The Current Knowledge of Cerebral Magnetic Resonance Imaging in Monochorionic Twins: A Systematic Review of the Last 20 Years.

The distinct placental angioarchitecture in monochorionic (MC) pregnancies increases the risk of complications such as twin-twin transfusion syndrome (TTTS), twin anemia polycythemia sequence (TAPS), and selective fetal growth restriction (sFGR). The aim of this systematic review was to evaluate the incidence, type, and severity of cerebral injury and structural brain development on fetal and/or neonatal cerebral magnetic resonance imaging (MRI) in MC twins with or without complications. Twenty-three studies were included, covering a wide range of complications observed during MC pregnancies, with studies involving sIUFD (n = 12), TTTS (n = 7), mixed complications (n = 2), TAPS (n = 1), and uncomplicated MC pregnancy (n = 1). TAPS and sFGR were largely underrepresented in the current literature. The included studies reported that MC pregnancies with single intrauterine fetal demise (sIUFD) are most at risk for cerebral injury during the fetal period. The overall median incidence of cerebral injury after sIUFD was 28.3% (0-55%). Severe antenatal cerebral injury after sIUFD was detected antenatally in 6.5% (0-36%) of the cases. Three of the included studies described the incidence, type, and severity of cerebral injury on neonatal MRI in MC twins. Structural brain development based on cerebral biometry was only assessed in two studies, revealing significantly smaller biometric measurements of the cerebrum in cases of single sIUFD or smaller twins compared to singleton pregnancies. To enhance our understanding of the potential risks and pathophysiological mechanisms associated with cerebral injury and structural brain development in MC twins, there is a need for future studies and standardized protocols using serial fetal and neonatal MRI imaging in addition to routine ultrasound imaging.

Neonatal management and outcome in complicated monochorionic twins: What have we learned in the past decade and what should you know?

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.

Large Hemoglobin Differences at Birth in Monochorionic Twins with a Placental Chorangioma and Delayed Cord Clamping.

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.

Twin Anemia Polycythemia Sequence in a Dichorionic Twin Pregnancy Leading to Severe Cerebral Injury in the Recipient.

Twin anemia polycythemia sequence (TAPS) is a form of chronic imbalanced feto-fetal transfusion through minuscule placental anastomoses leading to anemia in the TAPS donor and polycythemia in the TAPS recipient and has been reported only in monochorionic twins. We report a very unusual case of TAPS which developed in a dichorionic twin pair, born at a gestational age of 33+2. Twin 1 (recipient) was polycythemic and had a hemoglobin value of 22.4 g/dL, whereas twin 2 (donor) was anemic with a hemoglobin value of 9.8 g/dL and an increased reticulocyte count (72‰). Color dye injection of the placenta revealed the presence of a deep-hidden small veno-venous anastomosis. Dichorionicity was confirmed on histologic examination. Aside from respiratory distress syndrome, the donor twin had an uncomplicated neonatal course. The recipient twin developed a post-hemorrhagic ventricular dilatation requiring treatment with a ventriculoperitoneal shunt and Rickham reservoir. This report shows that in dichorionic twins, placental anastomoses can be present, which can lead to the development of TAPS with severe consequences. Therefore, when a pale and plethoric dichorionic twin pair is born, a complete diagnostic work-up is required, including a full blood count with reticulocytes and placental injection, to investigate the presence and nature of potential underlying feto-fetal transfusion. Once the diagnosis of TAPS has been established, cerebral ultrasound, hearing screening, and long-term follow-up are strongly recommended as these twins have increased risk for severe cerebral injury, hearing loss, and long-term neurodevelopmental impairment.

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.

Evaluation of Color Difference in Placenta with Twin Anemia Polycythemia Sequence.

Twin anemia polycythemia sequence (TAPS) occurs in 5% of monochorionic twins and is characterized by large inter-twin hemoglobin differences. The postnatal diagnostic criteria for TAPS are based on hematologic parameters and placental characteristics. Placental examination after birth shows that color of the maternal side between placental territories of the anemic and polycythemic twins is remarkably different. The color difference in TAPS placentas is higher compared to monochorionic placentas with acute peripartum feto-fetal transfusion; thus, this is used as an additional diagnostic criterion for TAPS. Software such as ImageJ enables the computer-based measurement of color intensity in TAPS placentas. However, a detailed method for the calculation of color differences between anemic and polycythemic components of TAPS placentas has not yet been described. The protocol presented here provides a step-by-step method for analyzing color differences in the maternal side of TAPS placentas using ImageJ software.

Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, p < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, p < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.

Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

OBJECTIVE: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome. METHODS: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated. RESULTS: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress. CONCLUSION: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

Prevalence, risk factors, and outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome: a large single-center case series.

BACKGROUND: Postprocedural amniotic band disruption sequence is a condition that is associated with intrauterine interventions, and it is characterized by a constriction of the limbs or umbilical cord by fibrous strands, leading to edema, amputation, and/or fetal demise. OBJECTIVE: To evaluate the prevalence of, risk factors for, and the outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome cases. STUDY DESIGN: All consecutive cases of twin-twin transfusion syndrome treated with fetoscopic laser coagulation of the vascular anastomoses at our center between January 2002 and March 2019 were included in the study. The occurrence of postprocedural amniotic band disruption sequence in these cases was recorded, and the potential risk factors were analyzed. RESULTS: Postprocedural amniotic band disruption sequence was detected, at birth, in 2.2% (15/672) of twin-twin transfusion syndrome cases treated with fetoscopic laser surgery, in both the recipients (10/15, 67%) and the donors (5/15, 33%). Postprocedural amniotic band disruption sequence primarily affected the lower extremities (11/15, 73%) and, less frequently, the upper extremities (2/15, 13%), both the upper and lower extremities (1/15, 7%), or the umbilical cord (1/15, 7%). Postprocedural amniotic band disruption sequence led to the amputation of toes in 5 of 15 cases (33%) and resulted in fetal demise because of constriction of the umbilical cord in 1 case (7%). The independent risk factors identified for postprocedural amniotic band disruption sequence were lower gestational age at laser surgery (odds ratio per week, 1.43; 95% confidence interval, 1.12-1.79; P=.003) and the presence of postprocedural chorioamniotic membrane separation on antenatal ultrasound examination (odds ratio, 41.66; 95% confidence interval, 5.44-319.25; P<.001). CONCLUSION: The prevalence of postprocedural amniotic band disruption sequence is low, but, when present, it may lead to severe consequences, with amputation of extremities or fetal demise occurring in more than one-third of the cases. Lower gestational age at the time of laser therapy and chorioamniotic membrane separation are independent risk factors for the postprocedural amniotic band disruption sequence.

Leukocyte Counts and Other Hematological Values in Twin-Twin Transfusion Syndrome and Twin Anemia-Polycythemia Sequence.

OBJECTIVE: The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). METHODS: We performed a retrospective cohort study in monochorionic twin pairs with TTTS or TAPS. TTTS and TAPS cases treated with fetoscopic laser surgery were excluded. Primary outcome was the difference in leukocyte levels at birth between donor and recipient twins and the presence of leukopenia (defined as leukocyte count <4 × 109/L). Secondary outcomes included early-onset sepsis, necrotizing enterocolitis, use of antibiotics during admission, and neonatal mortality. RESULTS: We included 99 twins pairs, of which 61 twin pairs were affected by TAPS and 38 twin pairs by TTTS. The mean leukocyte count at birth in donors and recipients was 7.5 × 109/L versus 7.4 × 109/L (p = 0.936), respectively. Leukopenia was significantly more common in donor twins compared to recipient twins (7.1% [7/99] vs. 0% [0/99], p = 0.016). Of the 7 donors with leukopenia, 6 were affected by TAPS and 1 by TTTS. Overall, donors were more often affected by early-onset sepsis than recipients, 23.7% (23/97) versus 13% (13.7/95) (p = 0.049), respectively. CONCLUSIONS: Leukocyte counts at birth in twins with TTTS or TAPS are similar between donors and recipients, but TAPS donors are at an increased risk of leukopenia. Overall, TTTS and TAPS donors seem to be at an increased risk of early-onset neonatal sepsis compared to recipient twins.

Twin-Twin Transfusion Syndrome with Anemia-Polycythemia: Prevalence, Characteristics, and Outcome.

The aim of this study was to estimate the prevalence of co-existing anemia-polycythemia (AP) in twin pregnancies with twin-twin transfusion syndrome (TTTS) prior to laser surgery, and to evaluate the characteristics and outcomes in TTTS twins with and without AP. All TTTS cases treated with laser between 2001 and 2019 were retrospectively reviewed for the presence of AP before surgery. AP was defined as delta middle cerebral artery-peak systolic velocity > 0.5 multiples of the median. The primary outcome was a composite of perinatal survival and severe neurodevelopmental impairment (NDI). Secondary outcomes included procedure-related characteristics, severe neonatal morbidity, and disease-free survival. In total, 66% (461/696) of TTTS twin pregnancies were eligible for analysis. AP was detected in 15% (70/461) of the TTTS twins prior to laser surgery. Gestational age at laser was higher in the TTTS+AP group compared to the TTTS-only group-21.0 weeks (interquartile rage (IQR): 18.8-24.0) versus 19.3 weeks (IQR: 17.3-21.9), respectively (p < 0.0001). Fewer placental anastomoses were detected in the TTTS+AP group than in the TTTS-only group-five (IQR: 4-6) versus six (IQR: 5-8), respectively (p < 0.0001). Perinatal survival was 77% (599/782) in the TTTS-only group and 83% (118/142) in the TTTS+AP group (p = 0.130). Severe NDI was 8% (28/370) in TTTS-only and 3% (2/74) in TTTS+AP. TTTS-only twins showed more severe neonatal morbidity than twins with TTTS+AP-23% (132/575) versus 11% (13/115), respectively (p = 0.005). Disease-free survival was lower in the TTTS-only group compared to the TTTS+AP group-62% (341/548) versus 73% (72/98), respectively (p = 0.046). Thus, AP complicates 15% of TTTS twins prior to laser. TTTS+AP twins show a different placental angioarchitecture, a later time of onset of the disease, and a more favorable outcome.

Twin-Twin Transfusion Syndrome with and without Selective Fetal Growth Restriction Prior to Fetoscopic Laser Surgery: Short and Long-Term Outcome.

As twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are both prevalent complications of monochorionic (MC) twin pregnancies, its coexistence is not uncommon. The aim of this study is to evaluate the short and long-term outcome in TTTS with and without sFGR prior to fetoscopic laser coagulation. All TTTS cases treated with laser surgery at our center between 2001-2019 were retrospectively reviewed for the presence of sFGR, defined as an estimated fetal weight (EFW) <10th centile. We compared two groups: TTTS-only and TTTS + sFGR. Primary outcomes were perinatal survival and long-term severe neurodevelopmental impairment (NDI). Of the 527 pregnancies eligible for analysis, 40.8% (n = 215) were categorized as TTTS-only and 59.2% (n = 312) as TTTS + sFGR. Quintero stage at presentation was higher in the TTTS + sFGR group compared to the TTTS-only group (57% compared to 44% stage III). Separate analysis of donors showed significantly lower perinatal survival for donors in the TTTS + sFGR group (72% (224/311) compared to 81% (173/215), p = 0.027). Severe NDI at follow-up in long-term survivors in the TTTS-only and TTTS + sFGR group was present in 7% (13/198) and 9% (27/299), respectively (p = 0.385). Both sFGR (OR 1.5;95% CI 1.1-2.0, p = 0.013) and lower gestational age at laser (OR 1.1;95% CI 1.0-1.1, p = 0.001) were independently associated with decreased perinatal survival. Thus, sFGR prior to laser surgery is associated with a more severe initial presentation and decreased donor perinatal survival. The long-term outcome was not affected.

The Impact of Selective Fetal Growth Restriction or Birth Weight Discordance on Long-Term Neurodevelopment in Monochorionic Twins: A Systematic Literature Review.

The aim of this review was to assess the impact of selective fetal growth restriction (sFGR) and/or birth weight discordance (BWD) on long-term neurodevelopment in monochorionic (MC) twins. Five out of 28 articles assessed for eligibility were included. One article concluded that the incidence of long-term neurodevelopmental impairment (NDI) was higher in BWD MC twins (11/26, 42%) than in BWD dichorionic (DC) (5/38, 13%) and concordant MC twins (6/71, 8%). BWD MC twins had a 6-fold higher risk of cerebral palsy compared to DC twins (5/26, 19% vs. 1/40, 3%, p < 0.05). Another article described a linear relationship between birth weight and verbal IQ scores, demonstrating a 13-point difference for a 1000 gram BWD between the twins, with a disadvantage for the smaller twin (p < 0.0001). Three articles analyzing within-pair differences showed that the smaller twin more frequently demonstrated mild NDI (6/80, 8% vs. 1/111, 1%) and lower developmental test scores (up to 5.3 points) as opposed to its larger co-twin. Although these results suggest that MC twins with sFGR/BWD are at increased risk of long-term NDI as compared to BWD DC or concordant MC twins, with a within-pair disadvantage for the smaller twin, the overall level of evidence is of moderate quality. As only five articles with a high degree of heterogeneity were available, our review mainly demonstrates the current lack of knowledge of the long-term outcomes of MC twins with sFGR/BWD. Insight into long-term outcomes will lead to improved prognostics, which are essential in parent counseling and crucial in the process of forming a management protocol specifically for twins with sFGR to optimally monitor and support their development.

Fatal Umbilical Cord Strangulation in the Remaining Co-Twin after Selective Foeticide with Radiofrequency Ablation for Twin-Twin Transfusion Syndrome.

We report a case of a monochorionic diamniotic twin diagnosed with twin-twin transfusion syndrome (TTTS; stage 3) with co-existing severe cerebral damage in the donor twin at 18 + 4 weeks' gestation. After counselling, the parents opted for selective foeticide of the donor twin. For the procedure, radiofrequency ablation (RFA) was used. Serial ultrasound examinations at 20 + 1 and 21 + 1 weeks' gestation showed good recovery of the ex-recipient, after which the patient was sent back to the referring hospital. At 29 + 5 weeks' gestation, an unexpected foetal death was diagnosed. On macroscopic placental examination, (iatrogenic) monoamnionicity was detected. In addition, the umbilical cord of the recipient was found to be constricted by the macerated umbilical cord of the ex-donor. This case demonstrates that iatrogenic monoamnionicity can be a serious complication of RFA in monochorionic twins complicated by TTTS, with a subsequent risk for cord entanglement leading to a fatal outcome for the remaining co-twin. Although the actual incidence of iatrogenic monoamnionicity after RFA remains unknown, increased attention to the intactness of the inter-twin membrane even weeks after the RFA may be required.

The prognostic value of tumor-stroma ratio in tumor-positive axillary lymph nodes of breast cancer patients.

The tumor-stroma ratio (TSR) has previously been found to be a strong prognostic parameter in primary breast cancer tumors. Since the presence of tumor cells in lymph nodes is important for clinical decision making, the influence of TSR in the primary breast tumor combined with the TSR in tumor-positive lymph nodes on prognosis was evaluated. Women with invasive breast cancer without distant metastasis who underwent an axillary lymph node dissection between 1985 and 1994 at the Leiden University Medical Center were retrospectively analyzed. TSR assessment was performed on hematoxylin and eosin stained tissue slides. In total, 87 (45.5%) primary tumors were scored as stroma-low and 104 (54.5%) as stroma-high. Patients with a high stromal percentage in the primary tumors had a statistically significant worse relapse free period (RFP) compared to stroma-low tumors (HR 1.97, 95% CI 1.37-2.82, p < 0.001). A total number of 915 lymph nodes were assessed for TSR. In 101 (52.9%) patients, heterogeneity was observed between stroma percentage category in primary tumor and lymph nodes. The combination of TSR of the primary tumor combined with TSR of tumor-positive lymph nodes strengthened each other as independent prognostic parameter for RFP (p = 0.019). Patients with primary tumor stroma-low/lymph nodes stroma-low tumors showed strongly improved RFP rates compared to patients with primary tumor stroma-high/lymph node stroma-high tumors with 10-year percentages of 58 versus 8%, respectively. Assessing the TSR on tumor-positive lymph nodes can provide additional prognostic information. Stromal activation strongly differs between primary tumors and lymph node metastasis.

Sudden Fetal Hematologic Changes as a Complication of Amnioreduction in Twin-Twin Transfusion Syndrome.

We present the first case of a monochorionic twin pregnancy in which sudden hematologic changes occurred as a complication of the amnioreduction procedure for twin-twin transfusion syndrome (TTTS). At 33 weeks of gestation, 4 days after the amnioreduction, the recipient developed severe anemia while the donor developed severe polycythemia. Postnatal placental examination revealed several arteriovenous and venoarterial anastomoses, a pale placental mass of the recipient and a congested and plethoric placental mass of the donor. We speculate on the pathophysiologic changes and potential deleterious effects provoked by the decompressive amnioreduction. Decompression of the placenta and anastomoses after the amnioreduction may have led to an acute blood shift from recipient to donor (thus also a reversal of feto-fetal transfusion), resulting in anemia in the recipient and polycythemia in the donor twin. In the past 15 years, 13 TTTS cases with late presentation were treated with amnioreduction. This is the first time we encountered this severe complication, yielding an incidence of 8%. Although the optimal treatment in TTTS with late presentation is not known, perinatologists should be aware that treatment with amnioreduction can lead to sudden hematologic changes.

Can color difference on the maternal side of the placenta distinguish between acute peripartum twin-twin transfusion syndrome and twin anemia-polycythemia sequence?

OBJECTIVE: To investigate the color difference between two placental shares in monochorionic placentas with acute peripartum twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). METHODS: We evaluated all digital pictures of TAPS, acute peripartum TTTS and a control group of uncomplicated monochorionic placentas examined at our center. We determined the color intensity of the individual placental share on the maternal side of each monochorionic placenta using an image-processing program and calculated the color difference ratio (CDR). RESULTS: Digital pictures of 5 acute peripartum TTTS, 25 TAPS and 54 control group placentas were included in this study. The median CDR in acute peripartum TTTS was significantly lower compared to TAPS placentas, 1.20 (inter-quartile range (IQR) 1.05-1.20) and 2.50 (IQR 1.85-3.34), respectively (p < 0.01), and was comparable to the control group (CDR 1.11, IQR 1.05-1.22). CONCLUSION: TAPS placentas have a higher CDR compared to acute peripartum TTTS placentas. Examining color difference on the maternal side of the placenta might help distinguish between acute peripartum TTTS and TAPS.

Twin Anemia Polycythemia Sequence: Current Views on Pathogenesis, Diagnostic Criteria, Perinatal Management, and Outcome.

Monochorionic twins share a single placenta and are connected with each other through vascular anastomoses. Unbalanced inter-twin blood transfusion may lead to various complications, including twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). TAPS was first described less than a decade ago, and the pathogenesis of TAPS results from slow blood transfusion from donor to recipient through a few minuscule vascular anastomoses. This gradually leads to anemia in the donor and polycythemia in the recipient, in the absence of twin oligo-polyhydramnios sequence (TOPS). TAPS may occur spontaneously in 3-5% of monochorionic twins or after laser surgery for TTTS. The prevalence of post-laser TAPS varies from 2% to 16% of TTTS cases, depending on the rate of residual anastomoses. Pre-natal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and 8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. Management includes expectant management, and intra-uterine blood transfusion (IUT) with or without partial exchange transfusion (PET) or fetoscopic laser surgery. Post-laser TAPS can be prevented by using the Solomon laser surgery technique. Short-term neonatal outcome ranges from isolated inter-twin Hb differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS. This review summarizes the current knowledge after 10 years of research on the pathogenesis, diagnosis, management, and outcome in TAPS.

Color Difference in Placentas with Twin Anemia-Polycythemia Sequence: An Additional Diagnostic Criterion?

OBJECTIVE: To determine the color intensity difference between the 2 placental shares in monochorionic placentas with twin anemia-polycythemia sequence (TAPS). METHODS: We evaluated all digital pictures of TAPS placentas examined at our center and compared them to a control group of uncomplicated monochorionic placentas. We determined the color intensity of individual placental share on the maternal side of each monochorionic placenta using an image processing program and calculated the color difference ratio (CDR). RESULTS: Digital pictures of 19 TAPS and 19 uncomplicated monochorionic placentas were included in this study. The TAPS group consisted of 12 spontaneous TAPS placentas (63%) and 7 post-laser TAPS placentas (37%). The median CDR in the group with TAPS was significantly higher than in the control group, 2.73 (range 1.73-6.36) versus 1.09 (range 1.00-1.35), respectively (p < 0.01). We found a positive correlation between CDR and inter-twin hemoglobin (Hb) difference in the TAPS group (R = 0.66, p < 0.01) but not in the control group (R = 0.04, p = 0.87). CONCLUSION: TAPS placentas have a significantly higher CDR compared to uncomplicated monochorionic twin placentas. Large inter-twin Hb differences in TAPS are associated with higher CDR.