Childhood lymphomatoid granulomatosis: a report of 2 cases and review of the literature.

Lymphomatoid granulomatosis (LG) is a B-cell type lymphoproliferative disease. It mainly affects the lungs but may have extrapulmonary manifestations, especially in the central nervous system. The purpose of this study was to review the pediatric cases in the literature and add 2 new cases to the existing literature. A review of the literature was performed on children (0 to 18 years of age at diagnosis) with pathologically proven LG. We found 47 case reports, which, together with 2 new cases, were systematically analyzed. The median age was 12 years. The main symptoms were general, pulmonary, and neurological. Approximately one third of the patients were immunocompromised. High mortality rate was observed. Pediatric LG is a rare disease, which appears to be more frequently seen in immunocompromised patients, especially patients with leukemia. The disease has a high mortality rate; therefore, aggressive therapy according to a high-grade B-cell lymphoma protocol is justified.

IGF1 promoter polymorphism and cranial growth in individuals born very preterm.

BACKGROUND: Major defects in the IGF1 gene are associated with severely reduced cranial and linear growth. The association between IGF1 promoter polymorphisms and growth is uncertain. AIMS: To test the effect of the IGF1 192-bp allele on cranial and linear growth and body mass index (BMI) from birth until age 5 years, and on IQ and serum IGF-1 at age 19 years. METHODS: In a birth cohort, including 285 individuals born at a gestational age <32 weeks from the Project On Preterm and Small-for-gestational age infants (POPS), cohort anthropometric measurements were analyzed. At age 19 years IGF1 genotype, serum IGF-1 level and IQ were determined. Regression analyses were performed with mixed models. RESULTS: Homozygotes for the 192-bp allele had a slower cranial growth from birth until age 5 years, and a tendency towards less brain sparing and a slower linear growth compared to the other 2 genotype groups. IGF1 genotype was not associated with IQ or BMI development. Head circumference SDS at age 5 years was positively associated with IQ at age 19 years. CONCLUSION: Homozygosity for the IGF1 192-bp allele is associated with a slower cranial growth from birth until age 5 years in individuals born very preterm.

Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life.

BACKGROUND: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. OBJECTIVES: To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm. DESIGN AND METHODS: Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses. RESULTS: Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (ß: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (ß: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (ß: -0.337, 95% CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (ß: 0.932, 95% CI: 0.022 - 1.843). CONCLUSIONS: Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.

Intrauterine growth restriction: no unifying risk factor for the metabolic syndrome in young adults.

BACKGROUND: The validity and appropriateness of the metabolic syndrome as a cardiovascular risk factor are increasingly debated, partly because of the lack of a unifying underlying pathophysiological mechanism. Intrauterine growth retardation (low birth weight by sex and gestational length) has been associated with several cardiovascular problems and could be an important underlying risk factor for the metabolic syndrome. METHODS: The association between intrauterine growth retardation (from the Norwegian Medical Birth Registry) and the metabolic syndrome in 7435 men and women aged 20-30 years from the population-based HUNT 2 study was studied with logistic regression using fractional polynomial models. RESULTS: In men, there were significant associations with several of the separate components of the metabolic syndrome: central obesity (exponential, P<0.001), raised triglycerides (negative linear, P = 0.018), reduced HDL-cholesterol (U-shaped, P = 0.086), raised blood pressure (negative linear, P = 0.036), and impaired glucose tolerance (negative linear, P = 0.036). In women, there were significant associations with central obesity (positive linear, P<0.001) and raised blood pressure (negative linear, P = 0.003) but not with the other components. When combining these components into the metabolic syndrome, an exponential association was found in men (P = 0.017), that is, increased risk in patients with high birth weight only. In women, there was no association at all (P = 0.959). CONCLUSION: Low birth weight was not associated with the metabolic syndrome at young adult age. Several associations between birth weight and the separate components of the syndrome were found, however, but these associations were partly in different directions.

Cohort studies: prospective versus retrospective.

Cohort studies form a suitable study design to assess associations between multiple exposures on the one hand and multiple outcomes on the other hand. They are especially appropriate to study rare exposures or exposures for which randomization is not possible for practical or ethical reasons. Prospective and retrospective cohort studies have higher accuracy and higher efficiency as their respective main advantages. In addition to possible confounding by indication, cohort studies may suffer from selection bias. Confounding and bias should be prevented whenever possible, but still can exert unknown effects in unknown directions. If one is aware of this, cohort studies can form a potent study design in nephrology producing, in general, highly generalizable results.

A practical approach to Bland-Altman plots and variation coefficients for log transformed variables.

OBJECTIVE: Indicators of reproducibility for log-transformed variables can often not be calculated straightforwardly and are subsequently incorrectly interpreted. METHODS AND RESULTS: We discuss meaningful Coefficients of Variation (CV) for log-transformed variables, which can be derived directly from the standard error of the log-transformed measurements. To provide easy interpretable Bland and Altman plots, we calculated limits of inter and intraobserver agreement (LA) for log-transformed variables and transform them back to the original scale. These LAs for agreement are subsequently plotted on the original scale in a conventional Bland and Altman plot. Both approaches were illustrated in a clinical example on the reproducibility of skinfold thickness measurements. CONCLUSION: In reproducibility, it is important to calculate meaningful CVs, LAs, and Bland-Altman plots for log-transformed variables. We provide a practical approach in which existing statistical methods are applied in the field of reproducibility, thus leading to parameters of reproducibility which can be interpreted on the original scale.

Effect of intrauterine growth restriction on kidney function at young adult age: the Nord Trøndelag Health (HUNT 2) Study.

BACKGROUND: The hypothesis of intrauterine origin of adult disease is debated. We tested whether intrauterine growth restriction is associated with later kidney function. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 7,457 Norwegian adults aged 20 to 30 years participating in the population-based Nord Trøndelag Health Study (1995-1997) with data for birth weight, gestational age, and maternal and perinatal risk factors registered at the Medical Birth Registry of Norway. PREDICTOR: Birth weight expressed as an SD score (SDS) to adjust for gestational age and sex. Subjects with a birth weight SDS less than -2.0, -2.0 to -1.3, and -1.3 to 1.3 were defined as very small, small, and appropriate for gestational age, corresponding to less than the 3rd, 3rd to 10th, and 10th to 90th percentiles, respectively. OUTCOME & MEASUREMENTS: Kidney function estimated using the Cockcroft-Gault and isotope dilution mass spectrometry-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Values less than the sex-specific 10th percentile were defined as low-normal kidney function. RESULTS: Compared with men with birth weight appropriate for gestational age (n = 2,755), odds ratios for low-normal creatinine clearance (<100 mL/min) were 1.66 (95% confidence interval [CI], 1.16 to 2.37) if small for gestational age (n = 261) and 2.40 (95% CI, 1.46 to 3.94) if very small for gestational age (n = 101). Kidney function estimated using the MDRD Study equation gave similar results. Women (n = 3,126, 283, and 112, respectively) had odds ratios of 1.65 (95% CI, 1.17 to 2.35) and 2.00 (95% CI, 1.21 to 3.29) for low-normal creatinine clearance (<80 mL/min), whereas the association was not significant using the MDRD Study equation. Using linear regression, creatinine clearance decreased by 4.0 mL/min (95% CI, 3.3 to 4.6) in men and 2.9 mL/min (95% CI, 2.2 to 3.5) in women per 1-SDS decrease. Adjusting for possible confounders did not influence results. LIMITATIONS: Selection bias could be a problem because the participation rate was 49%, but there were no statistically significant differences between participants and nonparticipants regarding maternal and perinatal characteristics. Adjusting kidney function for body size can be a special problem in people with intrauterine growth restriction. CONCLUSIONS: Although effects were still small in young adulthood, intrauterine growth restriction was significantly associated with low-normal kidney function. The effect was weaker and less consistent in women compared with men.

Reliability studies can be designed more efficiently by using variance components estimates from different sources.

OBJECTIVES: Reliability studies are frequently organized within the context of a large (multicenter) study, with only a small sample of subjects measured by the observers of the large study. To estimate interobserver reliability, data from the large study are not frequently used. In this article, the advantages of combining data from the reliability study and the large study to improve the estimation of intra-class correlation coefficients (ICCs) are highlighted. STUDY DESIGN AND SETTING: This was done within the scope of estimating fat percentages in the Project On Preterm and Small-for-gestational-age infants-19 (POPS-19) study and with simulations. To calculate ICCs, three approaches were used: (1) the classical approach using data from a reliability study only, (2) the combined variances approach using inter-subject variances from the POPS-19 study, and (3) the maximum likelihood approach using all data. RESULTS: The ICCs (95% confidence interval [CI]) for fat percentage calculated by the three approaches were 0.84 (0.57, 0.99), 0.94 (0.90, 0.97), and 0.94 (0.88, 0.97), respectively. CONCLUSION: The efficient use of data by combining data from a small reliability study with the data from the large study itself for the calculation of ICCs will lead to more precise ICCs.

Associations between prenatal and infancy weight gain and BMI, fat mass, and fat distribution in young adulthood: a prospective cohort study in males and females born very preterm.

BACKGROUND: Increasing evidence indicates that adult body composition is associated with prenatal and infancy weight gain, but the relative importance of different time periods has not been elucidated. OBJECTIVE: The objective was to study the association between prenatal, early postnatal, and late infancy weight gain and body mass index (BMI), fat mass, and fat distribution in young adulthood. DESIGN: We included 403 men and women aged 19 y from a Dutch national prospective follow-up study who were born at <32 wk of gestation. BMI, waist circumference, and waist-to-hip ratio SD scores and subscapular-to-triceps ratio, percentage body fat, fat mass, and fat-free mass at age 19 y were studied in relation to birth weight SD scores, weight gain from preterm birth until 3 mo postterm (early postnatal weight gain), and weight gain from 3 mo until 1 y postterm (late infancy weight gain). RESULTS: Birth weight SD scores were positively associated with weight, height, BMI SD scores, and fat-free mass at age 19 y but not with fat mass, percentage body fat, or fat distribution. Early postnatal and late infancy weight gain were positively associated with adult height, weight, BMI, waist circumference SD scores, fat mass, fat-free mass, and percentage body fat but not with waist-to-hip ratio SD scores or subscapular-to-triceps ratio. CONCLUSIONS: In infants born very preterm, weight gain before 32 wk of gestation is positively associated with adult body size but not with body composition and fat distribution. More early postnatal and, to a lesser extent, late infancy weight gain are associated with higher BMI SD scores and percentage body fat and more abdominal fat at age 19 y.