Floor K Grote

Diagnostic Approach in Children with Short Stature

For early detection of pathological causes of growth failure proper referral criteria are needed, as well as a thorough clinical, radiological and laboratory assessment. In this minireview we first discuss the two consensus-based and one evidence-based guidelines for referral that have been published. The evidence-based guidelines result in a sensitivity of approximately 80% at a false-positive rate of 2%. Then, relevant clues from the medical history and physical examination are reviewed, and specific investigations based on clinical suspicion listed. In the absence of abnormal clinical findings, an X-ray of the hand/wrist and a laboratory screen are usually performed. Scientific evidence for the various components of laboratory screening is scarce, but accumulated experience and theoretical considerations have led to a list of investigations that may be considered until more evidence is available.

Towards evidence based referral criteria for growth monitoring

Aims: To evaluate the performance of growth monitoring in detecting diseases. Turner’s syndrome (TS) is taken as the target disease. Methods: Case-control simulation study. Three archetypal screening rules are applied to longitudinal growth data comparing a group with TS versus a reference group from birth to the age of 10 years. Main outcome measures were sensitivity, specificity, and median referral age. Results: Clear differences in performance of the rules were found. The best rule takes parental height into account. Combining rules could improve diagnostic accuracy. Conclusion: Growth monitoring is useful to screen for TS. A combined rule that takes absolute height SDS, parental height, and deflection in height velocity into account is the best way to do this. Similar research is needed for other diseases, populations, and ages, and the results should be synthesised into evidence based referral criteria.

The diagnostic work up of growth failure in secondary health care; An evaluation of consensus guidelines

BackgroundAs abnormal growth might be the first manifestation of undetected diseases, it is important to have accurate referral criteria and a proper diagnostic work-up. In the present paper we evaluate the diagnostic work-up in secondary health care according to existing consensus guidelines and study the frequency of underlying medical disorders.MethodsData on growth and additional diagnostic procedures were collected from medical records of new patients referred for short stature to the outpatient clinics of the general paediatric departments of two hospitals (Erasmus MC – Sophia Childrens Hospital, Rotterdam and Spaarne Hospital, Haarlem) between January 1998 and December 2002. As the Dutch Consensus Guideline (DCG) is the only guideline addressing referral criteria as well as diagnostic work-up, the analyses were based on its seven auxological referral criteria to determine the characteristics of children who are incorrectly referred and the adequacy of workup of those who are referred.ResultsTwenty four percent of children older than 3 years were inappropriately referred (NCR). Of the correctly referred children 74–88% were short corrected for parental height, 40–61% had a height SDS <-2.5 and 21% showed height deflection (Δ HSDS < -0.25/yr or Δ HSDS < -1). In none of the children a complete detailed routine diagnostic work up was performed and in more than 30% no routine laboratory examination was done at all. Pathologic causes of short stature were found in 27 children (5%).ConclusionExisting guidelines for workup of children with suspected growth failure are poorly implemented. Although poorly implemented the DCG detects at least 5% pathologic causes of growth failure in children referred for short stature. New guidelines for referral are required with a better sensitivity and specificity, wherein distance to target height should get more attention. The general diagnostic work up for short stature should include testing for celiac disease in all children and for Turner syndrome in girls.

Growth monitoring and diagnostic work-up of short stature: an international inventorization.

BACKGROUND/AIMS Growth monitoring is almost universally performed, but few data are available on which referral criteria and diagnostic work-up are used worldwide for children with short stature. METHODS A short questionnaire, containing questions on auxological screening and on diagnostic criteria for short stature, was sent to all members of the European Society of Paediatric Endocrinology (ESPE) and to several pediatric endocrinologists outside Europe. RESULTS Responses were received from 36 countries. In 27 (75%) a child health care program existed and in 14 (39%) there was a protocol for referral of children with growth retardation. Height for age was mostly used as a referral criterion. Sixteen countries (45%) reported having a guideline in secondary health care for diagnostic work-up. Although all countries agreed on having biochemical, radiological and/or genetic tests in the diagnostic work-up, there was a wide variety of recommended tests. CONCLUSIONS There is little consensus on referral criteria and diagnostic work-up of children with short stature among industrialized countries. There is a need to establish evidence-based guidelines.

Screening rules for growth to detect celiac disease: a case-control simulation study.

BackgroundIt is generally assumed that most patients with celiac disease (CD) have a slowed growth in terms of length (or height) and weight. However, the effectiveness of slowed growth as a tool for identifying children with CD is unknown. Our aim is to study the diagnostic efficiency of several growth criteria used to detect CD children.MethodsA case-control simulation study was carried out. Longitudinal length and weight measurements from birth to 2.5 years of age were used from three groups of CD patients (n = 134) (one group diagnosed by screening, two groups with clinical manifestations), and a reference group obtained from the Social Medical Survey of Children Attending Child Health Clinics (SMOCC) cohort (n = 2,151) in The Netherlands. The main outcome measures were sensitivity, specificity and positive predictive value (PPV) for each criterion.ResultsBody mass index (BMI) performed best for the groups with clinical manifestations. Thirty percent of the CD children with clinical manifestations and two percent of the reference children had a BMI Standard Deviation Score (SDS) less than -1.5 and a decrease in BMI SDS of at least -2.5 (PPV = 0.85%). The growth criteria did not discriminate between the screened CD group and the reference group.ConclusionFor the CD children with clinical manifestations, the most sensitive growth parameter is a decrease in BMI SDS. BMI is a better predictor than weight, and much better than length or height. Toddlers with CD detected by screening grow normally at this stage of the disease.

Referral patterns of children with poor growth in primary health care

BackgroundTo promote early diagnosis and treatment of short stature, consensus meetings were held in the mid nineteen nineties in the Netherlands and the UK. This resulted in guidelines for referral. In this study we evaluate the referral pattern of short stature in primary health care using these guidelines, comparing it with cut-off values mentioned by the WHO.MethodsThree sets of referral rules were tested on the growth data of a random sample (n = 400) of all children born between 01-01-1985 and 31-12-1988, attending school doctors between 1998 and 2000 in Leiden and Alphen aan den Rijn (the Netherlands): the screening criteria mentioned in the Dutch Consensus Guideline (DCG), those of the UK Consensus Guideline (UKCG) and the cut-off values mentioned in the WHO Global Database on Child growth and Malnutrition.ResultsApplication of the DCG would lead to the referral of too many children (almost 80%). The largest part of the referrals is due to the deflection of height, followed by distance to target height and takes primarily place during the first 3 years. The deflection away from the parental height would also lead to too many referrals. In contrast, the UKCG only leads to 0.3% referrals and the WHO-criteria to approximately 10%.ConclusionThe current Dutch consensus guideline leads to too many referrals, mainly due to the deflection of length during the first 3 years of life. The UKCG leads to far less referrals, but may be relatively insensitive to detect clinically relevant growth disorders like Turner syndrome. New guidelines for growth monitoring are needed, which combine a low percentage of false positive results with a good sensitivity.

Growth hormone treatment in children with rheumatic disease, corticosteroid induced growth retardation, and osteopenia

Background: In children with severe rheumatic disease (RD), treatment with corticosteroids (CS) is frequently needed and growth retardation and osteopenia may develop. A beneficial effect of human growth hormone (hGH) has been reported but mostly in trials without a control group. Aims: To study the effect of hGH on growth, bone mineral density (BMD), and body composition, taking the disease activity and CS use into account. Methods: Randomised controlled trial on 17 prepubertal RD patients with growth retardation and/or decreased BMD. The hGH group (n = 10) received treatment with hGH 4 IU/m2/day (∼0.045 mg/kg/day) during two years. The controls (n = 7) received no GH treatment. Results: During the two year study period the disease activity, and use of CS and methotrexate (MTX) did not differ between the groups. There was a significant mean increase in height standard deviation score (HSDS) in the hGH group (0.42±0.16 SDS) and a non-significant decrease in the controls (−0.18±0.11 SDS). Change in BMD did not differ significantly between the groups, although the increase in BMD for lumbar spine within the hGH group was significant. Lean body mass improved significantly in the hGH group compared to controls (0.64±0.19 SDS versus −0.20±0.17 SDS), while the decrease in percentage fat was not significant. Conclusions: There was a significant effect of hGH on growth and lean body mass, but a longer duration of treatment might be necessary to evaluate the effect of hGH on BMD.

Growth monitoring to detect children with cystic fibrosis

Background/Aims: Cystic fibrosis (CF) in infancy and childhood is often associated with failure to thrive (FTT). This would suggest that in countries without a newborn screening program for CF, FTT could be used as a clinical screening tool. The aim of this study is to assess the diagnostic performance of FTT for identifying children with CF. Methods: Longitudinal length and weight measurements up to 2.5 years of age were used from CF patients (n = 123) and a reference group (n = 2,151) in The Netherlands. Growth measurements after diagnosis were excluded. We developed five potential screening rules based upon length, weight and body mass index (BMI) standardized by age and gender (SDS). Outcome measures were sensitivity, specificity and positive predictive value (PPV). Results: BMI SDS had the highest sensitivity at low false-positive rates. An efficient scenario is a BMI SDS below –2.5 SD in combination with a decrease in BMI SDS of at least 0.5 SD. This scenario had a sensitivity of 32%, a specificity of 98.3% and a PPV of 0.75%. Conclusion: In the absence of a newborn screening program, young children with FTT for BMI are candidates to consider testing for CF.

Should Blood Gas Analysis Be Part of the Diagnostic Workup of Short Children? Auxological Data and Blood Gas Analysis in Children with Renal Tubular Acidosis

Background: Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. Objective: To investigate the clinical, growth and laboratory parameters in children with RTA to estimate the possible value of laboratory screening for this disorder in infants and children referred for short stature according to a recent guideline. Method: Retrospective chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands and 3 centers in Belgium. Results: The current guideline for short stature detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6 per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and above 3 years, respectively. Sensitivity was 17/30 and 12/24 for a –2.0 SDS cutoff for weight and body mass index, respectively. In infants and toddlers diagnosed before 3 years of age, the mean weight loss was 1.5 SD, and 0.8 SDS in older children. In short children >3 years RTA was extremely rare, always associated with clinical symptoms, and rarely detected by blood gas analysis. Conclusion: According to our data a decreasing weight SDS for age is a sufficient indication to perform blood gas analysis in children <3 years of age, particularly in the presence of additional clinical features, whereas it can be omitted in short children >3 years of age.