The impact of laser surgery on angiogenic and anti-angiogenic factors in twin–twin transfusion syndrome: a prospective study*

Objective: To examine the effect of laser surgery on angiogenic and anti-angiogenic factors in patients with twin–twin transfusion syndrome (TTTS).

Methods: Cases of TTTS and uncomplicated monochorionic diamniotic twin pregnancies between 16 and 26 weeks’ gestation were prospectively enrolled into the study. Maternal blood samples were obtained to measure angiogenic factors (vascular endothelial growth factor-A [VEGF], placental-derived growth factor [PlGF], and endothelin) and anti-angiogenic factors (soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sEng), and sFlt-1/PlGF ratio). For cases, these factors were measured at visit 1 (pre-operatively), visit 2 (postoperative day one), and visit 3 (at least 3?weeks after surgery). In controls, the factors were measured at visit 1 (enrollment) and visit 2 (at least 3?weeks later). Levels of angiogenic and anti-angiogenic factors between cases and controls were compared.

Results: At enrollment, the TTTS cases demonstrated an anti-angiogenic state with significantly higher sFlt-1, sEng, sFlt-1/PlGF ratio, and lower PlGF. Laser surgery, comparing visit 1–3, had a partial corrective effect on TTTS cases. sFlt-1 significantly decreased several weeks after surgery. The other factors (PlGF, endothelin, sFlt-1, sEng, and sFlt-1/PlGF ratio) were not statistically significantly different by visit 3.

Conclusion: Laser surgery partially corrected the angiogenic profile in patients with TTTS.     

Monochorionic monoamniotic twin pregnancies

Monochorionic monoamniotic (MCMA) twin pregnancy is rare and associated with increased complication rates when compared with singletons, dichorionic and monochorionic diamniotic pregnancy in general. Monoamnionicity presents an enormous challenge following its accurate diagnosis, where the absence of an inter-twin membrane subsequently results in cord entanglement and consistently fluctuating foetal position. Furthermore, the detection of twin-twin transfusion syndrome (TTTS) in MCMA pregnancy can be challenging in the absence of amniotic fluid volume discordance without the presence of the inter-twin dividing membrane. Early surveillance of foetal anatomy permits early recognition of foetal structural anomalies, the twin reversed arterial perfusion (TRAP) sequence and conjoined twins. However, the evidence on how best to monitor MCMA pregnancies remains inadequate, though observational studies have demonstrated that once surveillance is initiated, the potential risk of foetal death decreases significantly. In-utero foetal demise can be acute and unpredictable in MCMA pregnancies, despite close surveillance. Elective preterm delivery is usually advocated when the risk of foetal loss upon continuing the pregnancy outweighs the risk of prematurity – around 33 weeks’ gestation by caesarean section. Nevertheless, the optimal prenatal surveillance regimen and prompts for delivery have yet to be defined.     

Twin pregnancy with intrauterine death of one twin

The antepartum death of one twin is a rare obstetric complication. Two cases are presented, accompanied by a review of the current literature. The premature and neonatal death rates are high in the surviving twins. Toxemia, fetal distress, abnormal presentation, and dystocia are also increased. Maternal disseminated intravascular coagulation has been demonstrated without a concomitant fetal coagulation defect. A more unique finding is fetal disseminated intravascular coagulation with a monochorionic placenta. The common circulation between the live and dead twins may result in fetal cerebral, renal, and cutaneous lesions, usually without demonstrable maternal disease. High-risk obstetric management is reviewed and a careful pediatric follow-up is recommended with monozygotic twins.     

Sonography interval and the diagnosis of twin–twin transfusion syndrome

Objective: To evaluate the relationship between sonography surveillance interval and Quintero stage at diagnosis.

Methods: This was a retrospective cohort study of monochorionic diamniotic pregnancies diagnosed with twin–twin transfusion syndrome (TTTS) and followed with serial sonography between 1997 and 2013. Women were divided into three cohorts: diagnosis at initial second-trimester sonogram, at a sonogram within 14 d of the prior exam, and at a sonogram greater than 14 d from the prior exam. Isolated amniotic fluid abnormalities were also recorded.

Results: TTTS was identified in 48 pregnancies, with 50% of cases diagnosed at the initial sonogram, 21% within 14 d of a prior sonogram, and 29% more than 14 d from a prior sonogram. There was no association between interval and TTTS stage at diagnosis. Of 24 cases diagnosed during a follow-up sonogram, 46% had an isolated amniotic fluid abnormality preceding diagnosis. When isolated oligohydramnios (29%) or hydramnios (17%) was present, the sonography interval was significantly shorter (p?=?0.003), but no difference in TTTS stage at diagnosis was found.

Conclusions: Although frequent surveillance of monochorionic diamniotic pregnancies is prudent, when close follow-up of isolated fluid abnormalities was practiced, we were unable to demonstrate an effect of surveillance interval on stage of TTTS at diagnosis.     

Neonatal mortality rates among growth-discordant twins, classified according to the birth weight of the smaller twin

OBJECTIVE: The purpose of this study was to evaluate neonatal mortality rates among discordant twins, classified according to the birth weight of the smaller twin. STUDY DESIGN: We compared neonatal mortality rates among three groups of discordant twins (>25%), distinguished by the birth weight of the smaller twin being <10th, 10th to 50th, or >50th percentile. RESULTS: Among the 10,683 pairs of twins who were studied, the respective proportions of the three groups were 62.4%, 32.9%, and 4.7%. The neonatal mortality rate was significantly higher among pairs in which the smaller twin weighed <10th birth weight percentile (29. vs 11.1 and 11 per 1000; odds ratio, 2.7; 95% CI, 1.3, 5.7). This difference results from the higher mortality rates among the smaller but not among the larger twins. CONCLUSION: Severely discordant twin pairs in whom the smaller twin is also small for gestational age are at an increased risk of neonatal death. Identification of this group is an imperative step in the management of birth weight discordance in twin gestations.     

Percutaneous ultrasonographically guided ablation of an acardiac twin

Acardiac twinning is caused by twin reversed arterial perfusion (TRAP). Normal "pump" twins may face early delivery and cardiac decompensation and have a high perinatal mortality. A primagravid patient had serial evaluation of a TRAP pregnancy beginning early in the second trimester. Rapid growth of the acardiac sibling, high diastolic velocity Doppler waveforms in the perfusing vessel, and early hydramnios prompted ablation of blood flow by a percutaneous ultrasonographically guided infusion of absolute alcohol. A term birth of a normal pump twin was the outcome. Ablation of blood flow into an acardiac sibling of a TRAP pregnancy may be indicated in cases with a poor prognosis by use of an effective percutaneous ultrasonographically guided technique.     

The natural history of twin–twin transfusion syndrome stratified by Quintero stage*

Objective: To describe the natural history of expectantly managed twin–twin transfusion syndrome (TTTS) specific to disease stage.

Methods: This was a retrospective study of monochorionic diamniotic pregnancies diagnosed with TTTS and delivered between 1997 and 2013. Staging was based on Quintero’s criteria, with sonogram images reviewed to confirm findings specific to stage. Progression and outcomes were evaluated in pregnancies that did not receive any form of therapy.

Results: Thirty-eight pregnancies were diagnosed with TTTS and delivered at our institution, representing 1.6 per 10 000 births. Twenty were expectantly managed, of which 50% were stage I at presentation. Progression occurred in 45% of pregnancies, including 50% initially diagnosed with stage I TTTS. Seventy percent of pregnancies experienced survival of at least one twin, with no stillbirths or neonatal deaths if TTTS resolved. Pregnancies in which TTTS was either stable or improved had higher overall survival, compared with pregnancies that experienced progression, 86% versus 22%, p?<?0.001, as well as more frequent survival of one or both twins, 91% versus 44%, p?=?0.02.

Conclusions: Among expectantly managed pregnancies with TTTS, most had early disease at diagnosis. Although 45% of cases progressed, which conferred poor prognosis, the majority experienced disease stabilization or improvement.     

Persistent pulmonary hypertension of the newborn in twin–twin transfusion syndrome following fetoscopic laser surgery

Objective: We investigated persistent pulmonary hypertension of the newborn (PPHN) among monochorionic-diamniotic (MD) twins. Methods: A retrospective cohort study examined MD twins from 195 deliveries and 373 live-born neonates at our center. Results: PPHN occurred in three cases (3/373: 0.8%), all of which were recipients of twin–twin transfusion syndrome (TTTS), after fetoscopic laser surgery (FLS) (3/117: 2.6%). Although the clinical course of the three cases differed, all cardiothoracic area ratios exceeded 40%, and other cardiac parameters also worsened after FLS. Conclusions: The occurrence of PPHN in TTTS recipients should be noted, particularly when fetal cardiac function declines following FLS.     

Twin reversed arterial perfusion syndrome in a monochorionic monoamniotic twin pregnancy

ObjectiveTwin-Reversed Arterial Perfusion (TRAP) sequence is a rare complication of monochorionic multiple gestation. Conservative management should be considered if there is no poor prognostic factor.Case reportThis is a 35 year-old female with twin pregnancy with acardiac monster. Under the request of the patient, there was no intervention during the whole pregnancy. We keep regular and close sonography weekly follow up. There was no maternal complication and there was also no heart failure sign or polyhydramnios of the donor twin. Minimal blood flow was noted at the anastomotic vessels under the sonography at late gestational age. Due to breech presentation, cesarean section was performed at gestational age 37 + 1/7 weeks. She delivers a healthy baby smoothly.ConclusionAntenatal sonography is an important tool to evaluate the fetus status. Under special condition, term pregnancy is still possible without any treatment.Case reportTwin reversed arterial perfusion syndrome in a monochorionic monoamniotic twin pregnancy.     

Trocar-assisted selective laser photocoagulation of communicating vessels: A technique for the laser treatment of patients with twin–twin transfusion syndrome with inaccessible anterior placentas

Objective.?To describe a new technique, trocar-assisted selective laser photocoagulation of communicating vessels (TA-SLPCV), for patients with twin–twin transfusion syndrome (TTTS) with inaccessible anterior placentas.

Materials and methods.?TA-SLPCV was performed through a single port in TTTS patients with an anterior placenta in whom the anastomoses were inaccessible with a standard technique (inaccessible anterior placentas). The anastomoses were first identified using a 25 or 70-degree rigid diagnostic endoscope. The anastomoses were then targeted with a zero-degree operating rigid endoscope by withdrawing it within the sheath a short distance and using the sheath to gently indent the placenta (trocar assistance). The technique was compared with patients with a posterior placenta treated with a standard technique. Surgeries were approved by the Institutional Review Boards and all patients signed informed consent.

Results.?Of 267 patients who met the criteria for the study, 143 (53.6%) had an anterior placenta and 124 (46.4%) had a posterior placenta. Perinatal survival (88.1% vs. 91.9%, p?=?0.3), residual patent anastomoses (4.3% vs. 2.7%, p?=?0.6), or premature rupture of membranes within 3 weeks of the procedure (7.7% vs. 4%, p?=?0.2), was no different relative to placental location (anterior vs. posterior, respectively). Operating time was significantly different between the groups (median 46?min vs. 36?min, p?<?0.05).

Conclusion.?Trocar assistance allows treatment of TTTS patients with inaccessible anterior placentas using a single port and a rigid endoscope with similar results as patients with a posterior placenta and a standard technique.     

An omphalopagus parasitic twin after intracytoplasmic sperm injection

OBJECTIVE: To describe a first case of parasitic twin achieved after intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: Perinatal center at a Japanese university hospital. PATIENT(S): A 30-year-old pregnant Japanese woman with a history of secondary infertility achieved after ICSI was diagnosed with an omphalopagus parasitic twin pregnancy by prenatal ultrasound at 28 weeks of gestation. INTERVENTION(S): A female infant was delivered by scheduled cesarean section at 30 weeks of gestation. The cesarean section was performed for dystocia. MAIN OUTCOME MEASURE(S): Brief review of parasitic twin and malformations in fetuses achieved after ICSI. RESULT(S): Resuscitation was not done because of the poor prognosis for both fetuses. Molecular analysis with informative genetic markers is consistent with monozygotic pregnancy. CONCLUSION(S): A careful ultrasound examination is indicated to detect additional anomalous findings in twin fetuses achieved after ICSI.     

Acute twin-twin transfusion syndrome in labor: pathophysiology and associated factors

Objective: To review reported cases of acute twin-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies to help define variants of disease and determine associated factors. Methods: PubMed literature review using the search terms, “acute” and “twin transfusion.” Articles were reviewed for clinical factors. Reference lists were carefully assessed for any additional articles. In order to rule out sudden progression of chronic TTTS as the cause, gestational age ≥31 weeks was chosen. Cases were classified into subsets of acute TTTS. Results: There were 150 publications from 1942–2010. There were 51 cases that were classified into four variants of acute TTTS. Four cases were difficult to classify, with hemoglobin levels that were high normal and low normal, high normal and anemic, or low normal and polycythemic. Three publications defined the incidence for acute perinatal TTTS of 1.8–5.5% of monochorionic twins. Common factors associated with acute perinatal TTTS included monochorionicity and labor. Conclusions: Monochorionicity and labor are common factors underlying the propensity to acute perinatal TTTS. A spectrum of severity is for acute TTTS was seen. Perinatal specialists and neonatologists should be aware of the possibility of acute TTTS during labor, so rapid volume replacement can be performed for neonatal resuscitation.     

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

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

Neonatal cerebral lesions predict 2-year neurodevelopmental impairment in children treated with laser surgery for twin–twin transfusion syndrome

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?Conclusions: Among ‘high-risk survivors’ of TTTS treated with laser surgery, cerebral lesions identified on neonatal imaging were associated with NDI at 2-years.     

Use of the Foetal Myocardial Performance Index in monochorionic,diamniotic twin pregnancy: a prospective cohort and nested case-control study

Aims: Assess clinical utility of the foetal Myocardial Performance Index (MPI) in evaluation and management of monochorionic, diamniotic twin (MCDA) pregnancies.

Methods: Prospective cohort of (a) initially uncomplicated MCDA (b) Complicated MCDA, including twin–twin transfusion syndrome (TTTS), selective intrauterine growth restriction (sIUGR), and liquor and/or growth discordance (L/GD) not meeting TTTS or sIUGR criteria. TTTS and sIUGR were case-control matched. Routine Dopplers and MPI were taken and correlated to diagnosis and final outcome.

Results: Twenty-six always uncomplicated pairs, 51 always complicated pairs, and seven uncomplicated to pathological pairs were included. TTTS recipient (n?=?25) left and right MPI and intertwin difference (ITD) were significantly elevated, however, were already elevated in Stage I (n?=?10), and did not predict progression or pregnancy outcome. sIUGR MPI (n?=?11) did not differ significantly from control. Of 15-L/GD pairs, two that progressed to TTTS had significantly higher left and right MPI values in the future recipient (0.61 and 0.72) versus future sIUGR larger twins (0.48 and 0.51) or stable L/GD (0.47 and 0.52): p?Conclusions: In this cohort, MPI did not add substantial diagnostic/prognostic information to current routine evaluation in established TTTS or sIUGR though potentially differentiated L/GD cases progressing to TTTS.