http://repub.eur.nl/res/aut/1189/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/40053/ 2013-06-01T00:00:00Z Pain is a common presenting complaint of emergency department patients. Providing instructions that can be easily recalled by patients is an important step in enabling patients to manage their pain following discharge. The effect of the introduction of written discharge instructions for pain medication on patients' recall of instructions was evaluated in this study. A patient-control study within a prospective follow-up study was performed. In the first phase, no written discharge instructions were available. Patients discharged on analgesics filled in a digital questionnaire regarding correct analgesics use. In the second phase, patients were discharged with additional written instructions and completed the same questionnaire. In the first phase, 40% of patients correctly recalled instructions for taking analgesics. In the second phase, significantly more patients, 71% (P<0.01), were able to recall the instructions correctly. Results of this study support the hypothesis that it makes sense to provide patients with written instructions about the appropriate use of analgesics, and that emergency departments that are not yet doing this should consider introducing this policy. It is a relatively low-cost measure that could lead to a significant improvement in quality of care. Copyright http://repub.eur.nl/res/pub/37732/ 2012-09-01T00:00:00Z We have noted that bone lesions on CT respond differently from soft-tissue lesions to treatment with [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). We therefore compared the response of bone lesions with that of soft-tissue lesions to treatment with177Luoctreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors (NETs). Methods: Forty-two patients with well-differentiated NETs who had bone metastases that were positive on [111In-DTPA0]octreotide somatostatin receptor scintigraphy (SRS) before treatment, and who had soft-tissue lesions, were studied. All patients had had a minimum of 1 follow-up CT scan. Lesions were scored on CT and bone lesions also on SRS before and after treatment. Tumor markers (chromogranin A and 5-hydroxyindoleacetic acid) before and after treatment were compared. Results: Because bone lesions were not visible on CT before treatment in 11 of 42 patients (26%), bone and softtissue lesions were evaluated in 31 patients. Whereas bone lesions increased in size, soft-tissue lesions decreased in size. The percentage change in bone and soft-tissue lesions was significantly different at all time points up to 12 mo of follow-up (P < 0.001). The intensity or number of bone lesions on SRS decreased after treatment in 19 of 23 patients (83%) in whom SRS after treatment was available. The tumor markers also decreased significantly after treatment. In 1 patient, bone lesions became visible on CT after treatment, mimicking progressive disease with "new" bone lesions, although there was an overall treatment response. Conclusion: In patients with NETs, the apparent increase in size of bone lesions or the appearance of new bone lesions on CT after treatment with177Lu-octreotate should be interpreted cautiously, as this finding may be therapy-related rather than indicative of tumor progression. Copyright http://repub.eur.nl/res/pub/33797/ 2011-11-24T00:00:00Z Maternal and fetal characteristics are important determinants of fetal growth potential, and should ideally be taken into consideration when evaluating fetal growth variation. We developed a model for individually customised growth charts for estimated fetal weight, which takes into account physiological maternal and fetal characteristics known at the start of pregnancy. We used fetal ultrasound data of 8,162 pregnant women participating in the Generation R Study, a prospective, population-based cohort study from early pregnancy onwards. A repeated measurements regression model was constructed, using backward selection procedures for identifying relevant maternal and fetal characteristics. The final model for estimating expected fetal weight included gestational age, fetal sex, parity, ethnicity, maternal age, height and weight. Using this model, we developed individually customised growth charts, and their corresponding standard deviations, for fetal weight from 18 weeks onwards. Of the total of 495 fetuses who were classified as small size for gestational age (<10th percentile) when fetal weight was evaluated using the normal population growth chart, 80 (16%) were in the normal range when individually customised growth charts were used. 550 fetuses were classified as small size for gestational age using individually customised growth charts, and 135 of them (25%) were classified as normal if the unadjusted reference chart was used. In conclusion, this is the first study using ultrasound measurements in a large population-based study to fit a model to construct individually customised growth charts, taking into account physiological maternal and fetal characteristics. These charts might be useful for use in epidemiological studies and in clinical practice. http://repub.eur.nl/res/pub/30719/ 2011-10-06T00:00:00Z Objective: We previously showed that accelerated growth predisposing to development of childhood-onset type 1 diabetes (T1D) is restricted to the first year after birth. We assessed whether this phenomenon of increased early growth is associated with variants of two genes, insulin-like growth factor-1 (IGF1) and insulin variable number of tandem repeats (INS-VNTR), whose products are components of the growth axis. Patients and methods: Patients and their siblings were genotyped for the INS-VNTR and for an IGF1 microsatellite. We tested for difference in first year growth, i.e., increased weight standard deviation score (SDS), a reliable measure of especially first year growth, between carriers and non-carriers of these gene variants, using a repeated measurement and regression analysis. Results: In patients, growth did not differ between carriers and non-carriers of the INS-VNTR*III allele, while carriership of this allele in siblings was positively associated with increased first year growth. In both patients and siblings, non-carriership of the IGF1*194 allele was positively associated with growth. Birth size was not associated with either variant. Conclusions/discussion: Non-carriership of the IGF1*194 allele was positively associated with accelerated first year growth in both patients and siblings, independent of disease. This IGF1 variant may therefore contribute to increased first year growth, but cannot explain the association of first year growth with diabetes. An effect on growth of the INS-VNTR was detected in healthy siblings, but not in patients, suggesting that disease supersedes a growth effect of INS-VNTR. http://repub.eur.nl/res/pub/26569/ 2011-07-01T00:00:00Z Fakhry F, Spronk S, de Ridder M, den Hoed PT, Hunink MGM. Long-term effects of structured home-based exercise program on functional capacity and quality of life in patients with intermittent claudication. Objectives: To evaluate effects of a structured home-based exercise program on functional capacity and quality of life (QoL) in patients with intermittent claudication (IC) after 1-year follow-up, and to compare these results with those from a concurrent control group who received supervised exercise training (SET). Design: Comparative longitudinal cohort study. Setting: Referral center. Participants: Patients (N=142) with IC. Interventions: Structured home-based exercise training or SET. Main Outcome Measures: The maximum (pain-free) walking distance and the ankle-brachial index (ABI) (at rest and postexercise) were measured at baseline and after 6 and 12 months' follow-up. Additionally, QoL was evaluated using a self-administered questionnaire consisting of the Euroqol-5D (scale 01), rating scale (scale 0100), Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; scale 0100), and the Vascular Quality of Life Questionnaire (VascuQol; scale 17). Comparison of the groups was performed with adjustment for the nonrandomized setting using propensity scoring. Results: One hundred forty-two patients with IC started the structured home-based exercise program, of whom 95 (67%) completed 12 months' follow-up. The mean relative improvement compared with baseline was statistically significant after 12 months' follow-up for the maximum and pain-free walking distance (342%, 95% confidence interval [CI], 169516; P<.01 and 338%, 95% CI, 42635; P=.03, respectively) and for the ABI postexercise (mean change, .06; 95% CI, .01.10; P=.02). For the QoL outcomes, the improvement compared with baseline was statistically significant after 12 months for the VascuQol (mean change, .42; 95% CI, .20.65; P<.01) and for the SF-36 physical functioning (mean change, 5.17; 95% CI, .779.56; P=.02). Compared with the structured home-based exercise program, patients in the control group showed significantly better results in the mean relative improvement of maximum and pain-free walking distance and change in the ABI at rest after 12 months' follow-up. Conclusions: Structured home-based exercise training is effective in improving both functional capacity and QoL in patients with IC and may be considered as a feasible and valuable alternative toSET, since supervised exercise programs are not often available. http://repub.eur.nl/res/pub/33478/ 2011-04-01T00:00:00Z Background/Objective: High-dose estrogen treatment to reduce final height of tall girls has been shown to interfere with fertility. Ovarian function has not been studied. We therefore evaluated fertility and ovarian function in tall women who did or did not receive such treatment in adolescence. Methods: This was a retrospective cohort study of 413 tall women aged 23-48 yr, of whom 239 women had been treated. A separate group of 126 fertile, normoovulatory volunteers aged 22-47 yr served as controls. Results: Fertility was assessed in 285 tall women (157 treated, 128 untreated) who had attempted to conceive. After adjustment for age, treated women were at increased risk of experiencing subfertility [odds ratio (OR) 2.29, 95% confidence interval (CI) 1.38-3.81] and receiving infertility treatments (OR 3.44,95%CI 1.76-6.73). Moreover, fecunditywasnotably affected because treated women had significantly reduced odds of achieving at least one live birth (OR 0.26, 95% CI 0.13-0.52). Remarkably, duration of treatment was correlated with time to pregnancy (r = 0.23, P = 0.008). Ovarian function was assessed in 174 tall women (119 treated, 55 untreated). Thirty-nine women (23%) exhibited a hypergonadotropic profile. After adjusting for age category, treated women had significantly higher odds of being diagnosed with imminent ovarian failure (OR 2.83, 95% CI 1.04-7.68). Serum FSH levels in these women were significantly increased, whereas antral follicle counts and serum anti-Müllerian hormone levels were decreased. Conclusion: High-dose estrogen-treated tall women are at risk of subfertility in later life. Their fecundity is significantly reduced. Treated women exhibit signs of accelerated ovarian aging with concomitant follicle pool depletion, which may be the basis of the observed subfertility. Copyright http://repub.eur.nl/res/pub/28069/ 2010-10-25T00:00:00Z Objectives/Hypothesis: Oxandrolone (Ox) increases height gain but may also cause voice deepening in growth hormone (GH)-treated girls with Turner syndrome (TS). We assessed the effect of Ox on objective and subjective speaking voice frequency in GH-treated girls with TS. Study Design: A multicenter, randomized, placebo (Pl)-controlled, double-blind study was conducted. Methods: One hundred thirty-three patients were included and treated with GH (1.33 mg/m2/d) from baseline, combined with Pl or Ox in a low (0.03 mg/kg/d) or conventional (0.06 mg/kg/d) dose from the age of 8 years and estrogens from the age of 12 years. Yearly from starting Ox/Pl until 6 months after discontinuing GH + Ox/Pl, voices were recorded and questionnaires were completed. Results: At start, mean (±standard deviation [SD]) voice frequency SD score (SDS) was high for age (1.0 ± 1.2, P < 0.001) but normal for height. Compared with GH + Pl, voices tended to lower on GH + Ox 0.03 (P = 0.09) and significantly lowered on GH + Ox 0.06 (P = 0.007). At the last measurement, voice frequency SDS was still relatively high in GH + Pl group (0.6 ± 0.7, P = 0.002) but similar to healthy girls in both GH + Ox groups. Voice frequency became lower than -2 SDS in one patient (3%) on GH + Ox 0.03 and three patients (11%) on GH + Ox 0.06. The percentage of patients reporting subjective voice deepening was similar between the dosage groups. Conclusions: Untreated girls with TS have relatively high-pitched voices. The addition of Ox to GH decreases voice frequency in a dose-dependent way. Although most voice frequencies remain within the normal range, they may occasionally become lower than -2 SDS, especially on GH + Ox 0.06 mg/kg/d. http://repub.eur.nl/res/pub/20919/ 2010-09-01T00:00:00Z Context The criteria for starting growth hormone (GH), an approved treatment for short children born small for gestational age (SGA), differ between Europe and the USA. One European requirement for starting GH, a distance to target height (DTH) of ≥1 standard deviation score (SDS), is controversial. Objective To investigate the influence of DTH on growth during GH treatment in short SGA children and to ascertain whether it is correct to exclude children with a DTH <1 SDS from GH. Patients A large group of short prepubertal SGA children (baseline n = 446; 4 years GH n = 215). Measurements We analysed the prepubertal growth response during 4 years of GH. We investigated the influence of the continuous variable DTH SDS on growth response and a possible DTH SDS cut-off level below which point the growth response is insufficient. Results Height gain SDS during 4 years of GH showed a wide variation at every DTH SDS level. Multiple regression analyses demonstrated that, after correction for other significant variables, an additional DTH of 1 SDS resulted in 0·13 SDS more height gain during 4 years of GH. We found no significant differences in height gain below and above certain DTH SDS cut-off levels. Conclusions DTH SDS had a weak positive effect on height gain during 4 years of GH, while several other determinants had much larger effects. We found no support for using any DTH cut-off level. Based on our data, excluding children with a DTH <1 SDS from GH treatment is not justified. http://repub.eur.nl/res/pub/27289/ 2010-09-01T00:00:00Z http://repub.eur.nl/res/pub/21736/ 2010-08-01T00:00:00Z Aim: To investigate the effect of 2 growth hormone (GH) doses on adult height (AH) in GH deficiency (GHD). Methods: A multicenter, randomized, controlled dose-response trial compared attained AH minus target height (TH) between children receiving 0.7 mg/m2/day biosynthetic GH (approx. 0.025 mg/kg/day) or 1.4 mg/m2/day (approx. 0.050 mg/kg/day). The patients enrolled in the trial were 20 'naïve' GHD children (had not received GH before) and 15 'transfer' GHD children (already on GH for at least 1 year). Results: In the naïve group, the mean ± SD AH minus TH was -5.3 ± 6.1 and -2.2 ± 6.9 cm in patients on 0.7 and 1.4 mg/m 2/day, respectively (mean ± SE difference 3.1 ± 2.9; p = 0.3). In the transfer group, the mean ± SD AH minus TH was -4.4 ± 6.4 and +0.6 ± 7.0 cm in patients on 0.7 and 1.4 mg/m 2/day, respectively (mean ± SE difference 5.0 ± 3.5; p = 0.17). Spontaneous puberty started 1.1 years earlier in children on 1.4 compared to 0.7 mg/m2/day. Induction of puberty was more often delayed in transfer children on 0.7 than on 1.4 mg/m2/day. Conclusion: In our GHD patients, AH was 4-5 cm less than TH in patients on 0.7 mg/m2/day GH, while it was 0-2 cm less in patients on 1.4 mg/m 2/day GH, but this difference did not reach statistical significance, probably due to limited numbers of patients, considerable variability in the growth response and earlier spontaneous puberty and pubertal induction in the children on 1.4 mg/m2/day. http://repub.eur.nl/res/pub/27890/ 2010-08-01T00:00:00Z Objective Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)-treated girls with TS. DesignPatients 133 patients were included in a randomized, placebo-controlled, double-blind study. Methods Patients were treated with GH (1·33 mgm2per day) from baseline, combined with placebo (Pl) or Ox in a low (0·03 mgkg per day) or previously conventional (0·06 mgkg per day) dose from the age of eight, and oestrogens from the age of twelve. Sitting height, biacromial and biiliacal distances compared with height (i.e. shape values), BMI, waist circumference, sum of 4 skinfolds (sum4skin) and upper arm muscle area (UAMA) SD scores (SDS) were assessed half-yearly. Results Compared with GH + Pl, adult shape values on GH + Ox tended to be higher for sitting height (Ox 0·03, P = 0·2; Ox 0·06, P = 0·02) and biacromial distance (Ox 0·03, P = 0·2; Ox 0·06, P = 0·07) and lower for biiliacal distance (Ox 0·03, P = 0·004; Ox 0·06, P = 0·08). Sum4skin SDS tended to decrease more (Ox 0·03, P = 0·2; Ox 0·06, P = 0·005) while UAMA SDS increased more (Ox 0·03, P < 0·001; Ox 0·06, P < 0·001) than on GH + Pl. The increase in BMI and waist circumference SDS was comparable between the dosage groups. Conclusions In GH-treated girls with TS, Ox 0·06 increases sitting height and tends to increase biacromial distance and decrease biiliacal distance, while Ox 0·03 significantly decreases biiliacal distance compared with height. Furthermore, Ox 0·06 reduces subcutaneous fat mass, and both Ox dosages increase muscle mass. http://repub.eur.nl/res/pub/27988/ 2010-05-01T00:00:00Z Objective Accelerated early growth prior to childhood type 1 diabetes onset is associated with an increased risk for type 1 diabetes (T1D). We aimed to study early growth, correcting for the previously neglected confounder of familial effects. Design Infant growth was studied in a retrospective family case-control study of diabetic children in which siblings acted as matched familial controls allowing correction for confounders related to family particulars. Patients Weight and height data were collected from 213 juvenile onset type 1 diabetic children and their 255 healthy siblings. Growth in the first 4 years of life was studied using repeated measurement. The degree of early overgrowth was correlated with age of clinical onset. Results Birth weight and length did not differ between later diabetic children and their siblings. In the first year of life, weight standard deviation score (SDS) differed between patients and sibs (P = 0·0001). After the first year, both diabetic children and sibs showed parallel enhanced weight and height gain SDS until age 4 years. Earlier onset diabetes was associated with a higher weight SDS at 6 months of age. Conclusion In this family case-control study the association of increased growth with development of T1D is limited to the first year of life implying that increased growth beyond the first year can be attributed to familial growth patterns, rather than predisposition to T1D per se. Age at disease onset correlated with increased weight in the first 6 months of life, indicating importance of features very early in life on later development of T1D. http://repub.eur.nl/res/pub/28072/ 2010-05-01T00:00:00Z Background: GnRH analogue (GnRHa) combined with GH treatment has been proposed to increase adult height. Effect on metabolic profile and GH, IGF1, and IGFBP3 levels in short small for gestational age (SGA) children is unknown. Objective: To assess fat mass and lean body mass SDS, percentage trunk fat, blood pressure (BP), insulin sensitivity (Si), β-cell function (disposition index, DI), lipid profile, and GH, IGF1, and IGFBP3 levels during 2 years of combined treatment. Subjects: Forty-one pubertal short SGA children with a mean (±S.D.) age of 12.1 (±1.0) years. Design: Children received 3.75 mg of leuprolide acetate depot subcutaneously every 4 weeks, and they were randomly assigned to receive 1 mg (group A) or 2 mg (group B) of GH/m2per day. Results: Percentage trunk fat increased in both groups, but to a lower extent in group B. Lean body mass SDS increased only in group B. Changes in BP, Si, DI, and lipids were similar in both groups. Si significantly decreased, but DI remained unchanged. Lipids remained normal. GH and IGF1 levels were significantly higher in group B. Conclusion: Our study is the first to report that 2 years of combined treatment with a GnRHa and either 1 or 2 mg GH/m2per day does not adversely affect body composition and metabolic profile of short SGA children who come under medical attention at the onset of puberty. There was a dose-dependent effect on fat mass SDSheight, percentage trunk fat, lean body mass SDSheight, and GH and IGF1 levels in favor of treatment with GnRHa and the higher GH dose of 2 mg/m2per day. http://repub.eur.nl/res/pub/27305/ 2010-03-01T00:00:00Z Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m2· d) from baseline, combined with placebo (Pl) or Ox in low(0.03mg/kg · d) or conventional (0.06 mg/kg · d) dose from the age of 8yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed. Results: Compared with GH+Pl, GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean ± SD, 9.5 ± 4.7 vs. 7.2 ± 4.0 cm, P = 0.02) and per-protocol analysis (9.8 ± 4.9 vs. 6.8 ± 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH + Ox 0.06 was not significantly different from that on GH+Pl (8.3 ± 4.7 vs. 7.2 ± 4.0 cm, P=0.3). Breast development was slower on GH+Ox (GH+Ox 0.03, P = 0.02; GH+Ox 0.06, P = 0.05), and more girls reported virilization on GH+Ox 0.06 than on GH+Pl (P = 0.001). Conclusions: In GH-treated girls with TS, we discourage the use of the conventional Oxdosage (0.06 mg/kg · d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg · d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development. Copyright http://repub.eur.nl/res/pub/25399/ 2009-09-08T00:00:00Z Context: Small for gestational age (SGA) subjects experience pre- and postnatal growth restriction, which might be influenced by polymorphisms in the IGF1 gene. The well-known -841(CA)n/192 bp polymorphism has been associated with birth size, cardiovascular disease, and IGF-1 levels, and is in linkage disequilibrium with the KG1245A single nucleotide polymorphism (SNP; rs35767). Objective: To associate the -G1245A SNP with head circumference (HC) and brain sparing (a greater head compared with height SDS) in short SGA and SGA catch-up subjects. Design: Gene association study. Patients: We studied 635 SGA subjects out of which 439 remained short and 196 had a postnatal height >-2.00 SDS. Measurements: The -G1245A SNP IGF1 gene polymorphism and head size. Results: All SGA subjects had a postnatal head size below the population mean (-1.01 SDS, P<0.001). Whereas SGA catch-up subjects had a head size that was in proportion with their height, short SGA subjects displayed extensive brain sparing (HC - height: SGA CU: 0.01 versus short SGA: 1.75 SDS, P<0.001). The most severely SGA born subjects had a 0.4 SDS smaller postnatal head size and 0.6 SDS less brain sparing when carrying the -1245 A-allele in contrast to G-allele carriers (P=0.03). The association between the -G1245A SNP and head size remained significant after correction for birth weight and postnatal height SDS (P=0.03). Birth weight, birth length and postnatal height SDS were not related with the - G1245A SNP. Conclusions: The -1245 A-allele of the IGF1 promoter SNP is associated with a small head size and less brain sparing in SGA born subjects and particularly those with the lowest birth weight. http://repub.eur.nl/res/pub/24927/ 2009-06-01T00:00:00Z Background: Short small-for-gestational-age (SGA) children experience pre- and postnatal growth restriction, which might be influenced by polymorphisms in the IGF1 gene. The well-known-841(CA)n/192 bp polymorphism has been associated with birth size and cardiovascular disease. Aims: To determine whether birth size, postnatal growth and growth during growth hormone (GH) treatment, were associated with IGF1 gene polymorphisms and haplotypes. Methods: 201 short SGA children were investigated for four IGF1 gene polymorphisms in the promoter (-G1245A,-841(CA)n), intron 2 (+3703(CT)n) and 3UTR (+A1830G). Spontaneous growth and growth during GH treatment were studied. Results: The-1245 A allele was identified as a marker-allele for the well-known-841(CA)n/non-192 bp allele, both part of haplotype 2. The-1245 A allele was not associated with head circumference at birth, but was associated with a postnatal 0.3 SDS smaller head circumference at age 1-3. The-1245 A allele was also associated with a 1-week shorter gestational age which explained the association with a smaller absolute birth size. No associations were found with gestational age-adjusted birth size, height and weight SDS during postnatal life and with growth during GH treatment. Conclusions: The-G1245A SNP appeared to be a marker for the well-known-841(CA)n/192 bp polymorphism. Haplotype 2, of which the-1245 A allele was the marker, was associated with a smaller head circumference SDS during spontaneous postnatal growth, but not during GH treatment. http://repub.eur.nl/res/pub/15128/ 2008-10-01T00:00:00Z Background/Aim: About 10-15% of children born small for gestational age (SGA) have at the age of 2 years a height standard deviation score (HSDS 2y) still below -2. There is no model to predict which children will catch up in height after 2 years of age. The aim of this study was to determine the percentage of children with catch-up growth to a normal height after the age of 2 years and to develop a prediction model for growth after that age. Methods: In a cohort of 724 SGA children, the percentage of children with HSDS above -2 at 8 years of age was determined. In data of 97 children with HSDS 2y below -2, a prediction model was developed for growth between 2 and 8 years. Results: Thirty-nine percent of children with HSDS2y below -2 reached an HSDSabove -2 between 2 and 8 years (6% of the total group). Determinants of growth after age 2 years, all with a positive influence, were the difference between target height SDS and HSDS2y, change in height SDS during first 2 years of life, female gender and multiple birth. Conclusions: Catch-up growth to a normal height occurred in 91% of SGA children, in 6% between 2 and 8 years of age. The difference between target height SDS and HSDS2y was the most important determinant. The presented prediction model can identify children with low or high probability of catch-up growth after the age of 2 years. This may assist to determine which children require medical follow-up. http://repub.eur.nl/res/pub/29906/ 2008-04-01T00:00:00Z Objectives: Correct assessment of gestational age and fetal growth is essential for optimal obstetric management. The objectives of this study were, first, to develop charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter and, second, to derive reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from 10 weeks of gestational age onwards. Methods: A total of 8313 pregnant women were included for analysis in this population-based prospective cohort study. All women had repeated ultrasound assessments to examine fetal growth. Results: Charts for ultrasound dating of pregnancy, based on crown-rump length and biparietal diameter, were derived. Internal validation with the actual date of delivery showed that ultrasound imaging provided reliable gestational age estimates. Up to 92% of deliveries took place within 37-42 weeks of gestation if gestational age was derived from ultrasound data, compared with 87% based on a reliable last menstrual period. The earlier the ultrasound assessment the more accurate the prediction of date of delivery. After 24 weeks of gestation a reliable last menstrual period provided better estimates of gestational age. Reference curves for normal fetal growth from 10 weeks of gestational age onwards were derived. Conclusions: Charts for ultrasound dating of pregnancy and reference curves for fetal biometry are presented. The results indicate that, up to 24 weeks of pregnancy, dating by ultrasound examination provides a better prediction of the date of delivery than does last menstrual period. The earlier the ultrasound assessment in pregnancy, preferably between 10 and 12 weeks, the better the estimate of gestational age. Copyright http://repub.eur.nl/res/pub/28904/ 2008-02-01T00:00:00Z Context: GH treatment is approved for short children born small for gestational age (SGA). The optimal dose is not yet established. Objective: Our objective was to develop a model for prediction of height at the onset of puberty and of adult height (AH). Design and Setting: Two GH studies were performed in short SGA children. Patients/Intervention: A total of 150 SGA children with height SD scores (SDS) less than -2, age 3 yr or older, no signs of catch-up growth, available height at the onset of puberty, and at least 1 yr of GH treatment before the onset of puberty were studied. In one study, patients were randomly assigned to either 0.033 or 0.067 mg/kg·d; in the other study all received 0.033 mg/kg·d. In 71 children, AH was reached. Main Outcome Measures: Height SDS at the onset of puberty and AH SDS were calculated. Results: Determinants positively related to height SDS at the onset of puberty were: height SDS at the start; target height SDS; and GH dose, whereas age at the start and female gender were negatively related. Positively related to AHSDS were: height SDS and chronological age - bone age at the start; target height SDS; and GH dose, whereas serum IGF binding protein (IGFBP)-3 SDS at the start was negatively related. There was a significant interaction between GH dose and IGFBP-3 SDS, indicating a smaller GH dose effect for higher levels of IGFBP-3. The final model explained 57% of the variance in height SDS at the onset of puberty and 41% of AH SDS. Conclusions: The prediction model for height SDS at the onset of puberty and AH SDS of short SGA children treated with GH provides useful information about the expected long-term growth. Because GH dosage is one of the determinants, the model aids in determining the optimal GH dose for each child. Copyright http://repub.eur.nl/res/pub/18608/ 2008-01-16T00:00:00Z http://repub.eur.nl/res/pub/29007/ 2008-01-01T00:00:00Z Objective: To examine the associations of maternal smoking in pregnancy with development of cholesterol levels from childhood to adulthood. Methods: Total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were measured annually from 1975 to 1993 and in 2002 in 350 subjects aged 5-19 years at baseline who participate in a prospective cohort study. Pregnancy and birth data were obtained through questionnaires sent to the parents. Results: Children of mothers who smoked in pregnancy showed a higher annual change in total cholesterol of 0.12 mmol/l per 10 years (95% confidence interval (CI): 0, 0.23) compared to children whose mothers did not smoke in pregnancy. Larger effect estimates were found in children with moderate overweight (0.39 mmol/l per 10 years (95% CI: 0.14, 0.63). HDL-cholesterol and LDL-cholesterol showed tendencies towards a decrease and increase, respectively, in children of mothers who smoked in pregnancy compared to children whose mothers did not smoke in pregnancy. Adjustment for potential confounders did not materially change the effect estimates. Conclusion: This study suggests for the first time that maternal smoking in pregnancy is associated with an increased rise in total cholesterol levels and a tendency towards an adverse lipoprotein profile in the offspring. http://repub.eur.nl/res/pub/29691/ 2008-01-01T00:00:00Z Aim: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate different patterns in gestation, delivery, postnatal growth, response to growth hormone (GH) treatment and parental height. Methods: 201 short SGA children were divided into three groups, SGAL, SGAL+Wand SGAL+W+HC, according to birth length (L), weight (W) and head circumference (HC) ≤-2.00 standard deviation score (SDS). Results: SGAL+W+HCchildren were born after the shortest gestational age and more often by caesarean section than SGALchildren (36.3 vs. 38.1 weeks, 68.4 vs. 24.4%). SGAL+Wchildren had an intermediate pattern and experienced most gestational hypertension (p = 0.01). At birth, SGAL+W+HCchildren were shorter than SGALor SGAL+W(-4.12 vs. -2.67 and -3.72 SDS, p ≤ 0.001). During the first 3 years of life, SGAL+W+HCchildren exhibited an increased growth in height (0.98 SDS) and HC (1.28 SDS) than SGAL(height, -0.06 SDS; HC, -0.30 SDS) and SGAL+W(height, 0.62 SDS; HC, -0.31 SDS). However, HC SDS remained smaller for SGAL+W+HCthan the other groups at age 3. The groups did not differ in growth response during GH treatment. SGALchildren tended to have shorter parents and target height than SGAL+W+HCchildren. Conclusions: Our study shows that subclassification of short SGA children might be a useful method for investigating SGA children as the subgroups revealed a different gestation, delivery and postnatal growth pattern. Response to GH treatment was not different between the groups. Copyright http://repub.eur.nl/res/pub/35446/ 2007-05-01T00:00:00Z The authors examined the associations of maternal smoking in pregnancy with various fetal growth characteristics among 7,098 pregnant women participating in the Generation R Study (2002-2006), a population-based prospective cohort study of pregnant women and their children in Rotterdam, the Netherlands. Maternal smoking was assessed by questionnaires administered in early, mid-, and late pregnancy. Fetal growth characteristics evaluated included head circumference, abdominal circumference, and femur length measured repeatedly in mid- and late pregnancy. Maternal smoking during pregnancy was associated with reduced growth in head circumference (-0.56 mm/week; 95% confidence interval (CI): -0.73, -0.40), abdominal circumference (-0.58 mm/week; 95% CI: -0.81, -0.34), and femur length (-0.19 mm/week; 95% CI: -0.23, -0.14). This reduced growth resulted in a smaller femur length from midpregnancy (gestational age 18-24 weeks) onwards and smaller head and abdominal circumferences from late pregnancy (gestational age ≥25 weeks) onwards. Analyses using standard deviation scores for the growth characteristics demonstrated the largest effect estimates for femur length. The authors concluded that maternal smoking during pregnancy is associated with reduced growth in fetal head circumference, abdominal circumference, and femur length. The larger effect on femur length suggests that smoking during pregnancy affects primarily peripheral tissues. Copyright http://repub.eur.nl/res/pub/36116/ 2007-03-01T00:00:00Z Background/Aim: In long-term growth studies with adult height (AH) as outcome, reporting is often required while data are incomplete because some participants have not yet reached AH whereas others might be lost to follow-up. Current practice is to analyze only participants who did reach AH, which can easily give biased results. We introduce a new method into the area of growth research. Methods: We used the data of patients from a registration database and a growth study. The new method uses growth data in time intervals. The percentage of children still growing and the mean growth at each interval are used to determine mean AH. Results: With the new method, estimated mean AHs had smaller bias and standard error than with commonly used methods. The method is not hampered by a correlation between AH and age at reaching AH, unlike methods merely using patients who have reached AH. Conclusion: In contrast to commonly used methods, the new method provides valid results on mean AH when complete actual measurements of AH are not (yet) available, provided that drop-out, if any, is not related to (disappointing) growth. As it also uses observed data of children with incomplete follow-up, the method employs the data more effectively. Copyright http://repub.eur.nl/res/pub/35555/ 2007-03-01T00:00:00Z Context: Several studies have searched for factors that significantly influence adult height (AH) of children with GH deficiency (GHD) who have been treated with biosynthetic GH, but a prediction model for AH has not yet been presented. Objective: Our objective was to develop models for prediction of AH, using information available at the start of GH treatment or after 1 yr of treatment. Design and Setting: For this retrospective study, data were collected from the National Registry of Growth Hormone Treatment in Children, which contained data of Dutch children treated with GH. Patients/Intervention: Patients included males born before 1985 and females born before 1987 with either diagnosis of GHD (syndromes, tumors, and other diseases were excluded) or a maximal GH response during provocation tests of less than 11 ng/ml, treated with biosynthetic GH for at least 1 yr. To be able to use the complete group of 342 children for the development of the models, multiple imputation was used for missing values. Main Outcome Measure: We assessed AH SD scores (SDS). Results: Each prediction model contained both target height SDS and current height SDS. The change in height SDS during the first year proved an important predictor for AH. In all models, addition of GH dose was not significant. The percent explained variance, after correction for overfitting, ranged from 37% (prepubertal children, prediction at start) to 60% (pubertal children, prediction after 1 yr). Conclusion: The presented prediction models give accurate predictions of AH for children with GHD at start and after 1 yr of GH treatment. They are useful tools in the treatment of these children. Copyright http://repub.eur.nl/res/pub/13510/ 2004-11-01T00:00:00Z Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account. http://repub.eur.nl/res/pub/10109/ 2003-01-01T00:00:00Z In 1999 a model was published for prediction of growth in children with idiopathic GH deficiency (IGHD) during GH therapy, derived using data from the Kabi Pharmacia International Growth Study (KIGS) database (Pharmacia \\|[amp ]\\| Upjohn, Inc., International Growth Database). We validated and calibrated this KIGS model for growth in the first year of GH therapy using data from 136 Dutch children with IGHD. Observed vs. predicted outcomes were plotted, and the fitted regression line was significantly different from the line of identity (P = 0.03). It appeared that the predictions were too extreme: relatively low predictions were too low, relatively high predictions were too high. This is a well known phenomenon in the context of prediction models, called overoptimism. For valid application to other data the KIGS predictions should be calibrated. Calibrated predictions are obtained using Y(cal) = Y(orig) + (2.153 - 0.192 x Y(orig)), where Y(cal) is the calibrated prediction, and Y(orig) is the KIGS prediction. The calibrated prediction will be higher than the original KIGS prediction when the original prediction is less than 11.2 cm/yr and will be lower otherwise. The variability of the prediction errors of the calibrated predictions was positively related to the value of the prediction (P < 0.001), described by the equation SD(pred err) = -1.017 + 0.286 x Y(cal). Our calibrated model will give better predictions for children with IGHD fulfilling the same criteria. http://repub.eur.nl/res/pub/8524/ 2003-01-01T00:00:00Z OBJECTIVE: To compare growth and body composition in preterm infants with bronchopulmonary dysplasia (BPD) with normal healthy term infants during the first year of life. DESIGN: Twenty nine preterm infants with BPD (mean (SD) gestational age 27.1 (1.6) weeks; birth weight 852 (173) g) were followed prospectively. Anthropometry and body composition determined by total body electrical conductivity were measured and compared with those of healthy term infants at the same post-term age. RESULTS: In infants with BPD, the mean weight standard deviation scores (SD scores) 6 weeks after term were significantly lower (-1.44 and -2.68, boys and girls respectively) than in healthy term infants of the same age and did not improve during the first year. The mean length SD score was significantly lower in infants with BPD 6 weeks after term than in healthy term infants of the same age, and, although it improved significantly during the first year, the mean length SD score in girls with BPD was significantly below 0 12 months after term. In infants with BPD, the mean free fat mass (FFM) SD score and the mean total body fat (TBF) SD score at 6 weeks post-term age were significantly below 0. The mean FFM SD scores (-1.01 and -2.56, boys and girls respectively) and the mean TBF SD scores (-1.14 and -2.40, boys and girls respectively) 12 months after term were significantly lower than in healthy term infants of the same age. CONCLUSIONS: Preterm infants with BPD have impaired growth, with a deficit in TBF and FFM already 6 weeks after term; FFM and TBF remain low compared with healthy term infants during the first year of life. Nutritional intervention studies in infants with BPD are needed to evaluate if nutrition is the major determinant of growth and body composition or if this pattern of growth in preterm infants with BPD is the result of disturbed endocrine control. http://repub.eur.nl/res/pub/10092/ 2002-01-01T00:00:00Z BACKGROUND: Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance. METHODS: A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters. RESULTS: In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+25.7%, p < 0.05) and IDLc (-30.1%, P < 0.05). In the HCTZ-treated group no significant changes in plasma lipid levels were observed. On follow-up visits systolic blood pressure in the doxazosin-treated group was 6 mm higher than in the HCTZ group. Nevertheless, the groups treated with doxazosin or HCTZ showed no differential effect on IMT after three years of treatment (p = 0.8). A significant reduction of the IMT of combined carotid and femoral arterial walls was shown in both treatment groups (p < 0.005). CONCLUSIONS: Hypertension treatment with doxazosin or HCTZ resulted in a comparable change in arterial IMT after three years, in spite of differences in effect on plasma lipids. The study emphasises the importance of blood pressure control in patients with peripheral vascular disease and hypercholesterolaemia. http://repub.eur.nl/res/pub/8519/ 2002-01-01T00:00:00Z AIMS: To obtain normative data on bone mineral density and body composition measured with dual energy x ray absorptiometry (DXA) from early childhood to young adulthood. METHODS: Cross sectional results from 444 healthy white volunteers (4-20 years) in the Netherlands were combined with the results from 198 children who agreed to participate in the follow up study approximately four years later. DXA (Lunar, DPXL) of lumbar spine and total body was performed to assess bone density and body composition. RESULTS: Bone density and lean body mass (LBM) increased with age. Maximal increase in bone density and LBM occurred around the age of 13 years in girls and approximately two years later in boys. Bone density of total body and lumbar spine showed an ongoing slight increase in the third decade. Mean fat percentage in boys remained at 10.5% throughout childhood, but increased in girls. CONCLUSIONS: Most of the skeletal mass in lumbar spine and total body is reached before the end of the second decade, with a slight increase thereafter. This study provides reference values for bone density and body composition measured with DXA for children and young adults. http://repub.eur.nl/res/pub/9835/ 2002-01-01T00:00:00Z OBJECTIVES: To determine the value of pulmonary artery Doppler velocimetry relative to fetal biometric indices and clinical correlates in the prenatal prediction of lethal lung hypoplasia (LH) in prolonged (>1 week) oligohydramnios. METHODS: Forty-two singleton pregnancies with oligohydramnios associated with premature rupture of membranes ([PROM]; n = 31) or bilateral renal pathology (n = 11) were examined using color-coded Doppler ultrasound in a cross-sectional study design. Mean gestational age was 28.0 +/- 4.3 weeks (range: 20-36 weeks). Thoracic, cardiac, and abdominal circumference and the largest vertical amniotic fluid pocket were measured. Pulsed Doppler measurements of the arterial pulmonary branches were made at the level of the cardiac 4-chamber view. Diagnosis of LH was based on clinical, radiologic, and pathologic criteria. Clinicians were blinded to the prenatal measurements. RESULTS: The prevalence of lethal LH was 43%. In the PROM subset, combination of onset of PROM at <or =20 weeks, duration of oligohydramnios at > or =8 weeks, and degree of oligohydramnios at < or =1 cm presented the highest clinical prediction rate for lethal LH. For both the total group and the PROM subset, the highest prediction rate for lethal LH was presented by thoracic circumference/abdominal circumference ratio, peak systolic velocity in the proximal branch, and time-averaged and end-diastolic velocity in the middle branch of the pulmonary artery. In the PROM subset, the combination of all 3 clinical, biometric, and Doppler parameters revealed the most favorable combination to predict lethal LH (positive predictive value: 100%; accuracy: 93%; and sensitivity: 71%). CONCLUSION: Doppler velocimetry may detect changes in pulmonary artery waveforms in the presence of LH but fails to be the ultimate test for the prenatal prediction of lethal LH. The best prediction can be achieved by combining clinical, biometric, and Doppler parameters. http://repub.eur.nl/res/pub/9914/ 2002-01-01T00:00:00Z Low birth weight is associated with an increased risk in adult life of type 2 diabetes, hypertension and cardiovascular disease (CVD). The fetal insulin hypothesis postulates that genes involving insulin resistance could effect birth weight and disease in later life (Hattersley, 1999). Besides insulin, there is extensive evidence that insulin-like growth factor-I and -II (IGF-I, IGF-II) play an important role in fetal growth. We hypothesized that minor genetic variation in the IGF-I gene could influence pre- and postnatal growth. Three microsatellite markers located in the IGF-I gene in 124 short children (height < -1.88 SDS) who were born small for gestational age (SGA) and their parents were studied. SGA was defined as both a birth weight and birth length below -1.88 SDS for gestational age. Two polymorphic markers showed transmission disequilibrium. Allele 191 of the IGF1.PCR1 marker was transmitted more frequently from parent to child (chi(2) = 4.8 and p = 0.02) and allele 198 of the 737/738 marker was transmitted less frequently from parent to child (chi(2)= 4.5 and p = 0.03). Children carrying the 191-allele had significantly lower IGF-1 levels than children not carrying this allele (-1.1 SDS vs. -0.05 SDS; p = 0.03). Also, head circumference SDS remained smaller in children with allele 191 compared to children without allele 191 (-2.1 SDS vs. -0.9 SDS; p = 0.003). Our results show that genetically determined low IGF-I levels may lead to a reduction in birth weight, length and head circumference and to persistent short stature and small head circumference in later life (proportionate small). Since low IGF-I levels are associated with type 2 diabetes and CVD, we propose that the IGF-I gene may provide a link between low birth weight and such diseases in later life. http://repub.eur.nl/res/pub/31851/ 2000-12-01T00:00:00Z Objectives: To establish the nature and gestational age dependency of flow velocity waveforms from fetal middle and distal arterial pulmonary branches in the second half of normal pregnancy and to determine repeatability and inter-relationship of flow velocity waveform recordings from proximal, middle and distal arterial pulmonary branches. Design: Cross-sectional study. Subjects/methods: A total of 111 singleton normal pregnancies between 20 and 40 weeks of gestation were studied using a color-coded Doppler ultrasound system. Pulmonary waveforms were obtained at the level of the fetal cardiac four-chamber view. Repeatability was tested from two recordings at 15 min time-intervals in 25 separate normal pregnancies. Results: Acceptable repeatability of flow velocity waveforms from fetal arterial pulmonary branches was established with coefficients of variation below 15%. The nature of middle arterial pulmonary flow velocity waveforms was similar to that of proximal waveforms and showed a gestational age-related change for diastolic velocity parameters, peak systolic/peak diastolic ratio and pulsatility index. The distal arterial pulmonary branch displayed a monophasic forward flow velocity profile throughout the cardiac cycle. All velocity parameters of the distal branch remained unchanged with advancing gestation, with the exception of the pulsatility index. Significant inter-pulmonary changes were found for all pulmonary arterial waveform parameters. Conclusions: Alteration in pulmonary vascular resistance may play a role in gestational age-related changes, whereas changes in vessel branching/diameter and in the distance between the heart and more distal arterial pulmonary vessels may cause inter-pulmonary differences. http://repub.eur.nl/res/pub/9275/ 2000-01-01T00:00:00Z OBJECTIVE: To describe the severity of adverse drug reactions as a factor in hospital admission of older patients, and to identify risk indicators for severe adverse drug reactions in these patients. DESIGN: Observational cross-sectional study. SETTING: Five wards in a university hospital in The Netherlands. SUBJECTS: Patients aged 70 and over admitted to general medical wards. METHODS: Use of statistical comparison and Kramer's algorithm. RESULTS: A severe adverse drug reaction was present in 25 (24%) of 106 patients. Thirteen patients (12%; 95% confidence interval 6.1-18.6%) were admitted probably because of an adverse drug reaction. Risk indicators for a severe adverse drug reaction were a fall before admission (odds ratio 51.3, P = 0.006), gastrointestinal bleeding or haematuria (odds ratio 19.8, P < 0.001) and the use of three or more drugs (odds ratio 9.8, P = 0.04). CONCLUSION: Adverse drug reactions are an important cause of hospital admissions in older people. A fall before admission may indicate a severe adverse drug reaction. http://repub.eur.nl/res/pub/9276/ 2000-01-01T00:00:00Z OBJECTIVE: To establish the relationship between subjective complaints of side effects of drugs and the objective presence of adverse drug reactions in older patients. DESIGN: Observational cross-sectional study. SETTING: Five medical wards at the University Hospital Rotterdam Dijkzigt. SUBJECTS: Patients aged 70 and over admitted to the general medical wards over a 3-month period. METHODS: Statistical comparison and Kramer's algorithm. RESULTS: Of 106 patients, 102 used medication, and 93 of these were able to report whether they believed they were experiencing drug side effects. Thirty-six [39% (95% confidence interval 28.8-48.6)] believed that they were experiencing side effects and the number of diagnoses per patient and the proportion of patients with chronic obstructive pulmonary disease was higher in these 36 'complainers' than in the group of the 'non-complainers'. We found a correct opinion (true positive and negative) about the objective presence or absence of mild or severe adverse drug reactions in 79% (95% confidence interval 70.2-86.8). Asking the patient about side effects of drugs had a sensitivity of 0.70 and a specificity of 0.85 patients. The severe adverse drug reactions in 21 patients were not recognized by 14 of them. CONCLUSION: At hospital admission, older patients should be asked about drug side effects because they are often correct in recognizing them. However, severe adverse drug reactions are not easily recognized. http://repub.eur.nl/res/pub/9503/ 2000-01-01T00:00:00Z Some very preterm neonates admitted to the neonatal intensive care unit show circulatory and respiratory problems that improve after administration of steroids. It is unclear whether these symptoms could be caused by adrenal insufficiency. The objective of our study was to investigate the cortisol levels and the cortisol release from the adrenals after ACTH in very preterm infants with and without severe illness and to find whether a relation exists between adrenal function and outcome. An ACTH test (0.5 microg) was performed on d 4 in 21 very preterm infants (gestational age, 25.6-29.6 wk; birth weight, 485-1265 g). Baseline cortisol and 17-hydroxyprogesterone (17OHP) levels and the cortisol levels 30, 60, and 120 min after ACTH administration were measured. The Score for Neonatal Acute Physiology was used to measure illness severity. All infants showed an increase in cortisol levels after ACTH, but the cortisol levels were significantly lower in the ventilated more severely ill infants. After adjusting for birth weight and gestational age, the mean baseline cortisol levels and cortisol/17OHP ratios were significantly lower and the 17OHP levels significantly higher in the ventilated infants compared with the nonventilated infants. Patients with an adverse outcome had significantly lower baseline cortisol/17OHP ratios and 60-min cortisol levels during ACTH testing (p = 0.002 and p = 0.03, respectively). These data suggest an insufficient adrenal response to stress in sick ventilated very preterm infants with gestational ages younger than 30 wk compared with nonventilated less sick preterm infants. Further studies are required to investigate whether supplementation with physiologic doses of hydrocortisone may benefit the outcome. http://repub.eur.nl/res/pub/8643/ 1997-01-01T00:00:00Z The association of height, weight, pubertal stage, calcium intake, and physical activity with bone mineral density (BMD) was evaluated in 500 children and adolescents (205 boys and 295 girls), aged 4-20 yr. The BMD (grams per cm2) of lumbar spine and total body was measured with dual energy x-ray absorptiometry. Lumbar spine volumetric BMD was calculated to correct for bone size. BMD and volumetric BMD increased with age. During puberty, the age-dependent increment was higher. After adjustment for age, the Tanner stage was significantly associated with all three BMD variables in girls and with spinal BMD in boys. In boys, positive correlations were found between BMD and both calcium intake and physical activity after adjustment for age. Stepwise regression analysis with weight, height, Tanner stage, calcium intake, and physical activity as determinants with adjustment for age resulted in a model with Tanner stage in girls and weight in boys for all three BMD variables. The major independent determinant of BMD was the Tanner stage in girls and weight in boys. http://repub.eur.nl/res/pub/8728/ 1997-01-01T00:00:00Z OBJECTIVES: This study examined the influence of lactational and in utero exposure to polychlorinated biphenyls (PCBs) on plasma PCB levels in children. METHODS: Plasma PCB levels were measured in 173 children at 3.5 years, of whom 91 were breast-fed and 82 were formula-fed in infancy. RESULTS: Median plasma PCB levels were 3.6 times higher in breast-fed children (0.75 microgram/L) than in their formula-fed peers (0.21 microgram/L). Breast-feeding period and breast-milk PCB levels were important predictors for PCB levels in the breast-fed group. For children in the formula-fed group, PCB levels were significantly related to their material plasma PCB levels. CONCLUSIONS: PCB levels in Dutch preschool children are related to transfer of maternal PCBs; therefore, strategies should be aimed at reducing maternal PCB body burden.