth are consistent with those reports. Hack et al³⁴ have previously shown that the influence of subnormal head circumference growth persists and is associated with a greater risk of poor cognitive function at school age. Furthermore, the importance of postnatal body weight gain and head circumference growth were recently demonstrated by Latal-Hajnal and coworkers³⁵; they reported that the neurodevelopmental outcomes of preterm infants who were appropriate for gestational age at birth, but <10th percentile at 2 years of age were significantly worse than infants who were SGA at birth but >10th percentile at 2 years.

Conclusions drawn from these analyses are limited by the fact that although the NICU growth, morbidity, and follow-up data were collected prospectively in the Growth Observational Study, nutritional practices were not specified during the NICU hospitalization or postdischarge and vary widely between NICHD Neonatal Research Network Centers. In addition, management decisions relating to such practices as the timing of initiation and speed of advancement of enteral feedings were probably determined by the clinical team’s impression of an infant’s health; specifically, infants thought to be healthier might have been started on enteral feedings sooner and advanced more rapidly. As shown in Table 2, compared with quartile 1, infants in quartile 4 had lower incidences of proven NEC, late-onset infection, BPD, and postnatal steroid therapy for pulmonary disease, and thus may represent primarily healthier infants. Nonetheless, although infants in quartile 4 had the highest rate of weight gain, they seemed to regain birth weight later. However, as noted previously, the explanation for this apparent paradoxic observation probably relates to differences in severity of illness and management practices. Specifically, the higher rates of morbidities noted in quartile 1 compared with quartile 4 may have resulted in fluid management practices that led to fluid overload or edema, accounting for the observation that birth weight was never lost or regained earlier.³⁶ This observation emphasizes the importance of closely monitoring the rate of in-hospital growth once birth weight has been regained. Because weight gain of >18 g/kg per day and head circumference growth of >0.9 cm per week are associated with better neurodevelopmental and growth outcomes, if those rates falter, the infant’s diet should be reviewed and steps to ensure adequate nutritional support such as by increasing the dietary protein/energy ratio should be taken, if necessary.

	CONCLUSIONS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS PARTICIPANTS IN THE NICHD... REFERENCES

 
This project was designed to use prospectively collected NICU growth, morbidity, and long-term follow-up data from a large heterogeneous population of ELBW infants to examine the impact of in-hospital growth velocity on outcomes at 18 to 22 months’ corrected age. Bivariate analyses demonstrated that as the rate of weight gain increased, the incidence of CP, MDI and PDI scores <70, abnormal neurologic examination, and NDI and the need for rehospitalization fell significantly. Similar findings were observed as the rate of head circumference growth increased. The rate of weight gain was significantly associated with the likelihood of body weight and length measurements below the 10th percentile at 18 months’ corrected age, but not head circumference. The rate of head circumference growth was significantly associated with the likelihood of head circumference measurements below the 10th percentile at 18 months’ corrected age. In addition, logistic-regression models, adjusted for center, and controlled for variables present at birth or experienced during the hospitalization demonstrated that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental outcomes of ELBW infants at 18 to 22 months’ corrected age.

	PARTICIPANTS IN THE NICHD NEONATAL RESEARCH NETWORK (1995–1999)

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS PARTICIPANTS IN THE NICHD... REFERENCES

 
Participants in the NICHD Neonatal Research Network were: chairman, Alan Jobe, MD, PhD; University of Alabama (U10 HD34216): Waldemar A. Carlo, MD, Kathy Nelson, MD, and Monica V. Collins, RN; Case Western Reserve University (U10 HD21364): Avroy A. Fanaroff, MB, BCh, Maureen Hack, MD, Nancy Newman, RN, and Harriet Friedman, MA; University of Cincinnati (U10 HD27853, M01 RR 08084): Edward F. Donovan, MD, Jean J. Steichen, MD, Cathy Grisby, RN, and Tari Gratton, RN; Emory University (U10 HD27851): Barbara J. Stoll, MD, Neal Simon, MD, and Ellen Hale, RN; RTI International (U01 HD36790): W. Kenneth Poole, PhD, and Betty Hastings; Indiana University (U10 HD27856, M01 RR 00750): James A. Lemons, MD, Anna Dusick, MD, Diane Appel, RN, and Julie Ahlrichs, RN; University of Miami (U10 HD21397): Charles R. Bauer, MD, Amy Mur Worth, RN, and Wendy Griffin, RN; NICHD: Linda L. Wright, MD, and Elizabeth McClure, MEd; University of New Mexico (U10 HD27881, M01 RR 00997): Lu-Ann Papile, MD, Conra Backstom, RN, Jeanne Lowe, PhD, and Barbara Woodward, MPH, OTR/L; Stanford University (U10 HD27880, M01 RR 00070): David K. Stevenson, MD, Barry E. Fleisher, MD, and Bethany Ball, CCRC; University of Tennessee, Memphis (U10 HD21415): Sheldon B. Korones, MD, Henrietta Bada, MD, and Tina Hudson, RN; University of Texas Southwestern Medical Center (U10 HD21373): Jon E. Tyson, MD, MPH, Sue Broyles, MD, Susan Madison, RN, and Jackie Hickman, RN; Wayne State University (U10 HD21385): Seetha Shankaran, MD, Geraldine Muran, RN, and Rebecca Bara, RN; Yale University (U10 HD27871, M01 RR 06022): Richard A. Ehrenkranz, MD, Linda Mayes, MD, Patricia Gettner, RN, and Elaine Romano, MSN; Brigham and Woman’s Hospital (U10 HD34167, M01 RR 02635, M01 RR 02172, M01 RR 01032): Ann R. Stark, MD, Kerri Fournier, RN, and Stacy Dow, RN; and Brown University (U10 HD27904): William Oh, MD, Betty Vohr, MD, Angelita Hensman, RNC, and Terri Leach, MED.

	FOOTNOTES

 
Accepted Sep 13, 2005.

Address correspondence to Richard A. Ehrenkranz, MD, Department of Pediatrics, Yale University School of Medicine, 333 Cedar St, PO Box 208064, New Haven, CT 06520-8064. E-mail: richard.ehrenkranz{at}yale.edu

This work was presented in part at the annual meeting of the Pediatric Academic Societies; May 12–16, 2000; Boston, MA.

The authors have indicated they have no financial relationships relevant to this article to disclose.

	REFERENCES

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1. Ehrenkranz RA, Younes N, Lemons JA, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999;104 :280 –289[Abstract/Free Full Text]
2. Lemons JA, Bauer CR, Oh W, et al. Very-low-birth-weight outcomes of the NICHD Neonatal Research Network, January 1995 through December 1996. Pediatrics. 2001;107(1) . Available at: www.pediatrics.org/cgi/content/full/107/1/e1
3. Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics. 2001;107 :270 –273[Abstract/Free Full Text]
4. Cooke RJ, Ainsworth SB, Fenton AC. Postnatal growth retardation: a universal problem in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2004;89 :F428 –F430[Abstract/Free Full Text]
5. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol. 1996;87 :163 –168[Abstract]
6. Hay WW, Jr, Lucas A, Heird WC, et al. Workshop summary: nutrition of the extremely low birth weight infant. Pediatrics. 1999;104 :1360 –1368[Free Full Text]
7. Dobbing J. Nutritional growth restriction and the nervous system. In: Davison AN, Thompson RHS, eds. The Molecular Basis of Neuropathology. London, United Kingdom: Edward Arnold; 1981:231–233
8. Levitsky DA, Strupp BJ. Malnutrition and the brain: changing concepts, changing concerns. J Nutr. 1995;125 :2212S –2220S[Medline]
9. Grantham-McGregor S. A review of studies of the effect of severe malnutrition on mental development. J Nutr. 1995;125 :2233S –2238S[Medline]
10. Brown JL, Pollitt E. Malnutrition, poverty and intellectual development. Sci Am. 1996;274(2) :38 –43
11. Fanaroff AA, Wright LL, Stevenson DK, et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, May 1991 through December 1992. Am J Obstet Gynecol. 1995;173 :1423 –1431[CrossRef][ISI][Medline]
12. Stevenson DK, Wright LL, Lemons JA, et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1993 through December 1994. Am J Obstet Gynecol. 1998;179 :1632 –1639[CrossRef][ISI][Medline]
13. Vohr BR, Wright LL, Dusick AM, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994. Pediatrics. 2000;105 :1216 –1226[Abstract/Free Full Text]
14. Ogden CL, Kuczmarski RJ, Flegal KM, et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics. 2002;109 :45 –60[Abstract/Free Full Text]
15. Dusick AM, Poindexter BB, Ehrenkranz RA, Lemons JA. Growth failure in the preterm infant: can we catch up? Semin Perinatol. 2003;27 :302 –310[CrossRef][ISI][Medline]
16. Ziegler EE, Thureen PJ, Carlson SJ. Aggressive nutrition of the very low birth weight infant. Clin Perinatol. 2002;29 :225 –244[CrossRef][ISI][Medline]
17. Walsh MC, Kliegman RM, Hack M. Severity of necrotizing enterocolitis: influence on outcome at 2 years of age. Pediatrics. 1989;84 :808 –814[Abstract/Free Full Text]
18. Sonntag J, Grimmer I, Scholz T, Metze B, Wit J, Obladen M. Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis. Acta Paediatr. 2000;89 :528 –532[CrossRef][ISI][Medline]
19. Hintz SR, Kendrick DE, Stoll BJ, et al., for the NICHD Neonatal Research Network. Neurodevelopmental and growth outcome of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115 :696 –703[Abstract/Free Full Text]
20. Simon NP. Follow-up for infants with necrotizing enterocolitis. Clin Perinatol. 1994;21 :411 –424[ISI][Medline]
21. Salhab WA, Perlman JM, Silver L, Broyles RS. Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth weight infants < 1000 g. J Perinatol. 2004;24 :534 –540[CrossRef][Medline]
22. Frank L, Sosenko IRS. Undernutrition as a major contributing factor in the pathogenesis of bronchopulmonary dysplasia. Am Rev Respir Dis. 1988;138 :725 –729[ISI][Medline]
23. Papile LA, Tyson JE, Stoll BJ, et al. A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants. N Engl J Med. 1998;338 :1112 –1118[Abstract/Free Full Text]
24. Romagnoli C, Zecca E, Vento G, De Carolis MP, Papacci P, Tortorolo G. Early postnatal dexamethasone for the prevention of chronic lung disease in high risk infants. Intensive Care Med. 1999;25 :717 –721[CrossRef][ISI][Medline]
25. Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics. 1998;101(5) . Available at: www.pediatrics.org/cgi/content/full/101/5/e7
26. O’Shea TM, Kothadia JM, Klinepeter KL, et al. Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age. Pediatrics. 1999;104 :15 –21[Abstract/Free Full Text]
27. Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants [Cochrane review]. Cochrane Database Syst Rev. 2003;1 :CD00146
28. Halliday HL, Ehrenkranz RA, Doyle LW. Delayed postnatal (>3 weeks) postnatal corticiosteroids for chronic lung disease in preterm infants [Cochrane review]. Cochrane Database Syst Rev. 2003;1 :CD00145
29. AAP, Committee on Fetus and Newborn. Postnatal corticosteroids to treat or prevent lung disease in preterm infants. Pediatrics. 2002;109 :330 –338[Abstract/Free Full Text]
30. Georgieff MK, Hoffman JS, Pereira GR, Bernbaum J, Hoffman-Williamson M. Effect of neonatal caloric deprivation on head growth and 1-year developmental status in preterm infants. J Pediatr. 1985;107 :581 –587[CrossRef][ISI][Medline]
31. Gross SJ, Oehler JM, Eckerman CO. Head growth and developmental outcome in very low-birth-weight infants. Pediatrics. 1983;71 :70 –75[Abstract/Free Full Text]
32. Hack M, Breslau N, Fanaroff AA. Differential effects of intrauterine and postnatal growth failure in infants of very low birth weight. Am J Dis Child. 1989;143 :63 –68[Abstract]
33. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292 :2357 –2365[Abstract/Free Full Text]
34. Hack M, Breslau N, Weissman B, Aram D, Klein N, Borawski E. Effect of very low birth weight and subnormal head size on cognitive abilities at school age. N Engl J Med. 1991;325 :231 –237[Abstract]
35. Latal-Hajnal B, Von Siebenthal K, Kovari H, Bucher HU, Largo RM. Postnatal growth in VLBW infants: significant association with neurodevelopmental outcome. J Pediatr. 2003;143 :163 –170[ISI][Medline]
36. Oh W, Poindexter BB, Peritt R, et al. Association between fluid and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants. J Pediatr. 2005;147 :786 –790[CrossRef][ISI][Medline]

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				S. Kusuda, M. Fujimura, I. Sakuma, H. Aotani, K. Kabe, Y. Itani, H. Ichiba, K. Matsunami, H. Nishida, and for the Neonatal Research Network, Japan Morbidity and Mortality of Infants With Very Low Birth Weight in Japan: Center Variation Pediatrics, October 1, 2006; 118(4): e1130 - e1138. [Abstract] [Full Text] [PDF]

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