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Objective: Although low birthweight (bw) and unfavorable intrauterine conditions have been associated with metabolic sequelae in later life, little is known about their impact on steroid metabolism. We studied genetically identical twins with intra-twin bw-differences from birth to adolescence to analyze the long-term impact of bw on steroid metabolism.Methods: 68 monozygotic twin pairs with a bw-difference of <1 standard deviation score (SDS; concordant; n = 41) and ≥1 SDS (discordant; n = 27) were recruited. At 14.9 years (mean age), morning urine samples were collected and analyzed with gas chromatography-mass-spectrometry.Results: No significant differences were detected in the concordant group. In contrast, in the smaller twins of the discordant group, we found significantly higher concentrations not only of the dehydroepiandrosterone sulfate (DHEAS) metabolite 16α-OH-DHEA (P = 0.001, 656.11 vs 465.82 µg/g creatinine) but also of cumulative dehydroepiandrosterone and downstream metabolites (P = 0.001, 1650.22 vs 1131.92 µg/g creatinine). Relative adrenal (P = 0.002, 0.25 vs 0.18) and overall androgen production (P = 0.001, 0.79 vs 0.65) were significantly higher in the formerly smaller discordant twins. All twin pairs exhibited significant intra-twin correlations for all individual steroid metabolites, sums of metabolites, indicators of androgen production, and enzyme activities. Multiple regression analyses of the smaller twins showed that individual steroid concentrations of the larger co-twin were the strongest influencing factor among nearly all parameters analyzed.Conclusion: In monozygotic twin pairs with greater intra-twin bw-differences (≥1 SDS), we found that bw had a long-lasting impact on steroid metabolism, with significant differences regarding DHEAS metabolites and relative androgen production. However, most parameters showed significant intra-twin correlations, suggesting a consistent interrelationship between prenatal environment, genetic background, and steroid metabolism. [ABSTRACT FROM AUTHOR]

Background: Low birth-weight (bw), low birth-length (bl), unfavourable intrauterine conditions and post-natal catch-up growth can have an impact on growth and metabolic health later in life. Objective: We studied genetically identical twins with intra-twin bw-differences due to twin-twin transfusion syndrome from birth to adolescence and analysed the long-term impact of bw and catch-up growth on metabolic parameters. Subjects and Methods: Forty-three postpubertal monozygotic twin-pairs (mean age 17.4 years) were examined. Twenty-two pairs were discordant (intra-twin bw- and/or bl-difference ≥1 SDS) of which 12 (55%) experienced catch-up growth. Auxological parameters and blood pressure were measured, a fasting blood sample was collected and bio-impedance spectroscopy was carried out. Results: Irrespective of differences in birth parameters and postnatal catch-up growth, a significant intra-twin correlation was found for nearly all measured parameters of body composition (skinfold, waist-hip circumference, relative body fat/lean body mass) and metabolic health (total, and low-density lipoprotein-C/high-density lipoprotein-C, Apolipoprotein A and B, C-peptide). As an exception to this, and only for the former smaller twins who showed postnatal catch-up growth, a significantly higher fasting insulin level was found compared to that of the co-twins (mean insulin level: 8.4 vs. 5.7 µIU/mL; p < 0.01). Auxology remained different until adulthood: even in subjects with catch-up growth the former smaller twins were significantly lighter (mean-body mass index-SDS: –0.42 vs. 0.21; p < 0.05) and shorter (mean height-SDS: –0.07 vs. 0.37; p < 0.05) than their co-twins. Conclusion: In this special group of monozygotic twins with intra-twin bw-differences and catch-up growth, we found that the genetic background was a more important factor in determining later metabolic health than bw and/or catch-up growth. [ABSTRACT FROM AUTHOR]

Background: Events during foetal or early extrauterine life may affect bodily structure and/or functions and even pave the way for adult diseases. Aims: To find whether extremely low birth weight (ELBW) infants differ from healthy controls regarding the excretion of steroid metabolites. Methods: The study compared 17 female and 10 male ELBW infants, all prepubertal, aged 8-11 years, birth weight <1,000 g, with 27 age- and sex-matched controls. All were healthy at the time of the study. Height, weight and BMI did not differ between the groups. Results were adjusted according to body surface area. 36 urinary steroid metabolites were quantified by gas chromatography-mass spectrometry. Results: In the ELBW girls 33/36 steroid metabolites were higher (19 significantly) than in the controls. All 36 steroid metabolites were higher in the ELBW boys (9 significantly) than in the controls. Sums of mineralocorticoid precursors, metabolites descriptive for cortisol and parameters of adrenal androgen production were significantly higher in ELBW infants (both sexes). Only the sum of the metabolites known to be illustrative for adrenal 11β-hydroxysteroid dehydrogenase activity was not different. Conclusion: Prepubertal ELBW children have an augmented urinary excretion of adrenal androgens, cortisol and mineralocorticoid precursors. These findings corroborate and help to explain the link between early-life adversity and subsequent adrenocortical function. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim To examine the impact of postnatal nutrition on long-term growth in extremely low birth weight infants. Method Retrospective analysis of postnatal nutrition and observational study of growth in 52 ELBW infants until the age of six. Results Changes (Δ) in weight and length standard deviation scores ( SDS) between birth to term correlated with protein intake (rw = 0.36; p = 0.009; rL = 0.35; p = 0.01), whereas Δ HC correlated with lipid intake (rHC = 0.38; p = 0.005). Analysis of various intervals (0-2, 3-5, 6-8 and 9-11 weeks) only showed significant impact on growth for energy (r = 0.3; p < 0.05) and lipids (r = 0.23; p < 0.05) at 6-8 weeks. No significant correlations were found between postnatal nutritional parameters and long-term growth. However, postnatal growth restraint was negatively associated with length SDS (r = −0.34; p = 0.015) and body mass index SDS (r = −0.34; p = 0.018) at the age of six. Infants with postnatal growth restraint (n = 25) caught up more in length (+1.78 SDS) than in weight (+0.43 SDS), whereas small for gestational age infants (n = 8) caught up more in weight (+1.35 SDS) than in length (+1.07 SDS). This difference remained significant at the age of six. Conclusion Although no direct association between postnatal nutrition and long-term growth was found, weight at discharge was a strong predictor for long-term growth. [ABSTRACT FROM AUTHOR]

Abstract: Background: Low birth weight predisposes to the development of insulin resistance. In addition to auxological parameters such as rapid catch-up growth, low IGFBP-1 serum levels in childhood have been linked to an increased risk of insulin resistance later in life. Concerning postnatal growth, we previously reported the GHRd3-variant to be associated with catch-up growth in preterm infants. In children born small for gestational age, a common IGFBP-1 promoter polymorphism −575G/A has been linked to IGFBP-1 serum levels and has been suggested to be an additional player in the interaction between the IGF-IGFBP-axis and metabolism. Study design: We analyzed postnatal growth, metabolic parameters, and genotypes for the GHRd3-variant and IGFBP-1 −575G/A in 51 former extremely low birth weight preterm infants (mean age 5.9years). Results: GHRd3 but not IGFBP-1 −575G/A was significantly associated with postnatal growth velocity. Catch-up growth, GHRd3, and IFGBP-1 −575G/A did not influence fasting insulin or HOMA-IR. However, we found significantly higher HbA1c and lower IGFBP-1 concentrations in GHRd3-carriers, a finding not seen with respect to IGFBP-1 −575G/A. Interestingly, HbA1c and IGFBP-1 levels also did not differ between children either with or without catch-up growth. Conclusions: In addition to an association with catch-up growth, GHR exon 3 genotype significantly modulates HbA1c and IGFBP-1 concentrations in former ELBW infants. In order to confirm this observation and to clarify whether the GHRd3-variant might be considered as an independent modulator of the low birth weight infant’s risk to develop insulin resistance later in life, larger studies extending to later ages are required. [Copyright &y& Elsevier]

Modern intensive care techniques have led to higher survival rates of extremely low birth weight infants (ELBW, birth weight <1,000 g). Previous studies have suggested a link between abnormal birth parameters and subsequent endocrine disturbances, but a possible impact on bone maturation during childhood has not been studied. ELBW children were studied (mean chronological age (CA), 6.01 years; range, 4.5-8.2). Skeletal maturation was assessed according to Greulich and Pyle (8). Bone age (BA) was defined as retarded when DeltaBA-CA was < -1 SD and accelerated when DeltaBA-CA was >+1 SD. BA was either retarded or accelerated in 15 patients (24.6%). Twenty-one of 61 radiograms (34.4%) showed a discordant BA with a marked gender difference (14/24 boys; 7/37 girls). DeltaBA-CA correlated significantly with BMI (r = 0.36; p = 0.005) and height SDS (r = 0.35; p = 0.006). We found significant correlations between BA and androgens. Insulin-like growth factor binding protein-1 (IGFBP-1), which decreases in insulin-resistant individuals, correlated negatively with BA. In conclusion, bone maturation in ELBW children is correlative with height and weight. It is modulated by a variety of metabolic factors, including IGFBP-1 and androgens. Bone age, together with height and weight catch-up, can thus possibly serve as early indicators of insulin resistance later in life. [ABSTRACT FROM AUTHOR]

The article examines the impact of birth weight, gender and catch-up growth on metabolic parameters in extremely low birth weight (ELBW) infants. Metabolic parameters considered in the analysis include Insulin-like Growth Factor Binding Proteins (IGFBP)-1, leptin and fasting insulin. Information is presented on the height and weight of ELBW-small-for-gestational age (SGA) and ELBW-appropriate for gestational age (AGA). It relates the role of catch-up growth and sex-dependent weight development in modulating the metabolic parameters in ELBW children.