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Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome.

ABSTRACT: Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress.

SUBMITTER: Parchem JG

PROVIDER: S-EPMC10415929 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome.

Parchem Jacqueline G JG Fan Huihui H Mann Lovepreet K LK Chen Qiuying Q Won Jong H JH Gross Steven S SS Zhao Zhongming Z Taegtmeyer Heinrich H Papanna Ramesha R

iScience 20230720 8

Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples fro ...[more]

PMID: 37575192

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Project description:ObjectiveTo investigate the fetal growth pattern after fetoscopic laser photocoagulation (FLP) in twin-twin transfusion syndrome (TTTS) and the effect of FLP on placental perfusion and intrauterine growth restriction (IUGR) incidence.MethodsTTTS cases with a live delivery of both twins at least 28 days after FLP and with a neonatal follow-up at our hospital at least 60 days after delivery were included. The biometric data obtained before FLP (based on ultrasound); time point M1), upon birth (M2), and at neonatal follow-up (M3) were analyzed. The body weight discordance (BWD) was defined as (estimated fetal weight [body weight] of the recipient twin - estimated fetal weight [body weight] of the donor twin)/(estimated fetal weight [body weight] of the recipient twin) × 100%. Total weight percentile (TWP) was defined as the donor + recipient twin weight percentile; the TWP indirectly reflected the total placental perfusion.Resultsthe BWDs decreased from M1 to M2 to M3 (24.6, 15.9, and 5.1, respectively, p < 0.001, repeated measurements). The weight percentiles of recipient twins decreased after FLP, that is, from M1 to M2 (53.4% vs. 33.6%, respectively, p < 0.001, least significant difference [LSD] test). However, the weight percentiles of donor twins increased after delivery, that is, from M2 to M3 (13.2% vs. 26.2%, respectively, p < 0.001, LSD test). Moreover, the TWPs decreased after FLP, that is, from M1 to M2 (66.2% vs. 46.8%, respectively, p = 0.002, LSD test) and increased after delivery, that is, from M2 to M3 (46.8% vs. 63.2%, respectively, p = 0.024, LSD test). The IUGR incidences in donor twins were significantly lower after FLP (77.4% vs. 56.6%, respectively, p = 0.019, McNemar test) and further decreased after delivery (56.6% vs. 37.7%, respectively, p = 0.041, McNemar Test); however, no significant difference was observed in recipient twins' IUGR incidences among M1, M2, and M3. The donor twin had catch- up growth in body weight, height, and head circumference after delivery, and the recipient twin had catch-up growth in only body height after delivery.Conclusionsthe BWD decreased after FLP in fetuses with TTTS mainly because of the decreased weight percentiles of recipient twins. Moreover, it further decreased after delivery mainly because of the increased weight percentiles of donor twins. FLP not only decreased placental perfusion but also improved the TTTS prognosis because of reduced BWD and donor twin IUGR incidence.

Project description:BackgroundTwin-to-twin transfusion syndrome (TTTS) is a serious complication of 10-15% of twin or triplet pregnancies in which multiple fetuses share a single placenta. Communicating placental vessels allow one fetus (the donor) to pump blood to the other (the recipient). Mortality rates without intervention are high, approaching 100% in some series, with fetal deaths usually due to cardiac failure. Surgical correction using laser photocoagulation of communicating placental vessels was developed in the 1980s and refined in the 1990s. Since it was introduced in Victoria in 2006, laser surgery has been performed in approximately 120 pregnancies. Survival of one or more fetuses following laser surgery is currently > 90%, however the neurodevelopmental outcomes for survivors remain incompletely understood. Prior to laser therapy, at least one in five survivors of TTTS had serious adverse neurodevelopmental outcomes (usually cerebral palsy). Current estimates of neurological impairment among survivors following laser surgery vary from 4 to 31% and long-term follow-up data are limited.MethodsThis paper describes the methodology for a retrospective cohort study in which children aged 24 months and over (corrected for prematurity), who were treated with laser placental photocoagulation for TTTS at Monash Health in Victoria, Australia, will undergo comprehensive neurodevelopmental assessment by a multidisciplinary team. Evaluation will include parental completion of pre-assessment questionnaires of social and behavioural development, a standardised medical assessment by a developmental paediatrician or paediatric neurologist, and age-appropriate cognitive and academic, speech and fine and gross motor assessments by psychologists, speech and occupational therapists or physiotherapists. Assessments will be undertaken at the Murdoch Children's Research Institute/Royal Children's Hospital, at Monash Health or at another mutually agreed location. Results will be recorded in a secure online database which will facilitate future related research.DiscussionThis will be the first study to report and evaluate neurodevelopmental outcomes following laser surgery for twin-to-twin transfusion syndrome in Victoria, and will inform clinical practice regarding follow-up of children at risk of adverse outcomes.

Dataset Information

Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome.

Publications

Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome.

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