Objective: Although low birthweight (bw) and unfavourable 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 analyse the long-term impact of bw on steroid metabolism.
Methods: 68 monozygotic twin-pairs with bw-difference of <1SDS (concordant; n=41, 18 female) and ≥1SDS (discordant; n=27, 15 female, 6 female and male pairs with catch-up) were recruited. At mean age of 14.9 yrs morning urine samples were collected and analysed by gas chromatography–mass spectrometry.
Results: In the concordant group no significant differences in urinary steroid metabolites were detected in females or males. In contrast, in the discordant female group with catch-up growth, we found significantly higher concentrations in the smaller twins for α-Cl, a cortisone metabolite (P=0.028, 1941 vs 1169 µg/l). Ratio of 11β-hydroxy-steroiddehydrogenase activity (cortols/cortolones) was significantly lower in smaller discordant females (P=0.032, 0.23 vs 0.27). Overall cortisol metabolite secretion was higher in female smaller twins with catch-up (11783 vs 7256 µg/l), although not significantly. Smaller female twins without catch-up showed slightly lower concentrations than their larger co-twins (11842 vs 13713 µg/l), again without significant difference. In the male pairs, the smaller discordant twins without catch-up showed significantly lower metabolite concentrations in 9/13 (69.2%) metabolites analysed and significantly lower cumulative major cortisol metabolites (P=0.046, 8053 vs 10060 µg/l) and overall cortisol metabolite secretion (P=0.028, 11879 vs 14867 µg/l). Male smaller twins with catch-up showed concentrations not significantly different than their larger co-twins (13483 vs 14284 µg/l). Within all twin pairs, we found significant intra-twin correlations in all steroid metabolites, cumulative metabolites, and enzyme activities analysed. 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 analysed.
Conclusion: In monozygotic twins with intra-twin bw-differences, we could show that bw has a long-lasting impact on steroid metabolism with significant differences regarding cortisol metabolites and enzyme activities in pairs with greater bw-differences. Pronounced in the male group, we could see that lower overall cortisol metabolite secretion was represented in smaller twins without catch-up. Whether this might be source or result of a missing catch-up growth in childhood remains unclear. However, most parameters showed highly significant intra-twin correlations, suggesting also a major importance of the genetic background.
15 Sep 2022 - 17 Sep 2022