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PEDIATRICS Vol. 111 No. 4 April 2003, pp. 750-758

Evaluation of and Recommendations for Growth References for Very Low Birth Weight (<=1500 Grams) Infants in the United States

Bettylou Sherry, PhD, RD, Zuguo Mei, MD, MPH, Laurence Grummer-Strawn, PhD and William H. Dietz, MD, PhD

From the Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia

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   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objective. To determine the best available growth reference for evaluating the growth status of very low birth weight (VLBW; <=1500 g) infants in the United States.

Methods. We evaluated currently available growth references for VLBW infants in studies by Casey (Infant Health and Development Program [IHDP]), Brandt, Gairdner and Pearson, and Babson and Benda. We selected the 1 that best met a priori criteria and compared it with the new Centers for Disease Control and Prevention (CDC) growth charts. We evaluated the performance of both the selected VLBW reference and the CDC growth charts for use with VLBW infants by plotting data from 2 external data sets of VLBW infants (from Child Health and Development Studies [CHDS]) and linked the CDC’s Pregnancy Nutrition Surveillance System/Pediatric Nutrition Surveillance System Data (PNSS/PedNSS) on both references. Age was adjusted for gestational age in all of the VLBW data set comparisons.

Results. The IHDP reference met the greatest number of our evaluation criteria. The IHDP charts are the most recent, are based on a relatively large sample of VLBW infants in the United States, and are adjusted for gestational age at birth (using the standard of birth at 40 weeks) to account for prematurity. The IHDP VLBW infants, based on corrected postnatal age, compared with the non-VLBW infants included in the new CDC growth charts showed more rapid growth in length-for-age from birth (40 weeks) to 24 months, were nearly equivalent in weight-for-age at birth (40 weeks), yet demonstrated less rapid growth in weight-for-age from 40 weeks to 24 months. The performance evaluation of the IHDP and CDC growth reference based on the 2 external VLBW data sets (CHDS and PNSS/PedNSS) showed that the IHDP charts more closely matched the external data sets in relative position on the graphs and growth patterns for length-for-age, but the CDC growth charts more closely matched the external data sets in the growth pattern for weight-for-length. In weight-for-age, because of the lack of stability in the pattern, we could not determine which reference the external data growth pattern more closely matched.

Conclusions. Our evaluation of growth references for VLBW infants yielded no clear, simple recommendation. The inconsistencies in the discrepancies across anthropometric indices between the 2 external combined VLBW data sets (CHDS and PNSS/PedNSS) and the IHDP reference and the CDC growth charts make it difficult to recommend 1 reference. Therefore, we recommend using either the IHDP reference or the CDC growth charts to evaluate the growth of VLBW infants. The choice of which to use depends on its purpose. The IHDP reference is the best available reference for comparisons of the growth of a VLBW infant with those of other VLBW infants. The CDC growth charts allow comparison of the growth of a VLBW infant with that of non-VLBW infants.

Key Words: very low birth weight infants • growth references • growth status • performance evaluation

Abbreviations: VLBW, very low birth weight • IUGR, intrauterine growth retardation • CDC, Centers for Disease Control and Prevention • LBW, low birth weight • IHDP, Infant Health and Development Program • CHDS, Child Health and Development Studies • PNSS/PedNSS, Pregnancy • Nutrition Surveillance System/Pediatric Nutrition Surveillance System


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Very low birth weight (VLBW) infants (birth weights of <=1500 g) are a unique, heterogeneous group with various degrees of prematurity, intrauterine growth retardation (IUGR), disability, and higher risks for morbidity and mortality than infants with higher birth weights. One important index used to monitor the overall health of VLBW infants is their growth status. Because the literature suggests that VLBW infants grow differently than higher birth weight infants, VLBW infants were not included in the data used to develop the Centers for Disease Control and Prevention (CDC) growth charts released in May 2000.1–10 Thus, an appropriate, currently available reference to evaluate the growth of VLBW infants remains a critical need. Ideally, this reference would portray optimal growth for VLBW infants and would exclude infants with IUGR, medical complications, frequent illness, or other conditions that may compromise growth. We need a reference that reflects ideal growth rather than typical growth that may be significantly comprised by illness. Unfortunately, no such reference exists because it is nearly impossible to find a large sample of VLBW infants without complications or frequent illness that would provide a stable estimate of growth for each age. Consequently, we rely on a reference that may not be appropriate for all VLBW infants in the United States.

Clearly, IUGR, medical complications, frequent illness, and other compromising conditions all can negatively affect the growth of VLBW infants. In addition to these negative impacts on growth, social class, the home environment, and maternal punitiveness may affect their growth. The 1958 British birth cohort (National Child Development Study) data demonstrated that white singleton low birth weight (LBW) infants had less catch-up growth in height when they were born to households in which the father’s occupation was defined as "partly manual" or "unskilled manual" when compared with white singleton LBW infants whose father’s occupations were classified as "professional" or "intermediate."11 Other studies have found that a poorer quality of the home environment was correlated with the presence of failure to thrive among a cohort of LBW infants12 and less catch-up growth in the presence of higher levels of maternal punitiveness.13

The changes in medical and nutritional care practices that occurred in the early 1990s may also have affected the growth of VLBW infants. Current standards of care, which include the use of prenatal steroids and prenatal surfactants as well as earlier, more aggressive nutritional therapy, potentially could improve the growth status and affect the patterns of growth of these infants.14–16

The goal of this study was to evaluate the available VLBW growth references and to recommend the best reference to assess the growth of VLBW infants in the United States. As part of our evaluation, we sought current data on the growth of VLBW infants to compare current patterns of growth with the best available VLBW infant growth reference.

We evaluated currently available VLBW references, selected the best one, and compared that reference with the new CDC growth charts to examine the differences between the growth patterns of VLBW infants and those of non-VLBW infants. We then conducted a performance evaluation of these 2 references by comparing the growth patterns found in 2 external data sets for VLBW infants with both the selected VLBW reference and the CDC growth charts to determine which of the 2 growth references better reflected the growth patterns of VLBW infants.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Six VLBW growth references were available: 1) Casey et al1–3 (Infant Health and Development Program [IHDP]), currently distributed by Ross Laboratories); 2) Brandt,4 distributed by Milupa; 3) Gairdner and Pearson,5,17–20 distributed by Castlemead Publications; 4) Babson and Benda6,21–23 (formerly distributed by Ross Laboratories); 5) Lubchenco et al7,8 and Battaglia and Lubchenco,9 (currently distributed by Mead Johnson Laboratories); and 6) Ehrenkranz et al.24 We excluded the Lubchenco et al7,8 and Battaglia and Lubchenco9 reference from our review because the data were based on size at birth and do not represent postnatal growth. In addition, these data were collected between 1948 and 1961 and limited to infants born in Denver, CO, a city with a relatively high altitude, which is a known risk factor for LBW25–27 and may lead to higher postnatal energy expenditure. We also excluded the contemporary reference developed by Ehrenkranz et al24 because this reference can be used only up to a postnatal age of 120 days or a maximum of 2000 g in weight, a practical limitation in private clinical practice and public health settings.

We evaluated the 4 remaining VLBW references against our a priori criteria shown in Table 1. We developed these criteria by focusing on the methods used to create the reference and selected them from key characteristics that we believe would form the basis of an "ideal" VLBW growth reference. The ideal reference should be based on recent, representative, technically accurate measurements. We chose the best available reference on the basis of our a priori criteria.


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  		TABLE 1. Criteria for Evaluating the Available VLBW Growth References

 
All of our comparisons are based on age corrected for gestational age. Conceptually, this has to be done and Wang and Sauve28 have documented substantial differences in growth status with and without adjusting for gestational age. We also examined these differences in the IHDP data and found them to be of similar magnitude reported by Wang and Sauve.28 In addition, the IHDP reference is adjusted for gestational age. The length of time that adjustment for gestational age should continue remains uncertain, but our findings indicate at least 2 years and others suggest even longer.28,29

We compared the best available VLBW reference with the CDC growth charts to examine differences in levels and patterns of growth. The CDC growth charts included infants who weigh >1500 g at birth, and age is chronological age.

We used 2 external longitudinal data sets with growth data on VLBW infants to evaluate the performance of the best available VLBW reference and the CDC growth reference for assessing the growth status of VLBW infants. These external data sets were available from the Child Health and Development Studies (CHDS)30 and CDC’s linked Pregnancy Nutrition Surveillance System/Pediatric Nutrition Surveillance Systems (PNSS/PedNSS).31,32 The CHDS data set included VLBW children who were born in California between 1960 and 1966. Infants selected from these data sets for our analyses had birth weights between 500 g and 1500 g. The CHDS infants were socioeconomically diverse but primarily middle class and of varied racial/ethnic composition; their families were members of the Kaiser Foundation Health Plan. The PNSS/PedNSS data included low-income infants and children who participated in publicly funded health and nutrition programs and who were born between 1994 and 1996. The sample sizes in the IHDP reference (the selected best available VLBW reference) and in the 2 external data sets are described in Table 2. Clearly, the external data sets have small sample sizes that will decrease the stability of the percentile values. To increase the sample size and stabilize the percentile values of VLBW infants in these external data sets, we combined the CHDS and the linked PNSS/PedNSS data sets and repeated the comparisons. We compared percentiles in length-for-age, weight-for-age, and weight-for-length from these external data sets with the IHDP reference and with the CDC growth charts. No data on head circumference-for-age were available for the 2 combined external data sets. In both of these external data sets, gestational age was based on calculation of the difference between date of last menstrual period and date of delivery.


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  		TABLE 2. Sample Sizes by Age Group by Gender for the IHDP, CHDS, and PNSS/PedNSS Linked Data Sets

 

   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
On the basis of our evaluation criteria, we found that the IHDP growth reference seemed to be the best available reference for VLBW infants. The IHDP growth reference included infants with birth weights <=1500 g. Compared with the Brandt,4 Gairdner and Pearson,5 and Babson and Benda6 references, the IHDP data were collected in 1985, whereas the others were collected from before 1954 to 1975. The IHDP reference was based on the most representative of the population groups with VLBW infants (more blacks, more less-educated mothers), whereas the other available references were based on white infants. The IHDP reference had a relatively large sample that ranged from 212 to 219 infants at each measurement point and included longitudinal data from 40 weeks’ gestational age. In contrast, the Brandt4 reference was based on sample sizes of <=80 for each category of gestational age, and the Gairdner and Pearson5 reference was based on aggregate data with different indices derived from different data set of different children. The Babson and Benda6 reference was based on birth data from 26 to 40 weeks and longitudinal data from approximately 4000 white children from 1 month to 1 year with no description of frequency of measurement or the sample size at each measurement point. Only the IHDP reference specified exclusions. The IHDP reference data were based on standardized, appropriate measurement techniques as was the Brandt4 reference. The IHDP reference was the only one that included growth charts by gender, desired anthropometric indices, and major percentiles from birth to 36 months of age. The IHDP reference was adjusted for gestational age on the basis of the Ballard score,33 whereas the others were adjusted on the basis of calculation of the difference between the date of last menstrual period and date of delivery.

The other 3 growth references4–6 had serious limitations and would not be appropriate for assessing the growth status of VLBW infants. All were based on data collected before 1976. The Brandt4 reference was limited to primarily white, middle- to upper-income German children but had 1 impressive strength: the infants were measured longitudinally at monthly intervals by the same researcher. The earlier Gairdner and Pearson5 and Babson and Benda6 references were based on small sample sizes of aggregated data sets of specific indices (eg, different data sets for height and weight), which greatly limited their usefulness.

The IHDP reference also had limitations on the basis of our a priori criteria. Although the IHDP data were the most recent of the available references, they were collected in 1985, before improved and current medical and nutritional treatment protocols14–16 were widely instituted. Between 32 and 40 weeks of gestational age, the IHDP data were cross-sectional because measurements were taken only at birth: the longitudinal portion of the study began at 40 weeks’ corrected gestational age. In addition, length charts were not available before 40 weeks of gestation, and the 4-month measurement intervals in the first 12 months of life did not fully capture patterns of growth. Gestational age was derived from an abbreviated assessment of physical and neurologic characteristics based on the Ballard score, a simplified Dubowitz scoring system, that may have overestimated gestational age.33,34

We next compared the IHDP reference with the CDC growth charts to demonstrate the differences between the growth of VLBW infants in the IHDP reference and that of non-VLBW infants. For both boys and girls, the 5th and 50th percentiles for length-for-age in the IHDP reference nearly caught up to those in the CDC reference by 24 months, with the differences at that age being <2 cm (Fig 1). In contrast, the 5th and 50th percentiles for weight-for-age in the IHDP reference are nearly equivalent to those of the CDC reference at birth (40 weeks’ corrected gestation), but the IHDP curves increase more slowly (Fig 2). The IHDP 50th percentile is considerably below that in the CDC reference at 24 months. The IHDP 50th and 10th (data are not available for the 5th percentile) weight-for-length percentiles (Fig 3) are above the corresponding CDC reference percentiles until these infants reach approximately 60 cm in length, after which the IHDP percentiles cross over and are below those of the CDC reference. The 2 references are more similar for head circumference-for-age (Fig 4), although the IHDP reference percentiles show less rapid growth than the equivalent CDC percentiles until approximately 6 to 12 months, and the IHDP 5th percentile remains below the CDC 5th percentile until 36 months.



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  		Fig 1. Length-for-age 5th and 50th percentile comparison of the CDC growth charts and the IHDP VLBW reference.

 


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  		Fig 2. Weight-for-age 5th and 50th percentile comparisons of the CDC growth charts and the IHDP VLBW reference.

 


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  		Fig 3. Weight-for-length 10th and 50th percentile comparisons of the CDC growth charts and the IHDP VLBW reference.

 


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  		Fig 4. Head circumference-for-age 5th and 50th percentile comparisons of the CDC growth charts and the IHDP VLBW reference.

 
We then compared the 5th and 50th percentiles for length-for-age and weight-for-age and the 10th and 50th percentiles for weight-for-length for the VLBW infants in the 2 combined external (CHDS and PNSS/PedNSS) data sets with those of the IHDP reference and CDC growth charts (Figs 5–7). We made these comparisons to determine whether the size and growth patterns of VLBW infants included in the external data sets more closely approximated those of the infants in the IHDP reference or the CDC growth charts. The length and weight measurements of the VLBW infants included in the 2 combined external data sets more closely matched the relative position on the curves (size of the infants) of the IHDP reference. However, patterns of growth in the external data sets varied by indices as to which reference they more closely matched. The patterns of growth in length-for-age matched those of the IHDP reference (Fig 5). However, the slope of the data for weight-for-age growth is less clear. We do not have a large enough sample in the external data sets to delineate a smooth or stable pattern of growth, making it impossible to determine which reference is a better match for this index (Fig 6). In weight-for-length, the growth pattern of the infants in the combined additional data sets more closely follows the pattern of the CDC reference (Fig 7). For all of these comparisons, lack of smoothness in the growth patterns for the external data sets reflects the small sample sizes.



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  		Fig 5. Length-for-age comparison of the combined external data sets (CHDS and PNSS/PedNSS) for VLBW infants with the CDC and IHDP references. Lower lines, 5th percentile; upper lines, 50th percentile.

 


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  		Fig 7. Weight-for-length comparison of the combined external data sets (CHDS and PNSS/PedNSS) for VLBW infants with the CDC and IHDP references. Lower lines, 10th percentile; upper lines, 50th percentile.

 


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  		Fig 6. Weight-for-age comparison of the combined external data sets (CHDS and PNSS/PedNSS) for VLBW infants with the CDC and IHDP references. Lower lines, 5th percentile; upper lines, 50th percentile.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Our evaluation of growth references for VLBW infants yielded no clear, simple recommendation. The inconsistencies across anthropometric indices between the 2 external combined VLBW data sets (CHDS and PNSS/PedNSS) and the IHDP reference and the CDC growth charts make it difficult to recommend 1 reference. VLBW infants seem to have early, more rapid growth in length-for-age and in head circumference-for-age than non-VLBW infants. We also found that the growth status of the small (low end of their distribution) VLBW infants was below the normal range of the CDC growth charts, ie, between the 5th and 95th percentiles.35 Our conclusion that the IHDP reference is the best of the available references specific to VLBW infants is consistent with the Low Birthweight Workshop in 1994.36

Both the CDC and the IHDP references have limitations. The CDC growth charts do not include VLBW infants, and age is chronological age, not adjusted gestational age. However, this lack of adjustment will at best have only a minor effect because VLBW infants were excluded from the data set, and the rate of LBW (<2500 g) was relatively low (7.6% in 2000).37 The IHDP reference is not based on recent data. Gestational age may have been estimated inaccurately in the IHDP reference because they estimated gestational age using an abbreviated assessment of physical and neurologic characteristics based on the Ballard score, a simplified Dubowitz scoring system.33 Alexander et al34 showed that the Ballard score, when compared with gestational age estimated from ultrasonography, overestimated gestational age by 2 or more weeks in nearly half of the infants born at 28 to 31 weeks’ gestation. Estimated gestational age based on dates is considered reliable, providing the date of the last menses is considered to be relatively accurate. Estimation of gestational age based on a combination of ultrasound and date of last menstrual period is generally accepted as the most accurate method of assessment. Another limitation of the IHDP reference is that the measurements were not taken frequently enough to define the pattern of growth clearly, especially during infancy.

The combined external data sets (CHDS and PNSS/PedNSS) that we used for our performance evaluation also had limitations. Both of these data sets had small sample sizes for monthly measurements, which lowered the precision of our estimates of growth patterns of these infants. In addition, the CHDS data were collected in the 1960s. Just by virtue of their survival, the CHDS sample of VLBW infants may have differed substantially from current VLBW infants in the United States and therefore may not represent appropriate growth patterns for contemporary VLBW infants.

We recommend using either the IHDP reference or the CDC growth charts to evaluate the growth of VLBW infants. The choice of which to use depends on its purpose. The IHDP reference is appropriate for comparisons of the growth of a VLBW infant with those of other VLBW infants. This reference reflected the level of infant growth and the pattern of infant growth in length for age but not the pattern of weight-for-length seen in the combined CHDS and PNSS/PedNSS data sets. The CDC growth charts allow comparison of the growth of a VLBW infant with that of non-VLBW infants. Catch-up growth occurs among VLBW infants, but the growth of VLBW infants does not completely catch up to that of non-VLBW infants1–7 by 36 months. Regardless of which growth reference is selected, VLBW infants will have to be evaluated with the CDC growth charts after 36 months of age. However, it may be most convenient to change to the CDC growth charts at 24 months of age because after this age, stature instead of length is used to assess growth.

Because the CDC growth charts can be used to compare VLBW infants with non-VLBW infants, public health clinics and/or private practices may decide, for practical reasons, to use only the CDC reference. The CDC growth charts provide a single reference that can be used for assessment throughout childhood (not just until 36 months), and the growth status percentiles and/or z scores are readily accessible on the CDC web site (www.cdc.gov/growthcharts).

Our findings indicate that additional research is needed to document the growth patterns of VLBW children who receive current treatment protocols. We need to determine whether and how catch-up growth is affected by new clinical practices and to determine whether VLBW infants who are treated with these protocols require a new reference based on current data.

In conclusion, because VLBW infants grow differently than non-VLBW infants, the following caveats should be kept in mind when evaluating the growth status of VLBW infants:

  1. Postnatal age should be corrected for gestational age at birth before growth data for VLBW infants are plotted on a reference chart.
  2. When the IHDP reference is used, in general, the following differences in growth can be expected: a) the position of VLBW growth data will be within or close to the range of the reference; b) in length-for-age, the pattern of growth will be similar to the reference; c) in weight-for-age, the pattern of growth may be similar to the reference for the 50th percentile and show slightly less growth at the 5th percentile; d) in weight-for-length, initially the VLBW infants may be thinner for their length than the reference, then they will catch up to the reference by 60 cm and then become increasingly heavier for their length than the reference.
  3. When the CDC growth charts are used, in general, the following differences in growth can be expected: a) the position of VLBW infant data may be in the lower percentiles or below the fifth percentile of the charts; b) in length-for-age, VLBW infants initially may fall in the lower percentiles but will show catch up to approximate the CDC growth charts; boys will show catch up by approximately 30 months, and girls will show catch up by approximately 18 to 24 months; c) in weight-for-age, VLBW infants may exhibit a similar pattern of growth as the reference, yet they will be lighter for their age; d) in weight-for-length, VLBW infants will show similar growth to the CDC growth charts; e) in head circumference-for-age, we did not have comparison external data to evaluate the performance of the IHDP reference and the CDC growth charts; however, the IHDP reference shows catch-up growth toward the CDC growth charts as the infants grow. After 4 months of age, the IHDP reference shows a rapid catch-up to the CDC growth charts, and after 8 to 12 months of age, the head circumference-for-age percentiles of the IHDP infants is similar to those of the CDC growth charts.


   ACKNOWLEDGMENTS
 
We thank Alex F. Roche, MD, PhD; Patrick Casey, MD; Clifford Johnson, PhD; Robert Kuczmarski, PhD; and Cynthia Ogden, PhD, for thoughtful insights and review of this manuscript. We also thank Shumei Guo, PhD, for giving us access to the Infant Health and Development Program data.


   FOOTNOTES
 
Received for publication Jan 18, 2002; Accepted Sep 16, 2002.

Reprint requests to (B.S.) Maternal and Child Nutrition Branch, Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Mail Stop K-25, 4770 Buford Hwy, NE, Atlanta, GA 30341-3717. E-mail: bls6{at}cdc.gov


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics



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