Skeletal Growth Arrest Lines in Fetal Remains: Histopathology and Correlative Placental Pathology.

INTRODUCTION: Skeletal growth arrest lines (GAL) are transverse lines of metaphyseal radiodensity accompanying episodic severe physiological stress. They are poorly described in fetal remains. MATERIALS AND METHODS: We searched our autopsy practice for instances of fetal GAL in post mortem radiology, and correlated them with long bone histology and placental pathology. We describe the appearance, distribution, and pathology of GAL in a cohort of fetal autopsies, and compare the placental pathology accompanying GAL to the placental pathology of asymmetrical growth restriction (AGR) in the same time period. RESULTS: In 2108 consecutive fetal post mortems, we found 20 cases with GAL. About 16 were in singletons with AGR. In these 16, the distribution of placental pathologies was similar to a contemporaneous cohort of 113 cases with AGR. Of the remaining 4, two twins out of 9 sets of monochorionic twins with AGR demonstrated GAL. One case of GAL had symmetrical growth restriction with cytomegalovirus infection, and one case had no AGR and an old, unexplained retroplacental hemorrhage. On histology, GAL are characterized by a region of mineralized chondroid, which is variably incorporated into irregular trabecular bone. DISCUSSION: GALs accompany a variety of placental pathologies and twin-twin transfusion, suggesting episodic disease progression.

Placental vessel segmentation and registration in fetoscopy: Literature review and MICCAI FetReg2021 challenge findings.

Fetoscopy laser photocoagulation is a widely adopted procedure for treating Twin-to-Twin Transfusion Syndrome (TTTS). The procedure involves photocoagulation pathological anastomoses to restore a physiological blood exchange among twins. The procedure is particularly challenging, from the surgeon's side, due to the limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to amniotic fluid turbidity, and variability in illumination. These challenges may lead to increased surgery time and incomplete ablation of pathological anastomoses, resulting in persistent TTTS. Computer-assisted intervention (CAI) can provide TTTS surgeons with decision support and context awareness by identifying key structures in the scene and expanding the fetoscopic field of view through video mosaicking. Research in this domain has been hampered by the lack of high-quality data to design, develop and test CAI algorithms. Through the Fetoscopic Placental Vessel Segmentation and Registration (FetReg2021) challenge, which was organized as part of the MICCAI2021 Endoscopic Vision (EndoVis) challenge, we released the first large-scale multi-center TTTS dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms with a focus on creating drift-free mosaics from long duration fetoscopy videos. For this challenge, we released a dataset of 2060 images, pixel-annotated for vessels, tool, fetus and background classes, from 18 in-vivo TTTS fetoscopy procedures and 18 short video clips of an average length of 411 frames for developing placental scene segmentation and frame registration for mosaicking techniques. Seven teams participated in this challenge and their model performance was assessed on an unseen test dataset of 658 pixel-annotated images from 6 fetoscopic procedures and 6 short clips. For the segmentation task, overall baseline performed was the top performing (aggregated mIoU of 0.6763) and was the best on the vessel class (mIoU of 0.5817) while team RREB was the best on the tool (mIoU of 0.6335) and fetus (mIoU of 0.5178) classes. For the registration task, overall the baseline performed better than team SANO with an overall mean 5-frame SSIM of 0.9348. Qualitatively, it was observed that team SANO performed better in planar scenarios, while baseline was better in non-planner scenarios. The detailed analysis showed that no single team outperformed on all 6 test fetoscopic videos. The challenge provided an opportunity to create generalized solutions for fetoscopic scene understanding and mosaicking. In this paper, we present the findings of the FetReg2021 challenge, alongside reporting a detailed literature review for CAI in TTTS fetoscopy. Through this challenge, its analysis and the release of multi-center fetoscopic data, we provide a benchmark for future research in this field.

Fetal surgery is not associated with increased inflammatory placental pathology.

OBJECTIVE: Fetal surgery has improved neonatal outcomes; however, it is unknown if the intervention contributes to the developmental of inflammatory pathologies in the placenta. Here, an association between fetal surgery and placental pathology was examined. METHOD: This case-control study compared pregnancies with fetal surgery (n = 22), pregnancies with an indication for fetal surgery but without an intervention being done (n = 13), and gestational-age and fetus-number matched controls (n = 36). Data on maternal, infant, and placental outcomes were abstracted. Additionally, immunohistochemistry identified expression of lymphoid and myeloid cells in the placenta on a subset of cases. Comparisons were performed using Kruskal-Wallis or Pearson's chi-squared tests. RESULTS: Maternal characteristics were comparable between groups. Most fetal interventions were for diaphragmatic hernia, spina bifida, or twin-to-twin transfusion syndrome. Fetuses who were operated on before birth were more likely to be born preterm (p = 0.02). There was no increase in the rate of observed placental pathologies or immune cell infiltration in fetal surgery cases compared to controls. CONCLUSION: The data suggest that fetal surgery is not associated with increased inflammatory or morphologic pathology in the placenta. This observation supports the growing field of fetal surgery.

The mystery of monozygotic twinning II: What can monozygotic twinning tell us about Amyoplasia from a review of the various mechanisms and types of monozygotic twinning?

Monozygotic (MZ) twins ("identical twins") are essentially unique to human beings. Why and how they arise is not known. This article reviews the possible different types of MZ twinning recognized in the previous article on twins and arthrogryposis. There appear to be at least three subgroups of MZ twinning: spontaneous, familial, and those related to artificial reproductive technologies. Each is likely to have different etiologies and different secondary findings. Spontaneous MZ twinning may relate to "overripe ova." Amyoplasia, a specific nongenetic form of arthrogryposis, appears to occur in spontaneous MZ twinning and may be related to twin-twin transfusion.

Monochorionic Triplet Pregnancies With Twin Reversed Arterial Perfusion and Acardiac Triplet: Report of Two Cases and Literature Review.

TRAP pregnancies involving monochorionic triplets are extremely rare, calculated to be 1 in 4.5 million. We report two cases of monochorionic triplet pregnancies with an acardiac triplet. In one case, the mother was a 33-year-old G2P1 who underwent dilation and evacuation at 20 weeks due to poor prognosis. The other case involved a 21-year-old G1P0 mother presenting in advanced preterm labor at 21 weeks who elected expectant management. Seventeen cases of monochorionic triplets with TRAP were identified in the literature. Invasive intervention was performed in 10 cases; 9 cases resulted in the survival of the nonacardiac twins and 1 case resulted in the survival of 1 fetus. Our two cases had common sonographic features which included polyhydramnios of all fetuses. Placental features shared between both cases included being large for gestational age and velamentous insertion of the acardiac twin. The acardiac twins in both of our cases were hydropic and demonstrated developed pelvis and lower extremities. One had an omphalocele. Most case reports in the literature review demonstrate similar findings. Two cases of monochorionic triplets with TRAP and acardiac twin are herein described. Successful treatment by invasive interventions have been described in this condition, highlighting the importance of early diagnosis.

Fused placentas: Till birth do us part.

Twinning and placental fusion occur at a low frequency in species like humans and mice. They are linked to reduced birth weight and intertwin growth discrepancy with important consequences for perinatal survival. Despite this, little is known about the histological characteristics of the twin or fused placenta and how these relate to fetal growth. In this case report, we characterise the histological changes of a fused mouse placenta showing intertwin growth discrepancy. Our study demonstrates that morphological changes in the placental exchange and endocrine regions and elevated calcification levels may contribute to the intertwin growth discrepancy observed in mouse pregnancy.

Study of the placental characteristics and time of onset of twin-to-twin transfusion syndrome.

INTRODUCTION: To investigate the correlation between placental superficial anastomoses, placental territory and the umbilical cord attachment site with the time of onset of twin-to-twin transfusion syndrome (TTTS), and to explore the influence of placental characteristics on the time of onset of TTTS. METHODS: A retrospective analysis was performed on 48 cases of TTTS managed conservatively at the Obstetrics Department of Peking University Third Hospital from April 2014 to April 2019. Placental superficial anastomoses, placental territory, the distance between the insertion points of the umbilical cord were measured after placental dye injection. Correlation analysis was conducted between placental characteristics and the time of onset of TTTS. RESULTS: (1) The incidence of AA anastomoses was 33.3% (16/48) with a mean total diameter of 2.3 ± 1.4 mm, that of AV anastomoses was 95.8% (46/48) with a mean total diameter of 1.2 ± 0.4 mm, and that of VV anastomoses 22.9% (11/48) with a mean total diameter of 2.3 ± 1.1 mm (2) The time of onset of TTTS was positively correlated with the umbilical insertion ratio (Spearman correlation coefficient = 0.404, P = 0.004), but not correlated with the total diameter of anastomoses in the three different types, or with placental territory discordance. DISCUSSION: The time of onset of TTTS was positively correlated with the umbilical insertion ratio, which suggest that the distance between umbilical cord insertion sites may affect the time of onset of TTTS. The smaller the distance between the umbilical cord insertion sites, the earlier the time of onset of TTTS is likely to be.

Chimerism involving a RB1 pathogenic variant in monochorionic dizygotic twins with twin-twin transfusion syndrome.

We report the first case of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic-dizygotic twins (MC/DZ) with the twin-twin-transfusion syndrome (TTTS), presumably caused by the exchange of stem-cells. Twin A developed bilateral retinoblastoma at 7 months of age. Initial genetic testing identified a de novo RB1 pathogenic variant, with a 20% allelic ratio in both twins' blood. Subsequent genotyping of blood and skin confirmed dizygosity, with the affected twin harboring the RB1 pathogenic variant in skin and blood, and the unaffected twin carrying the variant only in blood.

Placental histopathological features of fetoscopic laser photocoagulation for monoaminotic diamniotic twin pregnancies.

INTRODUCTION: This study aimed to compare the histopathological placental features of monochorionic diamniotic (MCDA) twins who did and did not undergo fetoscopic laser photocoagulation (FLP). METHODS: This was a retrospective single-institution cohort study on MCDA twins who underwent FLP between October 2010 and December 2018. The control group included MCDA twins who did not undergo FLP and were delivered during the same period in the institute. The incidence of chorioamnionitis (CAM), funisitis, and other pathological findings was compared between the FLP and control groups after matching by gestational age at delivery. RESULTS: In total, 292 MCDA pregnant women who underwent FLP and 356 controls gave birth during the study period. After matching the two groups in the ratio 1:1 by gestational age at delivery, each group comprised 194 subjects. The incidence of histological CAM with Blanc association (stage I, 6.2% vs. 3.1%, crude odds ratio (cOR) = 3.1, P = 0.052; stage II, 7.2% vs. 5.7%, cOR = 1.6, P = 0.30; stage III, 2.1% vs. 2.6%, cOR = 0.66, P = 0.52) and funisitis (artery, 5.2% vs. 3.6%, cOR = 1.3, P = 0.63; vein 7.2% vs. 4.1%, cOR = 1.6, P = 0.29) was not statistically significant difference between the FLP and control groups. The FLP group demonstrated a higher incidence of partial placental infarction than the control group (10.3% vs. 3.1%, cOR = 4.3, P = 0.004, adjusted OR = 2.8, P = 0.031). DISCUSSION: FLP did not appear to increase the incidence of histological CAM or funisitis in subjects matched by gestational age at delivery. The FLP group demonstrated a higher incidence of partial placental infarction than the control group.

Outcome of twin-twin transfusion syndrome according to Quintero stage of disease: systematic review and meta-analysis.

OBJECTIVES: To report the outcome of pregnancies complicated by twin-twin transfusion syndrome (TTTS) according to Quintero stage. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies reporting the outcome of pregnancies complicated by TTTS stratified according to Quintero stage (I-V). The primary outcome was fetal survival rate according to Quintero stage. Secondary outcomes were gestational age at birth, preterm birth (PTB) before 34, 32 and 28 weeks' gestation and neonatal morbidity. Outcomes are reported according to the different management options (expectant management, laser therapy or amnioreduction) for pregnancies with Stage-I TTTS. Only cases treated with laser therapy were considered for those with Stages-II-IV TTTS and only cases managed expectantly were considered for those with Stage-V TTTS. Random-effects head-to-head meta-analysis was used to analyze the extracted data. RESULTS: Twenty-six studies (2699 twin pregnancies) were included. Overall, 610 (22.6%) pregnancies were diagnosed with Quintero stage-I TTTS, 692 (25.6%) were Stage II, 1146 (42.5%) were Stage III, 247 (9.2%) were Stage IV and four (0.1%) were Stage V. Survival of at least one twin occurred in 86.9% (95% CI, 84.0-89.7%) (456/552) of pregnancies with Stage-I, in 85% (95% CI, 79.1-90.1%) (514/590) of those with Stage-II, in 81.5% (95% CI, 76.6-86.0%) (875/1040) of those with Stage-III, in 82.8% (95% CI, 73.6-90.4%) (172/205) of those with Stage-IV and in 54.6% (95% CI, 24.8-82.6%) (5/9) of those with Stage-V TTTS. The rate of a pregnancy with no survivor was 11.8% (95% CI, 8.4-15.8%) (69/564) in those with Stage-I, 15.0% (95% CI, 9.9-20.9%) (76/590) in those with Stage-II, 18.6% (95% CI, 14.2-23.4%) (165/1040) in those with Stage-III, 17.2% (95% CI, 9.6-26.4%) (33/205) in those with Stage-IV and in 45.4% (95% CI, 17.4-75.2%) (4/9) in those with Stage-V TTTS. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS. Overall, the incidence of PTB and neonatal morbidity increased as the severity of TTTS increased, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of pregnancies with Stage-I TTTS according to the type of intervention, the rate of fetal survival of at least one twin was 84.9% (95% CI, 70.4-95.1%) (94/112) in cases managed expectantly, 86.7% (95% CI, 82.6-90.4%) (249/285) in those undergoing laser therapy and 92.2% (95% CI, 84.2-97.6%) (56/60) in those after amnioreduction, while the rate of double survival was 67.9% (95% CI, 57.0-77.9%) (73/108), 69.7% (95% CI, 61.6-77.1%) (203/285) and 80.8% (95% CI, 62.0-94.2%) (49/60), respectively. CONCLUSIONS: Overall survival in monochorionic diamniotic pregnancies affected by TTTS is higher for earlier Quintero stages (I and II), but fetal survival rates are moderately high even in those with Stage-III or -IV TTTS when treated with laser therapy. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS treated with laser and expectant management, respectively. In pregnancies affected by Stage-I TTTS, amnioreduction was associated with slightly higher survival compared with laser therapy and expectant management, although these findings may be confirmed only by future head-to-head randomized trials. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado del síndrome de transfusión feto-fetal según el estadio de Quintero de la enfermedad: revisión sistemática y metaanálisis OBJETIVOS: Informar sobre el resultado de los embarazos complicados por el síndrome de transfusión feto-fetal (TTTS, por sus siglas en inglés) según el estadio de Quintero. MÉTODOS: Se hicieron búsquedas en las bases de datos de MEDLINE, EMBASE y CINAHL de estudios que hubieran informado sobre el resultado de embarazos complicados por TTTS, estratificados según el estadio de Quintero (I-V). El resultado primario fue la tasa de supervivencia fetal según el estadio de Quintero. Los resultados secundarios fueron la edad gestacional al nacer, el parto pretérmino (PPT) antes de las 34, 32 y 28 semanas de gestación y la morbilidad neonatal. Los resultados se reportan de acuerdo con las diferentes opciones de tratamiento (expectante, terapia de láser o amniorreducción) para los embarazos con TTTS en Estadio I. Sólo se consideraron los casos tratados con terapia de láser para aquellos con TTTS de las Etapas II-IV y sólo se consideraron los casos tratados de manera expectante para aquellos con TTTS de la Etapa V. Para analizar los datos extraídos se utilizó un metaanálisis directo de efectos aleatorios. RESULTADOS: Se incluyeron veintiséis estudios (2699 embarazos de gemelos). En total, 610 (22,6%) embarazos fueron diagnosticados con TTTS de Estadio I de Quintero, 692 (25,6%) de Estadio II, 1146 (42,5%) de Estadio III, 247 (9,2%) de Estadio IV y cuatro (0,1%) de Estadio V. La supervivencia de al menos un gemelo se produjo en el 86,9% (IC 95%, 84,0-89,7%) (456/552) de los embarazos en Estadio I, en el 85% (IC 95%, 79,1-90,1%) (514/590) de aquellos en Estadio II, en el 81,5% (IC 95%, 76,6-86,0%) (875/1040) de aquellos en Estadio-III, en el 82,8% (IC 95%, 73,6-90,4%) (172/205) de aquellos en Estadio-IV y en el 54,6% (IC 95%, 24,8-82,6%) (5/9) de aquellos en Estadio-V de TTTS. La tasa de embarazos sin supervivientes fue del 11,8% (IC 95%, 8,4-15,8%) (69/564) de aquellos en Estadio-I, 15,0% (IC 95%, 9,9-20,9%) (76/590) de aquellos en Estadio-II, 18,6% (IC 95%, 14,2-23,4%) (165/1040) de aquellos en Estadio-III, 17,2% (IC 95%, 9,6-26,4%) (33/205) de aquellos en Estadio-IV y en el 45,4% (IC 95%, 17,4-75,2%) (4/9) de aquellos en Estadio-V de TTTS. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V. En general, la incidencia de PPT y la morbilidad neonatal aumentaron a medida que se incrementó la gravedad del TTTS, pero los datos sobre estos dos resultados se vieron limitados por el pequeño tamaño de la muestra de los estudios incluidos. Al estratificar el análisis de los embarazos con TTTS en Estadio I según el tipo de tratamiento, la tasa de supervivencia fetal de al menos un gemelo fue del 84,9% (IC 95%, 70,4-95,1%) (94/112) en los casos tratados de forma expectante, del 86,7% (IC 95%, 82,6-90.4%) (249/285) en los sometidos a terapia láser y del 92,2% (IC 95%, 84,2-97,6%) (56/60) en los sometidos a amniorreducción, mientras que la tasa de supervivencia doble fue del 67,9% (IC 95%, 57,0-77,9%) (73/108), del 69,7% (IC 95%, 61,6-77,1%) (203/285) y del 80,8% (IC 95%, 62,0-94,2%) (49/60), respectivamente. CONCLUSIONES: La supervivencia en general en los embarazos biamnióticos monocoriónicos afectados por TTTS es mayor en los estadios tempranos de Quintero (I y II), pero las tasas de supervivencia fetal son moderadamente altas incluso en aquellos con TTTS en estadios III o IV cuando se tratan con terapia láser. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V tratados con láser y tratamiento expectante, respectivamente. En los embarazos afectados por TTTS en Estadio I, la amniorreducción estuvo asociada con una supervivencia ligeramente mayor en comparación con la terapia de láser y el tratamiento expectante, aunque estos hallazgos solo pueden confirmarse mediante futuros estudios aleatorizados directos. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Morphology, intrafetal vascular pattern, and umbilical artery Doppler indices of acardiac twins.

BACKGROUND: Twin reversed arterial perfusion (TRAP) sequence consists of acardiac twin (A) paradoxically perfused by pump twin (P) through an umbilical artery (UA). We proposed characterization of acardiac twins with intrafetal vascular pattern (IVP), and assessed its correlation with morphology and UA Doppler indices. METHODS: We prospectively evaluated 21 cases of TRAP sequence. Morphology (acardia vs hemicardia) and IVP (simple vs complex) of acardiac twins were characterized with ultrasound and color Doppler. Twins weight ratio (A/P Wt) and UA Doppler indices of acardiac and pump twins including (1) difference of systolic/diastolic ratio (UA ∆S/D), (2) difference of resistance index (UA ∆RI), and (3) ratio of pulsatility index (UA PI A/P) were calculated. RESULTS: The median (min, max) gestational age at diagnosis was 18 (11, 27) weeks. Acardia (n = 14) were associated with simple IVP (n = 16) (P < .05). After exclusion of acardia with complex IVP (n = 1), the A/P Wt, UA ∆S/D, UA ∆RI, and UA PI A/P of acardia with simple IVP (n = 13), hemicardia with simple IVP (n = 3), and hemicardia with complex IVP (n = 4) were not significantly different (P > .05). CONCLUSIONS: Most of acardiac twins were acardia with simple IVP. Morphology and IVP of acardiac twins were not associated with UA Doppler indices.

Effect of Chorionicity on Umbilical Cord Blood Acid-Base Analysis of the Second Twin.

Our objective was to determine whether chorionicity affects umbilical cord blood acid-base parameters of the second twin. This was a retrospective cohort of twin pregnancies delivered at ≥23 weeks of gestation at a tertiary hospital from 2010 to 2016. Patients were included if arterial and venous umbilical cord gas results were available for both newborns and chorionicity was confirmed histologically. Exclusion criteria included intrauterine fetal demise of either twin prior to labor, major fetal anomalies, monoamnionicity, uncertain chronicity and twin-to-twin transfusion syndrome. The primary outcome evaluated was the umbilical artery (UA) pH of the second twin. A total of 593 dichorionic (DC) and 86 monochorionic (MC) twin pregnancies were included. No difference in UA pH was observed between MC and DC twins. Among vaginal deliveries (n = 97), the UA pH of the first twin was higher than the second twin (7.26 vs. 7.24; p = .01). Twin-to-twin delivery interval (TTDI) ≥20 min was associated with a higher UA pH in the first twin compared to the second twin (7.25 vs. 7.16, respectively; p = .006). Multivariable logistic regression was used to predict arterial pH < 7.20 for the second twin; the most predictive factors were arterial pH < 7.20 for the first twin, chronic hypertension and prolonged TTDI. Chorionicity was not associated with any acid-base parameter of umbilical cord blood in either the first or second twin. No differences in neonatal outcomes were observed based on chorionicity or birth order. Populations with a lower cesarean delivery rate may yield different findings.

Cardiac Anomalies in Liveborn and Stillborn Monochorionic Twins.

BACKGROUND: Cardiovascular anomalies are more common in monochorionic twins, especially with twin-twin transfusion, compared to other twin types and to singletons. Because previous studies are based on fetal and neonatal echocardiography, more information is needed to study prevalence of cardiac anomalies in twin miscarriages, stillbirths, and children after the immediate neonatal period. METHODS: With specific attention to cardiac anomalies, we reviewed the medical records of 335 selected liveborn twin pairs from the Marshfield Clinic Twin Cohort (enriched for twin-twin transfusion) and all twins (175 pairs) identified in the Wisconsin Stillbirth Service Program cohort of late miscarriages and stillbirths. RESULTS: Structural cardiac defects occurred in 12% of liveborn monochorionic twin infants and 7.5% of stillborn infants with twin-twin transfusion compared to only 2% of liveborn dizygotic twins and no stillborn dizygotic infants. The most common cardiac lesion in liveborn twins was ventricular septal defect, which was usually isolated and discordant, preferentially affecting the smaller twin in monochorionic pairs. Among stillborn and miscarried monochorionic twins, the most common cardiac lesion was acardia. CONCLUSIONS: Monochorionic twins, particularly those with TTT, are at increased risk for a spectrum of structural cardiac malformations which we suggest may be related to asymmetry of the inner cell mass resulting in a smaller poorly perfused twin. In severe cases, limited cardiac and circulatory development in the affected twin leads to acardia. In less severe cases, the smaller infant has deficient septal growth that sometimes results in ventricular septal defect.

Dichorionic pregnancy complicated by a twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) is a serious complication typical of monochorionic pregnancies. Cases in dichorionic pregnancies have been described. The authors present a case report of a presumed TTTS in a dichorionic pregnancy followed at our institution in which the patient presented to the emergency department at 31 4/7 weeks' gestation complaining of lack of fetal movements. Both fetuses did not show any cardiac activity. On the first twin, an oligohydramnios was present and his bladder was not visualised and, on the second twin, a polyhydramnios and an augmented bladder were visualised. Pathological findings of the fetuses were compatible with a diagnosis of TTTS and placental study confirmed the presence of a dichorionic/diamniotic placenta, with superficial vessels crossing the dividing membrane.

Fetal and Neonatal Circulatory Disorders in Twin to Twin Transfusion Syndrome (The Secondary Publication).

Twin to twin transfusion syndrome (TTTS) is a major complication of monochorionic diamniotic (MD) twins, and its onset is known to be associated with placental vascular anastomoses and blood flow imbalance. In a typical case of TTTS, the recipient develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis in the uterus. In contrast, the donor develops oligohydramnios and intrauterine growth restriction. Recently, the significance of the renin-angiotensin-aldosterone system (RAAS) that transfers from the donor to the recipient has attracted interest in the fetal circulation of TTTS. The donor has decreased renal blood flow due to decreased circulating blood volume. For this reason, the secretion of RAAS hormones is augmented in the fetal kidneys of the donor. In TTTS, these RAAS hormones from the donor transfer to the recipient through the anastomosed vessels. In addition to excess preload, the recipient heart is exposed to excess afterload due to systemic vasoconstriction through RAAS hormones. Commonly occurring complications in the recipient include myocardial hypertrophy, atrioventricular valve regurgitation, and pulmonary valve stenosis or pulmonary atresia. Fetoscopic laser photocoagulation (FLP) has been introduced recently because neither mortality nor neurological morbidity have been satisfactorily improved with conventional treatment. FLP is a curative method that may improve the prognosis of TTTS. In Japan, this procedure has been performed frequently, and positive neurological outcomes have been achieved.

Monozygotic Twins with Birth-Weight Differences: Metabolic Health Influenced more by Genetics or by Environment?

BACKGROUND: Low birth-weight (bw), low birth-length (bl), unfavourable intrauterine conditions and post-natal catch-up growth can have an impact on growth and metabolic health later in life. OBJECTIVE: We studied genetically identical twins with intra-twin bw-differences due to twin-twin transfusion syndrome from birth to adolescence and analysed the long-term impact of bw and catch-up growth on metabolic parameters. SUBJECTS AND METHODS: Forty-three postpubertal monozygotic twin-pairs (mean age 17.4 years) were examined. Twenty-two pairs were discordant (intra-twin bw- and/or bl-difference ≥1 SDS) of which 12 (55%) experienced catch-up growth. Auxological parameters and blood pressure were measured, a fasting blood sample was collected and bio-impedance spectroscopy was carried out. RESULTS: Irrespective of differences in birth parameters and postnatal catch-up growth, a significant intra-twin correlation was found for nearly all measured parameters of body composition (skinfold, waist-hip circumference, relative body fat/lean body mass) and metabolic health (total, and low-density lipoprotein-C/high-density lipoprotein-C, Apolipoprotein A and B, C-peptide). As an exception to this, and only for the former smaller twins who showed postnatal catch-up growth, a significantly higher fasting insulin level was found compared to that of the co-twins (mean insulin level: 8.4 vs. 5.7 µIU/mL; p < 0.01). Auxology remained different until adulthood: even in subjects with catch-up growth the former smaller twins were significantly lighter (mean-body mass index-SDS: -0.42 vs. 0.21; p < 0.05) and shorter (mean height-SDS: -0.07 vs. 0.37; p < 0.05) than their co-twins. CONCLUSION: In this special group of monozygotic twins with intra-twin bw-differences and catch-up growth, we found that the genetic background was a more important factor in determining later metabolic health than bw and/or catch-up growth.

Characteristics of referred patients with twin-twin transfusion syndrome who did not undergo fetal therapy.

INTRODUCTION: Abundant research has reported twin-twin transfusion syndrome (TTTS) outcomes following fetal therapy. Our research describes TTTS patients who did not undergo fetal therapy. METHODS: Records from TTTS pregnancies evaluated at 16 to 26 gestational weeks were reviewed between January 2006 and March 2017. The study population comprised subjects who did not undergo fetal therapy. Based on initial consultation, patients were grouped as nonsurgical vs surgical candidates. TTTS progression and perinatal outcomes were assessed. RESULTS: Of 734 TTTS patients evaluated, 68 (9.3%) did not undergo intervention. Of these, 62% were nonsurgical candidates and 38% were surgical candidates. Nonsurgical candidates were ineligible for treatment because of fetal demise or maternal factors (placental abruption, severe membrane separation, and preterm labor). Of surgical candidates, 11 underwent expectant management, eight elected pregnancy termination, and seven planned fetal intervention but had a complication before the procedure. TTTS progression occurred in 10 (15.2%) of 66 cases. Neonatal survival in 64 cases was as follows: in 41 (64%), no survivors; in 11 (17.2%), one survivor; and in 12 (18.8%), two survivors. CONCLUSION: Nine percent of referred TTTS patients did not undergo fetal therapy, with many ineligible because of morbidity between referral and consultation. Studies of TTTS should acknowledge this subgroup and circumstances leading to lack of treatment.