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ing physical growth of infants and children in the UnitedStates and in many parts of the world.

Many physical growth studies of children with CLP havebeen published (Ross and Jhonston, 1972; Bowers et al.,1987; Felix-Schollaart et al., 1992; Cunningham andJerome, 1997; Becker et al., 1998; Gopinath and Muda,2005; Montagnoli et al., 2005). Although the results varybetween different investigators, most of them state thatthese children are smaller and lighter than the controlsubjects, mainly during the first years of age. A catch-upgrowth may occur later in childhood (Ross and Jhonston,1972; Lee et al., 1996).

Many factors such as feeding problems and recurrentrespiratory infections have been suggested to negativelyaffect normal growth. Reports indicate that growthproblems are more severe in early infancy and are morefrequent in children with isolated cleft palate (ICP) andCLP than in children with isolated cleft lip or normal

(unaffected) children (Felix-Schollaart et al., 1992; Lee etal., 1996; Montagnoli et al., 2005).

The limitations of previous growth studies includerelatively small numbers of children included in thesamples, possible inclusion of children with chronic healthconditions and syndromes, and inclusion of different typesof clefts or age ranges. Most studies were retrospective.

This article is part of a series of studies that summarizean 11-year prospective randomized clinical trial. Theobjective of this article is to analyze the physical growthof the large sample of nonsyndromic children withunilateral cleft lip and palate (UCLP), from birth to 2

years of age, according to gender, in a longitudinal andprospective study and to construct specific growth curves.

M ETHODS

In 1994, the University of Florida Craniofacial Centerinitiated a 10-year clinical trial sponsored by the NationalInstitutes of Health, in collaboration with the Hospital deReabilitacao de Anomalias Craniofaciais at the Universityof Sao Paulo (HRAC-USP), Bauru, Brazil. Physical growthwas one of the secondary outcome measures of this trial.

Length, weight, and head circumference were prospec-

tively measured for all enrolled children in a longitudinaland prospective study. This growth study included 627infants with complete UCLP who were followed throughthe HRAC-USP outpatient clinic. Children with associatedmalformations, genetic syndromes, or chronic disease thatcould affect their growth were not included in the study. Alittle more than 90% of the sample (90.58%; n 5 627) wereborn at term: between 38 and 42 weeks of gestation. Thesample did not present infants born at less than 32 weeks of gestation. Because only 9.22% of the studied children wereborn either between 32 and 37 weeks of gestation (6.43%)or at greater than 42 weeks of gestation (1.09%), or theirparents did not know the birth gestational age (1.70%), nochildren were excluded. None of the children included in

this study was tube fed, and only 2.5% were breast-fed formore than 30 days. All patients received care in the samefacility by three pediatricians. The pediatric protocol of care included serial examinations in growth measurements(weight, length, and head circumference). Growth mea-surement techniques were standardized. Weight wasobtained by using standard infant and toddler scales.Length was measured with a horizontal anthropometerwith the child in the supine position. Length, weight, andhead circumference were measured at each examination.Criteria defining small size were length, weight, and headcircumference greater than 2 standard deviations below themedian or below the third percentile for age and gender ascompared with the National Center of Health Statistics(NCHS; 2000) growth charts. The weight, length, and headcircumference at birth were obtained by informationprovided by the parents. This study was approved by theInstitutional Review Board (IRB) at the University of

Florida and by the Ethical Committee at HRAC-USP.

Statistical Methods

Values for weight, length, and head circumference wereimputed for each time point tabulated except for birth (age0), which used actual values (Table 1). The variables of length, weight, and head circumference were imputed asshown in Table 2 for boys and girls, respectively.

Top Priority

If a subject had a measurement at the specific targetmonth (i.e., 6, 12, 18, or 24 months, age rounded down towhole month), it was used.

Second Priority

If a subject had at least one measurement at an age in thewindow before the target age and at least one in the targetwindow after the age (see Table 1 for the window definitions),the value was interpolated from the latest before to the earliestafter. For example, if the target was 24 M and measures hadbeen obtained at 21, 30, and 33 M (three in the window for

the target age of 24 months), the 33 M measure would beignored and take 6/9(Measure at 21 M) + 3/9(Measure at 30months). Note that the date of assessment that is closer to thetarget date receives a higher weighted value. Graphically, we join the two measures in the window surrounding on eitherside of the target date and draw a straight line between theirvalues. The imputed value is where this line crosses the targetage (24 months in this example).

Last Priority

If a subject had only one measurement in the targetwindow, a general slope for the window was computed,consisting of all subjects with one measure before and one

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values, remaining even with the reference through the lastmeasures made at 2 years of age ( p 5 .52). Figure 1 alsosuggests a catch up in length for girls before 12 months of age. As shown in Figure 2, girls (n 5 249) median birthweight was at the 27th percentile, revealing them to havesignificantly less weight than the NCHS values ( p , .001).The girls remained below the median value in weight until 2years of age. At 2 years of age, the girls weight reached the47th percentile ( p 5 .14). Figure 2 also suggests a catch upin weight for girls beginning at 18 months of age. As shownin Figure 3, the girls (n 5 64) head circumference at birthwas at the 33rd percentile, revealing significantly smallerhead size compared with NCHS values ( p 5 .0030). At 6months of age, the girls head circumference reached theNCHS median value and at 9 months surpassed themedian. At 2 years of age, the girls head circumferencewas at the 65th percentile ( p , .001). As can be seen inFigure 4, boys (n 5 378) median lengths at birth and at 2years of age were at the 36th percentile ( p , .001 at bothbirth and age 2 years), revealing their length to be shortcompared with NCHS values but within normal limits asdefined for this study. Boys (n 5 378) birth weight, asgraphed in Figure 5, was at the 28th percentile, revealingweight to be significantly less than the NCHS values ( p ,.001). At 2 years of age, however, the boys weight was atthe 42nd percentile ( p 5 .0063), which, although signifi-cantly below the NCHS median, was less extreme than atbirth. Figure 5 also suggests a catch up in weight for boys

beginning at 18 months of age. Figure 6 illustrates the boys(n 5 96) head circumference to be at the 34th percentile,which is significantly less than the NCHS values ( p , .001).By 12 months of age, the boys head circumference crossedthe NCHS median curve, and by 2 years of age, the boyshead circumference was at the 59th percentile ( p 5 .018).

DISCUSSION AND CONCLUSIONS

Most studies reporting growth of children with cleftsdetected physical growth deficiencies in length and weightfor children with CLP and ICP, especially during the firstyear of life when the primary palatoplasty had not yet beendone (Day, 1985; Jones, 1988; Lee et al., 1996; Seth andMcWilliams, 1998; Pandya and Booman, 2001; Montagnoliet al., 2005). Growth deficiency observed during this periodhas been attributed to environmental factors including thehigh frequency of infectious diseases (Seth and McWil-liams, 1998) and the different degrees of difficultiesencountered in feeding children with cleft palate (Drillenet al., 1966; Coy et al., 2000; Montagnoli et al., 2005).

After 2 years of age, biological factors have a greaterinfluence than environmental factors in regulating growth(Coy et al., 2000). In the literature, there are speculationsregarding growth hormone (GH) deficiency in childrenwith CLP, the effects of which can be noted during thesecond or third year of life (Laron et al., 1969; Rudman etal., 1978). Controversy regarding GH deficiency and clefts

FIGURE 1 Median length for girls by age. FIGURE 2 Median weight for girls by age.


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is still found in the literature, with some authors reportingno associations between orofacial clefting and GH defi-ciency (Koster et al., 1984) nor between CLP and the riskfor short stature in children with UCLP between 4 and 10years of age (Nackashi et al., 1998).

Some studies have emphasized the importance of aprecise diagnosis of the type of CLP for growth assessmentusing populations as homogenous as possible. Theyassumed that a child with CLP without associated geneticsyndromes will follow a growth pattern that is reflected inone of the percentiles of the reference curve; thus,deviations from this growth trajectory should be takeninto account in the same way as for a child without cleft(Day, 1985; Bowers et al., 1987). In contrast, otherinvestigators (Rudman et al., 1978; Ranke, 1989; Cunning-ham et al., 1997; Lipman et al., 1999) have stated thatchildren with congenital malformations or genetic syn-dromes assume their own growth pattern, which mightdiffer from that of typical children, and represent groupswith their own disease-specific growth pattern.

Another controversial issue has been related to weight,length, and head circumference of children with clefts atbirth. Most studies demonstrated that children with CLPpresented with smaller body dimensions when comparedwith typical children (Ross and Jhonston, 1972; Rudman etal., 1978; Duncan et al., 1983). Some authors havesuggested an association between the severity of intrauter-ine growth deficiency with the width of the cleft, with

infants with CLP presenting greater risk for low birthweight for gestational age (Becker et al., 1998).

The contribution of the present study in relation to thequestions posed above has been the presentation of longitudinal growth data for length, weight, and headcircumference during the period between birth and 2 yearsof age in a large sample. The data set yielded theestablishment of gender-specific growth curves for childrenwith UCLP.

In the present study, we used the NCHS 2000 growthcurves as the reference for normal growth because they arerecommended by World Health Organization for interna-tional growth studies and by the Brazilian Health Servicefor growth monitoring. For growth studies, the idealprocedure would be to evaluate the children at regularintervals to facilitate the statistical analysis, but in thisstudy it was not possible. The HRAC-USP is one of themajor reference centers for craniofacial malformations inBrazil, and it receives patients from distant locations. Forthis reason, returns for reevaluations (preoperative andpostoperative) were established following the clinical trialprotocol and availability of the family. Even with thislimitation, this data set is one of the largest prospective andlongitudinal growth studies ever published for children withCLP.

In conclusion, children of both genders in this studypresented with smaller body dimensions in relation totypical children. The results, however, suggest a catch-up

FIGURE 3 Median head circumference for girls by age. FIGURE 4 Median length for boys by age.

Marques et al., BODY STATURE OF CHILDREN WITH CLEFT LIP-PALATE 607

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growth for length, weight, and head circumference for girlsand for weight and head circumference for boys. Eventhough boys did not present a catch-up growth for length,all median values found were within the normal rangeduring the 2 years studied. Weight was the mostcompromised parameter for both genders, followed bylength and then head circumference. The median for thehead circumference parameter was found to be very close tothe NCHS median during the entire period studied, belowthe median at birth, and the only growth parameter abovethe median at 2 years of age for girls and boys. Nutritionaldifficulties may have compromised growth since weight wasthe most compromised growth parameter and is theparameter most susceptible to inadequate nutrition. Theweight and length at birth were lower for the children withUCLP when compared with the norms. A pattern towardsmaller size wasfound particularly for weight for girls at birth.

Finally, the growth curves established in this study canbe used along with reference curves to monitor the growthof children with UCLP. The population studied wasenrolled using inclusion criteria to screen out othermalformations, syndromes, or health conditions that couldhave negatively affected the childrens overall health status.Deviations from these curves found in children with UCLPcould indicate other conditions or complications.

Acknowledgments. The authors wish to acknowledge the financialsupport of NIH/NIDCR (R01-DE10437), the members of the DSMBwho contributed without remuneration hundreds of hours of their timeover the course of this study, the patients and their families, staff andprofessionals at HRAC-USP who assisted in the conduct of this long-termstudy, and Dr. Sue McGorray for statistical support. Special gratitudegoes to Dr. Jose Alberto de Souza Freitas, Superintendant of HRAC-USP, for his support in the assessment of treatment outcomes.

REFERENCES

Becker M, Svensson H, Kallen B. Birth weight, body length, and cranialcircumference in newborns with cleft lip or palate. Cleft PalateCraniofac J . 1998;35:255261.

Bowers EJ, Mayro RF, Whitaker LA, Pasquariello OS, LaRossa D,Randall P. General body growth in children with clefts of the lip,palate and craniofacial structure. Scand J Plast Reconst Surg .

1987;21:714.Coy K, Speltz ML, Jones K, Hill S, Omnell ML. Do psychosocial

variables predict the physical growth of infants with orofacial clefts?J Dev Behav Pediatr . 2000;21:198206.

Cunningham ML, Jerome JT. Linear growth characteristics of childrenwith cleft lip and palate. J Pediatr . 1997;131:707711.

Day WD. Accurate diagnosis and assessment of growth in patients withorofacial clefting. Birth Defects . 1985;21:114.

Drillen CM, Ingram TTS, Wilkinson EM. The Causes and Natural Historyof Cleft Lip and Palate . Baltimore: Williams and Wilkins; 1966.

Duncan PA, Shapiro LR, Soley L, Turet SE. Linear growth patterns inpatients with cleft lip or palate or both. Am J Dis Child . 1983;137:159163.

Felix-Schollaart B, Hoesksma J, Phral-Andersen B. Growth comparisonbetween children with cleft lip and/or palate and controls. CleftPalate J . 1992;29:475480.

FIGURE 5 Median weight for boys by age.

FIGURE 6 Median head circumference for boys by age.


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