Abstract
Introduction: Dehydroepiandrosterone sulphate is increased in formerly small-for-gestational age singletons and in smaller twins compared to their normal-weight co-twin. Less is known concerning other adrenal hormones. We compared diurnal salivary profiles in monozygotic twins with intra-twin birthweight (bw) differences to analyse the long-term impact of bw and persistent intra-twin auxological differences on various adrenal hormones. Methods: Forty-six monozygotic pre-pubertal twin pairs with bw difference of <1 standard deviation score (SDS) (concordant; n = 29, 13 female) and ≥1 SDS (discordant; n = 17, 6 female) were recruited. At a mean age of 6.9 years, saliva samples were collected (7:00 a.m./waking, 1:00 p.m., 6:00 p.m., and 9:00 p.m.) and analysed with liquid chromatography-tandem mass spectrometry. Results: Diurnal salivary concentrations showed significant intra-twin correlations in all twin pairs for nearly all time points: progesterone and androstenedione (4/4 time points), 17-hydroxyprogesterone (2/4). However, in the discordant group, mean progesterone differed significantly (p = 0.018) between the smaller (3.27 nmol/L, SD 3.87) and the larger twin (0.72 nmol/L, SD 0.42) at 7:00 a.m., and intra-twin differences were observed at 3/4 time points. Regression analyses of intra-twin differences confirmed that actual hormonal parameters were explained mainly by the co-twin parameter. However, at 6:00 p.m., progesterone concentration of the smaller twin was explained by bw (Β −1.102; SE 0.563; p = 0.05) and actual weight (Β 0.799; SE 0.327; p = 0.019). Conclusion: The significant correlations within monozygotic twin pairs in all measured hormones at nearly all time points suggest a strong genetic influence on the adrenal axis. Among the discordant twin pairs, we found significant variations in progesterone, suggesting additional long-lasting influence from intrauterine conditions on adrenal hormones with possible metabolic consequences.
Plain Language Summary
Previous research has shown that low birthweight (bw), unfavourable intrauterine conditions, and rapid post-natal catch-up growth can have long-standing negative health impacts, including disruption of the endocrine system. Earlier studies have primarily focused on the impact of low bw on one particular adrenal hormone, dehydroepiandrosterone sulphate, but less is known about the impact on the production of other hormones. In our study, we compared salivary hormone levels and generic health parameters (bw, height, weight, etc.) in identical twin pairs, to investigate the long-standing impact of unfavourable intrauterine conditions. Our cohort consisted of identical twin pairs who suffered from twin-to-twin transfusion syndrome in utero, a condition in which there is unequal blood and nutrient supply among twin pairs. This condition often results in significant bw differences between twins. The twin pairs in this cohort have an identical genetic makeup, very similar post-natal conditions, but contrasting intrauterine conditions, making them an excellent cohort in which to investigate genetic and non-genetic influences on longer term health.
