Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin-twin transfusion syndrome

We developed a mathematical model of monochorionic twin pregnancies and twin-twin transfusion syndrome (TTTS), combining both fetal fluid dynamics and fetoplacental growth and circulation alterations and assuming that transplacental fluid flow from mother to fetus accounts for normal fetal and amniotic fluid volumes. Ten coupled differential equations, describing fetal total body and amniotic fluid volumes, their osmolalities, and fetal blood colloid osmotic pressure, for both donor and recipient twins, were solved numerically. Amniotic flows are controlled by fetal plasma osmolality and hydrostatic and colloid osmotic pressures. We included varying placental anastomoses and placental sharing of the circulations. Consistent with clinical experience, model predictions are: fetofetal transfusion from unidirectional arteriovenous anastomoses cause oligo-polyhydramnios, a normal size recipient but hypovolemic donor; compensating oppositely directed deep and superficial anastomoses moderate discordant development; and anhydramnios results from mild and severe TTTS, where milder forms may even present earlier in gestation than severe TTTS. Unequal placental circulatory sharing may exacerbate discordant development. In conclusion, our model simulates a wide variety of realistic manifestations of amniotic fluid volume and fetal growth in TTTS related to placental angioarchitecture. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS.     

A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations

The twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies caused by a net transfusion of blood from one twin (the donor) to the other (the recipient) through placental anastomoses. To examine the pathophysiology of TTTS evolving through clinical stages I to IV, we extended our mathematical model to include pulsating circulations propagating along the arterial tree as well as placental and cerebral vascular resistances, and arterial wall thickness and stiffness. The model demonstrates that abnormal umbilical arterial flow (TTTS stage III) in the donor twin results from increased placental resistance as well as reduced resistance in the cerebral arteries. In contrast, recipient twin abnormal umbilical arterial flow requires a significantly greater increase in placental resistance, resulting from the compressive effects of high amniotic fluid pressure. Thus simulated abnormalities of donor umbilical arterial pulsations occur in the donor more commonly and earlier than in the recipient. The "normal" staging sequence (I, II, III, IV) correlates with the presence of compensating placental anastomoses, constituting the majority of monochorionic twin placentas. However, TTTS stage III may occur before manifestations of stage II (lack of donor bladder filling), in our model correlating with severe TTTS from a single arteriovenous anastomosis, an infrequent occurring placental angioarchitecture. In conclusion, this mathematical model describes the onset and development of the four stages of TTTS, reproduces a variety of clinical manifestations, and may contribute to identifying the underlying pathophysiology of the staging sequence in TTTS.     

Accurate and simple evaluation of vascular anastomoses in monochorionic placenta using colored dye

The presence of placental vascular anastomoses is a conditio sine qua non for the development of twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS)(1,2). Injection studies of twin placentas have shown that such anastomoses are almost invariably present in monochorionic twins and extremely rare in dichorionic twins(1). Three types of anastomoses have been documented: from artery to artery, from vein to vein and from artery to vein. Arterio-venous (AV) anastomoses are unidirectional and are referred to as "deep" anastomoses since they proceed through a shared placental cotyledon, whereas arterio-arterial (AA) and veno-venous (VV) anastomoses are bi-directional and are referred to as "superficial" since they lie on the chorionic plate. Both TTTS and TAPS are caused by net imbalance of blood flow between the twins due to AV anastomoses. Blood from one twin (the donor) is pumped through an artery into the shared placental cotyledon and then drained through a vein into the circulation of the other twin (the recipient). Unless blood is pumped back from the recipient to the donor through oppositely directed deep AV anastomoses or through superficial anastomoses, an imbalance of blood volumes occurs, gradually leading to the development of TTTS or TAPS. The presence of an AA anastomosis has been shown to protect against the development of TTTS and TAPS by compensating for the circulatory imbalance caused by the uni-directional AV anastomoses(1,2). Injection of monochorionic placentas soon after birth is a useful mean to understand the etiology of various (hematological) complications in monochorionic twins and is a required test to reach the diagnosis of TAPS(2). In addition, injection of TTTS placentas treated with fetoscopic laser surgery allows identification of possible residual anastomoses(3-5). This additional information is of paramount importance for all perinatologists involved in the management and care of monochorionic twins with TTTS or TAPS. Several placental injection techniques are currently being used. We provide a simple protocol to accurately evaluate the presence of (residual) vascular anastomoses using colored dye injection.     

双胎输血综合征研究现状及新进展

双胎输血综合征(twin-twin transfusion syndrome,TTTS)是单绒毛膜双胎最常见的一种并发症。TTTS的发病机制尚不完全明确,胎盘间存在血管交通是其发病的必要条件,但它难以解释胎儿所有的病理生理,而内分泌改变为TTTS的发病机制提供了一种可能的解释。TTTS的临床诊断主要依靠超声。Quintero分期是目前使用最广泛的分期标准,但其不能提供预测信息,存在一定的局限性。治疗方面,选择性胎儿镜下激光消融术有着较好的胎儿存活率及神经系统预后,优于传统治疗方法,有较好的发展前景。     

双胎输血综合征研究现状及新进展

双胎输血综合征（twin-twin transfusion syndrome,TTTS）是单绒毛膜双胎最常见的一种并发症。TTTS的发病机制尚不完全明确,胎盘间存在血管交通是其发病的必要条件,但它难以解释胎儿所有的病理生理,而内分泌改变为TTTS的发病机制提供了一种可能的解释。TTTS的临床诊断主要依靠超声。Quintero分期是目前使用最广泛的分期标准,但其不能提供预测信息,存在一定的局限性。治疗方面,选择性胎儿镜下激光消融术有着较好的胎儿存活率及神经系统预后,优于传统治疗方法,有较好的发展前景。     

Differential transmission of parvovirus B19 in a twin gestation: a case report.

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus. Severe anemia may lead to nonimmune hydrops or fetal demise. In the case reported, the demise of one twin was diagnosed by ultrasonography in an asymptomatic 21-year-old para 1-0-2-1 African American at the gestational age of 25 weeks. The deceased twin (A) was grossly hydropic with anasarca, ascites, pleural and pericardial effusions, and a thickened placenta. Parvovirus B19 DNA was found in the amniotic fluid of Twin A using the polymerase chain-reaction technique. Serial scans of Twin B showed normal growth and no evidence of hydrops. The pregnancy was managed expectantly until 29 weeks when delivery was indicated by maternal disseminated intravascular coagulation. Maternal IgM antiparvovirus B19 antibodies were detected at the time of delivery. Antiparvovirus B19 IgM antibodies were not present in Twin B. These serologic studies suggest a recent acute maternal infection and refute such an infection in Twin B. We present a case of differential transmission of parvovirus B19 in a twin pregnancy with in utero death of the infected twin and subsequent maternal disseminated intravascular coagulation.     

The influence of gestational age and onset of labour on determinants of fetal-maternal fluid and electrolyte balance in sheep.

Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se.     

Perturbations in the biochemical composition of fetal fluids are apparent in surviving bovine somatic cell nuclear transfer pregnancies in the first half of gestation

Amniotic and allantoic fluid volumes and composition change dynamically throughout gestation. Cattle that are pregnant with somatic cell nuclear transfer (NT) fetuses show a high incidence of abnormal fluid accumulation (particularly hydrallantois) and fetal mortality from approximately midgestation. To investigate fetal fluid homeostasis in these pregnancies, Na, K, Cl, urea, creatinine, Ca, Mg, total PO(4), glucose, fructose, lactate, total protein, and osmolalities were measured in amniotic and allantoic fluids collected at Days 50, 100, and 150 of gestation from NT pregnancies and those generated by the transfer of in vitro-produced embryos or by artificial insemination. Deviations in fetal fluid composition between NT and control pregnancies were apparent after placental and fetal organ development, even when no gross morphological abnormalities were observed. Individual NT fetuses were affected to varying degrees. Elevated allantoic Na was associated with lower K and increased allantoic fluid volume or edema of the fetal membranes. Total PO(4) levels in NT allantoic and amniotic fluid were elevated at Days 100 and 150. This was not accompanied by hypophosphatemia at Day 150, suggesting that PO(4) acquisition by NT fetuses was adequate but that its readsorption by the kidneys may be impaired. Excessive NT placental weight was associated with low allantoic glucose and fructose as well as high lactate levels. However, the fructogenic ability of the NT placenta appeared to be normal. The osmolality of the fetal fluids was maintained within a narrow range, suggesting that the regulation of fluid composition, but not osmolality, was impaired in NT pregnancies.     

Guide wire assisted catheterization and colored dye injection for vascular mapping of monochorionic twin placentas

Monochorionic (MC) twin pregnancies are associated with significantly higher morbidity and mortality rates than dichorionic twins. Approximately 50% of MC twin pregnancies develop complications arising from the shared placenta and associated vascular connections. Severe twin-to-twin syndrome (TTTS) is reported to account for approximately 20% of these complications. Inter-twin vascular connections occur in almost all MC placentas and are related to the prognosis and outcome of these high-risk twin pregnancies. The number, size and type of connections have been implicated in the development of TTTS and other MC twin conditions. Three types of inter-twin vascular connections occur: 1) artery to vein connections (AVs) in which a branch artery carrying deoxygenated blood from one twin courses along the fetal surface of the placenta and dives into a placental cotyledon. Blood flows via a deep intraparenchymal capillary network into a draining vein that emerges at the fetal surface of the placenta and brings oxygenated blood toward the other twin. There is unidirectional flow from the twin supplying the afferent artery toward the twin receiving the efferent vein; 2) artery to artery connections (AAs) in which a branch artery from each twin meets directly on the superficial placental surface resulting in a vessel with pulsatile bidirectional flow, and 3) vein to vein connections (VVs) in which a branch vein from each twin meets directly on the superficial placental surface allowing low pressure bidirectional flow. In utero obstetric sonography with targeted Doppler interrogation has been used to identify the presence of AV and AA connections. Prenatally detected AAs that have been confirmed by postnatal placental injection studies have been shown to be associated with an improved prognosis for both twins. Furthermore, fetoscopic laser ablation of inter-twin vascular connections on the fetal surface of the shared placenta is now the preferred treatment for early, severe TTTS. Postnatal placental injection studies provide a valuable method to confirm the accuracy of prenatal Doppler ultrasound findings and the efficacy of fetal laser therapy. Using colored dyes separately hand-injected into the arterial and venous circulations of each twin, the technique highlights and delineates AVs, AAs, and VVs. This definitive demonstration of MC placental vascular anatomy may then be correlated with Doppler ultrasound findings and neonatal outcome to enhance our understanding of the pathophysiology of MC twinning and its sequelae. Here we demonstrate our placental injection technique.     

Photoacoustic imaging of the human placental vasculature

Minimally invasive fetal interventions require accurate imaging from inside the uterine cavity. Twin‐to‐twin transfusion syndrome (TTTS), a condition considered in this study, occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses. Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. However, white light fetoscopy provides limited visibility of placental vasculature, which can lead to missed anastomoses or incomplete photocoagulation. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, two PA systems were used to visualize chorionic (fetal) superficial and subsurface vasculature in human placentas. The first system comprised an optical parametric oscillator for PA excitation and a 2D Fabry‐Pérot cavity ultrasound sensor; the second, light emitting diode arrays and a 1D clinical linear‐array ultrasound imaging probe. Volumetric photoacoustic images were acquired from ex vivo normal term and TTTS‐treated placentas. It was shown that superficial and subsurface branching blood vessels could be visualized to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast. This study demonstrated the strong potential of PA imaging to guide minimally invasive fetal therapies.      

Regulatory response to washout of amniotic fluid in sheep

To test the hypothesis that a substance present in the amniotic fluid could serve as a regulator of amniotic fluid volume, we drained and discarded amniotic fluid while replacing it with lactated Ringer solution that was isotonic to amniotic fluid. Seven ewes with singleton fetuses at 119 +/- 1 days of gestation (mean +/- SE) were instrumented with multiple indwelling catheters in the pedal artery, pedal vein, and amniotic cavity. During the exchange periods, an average of 3,019 +/- 171 ml/day of lactated Ringer solution was infused into the amniotic cavity while an equal amount of amniotic fluid was pumped out and discarded. During the control period, amniotic fluid composition and volume were not altered. Exchange and control periods started with the same amniotic fluid volume, lasted 3 or 4 days, and were randomized with regard to order. Amniotic fluid volume measured by vacuum drainage was 556 +/- 98 ml at the end of the control period and 986 +/- 209 ml (P = 0.03) at the end of the exchange period. Fetal arterial blood gases, hemodynamic parameters and the osmolality gradient between fetal plasma and amniotic fluid were not altered by the exchange process. A linear relationship between the control amniotic fluid volume and the volume at the end of the exchange period (P = 0.003) suggests that the animals with larger control volumes responded to isovolumic dilution with a larger volume increase. We conclude that amniotic fluid may contain a substance that regulates amniotic volume.     

Absorption of amniotic fluid by amniochorion in sheep

Swallowing of amniotic fluid and lung fluid inflow were eliminated in 10 chronically instrumented fetuses. The urachus was ligated, and fetal was urine drained to the outside. At the beginning and the end of 21 experiments of 66 +/- 5 (SE) h duration, all amniotic fluid was temporarily drained to the outside for volume measurement and sampling. Amniotic fluid osmolalities and oncotic pressures were experimentally controlled. Amniochorionic absorption of amniotic fluid depended strongly on the osmolality difference between amniotic fluid and fetal plasma (P < 0.001), but at zero osmolality difference there still was a mean absorption rate of 23.8 +/- 4.7 (SE) ml/h (P < 0.001). Absorption was unaffected by the protein concentration difference between amniotic fluid and fetal plasma, but infused bovine albumin in the amniotic fluid was absorbed at a rate of 1.8 8 +/- 0.4 g/h (P < 0.001), corresponding to a volume flow of fluid of 33.8 8 +/- 6.1 ml/h (P < 0.001). Fluid absorption in the amniochorion is driven in part by crystalloid osmotic pressure, but about 25 ml/h is absorbed by a path that is permeable to protein. That path has the physiological characteristics of lymphatic drainage, although no anatomic basis is known to exist for a lymphatic system in the amniochorion.     

Early changes in vascular dynamics in relation to twin-twin transfusion syndrome.

A clearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.     

Maternal dehydration: impact on ovine amniotic fluid volume and composition

Maternal dehydration consistent with mild water deprivation or moderate exercise results in maternal and fetal plasma hyperosmolality and increased plasma arginine vasopressin (AVP). Previous studies have demonstrated a reduction in fetal urine and lung fluid production in response to maternal dehydration or exogenous fetal AVP. As fetal urine and perhaps lung liquid combine to produce amniotic fluid, maternal dehydration may affect the amniotic fluid volume and/or composition. In the present study, six chronically-prepared pregnant ewes with singleton fetuses (128 +/- 1 day) were water deprived for 54 h to determine the effect on amniotic fluid. Maternal plasma osmolality (306.5 +/- 0.9 to 315.6 +/- 1.9 mOsm/kg) and AVP (1.9 +/- 0.2 to 22.2 +/- 3.2 pg/ml) significantly increased during dehydration. Similarly, fetal plasma osmolality (300.0 +/- 0.9 to 312.7 +/- 1.7 mOsm/kg) and AVP (1.4 +/- 0.1 to 10.4 +/- 2.4 pg/ml) increased in parallel to maternal values. Amniotic fluid osmolality (276.8 +/- 5.7 to 311.6 +/- 6.5 mOsm/kg) and sodium (139.8 +/- 4.8 to 154.0 +/- 5.4 mEq/l) and potassium (9.1 +/- 1.3 to 13.9 +/- 2.4 mEq/l) concentrations increased while a significant (35%) reduction in amniotic fluid volume occurred (871 +/- 106 to 520 +/- 107 ml). These results indicate that maternal dehydration may have marked effects on maternal-fetal-amniotic fluid dynamics, possibly contributing to the development of oligohydramnios.     

Influence of maternal obesity and metabolic and vascular mediators in twin-twin transfusion syndrome

Obesity is a risk factor for complications in singleton and twin pregnancies; however, there are limited data regarding maternal body mass index (BMI) in the setting of twin-twin transfusion syndrome (TTTS). We hypothesized that increased BMI in TTTS is associated with adverse perinatal outcomes and vascular pathology. A retrospective study of twin reversed arterial perfusion (n = 4), selective intrauterine growth restriction (n = 10) and TTTS (n = 33) was conducted. Treatment included fetoscopic laser photocoagulation (FLP) (n = 35) or Solomon technique (n = 12). Ex vivo placental intravascular injections, immunohistochemistry, and perinatal outcomes were compared by maternal BMI. In pregnancy complicated by TTTS, 16/33 women were obese (BMI > 30 kg/m²) and 11/33 were overweight (BMI 25–29.9 kg/m²). Women who were overweight or obese had an increased rate of premature rupture of membranes (PPROM), cesarean delivery, and/or concomitant co-morbidities when compared to the normal weight group. Duration of neonatal intensive care unit (NICU) admission was longer in neonates of overweight/obese women versus normal weight. Placental examination of FLP sites in the obese group showed larger infarcts, increased adipose triglyceride lipase, and a proangiogenic phenotype. Increased BMI is common in our TTTS cohort and it is associated with higher rate of co-morbidity, PPROM, prolonged NICU stay, and an imbalance of placental metabolic and vascular mediators.     

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.     

The role of ultrasound in multiple pregnancy.

The advances in reproductive technologies have changed the demographics of multifetal pregnancies. In the first trimester, ultrasound allows to diagnose the number of multiples, chorionicity and amnionicity, the presence or absence of nuchal translucency, early growth discordance, severe malformations and the origin of activities and contacts between multiples. In the second and third trimester, the opportunity to examine the cervix by transvaginal ultrasound should not be missed to detect the risk of premature delivery. Ultrasound is essential for the early grading and treatment of twin-to-twin transfusion syndrome (TTTS), the diagnosis of malformations and growth disturbances. Doppler velocimetry has proven to be able to reduce perinatal mortality in twin pregnancies. Finally, ultrasound is used for the detection of the position of multiples and the decision of the optimal route of delivery. This is of main importance in delayed interval delivery and expectant management of multifetal pregnancies and early cervical dilatation.     

Ultrasound determination of chorionicity in twin pregnancy: accuracy and operator experience.

To evaluate the accuracy of ultrasound in early detection of chorionicity and amnionicity in twin pregnancies and evaluate the role of operator-experience, a prospective follow up of 87 consecutive twin pregnancies was performed. Chorionicity and amnionicity were determined by 17 different observers, divided in 2 groups on the basis of their experience, using a composite of US markers at the first US examination confirming a viable intrauterine twin pregnancy. Accuracy of prediction was determined for both groups by comparison with postnatal pathology. From the 87 pregnancies examined at 10.1 (minimum 5.5 weeks, maximum 26.0) weeks of gestation, pathology was available in 82 cases and a correct prediction of chorionicity was made in all but two cases, both being diagnosed as monochorionic while dichorionic by observers belonging the more experienced group. No monochorionic pregnancy was missed and amnionicity was correctly diagnosed in all cases, including two monoamniotic twins. We conclude that use of a composite of ultrasound markers for early detection of chorionicity and amnionicity is reliable in a clinical setting where physicians with a variable degree of experience perform ultrasound examination.     

Amniotic fluid cell morphology in early antenatal prediction of abortion and low birth weight.

The morphology of rapidly adherent (RA) amniotic fluid cells was examined in 201 pregnant women referred for amniocentesis because of two sequential high serum alpha-fetoprotein (AFP) concentrations. Out of 43 amniotic fluid samples containing increased amounts of AFP, 42 had neural or peritoneal cells predominating among the RA cells, the outcome being an infant with a neural-tube defect or exomphalos. In the other case with a raised amniotic fluid AFP concentration but only anterior placental cells the infant was normal. In 25 amniotic fluid samples containing normal amounts of AFP distinctive new patterns of RA cells were observed, termed fetal distress cells. These pregnancies resulted in five spontaneous abortions and 20 infants with birth weights under 2500 g. Fetal distress cells were not detected in any of the remaining 133 samples. One pregnancy was terminated because of a chromosomal abnormality, and there were seven twin pairs not recognised on ultrasonography before amniocentesis. The remaining 125 pregnancies went to term, resulting in infants with birth weights exceeding 2500 g. The results suggest that RA-cell morphology will prove to be of value in the early antenatal prediction of spontaneous abortion and low birth weight.     

The acardiac anomaly

Karyotype analysis of a premature human acardiac twin disclosed normal chromosomes. A review of previous cytogenetic, placental and animal studies suggests that chromosomal errors are not the cause of the acardiac anomaly. Rather, they point to the placental vascular anastomoses as the principal pathogenetic event.