M. A. J. de Ridder

Children Born Small for Gestational Age: Do They Catch Up?

ABSTRACT: Postnatal growth of 724 (423 premature, 301 full-term) small for gestational age infants (SGA. birth length less than the third length percemile (P3) for gestational age) was studied for the first 2 y of lile. The study group consisted of all SGA infants who had been admitted over a period of 8 y at the Departments of Neonatology of three University Hospitals in The Netherlands with exclusion of infants with well defined causes for growth retardation, such as chromosomal disorders, syndromes, severe malformations, or complications during the neonatal period or later on. The aim of the study was to describe postnatal growth of SGA infants and to find predictive factors for catch-up growth ≥P3 during the first 2 y of life. The majority (around 85%) of the healthy SGA infants showed catch-up growth to a height ≥P3 during the first 2 y of life. The percentage of premature SGA infants with catch-up growth ≥P3 at 2 y of age (82.5%) was not significantly different from that of full-term SGA infants (87.5%). Birth length SDS was more sensitive than birth weight SDS in predicting catch-up ≥P3 in premature SGA infants. In contrast, birth weight SDS was the best predictor for catch-up >P3 in full-term SGA infants. Gestational age, multiple birth, and sex were not significantly associated with catch-up in height ≥P3. For children with a length still below P3 at 3 or 6 mo of age, the actual length SDS at that age appeared positively associated with catch-up ≥P3. In SGA premature infants there was also a positive association between the weight gain during the first 6 mo and the catch-up growth ≥P3. SGA children with short stature (height <P3) at 2 y of age need further investigation.

New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study.

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.

Final Height and Its Predictive Factors after Renal Transplantation in Childhood

ABSTRACT: A retrospective study is reported assessing final height (FH) and its predictive factors in 52 patients (31 male, 21 female) who underwent renal transplantation (RTx) before the age of 15 y. They received prednisone daily or on alternate days as well as azathioprine. The study period covered 20 y. FH remained below the third height percentile [height standard deviation score for chronologic age (hSDSCA) < −1.88] for most of these patients (77% males, 71% females). Median (range) FH was 165.0 (143.0–176.8) cm in males and 153.0 (135.0–168.4) cm in females. Median difference between FH and target height was 15.0 and 15.4 cm for males and females, respectively. For both sexes, the median hSDSCA was already below −1.88 at the start of the first hemodialysis, after which it decreased significantly until the first RTx. After RTx, there was no significant improvement of hSDSCA. The predictive factors for FH were determined by evaluating various factors simultaneously in a multiple regression analysis. This analysis provided a regression equation for predicting FH. A higher hSDSCA at the time of the first RTx and alternate-day versus daily prednisone therapy both had a significantly positive influence on FH, whereas a longer duration of reduced GFR (<50 mL/min/1.73 m2) had a significantly negative effect on FH. Other factors such as age or bone age at first RTx, primary renal disease, duration of initial dialysis, repeat RTx, and the cumulative dose of prednisone did not influence FH significantly. In conclusion, 71–77% of patients that received their first renal transplant before the age of 15 ended up with severely short adult stature. Optimization of the hSDSCA at first RTx appears very important. Long-term administration of prednisone on alternate days would then result in optimal FH, particularly if the GFR remains above 50 mL/min/1.73 m2.

Growth and body composition in preterm infants with bronchopulmonary dysplasia

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.

Growth after Renal Transplantation in Prepubertal Children: Impact of Various Treatment Modalities

ABSTRACT: A retrospective study evaluated posttrans-plant growth of 70 prepubertal children during the first 2 y after renal transplantation (RTx). Immunosuppressive treatment consisted of prednisone administered either daily or on alternate days in combination with either azathioprine or cyclosporin A. The increment in height standard deviation score for chronologic age during the first 2 y after RTx was less than 0.5 SD for 70% of the study population. The predictive factors for posttransplant growth were determined by evaluating several factors and treatment modalities singly and simultaneously in a multiple regression analysis. Patients with the most severe growth retardation at RTx appeared to have the most pronounced growth spurt after RTx, but even they never had complete catchup growth, and 2 y after RTx they were still shorter than those with less severe growth retardation at RTx. Alternate-day instead of daily prednisone administration had a significantly positive influence, whereas a high cumulative dose of prednisone, azathioprine instead of cyclosporin A therapy, and a persistently reduced GFR (GFR < 50 mL/ min/1.73 m2) had a significantly negative influence on catch-up growth during the 2 y after RTx. Other factors, such as gender, chronologic and bone age at RTx, primary renal disease, duration of initial dialysis, repeat RTx, and target height SD score for chronologic age, whether evaluated singly or simultaneously with other significant factors, appeared to have no significant influence on post-RTx growth. Thus, 70% of the prepubertal children do not experience appreciable catch-up growth during the first 2 y after RTx. Optimization of pretransplant height appears very important. Immunosuppressive treatment with cyclosporin therapy in combination with a minimal dose of alternate-day prednisone would then result in optimal post-transplant growth, particularly if the GFR remains above 50 mL/min/1.73 m2).

Eight Years of Growth Hormone Treatment in Children With Prader-Willi Syndrome : Maintaining the Positive Effects

BACKGROUND The most important reason for treating children with Prader-Willi syndrome (PWS) with GH is to optimize their body composition. OBJECTIVES The aim of this ongoing study was to determine whether long-term GH treatment can counteract the clinical course of increasing obesity in PWS by maintaining the improved body composition brought during early treatment. SETTING This was a multicenter prospective cohort study. METHODS We have been following 60 prepubertal children for 8 years of continuous GH treatment (1 mg/m(2)/d ≈ 0.035 mg/kg/d) and used the same dual-energy x-ray absorptiometry machine for annual measurements of lean body mass and percent fat. RESULTS After a significant increase during the first year of GH treatment (P < .0001), lean body mass remained stable for 7 years at a level above baseline (P < .0001). After a significant decrease in the first year, percent fat SD score (SDS) and body mass index SDS remained stable at a level not significantly higher than at baseline (P = .06, P = .14, resp.). However, body mass index SDSPWS was significantly lower after 8 years of GH treatment than at baseline (P < .0001). After 8 years of treatment, height SDS and head circumference SDS had completely normalized. IGF-1 SDS increased to +2.36 SDS during the first year of treatment (P < .0001) and remained stable since then. GH treatment did not adversely affect glucose homeostasis, serum lipids, blood pressure, and bone maturation. CONCLUSION This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.

Renal transplantation and osteoporosis.

A cross sectional study assessed the bone mineral density (BMD) of 20 young adult patients who received a renal transplantation in childhood. The BMD of the lumbar spine, mainly trabecular bone, and of the total body, mainly cortical bone, were measured and expressed as an SD score. Fourteen patients (70%) had a BMD SD score of the lumbar spine below -1, of whom six patients were below -2. Fifteen patients (75%) had a BMD SD score of the total body below -1, of whom seven patients were below -2, Both trabecular and cortical bone appeared to be involved in the osteopenic process. The cumulative dose of prednisone was inversely correlated to both lumbar spine and total body BMD SD score. In a multiple regression analysis the cumulative dose of prednisone appeared to be the only factor with a significant effect on BMD SD score. Most young adult patients who had received a renal transplantation in childhood had moderate to severe osteopenia. Corticosteroid treatment played a major part in the development of osteopenia in these patients.

Fertility and Ovarian Function in High-Dose Estrogen-Treated Tall Women

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, fecundity was notably 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.

Standards for total body fat and fat-free mass in infants.

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altmans method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.

A rebreathing method to determine carbon monoxide diffusing capacity in children: Reference values for six 18‐year‐olds and validation in adult volunteers

The diffusing capacity of carbon monoxide (DL,CO) and its value normalized to alveolar volume (DL,CO/VA) are usually estimated with the single breath method at total lung capacity (TLC). Severely ill patients and small children are not able to deliver a satisfactory vital capacity (VC) or hold their breath for 10 s at TLC. The aim of this study was to develop a rebreathing procedure in which diffusing capacity can be determined during spontaneous tidal breathing. The conventional rebreathing method during hyperventilation was modified so that rebreathing volume and gas concentrations were kept constant by CO2 absorption and O2 supplementation. In adult healthy volunteers and in patients who were able to perform both tests, the diffusion indices obtained with this rebreathing method during resting ventilation were compared with those obtained by the single breath method. Predicted (reference) values for rebreathing DL,CO and DL,CO/VA for children were determined.