Twin‐twin transfusion syndrome is associated with alterations in the metabolic profile of maternal plasma in early gestation: a pilot study

Abstract

Objective Twin‐twin transfusion syndrome (TTTS) causes perinatal mortality and morbidity in monochorionic twins. The early recognition of and interventional therapy for TTTS is associated with a more favorable overall prognosis. However, the prediction by the use of ultrasound in the first trimester has relatively poor sensitivity and specificity. This study aimed to identify metabolic biomarkers to aid in ultrasound screening of TTTS. Methods Maternal plasma was prospectively collected between 11 and 15 weeks of gestation in apparently uncomplicated monochorionic‐diamniotic twin pregnancies. This cohort was divided into: (i) patients who were subsequently diagnosed with TTTS by using ultrasound; (ii) uncomplicated matched controls. Metabolome was profiled by using gas chromatography‐mass spectrometry. Results The levels of fatty acids, organic acids, oxaloacetic acid, and beta‐alanine were significantly lower in the TTTS maternal plasma at 11–15 weeks of gestation, and methionine and glycine were also higher (p < 0.05, FDR<0.12). Generally, in TTTS pregnancies, the metabolisms of amino acid, carbohydrate, cofactors, vitamins, and purine were “down‐regulated”; whereas bile secretion and pyrimidine metabolism were “upregulated.” Conclusions The metabolomics scanning of early gestation maternal plasma may identify those pregnancies that subsequently develop TTTS; in particular, downregulated fatty acid levels may be biologically plausible to be implicated in the pathogenesis of TTTS.

Comprehensive Metabolomic Profiling of Cord Blood and Placental Tissue in Surviving Monochorionic Twins Complicated by Twin-Twin Transfusion Syndrome With or Without Fetoscopic Laser Coagulation Surgery: A Retrospective Cohort Study

“…In the present study, disrupted fatty acid metabolism was observed in untreated TTTS fetuses’ umbilical cord plasma and placental tissue, which is consistent with our previous finding in the later diagnosed TTTS maternal serum collected at early pregnancy ( Yang et al, 2021 ). Compared with the FLC-treated group, the Un group had lower alpha-linolenic acid metabolism in placental metabolomes, and the recipients in the Un group also had less active biosynthesis of unsaturated fatty acids in the cord plasma metabolome.…”

“…However, since the metabolites in the amniotic fluid could be secreted by the placenta or fetal organs and their secretion could be induced by trophoblast or vessel destruction in FLC surgery or amniodrainage, we still lack solid evidence to confirm the sources of these perturbed metabolites and their role in the pathogenesis of TTTS. Another newly published retrospective cohort study conducted by our team also reported disrupted amino acid and fatty acid metabolism in serum samples prospectively collected during the first gestational trimester of TTTS pregnancies ( Yang et al, 2021 ).…”

“…However, notwithstanding the considerable merits of metabolomic studies, due to the low overall incidence of TTTS and the difficulty in retrieving biological samples, very little evidence has been reported to elucidate metabolomic disturbances in twins suffering from TTTS, not to mention those who underwent FLC procedures. In our analysis of maternal plasma, our laboratory previously found that TTTS-complicated pregnant women had an altered metabolome before 16 weeks of gestation, and these alterations included changes in fatty acids, Krebs cycle intermediates, and amino acids ( Yang et al, 2021 ). Correspondingly, it was previously implied that the altered carbohydrate and fatty acid profile in the amniotic fluid of the TTTS-complicated recipient co-twin has a close association with FLC treatment, fetal cardiovascular dysfunction, and anomalies ( Dunn et al, 2016 ).…”