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Incidence, origin, and character of cerebral injury in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery
Abstract
The objective of the study was to determine the incidence, origin, and character of cerebral lesions in monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.
This was a prospective study of monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and monochorionic twins without twin-to-twin transfusion syndrome delivered at our center between June 2002 and September 2005, using cranial ultrasonography.
Incidence of antenatally acquired severe cerebral lesions in the twin-to-twin transfusion syndrome group was 10% (8/84) and 2% (2/108) in the non-twin-to-twin transfusion syndrome group (P = .02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the twin-to-twin transfusion syndrome group and 6% (6/108) in the non-twin-to-twin transfusion syndrome group (P = .04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the twin-to-twin transfusion syndrome group.
Incidence of severe cerebral lesions in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery is high and results mainly from antenatal injury.
... However, there are concerns related to its possible impact on fetal neurodevelopment [13]. Despite advances in the technique, improved outcomes in terms of morbidity and mortality, and increased operator experiences, laser surgery as a treatment for TTTS has been associated with varying rates of severe cerebral injury (3% to 16%) [8,[14][15][16] and neurodevelopmental impairment (8% to 18%) [17]. ...
... In our case, the severe 2 year NDI rate was 2.38%, close to the lower range in studies in this synthesis. The overall rate of NDI in our series was 9.52%, and this data are in the range of those international studies published on this subject [14,23,[26][27][28][29]. ...
... In our case, the severe 2 year NDI rate was 2.38%, close to the lower range in studies in this synthesis. The overall rate of NDI in our series was 9.52%, and this data are in the range of those international studies published on this subject [14,23,[26][27][28][29]. [14,23,[26][27][28][29]. ...
Background:
Twin-twin Transfusion Syndrome (TTTS) represents a significant complication in monochorionic twin pregnancies, caused by an unbalanced shunting of blood through intertwin placental vascular anastomoses. Despite advances in fetoscopic laser surgery, TTTS is still associated with a high rate of cerebral injury. However, there are no studies comparing these pregnancies with uncomplicated monochorionic diamniotic (MCDA) twin pregnancies, establishing the baseline risk of neurodevelopmental impairment. The aim of this study is to evaluate the odds of neurodevelopmental impairment in MCDA twins who undergo fetoscopic laser surgery for twin-twin transfusion syndrome, in comparison to a cohort of uncomplicated MCDA twin pregnancies.
Study design:
This is a retrospective cohort study of children born from MCDA twin pregnancies at a single center between 2008 and 2019. A routine, standardized follow-up assessment was conducted at a minimum of 2 years after delivery. The primary outcome of this was a 2 year neurodevelopmental impairment. Neurological, motor, and cognitive development was assessed by using the revised Brunet-Lézine scale.
Results:
176 children met the enrolment criteria. Of these, 42 (24%; TTTS group) underwent fetoscopic laser surgery for TTTS during pregnancy, and 134 (76%; uncomplicated MCDA group) were uncomplicated MCDA pregnancies. The primary outcome was found in four children (9.52%) in the TTTS group and ten children (7.46%) in the uncomplicated MCDA group (p = 0.67, aOR 2.82, 95% CI 0.49-16.23). Major neurologic impairment was found in 2.38% after fetoscopic laser surgery and 1.49% in uncomplicated MCDA twins (p = 0.70, aOR 0.97, 95% CI 0.22-4.24). The data were adjusted by birth order, birth weight, and gestational age at birth.
Conclusions:
The outcome in MCDA twins who underwent fetoscopic laser surgery for TTTS is comparable to the outcome in uncomplicated MCDA twins. Our findings emphasize the need for long-term neurodevelopmental follow-ups in all children from monochorionic twin gestations.
... Postnatal neuroimaging has advanced our understanding of the relationship between brain injury and neurodevelopmental outcomes in preterm infants, however, data on cranial imaging in survivors of TTTS are currently limited [7][8][9][10][11]. Cerebral imaging studies examining survivors after laser surgery for TTTS have shown rates of severe cerebral lesions ranging from 0% to 14% [8,[11][12][13]. ...
... Postnatal neuroimaging has advanced our understanding of the relationship between brain injury and neurodevelopmental outcomes in preterm infants, however, data on cranial imaging in survivors of TTTS are currently limited [7][8][9][10][11]. Cerebral imaging studies examining survivors after laser surgery for TTTS have shown rates of severe cerebral lesions ranging from 0% to 14% [8,[11][12][13]. Further elucidation of the types of cerebral lesions and their impact on neurodevelopment would enhance preoperative counseling and guide postnatal neurologic follow-up. ...
... This study demonstrated that among 'high-risk' survivors of TTTS treated with laser surgery, neonatal cerebral lesions were significantly associated with NDI. Our result of 18% of twins having at least one cerebral lesion is slightly higher than previously reported incidences of 0-14% after SLPCV [8,[11][12][13]. We did not limit the postnatal imaging modality and included cranial ultrasound, CT, and MRI. ...
Objective: The objective of this study is to assess whether postnatally detected cerebral abnormalities are predictive of neurodevelopmental impairment (NDI) in survivors of twin–twin transfusion syndrome (TTTS) that underwent laser surgery.
Materials and methods: Ninety-nine children treated for TTTS had neurodevelopmental assessment at age 2-years (±6 weeks). ‘High-risk survivors’ had cerebral imaging in the neonatal period. ‘High-risk survivors’ were defined as (1) delivered at <32 weeks; or (2) cerebral imaging clinically indicated. NDI was a composite outcome of: Battelle Developmental Inventory 2nd edition (BDI-2) score <70, cerebral palsy, blindness, and/or deafness. Multilevel logistic regression with robust standard errors was used to evaluate associations between cerebral lesions and NDI.
Results: Fifty-six children were ‘high-risk survivors’ and had neonatal cerebral imaging. Ten twins (18%) had at least one cerebral lesion, including grade 1–2 intraventricular hemorrhage (8), cystic periventricular leukomalacia (2), ventriculomegaly (1), and bilateral subependymal cyst (1). The risk of NDI in the ‘high-risk survivors’ was 7% (4/56) compared with 0% (0/43) in the remaining group. Among ‘high-risk survivors’, cerebral lesions were a significant risk factor for NDI (OR = 19.28, p < .001).
Conclusions: Among ‘high-risk survivors’ of TTTS treated with laser surgery, cerebral lesions identified on neonatal imaging were associated with NDI at 2-years.
... En una pequeña serie clínica 61 , el procedimiento dio lugar a un riesgo 75% de MFIU para el feto más pequeño en la primera semana después de la aplicación de la terapia. Como compensación, esta terapeútica tiene efectos beneficiosos en el gemelo mayor con una reducción significativa en el riesgo de muerte concomitante de este gemelo después de la muerte intrauterina del feto pequeño 72 . En cualquier caso, el láser es un procedimiento complejo y que incluso podría ser inviable, en particular cuando ciertos factores como una placenta anterior, una gran anastomosis AA y / o inserciones de cordón umbilical muy cercanas uno del otro. ...
... Inklaar et al 70 , en una reciente revisión sistemática demostraron luego del análisis de 11 estudios que la incidencia de lesión cerebral grave en los gemelos MC con RCIUs y/o peso fetal discordante, varía desde el 0% al 33%, con un promedio de aproximado del 9,7% 45 a 57/661 . La incidencia parece ser similar en comparación con el riesgo de lesión cerebral grave reportado en los gemelos bicoriales (8%) y baja en comparación con los gemelos MC tienen STFF (rango: 9% a 38%) 71,72,73 . Además, reportaron que la mayor incidencia de lesión cerebral grave se informó en cohortes con menor mediana de edad gestacional en el nacimiento, en los estudios incluidos casos con MFIU de uno de los gemelos y finalmente, en los embarazos con resultados Doppler anormal de la arteria umbilical. ...
... Dos teorías diferentes podrían explicar este hallazgo. Según Gratacós et al 45,72 , el tipo III (Doppler AFFD -FFDR intermitente) fue identificado como el de mayor riesgo para MFIU del gemelo pequeño y daño neurológico en el gemelo más grande. Teóricamente, este grupo puede ser más propenso intraútero a transfusiones sanguíneas fetales a través de las grandes anastomosis A-A que resulta en lesión hipóxica, particularmente en el gemelo más grande. ...
Selective intrauterine growth restriction occurs in 10-19% of monochorionic twins, and is associated with increased mortality important and perinatal morbidity. The clinical course is given largely by the presence of placental vascular anastomosis and asymmetric distribution. It classified into three types according to the proposed Doppler umbilical artery smaller twin, the one that correlates with different clinical behaviors and characteristics of the placenta, which helps in counseling and obstetric conduct. The type I have a favorable prognosis for satisfactory perinatal outcome so closely monitored by ultrasound and Doppler is recommended. The type II has a poor prognosis and type III intermediate and unpredictable prognosis. In these last two you can make an expectant management until deterioration of the small fetus is observed, considering laser coagulation or cord occlusion (selective feticide). Both behaviors appear to increase the chances of survival of the fetus of normal weight.
... The reported incidence of cerebral injury after amnioreduction ranges from 6% to 38% compared to 8% to 18% following laser surgery (Cincotta et al., 2009;Lenclen et al., 2007;Lopriore et al., 2006;Senat et al., 2004). Several types of cerebral injury have been described, including cystic periventricular leukomalacia (PVL), cerebral white-matter cysts, severe intraventricular hemorrhage (IVH), ventricular dilatation, cerebral atrophy, and arterial ischemic stroke (Lopriore et al., 2006). ...
... The reported incidence of cerebral injury after amnioreduction ranges from 6% to 38% compared to 8% to 18% following laser surgery (Cincotta et al., 2009;Lenclen et al., 2007;Lopriore et al., 2006;Senat et al., 2004). Several types of cerebral injury have been described, including cystic periventricular leukomalacia (PVL), cerebral white-matter cysts, severe intraventricular hemorrhage (IVH), ventricular dilatation, cerebral atrophy, and arterial ischemic stroke (Lopriore et al., 2006). Donors and recipients appear to be equally at risk (Lopriore et al., 2006). ...
... Several types of cerebral injury have been described, including cystic periventricular leukomalacia (PVL), cerebral white-matter cysts, severe intraventricular hemorrhage (IVH), ventricular dilatation, cerebral atrophy, and arterial ischemic stroke (Lopriore et al., 2006). Donors and recipients appear to be equally at risk (Lopriore et al., 2006). Cerebral injury may result from antenatal injury and/or postnatal injury, partly due to extreme prematurity, an important risk factor for cystic PVL and IVH. ...
Twin–twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins with TTTS are often born prematurely after an extremely distressing and highly hazardous fetal period. Follow-up studies report varying rates of cerebral palsy (CP) and long-term neurodevelopmental impairment (NDI). This review discusses the latest findings on the long-term outcome of TTTS survivors, possible risk factors for long-term impairment, and provides recommendations for future research.
... They also found that low GA was the only significant factor associated with neurological impairment in twins treated with laser therapy due to TTTS [9]. Lopriore et al. [23] compared monochorionic twins with TTTS and laser therapy with monochorionic twins without TTTS. They described a significant higher incidence of severe cerebral lesions in twins with TTTS than in monochorionic twins without TTTS (10 vs. 2%, p = 0.02) [23]. ...
... Lopriore et al. [23] compared monochorionic twins with TTTS and laser therapy with monochorionic twins without TTTS. They described a significant higher incidence of severe cerebral lesions in twins with TTTS than in monochorionic twins without TTTS (10 vs. 2%, p = 0.02) [23]. ...
Introduction:
The only causal therapy is fetoscopic laser surgery (FLS). The aims of this study were to analyze the long-term outcome of monochorionic twins treated by FLS, including their school career, need for therapy and special aid equipment, and free-time activities, and compare their outcome to matched dichorionic twins.
Material and methods:
Among the 57 women treated at a single fetal treatment center between 2008 and 2017 with FLS because of twin-to-twin transfusion syndrome, 25 women with 42 children were included in the FLS group. The control group consisted of 16 dichorionic twin pairs matched for birth year, gestational age (GA), birth weight, and sex. The long-term outcome was assessed by a parental questionnaire and a standardized neurodevelopmental examination for children born before 32 gestational weeks or with a birth weight lower than 1500 g. They were also registered into the Swiss Neonatal Network database. The primary outcome was event-free survival, defined as normal neurology, behavior, vision, and hearing. The secondary outcomes were school career, need for therapy and special aid equipment, and free-time activities.
Results:
An event-free survival was found in 32 children (76%) in the laser and in 24 children (75%) in the control group (p = 0.91). Neurological anomalies were found in 5 children (12%) in the laser group and 3 children (9%) in the control group (p = 1.00). Multiple logistic regression analysis showed that GA at delivery was the only predictive factor for event-free survival. There were no significant differences regarding school career, therapies, or special aid equipment between the 2 groups. We found that children without FLS were involved in more free-time activities and needed fewer breaks during physical activity than children with FLS during pregnancy.
Conclusion:
The outcome of monochorionic twins treated with FLS is comparable to the outcome of dichorionic twins. Long-term neurodevelopment in the cohort was mainly dependent on GA at birth.
... Therefore, severe fetofetal transfusion syndrome exposes the donors and recipients to a higher risk of cerebral damage with wide spectrum of severity. In twin-twin transfusion syndrome, the prevalence of cerebral lesion was reported in 13-35% [24,25] and the incidence of long-term neurological morbidity was reported in 10-25% [24]. However, there is lacking of this information in monochorionic triplet pregnancies. ...
... Therefore, severe fetofetal transfusion syndrome exposes the donors and recipients to a higher risk of cerebral damage with wide spectrum of severity. In twin-twin transfusion syndrome, the prevalence of cerebral lesion was reported in 13-35% [24,25] and the incidence of long-term neurological morbidity was reported in 10-25% [24]. However, there is lacking of this information in monochorionic triplet pregnancies. ...
Background:
Monochorionic multifetal pregnancies are at increased risk of adverse perinatal outcome because of placental vascular anastomoses. We present a case of multicystic encephalomalacia and gastrointestinal injury in two surviving fetuses following single fetal death in first trimester and subsequent fetofetal transfusion syndrome in a monochorionic triplet pregnancy.
Case presentation:
A 31-year-old nulliparous woman had a spontaneous monochorionic triamniotic triplet pregnancy. Three live fetuses with single placenta were seen at 8-week ultrasound scan. One fetus demised at 11 weeks and 3 days of gestation. Dilated echogenic bowel and ascites were found in one surviving fetus at 23 weeks of gestation. At 28 weeks of gestation, the pregnancy was complicated by fetofetal transfusion syndrome in which discordant amniotic fluid volumes were found. Two days later, emergency Caesarean section was performed because of worsening of fetal Doppler and biophysical profile. One baby was found to have jejunal atresia requiring surgery at 4 days old. He had periventricular leukomalacia and intracranial haemorrhage, but subsequent normal neurological development. Another baby had gastric perforation requiring surgery at 2 days old. He was confirmed to have multicystic encephalomalacia by cranial ultrasound and magnetic resonance imaging. He suffered from developmental delay, epilepsy and cerebral palsy.
Conclusion:
This case alerts the obstetricians the possible hypoxic-ischemic injury to the survivors of monochorionic triplet pregnancy after the co-triplet death in the first trimester and fetofetal transfusion syndrome. Antenatal assessment and postnatal follow-up are important for these high-risk multiple pregnancies.
... The neurologic outcomes in the neonatal period following laser procedures, such as intraventricular hemorrhage, periventricular leukomalacia, cerebral white matter cysts, ventricular dilatation, and cerebral atrophy, range from 8 to 18% [51,72,73]. The long-term neurodevelopmental outcomes vary between 3 and 12% for cerebral palsy and 4 and 18% for neurodevelopmental impairment [73]. ...
... The neurologic outcomes in the neonatal period following laser procedures, such as intraventricular hemorrhage, periventricular leukomalacia, cerebral white matter cysts, ventricular dilatation, and cerebral atrophy, range from 8 to 18% [51,72,73]. The long-term neurodevelopmental outcomes vary between 3 and 12% for cerebral palsy and 4 and 18% for neurodevelopmental impairment [73]. In one study, the neurodevelopmental scores in preterm-born children treated with laser therapy for TTTS were similar in preterm-born DC children, suggesting that prematurity has the main role in the neurologic impairment in fetus treated with laser photocoagulation [74]. ...
... Brain magnetic resonance imaging at 1 month of age confirmed the injury as a focal hemorrhage in the frontoparietal lobe (Fig. 2C). The incidence of severe cerebral lesions on cranial ultrasonography has been reported 14 to range from 3% to 16% [11][12][13][14]. The exact mechanism responsible for antenatal cerebral injury in TTTS is unclear, as the methodologies and definitions vary. ...
Objective:
To report the experiences of triplet pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser coagulation at a single center.
Methods:
Herein, we conducted a retrospective analysis to investigate the management and perinatal outcomes of triplet pregnancies with TTTS treated at a single institution between 2017 and 2022.
Results:
Seven of the 98 triplet pregnancies (7.1%) encountered were complicated by TTTS, and all were dichorionic triamniotic triplets. Of the seven triplet pregnancies complicated by TTTS, four were treated with fetoscopic laser coagulation at our center, at a median gestational age of 20 weeks. No procedure-related complications or maternal complications were observed. The survival rate was higher and perinatal outcomes were better in fetoscopic laser coagulation cases than in other management cases. Four donor and four recipient triplets survived, with a median gestational age of 33 weeks at delivery. Although there were no cases of poor neonatal outcomes, one case was diagnosed with white matter injury, suspected to be hypoxic-ischemic encephalopathy on postnatal investigation.
Conclusion:
Fetoscopic laser coagulation is a feasible treatment option for triplet TTTS, provided the attending specialists have extensive experience with this technique.
... In twin pregnancies, there is an increased risk of abnormal postnatal neurological development in fetuses surviving TTTS [69][70][71]. Others showed a benefit of fetal brain MRI for the detection of brain abnormalities in TTTS [72,73]. ...
In open spina bifida we studied the use of MRI for the assessment of the posterior fossa and prevalence of supratentorial anomalies before and after in utero repair. New postprocessing techniques were applied to evaluate fetal brain development in this population compared to controls. In fetuses with congenital diaphragmatic hernia, we evaluated the brain development in comparison to controls. Diffusion weighted imaging was applied to study difference between fetuses with proven first trimester cytomegalovirus infection and controls. Finally, we investigated the value of third trimester fetal brain MRI after treatment for complicated monochorionic diamniotic pregnancies.
... 1,2 In the absence of treatment, the outcome is poor, leading to perinatal demise or severe neurological lesions in one or both twins. 3,4 The most commonly used classification remains the Quintero staging system. 5 However, it does not incorporate obstetric parameters such as gestational age, cervical length, placental location, or even the presence of a selective intrauterine growth restriction (sIUGR). ...
Objective:
To evaluate the effect of gestational age at laser therapy for twin-to-twin transfusion syndrome (TTTS) on perinatal outcome.
Design and settings:
Single retrospective observational cohort.
Population:
All consecutive pregnancies affected by TTTS and referred to our department between January 2013 and August 2020.
Methods:
Gestational age was modelled both as a categorical and as a continuous variable. Log-binomial regression was used to estimate the odds ratios (crude and adjusted for placental location, Quintero stage and cervical length) as well as the adjusted predicted probability of survival and fetal loss according to gestational age at laser.
Main outcomes:
Fetal and neonatal survival, preterm premature rupture of membranes (PPROM).
Results:
Of the 503 pregnancies referred for TTTS, 431 were treated by laser therapy. Gestational age at laser was positively and significantly associated with the overall survival at birth and at discharge (adjusted OR=1.12, 95% CI [1.05, 1.19]), as with a reduction in double fetal loss (adjusted OR=0.81, 95% CI [0.71, 0.92]). Conversely, the rate of PPROM prior to 24 weeks was significantly higher in early cases (32% of PPROM<24 weeks when laser was performed before 17 weeks vs 1.5% after 22 weeks, p<0.001, adjusted OR=0.60 95% CI [0.48, 0.72]). Among the survivors, preterm birth (PTB) before 28 weeks was significantly related to the gestational age at laser (OR=0.91, 95% CI [0.84, 0.99]), resulting in a significant impact on neonatal morbidity (OR=0.91, 95% CI [0.85, 0.97]).
Conclusion:
Our results suggest a significant and independent impact of the gestational age at laser surgery on perinatal survival, PPROM, and neonatal morbidity.
... weeks across the time period but mean survival increased for a both fetuses from 35% to 65% and for a single fetus from 70-88% (64). After laser surgery, hemorrhagic or ischemic cerebral lesions are observed in about 2-10% of both recipient and donor fetuses on ultrasound or MRI (92,93). This risk is not affected by single fetal demise after surgery but it was higher in cases of recurrent TTTS or post-laser TAPS (93). ...
Twin to twin transfusion syndrome (TTTS) is a common complication that typically presents in the second trimester of pregnancy in 10-15% of monochorionic twins due to net transfer of volume and hormonal substances from one twin to the other across vascular anastomoses on the placenta. Without recognition and treatment, TTTS is the greatest contributor to fetal loss prior to viability in 90-100% of advanced cases. Ultrasound diagnosis of monochorionicity is most reliable in the first trimester and sets the monitoring strategy for this type of twins. The diagnosis of TTTS is made by ultrasound with the findings of polyhydramnios due to volume overload and polyuria in one twin and oligohydramnios due to oliguria of the co-twin. Assessment of bladder filling as well as arterial and venous Doppler patterns are required for staging disease severity. Assessment of fetal cardiac function also provides additional insight into the fetal cardiovascular impacts of the disease as well as help identify fetuses that may require postnatal follow up. Fetoscopic laser ablation of the communicating vascular anastomoses between the twins is the standard treatment for TTTS. It aims to cure the condition by interrupting the link between their circulations and making them independent of one another. Contemporary outcome data after laser surgery suggests survival for both fetuses can be anticipated in up to 65% of cases and survival of a single fetus in up to 88% of cases. However, preterm birth remains a significant contributor to postnatal morbidity and mortality. Long term outcomes of TTTS survivors indicate that up to 11% of children may show signs of neurologic impairment. Strategies to minimize preterm birth after treatment and standardized reporting by laser centers are important considerations to improve overall outcomes and understand the long-term impacts of TTTS.
... The incidence of cerebral injury in TTTS has dropped considerably since the introduction of laser therapy and reported ranges are now between 2 and 18% [24,25,27,[62][63][64][65][66]. In our own center, the incidence has decreased since the start of our laser surgery program in 2000 from 14% in the first five years, to 6% in the most recently studied cohort treated between 2011 and 2014 [48,67]. Various reasons have been suggested to explain the decrease in brain injury, including improvement in laser technique and a learning curve effect, both associated with a decrease in residual anastomoses. ...
Introduction: Twin-twin transfusion syndrome (TTTS) is a devastating complication of monochorionic twin pregnancy and remains a major challenge for worldwide fetal medicine specialists. In TTTS, inter-twin transfusion through vascular anastomoses in the shared placenta leads to severe hemodynamic imbalance. This review summarizes the current knowledge of TTTS.
Areas covered: The most recent insights concerning the management of TTTS, as well as fetal and neonatal complications are described. Relevant articles were selected based on a Pubmed search using the keywords below. Understanding of the underlying pathophysiology has improved greatly as a result of placental injection studies. Advancements in antenatal management have led to increased perinatal survival and a decreased incidence of neonatal complications, including brain injury and neurodevelopmental impairment.
Expert opinion: Further opportunities for improvement comprise technological innovations in laser procedures and the prevention of preterm rupture of membranes with subsequent prematurity. A non-invasive treatment such as high-intensity focused ultrasound (HIFU) seems to hold promise for the future treatment of TTTS. Fetal MRI studies are important to improve our understanding of fetal brain injury and should relate their findings to long-term neurodevelopment. International collaboration and centralization of care are of paramount importance to ensure the best care for our patients.
... Furthermore, morbidities in the immediate postnatal period reflecting hemodynamic disturbances in the fetal period were analyzed in the present study. Newborns with TTTS may experience hemodynamic instability after birth; 30~70% of brain injuries occur during the postnatal period 5,24 . In the present study, one-third of the study population experienced hypotension during the first week of life, and 17% of the study population had AKI. ...
Altered hemodynamics associated with twin to twin transfusion syndrome (TTTS) can be manifested in the fetal and neonatal heart. This study evaluated the association between cardiac manifestations immediately after birth and brain injury in preterm infants with TTTS. Medical records of preterm infants who were born at <35 weeks of gestation with TTTS and admitted to the neonatal intensive care unit at Seoul National University Children’s Hospital between January 2011 and January 2018 were reviewed. TTTS was prenatally diagnosed and staged according to the Quintero criteria. Echocardiographic findings, brain ultrasound and MRI imaging findings were analyzed. Fifty-three infants were enrolled in this study. Thirty-two infants (60.3%) were treated by fetoscopic laser coagulation. Brain injury developed in 15 infants (28.3%). Hypotension within the first week and immediate postnatal cardiac manifestations were more prevalent in the brain injury group. In the multivariate analysis, acute kidney injury and cardiac manifestations, such as ventricular dysfunction and tricuspid regurgitation, were statistically associated with brain injury in the study population. Immediate postnatal cardiac manifestations, such as ventricular dysfunction and tricuspid regurgitation, can serve as surrogate markers for perinatal hemodynamic disturbance, which are associated with early neonatal brain injury in preterm infants with TTTS.
... TAPS was diagnosed according to antenatal and/or postnatal criteria [15]. Severe cerebral injury was defined as the presence of at least one of the following findings on cerebral ultrasound: intraventricular hemorrhage (IVH) ≥ grade III, periventricular leukomalacia (PVL) ≥ grade II, ventricular dilatation ≥97th percentile, and porencephalic cyst, arterial infarction, venous hemorrhagic infarction, or other severe cerebral lesions associated with adverse neurological outcome [16]. Neonatal cranial ultrasonography was performed by experienced neonatologists in accordance with our clinical protocol, as described in detail in our earlier studies [17]. ...
Despite many developments in its management, twin-to-twin transfusion syndrome (TTTS) remains an important risk factor for long-term neurodevelopmental impairment (NDI). Our objective was to compare the incidence of severe NDI in a recent cohort of TTTS survivors, treated with laser surgery from 2011 to 2014, with a previous cohort treated from 2008 to 2010. Neurological, cognitive, and motor development were assessed at two years of age. We determined risk factors associated with Bayley-III scores. Severe NDI occurred in 7/241 (3%) survivors in the new cohort compared to 10/169 (6%) in the previous cohort (p = 0.189). Disease-free survival (survival without severe impairment) did not significantly differ. Low birth weight and being small for gestational age (SGA) were independently associated with lower cognitive scores (both p < 0.01). Severe cerebral injury was related to decreased motor scores (B = −14.10; 95% CI −3.16, −25.04; p = 0.012). Children with severe NDI were born ≥32 weeks’ gestation in 53% of cases and had no evidence of cerebral injury on cranial ultrasound in 59% of cases. Our results suggest that improvement in outcome of TTTS has reached a plateau. Low birth weight, SGA, and cerebral injury are risk factors for poor neurodevelopmental outcome. Neither gestational age above 32 weeks nor the absence of cerebral injury preclude severe NDI.
... In our analysis, after controlling for antenatal steroids and birth weight, two factors associated with extremely preterm Results are expressed as mean ± SD and for continuous variables and by percentage for categorical variables GMFCS gross motor function classification score a Missing information for some patients-denominator for available data presented survival to discharge [30], laser-treated TTTS status had no effect of mortality. Several studies reported an increased risk of cerebral injury and neurological morbidity in TTTS newborns [31][32][33][34][35][36]. In the randomized trial by Senat et al. [8], infants in the laser group had a lower incidence of cystic PVL with very large cysts (≥grade 3) than in the amnioreduction group [8]. ...
Objective:
To compare short-term and long-term outcomes of preterm infants born at <29 weeks of gestational age (GA) with twin-twin transfusion syndrome (TTTS) treated with laser therapy to preterm twin infants without TTTS.
Design:
Retrospective case-control study comparing 33 preterm TTTS twins to 101 preterm diamniotic-dichorionic (di-di) twins born at our institution between 2006 and 2015.
Results:
GA at birth were 26.4 ± 1.4 weeks (TTTS) and 26.9 ± 1.6 weeks (di-di) (p = 0.07). TTTS premature newborns were less exposed to antenatal steroids (p = 0.01), more frequently born by C-section (p = 0.005), received more surfactant therapy (p = 0.004, and were smaller for GA (p < 0.001). When adjusted for antenatal steroids and birth weight, TTTS status was not associated with increased mortality (HR 1.66, 95% CI 0.77-3.56, p = 0.20). No differences were found on neurodevelopmental outcomes at 18 months of corrected GA.
Conclusion:
Premature TTTS newborns treated with fetal laser therapy had similar survival and neurodevelopmental outcomes compared to preterm di-di twins without TTTS.
... In our analysis, after controlling for antenatal steroids and birth weight, two factors associated with extremely preterm Results are expressed as mean ± SD and for continuous variables and by percentage for categorical variables GMFCS gross motor function classification score a Missing information for some patients-denominator for available data presented survival to discharge [30], laser-treated TTTS status had no effect of mortality. Several studies reported an increased risk of cerebral injury and neurological morbidity in TTTS newborns [31][32][33][34][35][36]. In the randomized trial by Senat et al. [8], infants in the laser group had a lower incidence of cystic PVL with very large cysts (≥grade 3) than in the amnioreduction group [8]. ...
BACKGROUND
Twin pregnancies and fetal therapies are associated with increased risk of preterm delivery. Limited literature exists on outcomes for extremely preterm infants born in the context of a pregnancy complicated with twin-twin transfusion syndrome (TTTS).
OBJECTIVES
To compare mortality of preterm newborns who received laser therapy for TTTS to preterm controls born in the context of a dichorionic-diamniotic (di-di) pregnancy. Secondary outcomes are: short-term neonatal morbidities and neurodevelopmental measures at 18 months of corrected gestational age (cGA).
DESIGN/METHODS
Case-control retrospective study of all twins infant born <29 weeks of gestation between 2006 and 2015 at Sainte-Justine Hospital. Preterm with TTTS and fetal laser therapy were compared to preterm di-di twins. Survival analysis was done using Cox proportional regression model.
RESULTS
Thirty-three preterms with TTTS (TTTS-laser group) were compared to 101 preterms without TTTS (non-TTTS group). Demographic data and comparisons for short-term morbidities are presented in Table 1. TTTS status was not associated with increased mortality when adjusting for birth weight and antenatal steroids (Table 2). No differences were found for Bayley-3rd edition score, cerebral palsy, vision impairment, hearing impairment and growth parameters at 18-month cGA.
CONCLUSION
Extremely premature newborns exposed to fetal laser therapy due to TTTS had similar survival and neurodevelopmental outcomes compared to contemporaneous extremely preterm di-di twins.
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... Survivors of intrauterine co-twin death (CD) have a greater than 20% average risk of NDI. [1][2][3] Although fetoscopic laser photocoagulation of placental anastomosing vessels (FLPAV) is now the treatment of choice for sonographically diagnosed TTTS of Quintero stage II or greater, 4 between 3% and 16% of survivors have brain abnormalities that are demonstrable on post-natal cranial ultrasonography [5][6][7] and 6% to 25% suffer from NDI. [8][9][10][11][12] In a recent evaluation of children participating in the Eurofoetus trial, 12% of survivors of TTTS treated with FLPAV were found to have neurological morbidity, either owing to prematurity or as a result of haemodynamic changes associated with the disease and its treatment. 13 However, survivors of CD have an even higher risk of NDI especially when the demise occurs prior to or without FLPAV treatment for TTTS. 1 An uncertain proportion of the total cerebral injuries that occur in complicated monochorionic gestations (cMCGs) are prenatal, and identification of such injuries has the potential to change pregnancy counselling and management. ...
Objective:
To determine the additional diagnostic information provided by prenatal (fetal) magnetic resonance imaging (pMRI) following tertiary ultrasound (US) for fetal cranial abnormalities in complicated monochorionic gestations (cMCGs) METHODS: Women with cMCGs complicated by twin - twin transfusion syndrome (TTTS), co-twin demise (CD), selective intrauterine growth restriction (sIUGR), and / or twin anemia - polycythemia sequence (TAPS) who were referred for pMRI after tertiary US were included.
Primary outcome:
additional diagnostic information by pMRI that changed prognostic counselling.
Results:
33 women with 48 live fetuses had pMRI at a median of 25 weeks (range: 21 - 29). 3/10 survivors of spontaneous CD, 1/8 survivors of CD after TTTS and 1/30 co-survivors had diagnostic information added by pMRI that altered counselling; US was normal in 2 and in the other 3 under- represented parenchymal injury (5/33 = 15%; 95% CI +/- 0.27 - 0.03). Additional findings included occipital lobe infarction, hemispheric injury, dural sinus thrombosis, ischemia producing polymicrogyria, and intraventricular hemorrhage. Another 8 /33 women had additional information provided by pMRI that did not alter counselling.
Conclusion:
pMRI resulted in changed prognostic counselling in 5/33 pregnancies. Evaluation of incorporation of pMRI into routine surveillance of complicated MCGs is needed.
... Hence, the reported incidences of cerebral palsy and major neurological deficiencies in TTTS are 6–23%. [52,53] Management options Several treatment options utilized in the management of TTTS include serial amniodrainage, fetoscopic laser coagulation, septostomy and selective feticide. [54‑56] Amniodrainage is a palliative procedure and involves the iatrogenic reduction of the volume of amniotic fluid. ...
The west Africa sub-region, notably Nigeria, records the highest twin and triplet birth rates globally. Therefore, the time has come for attention to be focused on an area of gemellology, feto-fetal transfusion syndromes in multiplets, in order to attend to what the authors consider a yet-to-be-explored major significant contributor to the overall unacceptably high fetal, perinatal and neonatal losses in the region. This review examines the genetics, embryology and pathophysiology of twinning in general to provide the background to the spectrum of clinical presentations of feto-fetal transfusion syndromes. Twin-to-twin transfusion syndromes (TTTS) are unique prenatal complications of monochorionic multiplets and manifest as twin oligohydramnios polyhydramnios sequence (TOPS), twin anaemia polyhydramnios sequence (TAPS) and twin reversed arterial perfusion syndrome (TRAPS). These grave complications are associated with fetal malformations and early miscarriages as well as fetal weight and haemoglobin discordances, discordant haemodynamic changes in addition to intrauterine deaths, perinatal asphyxia, cerebral palsy and brain damage. Most importantly, the management of TTTS requires highly skilled interventions, expensive equipment, rare expertise and costly treatment options that are currently not available in Nigeria and other developing countries. Moreover, these management options are unavailable in Nigeria because considerable attention of the health system is directed at the burden of high levels of maternal, perinatal, and childhood morbidity and mortality. Regardless of these overwhelming obstetric and paediatric challenges, there is still urgent need to develop feto-maternal medicine units in the country to focus attention on the management of TTTS because of high twinning rate and attending fetal, perinatal and neonatal wastages. Furthermore, Nigeria is now witnessing an increased incidence of twin births from the rapidly developing assisted reproductive therapy centres in the country. All these provide justification for devoting attention to this unique area of perinatal care that will, on balance, be robustly cost effective. Hence, this review of transfusion syndromes in monochorionic multiplets aims to sensitize health workers and researchers in Nigeria, particularly perinatologists and feto-maternal physicians, neonatal paediatricians, as well as policy makers and other stakeholders, on the need to focus attention on the problem.
... Severe cerebral injury was defined and recorded in accordance with a standard protocol at our center. 24 Early-onset neonatal sepsis was defined as the onset of sepsis within 72 hours after birth 25 and recorded as proven or suspected sepsis. Proven early-onset sepsis was diagnosed if the blood culture was positive. ...
Objective:
To estimate the incidence of histologic chorioamnionitis and funisitis after fetoscopic laser surgery for the management of twin-twin transfusion syndrome.
Methods:
A case-control study was performed at the Leiden University Medical Center from 2013 to 2014. All patients with twin-twin transfusion syndrome managed with laser surgery during the study period were included and compared with a control group of all monochorionic twins not treated with laser surgery. We excluded patients with fetal demise or higher order pregnancies. Placentas were reviewed for the presence and degree of chorioamnionitis and presence or absence of fetal inflammatory response. The primary outcome was the incidence of histologic chorioamnionitis and funisitis after laser surgery. Odds ratios (ORs) and 95% confidence intervals (CIs) for primary outcomes were calculated. A P value of <.05 was considered as statistical significance.
Results:
Sixty-two patients treated with laser surgery were included in the study group and compared with 64 patients in the control group. The incidence of histologic chorioamnionitis was 13% (8/62) in the laser group compared with 5% (3/64) in the control group (OR 3.0, 95% CI 0.8-11.9, P=.12). Funisitis occurred in 8% (10/124) in the laser group compared with 0% in the control group (OR 11.1, 95% CI 1.3-96.9, P=.03). Histologic chorioamnionitis with or without funisitis after laser surgery was associated with a shorter laser-to-delivery interval (median 6.6 [range 3.4-14.1] compared with 13.6 [4.4-20.1] weeks, P<.01) and lower gestational age at birth (median 28.1 [range 23.1-32.6] compared with 32.7 [24.4-37.0] weeks, P<.01).
Conclusion:
These findings suggest that laser surgery for twin-twin transfusion syndrome is associated with an increased risk of funisitis.
Objectives
To describe the types of brain injury and subsequent neurodevelopmental outcome, to determine risk factors for brain injury and to review the use of neuroimaging modalities in fetuses and neonates with twin‐twin transfusion syndrome (TTTS).
Methods
Retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. Primary outcome was the incidence of brain injury, divided into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment (NDI)), risk factors for brain injury and the numbers of magnetic resonance imaging (MRI) scans.
Results
Fetal and neonatal brain ultrasound was performed in all 466 TTTS pregnancies and 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. In the group with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow‐up was available for 29/34 (85%) long‐term survivors with brain injury and mean age at follow‐up was 46 months. NDI was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post‐laser twin anemia polycythemia sequence (TAPS) (OR 3.095, 95%‐CI 1.581 – 6.059, p = .001) and lower gestational age (GA) at birth (OR 1.381 for each week less, 95%‐CI 1.238 – 1.541, p < .001).
Conclusions
Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post‐laser TAPS and a lower GA at birth.
This article is protected by copyright. All rights reserved.
The prevalence of twin pregnancies accounts for about 2–3% of all other pregnancies. The world-spread use of assisted reproductive technologies (ART) as a method of conception and advanced maternal age have contributed to the increased rate of multiple pregnancies globally. In twin pregnancies, either structural defects or adverse pregnancy outcomes are major causes for prematurely and increased perinatal mortality and neurodevelopmental impairment in childhood. Ultrasound plays an important role in identifying this subgroup of twin gestation, which will require further counseling and correct management planning.KeywordsFetal defects and twinsZygocityChorionicityDichorionic diamniotic twinsMonochorionic diamniotic twinsMonochorionic monoamniotic twinsTTTS (Twin-to-twin transfusion syndrome)TAPS (Twin anemia-polycythemia sequence)TRAP (Twin reversed arterial perfusion) sequenceConjoined twinsAdverse pregnancy outcome in twin pregnancy
TTTS (twin–twin transfusion syndrome) is characterized by the relative hypovolemia of one twin and hypervolemia of the other, caused by multiple, large AV anastomoses in the placenta. It becomes clinically evident between 16 and 26 weeks of gestation. The donor fetus is demonstrating signs of intrauterine growth restriction and oligohydramnios. Hypervolemia of the recipient fetus causes polyhydramnios, polycythemia and heart failure.TTTS is diagnosed prenatally by ultrasound. Diagnostic criteria are the presence of a monochorionic diamniotic (MCDA) pregnancy and the presence of oligohydramnios (defined as a maximal vertical pocket [MVP] of amniotic fluid <2 cm) in one sac and polyhydramnios (an MVP of >8 cm) in the other sac. After the diagnosis, other findings associated with TTTS are investigated to assign the stage.Quintero staging system is the most commonly used for TTTS. Five stages were defined according to the ultrasound findings (Stage I–V).The management depends on the Quintero stage, maternal symptoms and signs, gestational age, and availability of technical expertise. Women with Stage I TTTS and no maternal symptoms are often managed expectantly. For women with Stage I TTTS with significant symptoms and women with Stage II-IV TTTS at 16–26 weeks of gestation, recommended fetoscopic laser ablation and at >26 weeks of gestation recommended amnioreduction. For women with Stage V TTTS serial ultrasound survey of the surviving co-twin should be performed.If the stage and symptoms remain stable, in the absence of complications necessitating earlier delivery it may be reasonable to continue the pregnancy until 37 weeks.KeywordsTwin-to-twin transfusion syndromeTTTSMonochorionic twinsQuinteroFetoscopic laser photocoagulation
The increased risks of various obstetric, maternal and fetal comorbidities of monochorionic twin pregnancies are widely known. However, despite its high prevalence and significance, the assessment of neurological morbidity as more commonly in Selective Fetal Growth Restriction (sFGR) is concerned with more health care. This literature review aims to provide more information about such an assessment. To this end, retrospective cases of sFGR were studied in monochorionic twins, already diagnosed, classified and who had the recommended management, published between 2001 and 2018 in 17 scientific articles. In the assessment of fetal mortality, the highest risk of death of the restricted fetus was found in type 3 of sFGR, while type 2 sFGR was responsible for the highest death rates of both fetuses and also the lowest mean gestational age at delivery, 30.9 weeks. Regarding neurological morbidity, however, studies have shown a higher risk of brain damage in the habitually growing twin compared to the restricted one in the case of sFGR. This may be due to prematurity or intermittent diastolic flow on Doppler in type 2 and 3 of sFGR, however, statements about its pathophysiology still lack further studies.
Objectives:
To determine the rate of fetal and neonatal brain lesions and define risk factors for such lesions in pregnancies complicated by Twin Anemia Polycythemia Sequence (TAPS) METHODS: A retrospective cohort study of monochorionic twin pregnancies which were diagnosed with TAPS in a single tertiary medical center between 2013 and 2021. Pregnancies were followed with fetal brain neurosonogram every 2 weeks and fetal brain MRI (magnetic resonance imaging) was performed when indicated at 28-32 weeks of gestation; post-natal brain imaging included neonatal brain ultrasound. Pregnancies with pre- and post-natal brain lesions were compared to those without such findings.
Results:
Overall, 23 monochorionic diamniotic pregnancies were diagnosed with TAPS over the study period resulting in perinatal survival of 91.3% (42/46).In 6/23 (26%) pregnancies and 7/46 (15.2%) fetuses pre- or post-natal brain lesions were detected, of whom five were the polycythemic twins and two were the anemic twins. Brain findings included intra-cerebral hemorrhage and ischemic lesions and were diagnosed prenatally in 6/7 (85.7%) cases. No risk factors for severe brain lesions were identified.
Conclusions:
TAPS may place the fetuses and neonates at increased risk for cerebral injuries. Incorporation of fetal brain imaging protocols may enhance precise prenatal diagnosis and allow for accurate parental counseling and post-natal care. This article is protected by copyright. All rights reserved.
Background
Complete coagulation of the vascular equator (i.e. ‘Solomon’ technique) has been suggested to reduce post-operative complications such as twin anemia polycythemia syndrome (TAPS) and recurrence of TTTS following fetoscopic laser coagulation of chorionic vessels for twin-twin transfusion syndrome (TTTS).
Objective
We aimed to evaluate the benefit of this technique on perinatal outcome, compared to selective ablation of anastomoses.
Study design
We conducted a monocentric retrospective study comparing selective laser coagulation of anastomoses to the Solomon technique, from January 2006 to august 2020. To adjust for potential confounders, cases operated by selective surgery were matched to cases operated with the ‘Solomon’ technique according to gestational age at laser therapy, placental localization and Quintero stage, using propensity score matching.
Results
Within a total of 994 cases, 399 matched pairs were included in the analysis. Compared with selective ablation, the ‘Solomon’ technique was associated significantly improved survival: Overall twin survival at delivery and at discharge were 72 % vs 79% (p=0.003) and 69% vs 75% (p=0.006) respectively, double twin survival rate at discharge was 55% vs 65% (p=0.02), and the rate of intrauterine death dropped from 18% to 12% (p=0.003). The ‘Solomon’ technique significantly reduced the rate of TAPS (10% vs 4%, p=0.02), leading to fewer rescue secondary procedures (13% vs 7.3%, p=0.01). However, the ‘Solomon’ technique was associated with an increased risk of PROM, especially at early gestational ages (3.8% vs 11%, p<0.001 for PROM<24 weeks). Among the survivors at delivery, both groups had similar gestational age at birth. Both neonatal mortality and severe neurological morbidity were similar in both groups. However, an increased risk of bronchopulmonary dysplasia was found in the ‘Solomon’ group (4.5% vs 12%, p<0.001).
Conclusions
Although the risk of PPROM has increased, the introduction of the Solomon technique has significantly improved the perinatal outcome in pregnancies affected with TTTS.
Objectives:
to ascertain the incidence of antenatally diagnosed brain injuries in twin pregnancies complicated by twin to twin transfusion syndrome (TTTS) and to quantify the perinatal mortality, morbidity and long-term neurodevelopmental outcomes of these fetuses.
Methods:
Medline, Embase, Clinicaltrials.gov and Cochrane Library databases were searched. Inclusion criteria were studies reporting on brain abnormalities diagnosed antenatally in twin pregnancies complicated by TTTS. The primary outcome was the incidence of prenatal brain abnormalities. The secondary outcomes were intrauterine demise (IUD), neonatal death, termination of pregnancy (TOP) and long-term morbidity. All these outcomes were explored in the overall population of fetuses with antenatal diagnosis of brain abnormalities. Sub-group analysis according to: type of treatment, gestational age and Quintero stage at diagnosis and/or treatment, co-twin death was planned. Meta-analyses of proportions were used to combine data and reported pooled proportion and their 95% confidence intervals (CI).
Results:
Thirteen studies including 1573 cases of TTTS and 88 fetuses with an antenatal diagnosis of brain abnormalities were included in the systematic review. The meta-analysis included only studies reporting on brain abnormalities in twin pregnancies complicated by TTTS cases and treated with laser. Overall, brain injuries occurred in 2.2% of fetuses (eight studies (52/2410 fetuses)). These brain abnormalities were reported in 1.03% and 0.82% of recipients or donors, respectively. These abnormalities were mainly ischemic lesions (30.4%, 95%CI 19.1-43), followed by destructive lesions (23.9%, 95%CI 13.7-35.9), ventriculomegaly (19.9%, 95% CI 10.6-31.3) and hemorrhagic (15.3%, 95%CI 7.1-25.8). Spontaneous IUD occurred in 13.4% (95%CI 5.1-24.8) of fetuses, while TOP was chosen by parents in 53.5% (95%CI 38.9-67.8) cases. Neonatal death was reported only by three studies with an incidence of 15.4% (95%CI 2.8-35.4). Finally, only two studies reported on composite morbidity with 20.4% of morbidity reported overall (95%CI 2.5-49.4) which occurred in 29.7% and 20.4% of the recipient and donor fetuses, respectively. Due to the small numbers, only composite morbidity was analyzed and no information on neonatal intensive care unit admission, respiratory distress syndrome or other long-term outcomes such as neurodevelopmental delay or cerebral palsy could be reliably retrieved.
Conclusions:
The overall incidence of antenatally diagnosed fetal brain abnormalities in fetuses from twin pregnancies complicated by TTTS treated with laser is around 2%, mainly ischemic (30.4%) in nature. TOP was chosen by parents in almost half of the cases (53.5%). No information could be retrieved on morbidity outcomes, highlighting the urgent need for long-term follow up studies of these children. This article is protected by copyright. All rights reserved.
This chapter examines the pathology of multigestational placentas. Although this includes a brief discussion on the zygosity and genetics of twinning, the majority of the chapter is focused on the placental anatomy of twin gestation. This includes the relationship between zygosity and placental formation, including monoamniotic, monochorionic, diamniotic, and dichorionic placentas, and techniques on recognizing the type of placentation. A special focus is made of vascular anatomy, particularly as pertaining to twin-twin transfusion syndrome. In addition, the more unusual fetal results of twinning, including acardiac twins, conjoined twins, and congenital anomalies, are briefly discussed. Finally, the chapter closes with a discussion of the morbidity and mortality associated with twin gestation.
Monochorionic twins are not only at increased risk of severe complications during pregnancy, but also after birth. Antenatal disorders such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS) may leave temporary or permanent marks in survivors and require specific management during the neonatal period. As most TTTS and TAPS survivors are born prematurely, these neonates are primarily at risk for morbidity associated with prematurity. Additionally, specific complications related to TTTS and TAPS may occur in neonatal survivors including cardiovascular morbidity (right ventricular outflow tract obstruction and persistent pulmonary hypertension of the newborn, renal failure and haematological disorders. The most important and dreaded complication in survivors is cerebral injury, as it may have profound and lifelong impact on these infants. In this chapter, we summarize the different risks of neonatal morbidity and discuss postnatal assessment and management in the various subgroups of complicated monochorionic twins.
Objective:
To determine the rate of and risk factors for fetal and neonatal brain lesions following laser ablation for twin-to-twin transfusion syndrome (TTTS).
Methods:
A retrospective cohort study of 83 women with monochorionic twin pregnancies who underwent ablation for TTTS at a single tertiary hospital. Post-laser survivors were followed-up with fetal neurosonogram every 2 weeks and fetal brain MRI at 28-32 weeks of gestation; post-natal brain imaging included neurosonogram. Cases with pre- and post-natal brain lesions were compared to those without.
Results:
153 fetuses survived the immediate post-laser period and underwent brain imaging. Of these, 17 (11.11%) exhibited brain lesions on prenatal imaging studies, and 36 (32.4%) on post-natal ultrasound. Later gestational age (GA) at the time of ablation (23.0 vs. 21.4 weeks, p = 0.0244), post-laser twin-anemia-polycythemia-sequence (TAPS) (29.41% vs. 9.56%, p = 0.035) and birthweight discordancy (30% vs. 9%, p = 0.0025) were associated with prenatal brain lesions. Earlier GA at delivery (31.0 weeks vs. 32.2, p = 0.0002) and post-laser TAPS (25% vs. 9.33%, p = 0.038) were associated with post-natal brain lesions.
Conclusions:
Survivors of ablation for TTTS are at risk for brain lesions, which can be detected prenatally. Incorporation of neurosonogram and fetal brain MRI into the routine surveillance of such pregnancies should be considered.
Aim:
The purpose of this study was to investigate the outcomes of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS) in Japan.
Methods:
The retrospective cohort study (2012-2018) was conducted in monochorionic twin pregnancies that underwent FLP for TTTS between 26 and 27 weeks from 2012 to 2018. The perioperative data, maternal complications, gestational age (GA) at delivery, neonatal complications, and survival of infants at 28 days of age were analyzed. At term-equivalent age, severe neurological complications were identified by imaging study.
Results:
Of 644 patients, 28 (4.3%) underwent FLP between 26 and 27 weeks, and 26 were analyzed. FLP procedures were technically successful in all cases. There were no cases of major maternal complications after surgery. Preterm rupture of membranes occurred in 34.6% of cases, and the mean GA at delivery was 33.2 ± 3.1 weeks. The survival of both twins was found in 23 (88.4%) cases, and the perinatal survival rate of at least one twin at 28 days of age was 100%. Severe neurological complications were found in six (12.2%) cases out of 49.
Conclusions:
FLP for TTTS between 26 and 27 weeks provided a good prognosis and caused no major maternal complications. However, severe neurological findings were found in 12% of infants.
Objective
Due to the increased risk of antenatal brain lesions, we offer a third-trimester magnetic resonance imaging (MRI) scan to all patients who underwent an in utero intervention for twin-twin transfusion syndrome (TTTS). However, the usefulness of such a policy has not been demonstrated yet. Therefore, we determined the prevalence of antenatal brain lesions detected on third-trimester MRI and the proportion of lesions detected exclusively on MRI.
Materials and methods
We conducted a retrospective cohort study of monochorionic diamniotic twin pregnancies complicated by TTTS that underwent laser coagulation of the vascular anastomoses or fetal reduction by umbilical cord occlusion between 2010 and 2017. We reviewed the third-trimester MRI findings and compared those with the prenatal ultrasonography.
Results
Of the 141 patients treated with laser coagulation and 17 managed by cord occlusion, 112/141 (79%) and 15/17 (88%) patients reached 28 weeks. Of those, 69/112 (62%) and 11/15 (73%) underwent an MRI between 28 and 32 weeks. After laser coagulation, MRI detected an antenatal brain lesion in 6 of 69 pregnancies (9%) or in 6 of 125 fetuses (5%). In 4 cases (67%), the lesion was detected only on MRI. In the 11 patients treated with cord occlusion, no brain lesions were diagnosed.
Conclusion
The prevalence of brain lesions detected by third-trimester MRI is higher compared to prenatal ultrasonography alone, making MRI a useful adjunct to detect antenatal brain lesions in twin pregnancies after in utero treatment for TTTS.
Background
Cerebral oxygenation (crSO2) monitoring is increasingly used in high-risk infants. Monochorionic twins suffer from specific fetal pathologies that can affect cerebral hemodynamics. Limited data are available on crSO2 and blood flow patterns in this population after birth.
Objective
To evaluate crSO2 changes in preterm monochorionic and dichorionic twins during the first 72 h of life.
Methods
Near-infrared spectroscopy was used to measure crSO2 in 62 infants from 31 twin pregnancies <32 weeks of gestation. The study group was divided into 4 subgroups: donor (1) and recipient (2) monochorionic twins (with twin-twin transfusion syndrome), fetal growth restriction (FGR) infants (3) and twins without fetal compromise (4).
Results
There was significant difference in birth weight (p < 0.001) among 4 subgroups. We observed significant variation in crSO2 among the subgroups using mixed model analysis (p < 0.001). The recipient twins exhibited the lowest crSO2 (mean ± SE) throughout the study period (76 ± 0.3%), whereas the FGR and donor twins presented with the highest values (86 ± 0.3% and 83 ± 0.4% respectively). We found no statistically significant differences in neonatal mortality and morbidity among subgroups.
Conclusion
Our study revealed significant correlation between crSO2 values postnatally and underlying fetal pathology in monochorionic and dichorionic preterm twins.
Twin-to-twin transfusion syndrome typically occurs in the second trimester in 10–15% of monochorionic twin pregnancies. Vascular anastomoses of monochorionic placentae are the underlying cause of the development of the syndrome. If a blood flow imbalance occurs, one fetus becomes the so-called donor twin and the other the recipient. If untreated, perinatal mortality is 80–90%. Fetoscopic laser coagulation of the vascular anastomoses destroys the cause of the syndrome and leads to dual twin survival rates of around 70% and more than 90% of pregnancies with at least one survivor. However, unequal placental sharing, intrauterine death, and severe prematurity are still limiting factors for further improvement of survival rates and decreases in long-term morbidity. Prematurity and neurodevelopmental impairment affect the donor and recipient twins, whereas cardiovascular failure and obstruction of the right ventricular outflow tract are typical complications of recipients, which can lead to long-term morbidity. In this Review, we summarise the literature on follow-up data for survivors of twin-to-twin-transfusion syndrome after laser therapy, including neurodevelopmental outcomes, cardiovascular outcomes, growth, renal function, and ischaemic events, as well as the potential effects of intrauterine programming on later life.
Background:
Twin-Twin Transfusion syndrome is associated with significant mortality and morbidity. Potential treatments require robust evaluation. The aim of this study was to evaluate outcome reporting across observational studies and randomised controlled trials assessing treatments for twin-twin transfusion syndrome (TTTS).
Methods:
Cochrane Central Register of Controlled Trials, EMBASE and Medline were searched from inception to August 2016. Observational studies and randomised controlled trials reporting outcomes following a treatment for TTTS in monochorionic-diamniotic twin pregnancies and monochorionic-triamniotic or dichorionic-triamniotic triplet pregnancies were included. We systematically extracted and categorised outcome reporting.
Results:
Six randomised trials and 94 observational studies, reporting data from 20,071 maternal participants and 3,199 children, were included. Six different treatments were evaluated. Included studies reported sixty-two different outcomes, including 10 fetal, 28 neonatal, 6 early childhood and 18 maternal outcomes. The outcomes were inconsistently reported across trials. For example, when considering offspring mortality, 31 studies (31%) reported live birth, 31 studies (31%) reported intrauterine death, 49 studies (49%) reported neonatal mortality, and 17 studies (17%) reported perinatal mortality. Four studies (4%) reported respiratory distress syndrome. Only 19 (19%) of studies were designed for long-term follow-up and 11 of these studies (11%) reported cerebral palsy.
Conclusions:
Most studies evaluating treatments for TTTS, have often neglected to report clinically important outcomes, especially neonatal morbidity outcomes. Most studies are not designed for long-term follow-up. The development of a core outcome set could help standardised outcome collection and reporting in Twin-Twin Transfusion syndrome studies.
Perinatal stroke has become increasingly recognized with the increased application of neuroimaging for neonatal seizures and encephalopathy. The frequency of perinatal stroke is estimated at 1 in 5000 births. Perinatal arterial ischemic stroke (AIS) accounts for 80% of neonatal stroke, while cerebral sinovenous thrombosis (CSVT) accounts for 20%. This chapter will summarize the neuropathology, pathophysiology, clinical presentation, management, and prognosis of perinatal AIS and CSVT. These conditions differ in their risk factors, presentation, management, and prognosis emphasizing the importance of their accurate diagnosis in the newborn infant.
Twin-twin transfusion syndrome (TTTS) is a serious condition that complicates roughly 8% to 15% of monochorionic, diamniotic twin pregnancies. Although the pathophysiology of TTTS remains incompletely understood, intertwin vascular connections (anastomoses) within the placenta are critical for its development. When TTTS develops early in pregnancy, it is associated with high rates of twin perinatal mortality and, among survivors, substantial risk for long-term neurological morbidity. Ultrasound is the mainstay of prenatal TTTS diagnosis and staging, with evidence of recipient twin polyhydramnios and donor twin oligohydramnios necessary to secure the diagnosis. In the second trimester, ultrasound surveillance on an every-other-week basis is recommended to identify pregnancies with TTTS or other pathology. Fetal echocardiography is additionally recommended, as it may detect structural and functional heart abnormalities. While early-stage TTTS may be managed conservatively with close observation, referral to a fetal therapy center that offers laser photocoagulation is advisable for further consultation and to discuss management options. Fetoscopic laser therapy is the optimal treatment for advanced-stage TTTS presenting by 26 weeks. Neuroimaging should be considered in pregnancies complicated by TTTS due to risk of major neurological morbidity among survivors.
Objective
The main objective of this study was to review the available scientific evidence about mid-term neurological outcomes in twins after laser therapy for twin-to-twin transfusion syndrome (TTTS).
Methods
A systematic review of studies on neurodevelopmental outcomes (cognition, motor development, communication skills and cerebral palsy) of twins after laser therapy for TTTS was conducted. Outcomes at 24 months of age and the use of validated scales for assessment were the selected criteria. Electronic and manual research identified 25 studies, and nine of them were eligible for the review.
Results
The global mean rate of neurological injury in twins treated with laser was 14.07%. The mean rate of cognitive impairment was 8.41%, 11.14% for motor delay, 16.5% for communication delay and 5.73% for cerebral palsy. These rates were higher than the results found in dichorionic twins, but lower than the results found in twins treated with amnio-reductions or conservative management.
Conclusion
Laser therapy is associated with a lower rate of neurological injury at 24 months of age compared to other therapeutic techniques. This tendency was also observed with specific incidences regarding cognition, motor skills and cerebral palsy.
Résumé
But
Rapporter les données préopératoires, caractéristiques chirurgicales, complications et le devenir périnatal des grossesses gémellaires compliquées de syndrome transfuseur-transfusé (STT) traitées par coagulation laser fœtoscopique. Analyser les facteurs prédictifs de survie néonatale et comparer les 100 cas les plus récents avec les 100 les plus anciens.
Matériels et méthodes
Étude de cohorte observationnelle monocentrique de 200 grossesses gémellaires monochoriales biamniotiques compliquées de STT prises en charge entre janvier 2004 et décembre 2014 et traitées par coagulation laser fœtoscopique.
Résultats
Parmi les 200 patientes traitées, on note 49 stades I, 88 stades II, 55 stades III et 8 stades IV. L’âge gestationnel moyen au laser était de 20,1 ± 3,0 semaines d’aménorrhée (SA) tandis que l’âge gestationnel à l’issue de grossesse était en moyenne de 31,6 SA ± 5,4. Le taux de survie néonatal global était de 68,0 % avec la survie d’au moins un enfant dans 84,0 % des cas. Une rupture prématurée des membranes est survenue dans 39 cas en moyenne à 28,8 SA ± 4,6. Les paramètres prédictifs d’avoir au moins un enfant vivant étaient le stade de Quintero et l’âge gestationnel à l’accouchement. Dans la période la plus récente, il y avait significativement plus de STT stade I de Quintero traités par laser, plus de coagulations selon Solomon et un nombre de vaisseaux coagulés plus important.
Conclusion
La survie néonatale en cas de STT est améliorée par la photocoagulation laser fœtoscopique, idéalement selon une technique de Solomon. L’intérêt d’une prise en charge active des stades I est à l’étude.
Twin-to-twin transfusion syndrome (TTTS) complicates 10% of monochorionic twin pregnancies and it is consequence of an unbalanced exchange blood through the vascular anastomoses at placental surface. If not treated, mortality rates in TTTS may be as high as 80 to 100%. Laser photocoagulation of the placental anastomoses is the first treatment option, however in some situations the damage of the placenta in the postpartum may become difficult the residual anastomoses identification. We propose a new non-invasive technique to assess the residual anastomoses using computed tomography (CT) scan data to generate a three-dimensional (3D) virtual placentoscopy.
Objective:
The primary objective of our study was to evaluate the long-term neurodevelopment outcome after laser surgery for twin-twin transfusion syndrome (TTTS). The secondary objective was to identify perinatal prognostic factors associated with neurodevelopmental impairment.
Method:
This was a single-center cohort prospective study carried out in pregnancies complicated by TTTS and treated by laser. Neurodevleopmental assesment included the administration of Ages and Stages Questionnaires® (ASQ), for the infants between two and five years of age.
Results:
A total of 187 patients underwent a laser for TTTS between 2004 and 2013. Significant brain lesions were detected in 8 (2.9%) cases by ultrasound and/or MRI including intraventricular hemorrhage, periventricular leukomalacia and porencephaly. Questionnaires were administered to 126 children (50.4%) at 24 months or older at the moment of testing. There were 13.5% of those infants who had an abnormal ASQ (established as 1 area or more scoring < 2SD) at 3.6 years +/- 1.3 follow-up. There was a higher rate of abnormal ASQ among the infants with a birth weight below the fifth percentile (p = 0.036).
Conclusion:
TTTS is associated with a risk of abnormal neurological development, even in case of laser surgery. Further studies are necessary to identify the risk factors for neurological impairment.
Objective:
To describe the incidence and nature of prenatal brain damage following fetoscopic laser selective coagulation (FLSC) of placental vessels for twin-to-twin transfusion syndrome (TTTS).
Design:
Retrospective observational study.
Setting:
Single center cohort.
Population:
All consecutive cases referred for TTTS treated by FLSC between 2003 and 2015.
Methods:
After the FLSC, patients were followed weekly by ultrasound. Fetal magnetic resonance imaging (MRI) scans were systematically planned at 30-32 weeks of gestation.
Main outcome measures:
Brain damage diagnosed prenatally by ultrasound or MRI.
Results:
In total, 1023 cases were reviewed. Brain damage was diagnosed prenatally in 22/1023 (2.1%) cases. Diagnosis was performed by ultrasound prior to MRI in 18 (82%) cases. All lesions were within the spectrum of ischaemic haemorrhagic lesions. Postoperative twin anaemia polycythaemia sequence and recurrence of TTTS were significantly associated with brain damage.
Conclusion:
The incidence of prenatal brain damage is low following FSLC, and is strongly associated with incomplete surgery.
Tweetable abstract:
Following FSLC for TTTS, prenatal brain damage occurs in 2% of cases and is associated with incomplete surgery.
In a remarkable paper that correlates prenatal events and discordance of twins with postnatal outcome, Price (1950) emphasized the importance of “prenatal biases.” He was much concerned with the influence of placentation upon twin development, an aspect that had not often been considered in twin studies. Similar ideas have more recently been echoed by Phillips (1993) who emphasized the influence of the proximity of twin placentas on their ability to support fetal growth. But it was Galton (1875), cousin of Charles Darwin, and after whom the Galton Institute of Genetics in London is named, who was probably the first to suggest that twins, if properly studied, would yield information that might allow us to discriminate between the effects of heredity and those of the environment. It was his famous “Nature vs. Nurture” concept. The extensive studies conducted by Friedrich Schatz at about the same time, suggested that prenatal influences among twins found reflection in the ultimate outcome of the twins. He was instrumental in clarifying that placental study is essential for this understanding. His extensive work is annotated in a bibliographic oddity (Schatz 1900). It summarized all of his papers and citations therein. Some of his numerous contributions were partially translated for the book on twin placentation by Strong and Corney (1967). A concise review of the biologic aspects of the human twinning process was published by Benirschke and Kim (1973), and the new volume on “Twinning and Twins” by MacGillivray and his colleagues (1988) summarizes most relevant aspects of this interesting phenomenon of nature. Baldwin (1994) has produced a remarkable volume that contains all relevant aspects of placentation of multiple pregnancies, and it is well illustrated. Finally, Gall (1996) has summarized all practical aspects of multiple gestations, especially the clinical manifestations and therapy. Several cases of hydatidiform mole in twin gestations have been reported (e.g., Chu et al. 2004). These are discussed in more detail in the Chap. 22.
Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia.
We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses.
Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent.
In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.
Twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. According to recent studies, different pathophysiologic mechanisms may play a role. Diagnosis of TTTS is no longer based on neonatal criteria such as birth weight discordance and hemoglobin difference, but on strict prenatal ultrasound criteria. A significant evolution in prenatal care strategies and management options for patients with TTTS has occurred during the last decade. Endoscopic laser ablation of communicating placental vessels is a new treatment modality that has led to an increase in survival rates. In perinatology, a decrease in mortality rates may be associated with an increase in morbidity rates. Follow-up studies in infants with TTTS are shedding more light on the wide range of morbidity associated with TTTS, such as neurological, cardiac and renal sequelae. This review analyzes the possible pathophysiologic mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS.
Objective To assess the clinical effectiveness of endoscopic laser coagulation of placental vessels in the
Design Prospective study.
Setting Three referral centres for the management of twin-to-twin transfusion syndrome.
Population One hundred and thirty-two pregnancies complicated by severe twin-to-twin transfusion syndrome, reflected by polyhydramnios and enlarged bladder of one twin and oligoanhydramnios and collapsed bladder of the other twin, presenting before 28 weeks of gestation.
Methods Prospective collection of data on pre-procedure assessment, the procedure and the follow up were collected prospectively. Laser coagulation of placental vessels crossing the intertwine membrane on the chorionic surface under sono-endoscopic guidance, followed by amniodrainage.
Main outcome measures Maternal and pregnancy complications, perinatal death and morbidity were assessed over the last five years with follow up of survivors.
Results Endoscopic laser was carried out at a median gestation of 21 weeks. The total number of surviving infants was 144 (55%) and there was at least one survivor in 97 cases (73%). At a minimum age of one year neurological handicap was suspected in six survivors (4.2%).
Conclusions The results of this multicentre study are similar to those in our original report on the first 45 cases. In comparison with serial amniodrainage, the survival rate may be similar, but the handicap rate in survivors appears much lower. This study stresses the need for a prospective study comparing treatment of severe transfusion syndrome threse two techniques.
Purpose: To examine the rate of monozygotic twinning associatedwith blastocyst transfer using commercially available,cell-free culture systems with unmanipulated blastocysts.
Methods: A retrospective analysis was conducted in multipleprivate and academic infertility centers throughout theUnited States, of 199 pregnant patients following in vitrofertilization (IVF) blastocyst embryo transfer (ET). Humanembryos obtained through standard IVF stimulation protocolswere cultured in commercially available, cell-free mediasystems and transferred as blastocysts. The main outcomemeasure was the rate of monozygotic twinning.
Results: A total of 199 blastocyst-ET pregnancies wereachieved during the study period at the fertility centersexamined. Monozygotic twinning was noted in 10/199 (5;pc)of these pregnancies. All were monochorionic diamnionic.
Conclusions: Monozygotic twinning previously has beenreported following IVF, especially in relation to assistedhatching. While blastocyst transfer has been available formany years using coculture, there have been no publishedmulticenter reports of monozygotic twinning associated withunmanipulated blastocysts. In a multicenter analysis, a definiteincrease in monozygotic twinning was seen followingblastocyst-ET. We believe this phenomenon is real and thatthis information should be considered when counselingpatients for treatment.
We developed a mathematical model of twin-twin transfusion syndrome (TTTS) that includes a hydropic recipient twin, adding interstitial and intracellular fluid compartments, fetal congestive cardiac failure, and the dynamics of renin-angiotensin system (RAS) mediators to our previous TTTS model. Ten differential equations for each twin, coupled by the net fetofetal transfusion of blood and blood components, i.e., colloids, osmoles, and RAS mediators, describe the development of fetal arterial and venous blood volumes, blood osmolality and colloid osmotic pressure (COP), interstitial fluid volume and COP, intracellular fluid volume, amniotic fluid volume and osmolality, and RAS mediator concentration. We included varying placental anastomoses, placental sharing, and amnionicity. The 20 differential equations were solved numerically from 0 to 40 wk with a 0.6-s time step. Consistent with clinical experience, model predictions are as follows. Unidirectional arteriovenous anastomoses and arteriovenous anastomoses inadequately compensated by oppositely directed anastomoses cause severe TTTS that includes a hydropic recipient. Adequately compensated arteriovenous anastomoses simulated TTTS without hydrops. The probability that oppositely directed anastomoses prevent onset of a hydropic recipient after TTTS onset, i.e., the largest interval between onset of TTTS and onset of hydrops in the recipient, was best for a venovenous anastomosis, closely followed by an arterioarterial and finally an oppositely directed arteriovenous anastomosis. Hydropic recipients have decreased amniotic fluid volume. Unequal placental sharing and amnionicity modify hydrops onset. In conclusion, our model simulates a sequence of events that results in a hydropic recipient twin in severe TTTS. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS cases that include a hydropic recipient twin.
Twin-twin transfusion syndrome in monochorionic twin pregnancies is not understood completely and is controversial which hampers development of acceptable diagnostic and rational treatment strategies. A haemodynamic model was developed that relates fetal growth with (1) fetoplacental blood flow and fetomaternal effects, and (2) net twin-twin transfusion from donor to recipient twin. Fluid balance mechanisms were neglected. Placental vascular anastomoses (arteriovenous, venoarterial, arterioarterial, venovenous) were modelled as straight blood vessels connecting the placental cord insertions that grow during pregnancy. Poiseuille's law predicts significantly decreasing anastomosing resistances, and when placental sharing is unequal it is assumed that smaller placental fractions cause smaller blood volumes and pressures. Two coupled first-order differential equations describing each twin's blood volume were determined and analysis showed that placental and anastomotic development cause anastomotic blood flow to increase faster than fetal growth. Hence, it is proposed as the syndrome's underlying pathophysiology that fetal discordance increases progressively, beyond fetal compensatory capacity. Fewer anastomoses cause larger discordance, but its onset can vary widely during pregnancy. Arteriovenous plus compensating anastomoses produce dynamic steady-state growth patterns with large, opposite, measurable anastomotic blood flows. Clinical study of fetal growth patterns may identify the syndrome's underlying placental anatomy. Predicted trends depend only weakly on implemented fetal physiology and are most likely realistic. This knowledge could improve future management of the syndrome.
The spectrum of leukomalacia using cranial ultrasound is discussed. Transient densities not evolving into cystic lesions may represent a mild degree of leukomalacia when persisting for at least a week. A unilateral parenchymal density may be due to bleeding into an ischaemic area, but can also be due to a venous infarction. Cystic leukomalacia can be confidently diagnosed using appropriate equipment and performing sequential scans. A distinction should be made between cysts in the periventricular white matter and cysts in the deep white matter, as the latter carries a higher risk for cerebral visual impairment. Careful ophthalmological examination of these infants will enable us to identify infants with cerebral visual impairment during the first few months of life, allowing the use of special programs aimed at promoting visual development.
Because published outcome studies are the only available source of data about the morbidity among surviving very low birthweight infants (VLBW, less than 1500 g) a search was carried out of 1136 references in the English language. A total of 111 outcome studies were found that reported morbidity data in cohorts of VLBW infants born since 1960. The methods used and results obtained in these studies were systematically assessed. No agreement exists about the definition of study populations, descriptive statistics, or measurement of outcome. Follow up ranged from six months to 14 years. In 85 cohorts the incidence of cerebral palsy was recorded, and in 106 that of disability. Studies that followed up infants for longer time periods reported higher incidences of disability. Studies from the United States reported higher incidences of disability than those from other countries. The median incidence of cerebral palsy among all the cohorts studied was 7.7%, and the median incidence of disability was 25.0%. Despite substantial improvements in the mortality of VLBW infants, poor outcomes among survivors are common.
Although cerebral palsy (CP) is the most common cause of motor deficiency in young children, it occurs in only a to 3 per 1000 live births. In order to monitor prevalence rates, especially within subgroups (birthweight, clinical type), it is necessary to study large populations. A network of GP surveys and registers was formed in 14 centres in eight countries across Europe. Differences in prevalence rates of GP in the centres prior to any work on harmonization of data are reported. The subsequent process to standardize the definition of CP, inclusion/exclusion criteria, classification, and description of children with CP is outlined. The consensus that was reached on these issues will make it possible to monitor trends in CP rate, to provide a framework for collaborative research, and a basis for services planning among European countries.
Aim-To define the normal range of systolic blood pressure in a non-selective population based sample of babies of low gestation throughout early infancy. Methods-Daily measurements of systolic blood pressure were made in all the babies of less than 32 weeks gestation born in the North of England in 1990 and 1991 during the first 10 days of Life. Additional measurements were obtained from 135 of these babies throughout the first year of life. Systolic pressure was measured by sensing arterial flow with a Doppler ultrasound probe. It was assumed that blood pressure had never been pathologically abnormal in the neonatal period if the child was alive and free from severe disability two years later. Data of adequate quality were available from 398 such children. Additional data were collected, for comparative purposes, from 123 babies of 32, 36, or 40 weeks of gestation. Results-Systolic pressure correlated with weight and gestation at birth, and rose progressively during the first 10 days of Life. The coefficient of variation did not vary with gestational or postnatal age (mean value 17%), the relation with gestation being closer than with birthweight. Systolic pressure rose 20% during the first 10 days from an initial mean of 42 mm Hg in babies of 24 weeks gestation, and by 42% from an initial mean of 48 mm Hg in babies of 31 weeks gestation. These findings were not altered by the exclusion of data from 14 babies who had inotropic support during this time. Simultaneous measurements in three centres using an oscillometric technique revealed that this technique tended to overestimate systolic pressure when this was below average. Systolic pressure finally stabilised at a mean of 92 (95% CI 72-112) mm Hg at a postconceptional age of 44-48 weeks irrespective of gestation at birth. Conclusion-Systolic blood pressure 4-24 hours after birth was less than gestational age (in weeks) in only 3% of non-disabled long term survivors. Systolic pressure rose with increasing gestation and increasing postnatal age, but stabilised some six weeks after term, regardless of gestation at birth.
We have performed brain scanning by computed tomography on 46 consecutive live-born infants whose birth weights were less than 1,500 gm; 20 of them had evidence of cerebral intraventricular hemorrhage. Nine of the 29 infants who survived had IVH. Four grades of IVH were identified. Grade I and II lesions resolved spontaneously, but there was prominence of the interhemispheric fissue on CT of the infants at six months of age. Hydrocephalus developed in infants with Grade III and IV lesions. Seven of the surviving infants with IVH did not have clinical evidence of hemorrhage. There were no significant differences between the infants with and without IVH in birth weight, gestational age, one- and five-minute Apgar scores, or the need for resuscitation at birth or for subsequent respiratory assistance.
Therapeutic amniocentesis has been accepted widely as a safe and efficacious way to treat the polyhydramnios-oligohydramnios sequence associated with twin-twin transfusion syndrome.
A 28-year-old woman, gravida 2, para 1, diagnosed with twin-twin transfusion syndrome at 28 weeks' gestation was treated with serial amniocenteses. The dividing membrane was ruptured inadvertently during therapeutic amniocentesis, with subsequent complete disruption of the amniotic membrane. Iatrogenic monoamniotic twins with cord entanglement and knotting resulted.
Creation of monoamniotic twins by disruption of the dividing membrane can be a complication of therapeutic amniocentesis for twin-twin transfusion syndrome. Such disruption may result in the same morbidity and mortality that are seen in naturally occurring monoamniotic twins.
Three infants with intrauterine disseminated intravascular coagulation are presented.Each was the product of a twin pregnancy with a macerated sibling. Renal cortical and cerebral necrosis were the predominant features. Two other similar patients have been previously reported. It appears likely that the feto-fetal exchange of thromboplastic material from a dead fetus through vascular shunts in a monochorionic placenta is responsible for this syndrome. With conservative management, the renal cortical necrosis may not necessarily be fatal, but the prognosis is probably poor because of the severity of the cerebral damage.
OBJECTIVE: To determine the neonatal outcome in TTTS pregnancies after intrauterine death of the co-twin (IUFD). Based on literature review, the reported risk of mortality or serious morbidity varies between 14 and 100%; however, most series are very small (3-9 cases) and larger series have not accurately differentiated between mono- and dichorionic twins. STUDY DESIGN: Thirty-one cases of TTTS were identified. The diagnosis was based on ultrasound criteria: single placenta, thin septum, oligo/polyhydramnios and discordant growth. Doppler studies were done but not used for the diagnosis. After delivery all placentas were confirmed as being monochorial with anastomoses. RESULTS: TTTS was diagnosed between 13 and 36 weeks (median, 22). IUFD occurred in 11 cases (35%, 18% of fetuses), between 24+3 and H2 + s weeks (median, 28+ !). Median interval between IUFD and delivery (7 CS, 4 vaginally) was 2 + a weeks (1 day to 7+2 weeks). Three infants died (IUFDdelivery intervals 3.5, 6.5 and 7 weeks): 2 due to periventricular leucomalacia (PVL) and one due to bilateral renal arter)' thrombosis. One infant developed PVL with spastic tetraplegia (interval, 1.5 weeks), 3 had cerebral echodensities with abnormal neurologic development in one case, and 4 had no problem detected. Only 2 of the 9 infants with lUFD-delivery >1 week showed no detectable morbidity. CONCLUSIONS: In our patients the incidence of mortality or serious morbidity after the death of a co-twin in TTTS was 45%, and only 2 twins with an lUFD-delivery interval >1 week escaped without detectable pathology.
Objectives. – If the pattern of neonatal lenticulostriate vasculopathies (NLSV) is well-known, the prognosis is unknown except in TORCH syndromes. This study was aimed to describe the short, mid and long-term outcome of NLSV of various origins.Population and methods. – Of 9138 neonates (1981–2000) which were submitted to an early brain ultrasound study, 70 presented with a pattern of minor (35), moderate (27) or severe (8) NLSV, a single finding in 42 cases and in association with minor peri-intraventricular haemorrhage and/or leukomalacias in 28. The maternal and neonatal charts were reviewed, and the survivors were followed according to our usual policy.Results. – Of nine deaths, eight cases included severe congenital defects (metabolic or malformations or acquired: transfused monochorial twins). Of 61 survivors, eight were lost to follow-up within the first year, 53 were followed for 21 months to 9 years and 7 months (median 4 years 5 months). Of 53 children, 35 (66%) were strictly normal, eight had minor deviations, four had moderate and six had major neurodevelopmental deficits. Of 34 survivors with isolated NLSV and known follow-up, 27 were normal (79%) versus 8/19 (42%) in associated NLSV.Conclusions. – Minor or moderate isolated NLSV generally have a good long-term prognosis. Associated forms of any severity depend mainly upon the severity of periventricular leukomalacias. Major forms of NLSV must be a warning sign of a possible underlying congenital anomaly which will rule the vital and functional prognosis.
The twin-twin transfusion syndrome is a serious complication of monochorionic twin pregnancies. Partly as a result of an inadequate understanding of the pathophysiology of the syndrome, there is a lack of consensus in clinical management. We sought to review the available information on the etiology of twin-twin transfusion syndrome, to identify parameters that contribute to the severity of the syndrome, and propose a rational management plan based on pathophysiology, clinical presentation and the efficacy of therapies. We therefore amalgamated recent advances in twin-twin transfusion syndrome computer modelling and clinical studies, particularly on therapeutic outcomes. We found that the oligo-polyhydramnios sequence that defines twin-twin transfusion syndrome prenatally represents a wide continuum of severity in the imbalance between the fetoplacental circulations of both twins. In severe twin-twin transfusion syndrome cases, in which the circulatory imbalance deteriorates beyond fetal control, fetoscopic laser therapy of all anastomoses along the placental vascular equator is predicted to have significantly better survival rates and fewer neurological sequelae than amnioreduction. In contrast, mild twin-twin transfusion syndrome cases have better outcomes after one or at most a few amnioreductions than laser therapy, as a result of significantly fewer procedure-related risks. In conclusion, optimal individual therapy may possibly achieve an 85% survival rate in twin-twin transfusion syndrome, but requires advancement in non-invasive criteria that predict the severity of the syndrome. Identifying such criteria is a future challenge. For the interim, twin-twin transfusion syndrome diagnosed before 26 weeks' gestation has significantly better survival rates and fewer neurological sequelae after laser therapy than amnioreduction. Twin-twin transfusion syndrome diagnosed after 26 weeks can best be treated by amnioreduction, or delivery. Contrary to previous claims, fetoscopic laser therapy has outgrown its experimental status. Although improvements in technique and technology are likely, laser placental ablation has a firm scientific and clinical basis.
Monochorionic monozygotic twins frequently suffer complications from the presence of vascular anastomoses in their monochorionic placentas. Also, sharing of perfusion zones may be unequal, leading to marked growth discordance.This paper analyzes four measures of perinatal outcome (gestational age at delivery, perinatal mortality, birth weight discordance, and presence/absence of hydramnios) according to the vascular patterns of the monochorionic placentas. The worst clinical outcomes were associated with arteriovenous anastomoses in the absence of arterio-arterial and veno-venous anastomoses.The vascular patterns of monochorionic placentas cause significant fetal environmental differences within pairs of monochorionic monozygotic twins. These differences may cause life-long discordance for several phenotypic traits that are not genetically based, and which cause monochorionic monozygotic twins to be “non-identical.” © 1996 Wiley-Liss, Inc.
Twin-twin transfusion syndrome (TTTS) complicates one in five monochorionic pregnancies and is generally associated with high mortality and morbidity. One twin (the recipient) grows appropriately and has polyhydramnios while the other (the donor) may have a reduced growth velocity and severe oligohydramnios. The disparities in amniotic fluid volumes represent differences in fetal urine output. These differences occur secondary to hemodynamic changes, in which the vascular arrangement of placental anastomoses in TTTS leads to unidirectional flow from the donor to the recipient twin. A better understanding of the pathophysiology may contribute to improved management of this morbid condition.
We studied three consecutive prospectively diagnosed stillborn twin pairs affected by early-onset TTTS. Renin gene expression was studied in sections of fetal kidneys with immunocytochemistry using a renin antiserum and with in situ hybridization using riboprobes complementary to renin mRNA, and renin-secreting cells (RCC) were counted. The overall maturation of the renal cortex was assessed by the percentage of immature glomeruli.
The donor twin kidneys were smaller than those of the recipients, but the maturation of the renal cortex was not significantly different (28.2% immature glomeruli in the donor and 24.4% in the recipient kidney). The donor kidney showed increased renin gene expression with hyperplastic juxtaglomerular apparatuses (JGAs) that contained excess RCCs (median 20.02 [25th–75th centiles, 5.4, 25.1 RCCs per 100 glomeruli]). In contrast, the recipient kidney was virtually devoid of these cells (0.04 [0, 0.36] RCCs per 100 glomeruli; P < 0.05).
In the donor kidney, increased renin release may, by a local action, contribute to renal vasoconstriction and oliguria. Increased renin and/or angiotensin II in the blood passing through the placental anastomoses may, by an endocrine action, suppress renin synthesis in the recipient kidney, thereby increasing renal blood flow and causing polyuria and polyhydramnios. These changes in the renal RAS could thus contribute to the pathogenesis of TTTS. The renal renin changes noted here may represent a contributory or compensating mechanism, the success of which may dictate the overall survival of the twin pregnancy and allow better understanding of the pathophysiology and perhaps therapy that may be employed in this condition.
By the use of the corrosion technique vascular communications between the fetal vascular beds were studied in 22 dichorionic diamniotic and 23 monochorionic diamniotic placentas.The following observations were made: 1.1. Vascular anastomoses were demonstrated in 20 monochorionic diamniotic placentas.2.2. Not in all of these cases superficial arterio-arterial were present, nor did each placenta show deep arteriovenous anastomoses.3.3. None of the placentas contained more than three cotyledons shared by both twins.4.4. Six main types of vascular communications were found; these appeared in twelve different combinations.5.5. The vascular connection in shared cotyledons is by way of the villous capillaries and the paravascular capillary network.6.6. Evidence of the twin transfusion syndromes was present in three cases of twins with monochorionic diamniotic placentas.
We have performed brain scanning by computed tomography on 46 consecutive live-born infants whose birth weights were less than 1,500 gm; 20 of them had evidence of cerebral intraventricular hemorrhage. Nine of the 29 infants who survived had IVH. Four grades of IVH were identified. Grade I and II lesions resolved spontaneously, but there was prominence of the interhemispheric fissue on CT of the infants at six months of age. Hydrocephalus developed in infants with Grade III and IV lesions. Seven of the surviving infants with IVH did not have clinical evidence of hemorrhage. There were no significant differences between the infants with and without IVH in birth weight, gestational age, one- and five-minute Apgar scores, or the need for resuscitation at birth or for subsequent respiratory assistance.
Eight patients with acute polyhydramnios were encountered in 31 103 pregnancies, an incidence of 1 in 3888. All patients with acute polyhydramnios had monozygous twin pregnancies and 14 of the 16 infants were normal. The condition occurred in the second trimester and usually ended in premature delivery within a few days. The perinatal mortality was 100 per cent and accounted for 14.9 per cent of the perinatal mortality in twins.
A method of clinical staging for infants with necrotizing enterocolitis (NEC) is proposed. On the basis of assigned stage at the time of diagnosis, 48 infants were treated with graded intervention. For Stage I infants, vigorous diagnostic and supportive measures are appropriate. Stage II infants are treated medically, including parenteral and gavage aminoglycoside antibiotic, and Stage III patients require operation. All Stage I patients survived, and 32 of 38 Stage II and III patients (85%) survived the acute episode of NEC. Bacteriologic evaluation of the gastrointestinal microflora in these neonates has revealed a wide range of enteric organisms including anaerobes. Enteric organisms were cultured from the blood of four infants dying of NEC. Sequential cultures of enteric organisms reveal an alteration of flora during gavage antibiotic therapy. These studies support the use of combination antimicrobial therapy in the treatment of infants with NEC.
The newborn has a limited capacity to tolerate acute haemorrhage. Prompt diagnosis and therapy are essential for survival. Blood loss can occur in the newborn due to occult haemorrhage, prior to birth or during delivery, obstetric accidents, maternal haemorrhage, or secondary to recurrent blood sampling.
Special precautions must be taken when events known to cause fetal haemorrhage have occurred during pregnancy. These include a maternal history of transfusion reaction in the absence of a transfusion, third trimester bleeding with placenta praevia, placenta abruptio and vasa praevia, emergency caesarean sections, twin pregnancies and amniocentesis.
The clinical manifestations of post-haemorrhagic anaemia at birth depend on the extent and duration of blood loss. When acute massive blood loss has occurred, the infant is extremely pale and requires immediate transfusions or volume expanders. Although the haemoglobin may be normal initially, it rapidly falls within six to eight hours after birth. Other causes of extreme pallor in the newborn include asphyxia and anaemia secondary to haemolysis. Infants who have developed acute post-haemorrhagic anaemia are hypovolemic, are neither jaundiced nor cyanotic, and respond to therapy with volume expanders. The clinical picture with chronic blood loss is usually mild and responds to conservative therapy with iron alone.
Internal haemorrhage should be suspected when a 24 to 72 hour newborn rapidly deteriorates and has evidence for hypovolaemic shock without signs of external blood loss. The blood withdrawn for laboratory evaluation in the high risk newborn must be carefully monitored so that it can be replaced before the newborn becomes compromised.
In 3 cases of severe twin transfusion syndrome we demonstrate that the concentration of atrial natriuretic factor (ANF) in the cord blood of recipient twins is significantly elevated compared to that of donor twins. The discrepancy between recipient and donor concentration correlates with the volume of transfusion. The following pathophysiological mechanism for explaining polyhydramnios in recipient twins is proposed: chronic overload in recipient twins causes enhanced release of ANF from the fetal heart. Consequently, increased fetal urine production leads to polyhydramnios, which is additionally enhanced by inhibition of ADH release.
Intrauterine death of one fetus in a multiple gestation is associated with significant morbidity and mortality in the surviving infant. This study is a retrospective review of 38 twin and 3 triplet gestations involving the intrauterine death of at least one fetus. The obstetrical history, placental pathology, autopsy findings, and neonatal history of the surviving infant are reviewed. Three cases involved the recent stillbirth of both twins, the remaining cases involved a surviving infant. In one case, neonatal death of a surviving twin occurred on day 19. In two sets of triplets, two stillbirths occurred, in the third case two infants were liveborn. The incidence of preterm delivery was 34%, which decreased to 18% if fetal cotwin death had occurred before 20 weeks gestation. Cesarean section was the method of delivery in 16 cases. There was an excess of velamentous cord insertions, which was most pronounced in the stillborn twin. Monochorionic placentation was found in 72%, also an excess.
Neurological damage was known to have occurred in 19 of the 39 surviving infants. Fifteen of these 19 (79%) were associated with monochorionic placentation. The neurologically damaged twin infants, when compared to the normal infants, had the cotwin die later in gestation (31 vs 16.5 weeks), had a shorter duration between the death of the cotwin and delivery (2.5 vs 21 weeks), and delivered earlier in gestation (36.5 vs 39.5 weeks). The probable cause of neurological damage, in our opinion, was either exsanguination into the dead twin fetus, or disseminated intravascular coagulation which occurred in at least 13 cases. The incidence of antepartum death in a multiple gestation, and the potential for neurological damage is probably higher than previously thought. A review of the literature is presented and the clinical implications of this phenomenon are discussed.
A rare case of acute intrapartum twin-twin transfusion occurred. The well-recognized criteria of long-standing chronic twin-twin transfusion were absent. Although a cesarean section was performed for obstetric reasons, the hyperperfused twin, A, died intrapartum. Twin B, the hypoperfused twin, although liveborn, died neonatally of renal failure attributed to renal cortical necrosis as a sequel to hypotension.
Amniocentesis and drainage were performed in 19 twin pregnancies initially seen at less than 28 weeks' gestation with acute polyhydramnios caused by the twin-twin transfusion syndrome. The procedure was performed an average of three times for each patient (range one to six), with the removal of a mean volume of amniotic fluid of 2600 ml on each occasion (range 500 to 6700 ml). The interval between initial examination and delivery averaged 7 weeks (range 1 day to 18 weeks); 14 (37%) of the 38 babies survived the neonatal period. In the pregnancies with poor outcomes, the intertwin disparity in fetal size and the mean volume of amniotic fluid drained at each amniocentesis were greater than in the pregnancies in which one or both twins survived.
The purpose of this study was to determine the frequency, distribution, and most likely etiology of hematologic and weight discordance in pathologically proven monochorionic twins, and to use this information to reevaluate the neonatally derived definition of the twin-twin transfusion syndrome.
We reviewed our experience with 97 pathologically proven monochorionic twin pregnancies. The frequency and distribution of weight and hemoglobin-hematocrit (hb-hct) discordance were determined for all twin pairs. Factors that may have contributed to the discordance were identified, and theoretical mechanisms were proposed.
All combinations of weight and hb-hct discordance were observed. Thirty-four twin pairs (35%) were discordant for weight. In half of these (17 of 34), the hb and hct were concordant. In 18% (six of 34), the smaller twin had the higher hb-hct, and in 32% (11 of 34), the smaller twin had the lower hb-hct. Twenty-three of 63 size-concordant pairs (36%) were discordant for hb-hct. Ten infants were infected at birth, eight had malformations, and 25 likely suffered an acute transfusion event.
Any combination of weight and hb-hct discordance can occur in monochorionic twins. Acute and chronic twin-twin transfusion, uteroplacental insufficiency, infection, malformations, or other factors may have accounted for the discordance observed. Thorough antenatal evaluation with invasive testing and marker studies (to identify a physiologically unbalanced placental anastomosis) may be necessary to establish an accurate diagnosis. We conclude that weight and/or hb-hct discordance is relatively common in monochorionic twins and in itself is not sufficient to diagnose twin-twin transfusion.
Neonatal follow-up studies of school age children, published in the last decade, were critically reviewed. Nine studies examined extremely low birthweight infants (less than or equal to 1000 g) and 16 involved very low birthweight infants (less than or equal to 1500 g). The majority of children had age appropriate I.Q. scores, however, there was a greater variability of test scores. There was an increased need for special education or remedial therapy. Visual-motor integration deficits were frequently reported. Behavioural difficulties were described. Fine and gross motor incoordination was identified. There was no conclusive correlation between perinatal course and school outcome. Gender did appear to influence outcome, in the small percent of studies which examined this variable, with females generally faring better. Low socioeconomic status was the most frequently reported predictor of poor outcome. Identified methodological limitations included heterogeneous samples, lack of control groups, high attrition, variable diagnostic criteria and lack of consensus regarding correction for prematurity.
In four twin pregnancies presenting with acute 2nd-trimester polyhydramnios due to presumed twin-twin transfusion syndrome, the fetal hemoglobin concentration was measured in samples obtained by cordocentesis. In no instance did the twin pair difference in the hemoglobin concentration exceed 2.7 g/dl.
Until the recent introduction of therapeutic amniocentesis, pregnancies complicated by the stuck twin phenomenon usually suffered poor outcomes. We report the first case in which a single amniocentesis of the cotwin was followed by equalization of amniotic fluid volume in both sacs, resolution of nonimmune hydrops in the cotwin, and delivery of 2 healthy infants. The cause of the phenomenon in this was most likely severe twin-twin transfusion, based on a negative hematologic and serologic immune and nonimmune hydrops evaluation, and placental histology revealing a superficial large-caliber arteriovenous anastomosis joining the twins' circulations without an intervening capillary bed. The mechanism proposed for the physiologic response in this case to therapeutic amniocentesis is based on the correction of abnormal amniotic fluid volumes and pressures. This contention is supported by histologic evaluation of the placenta and the intrapartum fetal heart rate tracing.
Intrauterine death of one twin in monochorionic pregnancies is associated with increased mortality and morbidity for the survivor. This has been attributed to the consequences of intrauterine disseminated intravascular coagulation (DIC) initiated by the dead twin. We describe a case in which the fetal cerebral and renal lesions typically found in survivors occurred without any derangement in coagulation. Instead, acute twin-twin transfusion was suggested by the presence of severe anemia in the surviving fetus at delivery. We suggest that the lesions frequently found in the survivors are often due to acute hemodynamic and ischemic changes resulting from acute twin-twin transfusion at the time of intrauterine death, rather than to late-onset DIC. This hypothesis has an important implication for future management: Intervention must occur before intrauterine death if neurologic sequelae in the survivor are to be prevented.
Necrosis of the cerebral white matter may be identified in living infants with echoencephalography. Echoencephalographic studies were performed in 89 twins and 12 triplets at less than 36 weeks of gestation to determine the incidence and complications associated with antenatal necrosis of the cerebral white matter. Antenatal necrosis of the cerebral white matter was identified when brain atrophy or cavities in the white matter were present by day 3 of life. Fourteen infants (13.8%) were considered to have antenatal necrosis of the cerebral white matter. The incidence of antenatal necrosis of the cerebral white matter was higher in monochorionic than in dichorionic infants (30% vs 3.3%; p less than 0.001). Univariate analysis showed that antenatal necrosis of the cerebral white matter was significantly associated with polyhydramnios, intrauterine fetal death of the cotwin, hydrops, multiple placental vascular connections, and placental artery-to-artery, vein-to-vein, and artery-to-vein anastomosis. Logistic regression analysis showed that antenatal necrosis of the cerebral white matter was predicted by the presence of either artery-to-artery or vein-to-vein anastomosis and by intrauterine fetal death of a cotwin. Vein-to-vein anastomosis had the strongest association, because 89% of seven infants with vein-to-vein anastomosis demonstrated antenatal necrosis of the cerebral white matter (p = 0.003). Monochorionic multiple gestations frequently are complicated by antenatal necrosis of the cerebral white matter. Multiple vascular connections with vein-to-vein anastomosis appear as the most important associated factor for antenatal necrosis of the cerebral white matter in this population.
Twin-twin transfusion syndrome associated with acute polyhydramnios in one sac and severe oligohydramnios in the other, which characteristically is diagnosed between 18 and 28 weeks, is associated with a high mortality rate for the involved twins. Patients who are managed without intervention have essentially 100% perinatal mortality. Nineteen patients with this diagnosis were treated at Good Samaritan Medical Center over a 5-year period. Because of the known perinatal mortality and because of early experiences with the twin-twin transfusion syndrome, we began to actively intervene in such patients with various modes of therapy. As experience was gained, it was found that repeated therapeutic amniocenteses, if performed before severe maternal abdominal distention or labor, appears to be beneficial.
Most pregnancies with severe twin-twin transfusion syndrome before 27 weeks' gestation result in perinatal death. Previous attempts at therapy have been generally unsatisfactory and rarely successful. We have developed a technique for intrauterine ablation of the vascular communications between the fetoplacental circulations with a fetoscopically directed neodymium:YAG laser. The operation was performed on three women at risk for pregnancy loss from acute hydramnios at 18.5, 22, and 22.5 weeks' gestation. The first two procedures were uneventful, but the third was complicated by a placental vessel perforation. The first two patients delivered at 27 and 34 weeks after premature rupture of membranes and spontaneous labor, whereas the third woman developed severe preeclampsia at 29 weeks which necessitated delivery. Four of the six infants survived. Clinical and ultrasonographic evidence, as well as pathologic examination of the placentas, suggested that stabilization or resolution of the syndrome was due to photocoagulation of the vascular communications. This initial experience suggests that fetoscopic laser occlusion of placental vessels is feasible and superior to previous therapies because it treats the underlying pathophysiology directly.
To develop prognostic indicators for those patients diagnosed with twin-twin transfusion before 28 weeks' gestation, we conducted a retrospective analysis of all cases diagnosed at Baylor College of Medicine from January 1985 through April 1989. Twenty-seven cases of twin-twin transfusion were diagnosed by ultrasound; the criteria for diagnosis were polyhydramnios in one amniotic cavity and oligohydramnios in the other cavity. The mean (+/- SD) age at diagnosis was 21.9 +/- 2.9 weeks and the mean age at delivery was 26.8 +/- 4.9 weeks. Gestational age at diagnosis was similar in survivors and non-survivors (21.7 +/- 3.7 versus 22.2 +/- 2.8 weeks; P = .35); however, surviving infants were delivered later in gestation (31.9 +/- 3.5 versus 25.9 +/- 3.4 weeks; P = .000008). The overall survival rate was 21%. Fetal hydrops correlated with poor survival. Amniocentesis for decompression and tocolysis failed to decrease perinatal mortality.
Multiple gestation carries a significant risk of perinatal complications and mortality. Often twin neonates are delivered small and early with a perinatal mortality rate five to seven times that of singleton neonates. Increased morbidity and mortality is due to an increased incidence of antepartum complications, monozygotic pathology, preterm labor, and uteroplacental insufficiency. The key to management is early diagnosis, risk assessment, serial ultrasonography for fetal growth, and antepartum testing from 28 weeks until delivery. Prophylactic cerclage or tocolysis have not proven valuable. Reduction of maternal activity (bedrest) has theoretical advantages and is supported by retrospective studies, but not by prospective trials. The timing of delivery is based on the usual considerations. Third trimester uteroplacental insufficiency is identified by serial ultrasonographic exam and antepartum testing. Discordant fetal testing creates a dilemma: the risk of continued hypoxic damage to the sicker twin and the risks of premature delivery in the healthy twin. The management of this dilemma should be based on as much information as possible, ie, oxytocin challenge testing, biophysical profile and fetal lung maturity studies, and as much experience as possible, ie, a perinatal center, equipped to handle very sick premature infants.
Atriopeptin, a peptide produced by mammalian atria that promotes diuresis, natriuresis, and vascular changes, was in much higher concentration in the recipient twin than in the donor in two cases of severe twin transfusion syndrome. This finding suggests a possible etiology for the changes seen in twin transfusion syndrome.
A recent review of 20 years' experience with neonatal intensive care for very-low-birth-weight infants provides reassurance that such care saves lives and that an increasing proportion survive free of moderate to severe handicap. However, data on the health status of these survivors largely reflect status in infancy. An increasing literature suggests that such early findings may be insufficient to characterize later outcomes, particularly those problems encountered as the child enters school. Since the specific health and developmental problems that might be encountered are still being defined, a broad conceptual framework is applied to organize a review of the existing literature. Some areas of concern about longer-term outcomes emerge, as well as important areas for which data are lacking. Further definition of longer-term outcomes is critical at the policy level to assess the utility of neonatal intensive care unit interventions and at the individual level for counseling families as to the health and educational needs of these children.
(JAMA. 1989;261:1767-1772)
One hundred seventy-eight consecutive twin pregnancies were studied to reevaluate the standard diagnostic criteria for chronic twin-to-twin transfusion syndrome of an intertwin hemoglobin difference greater than 5 gm/dl and a birth weight difference greater than 20%. Hemoglobin differences greater than 5 gm/dl were found in six pregnancies with monochorionic placentas but also in seven with dichorionic placentas. Birth weight differences greater than 20% occurred no more commonly in monochorionic than in dichorionic pregnancies. Of the four pregnancies with a coexisting hemoglobin difference greater than 5 gm/dl and birth weight difference greater than 20%, only one had a monochorionic placenta and therefore likelihood of vascular anastomoses. Diagnosis of twin-to-twin transfusion syndrome cannot be definitively established by current standard diagnostic criteria.