Investigating the Origins of Biochemical Dysregulation in Trisomy 21 Pregnancy.

Abstract

Genetic profiling of trisomy 21 (T21) shows disruptions in energy homeostasis and oxidative stress pathways. This study aimed to evaluate oxidative and metabolic dysregulation in T21 pregnancies and identify their genetic or systemic origins. After karyotype analysis, 20 women with T21 and 20 with euploid fetuses were enrolled. Inclusion criteria were referral for prenatal testing; exclusion criteria encompassed maternal chronic or acute diseases. Amniotic fluid and plasma samples were collected and total oxidative capacity (TOC), total antioxidant capacity (TAC), superoxide dismutase (SOD), nuclear factor-κB (NFκB), forkhead box O (FOXO), sirtuin 1 (SIRT1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), leptin, and adiponectin levels were measured. The amniotic fluid/plasma (AF/P) ratio was calculated to assess marker origin. In T21 pregnancies, maternal plasma showed decreased levels of TAC, SOD, FOXO, and leptin (P < .05). In amniotic fluid, levels of FOXO and leptin were also reduced, while SOD, TAC, TOC, adiponectin, and 8-OHdG were elevated (P < .05). The AF/P ratio was increased for SOD (P = .027), TAC (P < .001), TOC (P < .0001), and adiponectin (P = .002), suggesting a fetal origin, while decreased SIRT1 levels (P = .036) indicate impaired fetal oxidative regulation. A plasma biomarker panel comprising SOD, TAC, and leptin, assessed via regression modeling, demonstrated the highest clinical utility in distinguishing T21 pregnancies from euploid pregnancies (area under the receiver operating characteristic curve = .92, P < .001). The AF/P ratio supports a fetal origin for SOD, TAC, TOC, and adiponectin, while lower SIRT1 implies disrupted fetal oxidative regulation.