Clinical and genetic characteristics of Dutch children with central congenital hypothyroidism, early detected by neonatal screening.

OBJECTIVE: To evaluate clinical characteristics of patients with central congenital hypothyroidism (CH), detected in the Dutch neonatal screening program. This included patients with isolated central CH but the majority have multiple pituitary hormone deficiencies (MPHD). DESIGN: Nationwide, cross-sectional study. METHODS: Data was collected on clinical characteristics, endocrine tests and neuroimaging of central CH patients, detected by the Dutch neonatal screening and born between 1 January 1995 and 1 January 2015. Height and pubertal status were assessed during a study visit. Isolated central CH patients without a confirmed genetic diagnosis were offered genetic (re-)testing. RESULTS: During the 20-year period 154 central CH patients were detected (incidence of permanent central CH 1:25 642). After excluding deceased (15), severe syndromic (7) and transient patients (6), 92 of 126 eligible patients were included (57 MPHD; 79% male). Sixty-one patients (50 MPHD) had been hospitalized before screening results were reported, but central CH was diagnosed on clinical grounds in only three of them (5%). MRI abnormalities consistent with pituitary stalk interruption syndrome were seen in 50 (93%) MPHD patients. Among isolated central CH patients, 27 (84%) had an IGSF1, TBL1X or IRS4 gene variant (53, 16 and 16%, respectively). CONCLUSION: Many patients with central CH have neonatal health problems, especially MPHD patients. Despite hospital admission of two-thirds of patients, almost none were diagnosed clinically, but only after the notification of an abnormal screening result was received. This indicates that central CH, especially if isolated, is an easily missed clinical diagnosis.

Tracking of thinness and overweight in children of Dutch, Turkish, Moroccan and South Asian descent from 3 through 15 years of age: a historical cohort study.

BACKGROUND: Overweight is shown to track (= to maintain a relative position in a distribution) from childhood to adulthood, but is mostly studied in preobesogenic cohorts and in single ethnic groups. Little is known about tracking of thinness by ethnicity. OBJECTIVES: to determine (differences in) tracking of BMI (class) from 3 through 15 years and the prediction of BMI class at 13-15 years of age in contemporary Dutch, Turkish, Moroccan and South Asian children living in the Netherlands. METHODS: Historical cohort of 7625 children, born 1994-1997, with 24,376 measurements of BMI. BMI z-score and BMI class was analysed using universal criteria. South Asian children were also assessed using ethnic specific BMI criteria. Diagnostic odds ratios (OR) and test properties were calculated to estimate the ability of BMI class at 3-4 years to predict BMI class at 13-15 years. RESULTS: Tracking of thinness between 3 and 15 years was stronger than that of overweight, as indicated by a generally higher diagnostic OR. BMI trajectories between 3 and 15 years of age of thin, normal weight and overweight adolescents were, although significantly different, quite similarly shaped in children of Dutch, Turkish and Moroccan descent. The South Asian BMI trajectory deviated considerably from the other ethnic groups, but the differences disappeared when South Asian specific BMI criteria were applied. A substantial proportion of overweight developed between 5-10 years, after which less children shifted to other BMI classes. A total of 55-78% of children with overweight at 3-4 years retained their overweight at 13-15 years, and 10-20% of 3-4 year olds with thinness remained thin. CONCLUSIONS: In all ethnic groups, overweight and especially thinness highly tracked into adolescence. South Asian children differed from the other ethnic groups when universal BMI criteria were applied, but with South Asian specific BMI criteria tracking patterns became more concordant.

Specific language impairment is associated with maternal and family factors.

BACKGROUND: This study aimed to identify risk factors associated with specific language impairment (SLI). METHODS: In a nested case-control design, 253 children attending special needs schools for severe speech and language difficulties in the Netherlands were matched for sex and date of birth with 253 children attending mainstream education. Data on perinatal, maternal and family issues were retrieved from well-child care files registered shortly after birth. RESULTS: Children with SLI had younger mothers than children in the control group (mean 30 years 9 months vs. mean 31 years 9 months) (P = 0.02). Children with SLI were less frequently breastfed directly after birth (55% vs. 71%) (P = 0.0007) and were less frequently firstborns (33.3% vs. 46.2%) (P = 0.002). No statistically significant differences were found for any of the other risk factors. CONCLUSIONS: A relationship was found between SLI and maternal age, being breastfed and place in the birth order. Perinatal risk factors do not seem to be strongly associated with SLI.

To screen or not to screen for adolescent idiopathic scoliosis? A review of the literature.

OBJECTIVES: Over the years, there has been much debate about the desirability and efficacy of screening for adolescent idiopathic scoliosis. To analyse the current evidence from a public health point of view a renewed evaluation of the literature was performed. STUDY DESIGN: Literature review. METHODS: We performed two literature searches: from January 2000 to April 2015 for systematic reviews or guidelines on screening for adolescent idiopathic scoliosis and from January 2009 to April 2015 for all studies on adolescent idiopathic scoliosis and screening methods. We evaluated if screening for adolescent idiopathic scoliosis fulfils the criteria of the UK National Screenings Committee for appraising a screening programme. RESULTS: Adolescent idiopathic scoliosis is a condition with an unpredictable natural history. The optimal age and frequency of screening are unknown; it is not possible to predict which patients will need (conservative or surgical) treatment. The Forward Bending Test has a positive predictive value of 2.6% and a sensitivity of 56% (95% CI 23-88%) for (conservative or surgical) treatment, and is therefore not valid enough for use in a screening programme. There seems to be sufficient evidence that brace treatment is effective for preventing progression of adolescent idiopathic scoliosis. It is not clear if screening is cost effective. CONCLUSIONS: Despite evidence that brace treatment is effective for preventing progression of adolescent idiopathic scoliosis, the benefits from the screening programme do not outweigh the harms. From a Public Health point of view, there is not enough evidence to support a screening programme for adolescent idiopathic scoliosis.

Cost-effectiveness of newborn screening for cystic fibrosis determined with real-life data.

BACKGROUND: Previous cost-effectiveness studies using data from the literature showed that newborn screening for cystic fibrosis (NBSCF) is a good economic option with positive health effects and longer survival. METHODS: We used primary data to compare cost-effectiveness of four screening strategies for NBSCF, i.e. immunoreactive trypsinogen-testing followed by pancreatitis-associated protein-testing (IRT-PAP), IRT-DNA, IRT-DNA-sequencing, and IRT-PAP-DNA-sequencing, each compared to no-screening. A previously developed decision analysis model for NBSCF was fed with model parameters mainly based on a study evaluating two novel screening strategies among 145,499 newborns in The Netherlands. RESULTS: The four screening strategies had cost-effectiveness ratios varying from €23,600 to €29,200 per life-year gained. IRT-PAP had the most favourable cost-effectiveness ratio. Additional life-years can be gained by IRT-DNA but against higher costs. When treatment costs reduce with 5% due to early diagnosis, screening will lead to financial savings. CONCLUSION: NBSCF is as an economically justifiable public health initiative. Of the four strategies tested IRT-PAP is the most economic and this finding should be included in any decision making model, when considering implementation of newborn screening for CF.

Declining and stabilising trends in prevalence of overweight and obesity in Dutch, Turkish, Moroccan and South Asian children 3-16 years of age between 1999 and 2011 in the Netherlands.

OBJECTIVE: In many developed countries, overweight and obesity prevalence seems to stabilise. The aim of this study was to determine trends between 1999 and 2011 in overweight and obesity prevalence, and mean Body Mass Index (BMI) z-score in Dutch, Turkish, Moroccan and Surinamese South Asian children in the Netherlands. DESIGN: A cross-sectional population-based study with 136 080 measurements of height and weight of 73 290 children aged 3-16 years. BMI class and BMI z-score were determined with the latest International Obesity Taskforce (IOTF) criteria, with overweight defined as an adult BMI equivalent ≥ 25 and obesity ≥ 30. Time trends per year were analysed using logistic and linear regression analyses. RESULTS: The prevalence of overweight in Dutch children declined from 13% to 11% (OR 0.960; 95% CI 0.954 to 0.965), but increased in Turkish children from 25% to 32% (OR 1.028; 95% CI 1.020 to 1.036). In Moroccan and Surinamese South Asian children, overweight rates were stable, but obesity prevalence decreased (OR 0.973; 95% CI 0.957 to 0.989, OR 0.964; 95% CI 0.943 to 0.985, respectively) as well as the mean BMI z-score (B=-0.010; 95% CI -0.014 to -0.006, B=-0.010; 95% CI -0.016 to -0.004). In Turkish children, trends limited to the period 2007-2011 showed no statistically significant relationship for all outcome measures. CONCLUSIONS: The decrease in obesity prevalence in Dutch, Moroccan and Surinamese South Asian children suggests that overweight children became less adipose. The stabilising trend in overweight and obesity prevalence in Turkish children since 2007 may signify a levelling off for this ethnic group.

Evaluation of strained alkynes for Cu-free click reaction in live mice.

INTRODUCTION: We report on our evaluation of the strain-promoted cyclooctyne-azide cycloaddition reaction for use in tumor pretargeting, comprising a side-by-side comparison of probes 1-3 bearing three distinct cyclooctyne moieties based respectively on the 1st and 2nd generation difluorinated cyclooctyne and the 1st generation dibenzocyclooctyne. METHODS: The probes were synthesized and labeled with (177)Lu with high yields. The probe stability and reactivity towards azides were evaluated in PBS and mouse serum, and their blood clearance, biodistribution and in vivo reactivity were evaluated in tumor-free mice. RESULTS: In serum the three probes exhibited sufficient stability for a pretargeting application with half-lives of 12-19h. In PBS, probes 2 and 3 were more reactive towards azido-conjugated Rituximab (Rtx-N3) than 1, but in contrast to 1, their reactivity decreased in mouse serum and mouse serum albumin solutions, as a result of covalent and non-covalent interactions with albumin. Biodistribution data confirmed the interactions with serum proteins in circulation: (177)Lu-1 showed a fast elimination from blood (t1/2,ß = 0.31h), while (177)Lu-2 and (177)Lu-3 were retained in blood for longer periods of time (t1/2,ß = 1.08 and 3.58h, respectively). Dual isotope biodistribution experiments assessing the reaction between (125)I-Rtx-N3 and (177)Lu-1-3 in circulation in mice showed a very limited retention of 2 and 3 in blood rich organs, indicating a minimal reactivity, while no such retention was observed for 1. CONCLUSION: The low reactivity of the studied cyclooctynes, and their serum interactions preclude their use at the low in vivo concentrations typical for pretargeting applications.

Newborn hearing screening in youth health care in the Netherlands: National results of implementation and follow-up.

OBJECTIVE: The aim of this study is to investigate whether the quality of the Dutch, community based, universal newborn hearing screening programme is consistent over time. DESIGN: Universal newborn hearing screening data from three cohorts are compared on a number of quality targets concerning the outcome of the screening and the process of the screening in a three stage, community based, hearing screening programme. STUDY SAMPLE: A total of 552 820 children entered the study (189 794 in 2002-2006; 181 574 in 2008, and 181 452 in 2009). RESULTS: Participation in the programme is high from implementation onwards and increases over time for all screen stages to percentages above 99%. Refer rates are within quality targets and they are consistent over time. The screening is completed within 42 days of birth for 91.5% of the children in the last cohort. Of all children screened, 0.29% to 0.30% are referred to a speech and hearing centre. Participation in diagnostic testing is 93.3% to 95.2%. Of all referred children 77% to 85% receive a diagnosis within 122 days of birth. CONCLUSIONS: A good quality neonatal hearing screening programme in youth health care has been established in the Netherlands. However, both participation in diagnostic testing after a positive screen result and the timing of the diagnostic testing can still be improved.

Ten-year quality assurance of the nationwide hearing screening programme in Dutch neonatal intensive care units.

AIM: To evaluate 10-year quality assurance of newborn hearing screening (NHS) in Dutch neonatal intensive care units (NICU). METHODS: Results of the two-stage automated auditory brainstem response (AABR) screening and diagnostic examination in NICU graduates were centrally registered between October 1998 and December 2008. This registration facilitates screening, tracking and follow-up after abnormal screening results. Outcome measures are referral rates, prevalence rate of hearing loss and (trends of) coverage rates and timeliness of follow-up. RESULTS: Thirty-two thousand one hundred and two infants have been screened. Referral rates were 9.2% at the first and 26.3% at the second stage. Hearing loss was diagnosed in 728 infants (2.2%). Coverage rates were 98.7% at the first, 92.1% at the second stage, 92.3% for the diagnostic examination and 97.9% for the complete programme. After correction for gestational age, 95.8% of the infants had their first AABR<1 month, 81.8% of the referred infants had their second AABR<6 weeks and 67.1% were diagnosed<3 months. There was a positive trend in referred infants that had their second AABR<6 weeks (p=0.004) as well as in infants diagnosed<3 months (p<0.001). CONCLUSION: The NHS in Dutch NICUs is effective. Timely identification of hearing loss is improving over time.

One-third of the new paediatric patients with sickle cell disease in The Netherlands are immigrants and do not benefit from neonatal screening.

OBJECTIVES: To estimate the prevalence of children with sickle cell disease (SCD) in The Netherlands. To estimate the annual number of children newly diagnosed as having SCD and the proportion with diagnoses through neonatal screening To estimate the proportion of children with SCD receiving paediatric care in a comprehensive care setting. DESIGN: Data from two sources, a survey of paediatric practices (n=107) and a laboratory database (n=20), were analysed by the capture-recapture method. PARTICIPANTS: Children with SCD aged <18 years, either born before 2003 or newly diagnosed as having SCD between 2003 and 2007. MAIN OUTCOME MEASURES: Prevalence, annual number of children newly diagnosed as having SCD, proportion of children with diagnoses through neonatal screening, proportion of children receiving paediatric care. RESULTS: The prevalence of SCD in children living in The Netherlands on 1 January 2003 was 1:5152 (95% CI 1:4513 to 1:6015). In the next 4 years, the annual incidence was 1:2011 (95% CI 1:1743 to 1:2376). Nearly one-third (27%) of the children newly diagnosed as having SCD immigrated to The Netherlands after birth and would, therefore, be missed by the neonatal screening programme. Approximately 60% of all children with SCD were not reported by paediatricians. CONCLUSION: The number of children with SCD in The Netherlands is much higher than previously estimated, and the majority of these children seem not to be reviewed regularly by a paediatrician. Children born abroad (27% of new cases) do not benefit from neonatal screening and are at high risk of life-threatening complications before SCD is diagnosed. As this introduces disparities in healthcare, the initiation of adequate measures should be considered.

Risk indicators for hearing loss in infants treated in different neonatal intensive care units.

AIM: To assess which infants' characteristics and specialized procedures are risk indicators for unilateral or bilateral hearing loss (HL) and to evaluate whether these risk indicators are associated with variation in prevalence of HL between Neonatal Intensive Care Units (NICUs). METHODS: For 2002-2005, data from the NICU hearing screening database in the Netherlands were matched with the national neonatology database in which all NICU infants with their patient characteristics and specialized procedures are registered. Multivariate logistic regression analyses were performed to assess risk indicators for HL and to explain differences in prevalence rates between NICUs. RESULTS: A total of 10 830 infants were available for analyses. The prevalence of HL was 1.8% and ranged from 0.7 to 3.7% between NICUs. Infants' characteristics that significantly increased the risk of HL were the presence of craniofacial anomalies, chomosomal/syndromal anomalies, central nervous system conditions, circulatory system conditions and intra-uterine infections. The specialized procedures involving > or =12 days of intensive care and high frequency oxygenation ventilation were independent risk indicators for HL. Approximately 20% of the variance can be explained by the studied risk indicators. Differences in prevalence rates between NICUs were slightly reduced after adjustment for these risk indicators. NICUs with the highest prevalence rates of HL were situated in the largest cities in the Netherlands with a mixed population because of immigration. Therefore, ethnicity may be a risk indicator. CONCLUSIONS: Several independent risk indicators for HL were found, but they could not explain all differences in prevalence rates of HL between NICUs.

Trends in overweight and obesity prevalence in Dutch, Turkish, Moroccan and Surinamese South Asian children in the Netherlands.

OBJECTIVE: To determine trends in the prevalence of overweight and obesity in children in The Hague (the Netherlands) from 1999 through 2007. DESIGN: Population-based study of a series of cross-sectional assessments of height and weight from electronic health records. SETTING: Child Health Care (Municipal Health Service), The Hague. PARTICIPANTS: 50,961 children aged 3-16 years, with Dutch (59%), Turkish (17%), Moroccan (13%) or Surinamese South Asian (11%) ethnicity, representative of the four major ethnic groups in The Hague, with 85,234 weight and height measurements recorded in 1999-2007. MAIN OUTCOME MEASURES: (Trends in) the prevalence of overweight (excluding obesity) and obesity as defined by the International Obesity Taskforce cut-off points, using logistic regression with year as independent variable. RESULTS: From 1999 through 2007 there was a decrease in the prevalence of overweight in Dutch girls from 12.6% to 10.9% (OR 0.96; 95% CI 0.95 to 0.98) and an increase in Turkish boys from 14.6% to 21.4% (OR 1.08; 95% CI 1.04 to 1.11). Obesity prevalence rose significantly in Turkish boys from 7.9% to 13.1% (OR 1.04; 95% CI 1.01 to 1.06) and in Turkish girls from 8.0% to 10.7% (OR 1.04; 95% CI 1.01 to 1.08). Dutch boys, and Moroccan and Surinamese South Asian boys and girls showed no significant trends. CONCLUSIONS: The declining prevalence of overweight in Dutch girls may indicate reversal of previous trends in the Netherlands. However, in Turkish children overweight prevalence and obesity is high and increasing. Further public health action is necessary, especially for Turkish children.

Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU.

BACKGROUND: The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age. AIM: This study was conducted to investigate the course of the individual Phe tolerance and to assess the predictive value of both the pre-treatment Phe concentration and Phe tolerance at 1 and 6 months and 1, 2, 3 and 5 years for Phe tolerance at 10 years of age. METHOD: Data on blood Phe concentration, prescribed Phe intake and weight of 213 early and continuously treated Dutch PKU patients up to 10 years of age were collected. Data acquired under good metabolic control were used in the study. Tolerance was expressed in mg/day and mg/kg per day. RESULTS: Data at 1 and 6 months and at 1, 2, 3 and 5 years of 61, 58, 59, 57, 56 and 59 patients were included for comparison with the Phe tolerance at 10 years. Phe tolerances (mg/kg per day) at 2, 3 and 5 years showed a clear correlation with the tolerance at 10 years of age (r = 0.608, r = 0.725 and r = 0.661). Results for tolerance expressed as mg/day were comparable. Pre-treatment Phe concentrations did not correlate significantly with the tolerance. CONCLUSION: Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age.

Examination of long-lasting parental concern after false-positive results of neonatal hearing screening.

OBJECTIVE: To investigate whether false-positive outcomes on neonatal hearing screening cause long-lasting parental concerns. METHODS: A general population of parents whose children had participated in the universal neonatal hearing screening (UNHS) programme were examined. Parents filled out a questionnaire 6 months after UNHS. Outcomes were compared for all parents whose child tested positive or inconclusive in at least one of three tests but afterwards proved not to have hearing impairment (cases, n = 154) and a random sample of parents whose child passed the first test (controls, n = 288). Parental anxiety as measured with the State-Trait Anxiety Inventory (STAI), attitude towards the child (child health rating and experienced problems) and sensitivity to hearing problems were measured. RESULTS: Median STAI score was equal for cases and controls. Parental attitudes toward the child also did not differ. The difference in the proportion of parents who worried about their child's hearing was statistically significant between cases and controls (p = 0.001) and varied with the number of screens; 4% of controls were worried about the child's hearing, as compared to 10% of cases whose children were tested twice, and 15% of cases whose children were tested three times. CONCLUSIONS: False-positive UNHS test results do not cause long-term general parental anxiety. However, 6 months after screening, a considerable proportion of parents continued to experience hearing-specific worries regarding their child.

Developing evidence-based guidelines for referral for short stature.

OBJECTIVE: To establish evidence-based guidelines for growth monitoring on a population basis. STUDY DESIGN: Several auxological referral criteria were formulated and applied to longitudinal growth data from four different patient groups, as well as three samples from the general population. RESULTS: Almost 30% of pathology can be detected by height standard deviation score (HSDS) below -3 or at least two observations of HSDS below -2.5 at a low false-positive rate (<1%) in 0-3-year-old infants. For 3-10-year olds, a rule concerning distance to target height of >2 SD in combination with HSDS <-2.0 has the best predictive value. In combination with a rule on severe short stature (<-2.5 SDS) and a minor contribution from a rule on "height deflection", 85.7% of children with Turner syndrome and 76.5% of children who are short because of various disorders are detected at a false-positive rate of 1.5-2%. CONCLUSIONS: The proposed guidelines for growth monitoring show high sensitivity at an acceptably low false-positive rate in 3-10-year-old children. Distance to target height is the most important criterion. Below the age of 3 years, the sensitivity is considerably lower. The resulting algorithm appears to be suitable for industrialised countries, but requires further testing in other populations.

[Weight loss, serum sodium concentration and residual symptoms in patients with hypernatremic dehydration caused by insufficient breastfeeding]. / Gewichtsverlies, serumnatriumconcentratie en restverschijnselen bij patiëntjes met hypertone dehydratie door onvoldoende borstvoeding.

OBJECTIVE: To determine the relationship between serum sodium concentration and weight loss as well as residual symptoms in newborns with hypernatremic dehydration caused by insufficient breastfeeding; and to determine the sensitivity of the following rule of thumb 'if weight loss is less than 10%, the baby does not have hypernatremic dehydration caused by insufficient breastfeeding'. DESIGN: Systematic literature search. METHOD: Medline was searched using the terms 'dehydration AND breastfeeding' for case reports on patients with 'hypernatremic dehydration caused by insufficient breastfeeding'. Reference lists from the articles retrieved were also searched. Articles published in 1970-2004 in Dutch, English, French, and German were included. All cases that the author diagnosed as 'hypernatremic dehydration caused by insufficient breastfeeding' were included. RESULTS: A total of 47 articles were found, containing 128 relevant cases. Of these, 9 had less than 10% weight loss. Therefore, the sensitivity of the 10% rule was 93%. We found a linear relationship between the degree of weight loss and serum sodium concentration (Pearson's correlation coefficient = 0.71; p < 0.001). For every 10% increase in weight loss, the serum sodium concentration increased by 16 mmol/l (95% CI: 13-19). As the serum sodium concentration increased, the prevalence of residual symptoms increased. No residual symptoms were reported in patients with less than 10% weight loss. CONCLUSION: A relatively strong linear relationship was found between weight loss and serum sodium concentration. If the weight loss was more than 10%, the serum sodium concentration was beyond the range of normal values. The rule of thumb had a high sensitivity; however, the specificity should be determined before the rule of thumb is implemented.

Behavioural factors related to metabolic control in patients with phenylketonuria.

BACKGROUND: The objective of this study was to determine the importance of parental factors possibly related to dietary control in early and continuously treated patients with phenylketonuria (PKU). METHODS: A questionnaire was disseminated among parents of 238 patients with PKU born after the nationwide introduction of newborn screening for PKU (1 September 1974) until 31 December 1995. The questionnaire was based on a behavioural model measuring people's attitudes, subjective norms, and self-efficacy. Dietary control was defined on the basis of mean phenylalanine (Phe) concentration of the PKU patients measured between 1 January 1994 and 31 December 1996. RESULTS: Response rate was 71%. Attitudes: children of parents who believed that their child adheres well to the diet, even if his or her Phe concentrations are sometimes too high, had lower Phe concentrations than children of parents who disagree with this statement (adjusted difference -103 micromol/L, p < 0.001). Subjective norm: Phe concentrations were higher when parents answered that their relatives did not approve when their child deviates from the diet (p = 0.004). Self-efficacy: children of parents who reported difficulties in having their child eat the synthetic protein substitute three times a day had higher Phe concentrations than those of parents who did not have such difficulties (adjusted difference 156 micromol/L, p = 0.007). CONCLUSION: More attention should be given to parents having their child eat the synthetic protein substitute at least three times a day and to teaching parents to keep strictly to the diet without being too rigid. These factors were strongly associated to dietary control and may be amenable to change.

Individual growth curve models for assessing evidence-based referral criteria in growth monitoring.

The goal of this study is to assess whether a growth curve model approach will lead to a more precise detection of Turner sydnrome (TS) than conventional referral criteria for growth monitoring. The Jenss-Bayley growth curve model was used to describe the process of growth over time. A new screening rule is defined on the parameters of this growth curve model, parental height and gestational age. The rule is applied to longitudinal growth data of a group of children with TS (n=777) and a reference (n=487) group. The outcome measures are sensitivity, specificity and median referral age. Growth curve parameters for TS children were different from reference children and can therefore be used for screening. The Jenss-Bayley growth model, which uses all longitudinal measurements from birth to a maximum age of 5 years with at least one measurement after the age of 2, together with parental height and gestational age can achieve a sensitivity of 85.2 per cent with a specificity of 99.5 per cent and a median referral age of 4.2 (the last measurement between the age of 2 and 5 of each child is considered to be the moment of referral). Sensitivity increases by 2 percentage points when decreasing the specificity to 99 per cent. The Jenss-Bayley growth model from birth to a maximum age of 8 years with at least one measurement after the age of 2, together with parental height results in a sensitivity of 89.0 per cent with a specificity of 99.5 per cent and a median referral age of 6.1. For a specificity of 98 per cent, we obtain a sensitivity of 92.3 per cent. In comparison to conventional rules applied to the same data, sensitivity is about 11-30 percentage points higher at the same level of specificity for the Jenss-Bayley growth rule. We conclude that from the age of 4, growth curve models can improve the screening on TS to conventional screening rules.