Department of Women's and Children's Health, Karolinska Institutet, Pediatric Endocrinology Unit, Karolinska University Hospital, Stockholm, Sweden.
J Clin Endocrinol Metab. 2020 Jul 1;105(7):e2439-48. doi: 10.1210/clinem/dgaa280.
Prenatal treatment with dexamethasone (DEX) reduces virilization in girls with congenital adrenal hyperplasia (CAH). The treatment is effective but may result in long-lasting adverse effects. In this study we explore the effects of DEX on metabolism in individuals not having CAH but treated with DEX during the first trimester of fetal life.
All DEX-treated participants (n = 40, age range 5.1-26.4 years) and controls (n = 75, age range 4.5-26.6 years) were assessed with fasting blood samples to measure blood count, renal function, glucose homeostasis, and serum lipid profiles.
There were no significant differences between DEX and control participants for birth parameters, weight and height, or body mass index at the time of testing. Analyzing the entire cohort, we found no significant effects of DEX on blood count, renal function, or serum lipid profiles. However, a lower HOMA-β index in the DEX-treated individuals (U = 893.0; P = 0.049) was observed. Post hoc analyses revealed an effect in girls (U = 152.5; P = 0.024) but not in boys (U = 299.5; P = 0.550). The effect on HOMA-β persisted (U = 117.5; P = 0.048) after analyzing data separately in the participants < 16 years of age. In addition, we observed higher plasma glucose levels (F = 14.6; P = 0.001) in the DEX-treated group. The participants ≥ 16 years of age in the DEX-treated group had significantly higher total plasma cholesterol (F = 9.8; P = 0.003) and higher low-density lipoprotein cholesterol levels (F = 7.4; P = 0,009).
Prenatal DEX exposure in early pregnancy has negative effects on beta-cell function and lipid profile in individuals without CAH already at a young age.
在患有先天性肾上腺皮质增生症(CAH)的女性中,产前用地塞米松(DEX)治疗可降低男性化。这种治疗方法有效,但可能导致长期的不良影响。在这项研究中,我们探讨了在胎儿生命的第一个三个月接受 DEX 治疗的非 CAH 个体中,DEX 对代谢的影响。
所有接受 DEX 治疗的参与者(n=40,年龄范围为 5.1-26.4 岁)和对照组(n=75,年龄范围为 4.5-26.6 岁)均进行空腹血样检测,以测量血细胞计数、肾功能、葡萄糖稳态和血清脂质谱。
DEX 组和对照组在出生参数、体重和身高或测试时的体重指数方面无显著差异。对整个队列进行分析,我们发现 DEX 对血细胞计数、肾功能或血清脂质谱没有显著影响。然而,DEX 治疗组的 HOMA-β 指数较低(U=893.0;P=0.049)。事后分析显示,这种影响仅在女孩中(U=152.5;P=0.024),而在男孩中无影响(U=299.5;P=0.550)。在分析年龄<16 岁的参与者的数据时,这种对 HOMA-β 的影响仍然存在(U=117.5;P=0.048)。此外,我们观察到 DEX 治疗组的血浆葡萄糖水平更高(F=14.6;P=0.001)。DEX 治疗组中≥16 岁的参与者的总血浆胆固醇(F=9.8;P=0.003)和低密度脂蛋白胆固醇水平更高(F=7.4;P=0.009)。
在妊娠早期接受产前 DEX 暴露会对非 CAH 个体的胰岛β细胞功能和脂质谱产生负面影响,即使在年幼时也是如此。