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Summary: Background: Fetal growth restriction (FGR) can negatively affect lung development, leading to increased respiratory morbidity and reduced lung function later in life. Studies regarding the impact of FGR on lung function in singletons are influenced by genetic, obstetric, and maternal factors. To overcome these confounding factors, we aim to investigate lung function in identical twins with selective FGR (sFGR). Methods: Lung function assessments were performed in identical twins with sFGR born in our centre between March 1, 2002, and December 31, 2017, aged between 5 and 17 years. sFGR was defined as birthweight discordance ≥20%. Outcome measures consisted of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (DLCO) and were compared between the smaller and larger twin. Findings: Thirty-nine twin pairs performed spirometry of sufficient quality. Median gestational age at birth was 34.3 (interquartile range (IQR) 32.1–36.0) weeks with median birthweights of 1500 (IQR 1160–1880) grams and 2178 (IQR 1675–2720) grams for the smaller and larger twin, respectively. Smaller twins had significantly lower z-scores for FEV1 (−0.94 versus −0.41, p = 0.0015), FVC (−0.56 versus −0.06, p

Background: Fetal growth restriction (FGR) is thought to negatively affect lung development resulting in increased respiratory morbidity. However, research performed in singletons is often limited by a certain level of bias caused by individual differences in genetic constitution, obstetrical and maternal factors. Methods: Respiratory morbidity was compared between the smaller and the larger twin in monochorionic twins with selective fetal growth restriction (sFGR), defined as a birth weight discordance ≥ 20%, born in our center between 2010 and 2019 in this retrospective study. Respiratory distress syndrome (RDS) was diagnosed based on the clinical picture of a neonate with respiratory failure requiring mechanical ventilation and/or surfactant, confirmed by a chest X-ray. Bronchopulmonary dysplasia (BPD) was diagnosed when the neonate required treatment with >21% oxygen for at least 28 days. Findings: Median gestational age at birth for the 94 included pregnancies was 32.4 (IQR 30.4–34.3) weeks. Within-pair analyses showed that the prevalence of RDS was lower in the smaller twin compared to the larger twin, 19.1% (18/94) vs 34.0% (32/94), respectively (p = 0.004). The odds of RDS for the larger twin was doubled (OR 2.1 (CI95% 1.3–3.5). In contrast, the rate of BPD in the smaller twin was higher as opposed to the larger twin, 16.7% (15/90) vs 6.7% (6/89), respectively (p = 0.008), with a more than doubled odds (OR 2.5 (CI95% 1.3–4.9)). Interpretation: Despite being genetically identical, sFGR twins have different respiratory outcomes. Adverse growth condition in utero in the smaller twin is associated with a reduced odds of RDS at birth but a more than doubled odds of BPD, reflecting the pathophysiologic adverse effect of growth restriction on lung development. Funding: The Dutch Heart Foundation (2017T075).

To compare the whole genomic microRNA (miRNA) between the selective fetal growth restriction (sFGR) twin and the normally growing (control) co-twin in monochorionic (MC) twin pregnancies. MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled by microarray. The ratio of the placental miRNA of the sFGR twin to that of the normally larger co-twin were calculated and compared to that of the control twin pairs. The miRNA microarray intensity amongst normal and sFGR large and small twins are shown. The expression data presented here will facilitate other researchers who are working on placental regulation and mechanism in pregnancy complicated by fetal growth restriction.The dataset supports the research article entitle “Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies” [1].

Introduction: This study investigated the impact of the shared intertwin circulation in unequally divided monochorionic (MC) placentas on fetal growth., Methods: This retrospective analysis included color-dyed, unequally shared placentas from two tertiary centers. Exclusions included twin-twin transfusion syndrome, twin anemia polycythemia sequence, and lethal anomalies. Measurement of the external diameters and areas of the artery-to-artery (AA), artery-to-vein (AV), and vein-to-vein (VV) anastomoses was performed. The ratio of the shared circulation (AV ratio) was determined by comparing the areas of the summed venous components of shared AV anastomoses to those in the individual AV anastomoses of the smaller placental part. The birth weight ratio/placental ratio (BWR/PR), total AV size areas and net AV transfusion were calculated. Univariable and multivariable linear regressions were performed to assess the relationship between BWR/PR, the AV ratio, the areas of the different anastomoses and cord insertion discordance., Results: Among 352 placentas, 97 % (340) had intertwin AV anastomoses, and 50 % (176) were from pregnancies with selective growth restriction. The AV ratio, AA, VV, total AV areas, and cord insertion discordance negatively correlated with BWR/PR. Multivariable linear regression confirmed the independent negative association between BWR/PR and the AV ratio, suggesting that a larger shared circulation benefits the twin with the smaller placental part. Type III sFGR placentas exhibited the highest AV ratio, resulting in the lowest BWR/PR., Discussion: A larger shared circulation mitigates the impact of an unequally divided placenta on fetal growth. This effect surpasses the influence of AA and VV diameters and is most prominent in Type III sFGR placentas., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are common complications in monochorionic diamniotic (MCDA) pregnancies. The Diffusion-rElaxation Combined Imaging for Detailed Placental Evaluation (DECIDE) model, a placental-specific model, separates the T2 values of the fetal and maternal blood from the background tissue and estimates the fetal blood oxygen saturation. This study investigates diffusion and relaxation differences in uncomplicated MCDA pregnancies and MCDA pregnancies complicated by TTTS and sFGR in mid-pregnancy., Methods: This prospective monocentric cohort study included uncomplicated MCDA pregnancies and pregnancies complicated by TTTS and sFGR. We performed MRI with conventional diffusion-weighted imaging (DWI) and combined relaxometry - DWI-intravoxel incoherent motion. DECIDE analysis was used to quantify different parameters within the placenta related to the fetal, placental, and maternal compartments., Results: We included 99 pregnancies, of which 46 were uncomplicated, 12 were complicated by sFGR and 41 by TTTS. Conventional DWI did not find differences between or within cohorts. On DECIDE imaging, fetoplacental oxygen saturation was significantly lower in the smaller member of sFGR (p = 0.07) and in both members of TTTS (p = 0.01 and p = 0.004) compared to the uncomplicated pairs. Additionally, average T2 relaxation time was significantly lower in the smaller twin of the sFGR (p = 0.004) compared to the uncomplicated twins (p = 0.03)., Conclusion: Multicompartment functional MRI showed significant differences in several MRI parameters between the placenta of uncomplicated MCDA pregnancies and those complicated by sFGR and TTTS in mid-pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Psychosocial development in monochorionic (MC) twins born after selective fetal growth restriction (sFGR) has been unreported to date, despite its importance for daily functioning and future relationships., Aims: To investigate psychosocial development, attachment and school functioning in MC twins with sFGR and compare outcomes with the general population and between smaller and larger twins., Study Design: Observational cohort study., Subjects: MC twins with sFGR (defined as a birth weight discordance ≥20 %) born between 2002 and 2017 and aged 3-17 years., Outcome Measures: Multiple parent report questionnaires: the Child Behavior Checklist (social-emotional development and behavior), the (Early) Childhood Behavior Questionnaire Very Short Form (temperament), the Attachment Insecurity Screening Inventory (attachment) and a school functioning questionnaire., Results: Median age for the 48 twin pairs was 11 (interquartile range (IQR) 8-13) years. Attachment insecurity for both twins was higher than in the general population for ambivalence/resistance (34 % (21/62) vs. 16 %, p = 0.024) and total attachment insecurity (35 % (22/62) vs. 16 %, p = 0.016). Smaller twins had more internalizing behavioral problems, i.e. negative emotions and behaviors turned inwards (22 % (10/46) vs. 11 % (5/46), p = 0.021) and a higher negative affect, i.e. more likely to experience negative emotions (3.2 (2.9-3.7) vs. 2.9 (2.2-3.2), p = 0.009) than larger twins, as well as a lower secondary school level (p = 0.031)., Conclusion: MC twins with sFGR have more ambivalent/resistant attachment insecurity following the complicated pregnancy course. Smaller twins have a tendency towards negative emotions and internalizing behaviors compared to larger twins, indicating an increased sensitivity for depression and anxiety., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In monochorionic twin pregnancies, the fetuses share a single placenta. When this placenta is unequally shared, a discordant antenatal growth pattern ensues resulting in high rates of perinatal morbidity and mortality. Understanding placental pathophysiology is paramount in devising feasible antenatal management strategies. Unequal placental sharing is not the sole determinant of birthweight discordance as there is no one-to-one relationship with placental share discordance. Placental angioarchitecture, especially the presence of large bidirectional anastomoses, is thought to affect this relationship by allowing for a compensatory intertwin blood flow., Objective: This study aimed to assess whether placental angioarchitecture can affect birthweight discordance in live-born monochorionic twins, the aim of our study was 2-fold: (1) to assess the relationship between birthweight discordance and placental share discordance and (2) to examine to what extent large bidirectional anastomoses can compensate for the effect of unequal placental sharing on birthweight discordance, with a subgroup analysis for umbilical artery Doppler flow patterns in cases with a birthweight discordance of ≥20%., Study Design: This was a retrospective cohort study that included monochorionic twin pregnancies observed in our center between March 2002 and June 2021, in which twins with a birthweight discordance of ≥20% were classified according to umbilical artery Doppler flow patterns of the smaller twin. We excluded cases with twin-twin transfusion syndrome and twin anemia polycythemia sequence. Monochorionic placentas of live-born twins were injected with dye, and images were saved for computer measurements of placental sharing and the diameter of anastomoses. Univariate linear regressions of the relationship between placental share discordance and birthweight discordance (both calculated as larger weight or share-smaller weight or share/larger weight or share×100%) and the relationship between arterioarterial and venovenous diameters and birthweight ratio/placental territory ratio were performed., Results: A total of 449 placentas were included in the analysis. Placental share discordance was positively correlated with birthweight discordance (β coefficient, 0.325; 95% confidence interval, 0.254-0.397; P<.0001). The arterioarterial diameter was negatively correlated with birthweight ratio/placental territory ratio (β coefficient, -0.041; 95% confidence interval, -0.059 to -0.023; P<.0001), meaning that an increase in arterioarterial diameter leads to less birthweight discordance than expected for the amount of placental share discordance. There was no relationship between venovenous diameter and birthweight ratio/placental territory ratio (β coefficient, -0.007; 95% confidence interval, -0.027 to 0.012; P=.473)., Conclusion: Birthweight discordance in monochorionic twins was strongly associated with placental share discordance. Large arterioarterial anastomoses can mitigate the effect of unequal placental sharing., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Monochorionic twin pregnancies have an increased risk of morbidity and mortality. Due to the advancements in screening and treatment strategies, mortality rates have decreased. Improving survival rates demands a shift in scope toward long-term outcomes. In this review, we focus on neurodevelopmental outcome in survivors from complicated monochorionic twin pregnancies, including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), acute peripartum TTTS, acute perimortem TTTS, selective fetal growth restriction (sFGR) and monoamnionicity. Our aim is to provide an overview of the current knowledge on the long-term outcome in survivors, including psychomotor development and quality of life, and provide recommendations for future research and follow-up programs., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Monochorionic (MC) twin pregnancies are at increased risk of neonatal morbidity and mortality due to the shared placenta with vascular connections that can give rise to various complications, including twin-twin transfusion syndrome, twin anemia polycythemia sequence (TAPS), selective fetal growth restriction, and other hematological imbalances at birth. Each complication presents its own challenges and considerations in the neonatal period. Measurement of hemoglobin levels and reticulocyte count is required to establish a correct diagnosis. Placenta dye injection is needed to properly distinguish between the various conditions. Risk factors for adverse outcome in MC twins include prematurity, severe cerebral injury, and the type of MC pregnancy complication. We, therefore, recommend cerebral ultrasound examinations in all complicated MC twins at birth to rule out a severe brain injury. Lastly, we strongly encourage screening for hearing loss using automated auditory brainstem response in all spontaneous TAPS donors to prevent permanent speech development delay., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The underlying pathomechanism in placenta-related selective fetal growth restriction in monochorionic diamniotic twin pregnancy is not known., Objective: This study aimed to investigate any differences in placental transcriptomic profile between the selectively growth-restricted twins and the normally grown cotwins in monochorionic diamniotic twin pregnancies., Study Design: This was a prospective study of monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction. Placental biopsy specimens were obtained from the subjects in the delivery suite. The placental transcriptome of the selectively growth-restricted twin was compared with that of the normally grown cotwin. This study was divided into 2 stages: (1) gene discovery phase in which placental tissues from 5 monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction plus 2 control twin pregnancies underwent transcriptome profiling, and transcriptome profiling was carried out using whole-genome RNA sequencing; and (2) validation phase in which placental tissues from 13 monochorionic diamniotic twin pregnancies with selective fetal growth restriction underwent RNA and protein validation. RNA and protein expression levels of candidate genes were determined using quantitative real-time polymerase chain reaction and immunohistochemistry staining., Results: A total of 1429 transcripts were differentially expressed in the placentae of selectively growth-restricted twin pairs, where 610 were up-regulated and 819 were down-regulated. Endoplasmic reticulum lectin and mannose 6-phosphate receptor were consistently differentially up-regulated in all placentae of selectively growth-restricted twins. Quantitative real-time polymerase chain reaction and immunohistochemistry staining were used to validate the results (P<.05)., Conclusion: The expression of endoplasmic reticulum lectin and mannose 6-phosphate receptor, which are important for angiogenesis and fetal growth, was significantly increased in the placentae of selectively growth-restricted twin of a monochorionic twin pair., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Twin pregnancies are more likely to be affected by fetal growth restriction (FGR), preterm birth and perinatal loss. The management of fetal growth restriction in multiple pregnancy, particularly where only one fetus is affected is complicated by the need to consider the interests of both twins. Selective growth restriction in monochorionic (MC) twins is a pathophysiological process distinct from FGR in dichorionic (DC) pregnancies and management demands an understanding of the monochorionic placental structure and interdependent fetal circulations. The introduction of fetal therapy has introduced a range of potential interventions for the antenatal management of sFGR including selective fetal reduction and laser photocoagulation of the placental communicating vessels. This review summarizes up to date evidence on diagnosis, classification and management of sFGR and considers research directions likely to be of benefit in the future., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Monochorionic twin pregnancies are well known to be at risk for a variety of severe complications, a true challenge for the maternal-fetal medicine specialist. With current standards of care, monochorionicity should be established in the first trimester. Subsequently, frequent monitoring using the appropriate diagnostic tools, and in-depth knowledge about the pathophysiology of all possible clinical presentations of monochorionic twin abnormalities, should lead to timely recognition, and appropriate management. Virtually all unique diseases found in monochorionic twins are directly related to placental angio-architecture. This, however, cannot be established reliably before birth. The clinician needs to be aware of the definitions and symptoms of twin-to twin transfusion syndrome, selective fetal growth restriction, twin anaemia-polycythaemia sequence, and twin reversed arterial perfusion sequence, to be able to recognise each disease and take the required action. In this chapter, we address current standards on correct and timely diagnoses of severe complications of monochorionic twin pregnancies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)