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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

Background: Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders. Methods: This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ

Objective: Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. Methods: This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10th percentile and intertwin EFW discordance of ≥ 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis.Results: A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. Conclusions: Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort.

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

OBJECTIVE Type III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. Our objective was to describe the prospective risk of fetal death and the risk of adverse neonatal outcomes in a contemporary cohort. METHODS We retrospectively reviewed all monochorionic diamniotic twin pregnancies complicated by type III sIUGR managed at nine fetal centers over a 12-year time period. Higher order multiples, major fetal anomalies or other monochorionicity related complications at initial presentation were excluded. Fetal and neonatal outcomes were collected and management strategies were reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture proven sepsis, necrotizing enterocolitis (NEC) requiring treatment, intraventricular hemorrhage (IVH) >grade I, retinopathy of prematurity (ROP) >stage II or periventricular leukomalacia (PVL). The prospective risk of fetal death and the risk of neonatal complications at each gestational age were evaluated. RESULTS We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies which underwent selective reduction (n=18, 5.5%), there were 51 (8.3%) non-iatrogenic fetal deaths in 35 pregnancies (11.3%). Single deaths occurred in 19 (5.8%) pregnancies and double deaths in 16 (4.9%) pregnancies. The prospective risk of non-iatrogenic fetal death per fetus declined from 8.1% (95% CI 5.95-10.26) at 16 weeks, to less than 2% (95% CI 0.59-2.79) after 28.4 weeks and to less than 1% (95% CI -0.30-1.89) beyond 32.6 weeks. In otherwise uncomplicated type III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcomes was 29% (31/107 neonates). For twin pregnancies that continued to 34 weeks there was a very low risk of fetal demise (0.7%) and a low risk of adverse outcomes (11%). CONCLUSIONS In this contemporary cohort from tertiary fetal centers, the risk of fetal death in type III sIUGR was lower than previously reported. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can safely continue beyond 33 weeks of gestation. This article is protected by copyright. All rights reserved.

OBJECTIVE Little is known regarding fetal growth patterns of monochorionic twins complicated by type 3 selective fetal growth restriction (sFGR). We aimed to assess fetal growth and Doppler patterns in type 3 sFGR across gestation and evaluate the effect of changing Doppler flow patterns on growth and intertwin weight discordance. METHODS We retrospectively reviewed all type 3 sFGR pregnancies managed at nine fetal centers over a 12-year time period. Higher-order multiples, major fetal anomalies, or other monochorionicity-related complications at initial presentation were excluded. Estimated fetal weights (EFW) for each twin pair in each of five gestational age blocks (16-20, 21-24, 25-28, 29-32 and above 32���weeks' gestation) were reviewed and compared to singleton growth as well as uncomplicated monochorionic twin growth. EFW and intertwin growth discordance were compared between pregnancies with normalization of umbilical artery Dopplers of the smaller twin and those with persistently abnormal Dopplers . RESULTS 328 pregnancies (656 fetuses) met the study criteria. In type 3 sFGR, the smaller twin was smaller than the average singleton fetus (z-score ranging from -1.52 at 16���weeks to -2.7 at 36���weeks) and the average monochorionic twin (z-score ranging from -1.73 at 16���weeks to -1.49 at 36���weeks), throughout the entire pregnancy, while the larger twin was larger than an average singleton fetus until 22���weeks' gestation and similar in weight to an average monochorionic twin throughout gestation. As pregnancy advanced, both twin's growth velocities decreased with the larger twin remaining appropriately grown and the smaller twin becoming more growth restricted. Intertwin growth discordance remained stable throughout gestation. In multivariable longitudinal modelling, normalization of fetal Dopplers was associated with better growth of the smaller twin (p=0.002) but not the larger twin (p=0.1), without affecting the intertwin growth discordance (p=0.08). CONCLUSION Abnormal fetal growth of the smaller twin in type 3 sFGR was evident from early in pregnancy, while the larger twin's growth remained normal throughout gestation. Normalization of Dopplers resulted in improved fetal growth of the smaller twin. This article is protected by copyright. All rights reserved.

OBJECTIVE:To investigate the predictive value of delta middle cerebral artery - peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) compared to cut-off MCA-PSV values (>1.5 MoM in the donor, < 1.0 MoM in the recipient) for the diagnosis of twin anemia polycythemia sequence (TAPS).METHODS:Retrospective consecutive cohort study comprising consecutive uncomplicated monochorionic twins and twins with postnatal TAPS between 2003 and 2017 in the Dutch national referral center for fetal therapy. We compared the accuracy to predict postnatal TAPS between the current method using the specific MCA-PSV cut-off values (>1.5 MoM in the donor and 0.5 MoM.RESULTS:In total, 45 uncomplicated monochorionic and 35 TAPS twins were analyzed. The sensitivity and specificity of the cut-off MCA-PSV values (>1.5 MoM, 0.5 MoM, but did not reach both the cut-off MCA-PSV levels (>1.5 MoM, CONCLUSION:Delta MCA-PSV > 0.5 MoM has a higher diagnostic accuracy for predicting TAPS compared to the currently used MCA-PSV cut-off values. We therefore propose a new antenatal classification system. In case of a delta MCA-PSV > 0.5 MoM on Doppler ultrasound, but with normal MCA-PSV values in donor or recipient, obstetricians should be aware of the therapeutic implications and neonatal morbidities associated with TAPS. This article is protected by copyright. All rights reserved.

In this thesis we describe that Twin Anemia Polycythemia Sequence (TAPS) is a form of chronic feto-fetal transfusion in monochorionic (identical) twins based on a small amount of blood transfusion through very small anastomoses. For the antenatal diagnosis of TAPS, Middle Cerebral Artery __ Peak Systolic Velocity (MCA-PSV) Doppler measurements appear to be an accurate predictor for anemia and polycythemia. If antenatally detected, fetoscopic laser therapy might improve pregnancy outcome by treating the cause, and thereby prolonging the pregnancy. Another very important finding for the prevention of post-laser TAPS is that by using the Solomon technique for the treatment of Twin-Twin Transfusion Syndrome (TTTS) the incidence of post-laser TAPS is reduced. If laser is not feasible and intra uterine transfusion (IUT) is the preferred treatment option, we suggest adding partial exchange transfusion (PET) to prevent severe polycythemia and possible complications as limb necrosis and severe cerebral injury. Long-term neurodevelopmental outcome in post-laser TAPS is 9% and seems comparable with long-term outcome after treated TTTS. In conclusion, with this thesis we increased our knowledge on the pathophysiology, the diagnostic tools, management options, short and long-term outcome of TAPS.