Abstract
ObjectiveMicroRNAs (miRNAs) are used as biomarkers in cardiovascular disease and cancer. miRNAs are involved in placental development but have not previously been investigated in twin‐twin transfusion syndrome (TTTS). Our aim is to explore the miRNA profile of TTTS pregnancies.MethodInitial miRNA profiling was performed using a reverse transcription polymerase chain reaction (RT‐PCR) panel on maternal serum samples taken from five women prior to fetoscopic laser ablation for TTTS and compared with serum samples from five women with uncomplicated monochorionic diamniotic twin pregnancies. Validation RT‐PCR was performed in an additional cohort of eight TTTS pregnancies and eight uncomplicated pregnancies.ResultsMedian gestational age at sampling in the TTTS and control groups was 20+0 weeks (interquartile range [IQR], 19+4‐20+0) and 20+2 weeks (IQR, 20+0‐20+2), respectively. All samples passed quality control. One control sample was excluded as a biological outlier. Thirty‐one of 752 miRNAs were significantly different: 17 were upregulated and 14 downregulated in the TTTS group, although they did not remain significant following Benjamini‐Hochberg correction for multiple testing. The six miRNAs chosen for validation demonstrated no significant difference.ConclusionThis is the first study to investigate miRNA changes in TTTS pregnancies. We did not demonstrate a statistically significant difference in miRNAs in TTTS pregnancies, but further investigation is required.
Highlights
Twin‐twin transfusion syndrome (TTTS) complicates up to 15% of monochorionic diamniotic (MCDA) twins and if untreated is associated with a perinatal mortality of 80% to 90%1 and significant neurodevelopmental morbidity.[2]
Initial miRNA profiling was performed using a reverse transcription polymerase chain reaction (RT‐PCR) panel on maternal serum samples taken from five women prior to fetoscopic laser ablation for TTTS and compared with serum samples from five women with uncomplicated monochorionic diamniotic twin pregnancies
From the initial profiling array, eight candidate miRNAs were identified for validation based on being significantly different in the TTTS compared with control samples, prior to Benjamini‐Hochberg correction for multiple testing; being present in all investigation cohort samples; having validated targeted functional genes with strong evidence of miRNA‐target interaction (MTI) reported on MiRTarBase[39]; and biological plausibility for association with TTTS based on a literature search using keywords: placenta, pregnancy, twin, maternal, gestation, cardio‐$, renal‐$, vascul‐$, angio‐$, trophoblast, and fetal
Summary
Twin‐twin transfusion syndrome (TTTS) complicates up to 15% of monochorionic diamniotic (MCDA) twins and if untreated is associated with a perinatal mortality of 80% to 90%1 and significant neurodevelopmental morbidity.[2]. Timely detection of TTTS allows treatment by fetoscopic laser ablation (FLA) of the placental vascular anastomoses with a potential to modify the underlying disease process and significantly improve outcome.[7] The theoretical use of maternal circulating biomarkers in screening for TTTS in its preclinical state and aiding in the definition of adverse pregnancy outcome in a monochorionic twin pregnancy would be beneficial, either alone or in combination with ultrasound findings.[8,9]. We hypothesized that there was a difference in human maternal serum miRNAs in pregnancies complicated with TTTS compared with uncomplicated matched MCDA twin pregnancies and that there is the potential for these molecules to be used as “biomarkers” of disease
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