A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants
© Fenton and Kim; licensee BioMed Central Ltd. 2013
Received: 12 October 2012
Accepted: 10 April 2013
Published: 20 April 2013
Skip to main content
© Fenton and Kim; licensee BioMed Central Ltd. 2013
Received: 12 October 2012
Accepted: 10 April 2013
Published: 20 April 2013
The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring.
Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated.
Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks.
The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts.
The expected growth of the fetus describes the fastest human growth, increasing weight over six-fold between 22 and 40 weeks. Preterm infants, who are born during this rapid growth phase, rely on health professionals to assess their growth and provide appropriate nutrition and medical care.
In 2006, the World Health Organization (WHO) published their multicentre growth reference study, which is considered superior  to previous growth surveys since the measured infants were selected from communities in which economics were not likely to limit growth, among culturally diverse non-smoking mothers who planned to breastfeed . Weekly longitudinal measures of the infants were made by trained data collection teams during the first 2 years of this study . These WHO growth charts, although recommended for preterm infants after term age , begin at term and so do not inform preterm infant growth assessments younger than this age.
Optimum growth of preterm infants is considered to be equivalent to intrauterine rates [5–7] since a superior growth standard has not been defined. Perhaps the best estimate of fetal growth may be obtained from large population-based studies, conducted in developed countries , where constraints on fetal growth may be less frequent.
A recent multicentre study by our group (the Preterm Multicentre Growth (PreM Growth) Study) revealed that although the pattern of preterm infant growth was generally consistent with intrauterine growth, the biggest deviation in weight gain velocity between the preterm infants and the fetus and infant was just before term, between 37 and 40 weeks (Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R: Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant, The Preterm Infant Multicentre Growth Study. Submitted BMC Ped 2012). Rather than demonstrating the slowing growth velocity of the term infant during the weeks just before term, the preterm infants had superior, close to linear, growth at this age. This finding has been observed by others as well [9–11]. Therefore, there is evidence to support a smooth transition on growth charts between late fetal and early infant ages.
Several previous growth charts based on size at birth presented their data as completed age, which affects the interpretation and use of a growth chart . The use of completed weeks when plotting a growth chart requires all the measurements to be plotted on the whole week vertical axes. However, the use of completed weeks in a neonatal unit may not be intuitive, as nursery staff and parents think of infants as their exact age, and not age truncated to previous whole weeks. The advent of computers in health care, for clinical care and health recording, allow the use of the computer to plot growth charts, daily and with accuracy. It would make sense to support plotting daily measurements continuously by shifting the data collected as completed weeks to the midpoint of the next week to remove the truncation of the data collection as completed weeks.
The objectives of this study were to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) use more recent data on size at birth based on an inclusion criteria, b) harmonize the preterm growth chart with the new WHO Growth Standard, c) to smooth the data between the preterm and WHO estimates while maintaining integrity with the data from 22 to 36 and at 50 weeks, d) to derive sex specific growth curves, and to e) re-scale the chart x-axis to actual age rather than completed weeks, to support growth monitoring.
Corrected gestational ages through fetal ultrasound and/or infant assessment and/or statistical correction;
Data percentiles at 24 weeks gestational age or lower;
Sample of at least 25,000 babies, with more than 500 infants aged less than 30 weeks;
Separate data on females and males;
Data available numerically in published form or from authors,
Data collected within the past 25 years (1987 to 2012) to account for any secular trends.
Major bibliographic databases were searched: MEDLINE (using PubMed) and CINHAL, by both authors back to year 1987 (given our 25 year limit), with no language restrictions, and foreign articles were translated. The following search terms as medical subject headings and textwords were used: (“Preterm infant” OR “Premature Birth”[Mesh]) OR (“Infant, Premature/classification”[Mesh] OR “Infant, Premature/growth and development”[Mesh] OR “Infant, Premature/statistics and numerical data”[Mesh] OR “Infant, very low birth weight”[Mesh]) AND (percentile OR *centile* OR weeks) AND (weight OR head circumference OR length). Grey literature sites including clinical trial websites and Google were searched in February 2012. Reference lists were reviewed for relevant studies.
All of the found data was reported as completed weeks except for the German Perinatal Statistics, which were reported as actual daily weights . To combine the datasets, the German data was temporarily converted to completed weeks. A final step converted the meta-analyses to actual age.
To maintain integrity with the meta-analysis curves from 22 to 36 weeks. Integrity of the fit was assumed to be agreement within 3% at each week.
To ensure fit of the data to the WHO values at 50 weeks, within 0.5%.
Cubic splines were used to interpolate smooth values between selected points (22, 25, 28, 32, 34, 36 and 50 weeks). Extra points were manually selected at 40, 43 and 46 weeks in order to produce acceptable fit through the underlying data. The PreM Growth study (Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R: Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant, The Preterm Infant Multicentre Growth Study. Submitted BMC Ped 2012) conducted to inform the transition between the preterm and WHO data, was used to inform this step. The Prem Growth Study found that preterm infants growth in weight followed approximately a straight line between 37 and 45 weeks, as others have also noted [9–11].
LMS values (measures of skew, the median, and the standard deviation)  were computed from the interpolated cubic splines at weekly intervals. Cole’s procedures  and an iterative least squares method were used to derive the LMS parameters (L = Box-Cox power, M = median, S = coefficient of variation) from the multicentre meta-analyses for weight, head circumference and length. The LMS splines were smoothed slightly while maintaining data integrity as noted above.
The final percentile curves were produced from the smoothed LMS values.
A grid similar to the 2003 growth chart was used, but the growth curves were re-scaled along the x-axis from completed weeks to allow clinicians to plot infant growth by actual age in weeks, and a slight modification (scaled to 60 centimeters instead of 65) was made to the y-axis.
The revised growth charts were compared graphically with the original 2003 Fenton preterm growth chart. To make the differences in chart values more apparent, the 2003 chart data was also shifted to actual weeks for these comparison figures.
Details of the data sources
German Perinatal Survey
Pediatrix Medical Group hospitals
Canadian national file
Australian National Perinatal Statistics Unit
Scottish maternity data collection
Italian Neonatal Study
WHO multicentre growth reference study
n < 30 weeks
Lowest gestational age
1995 to 2000
1998 to 2006
1994 to 1996
1991 to 1994
1998 to 2003
2005 to 2007
Weight, head, length
Weight, head, length
Weight, head, length
None stated, included both live and stillborn
Multiple births, congenital anomalies, death before discharge, outlier measures (> 2 x interquartile range below the first and 3rd quartile).
Ontario province was excluded due to problems with data quality.
Omitted multiple and still births (births < 400 grams did not need to be recorded)
Multiple births, lethal anomalies, weights < 250 grams, and outlier measures (> 2 x interquartile range outside the first and 3rd quartile).
Multiple births, stillbirths, major congenital anomalies, and fetal hydrops
Maternal smoking, not breastfeeding, solids before 4 months. Screened for environmental or economic constraints.
Method to assess gestational age
Ultrasound assessment 8–14 weeks and Naegle’s rule.
“early ultrasound has increasingly been the basis for gestational age assessments in recent years”
Dates, prenatal, or postnatal assessment
Clinician assessment based on ultrasound, maternal dates, and clinical estimates
Ultrasound assessment first trimester
Cubic regression, LOESS smoothing, LMS parameter smoothing
LMS methods, with the skew set to one and further manual smoothing
Assumed a log normal distribution of birthweight at each gestational age and compared the probabilities of accurate versus misclassification of infant’s gestational age
Omitted outlier measures (> 2 x interquartile range below the first and 3rd quartile).
Cubic spline fitting
Generalized logistic functions
Omitted outliers > 3 SD, LMS parameter smoothing, skew set to one for weight, cubic spline fitting.
Number of infants each week from each study
We used a strict set of inclusion criteria to include only the best data available to convert fetal and infant size data into fetal-infant growth charts for preterm infants. The revised sex-specific actual-age (versus completed weeks) growth charts (Figure 9 and 10), are based on birth size information of almost four million births with confirmed or corrected gestational ages, born in developed countries (See Features of the new growth chart). The revised charts are based on the recommended growth goal for preterm infants, the fetus and the term infant, with smoothing of the disjunction between these datasets, based on the findings of our international multicentre validation study (Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R: Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant, The Preterm Infant Multicentre Growth Study. Submitted BMC Ped 2012). These charts are consistent with the meta-analysis data up to and including 36 weeks, thus they can be used for the assessment of size for gestational age for preterm infants under 37 weeks of gestational age. This growth chart is likely applicable to preterm infants in both developed and developing countries since the data was selected from developed countries to minimize the influence from circumstances that may not have been ideal to support growth.
Based on the recommended growth goal for preterm infants: The fetus and the term infant
Girl and boy specific charts
Equivalent to the WHO growth charts at 50 weeks gestational age (10 weeks post term age).
Large preterm birth sample size of 4 million infants;
Recent population based surveys collected between 1991 to 2007
Data from developed countries including Germany, Italy, United States, Australia, Scotland, and Canada
Curves are consistent with the data to 36 weeks, thus can be used to assign size for gestational age up to and including 36 weeks.
Chart is designed to enable plotting as infants are measured, not as completed weeks. The x axis was adjusted for this chart so that infant size data can be plotted without age adjustment, i.e. Babies should be plotted as exact ages, that is a baby at 25 3/7 weeks should be plotted along the x axis between 25 and 26 weeks.
Exact z-score and percentile calculator available for download from http://ucalgary.ca/fenton. Data is available for research upon request.
It may be more intuitive to plot on growth charts using exact ages rather than on the basis of complete weeks. Several years ago, the WHO used completed age for growth chart development . This recommendation was likely due to the way data had been collected in the past, that is all 26 0/7 through 26 6/7 week infants were included in the 26 week completed week category. However, with the use of computers to plot on growth charts comes the potential to more accurately plot measurements to the exact day of data collection. Thus the time scale of the horizontal axes of these new growth charts were re-scaled to actual age, for ease of use and understanding. For example, a baby at 25 3/7 can be intuitively plotted between 25 and 26 weeks.
Exact z-score and centile calculators for the revised charts are available for download: http://ucalgary.ca/fenton. Data is available for research upon request.
The data revealed that between 22 weeks to 50 weeks post menstrual age, the fetus/infant multiplies its weight tenfold, for example, the girls’ median weight increased from a median of 520 to 5360 grams. Using a fetal-infant growth chart allows clinicians to compare preterm infants’ growth to an estimated reference of the fetus and the term infant.
There was a remarkably close fit of the included preterm surveys for weight, head circumference and length from the 6 countries, especially at the 50th percentile, even though the data came from different countries.
The splining procedures we used have produced a chart that has integrity and good agreement with the original data. Smoothing of the LMS parameters is recommended since minor fluctuations are more likely due to sampling errors rather than physiological events . Experts recommend that growth charts be developed based on smoothed L, M and S, to constrain the adjacent curves so that they relate to each other smoothly . The World Health Organization set their L parameter to 1 for head circumference and length, while they maintained the exact L values for infants’ weights . The data under study here revealed the same effect as the WHO data; we found that both head circumference and length were close enough to normal distributions that normal distributions could summarize the data, while the exact L’s were needed to retain the nuances of the weight curves.
The differences between the revised growth charts and the 2003 Fenton preterm growth chart may reflect improvements since the selected preterm growth references for the new versions are more likely globally representative of fetal and infant growth. Some of the differences between the current charts and the 2003 version are likely due to the separation into girl and boy charts, since the shifts of the girls’ curves tend to be downward and the boys’ curves upward. The weight shifts after 40 weeks were upward for both sexes, due to the higher values for the WHOGS compared to the CDC growth reference  at 10 weeks post term.
The ideal growth pattern of preterm infants remains undefined. These revised growth charts were developed based on the growth patterns of the fetus (as has been determined by size at birth in the large population studies) and the term infant (based on the WHO Growth Standard) . Ultrasound studies and comparison of subgroups of prematurely born infants suggest that the fetal studies, such as those used in this development, may be biased by the premature birth since fetuses who remain in utero likely differ in important ways from babies who are born early [60, 61]. However, fetal size from these imperfect studies may be the best data available at this point in time for comparing the growth of preterm infants since the alternative, to compare to in utero infants requires extrapolation from ultrasound measurements. To use other premature infants as the growth reference for preterm infants may not be ideal since the ideal growth of preterm infants has not been defined, has been changing over time , and is influenced by the nutrition and medical care received after birth [63, 64].
Although the WHOGS is considered to be a growth standard, the infants in the population-based surveys of size at birth are more likely representative of the reference populations and were not selected to be healthy. Thus these growth charts are growth references and are not a growth standard. The INTERGROWTH study, currently underway, will rectify this problem, since their purpose is to develop prescriptive standards for fetal and preterm growth .
The inclusion of data from a number of developed countries increases the generalizability of the growth chart. The revised preterm growth chart, harmonized with the World Health Organization Growth Standard at 50 weeks, may support an improved transition of preterm infant growth monitoring to the WHO charts.
Many thanks to Patrick Fenton and Misha Eliasziw for statistical assistance, Roseann Nasser, Reg Sauve, Debbie O’Connor, and Sharon Unger for encouragement and advice, and Jayne Thirsk for editing advice.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.