Twin Anemia Polycythemia Sequence: Knowledge and Insights After 15 Years of Research

Twin anemia polycythemia sequence (TAPS) is a chronic form of unbalanced feto-fetal transfusion through minuscule placental anastomoses in monochorionic twin pregnancies, leading to anemia in the donor twin and polycythemia in the recipient twin. TAPS can occur spontaneously in up to 5% of monochorionic twins or can arise in 2%-16% of cases after incomplete laser surgery for twin-twin transfusion syndrome. TAPS can develop across the entire second and third trimester. Antenatal diagnosis for TAPS is reached via Doppler measurement of the fetal middle cerebral artery peak systolic velocity, showing an increased velocity in the donor, combined with a decreased velocity in the recipient. Treatment options for TAPS include expectant management, preterm delivery, intrauterine blood transfusion with or without a partial exchange transfusion, fetoscopic laser surgery and selective feticide. The best treatment option is unclear and is currently being investigated in an international multicenter randomized trial (the TAPS trial). Spontaneous fetal demise occurs in 5%-11% of TAPS twins, more often in donors (8%-18%) than in recipients (2%-5%). Severe long-term neurodevelopmental impairment is seen in 9% of TAPS twins, with donors having an increased risk for cognitive impairment and hearing problems (15%).     

Twin pregnancies in Cardiff and Vale of Glamorgan over four decades: natural twinning is on the increase

Objective

To assess trends in twinning over four decades using a population-based registry.

Design

Ecological study to conduct trend analysis of twin pregnancies in a geographically defined area over 40 years.

Setting

All pregnancies in the Cardiff and Vale of Glamorgan area of South Wales from 1965 to 2004, as recorded in the Cardiff Birth Survey (CBS) database.

Methods

Trends of the incidence of all twin pregnancies (≥18 weeks of gestation) were calculated in 5-year increments, beginning with 1965–1969 and ending in 2000–2004. Natural twinning rates could only be calculated for the terminal five time periods (i.e., 1980–1984, 1985–1989, 1990–1994, 1995–1999, and 2000–2004), when information regarding non-spontaneous (iatrogenic) twinning was first collected in the database. All results were adjusted for maternal age.

Results

The total twinning rate was 13.1 per 1000 pregnancies in the 1st time period (1965–1969). Subsequently, there was a gradual reduction in twinning, reaching a nadir of 10.3 per 1000 for the time period 1980–1985 (Z = 3.15, P value < 0.001). This was followed by a gradual increase in twinning, reaching a maximum of 15.7 per 1000 for both 1995–1999 and 2000–2004 (Z = −5.18, P value < 0.0001). After exclusion of the cases of iatrogenic pregnancies, the natural twinning rate showed a continuous and gradual increase from 10 per 1000 spontaneous pregnancies in 1980–1984 to 13.3 per 1000 in 2000–2004 (Z = −5.08, P value < 0.0001).

Conclusion

The data showed a gradual, continuous increase in natural twinning rates over the last two decades. Such an increase cannot be attributed to the rise in maternal age alone.     

The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome

The renin-angiotensin system (RAS) in twin-twin transfusion syndrome (TTTS) is up-regulated in the donor fetus's kidneys, but down-regulated in the recipient's. Ultrasonographic and echocardiographic features suggest that the recipient is also exposed to RAS components. In this study we investigated the role and origin of RAS components in the recipient fetus. Monochorionic diamniotic (MCDA) pregnancies were recruited from a tertiary fetal medicine service. Cord blood was collected from MCDA twins (TTTS and control non-TTTS) at delivery for renin and angiotensin II immunoassays. Placental tissue was flash-frozen for mRNA and protein expression or formalin-fixed for immunohistochemistry. Archival placenta and kidney samples were used for immunohistochemistry and in-situ hybridization. Plasma renin levels were elevated (p<0.05) in recipients (median 201pg/ml, range 54-315pg/ml) and donors (125pg/ml, 25-296) with TTTS compared to controls (2.5pg/ml, 1.1-1.5pg/ml). The same was found with angiotensin II with high levels in both recipients (300.5pg/ml, 86.1-488pg/ml) and donors (239pg/ml, 76.6-422) compared to controls (169.5pg/ml, 89-220pg/ml, p<0.05). Renin mRNA expression, and protein appeared qualitatively higher in the placental territory of the recipient compared to that of the donor and non-TTTS controls. We conclude that both fetuses in TTTS are exposed to high levels of RAS components; these appear to be produced from different sites, namely the kidney of the donor, and the placenta of the recipient. Given the markedly different phenotypes in the genetically identical fetuses with TTTS, we suggest that the source of RAS components may influence their clinical manifestations.     

Maternal mortality in the United States

Despite a significant improvement in the US maternal mortality ratio since the early 1900s, it still represents a substantial and frustrating burden, particularly given the fact that - essentially - no progress has been made in most US States since 1982. Additionally, the US Centers for Disease Control and Prevention has stated that most cases are probably preventable. Two disheartening issues within this topic include a gross underestimation of the magnitude of maternal mortality - particularly before 1987, but which likely persists to a lesser degree today - and the continued significant racial disparity in maternal mortality. Explanations for the plateau in maternal mortality include the recent trend of delayed childbearing, with the potential accompanying complications associated with older reproductive age (particularly over 35 years) and multiparity. The impressive increase in multifetal pregnancies related to delayed childbearing and assisted reproductive technology also plays a role. Finally, peripartum cardiomyopathy has become an increasingly recognized source of maternal mortality. Pregnancy-related mortality is largely accounted for by thromboembolic disease, hemorrhage, hypertension and its associated complications, and infection. However, since the inclusion of maternal deaths occurring after 42 days post-delivery as pregnancy related, traumatic injuries - including homicides and suicides - are an alarming source of maternal mortality. An especially important contemporary issue to consider within this topic is cesarean delivery "on maternal request", opponents of which cite concerns not only for immediate morbidity and mortality increased over that associated with a vaginal birth, but also for potential morbidity and mortality associated with future pregnancies. One particularly appealing opportunity to reduce maternal mortality is to recognize, examine, and learn from so-called "near-miss" cases.     

脐静脉血流量在产前评估双胎输血综合征中的应用

目的探讨胎儿脐静脉血流量（UVF）在产前评估双胎输血综合征（TTTS）中的应用价值。方法以22对产前诊断为TTTS双胎作为实验组,选取22对非TTTS的单绒毛膜双羊膜囊双胎（MCT）作为对照组。应用多普勒超声获取胎儿脐静脉血流频谱并测得此处胎儿脐静脉的横截面积,计算每个胎儿绝对的脐静脉血流量UVF、经体重校正的脐静脉血流量（UVF/kg）、每一对胎儿间UVF/kg的差值（ΔUVF/kg）、每一对胎儿间UVF/kg的比（R/D-UVF/kg）。对一对胎儿间及两组胎儿间脐静脉血流量参数进行比较。结果实验组受血儿与供血儿的脐静脉血流量差异及实验组和对照组的脐静脉血流量参数差异均有统计学意义（P〈0.05）。实验组中受血儿的UVF和UVF/kg明显高于供血儿;实验组ΔUVF/kg和R/D-UVF/kg亦明显高于对照组。结论胎儿脐静脉血流量的差异反映了TTTS胎儿间不平衡的血流状态,有助于TTTS的产前诊断及评估。     

Prenatal Diagnosis of Spontaneous Septostomy in Dichorionic Diamniotic Twins and Review of the Literature

Objective. We present 2 cases of spontaneous septostomy in dichorionic diamniotic twins and review the literature regarding the incidence, etiology, and complications of this condition. Methods. The following key words were used in the literature search: “rupture dividing membrane twin,” “disruption dividing membrane twin,” “pseudomonoamniotic twin,” “spontaneous septostomy twin,” “interfetal membrane disruption,” “intertwin membrane rupture,” and “intertwin membrane disruption.” Results. We present 2 cases in which an intertwin membrane defect was found prenatally in dichorionic diamniotic twins. In both cases, a portion of one twin's body was found traversing the spontaneous septostomy and in the sac of its cotwin. Umbilical cord Doppler studies showed no abnormalities in either case as the cord crossed the membrane disruption. In both cases, the fetuses had no notable sequelae from the ruptured intertwin membrane. The literature review revealed no cases of spontaneous septostomy in dichorionic diamniotic twins but 15 cases in monochorionic diamniotic twins. Possible etiologies include chorioamnionitis, trauma or physical rupture by the fetuses, developmental disturbances represented by amniotic plica, and polyhydramnios. In cases of monozygotic twins, a vascular etiology could explain this rare defect with formation of anastomoses of the outer embryonic vasculature. Complications of the spontaneous septostomy cases identified in the literature included cord entanglement (8 cases), preterm delivery (9 cases), and death (8 cases), although our 2 cases had minimal complications. Conclusions. Spontaneous septostomy in dichorionic diamniotic twins has not previously been reported.     

Etiology of obsessive–compulsive symptoms and obsessive–compulsive personality traits: common genes,mostly different environments

Background: Little is known about the etiologic relationship between obsessive–compulsive (OC) symptoms and traits of OC personality disorder. The traits include perfectionism and rigidity. Some theorists have proposed that OC personality disorder is one of several disorders falling within an OC spectrum. This implies that OC personality traits and symptoms should have etiologic factors in common, and this should not be simply because symptoms and traits are both shaped by nonspecific etiological influences, such as those shaping negative emotionality (neuroticism). Methods: To investigate these issues, a community sample of 307 pairs of monozygotic and dizygotic adult twins provided scores on six types of OC‐related symptoms, two markers of negative emotionality, and a measure of OC personality traits. Results: Analyses indicated that symptoms and traits arose from a combination of genetic and nonshared environmental factors. A matrix of genetic correlations was computed among the variables, which represented the correlations between the genetic components of pairs of variables. A matrix of environmental correlations was similarly computed. Each matrix was factor analyzed. One genetic factor was obtained, indicating that all variables were influenced by a common genetic factor. Three environmental factors were obtained, with salient loadings on either (a) all six OC symptoms, (b) negative emotionality and obsessing, or (c) OC personality traits and ordering. Conclusions: OC symptoms and traits were etiologically related primarily because they are shaped by the same nonspecific genetic factor that influenced negative emotionality. Implications for the concept of the OC spectrum are discussed. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Genetics and Twins

The phenomenon of twinning has fascinated scientists and others over the centuries. A twin pregnancy has a higher risk of fetal morbidity and mortality than a singleton pregnancy depending on the zygosity and chorionicity of the fetuses. Dizygotic twins originate from two separate ova that are fertilized by two different sperm and are no more alike than any two siblings, and monozygotic twins develop from a single fertilized ovum, develop from one zygote, and are genetically “identical.” Recent evidence has shown that “identical twins” are more genetically discordant than originally thought because of epigenetic factors. In addition, twins are more at risk for chromosomal abnormalities and congenital anomalies. In the last century, twins played and continue to play an important role in genetics research. Twin studies are the criterion standard for research on the importance of heritability and environmental influences on behavior and disease.