Anne M. Euser

Growth of preterm born children.

Background: In this review, we describe the growth of (very) preterm infants or (very) low-birth-weight infants from birth until adulthood. Methods: A systematic analysis of growth of these infants is thwarted by different definitions (classification by gestational age or birth weight) used in the literature. Results: The early postnatal period of these individuals is almost invariably characterized by substantial growth failure. In the majority of preterm infants this is followed by a period of catch-up growth, which starts in early infancy and usually stops at 2–3 years of age, although in some cases it may continue into adolescence. Catch-up growth is usually incomplete, so that infants born preterm remain shorter and lighter than term-born peers during childhood, adolescence, and adulthood. Disproportionate catch-up growth in height and weight may lead to an altered body composition in adulthood, especially in females. Conclusion: Though early catch-up growth has shown to be beneficial for neurodevelopmental outcome, it is also associated with adverse metabolic consequences in adulthood. As the first generation of (very) preterm infants is now reaching young adulthood, future follow-up studies on these effects are warranted.

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.

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 (β: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (β: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (β: -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 (β: 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. Eur J Cardiovasc Prev Rehabil 17:314-320