The prediction, diagnosis and management of complications in monochorionic twin pregnancies

Monochorionic twin pregnancies are high-risk and closely monitored antenatally. A systematic review revealed no existing predictive factors for twin-twin transfusion syndrome (TTTS), growth restriction, or intrauterine fetal death (IUFD). The Optimal Management of Monochorionic Twins (OMMIT) study found that first trimester inter-twin nuchal translucency discordance, crown-rump length discordance, β-hCG, PAPP-A, AFP, PlGF and sFlt-1 do not predict adverse outcome. A difference was seen in novel second trimester biomarkers: in the recipient twin amniotic fluid metabolites pre- and post-fetoscopic laser ablation; and a relationship with recipient twin cardiac function was demonstrated. Discovery work on miRNA in second trimester maternal serum of TTTS pregnancies found no difference compared to uncomplicated monochorionic twin pregnancies. A systematic review provided a more personalised risk prediction for the surviving co-twin in single IUFD, including that that the rate of abnormal brain imaging is 20% and the IUFDs occurring at 14-28 weeks are at higher risk. A preliminary study of parent-fetal antenatal and postnatal attachment and depression in TTTS pregnancies found maternal attachment increased postnatally and depressive symptoms decreased, whereas paternal scores did not change. This thesis has reported exciting findings which have clinical implications, and advance knowledge of complicated monochorionic twin pregnancies

Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status

Scope: Low maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression. Methods and results: A prospective observational study recruited pregnant adolescents and assessed third trimester folate status and placental function. miRNA array, QPCR, and bioinformatics identified placental miRNAs and target genes. Low maternal folate status is associated with higher incidence of SGA infants (28% versus 13%, p < 0.05) and placental dysfunction, including elevated trophoblast proliferation and apoptosis (p < 0.001), reduced amino acid transport (p < 0.01), and altered placental hormones (pregnancy-associated plasma protein A, progesterone, and human placental lactogen). miR-222-3p, miR-141-3p, and miR-34b-5p were upregulated by low folate status (p < 0.05). Bioinformatics predicted a gene network regulating cell turnover. Quantitative PCR demonstrated that key genes in this network (zinc finger E-box binding homeobox 2, v-myc myelocytomatosis viral oncogene homolog (avian), and cyclin-dependent kinase 6) were reduced (p < 0.05) in placentas with low maternal folate status. Conclusion: This study supports that placental dysfunction contributes to impaired fetal growth in women with low folate status and suggests altered placental expression of folate-sensitive miRNAs and target genes as a mechanistic link

First trimester ultrasound measurements and maternal serum biomarkers as prognostic factors in monochorionic twins: a cohort study

Background: Monochorionic twin pregnancies are high-risk of adverse outcomes, but it is not possible to predict which pregnancies will develop complications. The aim of the study was to evaluate, in monochorionic twin pregnancies, whether first trimester ultrasound (nuchal translucency [NT], crown-rump length [CRL]) and maternal serum biomarkers (alpha-fetoprotein (AFP), soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF)) are prognostic factors for fetal adverse outcome composite, twin-twin transfusion syndrome (TTTS), growth restriction, and intrauterine fetal death (IUFD). Methods: Cohort study of 177 monochorionic diamniotic twin pregnancies. Independent prognostic ability of each factor was assessed by multivariable logistic regression, adjusting for standard prognostic factors. Factors were analysed as continuous data, thus the reported ORs relate either 1% change in NT or CRL inter-twin percentage discordance, or one unit of measure in each serum biomarker. Results: The odds of the fetal adverse outcome composite was significantly associated with increased NT inter-twin percentage discordance (adjusted OR 1.03 [95%CI 1.01,1.06]), and CRL inter-twin percentage discordance (adjusted OR 1.17 [95%CI 1.07,1.29]). TTTS was significantly associated with increased NT discordance (adjusted OR 1.06 [95%CI 1.03,1.10]), and decreased PlGF (adjusted OR 0.42 [95%CI 0.19,0.93]). Antenatal growth restriction was significantly associated with increased CRL discordance (adjusted OR 1.20 [95%CI 1.08,1.34]). Single and double IUFD were associated with decreased PlGF (adjusted OR 0.34 [95%CI 0.12,0.98]) and (adjusted OR 0.18 [95%CI 0.05,0.58]) respectively. Conclusion(s): This study has identified potential individual prognostic factors in the first trimester (fetal biometric and maternal serum biomarkers) that show promise but require further robust evaluation in a larger, prospective series of MC twin pregnancies, so that their usefulness both individually and in combination can be defined. Trial registration: ISRCTN 13114861 (retrospectively registered