Growth Charts for Children With Down Syndrome in the ...pediatrics.aappublications.org/content/pediatrics/early/2015/10/21/... · Growth Charts for Children With Down Syndrome in

Growth Charts for Children With DownSyndrome in the United StatesBabette S. Zemel, PhDa,b, Mary Pipan, MDb,c, Virginia A. Stallings, MDa,b, Waynitra Hall, MSa, Kim Schadt, MSNb,c,David S. Freedman, PhDd, Phoebe Thorpe, MD, MPHe

abstractBACKGROUND AND OBJECTIVES: Children with Down syndrome (DS) have lower birth weights andgrow more slowly than children without DS. Advances in and increased access to medical carehave improved the health and well-being of individuals with DS; however, it is unknownwhether their growth has also improved. Our objective was to develop new growth charts forchildren with DS and compare them to older charts from the United States and morecontemporary charts from the United Kingdom.

METHODS: The Down Syndrome Growing Up Study (DSGS) enrolled a convenience sample ofchildren with DS up to 20 years of age and followed them longitudinally. Growth parameterswere measured by research anthropometrists. Sex-specific growth charts were generated for theage ranges birth to 36 months and 2 to 20 years using the LMS method. Weight-for-length andBMI charts were also generated. Comparisons with other curves were presented graphically.

RESULTS: New DSGS growth charts were developed by using 1520 measurements on637 participants. DSGS growth charts for children ,36 months of age showed markedimprovements in weight compared with older US charts. DSGS charts for 2- to 20-year-oldsshowed that contemporary males are taller than previous charts showed. Generally, the DSGSgrowth charts are similar to the UK charts.

CONCLUSIONS: The DSGS growth charts can be used as screening tools to assess growth andnutritional status and to provide indications of how growth of an individual child compareswith peers of the same age and sex with DS.

WHAT’S KNOWN ON THIS SUBJECT: Children withDown syndrome (DS) grow differently from otherchildren. Advances in medical care, access tocare, and improved life expectancy suggest thatcontemporary growth patterns may haveimproved over recent decades for children withDS in the United States.

WHAT THIS STUDY ADDS: New growth charts arepresented for length/height, weight, headcircumference, and BMI for children with DS(birth to 20 y). Weight gain in children,36 months, and stature for males areimproved compared with older growth charts.

Divisions of aGastroenterology, Hepatology, and Nutrition, and cBehavioral Pediatrics, The Children’s Hospital ofPhiladelphia, Philadelphia Pennsylvania; bDepartment of Pediatrics, The University of Pennsylvania PerelmanSchool of Medicine, Philadelphia, Pennsylvania; and Divisions of dNutrition, Physical Activity, and Obesity, andeBirth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia

Dr Zemel conceptualized and designed the study, analyzed the data, and drafted the initialmanuscript; Dr Pipan participated in conceptualization and design of the study, participantrecruitment, and review of analyses and revised the manuscript; Dr Stallings participated inconceptualization and design of the study and review of analyses and revised the manuscript;Ms Hall and Ms Kim Schadt participated in study design and implementation, participant recruitment,and data collection and revised the manuscript; Drs Freedman and Thorpe critically reviewed theanalyses and revised the manuscript; and all authors approved the final manuscript as submitted.

The findings and conclusions in this report are those of the authors and do not necessarilyrepresent the official position of the Centers for Disease Control and Prevention.

www.pediatrics.org/cgi/doi/10.1542/peds.2015-1652

DOI: 10.1542/peds.2015-1652

Accepted for publication Aug 19, 2015

Address correspondence to Babette S. Zemel, PhD, Division of Gastroenterology, Hepatology andNutrition, The Children’s Hospital of Philadelphia, 3535 Market St, Room 1560, Philadelphia,PA 19104-4399. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2015 by the American Academy of Pediatrics

PEDIATRICS Volume 136, number 5, November 2015 ARTICLE by guest on June 9, 2018www.aappublications.org/newsDownloaded from

Down syndrome (DS) occurs in ∼1in 700 births in the United States1

and is associated with a spectrum ofphysical and cognitive disabilities. In1988, growth charts for US childrenwith DS were published by using datafrom multiple centers collectedbefore 1988,2 showing slow growthand short stature of children with DS.Since 1988, much has changed in thecare of children with DS, and theapplicability of those charts to growthin contemporary children with DS hasbeen questioned.3,4 Currently, theAmerican Academy of Pediatricsrecommends using standardgrowth charts for evaluating childrenwith DS until such time as currentDS-specific charts are available.3

Advances in medical care, andincreased access to care, haveimproved health and well-being ofindividuals with DS in the UnitedStates such that life expectancy hasrisen from 35 years in 19825 to53 years in 2007.6 One would expectthat growth of contemporary childrenwith DS has also improved, and thusprevious growth charts would lackreliability. In Europe, growth chartsfor children with DS used more recentdata extracted from medical chartreview,7,8 most notably in the UnitedKingdom and Ireland.9 To addressconcerns that growth ofcontemporary US children with DS isnot adequately characterized by the1988 charts, the Down SyndromeGrowing Up Study (DSGS), as acooperative project with the Centersfor Disease Control and Prevention(CDC), developed growth curvesbased on systematically obtainedgrowth measurements and modernstatistical techniques for developingreference percentiles. We presentthese growth curves, characterizetrends in growth of children with DSliving in the United States over thepast few decades, and offercomparisons with the UK growthcharts9 to assess internationaldifferences in growth of childrenwith DS.

METHODS

Children with DS, from birth to20 years of age, were recruited fromthe Trisomy 21 Clinic at TheChildren’s Hospital of Philadelphia(CHOP), CHOP general pediatricpractices, parent interest groups,community events, and schools,mainly in the greater Philadelphiaarea. Children were ineligible if theyhad other major genetic disordersknown to affect growth (eg, sickle celldisease) or were not in a usual stateof health (eg, cancer therapy) at thetime of measurement. Enrollmentoccurred from January 18, 2010,to July 23, 2013. Follow-upmeasurements occurred every3 months for age ,12 months, every6 months for ages 12 to 36 months,and annually if age .36 months untildata collection closed. Most evaluationsoccurred at the CHOP Clinical andTranslational Research Center (43%) orPediatric and Adolescent Specialty CareCenters (47%). The remaining studyvisits took place at community locations(10%) in Maryland, Virginia, New York,and Texas (National Down SyndromeCongress).

After written informed consent wasobtained, children underwent ananthropometric examination. Headcircumference (to nearest 0.1 cm)was measured with a nonstretchabletape measure. Weight was measuredon an electronic digital scale in lightclothing for older children (to nearest0.1 kg) and without clothing ordiapers for infants and toddlers(to nearest 0.01 kg). Length(to nearest 0.1 cm) was measured onan infant lengthboard for infants andtoddlers unable to standunsupported. For all others, height(to nearest 0.1 cm) was measuredwith a stadiometer. Trained personnelobtained measurements followingstandardized techniques.10

Measurements taken at CHOPlocations used standard equipmentmonitored by the bioengineeringdepartment. At community locations,length and stature measurements

were obtained using a portablelengthboard/stadiometer (Shorrboard, Shorr Productions, Olney, MD)and a portable digital electronic scale(Scaletronix, White Plains, NY).

Parents completed questionnairesproviding demographic, medicalhistory, and puberty status11

information.

The study was approved by theCommittee for the Protection ofHuman Subjects of CHOP.

Data Analysis

Data were stored in researchelectronic data capture (REDCap)12

and analyzed by using Stata 12.0(Stata Corp, College Station, TX).Means and frequencies weregenerated, as appropriate, for alldata. Growth measurementswere compared with the CDC(ages 2–20 years) and World HealthOrganization (WHO) (ages birth–36months) growth charts,13,14 andz scores (SD scores) were calculatedto compare the growth of childrenwith DS to standard charts.

Growth charts were created by usingthe LMS Chartmaker version 1.16(Harlow Printing, South Shields,UK),15,16 as described by Cole andGreen.17 This method uses theBox-Cox transformation to accountfor skewness, and a maximumpenalized likelihood method toestimate smoothed values for L (l),M (median), and S (coefficient ofvariation) over the age range. Thesevalues are used to calculate centilecurves using the following equation:Centile ¼ Mð1þ LSZÞ1=L;where L, M, and S are age-specificvalues, and Z is the value of a givenpercentile in the cumulative standardnormal distribution. For example,for Z = 0, the 50th centile can beestimated, and for Z = –1.64, the fifthpercentile can be calculated. Exactz scores are calculated by using thefollowing equation:Z ¼ ½ðX=MÞL 21�=LS;where X is the measured value foran individual. The goodness of fit of

e2 ZEMEL et al by guest on June 9, 2018www.aappublications.org/newsDownloaded from

the centile curves was assessed byusing visual inspection and q-q plotscomparing the observed data to thatgenerated using the estimatedparameters.

To be consistent with criteria used indeveloping the CDC 2000 growthcharts13 for children ,3 years, verylow birth weight (,1500 g) childrenwere excluded; for children born34 to 37 weeks’ gestation,chronological age was adjusted forgestational age; and it was assumedthat length was 0.7 cm greater thanstanding height. Reported birthweight was included in thedevelopment of the weight-for-agecharts. For children with DS .2 yearsof age unable to stand withoutassistance, length was measured, andthe values were adjusted to beequivalent to stature measures.Measurements of participants.21 years who continued in thestudy were included in the analysesto provide stability for the curvesnear the age of growth cessation.However, final curves were truncatedat age 20 years. Sex-specific curveswere generated for weight andheight/length for ages birth to20 years. Head circumference curveswere created separately for ages birthto 3 years and 2 to 20 years of ageto achieve an optimal curve fit.Weight-for-length curves werecreated for children ,3 years of age,and BMI curves were created forchildren 2 to 20 years of age.

The curves for weight and length/height were compared graphically tothe 1988 growth curves for theUnited States by Cronk et al2,18 and2002 curves for the United Kingdomby Styles et al.9

Baseline differences between thosewith one versus multiple visits werecompared by t tests and x2 tests asappropriate. Differences in growthbetween ethnic groups werecompared using mixed-effectsregression models accounting formultiple observations per subject.The LMS method assumes

independent observations. Therefore,to evaluate the effect of multipleobservations per subject, growthcurves using a single observationper subject were created and foundto be similar to the longitudinal DSGScurves (Supplemental Fig 3).

RESULTS

The study enrolled 637 participantsfrom 25 states; 86% were fromPennsylvania and New Jersey. A totalof 1520 growth measurements wereacquired. The average number ofvisits per participant was 3 (range1–9). Participants with only 1 visitwere older (126 6 years [mean6 SD],n = 234) at baseline than those withmultiple visits (7 6 6 years, n = 403),but there were no meaningfuldifferences by sex or race/ethnicitybetween those with 1 versus .1 visit.The sample was 51% male, 9%Hispanic, 11% non-Hispanic black(African American), and 73%non-Hispanic white by self-report.Twenty-one percent of subjects wereborn premature (gestational age,37 weeks), and 7% were born,34 weeks’ gestation (SupplementalTable 3). The average reported birthweight of all participants was 2.97 60.62 kg. Nine subjects with a birthweight ,1500 g were excluded.Supplemental Table 3 shows theprevalence of selected commoncomorbidities in children with DS asreported by parents. Cardiac defectsaffected 53% of the sample, andthyroid disease affected 23% ofparticipants.

Table 1 provides descriptive statisticsfor growth outcomes and z scoresrelative to WHO growth charts14 forchildren ,3 years of age and CDC2000 growth charts19 for the 2- to20-year age range. Children with DSwere shorter with smaller headcircumference for age (low z scores)compared with reference charts.Deficits in weight-for-age were moremodest. Weight-for-length z scoresfor children with DS ,3 years weresimilar to the distribution of the

WHO charts,14 but the mean BMIz score for children with DS aged 2 to20 years was higher.

Supplemental Tables 4 through 19provide the sex- and age-specific L, M,and S values and selected centilesfor weight, length/height, weight-for-length, BMI and head circumferenceused to calculate z scores andpercentiles. To assist in thesecomplex calculations, a Web sitecalculator is available (http://www.research.chop.edu/web/zscore).Corresponding growth charts areprovided in Supplemental Figs 4 to 11.

The new DSGS length/height andweight curves were compared withthe Cronk 19882 US and Styles9 2002UK curves (Figs 1 and 2). Both theDSGS and UK 2002 curves show animprovement in weight gain in thefirst 3 years of life (Fig 1A and B)compared with the US 1988 curves.Length of girls birth to 3 years isquite similar for all 3 sets of curves(Fig 1D). Contemporary US boys haveslightly greater lengths than thosein the other studies (Fig 1C).

The DSGS weight curves for ages 2 to20 years (Fig 2A and B) approximatethe US 1988 weight curves at manyages,2 especially for the fifth and50th percentiles. Compared with theUS 1988 weight curves, the 95thpercentile of older girls (.8 years)and the fifth and 50th percentiles forolder boys ($12 years) are greater,yet the 95th percentile for boys islower than the correspondingpercentiles on the DSGS curves. The95th percentile for weight of DSGSchildren is greater than the 95thpercentile for the United Kingdom,especially for older boys.

For 2 to 18 year olds, DSGS boys aretaller than the 1988 US curves atmost ages (Fig 2C). At age 18 years(the oldest age in the 1988 UScurves), the tallest boys (95thpercentile) in the DSGS curves arenotably taller than the tallest boysin the US 1988 curves. DSGS girls aretransiently taller than US 1988 girls

PEDIATRICS Volume 136, number 5, November 2015 e3 by guest on June 9, 2018www.aappublications.org/newsDownloaded from

around the ages of early to midpuberty, but with no appreciabledifference in final height (Fig 2D).Overall, the new DSGS curves forlength and height are similar tothe UK 2002 curves, although

contemporary US boys are slightlytaller than UK boys at some ages.Height at age 20 years (Fig 2C and2D) for boys and girls in the DSGScurves is slightly below that of theUK curves.

The current study developed curvesfor weight-for-length for birth to 3years (Supplemental Fig 10), BMI for2 to 20 years (Supplemental Fig 11),and head circumferences for youngerand older children (SupplementalFigs 6 and 9). Because no previouslypublished data on these values wereavailable, examination of seculartrends was not possible.

DSGS z scores for growth outcomeswere calculated and compared amongnon-Hispanic blacks, Hispanics, andnon-Hispanic whites (Table 2).Non-Hispanic blacks had significantlygreater z scores for weight, length(or height), and BMI, and Hispanicshad significantly greater z scores forweight, BMI, and weight-for-length,compared with non-Hispanic whites.Although these comparisons reflectthe variability between the meanz values among racial/ethnic groups,they do not address the extravariability that arises from theestimations of the z valuesthemselves.

DISCUSSION

This study describes the growth ofa convenience sample ofcontemporary children with DS intheir usual state of health living in theUnited States. The characteristic shortstature, small head circumference,and normal to high relative weightmeasures (weight-for-length andBMI) associated with this geneticsyndrome are evident. These growthcharts are designed to be used asscreening tools to assess growth andnutritional status and provideindications of how the growth of anindividual child compares with peersof the same age and sex with DS.

Marked improvements in weightstatus for the first 36 months of lifeare evident from comparisons withpreviously published US referenceranges. For children aged 2 to20 years, the weight distribution isapproximately similar to thosepublished more than 25 years ago,with 2 exceptions: the 95th percentile

TABLE 1 Growth Characteristics (Mean and SD) of Children With Down Syndrome With z ScoresBased on the CDC13 and WHO14 Standard Growth Charts

Variable Age Birth to 3 y Age 2 to 20 y

n No. Obs Mean SD n No. Obs Mean SD

Age, y 162 539 1.4 0.8 553 1083 9.4 5.2Height/length, cm 162 538 73.6 8.9 512 979 123.8 23.4WHO/CDC z scorea 21.7 1.2 510 972 22.1 1.1Wt, kg 162 539 9.3 2.4 552 1081 33.2 20.4WHO/CDC z scorea 20.8 1.2 552 1081 20.5 1.3Head circumference, cm 162 536 43.7 2.7 541 1055 49.2 2.8WHO z scoreb 21.6 1.0 59 289 21.9 1.0Weight for length z scorea 162 538 0.2 1.1BMI, kg/m2 512 979 21.1 5.8CDC BMI z scorea 512 979 0.9 1.0

No. Obs: number of observations.a z scores calculated using standard WHO growth charts for age birth to 3 y14 and the CDC growth charts for ages 2 to20 y.13b z score calculated using standard WHO growth charts for birth to 5 y.

FIGURE 1Curve comparisons for weight in kilograms and length in centimeters for male and female subjects,birth to 36 months of age. Contemporary curves from the DSGS (solid line) are compared with thosefrom the US 1988 curves from Cronk et al (dotted line) and the UK 2002 curves from Styles et al(dashed line).

e4 ZEMEL et al by guest on June 9, 2018www.aappublications.org/newsDownloaded from

for girls is greater than the US 198895th percentile2 for age $8 years,and for boys $12 years, the fifth and50th percentiles are greater, yet the95th percentile is lower (beginningapproximately age 8 years) than thecorresponding US 1988 percentiles.Given the increasing prevalence ofpediatric obesity in the generalpopulation during this time period,20

it is surprising that greater shifts in

the weight-for-age distribution didnot occur.

Changes in linear growth over thepast few decades have mainlyoccurred in males. Boys, birth to3 years, have modestly longer lengththan previously estimated. The fifth,50th, and 95th percentiles are greaterthan previous correspondingpercentiles at most ages afterapproximately age 5 years, and the

95th percentile for boys is greaterthan the older growth curves. Theexplanation for this secular trend inboys but not girls is unclear. Sexdifferences in health complicationsof DS may possibly contribute to thispattern. For example, Freeman et alreported a higher preponderanceof female infants with DS who hadatrioventricular septal defects.21

Alternatively, short stature amonggirls may be more acceptable toparents and physicians than amongboys, as reported among childrenwithout DS,22 leading to lessinvestigation and intervention.However, the strong consistency inUS and UK weight and length/staturedistributions suggests that thesecurves represent growth patternsof well-nourished contemporarychildren with DS with access tocurrent medical care practices.

Feeding difficulties are commonfor infants with DS and may bedue to hypotonia; poor oromotor,pharyngeal, and esophagealcoordination; fatigue; difficultyinitiating sucking; slow suckingreflex; vomiting; and choking.23

Nutritional status in the early yearsis particularly concerning. We presentweight-for-length charts for childrenbirth to 3 years to aid in nutritionalscreening for growth faltering,wasting and excess weight gainduring this critical period of braindevelopment.

We present the first BMI charts for USchildren with DS, aged 2 to 20 years.Children with DS have shorter limbsthan children without DS, resulting in

FIGURE 2Curve comparisons for weight in kilograms and height in centimeters for male and female subjects, 2to 20 years of age. Contemporary curves from the DSGS (solid line) are compared with those from theUS 1988 curves from Cronk et al (dotted line) and the UK 2002 curves from Styles et al (dashed line).

TABLE 2 Differences Among Race/Ethnicity Groups In Growth Outcomes

DSGS z scores Non-Hispanic White Non-Hispanic Black Hispanic Othera

Mean 6 SD No. Obs n Mean 6 SD No. Obs n Mean 6 SD No. Obs n Mean 6 SD No. Obs n

Wt 20.10 6 0.93 1093 457 0.63 6 1.07*** 154 70 0.25 6 0.98** 138 58 20.07 6 0.94 94 36Length/height 20.08 6 0.97 1090 457 0.49 6 0.94*** 154 70 0.07 6 1.13 137 58 0.14 6 0.98 94 36BMIb 20.07 6 0.99 753 389 0.68 6 1.06*** 93 54 0.32 6 0.83* 79 43 0.03 6 1.02 55 28Head circumferencec 0.10 6 0.99 364 106 20.25 6 1.06 68 25 20.07 6 1.06 65 22 20.20 6 0.72 40 12Weight for lengthc 20.04 6 0.97 366 106 0.23 6 1.24 68 25 0.42 6 0.88* 63 21 20.50 6 0.93 40 12

All outcomes are expressed as age and sex-specific DSGS z scores. No. Obs: number of observations.a Other includes Asian, Native American, and mixed race. Significantly different from Non-Hispanic White group: ***P , .001; **P , .01; *P , .05.b Age .2 y.c Age ,3 y.

PEDIATRICS Volume 136, number 5, November 2015 e5 by guest on June 9, 2018www.aappublications.org/newsDownloaded from

a different distribution of body massrelative to height. Obesity is commonin DS24; among 1450 adults withdevelopmental disabilities, adults withDS had a higher prevalence than othergroups, with .50% of adults with DSbeing obese.25 It is unknown whetherthe use of the CDC 2000 BMI charts19

and traditional cutoffs26 to defineobesity are appropriate given thealtered body mass distributioncharacteristic of DS. Our average BMIvalues were nearly 1 SD above themedian of the CDC charts, comparedwith 0.5 SD among children examinedin recent US surveys.27 Excessadiposity is a concern, and thusa screening tool that is appropriate forchildren with DS is needed. It isimportant to recognize that the DSGSBMI charts merely describe thedistribution of BMI values in thissample. Plotting an individual BMIvalue on these charts providesinformation on how an individualcompares with other children with DS.The DSGS BMI charts do not representan ideal healthy distribution of BMI.Additional investigation is requiredto determine how best to apply theDSGS BMI charts to screen for excessadiposity and associated healthoutcomes.

Concerns have been raised regardingcondition-specific growth chartsbased on limitations of sample sizeand its representativeness as well asmeasurement quality.28 This studyaddressed some concerns by usingstandardized measurements on .600contemporary children with DS intheir usual state of health. Weincluded children with cardiac andthyroid complications, which couldaffect growth. Reassuringly, theprevalence of these importantcomorbidities is similar to otherstudies,29,30 suggesting that oursample is similar to the population ofchildren with DS in the United Stateswith respect to these comorbidities.

This study had several limitations.An assumption underlying statisticaltesting is that the data on which the

tests are based represents a randomsample from the target population. Inthis study, a convenience sample ofchildren attending clinics andcommunity events, not a randomsample, was used. We do not thinkthat the use of a convenience samplemeaningfully biased our results asshown in Supplemental Fig 3, but thisshould be kept in mind whenassessing the results of statisticaltesting. This sample is mostly fromthe greater Philadelphia region andmay not represent US regionalvariation in race/ethnicity and inobesity. This study includesnon-Hispanic blacks (11%) andHispanics (9%) at lower than nationalaverages (14%) non-Hispanic blackand 23% Hispanic children (age,18 years) based on the 2010 USCensus).31 For children with DS, therace/ethnicity distribution in the USpopulation is unknown. An 11-statesurveillance study found thatnon-Hispanic black mothers hada lower prevalence ratio (0.77)whereas Hispanic mothers hada higher prevalence ratio (1.12) of DSbirths compared with non-Hispanicwhite mothers.32 The impact on theDSGS curves of the lowerrepresentation of minority groups canbe inferred from the comparison ofgrowth z scores among groups.Non-Hispanic black children weretaller and heavier, and Hispanicchildren were heavier than theirnon-Hispanic white peers. On thebasis of these findings, it is possiblethat the DSGS growth curvesunderestimate length/height and weightdue to the underrepresentation ofnon-Hispanic blacks and Hispanics.

Because no data were collected fromfamilies who declined participation,the effect of recruitment bias cannotbe estimated. The effect of multipleobservations per subject in thislongitudinal convenience sample isalso difficult to ascertain. However,sensitivity analyses indicated that theimpact of this lack of independenceamong data points used to estimatethe growth curves was negligible.

Lastly, these growth curves are basedon a contemporary sample of childrenin their usual state of health and maynot represent “optimal” growth ofchildren with DS.

CONCLUSIONS

The DSGS growth charts presentedhere for children with DS residing inthe United States are based ona contemporary sample of infants,children, and adolescents in theirusual state of health, usingstandardized measurements, andmodern statistical techniques togenerate smoothed percentiles.Previously unavailable weight-for-length and BMI charts were alsodeveloped to provide additional toolsfor assessment of nutritional status.The improvements in growth in thepast 25 years and consistency with2002 charts from the United Kingdomprovide further evidence of theimportance and strengths of thesenew charts.

ACKNOWLEDGMENTS

Our greatest thanks go to the childrenand their families who participated inthis study and the parent interestgroups, schools, camps, and otherorganizations that assisted in reachingthose families. We also express ourappreciation to the Trisomy 21 Clinicand the Adolescent and PediatricSpecialty Care Centers of CHOP, toteam members of the DSGS and theClinical and Translational ResearchCenter, and to Dr Sonja Rasmussen forher efforts early in this process toshare her vision and ensure supportfor this project.

ABBREVIATIONS

CDC: Centers for Disease Controland Prevention

CHOP: The Children’s Hospital ofPhiladelphia

DS: Down syndromeDSGS: Down Syndrome Growing

Up StudyWHO: World Health Organization

e6 ZEMEL et al by guest on June 9, 2018www.aappublications.org/newsDownloaded from

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Supported by U01 DD000518, UL1RR024134 (National Center for Research Resources), and UL1TR000003 (National Center for Advancing Translational

Sciences).

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

REFERENCES

1. Parker SE, Mai CT, Canfield MA, et al;National Birth Defects PreventionNetwork. Updated National BirthPrevalence estimates for selected birthdefects in the United States, 2004–2006.Birth Defects Res A Clin Mol Teratol.2010;88(12):1008–1016

2. Cronk C, Crocker AC, Pueschel SM, et al.Growth charts for children with Downsyndrome: 1 month to 18 years of age.Pediatrics. 1988;81(1):102–110

3. Bull MJ; Committee on Genetics. Healthsupervision for children with Downsyndrome. Pediatrics. 2011;128(2):393–406

4. Rasmussen SA, Whitehead N, Collier SA,Frías JL. Setting a public health researchagenda for Down syndrome: summaryof a meeting sponsored by the Centersfor Disease Control and Preventionand the National Down SyndromeSociety. Am J Med Genet A. 2008;146A(23):2998–3010

5. Thase ME. Longevity and mortality inDown’s syndrome. J Ment Defic Res.1982;26(pt 3):177–192

6. Presson AP, Partyka G, Jensen KM, et al.Current estimate of Down syndromepopulation prevalence in the UnitedStates. J Pediatr. 2013;163(4):1163–1168

7. Myrelid A, Gustafsson J, Ollars B,Annerén G. Growth charts for Down’ssyndrome from birth to 18 years of age.Arch Dis Child. 2002;87(2):97–103

8. Van Gameren-Oosterom HB, VanDommelen P, Oudesluys-Murphy AM,Buitendijk SE, Van Buuren S, Van WouweJP. Healthy growth in children withDown syndrome. PLoS One. 2012;7(2):e31079

9. Styles ME, Cole TJ, Dennis J, Preece MA.New cross sectional stature, weight, andhead circumference references forDown’s syndrome in the UK and Republicof Ireland. Arch Dis Child. 2002;87(2):104–108

10. Lohman T, Roche AF, Martorell R.Anthropometric standardization

reference manual. Champaign, IL: HumanKinetics Books; 1988

11. Morris NM, Udry JR. Validation of a self-administered instrument to assess stageof adolescent development. J YouthAdolesc. 1980;9(3):271–280

12. Harris PA, Taylor R, Thielke R, Payne J,Gonzalez N, Conde JG. Researchelectronic data capture (REDCap)—a metadata-driven methodology andworkflow process for providingtranslational research informaticssupport. J Biomed Inform. 2009;42(2):377–381

13. Kuczmarski RJ, Ogden CL, Guo SS, et al.2000 CDC Growth Charts for the UnitedStates: methods and development. VitalHealth Stat. 2002;May11(246):1–190

14. WHO Multicentre Growth ReferenceStudy Group. WHO Child GrowthStandards: head circumference-for-age,arm circumference-for-age, tricepsskinfold-for-age and subscapularskinfold-for-age: methods anddevelopment. Geneva, Switzerland: WorldHealth Organization; 2007

15. Pan H, Cole T. LMSchartmaker,a program to construct growthreference data using the LMS method,Software Version 2.43. 2010. Available at:http://www.healthforallchildren.com/?product=lmschartmaker-pro

16. Pan H, Cole TJ. LMSgrowth, a MicrosoftExcel add-in to access growth referencesbased on the l method, Version 2.69.2010. Available at: http://www.healthforallchildren.com/shop-base/software/lmsgrowth

17. Cole TJ, Green PJ. Smoothing referencecentile curves: the LMS method andpenalized likelihood. Stat Med. 1992;11(10):1305–1319

18. Cronk CE. Growth of children with Down’ssyndrome: birth to age 3 years.Pediatrics. 1978;61(4):564–568

19. Ogden CL, Kuczmarski RJ, Flegal KM,et al. Centers for Disease Control andPrevention 2000 growth charts for the

United States: improvements to the 1977National Center for Health Statisticsversion. Pediatrics. 2002;109(1):45–60

20. Ogden CL, Carroll MD, Kit BK, Flegal KM.Prevalence of obesity in the UnitedStates, 2009–2010. NCHS Data Briefno. 82. Hyattsville, MD: National Centerfor Health Statistics; 2012:1–8

21. Freeman SB, Bean LH, Allen EG, et al.Ethnicity, sex, and the incidence ofcongenital heart defects: a reportfrom the National Down SyndromeProject. Genet Med. 2008;10(3):173–180

22. Grimberg A, Feemster KA, Pati S, et al.Medically underserved girls receive lessevaluation for short stature. Pediatrics.2011;127(4):696–702

23. Lewis E, Kritzinger A. Parentalexperiences of feeding problems in theirinfants with Down syndrome. DownsSyndr Res Pract. 2004;9(2):45–52

24. Roizen NJ, Patterson D. Down’ssyndrome. Lancet. 2003;361(9365):1281–1289

25. Hsieh K, Rimmer JH, Heller T. Obesity andassociated factors in adults withintellectual disability. J Intellect DisabilRes. 2014;58(9):851–863

26. Krebs NF, Himes JH, Jacobson D, NicklasTA, Guilday P, Styne D. Assessment ofchild and adolescent overweight andobesity. Pediatrics. 2007;120(suppl 4):S193–S228

27. Weber DR, Leonard MB, Shults J, ZemelBS. A comparison of fat and leanbody mass index to BMI for theidentification of metabolic syndrome inchildren and adolescents. J ClinEndocrinol Metab. 2014;99(9):3208–3216

28. U.S. Department of Health and HumanServices, Health Resources andServices Administration, Maternal andChild Health. The CDC growth charts forchildren with special health careneeds. Issues regarding the use ofcondition-specific growth charts.

PEDIATRICS Volume 136, number 5, November 2015 e7 by guest on June 9, 2018www.aappublications.org/newsDownloaded from

Available at: http://depts.washington.edu/growth/cshcn/text/page6b.htm.Accessed March 20, 2015

29. Morris JK, Garne E, Wellesley D, et al.Major congenital anomalies in babiesborn with Down syndrome: a EUROCATpopulation-based registry study.Am J Med Genet A. 2014;164A(12):2979–2986

30. Roizen NJ, Magyar CI, Kuschner ES, et al.A community cross-sectional survey ofmedical problems in 440 children withDown syndrome in New York State. JPediatr. 2014;164(4):871–875

31. Humes KR, Jones NA, Ramirez RR.Overview of Race and Hispanic Origin:2010. United States Census Bureau;March 2011. Available at: www.census.

gov/prod/cen2010/briefs/c2010br-02.pdf.Accessed December 4, 2014

32. Canfield MA, Honein MA, Yuskiv N,et al. National estimates and race/ethnic-specific variation of selectedbirth defects in the United States,1999–2001. Birth Defects Res AClin Mol Teratol. 2006;76(11):747–756

e8 ZEMEL et al by guest on June 9, 2018www.aappublications.org/newsDownloaded from

originally published online October 26, 2015; Pediatrics David S. Freedman and Phoebe Thorpe

Babette S. Zemel, Mary Pipan, Virginia A. Stallings, Waynitra Hall, Kim Schadt,Growth Charts for Children With Down Syndrome in the United States

ServicesUpdated Information &

015-1652http://pediatrics.aappublications.org/content/early/2015/10/21/peds.2including high resolution figures, can be found at:

Subspecialty Collections

http://www.aappublications.org/cgi/collection/nutrition_subNutritional_issues_subhttp://www.aappublications.org/cgi/collection/development:behaviorDevelopmental/Behavioral Pediatricsfollowing collection(s): This article, along with others on similar topics, appears in the

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtmlin its entirety can be found online at: Information about reproducing this article in parts (figures, tables) or

Reprintshttp://www.aappublications.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:

by guest on June 9, 2018www.aappublications.org/newsDownloaded from

originally published online October 26, 2015; Pediatrics David S. Freedman and Phoebe Thorpe

Babette S. Zemel, Mary Pipan, Virginia A. Stallings, Waynitra Hall, Kim Schadt,Growth Charts for Children With Down Syndrome in the United States

http://pediatrics.aappublications.org/content/early/2015/10/21/peds.2015-1652located on the World Wide Web at:

The online version of this article, along with updated information and services, is

http://pediatrics.aappublications.org/content/suppl/2015/10/21/peds.2015-1652.DCSupplementalData Supplement at:

ISSN: 1073-0397. 60007. Copyright © 2015 by the American Academy of Pediatrics. All rights reserved. Print the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,has been published continuously since 1948. Pediatrics is owned, published, and trademarked by Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it

by guest on June 9, 2018www.aappublications.org/newsDownloaded from