PEDIATRICS Vol. 111 No. 5 May 2003, pp. 986-990
Extrauterine Growth Restriction Remains a Serious Problem in Prematurely Born Neonates
* The Pediatrix-Obstetrix Center for Research and Education, Pediatrix Medical Group, Inc, Sunrise, Florida
Duke University Medical Center, Durham, North Carolina
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSAPPENDIXREFERENCES |
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Background. Poor growth is a common problem in premature neonates and may be associated with neurodevelopmental delay.
Objective. To evaluate the incidence of extrauterine growth restriction (growth values 
10th percentile of intrauterine growth expectation based on estimated postmenstrual age in premature (23–34 weeks’ estimated gestational age) neonates at the time they are discharged from the hospital.
Design/Methods. Using a database formed from a computer-assisted tool that generates clinical progress notes and discharge summaries on neonatal intensive care unit admissions, we reviewed data on neonates discharged from 124 neonatal intensive care units between January 1, 1997, and December 31, 2000. We evaluated neonates who were born between 23 and 34 weeks’ estimated gestational age without congenital anomalies and who were cared for at and discharged from the same hospital. For each patient, we compared the discharge growth values to the expected values based on our intrauterine growth data and postmenstrual age on the day of discharge. We defined extrauterine growth restriction as having a measured growth value (weight, length or head circumference) that was 10th percentile of the predicted value. In each specific birth weight and estimated gestational age group, we counted the number of neonates 10th percentile for each growth parameter and calculated the percentage of patients who had values 10th percentile at discharge. Using logistic regression, we evaluated the factors associated with extrauterine growth restriction for weight, length, and head circumference.
Results. Our sample included 24 371 premature neonates. Data on discharge weight, length, and head circumference was available on 23 970, 17 203, and 20 885 neonates, respectively. The incidence of extrauterine growth restriction was common (28%, 34%, and 16% for weight, length, and head circumference, respectively). For each growth parameter, the incidence of extrauterine growth restriction increased with decreasing estimated gestational age and birth weight. Factors independently associated with extrauterine growth restriction were male gender, need for assisted ventilation on day 1 of life, a history of necrotizing enterocolitis, need for respiratory support at 28 days of age, and exposure to steroids during the hospital course.
Conclusions. Extrauterine growth restriction remains a serious problem in premature neonates especially for neonates who are small, immature, and critically ill.
Key Words: neonate • growth • retrospective clinical study
Abbreviations: NICU, neonatal intensive care unit
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSAPPENDIXREFERENCES |
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In premature neonates, achieving recommended dietary intakes takes time and is rarely maintained throughout the duration of hospitalization. Nutrient deficits accrue and are rarely replaced. The term extrauterine growth restriction is descriptive of stunted growth resulting from severe nutritional deficit during the first weeks of life. Despite some catch-up growth during the second month of life, many neonates go home significantly smaller than expectations based on intrauterine growth rates. Their nutritional deficit affects not only their weight but their head circumference and length as well.1 Postnatal growth lag is associated with neurologic and sensory handicaps and poor school performance.2 This means that neonates who have extrauterine growth restriction may be at risk for long-term medical problems.1
Our objective was to evaluate the incidence of extrauterine growth restriction (growth values 10th percentile of intrauterine growth expectation based on estimated gestational age) in premature (23–34 weeks) neonates at the time they are discharged from the hospital.
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METHODS |
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Research Design
We conducted a retrospective review of an administrative database to describe the growth outcomes of premature neonates at the time of discharge from neonatal intensive care.
Study Population
Neonates discharged from 124 neonatal intensive care units (NICUs) managed by Pediatrix Medical Group, Inc between January 1, 1997, and December 31, 2000, who were 23 to 34 weeks’ estimated gestational age without congenital anomalies and who were born at and discharged from the same NICU (N = 24 371) were eligible for inclusion in the study. Data on discharge weight, length, and head circumference was available on 23 970, 17 203, and 20 885 neonates, respectively. In our data analysis each of these 3 groups was evaluated as an independent sample.
Data Collection
Using a database from a computer-assisted tool that generates clinical progress notes on neonates cared for by Pediatrix Medical Group, Inc., we reviewed data on birth weight, estimated gestational age (this represents the best estimate based on both obstetric data and neonatal examination), gender, Apgar scores at 5 minutes, race (choices in database are white, black, Hispanic, Native American and Asian), use of antenatal steroids, use of postnatal steroids (dexamethasone or hydrocortisone), use of assisted ventilation during the first day of life, use of surfactant, use of respiratory support at 28 days after birth (oxygen, continuous positive airway pressure, or assisted ventilation), and a diagnosis of necrotizing enterocolitis. We created dichotomous (1/0) variables for exposure to any type of postnatal steroids (hydrocortisone or dexamethasone), use of any surfactant, use of respiratory support at 28 days, and a diagnosis of necrotizing enterocolitis. Neonates discharged before 28 days were assigned 0 (no support) for the respiratory variable. We also evaluated data on discharge weight, length, head circumference, and length of hospital stay. Postmenstrual age was calculated using the estimated gestational age at birth and the length of hospital stay (ie, estimated gestational age + [length of stay/7]). The database did not include patient identifiers and is maintained as a clinical quality improvement tool.
Definition of Extrauterine Growth Restriction
Extrauterine growth restriction was defined as having a growth value 10th percentile of intrauterine growth expectation based on postmenstrual age at the time of discharge to home. We used our previously published growth curves generated from birth weights and estimated gestational age at birth to establish expected growth values for neonates discharged at an estimated gestational age between 33 to 40 weeks.3 Gender-specific values were used to make the assignment of extrauterine growth restriction. For neonates with an estimated gestational age of 41 to 44 weeks at discharge, we used the gender-specific national standards issued by the Centers for Disease Control and Prevention.4 Each growth parameter (weight, length, and head circumference) was assessed individually.
Statistical Analysis
We used multivariate logistic regression to identify factors independently associated with the occurrence of extrauterine growth restriction for each variable. We evaluated all the variables in Table 2, which on univariate analysis, were found to be associated with the outcome variable (P < .05). We incorporated the variables found to have significant interactions (P < .1) with the outcome variable in the final logistic regression analysis. Variables were entered into the model using a stepwise selection (P value for entry and retention .1). Cases with missing values for any of the independent variables were excluded from the analysis. The total number of neonates included in each of the final models is listed in the tables.
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RESULTS |
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Table 1 shows the sample size and rate of growth restriction by estimated gestational age at birth. The most important and significant differences between neonates who had extrauterine growth restriction and those who did not were that they had lower birth weights and were more immature (Tables 2 and 4). The effects of both gestational age and birth weight are graphically demonstrated in Fig 1. This graphic shows that neonates born small for gestational age (<10th percentile) remain small for gestational age at discharge. In addition, a significant proportion of neonates who were appropriately grown for gestational age at birth were discharged from the hospital with weights <10th percentile for the gestational age at discharge. Table 3 shows the sample size and the rate of growth restriction by postmenstrual age at discharge.
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In our multivariate analysis, low birth weight and immature gestational age were the most important factors associated with the occurrence of extrauterine growth restriction (Table 4). Multivariate logistic regression (including gestational age and birth weight) showed male gender, the need for assisted ventilation on day 1 of life, exposure to steroids during the hospital course, need for respiratory support on day 28 of age, and a diagnosis of necrotizing enterocolitis as independent risk factors that increase the odds of a neonate being labeled as extrauterine growth-restricted. Antenatal steroids appeared to have a small but significant protective effect. The adjusted odds ratios and their confidence intervals are listed in Table 4. As shown by the change in R2 values, adding risk factors beyond birth weight and gestational age at birth to the multivariate model did not dramatically improve the performance of the models in predicting extrauterine growth restriction.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSAPPENDIXREFERENCES |
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Our data demonstrate that extrauterine growth restriction remains a significant problem for prematurely born neonates especially those who develop significant morbidity or who are treated with postnatal steroids. If we successfully met the nutritional needs of hospitalized premature infants, we would expect to find 10% of the premature neonates we cared for going home with growth values <10th percentile. In contrast, we found 30% of the neonates born at <28 weeks’ estimated gestational age, who had head circumferences that were appropriate at birth, went home with head circumferences <10th percentile. This is the only article to report the birth weight and gestational age-specific occurrence of extrauterine growth restriction at discharge.
Others have reported similar findings. Ehrenkranz et al5 reported that at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. The incidence of failure-to-thrive (weight <5th percentile for age/sex) in extremely low birth weight neonates (400–1000 g) in the Neonatal Research Network cohort was 34% to 45% at 18 months’ corrected age.6 Postnatal growth lag is associated with neurologic and sensory handicaps and poor school performance.2 Very low birth weight infants with perinatal growth failure whose head size is not normal by 8 months of age have significantly poorer growth and neurocognitive abilities at school age than very low birth weight children with a normal head size at 8 months.7 The magnitude of the poor growth outcomes we (and others) report demand that we reassess the targets we set for adequate nutrition in NICUs and after discharge.
Although low birth weight and immature gestational age were the factors that had the most significant effect on the incidence of growth restriction, we also identified several other factors that appear to influence growth. All of the factors (gender, need for respiratory support at birth, necrotizing enterocolitis, and exposure to postnatal steroids) we identified may only be surrogate markers for severity of illness. As described by Ehrenkranz et al,5 premature neonates who require assisted ventilation and have significant adverse events (eg, necrotizing enterocolitis) are more likely to have poor growth than premature neonates who do not. This finding is not surprising. Sick neonates are often fed differently than healthier infants, have increased metabolic demands, and their nutritional needs are rarely met, all of which result in malnutrition and poor growth.
We remain concerned about the potential effects of postnatal steroids on body and brain growth. Numerous studies now show the profound and lasting effects that steroids can have on growth of the lungs, body, and brain.8–12 Our data suggest that neonates who are exposed to postnatal steroids are at greater risk of growth failure than those who are not, independent of other risk factors. The association between exposure to postnatal steroids and extrauterine growth restriction remains when multivariate analysis is used to correct for gestational age, birth weight, gender, need for assisted ventilation on day 1 of life, need for respiratory support at 28 days after birth, and a diagnosis of necrotizing enterocolitis. However, because neonates with chronic lung disease also fail to grow, it is impossible to separate the effect of chronic lung disease from that of postnatal steroids. In contrast to the negative effects of postnatal steroids, exposure to antenatal steroids appeared to have a slight protective effect. It should be emphasized that like most adverse neonatal outcomes, the most important risk factors associated with extrauterine growth restriction are immaturity and low birth weight.
There were limitations to our retrospective study design. Measurements of weight, length and height were site-specific and not rigorously standardized. We were missing data on length in a significant number of our study population and this may have created a selection bias (ie, patients with abnormal lengths may have had data reported more often than patients with normal lengths). In addition, proxies may not have reflected true severity of illness or the therapeutic approach. Also, there were site-specific differences in nutritional approach, which may also impact the growth restriction incident rates we reported. However, the large size of our population sample should help decrease these limitations and help better define the true population event rates, especially within specific birth weight and gestational age groups.
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CONCLUSIONS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSAPPENDIXREFERENCES |
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We have shown that extrauterine growth restriction remains a common and serious problem for prematurely born neonates. Although we have made significant advances in neonatal intensive care, we need a continued and aggressive effort to study and define new nutritional strategies that will improve the nutritional status of prematurely born neonates, especially the critically ill premature neonate.
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APPENDIX |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSAPPENDIXREFERENCES |
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In addition to the authors, the following physicians participated by providing data to the administrative dataset: Harrisburg, Pennsylvania, K. Lorah; Utica, New York, M. Siriwardena; Boynton Beach, Florida, L. Whetstine; Denver, Colorado, D. Eichorst, J. Toney; Houston, Texas, R. Rivas, H. Pierantoni, E. O’Donnell; Englewood, Colorado, K. Zarlengo; West Palm Beach, Florida, D. Kanter; Virginia Beach, Virginia, E. Bollerup; Fredericksburg, Virginia, J. Amin; Spartanburg, South Carolina, V. Iskersky; Watertown, New York, K. Komar; Tarzana, California, J. Banks; Ventura, California, J. van Houten; Hoboken, New Jersey, S. Mercado; Stratford, New Jersey, J. Coleman; Trenton, New Jersey, R. Axelrod; Covina, California, G. Martin; Newport Beach, California, L. Wickham, B. Hannam; Riverside, California, M. Leitner; Las Vegas, Nevada, M. Kaneta; Alexandria, Virginia, L. Goldberg; Albuquerque, New Mexico, R. Nederhoff, S. Swetnam; Aurora, Colorado, M. Brown; Phoenix, Arizona, J. Martin, R. Turbow; Dallas, Texas, J. Whitfield, T. Brannon; Roanoke, Virginia, R. Allen; Dayton, Ohio, N. Kantor, M. Belcastro; Ogden, Utah, N. Harper, J. Berger; Columbia, South Carolina, S. Ellis; Panama City, Florida, D. Sprague; Pensacola, Florida, A. Payne, J. Nagel; Reno, Nevada, G. Yup; Tacoma, Washington, J. Mulligan, G. Jordan, R. Knudson; Ponce, Puerto Rico, E. Ochoa, J. Rodriguez; Santurce, Puerto Rico, F. Caceras; Barrington, Illinois, F. Uraizee; Fort Worth, Texas, M. Stevener, R. Sidebottom, D. Turbeville, M. Stanley; Charleston, West Virginia, S. Maxwell; San Juan, Puerto Rico, A. Rivera, M. Ortega; Austin, Texas, J. Courtney, D. Wermer, J. Scharnberg; San Jose, California, E. Alderete; Rock Hill, South Carolina, W. Helmuth; South Bend, Indiana, R. White; Kansas City, Missouri, S. Shaffer, B. Heimes,; Pasadena, California, R. Liberman; Elmira, New York, J. Felix, R. Sanders; Wichita, Kansas, B. Bloom; Ft Lauderdale, Florida, E. Otero; Boca Raton, Florida, F. Miller, H. Brenker; Coral Springs, Florida, J. Colindres; Fountain Valley, California, V. Chundu; San Luis Obispo, California, S. VanScoy; Laguna Hills, California, R. Naglie; Colorado Springs, Colorado, D. Rommes, K. Meredith; Tucson, Arizona, C. Flores; El Paso, Texas, L. Ayo, R. Caviglia, E. Ponte; Oklahoma City, Oklahoma, S. Lopez, J. Pineda; Chattanooga, Tennessee, V. Thomas; Baltimore, Maryland, H. Birenbaum, T. O’Brien; Cheverly, Maryland, A. Fomufod; Seattle, Washington, J. Prueitt, T. Sweeney, Yakima, Washington, R. Skarin; Greenville, South Carolina, D. Wells, R. Newell; Augusta, Georgia, A. Blalock; Melbourne, Florida, J. Vallette; St Louis, Missouri, J. Brenner, M. Maurer; Chesterfield, Missouri, W. Chao; and Mayaguez, Puerto Rico, E. Sanchez.
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FOOTNOTES |
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Received for publication May 3, 2002; Accepted Oct 3, 2002.
Reprint requests to (R.H.C.) Pediatrix Medical Group, Inc, 1301 Concord Terr, Sunrise, FL 33323-2825. E-mail: reese_clark{at}pediatrix.com
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PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics
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