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In het Terneuzen Onderzoek naar Preventie zijn overgewicht en cardiometabole risicofactoren op jongvolwassen leeftijd bestudeerd in relatie tot de veranderingen in body mass index (BMI) tussen de geboorte en 18-jarige leeftijd. Deze studie is gebaseerd op het Terneuzen Geboorte Cohort, waarbij prospectief verkregen gegevens zijn verkregen via de jeugdgezondheidszorg (JGZ) van GGD Zeeland. Bij de analyses is gebruik gemaakt van de brokenstickmethode en van lineaire en logistische regressieanalyses. Het leeftijdsinterval 2-6 jaar was het meest voorspellend voor overgewicht en de meeste cardiometabole uitkomsten op jongvolwassen leeftijd. Deze resultaten vragen speciale aandacht van de JGZ voor een stijgende BMI-standaarddeviatiescore (SDS) gedurende het leeftijdsinterval 2-6 jaar, ook als er nog geen sprake is van overgewicht. Hierbij kunnen predictie-instrumenten nuttig zijn. Het monitoren en stabiliseren van de BMI SDS gedurende dit leeftijdsinterval draagt waarschijnlijk niet alleen bij aan de preventie van overgewicht op jongvolwassen leeftijd, maar ook aan een goede cardiometabole gezondheidstoestand op latere leeftijd.

Excess weight in early life is believed to increase susceptibility to obesity, and in support of such theory, excess weight and fast weight gain in early childhood have been related to overweight later in life. The aim of this study was to review the literature on body size and growth in 0- to 4-year-old children and the association with body size at age 5-13 years. In total, 43 observational studies on body size and/or growth were included, of which 24 studies had been published in 2005 or later. Twenty-one studies considered body size at baseline, and 31 studies considered growth which all included assessment of weight gain. Eight (38%) studies on body size, and 15 (48%) on weight gain were evaluated as high-quality studies. Our results support conclusions in previous reviews of a positive association between body size and weight gain in early childhood, and subsequent body size. Body size at 5-6 months of age and later and weight gain at 0-2 years of age were consistently positively associated with high subsequent body size. Results in this review were mainly based on studies from developed Western countries, but seven studies from developing countries showed similar results to those from developed countries.

Background: Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens. Objective: To describe the pubertal development and uterine dimensions achieved by low-dose 17β-oestradiol (17β-E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression. Design: In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low-dose 17β-E2 (5 μg/kg/day) during GH treatment at mean (SD) age 12.7 (0.7) years. Hormone levels were measured at start, 3 months after start and after increasing 17β-E2 dosage. Uterine dimensions were measured in 39 TS women at age 19.9 (2.2) years. Results: Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17β-E2 dose of 5 μg/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17β-E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10.2%), cylindrical in four and mature-adult shaped in 31 (79.5%) of TS patients. Conclusions: During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2-year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age-appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS. © 2009 The Authors.

Introduction: Infant growth has not been studied in developing countries in relation to maternal factors related to malaria in pregnancy and maternal illiteracy. Objective: To describe growth patterns in infants with low and normal birthweight and determine maternal risk factors for infant undernutrition. Methods: Babies born in a rural district of southern Malawi were recruited. An infant cohort was selected on the basis of low or normal birthweight. Weight and length were recorded at birth and at 4-weekly intervals until at 52 weeks after birth. Maternal characteristics at first antenatal attendance and delivery were obtained. Odds ratios in univariate analysis were adjusted for birthweight. Factors included in the multivariate regression included maternal illiteracy, season of birth, maternal iron deficiency and number of infant illness episodes. Results: Low birthweight infants were shorter and lighter throughout infancy than either normal birthweight or international reference values. At 12 months, placental or peripheral malaria at delivery (adjusted odds 1.8; 1.0, 3.1), number of infant illness episodes (AOR = 2.1; 1.2, 3.6) and maternal illiteracy (AOR = 2.7; 1.5, 4.9) were independently associated with low weight for age. Maternal short stature (AOR = 1.8; 1.1. 3.2), male sex (AOR = 2.4; 1.4, 4.1), number of infant illness episodes (AOR = 2.6; 1.5, 4.4), and birth in the rainy season (2.1; 1.2, 3.7) were independently associated with stunting. Placental or peripheral malaria at delivery (AOR = 2.2; 1.1, 4.4) and number of illness episodes (AOR = 2.2; 1.1, 4.5) were independently associated with thinness. Conclusion: Malaria during pregnancy and maternal illiteracy are important maternal characteristics associated with infant undernutrition. Innovative health/literacy strategies are required to address malaria control in pregnancy in order to reduce the magnitude of its effects on infant undernutrition. © 2005 Elsevier Ireland Ltd. All rights reserved.

The aim of this analysis was to construct cross-sectional gestational age specific percentile curves for birthweight, length, head and mid-arm circumference for Malawian babies, and to compare these percentiles with reference values for babies born to women with normal pregnancies, from a developed country. A cross-sectional study which enrolled pregnant women attending two study hospitals between March 1993 and July 1994 was undertaken. Data on maternal socio-economic status, newborn anthropometry, previous obstetric history and current pregnancy were collected. Smoothed percentile values were derived using the LMS method. Malawian reference percentiles were constructed for fetal growth from 35 weeks' gestation for singleton births. Mean birthweight, length and head circumference were lower at all gestational ages for Malawian compared with Swedish newborns. Fetal growth per completed gestational week was higher by 60 g in weight, 0.5 cm in length and 0.2 cm in head circumference in Swedish compared with Malawian babies. Growth restriction was present from 35 to 41 weeks' gestation. The pattern for the 10th percentile suggested that this was occurring from well before 35 weeks' gestation in a proportion of babies. © 2005 Taylor & Francis.

The World Health Organization (WHO), in collaboration with a number of research institutions worldwide, is developing new child growth standards. As part of a broad consultative process for selecting the best statistical methods, WHO convened a group of statisticians and child growth experts to review available methods, develop a strategy for assessing their strengths and weaknesses, and discuss methodological issues likely to be faced in the process of constructing the new growth curves. To select the method(s) to be used, the group proposed a two-stage decision-making process. First, to select a few relevant methods based on a list of set criteria and, second, to compare the methods using available tests or other established procedures. The group reviewed 30 methods for attained growth curves. Using the pre-defined criteria, a few were selected combining five distributions and two smoothing techniques. Because the number of selected methods was considered too large to be fully tested, a preliminary study was recommended to evaluate goodness of fit of the five distributions. Methods based on distributions with poor performance will be eliminated and the remaining methods fully tested and compared. Copyright © 2005 John Wiley & Sons, Ltd.

AIM: To provide growth and sexual maturation reference data for Moroccan children living in The Netherlands and to compare them with the reference data of children of Dutch origin. METHODS: Cross-sectional growth and demographic data were collected from 2880 children of Moroccan origin and 14,500 children of Dutch origin living in The Netherlands in the age range 0-20 y. Growth references for length, height, weight, weight-for-height, body mass index (BMI) and head circumference were constructed with the LMS method. Predictive variables for height and BMI were assessed by regression analyses. Reference curves for sexual maturation were estimated by a generalized additive model. RESULTS: Moroccan young adults were on average 9 cm shorter than their Dutch contemporaries. Mean final height was 174.7 cm for males and 161.3 cm for females. Height differences in comparison with Dutch children increase from 2 y onwards. Height SDS was predominantly associated with target height. Compared to Dutch children, maturation started 0.2 and 0.9 y later for girls and boys, respectively. Median age at menarche was 12.9 y, 3.6 mo earlier than in Dutch girls (p = 0.001). BMI of Moroccan children was above that of Dutch children, especially for girls. BMI SDS was associated with birthweight in the age group 0 - < or = 5 y. CONCLUSION: Moroccan children living in The Netherlands are substantially shorter than Dutch children. Girls have higher weight-for-height and BMI for age. Median age at menarche occurs earlier. Given these differences, separate growth charts for the Moroccan children are useful.

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 sub-scales of the SF-36 in the Dutch National Study are investigated with respect to unidimensionality and reliability. It is argued that these properties deserve separate treatment. For unidimensionality we use a non-parametric model from item response theory, called the Mokken scaling model, and compute the corresponding scalability coefficients. We estimate reliability under the Mokken model, assuming that the items are double homogeneous, and compare it to Cronbach's α. The scalability of the sub-scale general health perceptions is medium (H = 0.46), and for the other sub-scales it is strong (H ≥ 0.6). The reliability in terms of α indicates that all sub-scales can be used in basic research (α > 0.70), but that only physical functioning can be used for clinical applications of quality of life (α > 0.90). The relative merits of our approach are discussed.

BACKGROUND: Although children both at the upper and lower tail of the body mass index (BMI) distribution are at greater health risk, relatively little is known about the development of thinness prevalence rates in developed countries over time. We studied trends in childhood thinness and assessed changes in the BMI distribution since the onset of the obesity epidemic. METHODS: Growth data from 54 814 children aged 2-18 years of Dutch, Turkish and Moroccan origin living in The Netherlands were used. Anthropometric measurements were performed during nationwide cross-sectional growth studies in 1980 (only Dutch), 1997 and 2009. Prevalence rates of thinness grades I, II and III were calculated according to international cut-offs. BMI distributions for 1980, 1997 and 2009 were compared. RESULTS: Since 1980, thinness (all grades combined) reduced significantly from 14.0% to 9.8% in children of Dutch origin, but the proportion of extremely thin children (grade III) remained constant. Thinness in children of Moroccan origin decreased significantly from 8.8% to 6.2% between 1997 and 2009. No significant difference was observed in children of Turkish origin (5.4% in 1997 vs. 5.7% in 2009). Thinness occurred most often in children aged 2-5 years. There were no differences between boys and girls. The BMI distribution widened since 1980, mainly due to an upward shift of the upper centiles. CONCLUSION: Since the onset of the obesity epidemic, prevalence rates of thinness decreased. However, we found a small but persistent group of extremely thin children. More research is needed to gain insight into their health status.

Standard approaches to implement multiple imputation do not automatically incorporate nonlinear relations like interaction effects. This leads to biased parameter estimates when interactions are present in a dataset. With the aim of providing an imputation method which preserves interactions in the data automatically, the use of recursive partitioning as imputation method is examined. Three recursive partitioning techniques are implemented in the multiple imputation by chained equations framework. It is investigated, using simulated data, whether recursive partitioning creates appropriate variability between imputations and unbiased parameter estimates with appropriate confidence intervals. It is concluded that, when interaction effects are present in a dataset, substantial gains are possible by using recursive partitioning for imputation compared to standard applications. In addition, it is shown that the potential of recursive partitioning imputation approaches depends on the relevance of a possible interaction effect, the correlation structure of the data, and the type of possible interaction effect present in the data.

The Severity of Disabilities Scale (SDS) of the ICIDH reflects the degree to which an individual's ability to perform a certain activity is restricted. This paper describes the application of two models from item response theory (IRT), the graded response model and the partial credit model, in order to derive a tentative proposal for a revised SDS. The key ingredient of the approach is to scale existing disability items obtained in different studies on a common scale by exploiting the overlap. Both IRT models are fitted to a linked data set containing items for measuring walking disability. Based on these solutions, a tentative SDS is constructed. The paper concludes with a discussion of the implications, limitations and advantages of the approach. Copyright © 2001 John Wiley & Sons, Ltd.

The worm plot visualizes differences between two distributions, conditional on the values of a covariate. Though the worm plot is a general diagnostic tool for the analysis of residuals, this paper focuses on an application in constructing growth reference curves, where the covariate of interest is age. The LMS model of Cole and Green is used to construct reference curves in the Fourth Dutch Growth Study 1997. If the model fits, the measurements in the reference sample follow a standard normal distribution on all ages after a suitably chosen Box-Cox transformation. The coefficients of this transformation are modelled as smooth age-dependent parameter curves for the median, variation and skewness, respectively. The major modelling task is to choose the appropriate amount of smoothness of each parameter curve. The worm plot assesses the age-conditional normality of the transformed data under a variety of LMS models. The fit of each parameter curve is closely related to particular features in the worm plot, namely its offset, slope and curvature. Application of the worm plot to the Dutch growth data resulted in satisfactory reference curves for a variety of anthropometric measures. It was found that the LMS method generally models the age-conditional mean and skewness better than the age-related deviation and kurtosis. Copyright © 2001 John Wiley & Sons, Ltd.

Objective: (1) To describe the sex-specific, birth weight distribution by gestational age of babies born in a malaria endemic, rural area with high maternal HIV prevalence; (2) to assess the contribution of maternal health, nutritional status and obstetric history on intra-uterine growth retardation (IUGR) and prematurity. Methods: Information was collected on all women attending antenatal services in two hospitals in Chikwawa District, Malawi, and at delivery if at the hospital facilities. New-borns were weighed and gestational age was assessed through post-natal examination (modified Ballard). Sex-specific growth curves were calculated using the LMS method and compared with international reference curves. Results: A total of 1423 live-born singleton babies were enrolled; 14.9% had a birth weight < 2500 g, 17.3% were premature (< 37 weeks) and 20.3% had IUGR. A fall-off in Malawian growth percentile values occurred between 34 and 37 weeks gestation. Significantly associated with increased IUGR risk were primiparity relative risk (RR) 1.9; 95% CI 1.4-2.6), short maternal stature (RR 1.6; 95% CI 1.0-2.4), anaemia (Hb < 8 g/dl) at first antenatal visit (RR 1.6; 95% CI 1.2-2.2) and malaria at delivery (RR 1.4; 95% CI 1.0-1.9). Prematurity risk was associated with primiparity (RR 1.7; 95% CI 1.3-2.4), number of antenatal visits (RR 2.2; 95% CI 1.6-2.9) and arm circumference < 23 cm (RR 1.9; 95% CI 1.4-2.5). HIV infection was not associated with IUGR or prematurity. Conclusion: The birth-weight-for-gestational-age, sex-specific growth curves should facilitate improved growth monitoring of new-borns in African areas where low birth weight and IUGR are common. The prevention of IUGR requires improved malaria control, possibly until late in pregnancy, and reduction of anaemia. Chemicals/CAS: Antimalarials

Background In 2002, we developed a list of 60 potential relevant determinants that are critical for a successful implementation of innovations in health care, such as guidelines. This list was a result of a review of empirical studies and a Delphi study among implementation experts. Since 2002, we used the list in eight empirical studies concerning the implementation of guidelines/programs. Objectives The development of a generic measurement instrument for the assessment of determinants of implementation of innovations. Methods In each study, a similar method was used to measure implementation of the guideline/program as well as the determinants. The information of the eight empirical studies were combined into one data set. Missing values in the final data set were replaced by plausible values using multiple imputation. We assessed which determinants ‘predict’ the implementation: separately and in combination with each other. In addition, 22 implementation experts commented on the results of the meta-analyses. Results An instrument with 29 determinants was established; 7 are related to the guideline/programme itself; 11 to the user; 11 to the organisation and socio-political context. Discussion This instrument is to be used before or after a guideline is introduced in order to gain insight into critical determinants that need to be targeted in order to improve implementation. Implications for Guideline Developers/Users Since 7 determinants are related to the innovation itself (e.g. clear procedures) developers should take these into account when developing a guideline.

Of nearly 1900 live-born singletons, born from April 1988 to October 1989 inclusive, nine measurements of length and weight have been taken between the ages of 1 and 24 months. In the first part of the study, differences in attained length and weight at 1 and 2 years of age are analysed according to socioeconomic status (SES). Multiple regression analyses are used to investigate the association of SES and other background characteristics with length and weight. The second part focuses on the analysis of differences in linear length and weight gain in the first 2 years of life, using a two-step regression technique. At 1 and 2 years of age, differences in attained length and weight and in length and weight gain according to SES are small and not significant, except for the children of Mediterranean parents in the low-SES group, who are significantly heavier than children of all other groups and gain significantly more in weight compared to children of Dutch parents in the low-SES group. Of all the factors studied it appears that parental height, birthweight, parity and ethnic descent of the parents are associated with attained length and weight at 1 and 2 years of age. Of these factors, ethnic descent, however, is not associated with length gain. A small but statistically significant catch-up growth is found in children of mothers who smoked during pregnancy.

Excess weight in early life is believed to increase susceptibility to obesity, and in support of such theory, excess weight and fast weight gain in early childhood have been related to overweight later in life. The aim of this study was to review the literature on body size and growth in 0- to 4-year-old children and the association with body size at age 5-13 years. In total, 43 observational studies on body size and/or growth were included, of which 24 studies had been published in 2005 or later. Twenty-one studies considered body size at baseline, and 31 studies considered growth which all included assessment of weight gain. Eight (38%) studies on body size, and 15 (48%) on weight gain were evaluated as high-quality studies. Our results support conclusions in previous reviews of a positive association between body size and weight gain in early childhood, and subsequent body size. Body size at 5-6 months of age and later and weight gain at 0-2 years of age were consistently positively associated with high subsequent body size. Results in this review were mainly based on studies from developed Western countries, but seven studies from developing countries showed similar results to those from developed countries.

Growth and body height have always been topics interesting to the public. In particular, the stupendous increase of some 15-19. cm in final adult height during the last 150 years in most European countries (the " secular trend" ), the concomitant changes in body and head proportions, the tendency towards early onset of sexual maturation, the changes in the age when final height is being reached, and the very recent trend in body mass index, have generated much scientific literature. The marked plasticity of growth in height and weight over time causes problems. Child growth references differ between nations, they tend to quickly become out of date, and raise a number of questions regarding fitting methods, effects caused by selective drop-out, etc. New findings contradict common beliefs about the primary importance of nutritional and health related factors for secular changes in growth. There appears to be a broad age span from mid-childhood to early adolescence that is characterised by a peculiar insusceptibility. Environmental factors that are known to influence growth during this age span appear to have only little or no impact on final height. Major re-arrangements in height occur at an age when puberty has almost been completed and final height has almost been reached, implying that factors, which drive the secular trend in height, are limited to early childhood and late adolescence. © 2010 Elsevier GmbH.

Objectives:Studies regarding the association of child-care use with body mass index (BMI), overweight or obesity development show contradictory results. This study examined the relationship between child-care use and BMI z-scores and overweight, as well as associates of child-care use in children up to 2 years old.Methods:Longitudinal data originated from the Dutch KOALA Birth Cohort Study. Questionnaires assessed child-care use at ages 7 months and 1 and 2 years (N=2396). Height and weight assessed at 1 and 2 years were used to calculate BMI z-scores. Overweight was defined as a BMI z-score of >/=85th percentile. The influence of child-care use on weight development was tested using backward linear and logistic regression analyses. Outcomes were: (1) BMI z-score at 1 and 2 years; (2) change in BMI z-score between 1 and 2 years; (3) overweight vs non-overweight at 1 and 2 years; and (4) change from normal weight to overweight vs remaining normal weight between 1 and 2 years. The association between child-care use and parental background characteristics was tested using backward logistic regression analyses.Results:Child-care use (no/yes) at 1 and 2 years positively predicted BMI z-scores at age 2 years, as well as change in BMI z-score between 1 and 2 years. These associations were adjusted for various covariates (for example, parental working hours). Furthermore, child-care use significantly increased the odds of being overweight at age 1year. There were few differences in BMI or overweight between intensive (>16 h per week) and limited child-care use (

Regional or national growth distributions can provide vital information on the health status of populations. In most resource poor countries, however, the required anthropometric data from purpose-designed growth surveys are not readily available. We propose a practical method for estimating regional (multi-country) age-conditional weight distributions based on existing survey data from different countries. We developed a two-step method by which one is able to model data with widely different age ranges and sample sizes. The method produces references both at the country level and at the regional (multi-country) level. The first step models country-specific centile curves by Box-Cox t and Box-Cox power exponential distributions implemented in generalized additive model for location, scale and shape through a common model. Individual countries may vary in location and spread. The second step defines the regional reference from a finite mixture of the country distributions, weighted by population size. To demonstrate the method we fitted the weight-for-age distribution of 12 countries in South East Asia and the Western Pacific, based on 273 270 observations. We modeled both the raw body weight and the corresponding Z score, and obtained a good fit between the final models and the original data for both solutions. We briefly discuss an application of the generated regional references to obtain appropriate, region specific, age-based dosing regimens of drugs used in the tropics. The method is an affordable and efficient strategy to estimate regional growth distributions where the standard costly alternatives are not an option. Copyright © 2009 John Wiley & Sons, Ltd.

Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens.To describe the pubertal development and uterine dimensions achieved by low-dose 17beta-oestradiol (17beta-E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression.In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low-dose 17beta-E2 (5 microg/kg/day) during GH treatment at mean (SD) age 12.7 (0.7) years. Hormone levels were measured at start, 3 months after start and after increasing 17beta-E2 dosage. Uterine dimensions were measured in 39 TS women at age 19.9 (2.2) years.Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17beta-E2 dose of 5 microg/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17beta-E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10.2%), cylindrical in four and mature-adult shaped in 31 (79.5%) of TS patients.During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2-year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age-appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS.

OBJECTIVE. Prevalence of asthma and overweight has increased simultaneously during the past decades. Several studies have reported an association between these two health problems, but it is unclear whether this relation is causal. We hypothesize that children with asthmatic symptoms are less physically active, which may contribute to the development of overweight. PATIENTS AND METHODS. The study included children from the KOALA Birth Cohort Study who were invited at 4 to 5 years of age to wear an Actigraph accelerometer for 5 days (n = 305; 152 boys). Information on wheezing was gathered by repeated questionnaires completed by parents at child ages 7 months and 1, 2, and 4 to 5 years. Questionnaires on physical activity were completed at child age 4 to 5 years, and height, weight, and abdominal circumference were measured. Accelerometer data were expressed as mean counts per minute, minutes per day performing vigorous activity, and moderate-to-vigorous physical activity during ≥1 minute. RESULTS. Children who had wheezed in the last 12 months showed very similar activity levels compared with children who had never wheezed. By contrast, boys who had wheezed at least once but not in the last 12 months were more physically active than boys who had never wheezed (geometric mean: 694 vs 625 cpm; adjusted geometric mean ratio: 1.11). This was not found for girls. Similar results were found in parent-reported physical activity data. No association was found between wheezing at any age and overweight at the age of 4 to 5 years. CONCLUSIONS. These results do not support our hypothesis and previous studies that showed that wheezing children are less physically active. Our data provide no evidence that asthmatic symptoms induce a lower physical activity level and more overweight. Additional research could concentrate on the effect of physical activity and overweight on the development of asthmatic symptoms.

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 (2 SD in combination with HSDS

Previous studies have suggested an association between multiple sclerosis (MS) and infectious mononucleosis (IM) but data on the exact strength of this association or its selectivity have been conflicting. In this study we have evaluated the association between MS and a variety of common childhood infections and afflictions in a large population-based case-control study involving 2877 MS cases and 2673 controls in the Netherlands. We examined the frequency of different common infections and afflictions before the age of 25 and the age at which they occurred, using a self-administered questionnaire. The Odds ratios (ORs) for the occurrence of a variety of clinically manifest common childhood infections including rubella, measles, chicken pox and mumps before the age of 25 for MS cases versus controls ranged between 1.14 and 1.42, values similar to those for irrelevant probe variables used to reveal recall bias. In contrast, the OR for clinically manifest IM in MS cases versus controls, corrected for demographic variables, was 2.22 (95% confidence interval 1.73 — 2.86; P

The use of the Gibbs sampler with fully conditionally specified models, where the distribution of each variable given the other variables is the starting point, has become a popular method to create imputations in incomplete multivariate data. The theoretical weakness of this approach is that the specified conditional densities can be incompatible, and therefore the stationary distribution to which the Gibbs sampler attempts to converge may not exist. This study investigates practical consequences of this problem by means of simulation. Missing data are created under four different missing data mechanisms. Attention is given to the statistical behavior under compatible and incompatible models. The results indicate that multiple imputation produces essentially unbiased estimates with appropriate coverage in the simple cases investigated, even for the incompatible models. Of particular interest is that these results were produced using only five Gibbs iterations starting from a simple draw from observed marginal distributions. It thus appears that, despite the theoretical weaknesses, the actual performance of conditional model specification for multivariate imputation can be quite good, and therefore deserves further study. © 2006 Taylor & Francis.

Aims: To obtain age references for sitting height (SH), leg length (LL), and SH/H ratio in the Netherlands; to evaluate how SH standard deviation score (SDS), LL SDS, SH/H SDS, and SH/LL SDS are related to height SDS; and to study the usefulness of height corrected SH/H cut-off lines to detect Marfan syndrome and hypochondroplasia. Methods: Cross-sectional data on height and sitting height were collected from 14 500 children of Dutch origin in the age range 0-21 years. Reference SD charts were constructed by the LMS method. Correlations were analysed in three age groups. SH/H data from patients with Marfan syndrome and genetically confirmed hypochondroplasia were compared with height corrected SH/H references. Results: A positive association was observed between H SDS, SH SDS, and LL SDS in all age groups. There was a negative correlation between SH/H SDS and height SDS. In short children with a height SDS

Objective: To describe fetal growth centiles in relation to maternal malaria and HIV status, using cross sectional measurements at birth. Design: A cross sectional study of pregnant women and their babies. Data on maternal socioeconomic status and current pregnancy, including HIV status and newborn anthropometry, were collected. Malaria parasitaemia was assessed in maternal peripheral and placental blood, fetal haemoglobin was measured in cord blood, and maternal HIV status was determined. Setting: Two district hospitals in rural southern Malawi, between March 1993 and July 1994. Outcome variables: Newborn weight, length, Rohrer's ponderal index. Results: Maternal HIV (adjusted odds ratio (AOR) 1.76 (95% confidence interval 1.04 to 2.98)) and first pregnancy (AOR 1.83 (1.10 to 3.05)) were independently associated with low weight for age. Placental or peripheral parasifaemia at delivery (AOR 1.73 (1.02 to 2.88)) and primigravidae (AOR 2.13 (1.27 to 3.59)) were independently associated with low length for age. Maternal malaria at delivery and primiparity were associated with reduced newborn weight and length but not with disproportionate growth. Maternal HIV infection was associated only with reduced birth weight. The malaria and parity effect occurred throughout gestational weeks 30-40, but the HIV effect primarily after 38 weeks gestation. Conclusion: Fetal growth retardation in weight and length commonly occurs in this highly malarious area and is present from 30 weeks gestation. A maternal HIV effect on fetal weight occurred after 38 weeks gestation. Chemicals / CAS: hemoglobin F, 9034-63-3

To determine the cut-off values for the body-mass index (BMI) for underweight and serious underweight in children up to 18 years of age based on the Dutch growth standards of 1980, and to determine the prevalence of underweight and serious underweight in the 1997 Dutch growth-study figures.Secondary data analysis.Cut-off values for underweight were determined by first calculating the percentage of 18-years old with a BMI18.5 kg/m2 in 1980, followed by a calculation of the BMI at younger ages under which the same percentage fell. Serious underweight in 18-year olds was defined as a BMI17.0 kg/m2.Between 1980 and 1997 the prevalence of serious underweight increased in children aged between 2 and 6 years from 1.5% to 3.6% and from 2.9% to 3.3%, in boys and girls respectively. In older children (7-18 years) the prevalence decreased from 1.5% to 1.4% for boys and from 2.9% to 1.7% for girls.Not only did the median weight of the population increase between 1980 and 1997, but there was also a rise in the variation of the weights at any given age. The latter could reflect more marked health differences.

To determine the magnitude of the growth retardation in Dutch monozygotic and dizygotic twins during infancy in comparison with the Dutch reference growth charts for general population infants from 1997 and to construct reference growth charts for twins.Descriptive.The growth of twins was studied using longitudinal data on over 4000 Dutch twin pairs from birth until 2.5 years of age. The LMS method was used to obtain growth charts for height, weight and body-mass index (BMI) for twin pairs during infancy. Centiles were estimated by the Box-Cox power curve (L), the median curve (M) and the coefficient of variation curve (S).From birth until the age of half a year, the average height and weight of twin pairs were at about the 10th percentile of the Dutch reference population. One year later this difference had decreased to about the 25th percentile, and when the twin pairs were between 1.5 and 2.5 years of age the difference was further decreased to the 35th percentile. The BMI deviated less from that of the reference population: during the first half a year the BMI of twin pairs was at about the 25th percentile. Subsequently, the BMI improved, but remained slightly below the median of the reference population at the age of about two years. Approximately half (50% for height, 58% for weight) of the growth retardation from birth until 1.5 years was attributable to gestational age. Between 1.5 years and 2.5 years of age, this difference was reduced to one third: 33% for both height and weight. Thus, a substantial part of the growth difference could not be explained by gestational age.Correcting for gestational age alone is not sufficient to make possible a comparison of the growth of twin pairs with the growth of general population infants. The development of twins can, however, be followed by means of the reference growth charts designed by the authors.

The number of referrals under strict adherence to the Dutch consensus guidelines for short stature was estimated using longitudinal data from 970 children (0-10 years). Results showed that over 38% of all children would have to be referred one or more times. There is therefore a clear need to revise the current guidelines.

Background: Comparability of health data is a major challenge within the context of the Health Monitoring Programme of the European Commission. A common problem in surveys is that many variations of essentially the same question exist. Methods: Response conversion is a new method for improving comparability by scaling the data onto a common scale. Comparisons between member states can then be made in terms of the common scale. A first step is the construction of a conversion key. This is a relatively complex activity, but needs to be done only once. The second step is the actual data transformation. This is simple, and can be repeatedly done on a routine basis as new information arrives. Construction of the key is only possible if enough overlapping information can be found. Results: The method is illustrated for dressing disability from five European countries. Differences occur between countries, between sexes and between age groups. These were similar in magnitude. Conclusion: Response conversion is a new method for enhancing comparability among existing data. Conversion can only be done if a key is available. More work is needed to establish the technique. Future implications within the Health Monitoring Programme are discussed.

The sub-scales of the SF-36 in the Dutch National Study are investigated with respect to unidimensionality and reliability. It is argued that these properties deserve separate treatment. For unidimensionality we use a non-parametric model from item response theory, called the Mokken scaling model, and compute the corresponding scalability coefficients. We estimate reliability under the Mokken model, assuming that the items are double homogeneous, and compare it to Cronbach's alpha. The scalability of the sub-scale general health perceptions is medium (H = 0.46), and for the other sub-scales it is strong (Hor = 0.6). The reliability in terms of alpha indicates that all sub-scales can be used in basic research (alpha0.70), but that only physical functioning can be used for clinical applications of quality of life (alpha0.90). The relative merits of our approach are discussed.

Doel Het ontwikkelen van een predictieregel om patiënten te identificeren die een hoog risico lopen op het ontwikkelen van werkverzuim langer dan 6 maanden door lage rugpijn. Methode Secundaire data-analyse in een cohort van 628 werknemers die 3 tot 6 weken verzuimen van het werk vanwege lage rugpijn. We onderzochten de relatie tussen een breed scala aan prognostische factoren, zoals: demografische, werk-, rugpijn- en psychosociaal gerelateerde factoren op werkverzuim langer dan 6 maanden. Relaties werden onderzocht door gebruik te maken van Cox regressie overlevingsanalyse en backward selectietechnieken (achterwaartse stapsgewijze regressie). Daarnaast werd een predictieregel ontwikkeld. Variabele en modelselectie en de kwaliteit van de predictieregel werden bepaald met behulp van bootstrappingtechnieken. Ook werden de testeigenschappen van de klinische predictieregel onderzocht. Resultaten Matige tot slechte arbeidstevredenheid, een hogere score op vermijdingsgedrag, een hogere pijnintensiteit, een langere klachtenduur en van het vrouwelijke geslacht zijn, waren gerelateerd aan een hoger risico op werkverzuim langer dan 6 maanden. De prestatie van de predictieregel liet zien dat de index voor discriminatie (c-index) en kalibratie (slope) respectievelijk 0,63 en 0,90 waren. De testeigenschappen van de regel voor verschillende afkapwaarden van risicoscores voor sensitiviteit, specificiteit, positief en negatief voorspellende waarden waren redelijk. Conclusie Onze predictieregel kan gebruikt worden door bedrijfsartsen en bedrijfsfysiotherapeuten om patiënten te identificeren die een hoog risico lopen op langdurig verzuim.

Objective: The majority of children with Down syndrome (DS) have concomitant disorders, such as congenital heart defects (CHD), celiac disease, and hypothyroidism. We aim to establish growth patterns of height in Dutch children with DS, while taking into account the influence of the concomitant disorders. Methods: Out of the 30 regional outpatient clinics for children with DS in the Netherlands 25 participated. Children with Trisomy 21 karyotype of Dutch descent born after 1982 were included. Growth data were retrospectively collected from their medical records, as were data on concomitant medical conditions and treatments administered. The LMS method was applied to fit the growth references. Results: We enrolled 1,596 Dutch children with Trisomy 21 (56% boys). Children with DS without concomitant disorders and children with DS who suffer from only mild CHD showed similar growth patterns. Reference growth curves were therefore fitted from all measurements (n=3,728) of these subgroups. Mean final height was determined at 163 and 152 cm, respectively in boys and girls with DS. On the reference growth curves of the general Dutch population, the DS curves roughly follow the -2 SDS line with a deflection to the -2.8 SDS line after the age of 12 years. Conclusions: Children with DS without concomitant disorders and those with only a mild CHD show similar growth patterns of height. As compared to the general Dutch population, they are of short stature with an increasing height difference at older ages.

To determine the effectiveness of a special form of exercise therapy ('Cesar therapy') on self reported recovery and improvement of posture amongst patients with chronic aspecific lower back pain.Prospective randomized controlled and blinded investigation.After informed consent had been obtained, patients with chronic aspecific lower back pain were given, on a randomized basis, either an exercise therapy (experimental group, n = 112) or a standard treatment by their general practitioner (control group, n = 110). Outcome measures were self reported recovery of back pain and improvement of posture (thoracic and lumbar spine, pelvis). Self reported recovery was determined by means of a dichotomized 7-point scale (questionnaire). Posture was measured qualitatively by a panel of 11 Cesar therapists (blinded) and quantitatively by an optical-electronic posture recording system (Vicon). Measurements were taken at baseline (pre-randomization) and at 3, 6 and 12 months after randomization.Three months after randomization, patients who were treated according to Cesar therapy, reported an improvement in their back symptoms (80%) significantly more often than the control group (47%). In both groups, however, only small improvements in posture were found. The judgement of the Cesar panel exhibited a significant difference between the two groups, with respect to the spine, in favour of Cesar therapy. Differences between the groups were still present 6 months after randomization, but could no longer be detected at 12 months after randomization.Cesar therapy was significantly more effective than standard treatment among patients with chronic lower back pain for a period of 6 months after randomization.

Since 1858, an increase of mean stature has been observed in the Netherlands, reflecting the improving nutritional, hygienic, and health status of the population. In this study, stature, weight, and pubertal development of Dutch youth, derived from four consecutive nationwide cross- sectional growth studies during the past 42 y, are compared to assess the size and rate of the secular growth change. Data on length, height, weight, head circumference, sexual maturation, and demographics of 14500 boys and girls of Dutch origin in the age range 0-20 y were collected in 1996 and 1997. Growth references for height and weight were constructed with a method that summarizes the distribution by three smooth curves representing skewness (L curve), the median (M curve), and coefficient of variation (S curve). The relationship between height and demographic variables was assessed by multivariate analysis. Reference curves for menarche and secondary sex characteristics were estimated by a generalized additive model using a logit transformation. A positive secular growth change has been present in the past 42 y for children, adolescents, and young adults of Dutch origin, although at a slower rate in the last 17 y. Height differences according to region, educational level of child and parents, and family size have remained. In girls, median age at menarche has decreased by 6 mo during the past four decades to 13.15 y. Environmental conditions have been favorable for many decades in the Netherlands, and the positive secular change in height has not yet come to a halt, in contrast to Scandinavian countries. Main contributors to the increase in height may be improved nutrition, child health, and hygiene, and a reduction of family size.

This paper studies a non-response problem in survival analysis where the occurrence of missing data in the risk factor is related to mortality. In a study to determine the influence of blood pressure on survival in the very old (85+ years), blood pressure measurements are missing in about 12.5 per cent of the sample. The available data suggest that the process that created the missing data depends jointly on survival and the unknown blood pressure, thereby distorting the relation of interest. Multiple imputation is used to impute missing blood pressure and then analyse the data under a variety of non-response models. One special modelling problem is treated in detail; the construction of a predictive model for drawing imputations if the number of variables is large. Risk estimates for these data appear robust to even large departures from the simplest non-response model, and are similar to those derived under deletion of the incomplete records.

This paper studies a non-response problem in survival analysis where the occurrence of missing data in the risk factor is related to mortality. In a study to determine the influence of blood pressure on survival in the very old (85+ years), blood pressure measurements are missing in about 12.5 per cent of the sample. The available data suggest that the process that created the missing data depends jointly on survival and the unknown blood pressure, thereby distorting the relation of interest. Multiple imputation is used to impute missing blood pressure and then analyse the data under a variety of non-response models. One special modelling problem is treated in detail; the construction of a predictive model for drawing imputations if the number of variables is large. Risk estimates for these data appear robust to even large departures from the simplest non-response model, and are similar to those derived under deletion of the incomplete records.

To determine whether the inverse relation between blood pressure and all cause mortality in elderly people over 85 years of age can be explained by adjusting for health status, and to determine whether high blood pressure is a risk factor for mortality when the effects of poor health are accounted for.5 to 7 year follow up of community residents aged 85 years and older.Leiden, the Netherlands.835 subjects whose blood pressure was recorded between 1987 and 1989.All cause mortality.An inverse relation between blood pressure and all cause mortality was observed. For diastolic blood pressure crude 5 year all cause mortality decreased from 88% (52/59) (95% confidence interval 79% to 95%) in those with diastolic blood pressures65 mm Hg to 59% (27/46) (44% to 72%) in those with diastolic pressures100 mm Hg. For systolic blood pressure crude 5 year all cause mortality decreased from 85% (95/112) (78% to 91%) in those with systolic pressures125 mm Hg to 59% (13/22) (38% to 78%) in those with systolic pressures200 mm Hg. This decrease was no longer significant after adjustment for indicators of poor health. No relation existed between blood pressure and mortality from cardiovascular causes or stroke after adjustment for age and sex, but after adjustment for age, sex, and indicators of poor health there was a positive relation between diastolic blood pressure and mortality from both cardiovascular causes and stroke.The inverse relation between blood pressure and all cause mortality in elderly people over 85 is associated with health status.

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Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz, the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen beta-gene. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the Bcl] polymorphism of the fibrinogen beta-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA). In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student l-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen beta-gene polymorphisms. Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen beta-gene polymorphisms.

OBJECTIVE To determine the number and duration of hospital admissions due to diabetes in children aged 0–19 years between 1980–1991. RESEARCH DESIGN AND METHODS Secondary analysis of data collected by the SIG Health Care Information was based on the 9th revision of the International Classification of Diseases. The subjects were all children in The Netherlands, aged 0–19 years. The main outcome measures were number and duration of hospital admissions due to type I diabetes (ICD 9 code 250.0–250.9). RESULTS The hospital admission rate due to diabetes decreased > 30%. This decrease was statistically significant in all age subgroups. The total number of days in hospital due to diabetes decreased dramatically: from 24,961 in 1980 to 11,305 in 1991. The average duration of hospital stay length due to diabetes decreased as well from 14.5 days in 1980 to 11.9 days in 1991. CONCLUSIONS The hospital admission rate and the length of hospital stay for diabetes in children aged 0–19 years have decreased, in spite of an increasing incidence. The hospital admission rate may decrease still further if more children with newly diagnosed diabetes can be adequately managed by team management at home in the initial phase.

This paper describes a method for finding optimal transformations for analyzing time series by autoregressive models. 'Optimal' implies that the agreement between the autoregressive model and the transformed data is maximal. Such transformations help 1) to increase the model fit, and 2) to analyze categorical time series. The method uses an alternating least squares algorithm that consists of two main steps: estimation and transformation. Nominal, ordinal and numerical data can be analyzed. Some alternative applications of the general idea are highlighted: intervention analysis, smoothing categorical time series, predictable components, spatial modeling and cross-sectional multivariate analysis. Limitations, modeling issues and possible extensions are briefly indicated.

Elevated plasma fibrinogen levels represent an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz. the acute phase reaction, total fibrin and fibrinogen degradation (TDP) levels and the fibrinogen G/A4 -gene polymorphism. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study versus placebo. Functional plasma fibrinogen levels were measured with the Clauss assay and antigen levels with an enzyme immunoassay. C-reactive protein (CRP) and TOP levels were measured with an enzyme immuno assay. In the healthy volunteers the mean (SD) baseline level of functional plasma fibrinogen was 2.35 g/L (SD 0.35) and for fibrinogen antigen this was 2.49 g/L (SD 0.63). The geometrical mean (central 95% range) of CRP as 0.21 mg/L (0.02-2.36) and for TOP this was 0.18 ng/mL (0.03-1.00). After 4 weeks of ticlopidine administration, the functional fibrinogen levels had decreased with 0.20 g/L (9%, p=0.005 using the paired Student t-test) whereas the fibrinogen antigen levels, the CRP and the TOP levels had not significantly changed. In the stable angina pectoris patient the mean (SD) baseline levels of functional plasma fibrinogen were 3.44 g/L (SD 0.61) and of fibrinogen antigen they were 2.60 g/L (SD 0.49). The geometrical mean (central 95% range) of CRP was 1.45 mg/L (0.15-14.44) and for TOP this was 0.28 ng/mL (0.05-1.62). These baseline fibrinogen, CRP and TOP levels were significantly higher than in the volunteer group. After four weeks ticlopidine administration the functional fibrinogen levels had decreased with 0.39 g/L (11%, p

OBJECTIVE A nationwide retrospective study was conducted to assess the incidence of type I diabetes in The Netherlands among children RESEARCH DESIGN AND METHODS The capture recapture census method was chosen for analysis of the data. A questionnaire was sent to all Dutch pediatricians and internists, and for the ascertainment, a similar questionnaire was sent out separately to members of the Dutch Diabetes Association, which is the national patient association. RESULTS The average achieved ascertainment rate was 81%. The ascertainmentadjusted annual incidence was 13.2/100,000 for 0- to 19-year-old children, indicating an increase of 23% compared with the 1978–1980 survey; for 0- to 14-year-olds, the increase amounted to 17%. CONCLUSIONS This study suggests a sustained increase of type I diabetes in The Netherlands because the cumulative incidence studied previously in the 1960–1970 birth cohorts of male army conscripts 18 years of age was also found to rise. In contrast to Northern European countries, an increase in incidence for the age category 0–4 years could not be found.

Introduction Due to the overweight and obesity epidemic, growth references based on recent data may no longer be appropriate for monitoring childhood body mass index (BMI) as they may underestimate the problem. Our aim is to determine the difference in signalling overweight and obesity between the use of up to date references and cut-offs for BMI according to the International Obesity Task Force (IOTF). Methods The growth references for BMI were constructed using cross-sectional growth data from the Fifth Dutch Growth Study in 2009 (n=10 129). We plotted the IOTF cut-offs against the Dutch growth references for ages 2–18 y. Moreover, we compared the prevalence of overweight and obesity according to IOTF with respectively the +1.6 and +2.7 SD score (SDS) on the Dutch growth references. These SDS cut-offs correspond to a BMI of 25 and 30 kg/m 2 at age 18 y in the Third Dutch Growth Study in 1980, which was part of the sample to construct the IOTF cut-offs. Results The IOTF cut-offs for overweight and obesity were lower than +1.6 and +2.7 SDS at all ages. The difference between IOTF and the cut-offs for SDS ranged from −1.8 to −2.5 SDS for overweight and −1.2 to −2.3 SDS for obesity. Conclusion Using up to date population based references for BMI with recommended SDS cut-offs for Dutch children results in an underestimation of the problem. In countries with substantial overweight and obesity, we recommend using pre-epidemic references or cut-offs, such as proposed by the International Obesity Task Force.