The challenge pays off: Early enhanced nutritional intake for VLBW small-for-gestation neonates improves long-term outcome

Abstract

See related article, p 463.Although advances in perinatal care have resulted in significant improvements in survival of very-low-birth-weight (VLBW) infants, survivors have remained at increased risk of less optimal growth and development. Infants with intrauterine growth restriction are known to be at increased risk of sequelae when compared with appropriate for gestation (AGA) controls. Neonates considered at double jeopardy for poor outcomes are infants born both prematurely and with intrauterine growth restriction. Adequate provision of nutrition both in the intrauterine environment and in the neonatal unit has been considered key to the premature infant's recovery and intact survival, although controversies remain regarding what and how to feed the VLBW infant.The need for adequate nutrition for premature infants has been recognized by the Academy of Pediatrics Committee on Nutrition, which has recommended that sufficient nutrients be provided to support rates of growth and nutrient accretion equal to intrauterine rates.1American Academy of Pediatrics Committee on Nutrition Nutritional needs of preterm infants.in: Pediatric nutrition handbook. 4th ed. : American Academy of Pediatrics, Elk Grove Village (IL)1998: 55-87Google Scholar This has been a challenge for neonatologists because VLBW infants do not tolerate enteral intake to meet their needs for the first 2 to 3 weeks after birth and often longer. As a result, premature infants incur significant deficits before achieving sufficient intake to support growth. Today, parenteral nutrition provides essential nutrition support until infants reach full enteral feedings of fortified breast milk or premature formula. Variations in practice regarding implementation of parenteral and enteral feedings (for example, when they are started and how they are advanced) may affect growth,2Olsen IE Richardson DK Schmid CH Ausman LM Dwyer JT. Intersite differences in weight growth velocity of extremely premature infants.Pediatrics. 2002; 110: 1125-1132Crossref PubMed Scopus (141) Google Scholar, 3Carlson SJ Ziegler EE. Nutrient intakes and growth of very low birth weight infants.J Perinatol. 1998; 18: 252-258PubMed Google Scholar and nutrient deficits are likely to occur with current recommendations.4Embleton NE Pang N Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants?.Pediatrics. 2001; 107: 270-273Crossref PubMed Scopus (590) Google Scholar As a result of these findings, early, aggressive parenteral and enteral nutrition have recently been advocated to prevent postnatal nutrient and calorie deficits.5Thureen PJ Henderson AH Baron KA Melara DL Hay WW Fennessey P. Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition.Am J Clin Nutr. 1998; 68: 1128-1135PubMed Google Scholar Consequences of nutrition deficits on outcome remain uncertain and have been difficult to document because neurodevelopment of preterm infants is a composite of multiple factors including genetics, morbidities such as intraventricular hemorrhage and periventricular leukomalacia, chronic lung disease, environmental factors, health status, and nutritional intake.Ehrenkranz et al6Ehrenkranz RA Younes N Lemons JA Fanaroff AA Donovan EF Wright LL et al.Longitudinal growth of hospitalized very low birth weight infants.Pediatrics. 1999; 104: 280-289Crossref PubMed Scopus (677) Google Scholar reported growth data from the National Institute of Child Health and Human Development Neonatal Research Network Centers for VLBW infants born in 1994 and 1995, showing that the majority of AGA VLBW infants become growth-restricted infants with growth parameters below the 10th percentile by 36 weeks' corrected age. Similar growth curves were identified for length and head circumference in the neonatal intensive care unit (NICU), and essentially the entire cohort of VLBW infants had “postnatal growth restriction.” The mean age that birth weight was regained was 14.4 to 17.2 days for infants <1000 g and 11.5 to 13.2 days for infants 1000 to 1500 g. This is significant, because growth rates approximating intrauterine growth cannot be achieved until after birth weight is regained. Therefore, to eventually “catch up,” rates of growth higher than intrauterine rates are needed. The neonatal environmental impact on growth, relative to growth standards, was even worse for small for gestation (SGA) infants. Neonatologists have responded to the difficulties of providing adequate enteral nutrition to extremely-low-birth-weight (ELBW) infants as a challenge, and in recent years, increasing attention has been given to nutritional management in the NICU.In addition, there is growing evidence that malnutrition during critical periods of central nervous system development will result in irreversible long-term brain deficits.7Dobbing J Sands J. Comparative aspects of the brain growth spurt.Early Hum Dev. 1970; 3: 79-83Abstract Full Text PDF Scopus (2134) Google Scholar The premature infant grows and develops in a stressful extrauterine environment (the NICU) during a critical period of brain development. Follow-up studies have shown that VLBW infants are at increased risk of developmental delays and learning disabilities that cannot be accounted for by intraventricular hemorrhage, perivalvular leakage, or ventriculomegaly. There is some evidence pointing to nutrition as being the important missing link.What is the evidence for links between nutrition, growth, and outcome for VLBW infants? When Ehrenkranz et al6Ehrenkranz RA Younes N Lemons JA Fanaroff AA Donovan EF Wright LL et al.Longitudinal growth of hospitalized very low birth weight infants.Pediatrics. 1999; 104: 280-289Crossref PubMed Scopus (677) Google Scholar compared the growth curves of infants who received their first enteral feeds at the median age, or earlier, to infants who started receiving enteral feeds later than the median age, the infants who started earlier gained weight faster. In addition, infants who received full enteral nutrition sooner gained weight faster. Lucas et al8Lucas A Morley R Cole TJ Gore SM Lucas PJ Crowle P et al.Early diet in preterm babies and developmental status at 18 months.Lancet. 1990; 335: 1477-1481Abstract PubMed Scopus (351) Google Scholar, 9Lucas A Morley R Cole TJ. Randomized trial of early diet in preterm babies and later intelligence quotient.BMJ. 1998; 317: 1481-1487Crossref PubMed Scopus (526) Google Scholar demonstrated the relationship between higher nutrient intake for VLBW infants in the NICU and more optimal neurodevelopmental outcome, whereas Georgieff et al10Georgieff MK Hoffmann 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: 581-587Abstract Full Text PDF PubMed Scopus (77) Google Scholar demonstrated that early caloric deprivation (<85 kcal/kg/day) was directly related to slow head growth and lower developmental scores at 1 year of corrected age in a cohort of premature AGA and SGA infants. Hack et al11Hack M Breslan N Faranoff AA. Differential effects on intrauterine and postnatal brain growth failure in infants of very low birth weight.Am J Dis Child. 1989; 143: 63-68PubMed Google Scholar reported that 25% of SGA VLBW infants and 14% of AGA VLBW infants had a subnormal head circumference at 8 months' corrected age. Subnormal head size at 8 months was independently associated with a low 20-month Bayley Mental Development Index for AGA infants in multivariate analyses. SGA subnormal head size, however, was not associated with a low MDI when neonatal illness, neurologic impairment, socioeconomic status, and race were added to the model, reminding us that multiple factors contribute to development. Recent magnetic resonance imaging studies show that VLBW survivors have significantly smaller cortical white and gray matter brain volumes at 8 years of age compared with term controls, and that these decreases in brain cortical volume are associated with lower cognitive test scores.12Peterson BS Vohr B Staib LH Cannistraci CJ Dolberg A Schneider KC et al.Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.JAMA. 2000; 284: 1939-1947Crossref PubMed Scopus (785) Google Scholar This decrease in brain volume cannot be accounted for by brain injury.The longitudinal study of the growth and development of SGA VLBW infants reported by Brandt et al13Brandt I Stickee EJ Lentze MJ. Catch-up growth of head circumference of very-low-birth-weight small-for-gestational age preterm infants and mental development to adulthood.J Pediatr. 2003; 142: 463-468Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar in this issue of The Journal is remarkable because of the study design and the findings. First, caloric data were collected during the first 10 days of life for SGA and AGA VLBW infants. Second, sequential growth data were collected from birth to 23 years of age. Third, serial developmental and intelligence tests were performed on the study population. The SGA infants in this study, primarily infants with symmetric growth restriction, were divided into 2 study samples on the basis of whether there was head growth catch-up similar to AGA controls at 12 months' corrected age. During the study period both early feeding (3-6 hours after birth vs 24 hours) and higher-energy intake feeding were introduced to the nurseries. SGA infants receiving the new feeding protocol were significantly more likely to have head growth catch-up, and their caloric energy quotients were consistently higher between days 2 and 10 of life.There are a few aspects of the Brandt et al13Brandt I Stickee EJ Lentze MJ. Catch-up growth of head circumference of very-low-birth-weight small-for-gestational age preterm infants and mental development to adulthood.J Pediatr. 2003; 142: 463-468Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar study design, however, that need to be considered if we wish to extrapolate their findings to the current NICU populations. First, the infants in the study sample were more mature and less medically compromised than ELBW survivors currently. Therefore, they may have had an easier time achieving head growth catch-up. Second, we need to consider the feeding protocol because it was an essential part of the study design. The investigators report starting a feeding protocol14Davies PA Robinson RJ Scopes JW Tizard JPM Wigglesworth JS. Feeding the low-birthweight infant.in: Medical care of newborn babies. Clinics in developmental medicine, Nos. 44/45. : William Heinemann Medical Books Ltd, London (UK)1972: 96-98Google Scholar for infants born between 1972 and 1975, which was used to feed infants earlier and with a higher energy intake than had been done with infants born before 1972. The protocol was not described further. The study formula used was “Humana 0” formula (Humana GmbH, D-32051, Herford). It contained 75 kcal/100 mL (or 22.5 kcal/oz) and provided 2.3 g protein/100 mL (or 3.07 g protein/100 kcal)—a protein content similar to today's formulas for premature infants. Today's fortified breast milk or preterm formulas at 24 kcal/oz and 150 mL/kg/day will provide 120 kcal/kg/day, as well as an appropriate nutrient intake for the healthy, preterm infant. The age at which 24 kcal/oz formula is introduced varies but ranges from the start of enteral feedings to after full enteral feedings are attained. Additional calories or nutrients may be added to breast milk or formula, as appropriate, to support growth and development of premature infants with increased calorie or nutrient needs after infants are receiving full enteral feedings and well past the 10th day of life. It is unclear whether all study infants were exclusively receiving formula or whether some were receiving breast milk. The use and composition of parenteral nutrition was not described. If intravenous solutions were used, were they just dextrose water or a more complete parenteral nutrition with dextrose, protein, lipid, vitamins, and minerals? Without information about the parenteral intake, it difficult to understand the role of enteral versus parenteral feedings in calorie or nutrient intake. With that information, it might be possible to posit the role of protein as well as calories. Although calories are important, protein intake may also have played a role in the results. And, protein may play an even greater role for micropreemies than for the study infants because protein stores in micropreemies are limited and combined with inadequate nutrition, leave the infant more vulnerable to poor muscle growth to support breathing and to decreased availability of amino acids needed for glucose utilization, immune system functioning, brain development, and somatic growth.The remarkable finding, however, was that not only did the SGA head catch-up group have developmental quotients significantly higher than the SGA no-catch-up group between 2 years and 6 years of age, but the caloric energy quotients between 2 and 4 days and 2 and 10 days correlated with the children's developmental/intelligence quotients between 18 months and 6 years. Correlations did not persist at the 23-year visit, when presumably greater variance is secondary to social and environmental factors. It is unclear whether the study findings were a result of increased calorie intake alone or increased calorie intake with increased protein intake.What is remarkable is that very early postnatal energy intake in the first 10 days of life was so significant for SGA preterm infants. These data indicate that there appears to be a critical window of nutritional opportunity for both brain growth and brain function and that early postnatal high energy nutrient intake in the first 10 days of life promotes head growth and prevents the consequences of poor nutrition for SGA VLBW infants. Although changes in nutritional management in the NICU have obviously occurred since the last patients were enrolled in 1975, the study by Brandt et al13Brandt I Stickee EJ Lentze MJ. Catch-up growth of head circumference of very-low-birth-weight small-for-gestational age preterm infants and mental development to adulthood.J Pediatr. 2003; 142: 463-468Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar opens the door for further prospective investigations of early nutrient intake and the opportunity for improved outcomes for ELBW infants. See related article, p 463. Although advances in perinatal care have resulted in significant improvements in survival of very-low-birth-weight (VLBW) infants, survivors have remained at increased risk of less optimal growth and development. Infants with intrauterine growth restriction are known to be at increased risk of sequelae when compared with appropriate for gestation (AGA) controls. Neonates considered at double jeopardy for poor outcomes are infants born both prematurely and with intrauterine growth restriction. Adequate provision of nutrition both in the intrauterine environment and in the neonatal unit has been considered key to the premature infant's recovery and intact survival, although controversies remain regarding what and how to feed the VLBW infant. The need for adequate nutrition for premature infants has been recognized by the Academy of Pediatrics Committee on Nutrition, which has recommended that sufficient nutrients be provided to support rates of growth and nutrient accretion equal to intrauterine rates.1American Academy of Pediatrics Committee on Nutrition Nutritional needs of preterm infants.in: Pediatric nutrition handbook. 4th ed. : American Academy of Pediatrics, Elk Grove Village (IL)1998: 55-87Google Scholar This has been a challenge for neonatologists because VLBW infants do not tolerate enteral intake to meet their needs for the first 2 to 3 weeks after birth and often longer. As a result, premature infants incur significant deficits before achieving sufficient intake to support growth. Today, parenteral nutrition provides essential nutrition support until infants reach full enteral feedings of fortified breast milk or premature formula. Variations in practice regarding implementation of parenteral and enteral feedings (for example, when they are started and how they are advanced) may affect growth,2Olsen IE Richardson DK Schmid CH Ausman LM Dwyer JT. Intersite differences in weight growth velocity of extremely premature infants.Pediatrics. 2002; 110: 1125-1132Crossref PubMed Scopus (141) Google Scholar, 3Carlson SJ Ziegler EE. Nutrient intakes and growth of very low birth weight infants.J Perinatol. 1998; 18: 252-258PubMed Google Scholar and nutrient deficits are likely to occur with current recommendations.4Embleton NE Pang N Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants?.Pediatrics. 2001; 107: 270-273Crossref PubMed Scopus (590) Google Scholar As a result of these findings, early, aggressive parenteral and enteral nutrition have recently been advocated to prevent postnatal nutrient and calorie deficits.5Thureen PJ Henderson AH Baron KA Melara DL Hay WW Fennessey P. Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition.Am J Clin Nutr. 1998; 68: 1128-1135PubMed Google Scholar Consequences of nutrition deficits on outcome remain uncertain and have been difficult to document because neurodevelopment of preterm infants is a composite of multiple factors including genetics, morbidities such as intraventricular hemorrhage and periventricular leukomalacia, chronic lung disease, environmental factors, health status, and nutritional intake. Ehrenkranz et al6Ehrenkranz RA Younes N Lemons JA Fanaroff AA Donovan EF Wright LL et al.Longitudinal growth of hospitalized very low birth weight infants.Pediatrics. 1999; 104: 280-289Crossref PubMed Scopus (677) Google Scholar reported growth data from the National Institute of Child Health and Human Development Neonatal Research Network Centers for VLBW infants born in 1994 and 1995, showing that the majority of AGA VLBW infants become growth-restricted infants with growth parameters below the 10th percentile by 36 weeks' corrected age. Similar growth curves were identified for length and head circumference in the neonatal intensive care unit (NICU), and essentially the entire cohort of VLBW infants had “postnatal growth restriction.” The mean age that birth weight was regained was 14.4 to 17.2 days for infants <1000 g and 11.5 to 13.2 days for infants 1000 to 1500 g. This is significant, because growth rates approximating intrauterine growth cannot be achieved until after birth weight is regained. Therefore, to eventually “catch up,” rates of growth higher than intrauterine rates are needed. The neonatal environmental impact on growth, relative to growth standards, was even worse for small for gestation (SGA) infants. Neonatologists have responded to the difficulties of providing adequate enteral nutrition to extremely-low-birth-weight (ELBW) infants as a challenge, and in recent years, increasing attention has been given to nutritional management in the NICU. In addition, there is growing evidence that malnutrition during critical periods of central nervous system development will result in irreversible long-term brain deficits.7Dobbing J Sands J. Comparative aspects of the brain growth spurt.Early Hum Dev. 1970; 3: 79-83Abstract Full Text PDF Scopus (2134) Google Scholar The premature infant grows and develops in a stressful extrauterine environment (the NICU) during a critical period of brain development. Follow-up studies have shown that VLBW infants are at increased risk of developmental delays and learning disabilities that cannot be accounted for by intraventricular hemorrhage, perivalvular leakage, or ventriculomegaly. There is some evidence pointing to nutrition as being the important missing link. What is the evidence for links between nutrition, growth, and outcome for VLBW infants? When Ehrenkranz et al6Ehrenkranz RA Younes N Lemons JA Fanaroff AA Donovan EF Wright LL et al.Longitudinal growth of hospitalized very low birth weight infants.Pediatrics. 1999; 104: 280-289Crossref PubMed Scopus (677) Google Scholar compared the growth curves of infants who received their first enteral feeds at the median age, or earlier, to infants who started receiving enteral feeds later than the median age, the infants who started earlier gained weight faster. In addition, infants who received full enteral nutrition sooner gained weight faster. Lucas et al8Lucas A Morley R Cole TJ Gore SM Lucas PJ Crowle P et al.Early diet in preterm babies and developmental status at 18 months.Lancet. 1990; 335: 1477-1481Abstract PubMed Scopus (351) Google Scholar, 9Lucas A Morley R Cole TJ. Randomized trial of early diet in preterm babies and later intelligence quotient.BMJ. 1998; 317: 1481-1487Crossref PubMed Scopus (526) Google Scholar demonstrated the relationship between higher nutrient intake for VLBW infants in the NICU and more optimal neurodevelopmental outcome, whereas Georgieff et al10Georgieff MK Hoffmann 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: 581-587Abstract Full Text PDF PubMed Scopus (77) Google Scholar demonstrated that early caloric deprivation (<85 kcal/kg/day) was directly related to slow head growth and lower developmental scores at 1 year of corrected age in a cohort of premature AGA and SGA infants. Hack et al11Hack M Breslan N Faranoff AA. Differential effects on intrauterine and postnatal brain growth failure in infants of very low birth weight.Am J Dis Child. 1989; 143: 63-68PubMed Google Scholar reported that 25% of SGA VLBW infants and 14% of AGA VLBW infants had a subnormal head circumference at 8 months' corrected age. Subnormal head size at 8 months was independently associated with a low 20-month Bayley Mental Development Index for AGA infants in multivariate analyses. SGA subnormal head size, however, was not associated with a low MDI when neonatal illness, neurologic impairment, socioeconomic status, and race were added to the model, reminding us that multiple factors contribute to development. Recent magnetic resonance imaging studies show that VLBW survivors have significantly smaller cortical white and gray matter brain volumes at 8 years of age compared with term controls, and that these decreases in brain cortical volume are associated with lower cognitive test scores.12Peterson BS Vohr B Staib LH Cannistraci CJ Dolberg A Schneider KC et al.Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.JAMA. 2000; 284: 1939-1947Crossref PubMed Scopus (785) Google Scholar This decrease in brain volume cannot be accounted for by brain injury. The longitudinal study of the growth and development of SGA VLBW infants reported by Brandt et al13Brandt I Stickee EJ Lentze MJ. Catch-up growth of head circumference of very-low-birth-weight small-for-gestational age preterm infants and mental development to adulthood.J Pediatr. 2003; 142: 463-468Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar in this issue of The Journal is remarkable because of the study design and the findings. First, caloric data were collected during the first 10 days of life for SGA and AGA VLBW infants. Second, sequential growth data were collected from birth to 23 years of age. Third, serial developmental and intelligence tests were performed on the study population. The SGA infants in this study, primarily infants with symmetric growth restriction, were divided into 2 study samples on the basis of whether there was head growth catch-up similar to AGA controls at 12 months' corrected age. During the study period both early feeding (3-6 hours after birth vs 24 hours) and higher-energy intake feeding were introduced to the nurseries. SGA infants receiving the new feeding protocol were significantly more likely to have head growth catch-up, and their caloric energy quotients were consistently higher between days 2 and 10 of life. There are a few aspects of the Brandt et al13Brandt I Stickee EJ Lentze MJ. Catch-up growth of head circumference of very-low-birth-weight small-for-gestational age preterm infants and mental development to adulthood.J Pediatr. 2003; 142: 463-468Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar study design, however, that need to be considered if we wish to extrapolate their findings to the current NICU populations. First, the infants in the study sample were more mature and less medically compromised than ELBW survivors currently. Therefore, they may have had an easier time achieving head growth catch-up. Second, we need to consider the feeding protocol because it was an essential part of the study design. The investigators report starting a feeding protocol14Davies PA Robinson RJ Scopes JW Tizard JPM Wigglesworth JS. Feeding the low-birthweight infant.in: Medical care of newborn babies. Clinics in developmental medicine, Nos. 44/45. : William Heinemann Medical Books Ltd, London (UK)1972: 96-98Google Scholar for infants born between 1972 and 1975, which was used to feed infants earlier and with a higher energy intake than had been done with infants born before 1972. The protocol was not described further. The study formula used was “Humana 0” formula (Humana GmbH, D-32051, Herford). It contained 75 kcal/100 mL (or 22.5 kcal/oz) and provided 2.3 g protein/100 mL (or 3.07 g protein/100 kcal)—a protein content similar to today's formulas for premature infants. Today's fortified breast milk or preterm formulas at 24 kcal/oz and 150 mL/kg/day will provide 120 kcal/kg/day, as well as an appropriate nutrient intake for the healthy, preterm infant. The age at which 24 kcal/oz formula is introduced varies but ranges from the start of enteral feedings to after full enteral feedings are attained. Additional calories or nutrients may be added to breast milk or formula, as appropriate, to support growth and development of premature infants with increased calorie or nutrient needs after infants are receiving full enteral feedings and well past the 10th day of life. It is unclear whether all study infants were exclusively receiving formula or whether some were receiving breast milk. The use and composition of parenteral nutrition was not described. If intravenous solutions were used, were they just dextrose water or a more complete parenteral nutrition with dextrose, protein, lipid, vitamins, and minerals? Without information about the parenteral intake, it difficult to understand the role of enteral versus parenteral feedings in calorie or nutrient intake. With that information, it might be possible to posit the role of protein as well as calories. Although calories are important, protein intake may also have played a role in the results. And, protein may play an even greater role for micropreemies than for the study infants because protein stores in micropreemies are limited and combined with inadequate nutrition, leave the infant more vulnerable to poor muscle growth to support breathing and to decreased availability of amino acids needed for glucose utilization, immune system functioning, brain development, and somatic growth. The remarkable finding, however, was that not only did the SGA head catch-up group have developmental quotients significantly higher than the SGA no-catch-up group between 2 years and 6 years of age, but the caloric energy quotients between 2 and 4 days and 2 and 10 days correlated with the children's developmental/intelligence quotients between 18 months and 6 years. Correlations did not persist at the 23-year visit, when presumably greater variance is secondary to social and environmental factors. It is unclear whether the study findings were a result of increased calorie intake alone or increased calorie intake with increased protein intake. What is remarkable is that very early postnatal energy intake in the first 10 days of life was so significant for SGA preterm infants. These data indicate that there appears to be a critical window of nutritional opportunity for both brain growth and brain function and that early postnatal high energy nutrient intake in the first 10 days of life promotes head growth and prevents the consequences of poor nutrition for SGA VLBW infants. Although changes in nutritional management in the NICU have obviously occurred since the last patients were enrolled in 1975, the study by Brandt et al13Brandt I Stickee EJ Lentze MJ. Catch-up growth of head circumference of very-low-birth-weight small-for-gestational age preterm infants and mental development to adulthood.J Pediatr. 2003; 142: 463-468Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar opens the door for further prospective investigations of early nutrient intake and the opportunity for improved outcomes for ELBW infants. Catch-up growth of head circumference of very low birth weight, small for gestational age preterm infants and mental development to adulthoodThe Journal of PediatricsVol. 142Issue 5PreviewObjective To examine the influence of postnatal energy quotient (EQ, energy intake/kg body weight per day) on head circumference (HC) growth and mental development of very low birth weight (VLBW), small for gestational age (SGA, <10th percentile) preterm infants. Study design SGA VLBW preterm infants (n = 46) with primarily symmetric intrauterine growth restriction were compared with 62 appropriate for gestational age (AGA) VLBW preterm infants and 73 term infants from the Bonn Longitudinal study. Full-Text PDF