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Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: This study aims to examine the association between the presence and size of a vein-to-vein (VV) anastomosis and birth weight discordance relative to placental discordance in monochorionic diamniotic twin pregnancies., Methods: Placentas of two previous prospective studies were included in this retrospective analysis. After injection with color dye, we measured the placental surface of each twin and VV, artery-to-artery (AA), and artery-to-vein (AV) anastomoses on a digital photograph. We calculated the birth weight ratio (BWR), placental ratio (PR), and birth weight ratio/placenta ratio (BWR/PR), as well as total AV size and net AV transfusion. Placental characteristics were compared between placentas with and without VV anastomoses. We performed univariate analyses to assess the following predictors for BWR/PR: VV size, AA size, total AV size, and net AV transfusion. Multivariate analysis was then performed, including the variables significant in univariate analysis., Results: We analyzed 247 placentas: 58 (23%) with VV anastomoses and 189 without (77%). The BWR and PR were higher in the group with VV. In contrast, BWR/PR was lower in the group with VV anastomoses than in those without. The size of AA anastomoses was larger in placentas with VV anastomoses than in those without. In univariate analysis, VV size and AA size were significantly associated with BWR/PR. However, in multivariate regression, only VV size remained significantly associated with the BWR/PR., Discussion: VV anastomoses are associated with a decreased birth weight discordance relative to the placental sharing discordance, independent of the AA anastomoses., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Our objective was to explain the clinical presentations of sustained arteriovenous anastomotic transfusion of blood after incomplete laser therapy in twin-to-twin transfusion syndrome (TTTS). We extended our mathematical model of TTTS by adding the dynamics of hematocrit, and simulated incomplete laser therapy, first, by leaving one patent opposite arteriovenous anastomosis from the recipient to the donor and, second, by leaving one patent arteriovenous anastomosis from the donor to the recipient. In both simulations we reproduced the clinical observation of severe hematocrit discordance preceding delayed amniotic fluid imbalance. In conclusion, incomplete laser therapy may cause a severe circulatory imbalance between the twins which presents predominantly as discordant hematocrits rather than discordant amniotic fluid volumes as in primary TTTS. These results imply that the anemia-polycythemia sequence is a sensitive mechanism to identify transfusion reversal after complicated laser therapy, confirming the suggested role of middle cerebral artery peak systolic velocity Doppler measurements as a useful method of follow-up.