PEDIATRICS Vol. 120 No. 6 December 2007, pp. 1286-1296 (doi:10.1542/10.1542/peds.2007-0545)
ARTICLE |
Effects of Two Different Doses of Amino Acid Supplementation on Growth and Blood Amino Acid Levels in Premature Neonates Admitted to the Neonatal Intensive Care Unit: A Randomized, Controlled Trial
a Pediatrix Medical Group, Sunrise, Florida
b Pediatrix Analytical, Bridgeville, Pennsylvania
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
OBJECTIVES. The goal was to measure the effects of 2 distinct strategies for parenteral nutrition on neonatal growth and blood amino acid profiles.
METHODS. In a multicenter trial (n = 11 sites), we randomly allocated premature (23–29 weeks and 6 days of gestation) neonates to 1 of 2 approaches to intravenous amino acid administration. In one group, amino acid supplementation was started at 1.0 g/kg per day and advanced by 0.5 g/kg per day to a maximum of 2.5 g/kg per day (2.5 g/kg per day group). The other group received amino acids starting at 1.5 g/kg per day and advancing by 1.0 g/kg per day to a maximum of 3.5 g/kg per day (3.5 g/kg per day group). Filter paper blood spots were obtained from each infant on the day of random assignment and on days 7 and 28 of age, to monitor blood amino acid levels.
RESULTS. We enrolled 122 neonates (64 in the 3.5 g/kg per day group and 58 in the 2.5 g/kg per day group). There were no differences in demographic or baseline characteristics between the 2 treatment groups. There was no significant difference in growth by day 28 after birth (median weight gain: 12.9 and 11.4 g/kg per day for the 3.5 and 2.5 g/kg per day groups, respectively), and the incidences of secondary morbidities were similar in the 2 groups. On day 7, blood levels of several amino acids and the serum urea nitrogen level were higher in the 3.5 g/kg per day group, compared with the 2.5 g/kg per day group; none of the amino acid levels were lower.
CONCLUSIONS. Higher doses of amino acid supplementation did not improve neonatal growth and were associated with increased blood amino acid and urea nitrogen levels.
Key Words: neonates • parenteral nutrition • amino acids • acylcarnitines • nutrition
Studies have indicated that premature neonates often develop severe nutritional deficits during the first weeks after birth,1–5 and inhibited growth during the early postnatal period has been associated with poor long-term outcomes.2,5,6 Variations in dietary intake may account for 45% of the variations in growth.7,8 As a result, efforts have focused on determining whether nutritional deficiency and growth restriction in premature infants can be prevented through better nutritional intake.6,9,10
On the basis of animal studies that showed high levels of in utero amino acid flux during the later phases of gestation, several authors have suggested that higher doses of amino acid supplementation may minimize extrauterine growth restriction and enhance the outcomes of very low birth weight infants.9–11 Although standard doses of amino acids may be inadequate to promote normal growth, higher doses may lead to elevated blood amino acid levels and increased toxicity. Given the limited metabolic capacity of very low birth weight infants, excess administration of amino acids (protein) may result in saturation of both catabolic and anabolic pathways of protein metabolism, leading to larger amino acid pools for longer periods of time. Through the implementation of a multicenter randomized trial and tandem mass spectrometric analysis of key amino acids from dried filter paper blood spots, the effects of 2 distinct strategies for amino acid supplementation on amino acid profiles and growth in premature infants were evaluated.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Study Subjects
Eligible infants had estimated gestational ages between 23 weeks 0 days and 29 weeks and 6 days, were inborn, and had parental consent for participation in the study. Patients were approached for random assignment during the first 48 hours after birth and were excluded if they were >48 hours of age or had a major congenital anomaly. Investigational review boards of each hospital (n = 11) approved the protocol.
Random Assignment and Blinding
We used an electronic system to assign a randomized code, which was delivered to the health care provider responsible for preparing parenteral nutrition. That individual used the random assignment code to determine the treatment assignment and mixed the parenteral solution according to study and pharmacy protocols. The parenteral nutrition solution was labeled "study AA," and the concentrations of amino acids were not indicated on the bag. A pharmacy log tracked the amounts of amino acids in the solution for each patient. This approach blinded the clinical care staff members to the amount of amino acid supplementation that each neonate received. Random assignment was stratified according to site.
Treatment
For the group with a maximal dose of 2.5 g/kg per day (2.5 g/kg per day group), amino acid supplementation was started at 1.0 g/kg per day and advanced 0.5 g/kg per day to a maximum of 2.5 g/kg per day on day 4 of treatment. For the group with a maximal dose of 3.5 g/kg per day (3.5 g/kg per day group), amino acid supplementation started at 1.5 g/kg per day of amino acids and advanced 1 g/kg per day to a maximum of 3.5 g/kg per day on day 3 of treatment.
When enteral feedings were started, parenteral supplementation of amino acids continued, with the goal of delivering the maximal dose of amino acids allowed by the protocol. As feedings were advanced, intravenous fluids were decreased accordingly, to keep total fluids at 
150 mL/kg per day. Parenteral nutrition was mixed to provide the maximal amount of protein allowed by the protocol. As feedings were advanced, the total amount of protein per kilogram per day increased as a result of the protein in the enteral feedings. When the parenteral nutrition was being administered at a rate of <70 mL/kg per day, the amount of amino acids that could be added to the parenteral nutrition decreased (limited by the solubility of the elements in the parenteral nutrition). Therefore, when feedings reached 80 to 100 mL/kg per day, we decreased amino acid supplementation to 1 g/kg per day for the 2.5 g/kg per day group and to 2.0 g/kg per day for the 3.5 g/kg per day group. For both groups, amino acid supplementation was stopped when feedings reached 100 to 130 mL/kg per day. When enteral nutrition was at the level of 100 to 130 mL/kg per day, the patient was considered to have completed treatment. Subsequent parenteral nutrition was administered at the discretion of the health care team.
Nutritional Support Guidelines
We recommended starting parenteral lipid administration at the same time that the study amino acid supplementation was started, beginning at a rate of 0.5 g/kg per day and advancing 0.5 g/kg per day to a maximum of 3.5 g/kg per day.12–14 We discouraged the use of insulin and recommended limiting the glucose infusion rate to 8 to 12 mg/kg per minute as tolerated. Although the quantity and quality of enteral nutritional support were not structured in this trial, we offered the following feeding guidelines, in an attempt to maintain consistency: small-volume (<10 mL/kg per day) feedings should begin within the first week of life; low-dose dopamine treatment (defined as <5 µg/kg per minute) was not considered a contraindication for trophic feedings; feedings could be initiated even if umbilical catheters were in place; feedings could be advanced at a rate of as much as 30 mL/kg per day and were not to be advanced at a rate of <10 mL/kg per day; and 150 mL/kg per day, with consistent weight gain of 20 to 30 g/kg per day, was considered adequate nutrition.
Study End Points
Our primary outcome measure was growth, assessed as changes in weight, length, and head circumference over the first 28 days after birth. Weight gain was calculated as weight gain (in grams per kilograms per day) = (weight at 28 days – birth weight) divided by birth weight divided by 28 days. We also assessed length and head growth changes in centimeters per week, as (measurement at 28 days – measurement at birth) divided by 4 weeks.
Secondary outcome measures included blood amino acid profiles and incidence of major morbidities during the first 28 days after birth. Blood amino acid profiles were obtained on the day of random assignment (usually day 1) and on day 7 (parenteral phase of nutrition) and day 28 (enteral phase of nutrition) of life.
Data Collection and Monitoring
All information was collected by using an Internet-based case report form that could not be finalized until all required fields were completed. Site visits were conducted to monitor the accuracy of data collection and adherence to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use good clinical practice guidelines.
Study logs of amino acid contents in the parenteral nutrition were maintained for each subject for the first 28 days of life, by pharmacy personnel. Amino acid contents were recorded each day that the subject received either study or nonstudy parenteral nutrition. Pharmacy logs and source documents were monitored to validate each of the growth measurements and the amount of amino acid supplementation that was recorded on the case report form of each subject.
Measurement of Amino Acid and Acylcarnitine Levels
Amino acid and acylcarnitine profiles were analyzed from dried blood spots by using tandem mass spectrometry, as described by Chace and Kalas.15 All quantitative results were provided to study investigators and were reported as micromoles per liter.
To provide "normal" reference values (reference values in Fig 1), we calculated the median and the 10th and 90th percentiles for each metabolite by using 1000 normal term newborn values (from samples obtained in the first 7 days after birth). These values were derived from samples sent to our laboratory for screening for inborn errors of metabolism. The values represent our internal normal newborn control values (reference values). To try to identify the amino acid and acylcarnitine values that were commonly (>50% of the patients) abnormal, relative to our internal reference newborn levels, we calculated the proportion of patients with values greater than the 90th percentile (high levels) and the proportion of patients with values less than the 10th percentile (low values) for the overall study population and each treatment group.
|
Statistical Analyses and Sample Size Calculation
Our hypothesis was that the higher-dose group would have a growth velocity (13.0 g/kg per day) 3 g/kg per day more than that of the lower-dose group (10 g/kg per day). On the basis of previous work with premature neonates,6 we calculated that a sample size of 108 patients (54 patients in each group) would allow us to detect a difference of 3.0 g/kg per day in weight gain between the 2 treatment groups (
= .025, power = 80%, assuming SD = 5.0 g/kg per day). The level was set at .025 on the basis of a 2-sided, 2-sample t test. We anticipated a 10% dropout rate resulting from morbidity and death; therefore, we enrolled 122 subjects.
We performed an intent-to-treat analysis. Categorical variables were evaluated by using a 2-tailed 
2 test and Fisher's exact test. Continuous variables were compared by using a 2-tailed t test for parametrically distributed data and Kruskal-Wallis analysis of variance for nonparametrically distributed data. Rank data were assessed by using a 2-tailed, Mann-Whitney, nonparametric test. Analysis of variance for repeated measures was used to evaluate the changes in all laboratory values over time, from the day of random assignment to days 7 and 28 of age. Both time and treatment groups were evaluated. To evaluate the influence of covariates (gestational age, birth weight, gender, and postnatal exposure to steroids) on our study results, we performed a linear regression analysis. Our goal was to determine the treatment-influenced weight gain when these covariates were included in the regression model.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Enrollment
Between September 1, 2005, and June 1, 2006, site logs showed that 230 neonates were screened and 122 neonates (53%) were enrolled from 11 sites, 64 in the 3.5 g/kg per day group and 58 in the 2.5 g/kg per day group. The 2 reasons for nonenrollment were parent refusal (n = 57) and missed opportunities for obtaining consent (n = 51). The median enrollment per site was 11 patients (range: 3–16 patients).
Report on Patients Who Did Not Complete the Study
Of the 122 patients enrolled, 11 patients did not complete the study. Three patients died before 28 days. Five patients were withdrawn from the study (3 in the 3.5 g/kg per day group and 2 in the 2.5 g/kg per day group). One patient was considered by the attending neonatologist to be too sick to continue in the study, and 2 patients were transferred out of the study facility before 28 days. Follow-up laboratory assessments were not available for those patients. The primary reason for a patient being withdrawn from the study was a serum urea nitrogen level of >50 mg/dL (n = 4). Two of the 11 patients who did not complete the study did not receive study parenteral nutrition. Removal of the 11 patients who failed to complete the study protocol did not change our results, and we report only the intent-to-treat analysis.
Protocol Experience
Fifty percent of the patients were enrolled during the first 24 hours after birth, and there was good separation of the 2 treatment groups regarding the amounts of amino acids delivered after random assignment (Fig 1A). By design, from day 1 to day 28, neonates in the 3.5 g/kg per day group received a larger dose of amino acids than did those in the 2.5 g/kg per day group (Fig 1). There was no difference in the number of days of study amino acid support or the total number of days of any parenteral nutrition (Table 1).
|
Demographic Data and Primary and Secondary Morbidity Outcomes
We used an intent-to-treat approach, and all tables reflect all enrolled infants, categorized according to treatment group. There were no significant differences in the demographic or baseline characteristics of the 2 treatment groups (Table 1). On day 7, there were no differences in weight, length, head circumference, or degree of nutritional support (Table 1). Similarly, there was no significant difference in growth (or any growth parameter) on day 28 (Table 2). The incidences of morbidities were similar for the 2 treatment groups (Table 2). Multivariate regression analysis showed that gestational age, birth weight, and postnatal exposure to steroids each had an independent influence on weight gain. The neonates with the poorest weight gain were small neonates who were gestationally immature and who were exposed postnatally to dexamethasone. In multivariate analyses, treatment group did not influence growth or the occurrence of the patient's weight being below the 10th percentile for weight at 28 days of age.
|
Changes in Amino Acid Levels
Differences in Levels According to Treatment Group
There were no differences in amino acid levels on the day of random assignment (Table 3). On day 7 (parenteral phase of nutrition), blood levels of several amino acids (alanine, arginine, glutamate, leucine/isoleucine, methionine, ornithine, phenylalanine, serine, tyrosine, and valine) were higher in the 3.5 g/kg per day group than in the 2.5 g/kg per day group. On day 28 (enteral phase of nutrition), tyrosine levels were higher for the neonates in the 3.5 g/kg per day group, compared with those in the 2.5 g/kg per day group. None of the amino acids levels was lower in the 3.5 g/kg per day group, compared with the 2.5 g/kg per day group, on either day 7 or day 28.
|
Changes Over Time
There were significant changes over time in most of the blood amino acid levels, and these changes were similar for the 2 treatment groups (Table 3). In the 3 samples (day of random assignment, day 7, and day 28), glutamate, glycine, phenylalanine, and tyrosine levels decreased. Arginine, aspartate, ornithine, and serine levels increased. Alanine and citrulline levels were relatively constant. Histidine, leucine/isoleucine, methionine, and valine levels increased and then decreased back to baseline (day of random assignment) levels. There was no treatment group/sample time interaction.
Differences From Our Reference Sample of Normal Term Newborns
In the study population, blood alanine and glutamate levels were commonly (>50% of the patients) low (<10th percentile), relative to our reference values, for all 3 determinations. Sixty-one percent of the patients had low alanine levels on the day of random assignment. Although the frequency of low alanine levels decreased with time (56% of the patients on day 7 and 51% on day 28), it remained consistent. For glutamate, 51% of the patients had low values on the day of random assignment, and 75% and 64% of the patients had low values on days 7 and 28, respectively. On day 28, phenylalanine levels were low for 57% of the neonates.
For 5 amino acids (arginine, leucine/isoleucine, methionine, ornithine, and tyrosine), there was 1 treatment group for which the values were commonly abnormal. All of these differences occurred on day 7 (parenteral phase of nutrition), and high (>90th percentile) values occurred more frequently in the 3.5 g/kg per day group than in the 2.5 g/kg per day group (arginine: 53% vs 25%; P = .003; leucine/isoleucine: 64% vs 26%; P < .001; methionine: 53% vs 35%; P = .09; ornithine: 66% vs 39%; P = .006). On day 7, tyrosine levels were low for 47.5% of the patients, and low levels occurred less frequently in the 3.5 g/kg per day group than in the 2.5 g/kg per day group (36% vs 60%; P = .02).
Changes in Acylcarnitine Levels
Differences in Levels According to Treatment Group
On the day of random assignment and day 28, there were no differences in the acylcarnitine levels between the 2 treatment groups (Table 3). On day 7 (parenteral phase of nutrition), levels of 4 acylcarnitines (palmitoleoyl, propionyl, isovaleryl, and 3-hydroxyisovaleryl carnitine) were higher in the 3.5 g/kg per day group, compared with the 2.5 g/kg per day group; no acylcarnitine levels were lower.
Changes Over Time
There were significant changes over time in most acylcarnitine levels, and these changes were similar for the 2 groups (Table 3). In the 3 samples (day of random assignment, day 7, and day 28), palmitoyl, palmitoleoyl, steroyl, acetyl, propionyl, and butyryl carnitine levels decreased. Linoleyl and oleyl carnitine levels increased and then decreased back to baseline (day of random assignment) levels. There was no treatment group/sample time interaction in the acylcarnitine levels.
Differences From Our Reference Sample of Normal Term Newborns
In our study population, blood levels of 4 acylcarnitines (oleyl, palmitoyl, palmitoleoyl, and stearoyl carnitine) were commonly (>50% of the patients) low (<10th percentile) for both treatment groups on all 3 days. On days 7 and 28, acetyl and propionyl carnitine levels were low for >50% of the patients in both treatment groups. On the day of random assignment and day 7, isovaleryl carnitine levels were high for >80% of the patients in both treatment groups; on day 7, linoleyl carnitine levels were high for >70% of the patients in both groups. There were no treatment group differences in the occurrence of high or low values. Serum urea nitrogen levels on days 7 and 28 were higher in the 3.5 g/kg per day group, compared with the 2.5 g/kg per day group (Fig 1B), but bicarbonate, creatinine, and bilirubin levels were similar for the 2 groups (Table 1).
Adverse Events
There were 99 adverse events reported (respiratory distress, n = 15; apnea/bradycardia, n = 14), 52 in the 3.5 g/kg per day group and 47 in the 2.5 g/kg per day group. There were 10 serious adverse events reported (6 in the 3.5 g/kg per day group and 4 in the 2.5 g/kg per day group). The serious adverse events were death (n = 3), acute renal failure (n = 1), necrotizing enterocolitis (n = 1), serum urea nitrogen level of >50 mg/dL (n = 3), overwhelming sepsis (n = 1), and 1 patient with a laboratory panel consistent with an inborn error of metabolism (repeat values were normal). A single patient could have >1 adverse event. The 99 adverse events occurred in 35 patients (18 patients in the 3.5 g/kg per day group and 17 patients in the 2.5 g/kg per day group).
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
The use of a higher dose (higher initial dose, faster advancement, and higher maximal dose) of amino acids in parenteral nutrition did not promote improved growth (weight gain or changes in length and head circumference), compared with a lower dose of amino acid supplementation. In addition, several blood amino acid levels and the serum urea nitrogen level were higher by day 7 in patients treated with the higher dose. In both treatment groups, some amino acid levels were commonly above the 90th percentile, whereas other amino acid levels were commonly below the 10th percentile, compared with a normal term newborn reference. Although none of the values reached the threshold for diagnosis of serious metabolic disease, we cannot be certain that these levels are safe for preterm infants.
Several studies showed that postnatal malnutrition and growth restriction are inevitable if infants receive currently recommended dietary intakes and that the neonates at highest risk for poor growth are neonates who are critically ill and born very premature.1–5 Evaluation of dietary intakes in preterm infants showed cumulative energy and protein deficits of >1200 J/kg (>300 kcal/kg) and 12 g of protein per kg after 1 week of life, respectively1; this deficit continued to accumulate during the first month after birth.1,5 Stepwise regression analysis indicated that differences in dietary intake accounted for 45% of the variation in growth of premature infants treated in different hospitals.7,8 Olsen et al7 suggested that the addition of 1 g of protein per kg per day to the mean intake could increase growth by 4.1 g/kg per day in premature neonates. Poindexter et al9 showed that early supplementation of amino acids was associated with better growth at postmenstrual age of 36 weeks. We powered our study to detect a difference in weight gain of 3 g/kg per day, similar to what we found in a previous study6 and less than that predicted by Olsen et al.7 We were unable to support the hypothesis of Olsen et al7 or the retrospective findings of Poindexter et al9 of improved growth, but our study was not powered adequately to detect the smaller differences in growth reported by Poindexter et al.9 Our study suggests that, without additional energy, administration of more protein does not increase growth.
Similar to the findings of te Braake et al16 and Poindexter et al,17 our study demonstrated that the dose of parenteral amino acid supplementation increased blood amino acid levels, especially during the parenteral phase of nutrition. Neonates born prematurely have immature metabolic pathways for using amino acids during catabolism and anabolism.18–21 The increase in amino acid levels seen on day 7 suggests that some amino acids accumulate in the blood, presumably because protein anabolism is saturated or the anabolic pathway is immature and the premature neonate cannot process the extra amino acids. Leucine and isoleucine are major amino acid components of both TrophAmine (BBraun, Bethlehem, PA) and Aminosyn (Hospria, Lake Forest, IL) (Appendix ). The elevated levels of leucine/isoleucine (Fig 1C) and isovaleryl carnitine (a product of L-leucine metabolism) (Fig 1D) provide evidence that administration of higher doses of leucine to premature infants would be futile (because of pathway saturation). Furthermore, the elevated concentrations of isovaleryl carnitine suggest that blood isovaleric acid levels may begin to approach levels that are associated with toxicity in some premature infants, as seen in isovaleric acidemia. L-Carnitine administration in the parenteral nutrition mixture might explain why some acylcarnitine levels were high, but it does not explain the day 7 differences in isovaleryl carnitine levels between the 2 treatment groups (Fig 1D).
|
Levels of some amino acids (alanine, glutamate, phenylalanine, and tyrosine) were low, compared with normal newborn levels, and supplementation also influenced the incidence of low values (Fig 1 E and F). The patients in the 3.5 g/kg per day group had lower tyrosine levels less often than did those in the 2.5 g/kg per day group (36% vs 60%), but the proportions with low levels were large in both groups.
Our data suggest that current strategies for amino acid supplementation result in excess levels of some amino acids and inadequate concentrations of other amino acids. There is an important limitation to this observation, that is, there is no standard reference. Each state has its own set of procedures for identifying neonates with inborn errors of metabolism, and there are no nationally accepted standards that are universally applied.22–24
Establishing a consensus regarding what represents a normal amino acid profile in premature neonates would allow investigators to identify neonates with abnormal values and to evaluate the impact of those abnormal values on important health outcomes (liver injury, growth, and neurodevelopmental outcomes). Establishing normal values would also improve our ability to monitor the adequacy of amino acid supplementation. Failure to establish normal values might prevent the development of a better understanding of amino acid metabolism in premature neonates. Similar problems exist in identifying premature neonates with abnormal thyroid function. Careful research into what defines normal should be a priority.
|
CONCLUSIONS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Our data demonstrate that providing higher-dose supplementation (higher initial dose, faster advancement, and higher maximal dose, as outlined in our study) of amino acids in parenteral nutrition does not improve growth. Careful research into the ideal way to promote optimal growth is needed, and the degree of nutritional amino acid support that we provide parenterally needs to be reevaluated. For very immature neonates, the quantity and quality of amino acid supplementation may need to be individualized and tailored to the specific needs of the infant.25 Monitoring electrolyte, glucose, and triglyceride levels does not allow us to evaluate amino acid balance or amino acid tolerance in extremely low birth weight infants. We cannot be certain that subtle increases in amino acid levels in the higher-dose group in our study are safe for the developing brain of premature neonates. Similarly, deficits in essential amino acids may hinder normal growth and development. Additional studies that use alternative approaches and larger sample sizes may uncover different results and are urgently needed.
|
ACKNOWLEDGMENTS |
|---|
The Pediatrix Amino Acid Study Group is as follows: principal investigators: Debra Bender, ARNP, Swedish Medical Center (Seattle, WA); Barbara Carr, MD, St Luke's Hospital (Chesterfield, MO); Carlos Flores, MD, Tucson Medical Center (Tucson, AZ); Jose Gierbolini, MD, Stormont-Vail Regional Health Center (Topeka, KS); David W. Green, MD, Presbyterian Hospital of Dallas (Dallas, TX); Joseph Harlan, MD, McLeod Regional Medical Center (Florence, SC); Michael Kamitsuka, MD, Swedish Medical Center (Seattle, WA); Sridhar Kaushik, MD, Pinnacle Health-Harrisburg Hospital (Harrisburg, PA); Amy S. Kelleher, BS, Pediatrix Medical Group (Sunrise, FL); Jose Perez, MD, Arnold Palmer Medical Center (Orlando, FL); Meera Sankar, MD, Good Samaritan Hospital (San Jose, CA); Bindya Singh, MD, Good Samaritan Hospital (San Jose, CA); Margaret Steinbach, NNP, Pediatrix Medical Group (Sunrise, FL); Robert White, Memorial Hospital of South Bend (South Bend, IN); Henry H. Wooldridge, MD, East Tennessee Children's Hospital (Knoxville, TN); contributors: P. Kathine Fulton, RNC, NNP, East Tennessee Children's Hospital (Knoxville, TN); Chrissy Weng, RN, Good Samaritan Hospital (San Jose, CA); Evelyn Fulmore, PharmD, McLeod Regional Medical Center (Florence, SC); Delores Troyer, NNP, Memorial Hospital of South Bend (South Bend, IN); Penny Barcavage, NNP, Pinnacle Health-Harrisburg Hospital (Harrisburg, PA); Renuka K. Reddy, MD, Presbyterian Hospital of Dallas (Dallas, TX); Renee Hunt, RNC, NNP, Stormont-Vail Regional Health Center (Topeka, KS); Colleen Bakewell, Tucson Medical Center (Tucson, AZ).
|
FOOTNOTES |
|---|
Accepted Jun 12, 2007.
Address correspondence to Reese H. Clark, MD, Pediatrix Medical Group, 1301 Concord Terrace, Sunrise, FL 33323-2825. E-mail: reese_clark{at}pediatrix.com
This trial has been registered at www.clinicaltrials.gov (identifier NCT00120926).
Financial Disclosure: Drs Clark, Chace, and Spitzer are employees of Pediatrix Medical Group, which owns Pediatrix Screening, a company that offers newborn screening for inborn errors of metabolism and hearing loss.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
- 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] - Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a serious problem in prematurely born neonates.
Pediatrics. 2003;111
:986
–990
[Abstract/Free Full Text] - Coverston CR, Schwartz R. Extrauterine growth restriction: a continuing problem in the NICU. MCN Am J Matern Child Nurs. 2005;30 :101 –106[CrossRef][Medline]
- de Curtis M, Rigo J. Extrauterine growth restriction in very-low-birthweight infants. Acta Paediatr. 2004;93 :1563 –1568[CrossRef][Web of Science][Medline]
- Ehrenkranz RA, Dusick AM, Vohr BR, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants.
Pediatrics. 2006;117
:1253
–1261
[Abstract/Free Full Text] - Bloom BT, Mulligan J, Arnold C, et al. Improving growth of very low birth weight infants in the first 28 days.
Pediatrics. 2003;112
:8
–14
[Abstract/Free Full Text] - Olsen IE, Richardson DK, Schmid CH, Ausman LM, Dwyer JT. Intersite differences in weight growth velocity of extremely premature infants.
Pediatrics. 2002;110
:1125
–1132
[Abstract/Free Full Text] - Blackwell MT, Eichenwald EC, McAlmon K, et al. Interneonatal intensive care unit variation in growth rates and feeding practices in healthy moderately premature infants. J Perinatol. 2005;25 :478 –485[CrossRef][Medline]
- Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA. Early provision of parenteral amino acids in extremely low birth weight infants: relation to growth and neurodevelopmental outcome. J Pediatr. 2006;148 :300 –305[CrossRef][Web of Science][Medline]
- Embleton NE, Cooke RJ. Protein requirements in preterm infants: effect of different levels of protein intake on growth and body composition. Pediatr Res. 2005;58 :855 –860[CrossRef][Web of Science][Medline]
- Thureen PJ, Melara D, Fennessey PV, Hay WW Jr. Effect of low versus high intravenous amino acid intake on very low birth weight infants in the early neonatal period. Pediatr Res. 2003;53 :24 –32[CrossRef][Web of Science][Medline]
- Putet G. Lipid metabolism of the micropremie. Clin Perinatol. 2000;27 :57 –69[CrossRef][Web of Science][Medline]
- Uauy R, Mena P, Rojas C. Essential fatty acid metabolism in the micropremie. Clin Perinatol. 2000;27 :71 –93[CrossRef][Web of Science][Medline]
- Thureen PJ. Early aggressive nutrition in the neonate.
Pediatr Rev. 1999;20
:e45
–e55
[Free Full Text] - Chace DH, Kalas TA. A biochemical perspective on the use of tandem mass spectrometry for newborn screening and clinical testing. Clin Biochem. 2005;38 :296 –309[CrossRef][Web of Science][Medline]
- te Braake FW, van den Akker CH, Wattimena DJ, Huijmans JG, van Goudoever JB. Amino acid administration to premature infants directly after birth. J Pediatr. 2005;147 :457 –461[CrossRef][Web of Science][Medline]
- Poindexter BB, Ehrenkranz RA, Stoll BJ, et al. Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birthweight infants.
Am J Clin Nutr. 2003;77
:737
–743
[Abstract/Free Full Text] - Kadrofske MM, Parimi PS, Gruca LL, Kalhan SC. Effect of intravenous amino acids on glutamine and protein kinetics in low-birth-weight preterm infants during the immediate neonatal period.
Am J Physiol Endocrinol Metab. 2006;290
:E622
–E630
[Abstract/Free Full Text] - Van Den Akker CHP, Te Braake FWJ, Wattimena DJL, et al. Effects of early amino acid administration on leucine and glucose kinetics in premature infants. Pediatr Res. 2006;59 :732 –735[CrossRef][Web of Science][Medline]
- Kalhan SC, Parimi PS, Gruca LL, Hanson RW. Glutamine supplement with parenteral nutrition decreases whole body proteolysis in low birth weight infants. J Pediatr. 2005;146 :642 –647[CrossRef][Web of Science][Medline]
- Parimi PS, Gruca LL, Kalhan SC. Metabolism of threonine in newborn infants.
Am J Physiol Endocrinol Metab. 2005;289
:E981
–E985
[Abstract/Free Full Text] - Therrell BL, Hannon WH. National evaluation of US newborn screening system components. Ment Retard Dev Disabil Res Rev. 2006;12 :236 –245[CrossRef][Web of Science][Medline]
- Therrell BL, Johnson A, Williams D. Status of newborn screening programs in the United States.
Pediatrics. 2006;117
:S212
–S252
[Abstract/Free Full Text] - Frazier DM, Millington DS, McCandless SE, et al. The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005. J Inherit Metab Dis. 2006;29 :76 –85[CrossRef][Web of Science][Medline]
- Cooke RJ. Adjustable fortification of human milk fed to preterm infants. J Perinatol. 2006;26 :591 –592[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  B. E. Stephens, R. V. Walden, R. A. Gargus, R. Tucker, L. McKinley, M. Mance, J. Nye, and B. R. Vohr First-Week Protein and Energy Intakes Are Associated With 18-Month Developmental Outcomes in Extremely Low Birth Weight Infants Pediatrics, May 1, 2009; 123(5): 1337 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Franz, F. Pohlandt, H. Bode, W. A. Mihatsch, S. Sander, M. Kron, and J. Steinmacher Intrauterine, Early Neonatal, and Postdischarge Growth and Neurodevelopmental Outcome at 5.4 Years in Extremely Preterm Infants After Intensive Neonatal Nutritional Support Pediatrics, January 1, 2009; 123(1): e101 - e109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. P. van den Akker, F. W. J. te Braake, W. W. Rovekamp-Abels, and J. B. van Goudoever Quality of Amino Acid Solutions for Preterm Infants Pediatrics, April 1, 2008; 121(4): 865 - 866. [Full Text] [PDF]
|
|
|
|
|
|
I. Minoli and N. C. Raiha Effects of Two Different Doses of Amino Acid Supplementation on Growth and Blood Amino Acid Levels in Premature Neonates Admitted to the Neonatal Intensive Care Unit: A Randomized, Controlled Trial Pediatrics, March 1, 2008; 121(3): 655 - 656. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
