Skeletal Maturation In Children Research Articles

The Role of Bone Alkaline Phosphatase and Osteocalcin in Saliva as Indicators of Skeletal Maturity in Children

The Role of Bone Alkaline Phosphatase and Osteocalcin in Saliva as Indicators of Skeletal Maturity in Children

Impact of genetic variations in the WNT family members and RUNX2 on dental and skeletal maturation: a cross-sectional study

BackgroundThis study evaluated if genetic variations in the WNT family members and RUNX2 are associated with craniofacial maturation, investigating dental and skeletal maturity in children and teenagers.MethodsRadiographs from pre-orthodontic treatment of Brazilian patients (7 to 17 years-old) were used to assess dental (panoramic radiographs) and skeletal maturity (cephalometric radiographs). The chronological age (CA) was calculated based on the date of birth and the time the radiographs were performed. For the dental maturity analysis, the Demirjian (1973) method was used and a delta [dental age - chronological age (DA-CA)] was calculated. For the skeletal maturity analysis, the Baccetti et al. (2005) method was used and the patients were classified as “delayed skeletal maturation”, “advanced skeletal maturation” or “normal skeletal maturation”. DNA isolated from buccal cells was used for genotyping of two genetic variations in WNT family genes: rs708111 (G > A) in WNT3A and rs1533767 (G > A) in WNT11; and two genetic variations in RUNX2: rs1200425 (G > A) and rs59983488 (G > T). A statistical analysis was performed and values of p < 0.05 indicated a significant difference.ResultsThere were no associations between dental maturity and genotypes (p > 0.05). In the skeletal maturity analysis, the allele A in the rs708111 (WNT3A) was statistically more frequent in patients with delayed skeletal maturation (Prevalence Ratio = 1.6; 95% Confidence Interval = 1.00 to 2.54; p-value = 0.042).ConclusionsThe rs708111 in the WNT3A gene impacts on skeletal maturation.

Association between dental and skeletal maturation in Scandinavian children born between 2005 and 2010

Objective The aim of this cross-sectional study was to analyse the association between dental and skeletal maturation in children born between 2005 and 2010. Materials and methods Dental and skeletal maturation of 117 ethnic Scandinavian children born between 2005 and 2010 (70 girls, 47 boys, mean age 11.48 years) was analysed. Dental maturation (DM) was assessed on orthopantomographs (OPs) by using Demirjian’s and Haavikko’s methods while skeletal maturation was assessed on hand-wrist radiographs by use of Helm’s method. The correlation between skeletal and DM was analysed using Spearman’s rho (Rs). Additionally, the most frequent DM stage in relation to the skeletal maturation stage was analysed by logistic regression adjusted for age and sex. Results The correlation between dental and skeletal maturation was significant for all teeth (Rs = 0.071–0.562; p < .000–p = .035) except for the first incisor and the first molar. Logistic regression analysis showed that when the mandibular and maxillary canines are ¾ mineralized, this is significantly associated with the beginning of the adolescent period before peak height velocity (PHV) (PP2= p < .005–< .05). Likewise, when the mandibular second premolars are ¾ mineralized, this is significantly associated with the maturation stage PP2= or S (PP2= p < .05, S: p < .005–< .05), both of which are before PHV at the beginning of the adolescent period. Limitations Limited sample size and the X-rays were taken before orthodontic treatment, which may have introduced a selection bias. Conclusions When the root of the canines or second premolars is ¾ mineralized, it may indicate the beginning of the adolescent period with increased skeletal growth intensity.

Long-Term Growth Hormone Therapy Does Not Advance Skeletal Maturation in Children and Adolescents

Context: There is no consensus on the effect of recombinant human growth hormone (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims: To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data. Methods: A retrospective longitudinal study of 71 subjects aged 2-18 years, mean 9.9 ± 3.8y, treated with rhGH for non-syndromic short stature for a duration of 2-14y, mean, 5.5 ± 2.6y. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded. Results: Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 ± 1.42 vs -0.69 ± 1.63, p=0.09). Piece-wise regression however showed a quantifiable catch-up phenomenon in BA of 1.6 months per year of rhGH therapy in the first 6.5y, 95%CI 0.023 - 0.229, p=0.017, that plateaued thereafter, β=0.015, 95% CI -0.191-0.221, p=0.88. There was no relationship between BAPAH z score – height z score and the duration of rhGH therapy, p=0.68. BAPAH overestimated final adult height in younger subjects but became more precise in older subjects (p<0.0001). Conclusion: Long-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5y that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and do not support the practice of yearly monitoring of skeletal maturation with bone age in children on rhGH therapy, especially in younger subjects where BAPAH is imprecise.

Long-term GH Therapy Does Not Advance Skeletal Maturation in Children and Adolescents.

ContextThere is no consensus on the effect of recombinant human GH (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy.AimsTo investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age-predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data.MethodsA retrospective longitudinal study of 71 subjects aged 2 to 16 years, mean 9.9 ± 3.8 years, treated with rhGH for nonsyndromic short stature for a duration of 2 to 14 years, mean, 5.5 ± 2.6 years. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded.ResultsBone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 ± 1.42 vs -0.69 ± 1.63, P = 0.09). Piecewise regression, however, showed a quantifiable catch-up phenomenon in BA of 1.5 months per year of rhGH therapy in the first 6.5 years (P = 0.017) that plateaued thereafter (P = 0.88). BAPAH overestimated near-adult height in younger subjects but became more accurate in older subjects (P < 0.0001). IGF-I levels correlated significantly with increases in child’s height and BA-CA.ConclusionLong-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5 years that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and support strategic, but not the insurance company mandated reflexive annual monitoring of skeletal maturation with bone age in children receiving rhGH therapy.

Determination of bone age using deep convolutional neural networks

Aim: Bone age assessment is an important measure of skeletal maturity in children with a growth development disorder. Furthermore, age estimation is an important method applied in various situations such as growth observation, immigrant registration, legal criminal justice, and body detection. In this study, we aimed to develop a computer-assisted bone age detection system. Materials and Methods: This detection is usually evaluated by a trained physician using a radiological examination of the left wrist and a reference model. However, this evaluation method was stated to cause differences brought by interobserver and intraobserver variabilities. Several automated approaches have been proposed to overcome these problems, but none of them have been proven to be generalized according to different races, age ranges, and gender. Considering today's technology, it is observed that developments in the software are already used in the field of health. In this study, bone age was determined from X-rays of the left wrist using convolutional neural networks, which are a popular subject of recent years. Results: In the study, in which a total of 150 patients' images were used, different deep learning architectures were used and the results were compared. On average, the success rate was best at 98.39% with different training-testing split rates. Conclusion: This study demonstrated that deep learning could be used to determine bone age.

English

BACKGROUND Study of ossification of carpal bones in children indicates the level of structural maturity and age estimation. For the assessment of skeletal maturity in children, radiologists often use hand and wrist radiograph because of low level of radiation. Carpals are the most commonly used bones for determining the age of a child. We wanted to study the appearance of ossification centers in the carpal bones in age group of 3 - 14 years. METHODS This is a prospective observational study of one-year duration conducted between January 2019 and December 2020 in the Department of Forensic Medicine and Toxicology at Maheshwara Medical College and Hospital, Patancheru, Telangana. Children 3 to 14 years of age from nearby schools were randomly selected, and X-rays of the carpal bones were taken. Appearance of carpal bones and ossification were studied to estimate the age. RESULTS The study included 70 school children. We found that capitate and hamate carpals ossified during the first year of life in children of both sexes. Triquetral and lunate appeared at 3 - 4 years, trapezium, trapezoid and scaphoid carpals appeared between 5 and 8 years. Pisiform appeared at 9 years of age in females and at 13 years in males. CONCLUSIONS Capitate and hamate ossify at an early age. Triquetral and lunate carpals appear after capitate and hamate. Their appearance is slightly earlier in females than in males. KEYWORDS Ossification, Carpal Bones, Capitate, Hamate

Predicting ambulatory function at skeletal maturity in children with moderate to severe osteogenesis imperfecta.

Maximizing ambulation is a key treatment aim in moderate to severe osteogenesis imperfecta (OI). Here we investigated which early clinical characteristics predicted ambulation function at skeletal maturity. We assessed Bleck ambulation scores in 88 individuals with OI at 5 to 6 years of age and again at final height (at 15 to 24 years of age). At 5 to 6 years of age, 33 (38%) children were non-ambulators, 32 (36%) were fully independent ambulators, and 23 (26%) had intermediate ambulation skills. At skeletal maturity, 58% of the study participants had the same mobility level as at first assessment. The ability to ambulate independently at skeletal maturity was predicted by independent ambulation at 5 to 6 years (odds ratio [OR] 22.6, 95% confidence interval [CI] 4.9-105; P < 0.001), height z score at 5 to 6 years (OR 3.1, CI 1.6-6.3; P = 0.001) and weight z score at 5 to 6 years (OR 0.44, CI 0.19-0.99; P = 0.04).Conclusion: Independent ambulation at 5 to 6 years was the main determinant of independent ambulation at skeletal maturity. This highlights the importance of maximizing ambulation in children below 5 years of age. What is Known: •walking ability varies markedly between OI types. The highest level of mobility was found in OI type I, the lowest in OI type III who require mobility aids; intermediate levels were reported for OI type IV. • OI type is a key predictor of ultimate ability to ambulate, whereas the timing of developmental milestones was not associated with walking ability What is New: • overall key predictors of mobility function at skeletal maturity were mobility status and height z-score at 5-6 years of age • Childrenwho were non-ambulators at 5 to 6 years of age had a higher chance of having better mobility at skeletal maturity if they had good upper extremity function, as expressed in the PEDI Self Care Score.

Displaced Physeal and Metaphyseal Fractures of Distal Radius in Children. Can Wire Fixation Achieve Better Outcome at Skeletal Maturity than Cast Alone?

Introduction:Redisplacement following fracture reduction is a known sequela during the casting period in children treated for distal radius fracture. Kirschner wire pinning can be alternatively used to maintain the reduction during fracture healing. This study was conducted to compare the outcomes at skeletal maturity of distal radius fractures in children treated with a cast alone or together with a Kirschner wire transfixation.Material and Methods:This was a retrospective study involving 57 children with metaphyseal and physeal fractures of the distal radius. There were 30 patients with metaphyseal fractures, 19 were casted, and 11 were wire transfixed. There were 27 patients with physeal fractures, 19 were treated with a cast alone, and the remaining eight underwent pinning with Kirschner wires. All were evaluated clinically, and radiologically, and their overall outcome assessed according to the scoring system, at or after skeletal maturity, at the mean follow-up of 6.5 years (3.0 to 9.0 years).Results:In the metaphysis group, patients treated with wire fixation had a restriction in wrist palmar flexion (p=0.04) compared with patients treated with a cast. There was no radiological difference between cast and wire fixation in the metaphysis group. In the physis group, restriction of motion was found in both dorsiflexion (p=0.04) and palmar flexion (p=0.01) in patients treated with wire fixation. There was a statistically significant difference in radial inclination (p=0.01) and dorsal tilt (p=0.03) between cast and wire fixation in physis group with a more increased radial inclination in wire fixation and a more dorsal tilt in patients treated with a cast. All patients were pain-free except one (5.3%) in the physis group who had only mild pain. Overall outcomes at skeletal maturity were excellent and good in all patients. Grip strength showed no statistical difference in all groups. Complications of wire fixation included radial physeal arrests, pin site infection and numbness.Conclusion:Cast and wire fixation showed excellent and good outcomes at skeletal maturity in children with previous distal radius fracture involving both metaphysis and physis. We would recommend that children who are still having at least two years of growth remaining be treated with a cast alone following a reduction unless there is a persistent unacceptable reduction warranting a wire fixation. The site of the fracture and the type of treatment have no influence on the grip strength at skeletal maturity.

Clinical, laboratory and radiological assessment of skeletal maturation in children and adolescents with obesity

BackgroundChildhood obesity is related to multiple serious health problems and an enhanced risk of premature onset of diseases. The relation of skeletal maturation to obesity is undetermined. The study aims to evaluate skeletal maturation in children and adolescents with obesity, to correlate it with their anthropometric data, body fat content, BMI, fat mass and pubertal stage.ResultsOur study shows that obese children and adolescents have accelerated skeletal maturation compared to control normal-weight healthy subjects (mean skeletal age difference of 0.123 ± 0.67 years versus − 0.175 ± 0.32 years). Also, there were significant positive correlations between bone age and BMI (r = 0.435, P value 0.00).ConclusionThe mean skeletal age difference was more in the obese group as compared to the control group and suggesting accelerated skeletal development in the obese group. It is important to assess skeletal maturity in growing patients to determine the best timing for orthopedic and orthodontic treatment around the growth spurt.

Early maturity as the new normal: a century-long study of bone age

AbstractBackgroundEpiphyseal fusion (EF) marks the completion of longitudinal bone growth, a critical milestone monitored during treatment of skeletal growth and/or developmental disorders. Recently, a trend toward accelerated skeletal maturation in children has been documented. Because current meth

Lower-extremity growth patterns and skeletal maturation in children with unilateral fibular hemimelia.

Fibular hemimelia is the most common congenital long-bone deficiency. It is usually unilateral and results in a limb-length discrepancy. The literature generally subscribes to the concept of constant inhibition, a process by which limb-length ratios between the shorter and longer extremity remain constant throughout growth, but scientific data supporting this concept are sparse. Additionally, recent literature suggests that these children have abnormal skeletal maturation. To elucidate the lower-extremity long-bone growth patterns and skeletal maturation of children with unilateral fibular hemimelia. We reviewed medical records of children with unilateral fibular hemimelia seen at a large pediatric hospital over a 17-year period. Inclusion criteria were: at least two scanograms prior to any shortening/lengthening procedure, and no other congenital or acquired disorders. We collected the study cohort's femoral and tibial lengths (scanogram reports), plotted them against patient chronological ages and compared them to published growth standards. When these children's bone ages (Greulich and Pyle) were available, we plotted them against the children's chronological ages. Twenty-three children were included (total=115 scanograms). At least 1 bone-age assessment was performed in 19 children (total=84 bone ages). All bone growth curves were within normal growth standards for the femur and tibia. Length ratios between shorter and longer limbs remained constant. Skeletal maturation was within two standard deviations of normal in 90% of bone ages. Lower-extremity long bones of children with unilateral fibular hemimelia have relatively normal growth curves, supporting and confirming the concept of constant inhibition. Most children show normal skeletal maturation.

Automated Assessment of Bone Age Using Deep Learning and Gaussian Process Regression.

Bone age is an essential measure of skeletal maturity in children with growth disorders. It is typically assessed by a trained physician using radiographs of the hand and a reference model. However, it has been described that the reference models leave room for interpretation leading to a large inter-observer and intra-observer variation. In this work, we explore a novel method for automated bone age assessment to assist physicians with their estimation. It consists of a powerful combination of deep learning and Gaussian process regression. Using this combination, sensitivity of the deep learning model to rotations and flips of the input images can be exploited to increase overall predictive performance compared to only using the deep learning network. We validate our approach retrospectively on a set of 12611 radiographs of patients between 0 and 19 years of age.

Assessment of sella turcica area and skeletal maturation patterns of children with unilateral cleft lip and palate.

The aim of this case-control study was to assess sella turcica area and skeletal maturity in children with unilateral cleft lip and palate (UCLP) and compare with those of non-cleft children. A total of 85 UCLP patients aged 7.5-17.08years (Group 1: age 7-11years, Group 2: age 11-14years and Group 3: age 14-18years) were compared with 85 control subjects without clefts who were divided into similar age groups. Hand-wrist radiographs and cervical vertebra maturation stages (CVMS) were used to evaluate growth. Lateral cephalograms were traced, and reference points of sella were determined. Sella turcica area was measured using a digital planimeter. Comparison of overall growth on hand-wrist radiographs revealed no significant difference between cleft and non-cleft subjects. However, according to the chronological age groups, Group 1-UCLP showed statistically significant delay in skeletal maturation when compared with the age-matched control subjects (P=.05). This difference was due to the delay among male subjects (P=.05). As for CVMS, more significant maturation delay was observed in Group 1-UCLP (P=.001) and was attributable to both male and female subjects (P=.05). Comparison of sella turcica area showed no significant difference between UCLP patients and controls. Although children with CLP showed significant delay in growth when they are younger compared with the non-cleft children, sella turcica area measurements were similar for individuals in both groups.

Advanced skeletal maturity in children and adolescents with myelomeningocele.

Atypical skeletal development is common in youth with myelomeningocele (MM), though the underlying reasons have not been fully elucidated. This study assessed skeletal maturity in children and adolescents with MM and examined the effects of sex, age, sexual development, ethnicity, anthropometrics and shunt status. Forty-three males and 35 females with MM, 6-16 years old, underwent hand radiographs for bone age determination. The difference between bone age and chronological age was evaluated using Wilcoxon sign rank tests. Relationships between age discrepancy (skeletal-chronological) and participant characteristics were assessed using multiple linear regression with forward selection. Overall, forty percent (31/78) of MM participants had an advanced bone age of 1 year or greater (median: 2.5 years), while 47% (37/78) were within 1 year above or below their chronological age (-0.001 years) and 13% (10/78) were delayed by more than 1 year (-1.4 years). Bone age was advanced compared to chronologic age in both males and females (p⩽ 0.024). Advanced bone age was observed in early to late puberty and after maturation (p⩽ 0.07), as well as in Hispanic participants (p= 0.003) and in those with a shunt (p= 0.0004). Advanced bone age was positively correlated with height, weight and body mass index (BMI) percentiles (p= 0.004). In multiple linear regression analysis, advanced bone age was most strongly associated with higher Tanner stage of sexual development, and higher weight, height or BMI percentile. Advanced skeletal maturity is common in children/adolescents with MM over 8 years of age who have reached puberty (65%), particularly those who are overweight (80%). Hormonal effects associated with adiposity and sexual maturity likely influence skeletal maturation. Clinicians may use Tanner stage and weight or BMI to gain insight into skeletal maturity.

Holistic contrast enhancement of carpals ossification sites for skeletal age assessment system

Pediatricians often apply bone age assessment to measure the skeletal maturity of children and to predict the future height. These discrepancies are good indicators for diagnosing growth disorders. Normally, left hand skeletal is employed in this assessment. The low quality of ossification sites of carpals deteriorates the pediatrician's visibility in inspecting the pertinent radiographic manifestations. This in turn affects the bone age assessment. Therefore, we have to enhance the quality before assessing them. Histogram equalization is one of the contrast enhancement techniques that suit this enhancement. Existing histogram equalizations, however, are confronting with problems in preserving the brightness and details as well as preventing the contrast from being over-enhanced or under-enhanced simultaneously. We propose the comprehensive histogram equalization considering all criteria of desired histogram-equalized image to produce moderately contrast enhanced carpals' ossification sites. Qualitative results show that the determining features of maturity stages have been emphasized in some of the Pareto optimized image. The improvement for Pareto optimized bi-histogram equalization is significant for all stages: 7.16%, 12.4%, 16.03%, 21.21% and 18.51%. We conclude that the Pareto optimized images able to improve the classifier accuracy that estimate the maturity stage of the carpal bones.

Radiological Indicators of Bone Age Assessment in Cephalometric Images. Review

SummaryThe ability to assess bone age accurately is important and allows to diagnose the patient correctly and to plan orthodontic treatment appropriately. The aim of the work is to present views of different authors on the subject of using cephalometric images to determine bone age and its significance for conducting appropriate orthodontic treatment.Publications from the PubMed medical database were analyzed. Search criteria: bone age assessment, CVM method. Ultimately, 36 papers out of 1354 publications were selected.The research of many authors confirms the usefulness of various methods using cephalometric images to assess skeletal age. Currently, the CVM method devised by Baccetti et al. is the most frequently mentioned one in literature.It seems that bone age assessment methods based on evaluating the morphological structure of the cervical vertebrae in cephalometric images can clearly differentiate skeletal maturity in children regardless of their race or sex. Bearing in mind the constant technological progress in medicine and stomatology, bone age assessment methods need to be perfected in order to alleviate their impact on the patient as much as possible.

Growth and skeletal maturation in children with type 1 diabetes mellitus

Objective: To study growth and skeletal maturation in children with type 1 diabetes mellitus (T1DM). Methods: We prospectively studied the anthropometric data of 56 children with T1DM at our tertiary care teaching hospital. Height was re-measured at one year to assess height velocity. A plain radiograph of the left hand was obtained for assessment of skeletal maturation. Glycosylated haemoglobin and thyroid stimulating hormone were measured in all the patients. Results: Short stature [height standard deviation score (HtSDS) <-2] was seen in 15/56 (27%) patients. A negative correlation was observed between HtSDS at recruitment and duration of T1DM (r = -0.347, p = 0.009). Ten of the 25 patients followed up over one year had impaired (< 3rd centile) height velocity (HV). A negative correlation was observed between glycosylated haemoglobin (r = -0.664, p=<0.001) and HV. The proportion of patients with an impaired HV was more in those with an age of onset more than 7.5 yrs (42% Vs 14%, p=0.005). A delayed bone age was observed in 10/37 (27%) patients assessed for skeletal maturation. It correlated negatively with the body mass index standard deviation score (r = -0.484, p=0.002). Conclusion: Poor glycaemic control causes impaired growth in patients with T1DM. Further, T1DM may also be associated with delayed skeletal maturation.

Skeletal maturity of children with multiple osteochondromas: is diminished stature due to a systemic influence?

BackgroundMultiple ostechondromas (MO) is an autosomal dominant inherited disease caused by mutated exostosin genes. It mostly affects the long bones and can lead to growth disturbances, especially disproportionate short stature. Both the local effect on growth plates and the systemic influence of the gene disorder on growth mechanisms might explain the diminished stature.PurposeThe hypothesis of this study is that the diminished stature in adults with MO is due to a systemic influence, leading to early skeletal maturation and early closure of the growth plate. Therefore, in these patients the skeletal age in adolescence is hypothesized to be higher than the calendar age.MethodsRadiographs of the left hand were collected from 50 MO-affected children. The skeletal age was calculated using these radiographs according to the Greulich–Pyle bone scale and was compared to the calendar age at the time of radiography.ResultsChildren aged 3–12 years had a significantly lower skeletal age compared to their calendar age (p = 0.030). Children aged 12–17 years had a significantly higher skeletal age (p = 0.019), especially boys. Skeletal maturation in children with MO therefore differs from their peers.ConclusionIn this study, the skeletal age in younger children with MO is lower than their calendar age. For adolescents, particularly boys, this is reversed, suggesting an earlier or faster closure of the growth plates. These findings support a systemic influence of the gene defect on growth rate.

Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth.

Background Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians. Objectives To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma. Search methods We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014. Selection criteria Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma. Data collection and analysis Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Main results Among 22 eligible trials, 17 pairs of groups comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X2 = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, body mass index and skeletal maturation reported with low quality of evidence due to imprecision. Authors' conclusions In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents’ and physicians’ concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.