Original Article

The Cleft Palate-Craniofacial Journal

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A Retrospective Mixed Longitudinal Study ª 2020, American Cleft Palate-
Craniofacial Association

of Tooth Formation in Children With Clefts Article reuse guidelines:

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DOI: 10.1177/1055665620903186
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Sarah B. Kimbrough, DMD1 , William G. Parris, DDS, MS1,

Richard A. Williams, DDS, MS1, and Edward F. Harris, PhD1

Abstract
Objective: To test for systematic age changes in cleft children based on dental age.
Design: Retrospective case–control longitudinal study.
Setting: One orthodontic solo practice.
Patients: Nonsyndromic, complete cleft lip and palateCLP cases, either unilateral or bilateral (102 children; 370 radiographs),
between 4 and 16 years of age.
Interventions: Children were treated with a team approach, but only orthodontic radiographs were studied.
Main Outcome Measure: The principal outcome measure was dental age of the cleft cases compared to a sex-specific sample of
phenotypically normal children (1107 children), from the same geographical region. Multiple panoramic radiographs taken during
the course of orthodontic treatment were examined to track patterns of dental age as children matured. Analysis used linear
mixed models primarily testing for sex, cleft type (unilateral, bilateral), and hypodontia differences. Initial expectation was that
cleft children would exhibit delayed dental ages from postnatal stressors and would become more deviant with maturity.
Results: In childhood (4-6 years), both sexes were significantly delayed (P < .001), but dental age normalized around 8 to 10 years.
Boys experienced faster maturation thereafter than girls (P < .001). Only trivial differences occurred between unilateral CLP and
bilateral CLP samples.Hypodontia further depressed maturation rates (P < .001). Dental age improved in a decidedly curvilinear
fashion (P < .001), with greater change at earlier ages.
Conclusions: This report agrees with other contemporary studies, showing childhood catch-up. Older studies observed that
clefting caused significant delays that worsened with growth. This potential “seachange” suggests better recovery and quicker
normalization of children with clefts, perhaps due to improved management.

Keywords
dental maturation, dental age, environmental stress, age differences, critical period

Introduction Physiological age contrasts with the method of calendric

time, where children are born at age “0” and they advance en
Biological (physiological) age is the concept that all children
bloc toward adulthood. Calendar age supposes that children
progress from immaturity to maturity, but the rate or tempo can
mature in lockstep, whereas a child’s biological age can follow
differ from person to person (Tanner et al., 1975; Cole, 2012;
its own tempo, with ebbs and flows. All children progress from
Cameron, 2015). A child’s tempo of maturity responds both to
immaturity to maturity, but the rate or “tempo” can vary, so a
intrinsic and environmental conditions. It is slowed by some
factors (eg, undernutrition, chronic disease, some genetic dis-
eases; Roberts et al., 1985; Hass et al., 2001; Hattab, 2013) and
quickened by other diseases (Lehtinen et al., 2000; Vuorimies 1
Department of Orthodontics, College of Dentistry University of Tennessee,
et al., 2017) and by “overnutrition” (Hilgers et al., 2006; Car- The Health Sciences Center, Memphis, TN, USA
neiro et al., 2017; Nicholas et al., 2018). Variability occurs
among children when a biological year is out of synch with a Corresponding Author:
Sarah B. Kimbrough, Department of Orthodontics, College of Dentistry
calendar year. A principal use of biological age—gauged from University of Tennessee, The Health Sciences Center, Memphis, TN 38163,
bone, teeth, or integument—is to evaluate the difference USA.
between a child’s chronological and biological ages. Email: [email protected]
2 The Cleft Palate-Craniofacial Journal XX(X)

“chronological year” need not equal a “maturational year” have followed children longitudinally, finding an improvement
(Boas, 1933; Demirjian, 1978; Cole, 2012). in dental maturation with age (ie, a catch-up or compensatory
Each tooth progresses seamlessly through cusp formation, response).
crown completion, and root development, advancing in its
degree of maturity as it does so. The tooth root begins to form
after the crown (enamel and dentin) have completed develop-
Materials and Methods
ment. The third type of tooth hard tissue, cementum, is secreted Prior institutional review board approval was granted (IRB
by cementoblasts proliferating from the dental follicle #18-06094-XP), and the study examined anonymized panora-
mesenchyme (Thesleff and Trummers, 2008). mic radiographs from 1 solo orthodontic practice that focuses
The final stage, when the root apex closes around its neu- on the treatment of children with craniofacial anomalies. The
rovascular bundle, marks complete maturity—a status that per- sample consisted of 102 nonsyndromic cases with complete
sists throughout that tooth’s subsequent life. Age-progressive CLP (72 boys; 30 girls): 70 with unilateral clefts (51 boys,
changes do continue into adulthood (eg, secondary dentine, 19 girls) and 32 bilateral clefts (21 boys, 11 girls). All cases
root translucency, cementum accumulation), but the tooth’s were American whites by self-assessment (Edgar et al., 2011).
morphology is complete. Combined across teeth, staging yields Dental mineralization of the lower left permanent teeth
a child’s “dental age,” which is the age at which the average (Figure 1) was scored using the grading scheme of Demirjian
child in the reference group achieved the observed degree of et al. (1973). All panoramic radiographs (n ¼ 370 films) taken
dental development. This procedure works until about 16 years between the chronological ages of 4 and 16 years were studied.
when all teeth (except wisdom teeth) reach morphological No radiographs were less than a year apart. The highest stage
maturity. actually attained was recorded, without interpolation (Dahlberg
A child’s dental age is not commonly the same as judged and Menegaz-Bock, 1958). All teeth were independently
from other tissue systems (such as handwrist bone age) because scored twice by the senior author with sessions over 2 months
different tissues respond to different growth axes (Demirjian apart. The few inconsistencies were resolved through rescoring
et al., 1985; Sukhia and Fida, 2010; Ró_zyło-Kalinowska et al., and consensus with the other authors.
2011). Correlations between methods normally are positive, Interobserver reliability was gauged by a second author
but not particularly high (commonly r2 < 0.50), because of scoring teeth on 40 films selected at random across the span
different responsiveness. of ages (280 teeth). The intraclass correlation (supposing a 2-
Postnatal growth of children with nonsyndromic clefts is way random effects model) was high, at r ¼ 0.987. This strong
slower than normal (Nyström and Ranta, 1988; Heidbüchel concordance argues against the improbable chance that the
et al., 2002; Heliövaara and Nystrom, 2009; Hazza’a et al., original scorer was biased. It also supports the clarity of Demir-
2009; Tan et al., 2012; Bindayel et al., 2014). There are many jian’s grades and criteria.
causes for this, but a major factor is the postnatal A 15-year cohort was sampled. Birthdates were between
“environment” broadly defined. Children with clefts experi- 1996 and 2010, and all nonsyndromic cleft cases from the
ence problems with feeding, respiration, speech, social inter- practice meeting inclusion criteria were included. The intent
actions, and many other physical and psychosocial problems was to record the consequences of contemporary treatment
(Berkowitz, 2013; Losee et al., 2015). The permanent teeth rather than older approaches. Treatment varied by individual’s
mineralize during this debilitating postnatal milieu (Kitamura, needs, but the general orthodontic protocol was (1) presurgical
1989), where several environmental stressors slow growth (eg, nasal molding in infancy (Massie et al., 2018), (2) lip repair at 3
feeding problems, airway problems, aspiration problems, to 4 months, (3) palate repair at 12 months, (4) orthodontic
recurrent surgeries, etc). treatment in the mixed dentition, including arch expansion and
The focus of this study was on quantifying the degree of reverse pull facemask headgear in preparation for bone graft-
difference between children with clefts vis-à-vis comparable ing, and (5) comprehensive orthodontics in the permanent den-
noncleft norms. This has been studied before, notably the series tition including additional arch expansion, headgear treatment,
of papers by Ranta (Nyström and Ranta, 1988; Nyström et al., or orthognathic surgery as needed.
1988; Ranta, 1984, 1986; Pöyry et al., 1989), but traditional Each grade in the Demirjian system (Figure 1) has a stan-
prior studies have been cross-sectional—children with clefts dard deviation close to 0.3 years (Liversidge, 2011). Prospec-
were studied just once. The present study monitored the dental tively, a power analysis was computed (Faul et al., 2007)
formation of children with clefts across time. This was done assuming a 1-sample difference of at least 1 grade (with a ¼
retrospectively, using panoramic radiographs taken periodi- .05 and b ¼ 80%). This indicated a need for sample size of 30
cally for clinical purposes. patients per grade. This estimate was doubled to accommodate
Pöyry et al. (1989) compared children with clefts in 2 age sex-specific tests. In actuality, we chose to examine all cases in
groups (3-9 and 8-14 years). The younger group had a dental the orthodontic office that met the inclusion criteria, and this
delay of 0.5 years, and this diminished to 0.2 years in the teen- exceeded the limit of 70 patients at each grade. A total of 102
age group. However, these 2 groups consisted of different indi- patients was studied (ie, the complete available sample meeting
viduals, so there is no guarantee that 1 sample transitioned into selection criteria), with multiple films per individual. Cases and
the other. Others (Heidbüchel et al., 2002; Tan et al., 2017) controls were not matched. The sample of phenotypically
Kimbrough et al 3

Figure 1. Schematic drawings of the 8 ordinal stages per tooth type developed by Demirjian et al. (1973). The visually assessed ordinal stages
(A!H) are labeled with letters. Grades not illustrated occur at very young ages never encountered in this study. The Demirjian paper includes
photos and detailed written descriptions of each stage. Dashed lines in root areas mark the bony vacuolization that precedes tooth formation.
The lines within the tooth crowns denote the coronal limits of the formative dental pulp.

normal children (n ¼ 1100) was treated as the population stan- Each patient’s chronological age at each radiograph was
dard, and the cleft cases were compared to it. That is, dental assigned to a 2-year age interval (4-6, 6-8, 8-10, 10-12, and
ages of the children with clefts were compared, by sex, to 14-16 years) with just 1 X-ray per interval. This step is unne-
normal noncleft American white children living in the same cessary, but it helps interpretation and permits “age interval” to
region of the country and the same range of birthdates (EF be cast as a fixed effect.
Harris, 2019). Each radiograph of the children with clefts was Since hypodontia is elevated in cleft cases (De Stefani et al.,
studied to (A) identify the stage of each tooth in the lower-left 2019) and because hypodontia slows dental development
quadrant (1 of 8 stages), then (B) the z-score was calculated for (Dhamo et al., 2016), the number of congenitally missing per-
that tooth-stage-sex. This converted tooth mineralization stages manent teeth (ignoring maxillary lateral incisors in the cleft
to standard deviations (years) between that CLP case and the proper and third molars) was used as a covariate in the statis-
normative data. Transformation harmonizes data to the same tical analysis. Hypodontia was categorized into 3 grades: none
units. The z-score formula was (all 26 teeth present), slight (1-2 teeth), and more (3þ teeth).
Analysis used linear mixed model (LMM) analysis (Ver-
ðCA norm  CA cleft Þ
z¼ beke and Molenberghs, 2001; Singer and Willett, 2003). Two
sd norm
fixed predictors were sex (boy and girl) and type of cleft (uni-
In words, the chronological age at the patient’s film was lateral, bilateral). “Cases” were a random effect, and the out-
subtracted from the normative age at that stage, and this come variable was tooth mineralization z-score (years).
difference was divided by the normative group’s standard Repeated measures were the series of radiographic examina-
deviation. Positive z-scores indicate that the cleft case was tions taken for each patient, and the number of films and ages
developmentally advanced relative to the normative data; varied based on clinical needs. With LMMs, fixed effects are
negative values showed the cleft case was less mature. Z- interpreted in the usual analysis of variance fashion, but the
scores were calculated for each of the 7 lower left teeth. random effects are variances—distributions of ages around
To provide a composite measure for each child’s examina- which an event was distributed—so interpretation can be off-
tion, the mean of the 7 tooth-specific z-scores was putting to researchers accustomed to dealing with variance
averaged. ratios.
4 The Cleft Palate-Craniofacial Journal XX(X)

Figure 2. A, Plot of average z-score across the mandibular permanent 7 left teeth (sexes combined). A cubic polynomial was fit to the data to
emphasize the nonlinear change in scores across time. B, Plot of z-scores, by tooth, against age interval, treating the data cross-sectionally.
Splines connect the means. The principal observation is that tooth formation was delayed at the early age interval, but, by roughly 10 years of age,
compensatory growth had accelerated maturation to that of the normative standards. Tooth abbreviations are central incisor (I1), lateral incisor
(I2), canine (C), first premolar (P1), second premolar (P2), first molar (M1), and second molar (M2).

Two cardinal issues were (1) whether dental age of the very slowly. This variability suggests that different growth
sample with clefts matured at different rates than nonclefts and trajectories (slopes) should be incorporated. (4) There were
(2) whether the difference between dental age minus chrono- several missing data. Indeed, no patient had a radiograph at
logical age (DA  CA) changed over age. Preliminary testing each of the 7 age intervals. For these several reasons, conven-
indicated that random intercept and random slopes contributed tional analysis of variance statistics would do a poor job of
significantly to explained variation. That is, each case was representing these data (Singer and Willett, 2003).
permitted to have its own starting point (intercept) and proceed Results of the LMM analysis show several statistically sig-
at his/her own pace (slope). A quadratic term (age2) and a cubic nificant differences (Table 1) among the 7 teeth because teeth
term (age3) were used in the models as fixed effects to accom- mineralize at different ages. For example, incisors have almost
modate curvilinear change in dental maturity with child’s age. completed formation at the earliest age interval (4-6 years),
Variance composition can be altered within an LMM, but while a fuller picture is available for the canine, premolars, and
Akaike information criteria (West et al., 2014) indicated that second molar. Consequently—and because the individual teeth
a “heterogenous first-order autoregressive” covariance struc- exhibit redundant patterns (Figure 3)—results of the “averaged”
ture was the preferred fit. This means the data (formation stages or composite measure are emphasized here. Moreover, tooth
among a person’s radiographs) were correlated, but depen- formation tempos are intercorrelated (Moorrees and Kent, 1981).
dency degraded with increasing time (age) between radio- All intercepts were significantly less than 0. Indeed, the F
graphs. Tests were 2 tail, and statistical significance was ratios associated with the intercepts were the largest encoun-
evaluated at a ¼ .05. tered. The exception was the lower central incisor, which is the
first tooth to mineralize (Kitamura, 1989), so this tooth seems
to have largely escaped the debilitating effects of infancy. The
Results other teeth show that, as newborn, the children with clefts
As a preliminary view (Figure 2), data were plotted by sex and exhibited significantly delayed dental ages. However, this
age interval, but these figures combine examinations of multi- assumes a linear trajectory of maturation, which is known to
ple ages for the children, thus ignoring statistical dependencies be false, and since examinations did not begin until 4 years of
among tooth stages within the same child. Still, these approx- age, true intercepts at the origin (conception) are very poorly
imate results suggest avenues of exploration (Figure 2), notably extrapolated by these postnatal data. The most that can be said
(1) upward slopes of the scores of each tooth with age. Z-scores is that dental age significantly improved relative to calendar
were negative at the younger chronological ages, indicating age as time went on.
these children with clefts were maturing more slowly than The principal finding was the upward slopes of the scores of
controls. However, with advancing age, z-scores of these same each tooth (Table 1). Mean z-scores changed significantly (nor-
children advanced closer to a z-score of 0. (2) Girls appeared to malized) as the children grew. This “catch-up” is evident in the
possess smaller (less deviant) z-scores than boys, particularly at mixed model (Table 1) as the significant linear effect, but,
the older age intervals (Figure 3), but any difference between notably, also by a significant quadratic term (age2) as the
unilateral and bilateral cases was indeterminant. (3) Different quickened rate of maturation temporizes and there was a sub-
children appeared to mature at different tempos. Some showed sequent plateauing (cubic term, age3) once the child’s target
little retardation relative to noncleft controls. Others developed growth rate supposedly has been reached.
Kimbrough et al 5

Figure 3. Plots of mean z-score by age grade and sex. The last graph (labeled “Ave”) is the average z-scores for the 7 individual teeth. Girls’ data
were coded as round symbols; boys as squares. C, canine; I1, central incisor; I2, lateral incisor; M1, first molar; M2, second molar, P1, first
premolar; P2, second premolar, and average of all 7 teeth (“Ave”). Error bars are not shown since they are biased because formation status
among age grades are intercorrelated within individuals.

The “sex” difference reported by several studies (Nolla, scores than boys. This sex difference in how children were
1960; Moorrees et al., 1963; Demirjian et al., 1973) was affected by the cleft also increased over time. It was not
statistically significant, with girls having less severe z- detectable for early-forming teeth (incisors, first molar) but
6 The Cleft Palate-Craniofacial Journal XX(X)

Table 1. Results of Linear Mixed Models Analyzing 7 Permanent Mandibular Teeth and a Composite Measure of Dental Maturity.a

I1 I2 C P1 P2 M1 M2 Mean Z

Dependent F P F P F P F P F P F P F P F P
Intercept 0.0 .990 13 .001 57 .000 512 .000 232 .000 146 .000 166 .000 49 .000
Sex 0.0 .990 0.0 .952 0.7 .392 5.8 .030 7.1 .010 0.8 .385 11.8 .001 8.2 .005
Cleft type 2.6 1.000 1.5 .231 7.0 .010 0.2 .644 0.0 .986 0.0 .972 0.1 .816 0.7 .392
Sex  cleft type 1.0 1.000 1.0 .332 2.2 .139 0.5 .497 0.0 .983 0.0 .947 0.4 .552 0.6 .445
Age2 4.4 .047 9.8 .006 0.6 .445 106.5 .000 67.1 .000 43.7 .000 129.0 .000 53.2 .000
Age3 0.8 .369 2.8 .109 0.5 .500 88.0 .000 56.1 .000 9.6 .013 98.6 .000 42.3 .000
Hypodontia 0.1 .731 0.2 .667 8.0 .007 3.0 .085 5.3 .024 0.0 .997 16.2 .000 9.5 .003

Abbreviations: C, canine; F, F ratio; I1, central incisor; I2, lateral incisor; M1, first molar; M2, second molar; P1, first premolar; P2, second premolar; P, P value.
a
“Mean z” was the average z-score of the 7 teeth and is used as a summary index of the sample’s dental status. Each tooth was a separate analysis, and results
depended on how many stages were represented at the examinations. Probabilities were 2 tailed. P values significant at .05 or less are given in italics .

Figure 4. A, Plot of the distribution of hypodontia by number of congenitally missing teeth (third molars omitted). There were 163 missing
teeth in 102 cleft cases; percentages are shown above the bars. B, Range of missing teeth was categorized into 3 grades (none, 1-2 teeth, and 3þ
teeth). *In B, missing upper lateral incisors were omitted.

became apparent with the later-forming teeth, like the sec- Figure 3 also makes the point that change across ages was
ond molar. curvilinear. This altered velocity was accommodated in the
Hypodontia had a further delaying effect on dental age present models by including quadratic (age2) and cubic (age3)
(Table 1). Hypodontia ranged from 0 to 7 teeth in this series terms. Expectation (Figure 6) was that the linear effect tested
(Figure 4). Hypodontia significantly depressed dental age for for change in z-score across age intervals, while age2 evaluated
C, P2, M2, and the averaged summary. This agrees with prior whether the rate of change altered across time, and age3 tested
research (Ranta, 1982; Eerens et al., 2001; Dhamo et al., 2016) for a plateau as z-scores normalized near 0. Results (Table 1)
and others, although Eerens et al. (2001) results were show that age2 was significant for teeth that formed by late
nonsignificant. childhood. Incisors mineralized prior to the interval of normal-
There was scant evidence that children with bilateral clefts ization. Age3 was statistically significant for those teeth, nota-
developed differently than those with unilateral clefts. Just the bly the canine and second molar, that completely mineralized
canine showed a significant effect, with bilateral cases being during the older age intervals.
more delayed at the 4 to 6 age interval (Figure 5), and the
composite measure had indistinguishable z-scores between uni-
lateral and bilateral clefts (P ¼ .392). Discussion
It was unexpected to see a “catch-up” in dental maturation Prior studies often found that children with clefts were devel-
(Figure 3). For example, Ranta (1986) reviewed the older lit- opmentally delayed (Nyström and Ranta, 1988; Heidbüchel
erature and concluded that dental delay was “more severe in the et al., 2002; Hazza’a et al., 2009; Heliövaara and Nystrom,
older age group than in the younger age group” with isolated 2009; Tan et al., 2012; Bindayel et al., 2014) and that bilateral
CLP. Striking differences were found in the present compari- clefts were more delayed on average than unilateral samples.
sons; maturation improved rather than worsened with age. Girls Studies of dental maturation measure how children are inter-
moved close to z ¼ 0 (normal maturation), while boys signif- acting with their environment (defined broadly), so less refined
icantly exceeded z ¼ 0 and matured faster than anticipated and less comprehensive treatment protocols should impact
during the older age intervals (>8-10 years). growth more dramatically. Parenthetically, we appreciate that
Kimbrough et al 7

1963; Demirjian et al., 1973). Here, these children with clefts

were “normalized” with regard to tooth formation much earlier
than if duration of examination simply were protracted. By 8 to
10 years of age, dental maturity was statistically indistinguish-
able from noncleft norms. We emphasize that results apply to
“these children” because we suspect that those in historically
different times and/or with different access to cleft care may
not have done as well. Prahl-Andersen (1976) may well have
been the first to document this compensatory improvement in
Figure 5. Plot of canine z-scores across age intervals. This was the later childhood, and others have confirmed this trend (Heidbü-
only tooth to exhibit a significant difference between cleft types. Z- chel et al., 2002; Huyskens et al., 2006; Tan et al., 2017).
scores were lower in the bilateral clefts (adjusted for sex), but neither Reasons for the catch-up in dental maturity are not clear, but
group (univariate or bilateral) differed significantly from 0 except at
the 4- to 6-year examination.
its recognition accounts for some of the variability among
studies—depressed dental development is significant early on
but typically ameliorates with advancing age.
Girls normally have faster dental maturity tempos than boys
(Garn et al., 1958; Nolla, 1960; Moorrees et al., 1963) and this
female-precedence likewise occurs in children with clefts. Fig-
ure 3 also shows that girls with clefts are less affected than boys
with clefts—which is a common sex difference (Stinson, 1985)
but without an obvious explanation.
Clinical implications of these results revolve on recogni-
tion of the delayed growth in infancy and childhood. We
assume that tooth formation observed here is just 1 indicator
Figure 6. Hypothetical pattern of change in z-score with age occur- that the child with a cleft can be developmentally delayed (eg,
ring in the present data. Z-scores were strongly negative at early ages, Bardach, 1990; Berkovitz et al., 2009). This is by no means
but the subsequent slope diminished with age, such that dental new information, but since health-care workers treat individ-
maturation was not statistically different from noncleft controls by late ual children and not some abstract norm, these results reaffirm
childhood. that treatment generally may be delayed (and perhaps length-
ened) relative to noncleft cases for early procedures. It is
fortuitous that the significant delay seen in the children with
there may be unidentified genetic predispositions to clefting
clefts significantly ameliorated over time. For the majority of
(Thieme and Ludwig, 2017; Gu et al., 2018), but we choose
the sample, treatment after about 10 years of age should pro-
to emphasize environmental responses—which can be altered
ceed normally. For example, the modal age for definitive
by earlier and less-invasive treatments. Children with clefts
orthodontic treatment is around 12 years of age, once all
have been labeled “weakly buffered” (Bailit et al., 1968; permanent teeth (excluding wisdom teeth) have erupted. The
Sofaer, 1979; Ranta, 1986). present study suggests that children with clefts can be
It is confirmatory that the 7 individual teeth showed consis- expected to respond normally as regard to development,
tent changes across time. Teeth within an individual are inter- though there may be anatomical issues specific to the cleft
correlated, not only regarding size (Harris and Bailit, 1988) but (Böhn, 1963; Ranta, 1982).
also formation and eruption (Moorrees and Kent, 1981). Also, A limitation of this study was that only a single geographic
teeth develop using similar, repetitive biochemical signaling location—and 1 orthodontist—was sampled. Results would be
(Jernvall and Thesleff, 2000; Kangas et al., 2004; Tummers more generalizable if multiple clinicians had been included.
and Thesleff, 2009). A benefit of examining multiple teeth is Likewise, cases were all were American whites. And, we
to obtain a longer record of how the child was coping with his/ depended on an orthodontist’s radiographs, which seldom are
her environment than afforded by any single tooth. Some teeth taken until indicated for tooth alignment once most permanent
seem to be more informative than others (Figure 3), but this teeth are present. Earlier treatment, such as nasal molding,
involves the ages at formation relative to the ages at the exam- rarely requires radiographic examination. More encompassing
ination. So, as an example, most of the incisors’ formation records (perhaps by adding surgeons’ records) would provide a
occurred earlier than recorded by the radiographic record. Best more complete growth record. It would be interesting, for
represented were the canine and premolars since their forma- example, whether tooth formation is delayed at birth and how
tion coincided with treatment ages. slowed dental maturation becomes in infancy prior to the
If children are followed long enough, they all will attain observed catch-up in late childhood.
biological maturity. Typically, children reach complete tooth Development of children with facial clefts has been studied
mineralization around 16 years of age, ignoring the late- extensively, and several researchers report slowed tempos of
forming and highly variable third molars (Moorrees et al., bone development (Bowers, 2011; Batwa et al., 2018), and
8 The Cleft Palate-Craniofacial Journal XX(X)

dental maturation is delayed (Ranta, 1986; Mitsea and Spyro- Bindayel NA, AlSultan MA, ElHayek SO. Timing of dental develop-
poulos, 2001), as well as somatic growth (Drillien et al., 1966; ment in Saudi cleft lip and palate patients. Saudi Med J. 2014;
Ranalli and Mazaheri, 1975). Moreover, tooth size is dimin- 35(1):304-308.
ished (Sofaer, 1979; Antonarakis et al., 2013) because enamel Boas F. Studies in growth II. Hum Biol. 1933;5(6):429-444.
and dentin have virtually no reparative ability, so they forever Böhn A. Dental anomalies in harelip and cleft palate. Acta Odont
reflect their environment during formation. Since teeth rarely Scand. 1963:21(suppl 38):1-109.
begin to erupt without substantial root development (Grøn, Bowers EJ. Growth in children with clefts: serial hand-wrist x-ray
1962), tooth emergence also tends to be delayed in children evidence. Cleft Palate Craniofac J. 2011;48(6):762-772.
with clefts (de Carvalho et al., 2004; Kobayashi et al., 2010) Cameron N. Can maturity indicators be used to estimate chronological
and the crown–root ratio can be impaired (Al-Jamal et al. age in children? Ann Hum Biol. 2015;42(2):302-307.
2010), along with other dental anomalies (Nicholls, 2016; Sá Carneiro JL, Caldas IM, Afonso A, Cardoso HF. Examining the socio-
et al., 2016). economic effects on third molar maturation in a Portuguese sample
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131(1):235-242.
Conclusion Cole TJ. The development of growth references and growth charts.
This retrospective mixed longitudinal study examined dental Ann Hum Biol. 2012;39(9):382-394.
mineralization in children with clefts (n ¼ 102) using LMMs. Dahlberg AA, Menegaz-Bock RM. Emergence of the permanent teeth
The study confirmed that the sample with clefts was signifi- in Pima Indian children. J Dent Res. 1958;37(6):1123-1140.
cantly delayed as young children, but the same children became de Carvalho Carrara CF, de Oliveira Lima JE, Carrara CE, Gonzalez
normalized in a curvilinear fashion by 8 to 10 years of age. Vono B. Chronology and sequence of eruption of the permanent
Females, as a group, fared significantly better than boys, but teeth in patients with complete unilateral cleft lip and palate. Cleft
little difference distinguished unilateral and bilateral clefts. Palate Craniofac J. 2004;41(6):642-645.
Hypodontia further slowed dental maturation. De Stefani A, Bruno G, Balasso P, Mazzoleni S, Baciliero U, Gracco
A. Prevalence of hypodontia in unilateral and bilateral cleft lip and
Declaration of Conflicting Interests palate patients inside and outside cleft area: a case-control study. J
Clin Pediatr Dent. 2019;43(5):126-130.
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article. Demirjian A. Dentition. In: Falkner R, Tanner JM, eds. Human
Growth. Vol. II: Post Natal Growth. New York, NY: Plenum Press;
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Funding
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The author(s) received no financial support for the research, author-
ships among measures of somatic, skeletal, dental, and sexual
ship, and/or publication of this article.
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