Fetal Thoracic Pathology (pleural effusion;macrocystic CCAM)
Quality of Evidence III
Strength of Recommendation B
Prenatal assessment of the fetal condition including fetal karyotype (amniocentesis or chorionic villus sampling [CVS])
Ultrasound guidance for the thoracocentesis and thoracoamniotic (TA) shunt placement
Continued antepartum ultrasound surveillance (chest fluid volume, fetal growth, amniotic fluid volume, Doppler UA/UV, DV, middle cerebral artery [MCAs]) to monitor treatment success or complication
The specific techniques for the TA shunt procedure have been well documented and are not discussed in detail in this chapter.23 In utero surgical intervention should be considered for fetuses with secondary complications such as early onset hydrops or progressive polyhydramnios. Initially, ultrasound-guided thoracocentesis should be utilized to drain the CCAM dominant macrocyst or pleural effusion, with serial ultrasound scanning to evaluate if the fluid reaccumulates, the time interval for reaccumulation, and to determine if chronic TA shunting will correct the physiology/ pathology. Polyhydramnios may require ultrasound-guided amnioreduction to keep the amniotic fluid volume within the normal gestational age limits. If polyhydramnios is present, maternal endovaginal ultrasound cervical measurements are necessary to assess the risks of preterm labor and delivery. Maternal oral broad-spectrum antibiotic prophylaxis is recommended following the TA shunt placement for 7 to 10 days. The prophylactic use of oral tocolysis (indomethacin; nifedipine) has not been evaluated in a systematic process and will vary from center to center. Tocolytic use will be gestational age dependent as well. The CHOP protocol uses oral indomethacin, 50 mg 1 hour prior to shunt insertion, and rarely requires any additional tocolysis (terbutaline 0.25 mg subcutaneously [SC] every 15 minutes (2 injections; nifedipine, 20 mg orally).
Fetal pleural effusions (PE) are divided into primary and secondary causes (Figure 27-3).24 Primary PE is a lymphatic malformation while secondary PE has associated abnormalities such as cardiac dysfunction, anemia, infection, and aneuploidy. Primary PE has a frequency of 1 in 12,000 pregnancies with a 2:1 male-to-female ratio. Gestational age at presentation is usually less than 32 weeks' gestation, and the presence of hydrops is associated with high perinatal mortality rates (36% to 46%). The PE acts as a "space-occupying" lesion with resulting intrathoracic compression of the developing lungs and potential disturbance of intrathoracic blood flow secondary to the increased intrathoracic pressure and mediastinal shift of the heart and great vessels. The risk of lung deformation from the PE is directly related to the fluid volume. Bilateral PE has an increased risk for lung deformation/hypoplasia.
A: Bilateral pleural effusion at 26 weeks' gestation. B: Bilateral pleural effusion after thoracoamniotic shunt treatment.
Indications for fetal therapy (TA shunt) for PE requires a primary lymphatic component PE etiology with normal karyotype, negative viral cultures, normal fetal echocardiogram, no other significant fetal anomalies, rapid reaccummulation of the PE after thoracocentesis (within 24 to 72 hours), and gestational age less than 32 weeks.24 Perinatal outcomes have not been well evaluated for secondary PE etiologies treated with traditional fetal therapy techniques.
The most common complications of thoracic shunt procedures are displacement of the shunt into the amniotic cavity, or less commonly into the thoracic pleural space.24 The shunt should be placed as low in the thoracic cavity as possible. Occlusion of the catheter is due to fetal blood collection at the insertion site or the viscosity of the proteinaceous material within the effusion. Pregnancy loss (preterm delivery) associated with shunt insertion is estimated at 5%. Thoracocentesis risks for fetal loss are estimated at 0.5% to 1.0%.
The benefit for the ultrasound-guided fetal therapy is dependent on patient/fetal selection. Aubard et al25 identified fetal hydrops as the only prognostic feature for the outcome after multivariant analysis. Survival rate after TA shunt with or without hydrops was 67% and 100%, respectively, whereas without shunt treatment the survival was 21% to 23% in both groups.
Isolated fetal hydrothorax with hydrops was evaluated by systematic review of prenatal treatment options. Treatment options reviewed included thoracocentesis (single, serial), TA shunt, or combination. Overall population survival rate was 63%, ranging from 54% for single thoracocentesis to 67% with multiple thoracocentesis. In a limited cohort of 5 fetal cases treated with pleurodesis, there was an 80% survival. Shunt placement in fetuses with hydrops, with or without prior thoracocentesis, reported survival rates of 67% and 61%, respectively.26 A summary of pleural effusions treated by TA shunting with minimal case reporting overlap had a total of 154 cases with hydrops in 64% (99) and a survival of 67% (103). Another "overlapping" comparison summary reviewed 203 cases (153 hydrops, 75%) reporting a survival with thoracocentesis only (35) of 60% and with TA shunting (158) of 66%, while the presence of hydrops decreased the survival rate to 50% and 62%, respectively.27 An additional series of 54 hydropic fetuses treated with TA shunting had a survival rate of 57% but reported on the other TA shunt morbidities. Chorioamnionitis was found in 10% of the survivor group compared to 14% in the neonatal death group. Premature rupture of membranes occurred in 16% of the survivor group and 40% of the neonatal death group. The difference in shunt duration was 28 days for the survivor group and 7 days for the neonatal death group. The overall survival for fetuses with PE and hydrops based on these combined but overlapping summaries can be estimated at 65%.
Rustico et al27 provide an algorithm for management of apparently isolated fetal PE, using 34 weeks' gestation as a significant triage gestational age. For fetuses less than 34 weeks, with hydrops and/or polyhydramnios, TA shunting is recommended, whereas fetuses with no hydrops and normal amniotic fluid would continue with weekly observation. For those fetuses greater than 34 weeks' gestation, consider thoracocentesis immediately prior to delivery.
One of difficulties with determining whether PE is isolated is congenital pulmonary lymphangiectasis (CPL), a primary lung lymphatic anomaly, which can only be identified by lung biopsy.28 This rare CPL lesion increases the risk of hydrops (intestinal lymphatic component) being present but with a high neonatal lethality outcome.
Congenital cystic adenomatoid malformations (CCAMs) are benign space-occupying tumors caused by overgrowth of terminal respiratory bronchioles.24,29 CCAMs are most often unilobar (80% to 95%) and may affect any lobe. They are usually classified by prenatal imaging (ultrasound [US], magnetic resonance imaging [MRI]) as microcystic (50%) or macrocystic (50%), depending on the size of the CCAM cysts. The CCAMs can occasionally contain a single or several dominant macrocysts, which are filled with lung fluid and can progressively enlarge until forming large space-occupying lesions within the fetal lung (Figure 27-4). The larger volume lesions can cause mediastinal shift, fetal hemodynamic compromise, and hydrops. Depending on gestational age when the large volumes are identified, critical lung development occurring between 18 and 24 weeks' gestation may be affected. Polyhydramnios can develop due to esophageal occlusion secondary to an enlarging lesion, with an increased risk of preterm labor. The rate of CCAM growth is increased between 20 and 25 weeks with an anticipated plateau of growth at 26 weeks' gestation. The natural history of CCAMs with a dominant macrocyst is more unpredictable than microcystic lesions due to the differential growth of the macrocystic and microcystic CCAM components.
A: Left-sided microcystic cystic adenomatoid malformation with mediastinal and heart shift to the right; component of normal left lung is identified. B: Macrocystic cystic adenomatoid malformation CVR 2.05 right-sided lesion with heart shift to the left.
Ultrasound surveillance, CCAM volume calculation, and hydrops risk assessment uses the cystic adenomatoid malformation (CAM) ratio or CCAM to head circumference ratio (CVR) for triage of the prenatally diagnosed fetus with a CCAM.29 The CAM volume is obtained from the CAM ultrasound images with height, length, and width measurements and calculating the volume using the ellipse shape formula (length × height × width × 0.52). The CVR is then calculated by taking the CAM volume divided by the head circumference to correct for the gestational age. The CVR allows initial and serial evaluation of CCAM size or growth for risk assessment related to the development of hydrops. A CVR of greater than 1.6 at presentation predicts an increased risk of hydrops, developing due to the CCAM size. A CVR less than 1.6 at presentation suggests that the risk of hydrops developing in the absence of a dominant macrocyst is less than 3%.29 Proposed fetal surveillance depending on the CVR at presentation is weekly if the CVR is less than 1.0; twice a week if the CVR is between 1.0 and 1.4; 3 times a week if the CVR is greater than 1.4. Fetal therapy options will vary dependent on the ultrasound appearance of microcystic or macrocystic CCAM lesions.
Medical therapy for CCAM therapy has been used in a small number of cases.30 There is preliminary information that maternal steroid treatment (betamethasone 12 mg intramuscularly [IM] × 2 doses 24 hours apart) has an inhibiting effect on CCAM growth. Recent data evaluated 11 fetuses (5 with hydrops; 7 with CVR >1.6) with significant CCAM pathology and risk of hydrops development. CCAM growth rates were variable after maternal steroid administration, and when compared to historical controls, the CVR and CCAM growth rates decreased in 72% and 50% of patients, respectively, from the time of steroid administration to 28 weeks' gestation. This therapy has not been proven and a blinded/placebo RCT is planned to document the potential benefit for this noninvasive fetal treatment.
Because the fetal risks with the higher CVR macrocystic lesions, the TA shunt therapy may need to be used at earlier gestational ages. A case series reports that TA shunting at less than 21 weeks' gestation may increase the risk of a postnatal chest deformity due to rib development disruption.31 This potential risk should be included in the pre-procedure counseling with gestational ages less than 21 weeks at TA shunt insertion.
Laser therapy for CCAM, CCAM hybrid, and BPS pathology has been reported.32,33,34,35,36, and 37 Six cases have been reported with survival in 50%. Gestational age at treatment was 19 to 24 weeks. Table 27-4 summarizes the published reports.
Table 27-4CCAM/BPS PRENATAL LASER TREATMENT ||Download (.pdf) Table 27-4 CCAM/BPS PRENATAL LASER TREATMENT
|References ||GA Weeks at Treatment ||Lesion ||Micro ||Macro ||Hydrops ||Outcome |
|Fortunato et al32 ||21/23 ||CCAM || || ||X ||Laser ×3: PNM |
|Bruner et al33 ||23/24 ||CCAM || || || ||PNM 26 wk Myocardial necrosis Chest wall deformity |
|Ryan et al34 ||19 ||Hybrid || ||X ||X ||Shunt and laser at 19 wk Delivery at 39 wk |
|Davenport et al35 ||19/31 ||CCAM ||— ||X ||X ||Delivery at 38 wkPNM day 4; sepsis |
|Ong et al36 ||21 ||CCAM ||— ||X ||X ||Sulindec AR at 27 wk Delivery at 39 wk |
|Oepkes et al37 ||23 ||Hybrid ||X || ||X ||Delivery at term Well at 2 y |
The outcomes of fetuses with large macrocystic CCAMs treated with TA shunts are summarized in Table 27-5.24,38,39,40,41,42,43,44,45, and 46
Other fetal thoracic pathology that may require in utero therapy includes mainstem bronchial atresia47 and congenital lobar emphysema (CLE).48 For the mainstem bronchial atresia, maternal-fetal surgery was unsuccessful with an intraoperative death at 24 weeks' gestation. CLE can have a prenatal ultrasound appearance similar to CCAM.
Table 27-5CCAMS IN UTERO THORACOAMNIOTIC (TA) SHUNT THERAPY WITH SURVIVAL COMPARISON WITHOUT AND WITH TA SHUNT ||Download (.pdf) Table 27-5 CCAMS IN UTERO THORACOAMNIOTIC (TA) SHUNT THERAPY WITH SURVIVAL COMPARISON WITHOUT AND WITH TA SHUNT
|Study ||Cases ||Shunts ||Hydrops ||Survival ||Shunt survival |
|Bernaschek et al38 ||4 ||4 ||2 ||75% ||75% |
|Miller et al39 ||17 ||1 ||4 ||71% ||100% |
|Dommergues et al40 ||33 ||9 ||9 ||79% ||67% |
|Monni et al41 ||26 ||0 ||2 ||65% ||0 |
|Bunlaki et al42 ||18 ||1 ||7 ||72% ||100% |
|DeSantis et al43 ||17 ||0 ||2 ||76% ||0 |
|Laberge et al44 ||48 ||1 ||5 ||75% ||0 |
|Wilson et al24 ||10 ||10 ||6 ||70% ||70% |
|Viggiano et al45 ||1 ||1 ||0 ||100% ||100% |
|Isnard et al46 ||1 ||1 ||1 ||100% ||100% |
|Total ||171 ||28 ||38 ||74% ||71% |
Evidence-based prenatal therapy for congenital thoracic anomalies (excluding congenital diaphragmatic hernia) is presented in Table 27-6.49
Table 27-6PRENATAL THERAPY FOR CONGENITAL THORACIC ANOMALIES (EXCLUDING CDH) WITH EVIDENCE-BASED RECOMMENDATION49 ||Download (.pdf) Table 27-6 PRENATAL THERAPY FOR CONGENITAL THORACIC ANOMALIES (EXCLUDING CDH) WITH EVIDENCE-BASED RECOMMENDATION49
A. a) Amnioreduction (polyhydramnios)(amniotic fluid removal or medication EA decreased urine production)
TEF ± EA
Neck mass (teratoma; lymphangioma)
Mediastinal mass (teratoma, neurenteric cyst)
|b) Maternal betamethasome ||CCAM ||— |
|B. Thoracocentesis || |
CCAM macrocyst III-B
BPS pleural effusion
CCAM/BPS hybrid pleural effusion
|C. a) Thoracoamniotic shunt || |
BPS/hybrid pleural effusion
|b) Laser ||CCAM/BPS/hybrid ||— |
|D. Maternal–fetal surgery || |
CCAM (micro- or macrocystic)
|E. EXIT (excision, tracheal management) || |
Neck mass (teratoma, lymphangioma)
Lower Urinary Tract Obstruction (LUTO)
Quality of Evidence III
Strength of Recommendation B
Prenatal assessment of the fetal condition including fetal karyotyping (amniocentesis or CVS)
Ultrasound guidance for the serial vesicocentesis and vesicoamniotic shunt placement
Continued antepartum ultrasound surveillance (bladder volume, fetal growth, amniotic fluid volume, Doppler UA/UV, DV, MCA) to monitor treatment success or complication
Lower urinary tract obstruction is a heterogeneous fetal pathology group with posterior urethral valves and urethral atresia as the most common obstructive etiologies, accounting for one-third of the renal tract anomalies detected at autopsy after termination for ultrasound-diagnosed fetal anomalies.50 Untreated fetuses with complete LUTO have abnormal renal development and function, leading to oligohydramnios, pulmonary hypoplasia, deformation type limb/facial anomalies with a high perinatal mortality rate. Although the posterior urethral valves and urethral atresia are specific for male fetuses, there are nonobstructive megacystis cases identified in female fetuses with a possible diagnosis of an autosomal recessive syndrome identified as megacystis, microcolon, hyperperistalsis syndrome.
Early fetal therapy procedures were directed at these urinary obstructive anomalies with bladder drainage by vesicocentesis and continuous drainage with vesicoamniotic shunt placement/drainage by vesicostomy using maternal-fetal surgery (Figure 27-5). These therapies have been available and used for many years due to the easily identified bladder obstruction and oligohydramnios appearance on ultrasound scanning. Systematic review/meta-analysis have shown that there is a lack of high-quality evidence to reliably direct clinical practice regarding prenatal bladder drainage in fetuses with ultrasonic evidence of LUTO. This lack of good evidence-based information emphasizes the need for protocol approaches to these obstructive bladder cases so that appropriate analysis can direct appropriate clinical decisions (treatment, no treatment).
A: fetal therapy equipment and pig-tailed shunt used for chest and bladder shunt placement. B: Newborn at third trimester EXIT delivery with thoracoamniotic shunt in situ.
The comparison of prenatal ultrasound imaging and postnatal anatomical pathologic analysis (autopsy) of male fetuses with LUTO prior to 25 weeks' gestation has shown that hyperechogenic kidneys were predictive of renal dysplasia in 95% of cases.51 In the 24 male cases, postmortem examination identified the pathological etiologies as urethral atresia (6), severe urethral stenosis (8), posterior urethral valves (9) and normal (1). Renal dysplasia was confirmed in 23 of 24 cases. Urethral atresia was the most common urethral anomaly at 12 to 17 weeks. Assessment of fetal bladder size and presence of hydronephrosis may possibly allow improved detection of the correct prenatal obstructive diagnosis. A saggital bladder diameter of 40 mm as associated with hydronephrosis before 28 weeks' gestation had a positive predictive value (PPV) for posterior urethral valves of 44%, the absence of hydronephrosis and bladder diameter of less than 40 mm had a PPV for urethral atresia/ stenosis of 100%, and the absence of hydronephrosis had PPV of urethral atresia of 67%.
Prenatal selection criteria for vesicoamniotic shunting are isolated megacystis, bilateral hydronephrosis, decreased amniotic fluid volume, no other associated congenital anomalies, normal male karyotype 46,XY, and serially improving urinary/renal function values (Table 27-7).23
Table 27-7PRENATAL URINARY PARAMETERS INDICATING ADEQUATE RENAL FUNCTION FOR CONSIDERATION OF IN UTERO VESICOAMNIOTIC SHUNTING23 ||Download (.pdf) Table 27-7 PRENATAL URINARY PARAMETERS INDICATING ADEQUATE RENAL FUNCTION FOR CONSIDERATION OF IN UTERO VESICOAMNIOTIC SHUNTING23
|Osmolality ||<200 mOsm/L |
|Sodium ||<100 mEq/L |
|Chloride ||<90 mEq/L |
|Calcium ||<8 mg/dL |
|Total protein ||<20 mg/dL |
|β2-microglobulin ||<6 mg/L |
In serial ultrasound-guided vesicocentesis it is recommended that 3 fetal specimens be obtained over 5 to 7 days, showing improving renal function values but with specimen 2 or 3 reflecting retained renal function parameters, thereby identifying the male fetus as a candidate that may benefit from vesicoamniotic shunting (VAS).23 The VAS insertion technique has been described.23
Systemic review has compared the effect of bladder drainage versus no bladder drainage on perinatal survival.52 Among the controlled studies, bladder drainage appeared to improve perinatal survival relative to no drainage (OR 2.5; 95% CI = 1.1 to 5.9; P = .03). The contradictory finding from this review was that this improved outcome observation was largely in the subgroup of fetuses with a prenatally predicted poor prognosis based on ultrasound and fetal urinary electrolytes criteria (OR 8.1; 95% CI = 1.2 to 52.9; P = .03). An improved outcome was also suggested in the good prognosis group (OR 2.8; 95% CI = 0.7 to 10.8; P = .13) but without significant values. The conclusions from this systematic review reported that the limited available evidence suggests that prenatal bladder drainage may improve perinatal survival in these bladder-obstructed fetuses, particularly those fetuses with a poor predicted renal prognosis by ultrasound and urinary renal function parameters.52
An RCT (PLUTO, University of Birmingham, UK) is presently enrolling fetuses to investigate the role of fetal vesicoamniotic shunting in moderate/severe LUTO.53 The study plans to recruit 200 women over 3 years with the criteria of a singleton pregnancy, viable intrauterine gestation with a diagnosis of isolated bladder outflow obstruction at less than 28 weeks (hydronephrosis, megacystis, oligohydramnios less than the 5th centile, and no other structural or chromosomal abnormalities). Fetuses will be randomized to VAS or conservative observation following maternal consent. Follow-up is scheduled for 5 years looking at obstetrical outcomes, procedural complications, survival, renal function/pathology, disability, and continence.
Complications from the VAS must be part of the informed consent process. These risks include chorioamnionitis, premature rupture of membranes, direct trauma to the fetus, placental bleeding, and possible preterm labor. Transient vesicoperitoneal fistulas occasionally result in urinary ascites. Fistula closure usually takes 10 to 14 days. Shunt displacement occurs in 30% to 45% of VAS cases. The fetal death rate following shunt placement is reported to be 5% (9 of 169 cases). Vesicocentesis risks for pregnancy loss are considered similar to amniocentesis rates at 0.5% to 1.0%, but are additive with the serial procedure requirements.
VAS under ultrasound guidance is usually done at gestational ages of 20 to 30 weeks following identification and evaluation of the fetal urinary obstruction.23 VAS has been done as early as 13+5 weeks using a double-basket catheter in a fetus with posterior urethral valves (PUV), delivery at 33 weeks, and normal renal function at age 3 years.54
Large database evaluation has reported on the diagnosis and outcome of fetal lower urinary tract obstruction.55 The incidence of LUTO was 2.2 per 10,000 births. The prenatal detection improved over the study period from 33% to 62%. The sensitivity for prenatal ultrasound prediction of renal dysplasia on autopsy or chronic renal failure based on fetal urine parameters (sodium, calcium or β2-microglobulin) was 59%, 33%, 66%, and 63%, respectively. This study supports the poor prognosis natural history for fetuses with LUTO.
Long-term outcome for 23 pregnancies complicated by antenatal oligohydramnios had 9 male fetuses with posterior urethral valves and survival in 7 (78%).56 Developmental delay was present in 3 of the 7 survivors. Amnioinfusion was used in 1 survivor at 19 weeks' gestation with postnatal outcome reporting neonatal peritoneal dialysis, vascular dialysis at age 2, and renal transplant at age 4. Postnatal renal function was variable, but long-term outcome results in the survivors was reported to be encouraging. Biard et al reported long-term outcomes in fetuses treated with in utero shunting and found significant morbidity in survivors.57 Clinical outcomes from 20 singleton male fetuses with oligohydramnios and LUTO had a 1-year survival of 91% (with 2 neonatal deaths from pulmonary hypoplasia). Mean age to follow-up was 5.8 years. Pathology for the LUTO was PUV (7), UA (4), and prune belly syndrome (7).
Neurodevelopmental outcomes for this group were 78% normal with learning, speech, and physical therapy issues in 11%, 16%, and 16%, respectively. Eight children had acceptable renal function, 4 had mild renal insufficiency, and 6 required dialysis with eventual renal transplant. Other comorbidities included respiratory (8) and musculoskeletal problems (9). Self-completed Quality of Life questionnaires showed no reported difference compared to healthy controls in a validated evaluation for parents and children in this cohort.
Congenital megalourethra is characterized by ultrasound features of LUTO in association with dilatation and elongation of the penile urethra.58 Severe oligohydramnios was found in only 1 of 4 prenatal cases between 20 and 24 weeks' gestation. Neonatal deaths occurred in 3 cases with 1 pregnancy termination. No prenatal therapy was used in these cases.
Urinary congenital anomalies for female fetuses involves cloacal anomalies (isolated) or as part of a larger OEIS complex (omphalocele, bladder extrophy, imperforate anus, spinal defect). Cloacal anomaly is a contraindication to in utero therapy, as isolated attempts to shunt large cystic spaces have not indicated benefit. OEIS has variable outcomes but survival with significant genitourinary/ reproductive morbidity is possible, even with no in utero therapy considerations.59
Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) presents most commonly in females with megacystis and normal amniotic fluid volume. Vesicocentesis has been reported with vesicoamniotic shunting.60 Normal renal function is usually identified with urinary fluid analysis. The vesicocentesis to completely empty the bladder allowed the dilated fetal bowel to be identified, confirming the MMIHS diagnosis. Amniotic fluid analysis for fetal gastrointestinal enzymes has also been used in conjunction with the normal renal function findings to diagnose MMIHS.61 Survival with an MMIHS diagnosis is estimated at 70%.
Monochorionic Twin Pathology: Twin-to-Twin Transfusion Syndrome (TTTS)
Quality of Evidence Ib
Strength of Recommendation A
Ultrasound evaluation of the monochorionic diamniotic twin (MCDA) for criteria to evaluate TTTS or other MCDA pathology
Ultrasound allows identification of the vascular equator using placental location and twin placental cord insertion sites to establish the best site of entry for the endoscopic laser coagulation site
Ultrasound is used throughout the procedure to assess the fetal status, location, and amniotic fluid volume
Following the completion of the endoscopic laser coagulation, ultrasound is used to evaluate fetal Doppler status, amniotic fluid volumes, and laser port entry site after removal
The extensive literature regarding TTTS can only be summarized. Review articles summarize the topic (Figure 27-6).62 Monochorionic diamniotic twinning has a higher risk of perinatal complications than dichorionic twinning, even after exclusion of disorders unique to monochorionic placentation.63 Severe TTTS occurs in 10% to 15% of monochorionic diamniotic twin pregnancies and carries a significant risk of perinatal morbidity and mortality. TTTS results from placental vascular anastomoses that result in a differential distribution of blood and vasoactive substances between the donor and recipient twin. The natural history of severe TTTS results in extreme preterm delivery (prior to 25 weeks) with neonatal death in 90%. Disease severity in TTTS is predicted by the ultrasound parameters in the Quintero staging system, which describes progressive changes that begin with intertwin differences in growth and amniotic fluid volume, and progress to an absence of visualization of the urinary bladder as a surrogate for hypovolemia in the donor, abnormalities of umbilical Doppler ultrasonography, and ultimately the development of hydrops and fetal death in the overloaded recipient.64 Whereas the Quintero staging system has provided a valuable platform for comparison and staging of TTTS between pregnancies and institutions, fetal echocardiography evaluations have provided new insight and assessment into the pathophysiology of TTTS. Fetal cardiac parameters (ventricular hypertrophy, dilatation, function, valve regurgitation, great artery size, and diastolic properties in the recipient and umbilical artery flow in the donor) have been shown to enhance the clinical assessment for staging and treatment triage as well as to evaluate post-endoscopic laser treatment success.65
A: Monochorionic diamniotic twins with twin to twin transfusion syndrome showing placental cord insertion sites for this twin pair (n unusually close). B: monochorionic diamniotic twins with twin to twin transfusion syndrome post laser coagulation: anastomosis with vein on left and artery on right.
Several treatment options have been used over a number of years with the goal of improving neonatal outcome. Techniques that have been used include serial amniodrainage, intertwin amniotic septostomy, selective termination of one fetus, and the present treatment, "gold standard" endoscopic laser coagulation of the placental vascular anastomosis.1,2, and 3
Fetoscopic laser coagulation for TTTS was first described by Dr Julian DeLia as a technique that functionally converts a monochorionic placenta to a functionally dichorionic placenta by occluding vascular connections between the twins. A subsequent laser technique used a more selective location for the coagulation site, as the vascular equator between the twins did not correspond with the placental location of the intertwin membrane.1,2, and 3,64 This selective laser technique is hypothesized to preserve noncommunicating vessels and has been associated with improved survival rates of 62% to 77%.
Two RCTs have evaluated the TTTS treatment with comparison between the previous "gold standard" amnioreduction (AR) and the experimental endoscopic laser coagulation/separation.2–3 These 2 studies have contradictory conclusions with the "Eurofetus" trial2 corresponding with a larger body of cohort studies. The "Eurofetus" study identified pregnant woman with severe TTTS prior to 26 weeks' gestation and randomized 70 women to AR and 72 to endoscopic laser coagulation. The laser group had a higher likelihood of the survival of at least 1 twin to 28 days of age (76% vs 56%). Infants in the laser group had a lower incidence of neurological injury (6% vs 14%). Endoscopic laser coagulation of anastomosis was a more effective first-line treatment than serial AR for severe TTTS diagnosed before 26 weeks' gestation. The National Institute of Child Health and Human Development (NICHD) trial3 was not fully completed and the trial was closed to enrollment as the TTTS "Eurofetus" results caused clinicians to be convinced that endoscopic laser coagulation was the treatment of choice for severe TTTS.
Prospective studies continue to report improved neonatal outcomes with endoscopic laser coagulation. Huber et al reports an overall survival rate of 71.5% with survival of both twins at 59.5% and survival of at least 1 twin at 83.5% in a 200-twin-pair, consecutive pregnancies cohort.66 The mean gestational age at delivery was 34.3 weeks (23 to 40 weeks). There was a reduced neonatal survival as the TTTS increased in staged severity: stage I—both twins 76%, at least one 93%; stage II—both twins 60%, at least one 83%; stage III—both twins 54%, at least one 83%; stage IV—both twins 50%, at least one 70%. The overall survival rate for donor fetuses was 70.5% and for recipient fetuses 72.5%. Other studies continue to support this level of outcome.67,68
Long-term neonatal outcome studies report good neurological and growth outcomes with follow-up intervals of 2 to 6 years. Graef et al69 report on 167 surviving infants from TTTS with endoscopic laser coagulation followed to a median age of 3 years and 2 months. Normal neurodevelopmental outcomes were seen in 86.8%, and an incidence of major neurological deficiencies in 6%. Lopriore et al70 reports on 82 twin pairs from TTTS and a survival of 70% with neurodevelopmental impairment in 17% (19 of 115) including cerebral palsy (8), mental developmental delay (9), psychomotor developmental delay (12), and deafness (1). Lenclen et al71 assessed the neonatal outcome in 137 TTTS preterm neonates treated with AR (36) and laser (101). These 137 monochorionic twins were compared to 242 dichorionic twins. Gestational ages at delivery for the groups was 24 to 34 weeks. Adverse neonatal outcomes (death or severe cerebral lesions) was more frequent in the AR group. The overall neonatal outcomes were comparable for the laser and dichorionic groups. However, the neonatal morbidity was higher in the endoscopic-laser-exposed neonates born at 30 weeks' gestation mainly due to failed laser therapy. Lopriore et al70 reported on monochorionic twins with TTTS treated with endoscopic laser compared to monochorionic twins without TTTS. Antenatally acquired severe cerebral lesions in the TTTS and non-TTTS groups was 10% and 2%, respectively. At discharge, the incidence of severe cerebral lesions in the TTTS and non-TTTS groups was 14% and 6%, respectively. Antenatal injury was responsible for severe cerebral lesions in 67%. A smaller non–endoscopic laser Japanese study of 18 monochorionic twins (33 survivors) and 12 treated with AR were followed to age 6.72 No difference in cerebral palsy, epilepsy, mental retardation, neurological deficits at school age, or growth when compared to weight-matched singleton controls was found. The median and range for diagnosis and birth for the TTTS pregnancies were 23 (10 to 33) and 28.5 (23 to 36) weeks, respectively.
Specific fetal cardiac features of TTTS were introduced in the screening evaluation portion of this chapter with the CHOP cardiovascular score for TTTS.65 In TTTS, the donor and recipient are exposed to differing volume loads and show discordant intertwin vascular compliance in childhood despite identical genotype. Vascular programming is evident in monozygotic twins with intertwin transfusion and is altered but not abolished by intrauterine therapy to resemble that seen in dichorionic twins.73 A similar analysis to evaluate cardiac morphology and function in survivors of severe TTTS after laser coagulation reported similar cardiac changes post-laser with improved biventricular systolic function and tends to improve diastolic function in the recipient twin.74 Barrea et al reported on the fetal cardiovascular changes in TTTS recipients after AR. Despite AR, the recipient twin had progressive biventricular hypertrophy with predominant right ventricular systolic and biventricular diastolic dysfunction.74 The prevalence of congenital heart disease (particularly pulmonary stenosis) was increased in the TTTS recipients with 11.2% and 7.8% compared to the general population with 0.3% and 0.03%, respectively.
Renal function in twins complicated with TTTS is affected by the hypertensive status in the recipient (polyuria) and hypotension status in the donor (anuria).75 No significant difference in long-term renal function was found between recipient and donors from 18 surviving twin pairs after endoscopic laser coagulation. The laboratory findings for all 36 children were within normal limits at mean age 3 years and 1 month (range 1 year and 9 months to 4 years and 5 months).
Fetal growth analysis of monochorionic twins after endoscopic laser treatment for TTTS has shown a slowdown in recipient growth and maintained growth in the donor, leading to a decrease in intertwin discordance.
Maternal cervical length as a surrogate marker for the maternal risk of preterm labor was evaluated in a cohort of severe TTTS following endoscopic laser coagulation prior to 26 weeks' gestation. The mean cervical length was 32 and 38 mm in women delivering before and at or before 34 weeks, respectively (P < .0001). For a cervical length of less than 30 mm, the risk of delivery before 34 weeks was 74%. Three independent factors to predict preterm delivery were identified: short cervical length (increased risk), parity (increased risk), and intrauterine death of 1 twin (decreased risk).76
Perioperative endoscopic laser complications occur, and this potential risk should be part of the informed consent counseling. Perioperative complications were reported from 175 percutaneous endoscopic laser procedures completed under local anesthesia.77 Placental abruption and miscarriage occurred in 3 and 12 (7%) cases, respectively. Premature rupture of membranes (PROM) occurred in 28% (49 cases) with 12, 29, and 46 cases that occurred before 24, 28, and 34 weeks, respectively. The trocar entry tract was transplacental in 27% (48 cases) but no significant adverse outcomes resulted.
Late fetal complications following 151 consecutive successful laser therapy cases reported miscarriage, double intrauterine fetal death (IUFD), and single IUFD occurred in 4% (6 of 151), 5% (7 of 151), and 26% (39 of 151), respectively. At 7 days after the procedure, 67% (101 of 151) had 2 living fetuses. Recurrence of the TTTS features occurred in 14 cases (14%). Middle cerebral artery-peak systolic velocity (MCA-PSV) evaluation identified 2 cases with values indicating anemia (increased) and polycythemia (decreased). This result was hypothesized to be due to unidirectional fetofetal blood transfusion, mainly from former recipients into former donors.78 Late complications were managed accordingly by repeat laser, AR, cord coagulation, intrauterine blood transfusion, or elective delivery. MCA-PSA Doppler measurements were useful in double survivor follow-up to identify late vascular changes.
When the diagnosis of monochorionic diamniotic twins with severe TTTS is made, therapeutic AR should be discouraged in patients considering endoscopic laser coagulation and should only be utilized for maternal findings of cervical dilation/internal cervical os "beaking" or maternal respiratory compromise. Membrane detachment from the uterine wall is a complication of AR and results in delayed or no access to endoscopic laser coagulation therapy. Amniopatch techniques have been proposed to treat this TTTS complication.64
At the present time, monochorionic diamniotic twin pairs complicated by severe TTTS prior to 26 weeks have improved outcomes for survival, gestational age at delivery, and outcomes for neurological, renal, and cardiac disease if treated with endoscopic laser coagulation therapy. The experience of the operator is an important aspect in the successful treatment outcome. Treatment centers should attempt to maintain caseload volumes of greater than 40 cases per year for maintenance of skills and management by the operative team (medical, anesthesia, nursing).
Monochorionic Twin Pathology and Selective Termination for TTTS, TRAP, Discordant Fetal Anomaly
Quality of Evidence III
Strength of Recommendation B
Ultrasound evaluation of the monochorionic diamniotic twin (MCDA) for criteria to evaluate TTTS or other MCDA pathology
Ultrasound allows identification of the vascular equator using placental cord insertion sites to establish the best site of entry for the invasive procedure
Ultrasound is used throughout the procedure to assess the fetal status, location, and amniotic fluid volume
Following the procedure, ultrasound is used to evaluate fetal Doppler status, amniotic fluid volume, and uterine procedure site
Monochorionic twinning is a congenital anomaly with the timing of the embryonic splitting determining the fate of the twin pair. The placental vascular sharing contributes to monochorionic twin pathologies including severe twin-to-twin transfusion syndrome (TTTS), twin reversed arterial perfusion (TRAP), discordant fetal anomalies, and placental insufficiency with discordant intrauterine fetal growth restriction (IUGR).
TTTS has been described in this chapter. TRAP or acardiac twinning has a prevalence of 1 in 35,000 pregnancies. The presence of an arterioarterial and venous anastomosis between the cord insertions in monochorionic twins may lead to a reversal of perfusion via the umbilical artery of one twin, if one pulse wave predominates over the other pulse wave, early in the gestation development (Figure 27-7).79 In the reversely perfused twin, there is no cardiac development at all or only a rudimentary heart tube can be detected. The development of the upper part of the body is severely impaired, and most acardiac twins show acrania and hydrops.79 The normally developed "pump" twin is at risk for heart failure, preterm delivery, and intrauterine death. The "pump" twin mortality was 51% and delivery prior to 34 weeks occurred in 76%.
A: fetal therapy bipolar cord coagulation equipment. B: TRAP twin showing the two vessel umbilical cord with reversed flow, the abnormal twin development, and the arrow showing the anticipated location for the bipolar cord coagulation site.
A wide variety of innovative techniques have been reported for the selective separation of the normal "pump" twin from the acardiac twin. Quintero et al reported on 74 monochorionic twin pregnancies complicated by TRAP (1993 to 2004) with 51 pregnancies having a procedure for cord occlusion to the abnormal twin.80 Because of the reported time period, a variety of techniques were used for umbilical cord occlusion (UCO) including umbilical cord ligation, UCO via laser coagulation of the cord, cord ligation and transaction (monoamniotic twin pair), and endoscopic laser coagulation of the arterioarterial and venovenous anastomoses. The overall perinatal survival in the surgical group was 65% compared to 43% in the nonsurgical group. Surgery within the acardiac twin's gestational sac was possible in 24%. There were no significant differences in the perinatal outcomes relative to the specific surgical technique reported. Hecher et al79 reports on 60 consecutive pregnancies complicated with TRAP using endoscopic laser treatment of placental anastomoses (18) and umbilical cord (42). Median gestational age at treatment was 18.3 weeks (14.3 to 24.7 weeks). Vascular coagulation with arrest of blood flow was achieved in 82% by laser alone and in a further 15% by laser coagulation in combination with bipolar forceps. The overall survival of the "pump" twin was 80%. Median gestational age at delivery was 37 weeks (24 to 41 weeks). PROM prior to 34 weeks' gestation occurred in 18%. One of the proposed advantages reported by Hecher et al is that this technique can be used at gestational ages less than 18 weeks as bipolar cord cautery was reported to have an increased fetal demise when performed at 16 to 17 weeks compared to 18 weeks or later (41% vs 3%).
Lewi et al report on selective fetal termination by cord coagulation in 80 complicated monochorionic multiple pregnancies (67 monochorionic diamniotic [MCDA]; 6 monochorionic monoamniotic [MCMA]; 4 monochorionic triamniotic [MCTA]; 3 dichorionic triamniotic [DCTA]) using endoscopic laser and/or bipolar techniques.81 The indications for the fetal cord cautery were reported as discordant fetal anomaly (35%), TTTS (30%), TRAP (27.5%), and severe IUGR (7.5%). For 69% (55 of 80) of cases, laser was used as the primary technique, but half the cases required additional bipolar coagulation to achieve arrest of flow. Bipolar cord cautery was used as the primary technique in the remaining 31% (25 of 80). Median gestational age at procedure was lower in the primary laser group compared to the bipolar group (19.4 weeks vs 22.4 weeks). Only 1 bipolar case was unsuccessful in a TRAP with cord perforation and an intraoperative IUFD. The survival rate was 83% (72 of 87) with no significant differences for twins and triplets. There were 9 IUFDs (10%) with 5 early and 4 late losses. There was 1 pregnancy termination and 5 perinatal deaths due to PROM prior to 25 weeks' gestation. Ongoing pregnancies had a mean gestational age at delivery of 35 weeks. Delivery before 28 weeks gestation was 85 (6 of 71) and between 28 and 32 weeks in 13% (9 of 71). Preterm PROM (PPROM) occurred in 38% (27 of 71). Developmental outcome was available for all 72 survivors, and the children greater than 1 year of age 92% (62 of 67) had normal development.
Each of these complicated monochorionic and monochorionic multiple pregnancies are individual and unique due to the placental locations, twin pathology, maternal body mass index (BMI), gestational age at presentation, and a variety of the maternal/fetal/obstetrical issues. Techniques and approaches will be dependent on operator expertise and experience. The above reports have skilled operators using multiple and combined techniques for the selective termination. Tables 27-882,83,84,85,86, and 87 and 27-988,89, and 90 compare the ultrasound-guided percutaneous single device techniques of bipolar umbilical cord cautery (BUCC) and radiofrequency ablation (RFA) with the complicated monchorionic twin/triplet pathology for selective termination. While RFA is a purely ultrasound-guided technique with ultrasound Doppler assessment for completion of blood flow arrest, BUCC is an ultrasound-guided technique for the bipolar instrument port insertion and cord location/ cautery/cord transection. The fetoscope can be used via the 3-mm port to visualize the cord cautery coagulation sites, but confirmation of blood flow occlusion requires Doppler flow evaluation. The RFA technique does not require amnioinfusion of the abnormal gestational sac if oligohydramnios is present, while BUCC may, in certain situations, require this additional procedure of amnioinfusion to allow umbilical cord access.
The technique that provides the best benefit:risk for the selective termination of a monochorionic twin with discordant anomalies or physiology has not as yet been determined. It is not likely that an RCT will be available to determine the best technique for these indications, but gestational age and vascular diameter may determine that RFA can be used at gestational ages less than 20 weeks and bipolar cord cautery may be a better choice for gestational ages greater than 20 weeks. Post-procedure loss rates are estimated at 20% for RFA and 15% for bipolar cord cautery. PROM rates for both techniques are estimated at 18% to 20% (Table 27-10).
Table 27-8BIPOLAR UMBILICAL CORD COAGULATION IN MONOCHORIONIC GESTATIONS ||Download (.pdf) Table 27-8 BIPOLAR UMBILICAL CORD COAGULATION IN MONOCHORIONIC GESTATIONS
|Author ||Procedures ||EGA at Surgery(Weeks) ||Success ||PPROM ||Post Procedural Losses ||EGA at Delivery(Weeks) ||Indication |
|Nicolini et al. ||17 ||18–27 ||17/17 ||3 ||4 ||27-41 || |
TRAP = 2
TTTS = 9
DA = 6
|Johnson et al. ||21 ||Mean = 21 ||21/21 ||2 ||2 ||Mean = 32 || |
TTTS = 6
DA = 6
|Taylor et al. ||15 ||18–28 ||15/15 ||3 ||2 ||24-38 ||TTTS = 15 |
|Moldenhauer et al. ||45 ||13–24 ||45/45 ||11 ||9 ||25-40 || |
TRAP = 9
TTTS = 7
DA = 29
|Robyr et al. ||46 ||16–35 ||44/46 ||11 ||6 ||27-41 || |
TRAP = 17
TTTS = 22
DA = 7
|Ilagan et al ||27 ||21 ||100% ||5 (17.8%) ||3 (10.3%) ||34.4 || |
TRAP = 11
TTTS = 11
Anomaly = 4
Chrom = 1
|Total ||171 ||21 ||99% ||35 (20%) ||26 (15%) ||34 wks || |
TRAP = 49
TTTS = 70
Anomaly = 52
Table 27-9RADIO FREQUENCY ABLATION SELECTIVE TERMINATION OUTCOME SUMMARY ||Download (.pdf) Table 27-9 RADIO FREQUENCY ABLATION SELECTIVE TERMINATION OUTCOME SUMMARY
| ||Procedure ||EGA ||Success ||PPROM ||Other Twin Loss ||Del EGA ||Fetal Indication |
|Sherell et al ||1 ||17 ||100% ||- ||- ||37 ||Anomaly 1 |
|Lee et al ||29 ||- ||100% ||5 (17%) ||4/29(14%) ||34.8 ||TRAP 29 |
|Bebbington et al ||21 ||19.2 ||100% ||4 (19%) ||7/21 (34%) ||29.2 || |
| ||51 ||18 ||100% ||18% ||22% ||32.5 || |
Table 27-10MONOCHORIONIC SELECTIVE TERMINATION OUTCOME SUMMARY: ULTRASOUND ASSISTED ||Download (.pdf) Table 27-10 MONOCHORIONIC SELECTIVE TERMINATION OUTCOME SUMMARY: ULTRASOUND ASSISTED
| ||Technique ||GA(week) ||Success ||Preg Loss ||PPROM |
|1. ||BUCC ||18-35 ||99% ||15% ||20% |
|2. ||RFA ||17-24 ||100% ||22% ||18% |
|3. || |
Other monochorionic placental functional abnormalities can result in unequal placental sharing with one twin having normal growth while the other twin has IUGR. In singleton pregnancies, fetuses with IUGR are at higher risk for poor perinatal and long-term outcome compared to fetuses with appropriate growth. Placental factors are the most significant etiology for growth restriction interrelated to cardiovascular and behavioral responses, and metabolic status. Factors that impact the neonatal outcomes in singleton fetuses with placental-based growth restriction are gestational age, birth weight, and ductus venosus Doppler parameters.91 Other physiological assessment has evaluated Doppler values (umbilical artery [UA], ductus venosus [DV]) and short-term fetal heart rate variation to predict perinatal outcome in the severe, early IUGR fetus. The DV pulsatility index for veins (PIV) measurement was the best predictor of perinatal outcome with a cutoff value of 2 to 3 SD as appropriate for delivery. Considering placental insufficiency perinatal outcomes in monochorionic twin pregnancies, amniotic fluid discordance, IUGR, and umbilical artery absent or reversed end-diastolic (ARED) flow in one fetus represents an extremely high-risk constellation for adverse pregnancy outcome.
Placental Chorioangioma Management With Ultrasound-Guided Techniques
Quality of Evidence III
Strength of Recommendation B
Ultrasound assessment of the location placenta, placental cord insertion site, and size and appearance of the placental lesion
Ultrasound guidance is dependent on technique being used to decrease the placental arteriovenous shunting through the placental chorioangioma
Assessment of the fetus by fetal heart rate, and Doppler studies UA/UV and DV following the procedure
Placental Chorioangioma Management With Ultrasound-Guided Techniques Chorioangiomas are placental lesions due to an abnormal proliferation of blood vessels in chorionic villi. Histologically, they consist of small blood vessels that are embedded within the stroma of enlarged placental villi and are covered with a trophoblastic layer. They are the most common placental tumor with a 1% incidence. Sepulveda et al followed 11 pregnancies with placental chorioangiomas.92 The mean age at diagnosis was 26 weeks (range 20 to 36 weeks). Size was greater than 4 cm in 9 of 11 cases. Polyhydramnios and preterm labor were the most common pregnancy complications. Amnioreduction at 27 weeks was used in one case with a successful term delivery. A second treatment case of alcohol ablation was used at 26 weeks in a hydropic/cardiac failure fetus with early post-treatment fetal demise. Ultrasound surveillance was used including fetal biometry, amniotic fluid volume, and Doppler flow studies, with fetal echocardiography in selected cases. Serial ultrasound assessments with nonstress fetal heart rate monitoring were used in the third trimester.
Guschmann et al examined 22,439 unselected third trimester placentas and identified chorioangiomas in 0.61% of the pregnancies.93 The incidence of chorioangiomas corresponded with increasing maternal age, most often in women greater than 30 years of age, as well as maternal hypertension and diabetes. The rate of preterm birth was increased (3×) in the pregnancies complicated by chorioangiomas. A rare neonatal complication of chorioangiomas are diffuse, multiple hemangiomas.94 There is a case report of a euploid female fetus with prenatal identification of a chorioangioma and delivery at 35 weeks due to polyhydramnios. Maternal serum screening was abnormal with an α-fetoprotein (AFP) level of 14.9 multiples of the median (MoM). The newborn was found at birth to have multiple diffuse cutaneous and liver angiomatosis. Neonatal death occurred at 1 month of age secondary to cardiac failure and infection.
Chorioangioma complications in the fetus/neonate, and maternal and placental compartments occur in the antepartum, intrapartum, and postpartum time periods.95,96,97,98,99,100, and 101 Most chorioangiomas are small and have no clinical significance, but lesions greater than 40 mm are associated with pregnancy complications. Fetal effects include antepartum cardiac failure, hepatosplenomegaly, IUGR, microangiopathic anemia, thrombocytopenia, fetomaternal hemorrhage with intrapartum nonreassuring fetal heart rate tracing, and newborn heart failure, apnea, and hemangiomas. Maternal complications are preterm labor (polyhydramnios, antepartum hemorrhage, PROM), pregnancy-induced hypertension, proteinuria, thrombocytopenia, and postpartum hemorrhage. Direct placental complications include abruption and infarction with placental retention at delivery.
Ultrasound-guided placental chorioangioma treatments have included laser therapy (interstitial tumor, surface feeding vessel), intrauterine transfusion, embolization (enbucrilate, microcoil), and alcohol injection. Timing and outcomes are summarized in Table 27-11.95,96,97,98,99,100, and 101
Table 27-11OUTCOME FOR CHORIOANGIOMA TREATMENT CASE REPORTS (TECHNIQUE AND GESTATIONAL AGE; 2003 TO 2007) ||Download (.pdf) Table 27-11 OUTCOME FOR CHORIOANGIOMA TREATMENT CASE REPORTS (TECHNIQUE AND GESTATIONAL AGE; 2003 TO 2007)
|Technique ||GA ||Outcome ||Complication ||Reference |
|Laser: interstitial ||24 ||tumor hilum || || |
| ||26 ||Delivery 32 wk ||C section ||Bhide et al95 |
| || ||LB || || |
|Laser: surface ||25 ||Feeding vessels || || |
| || ||Delivery 39 wk ||C section ||Quarello et al96 |
| || ||LB || || |
|IUT ||26 ||Delivery 39 wk ||C section ||Escribano et al97 |
| || ||LB || || |
|Microcoil: IUT ||24 || || || |
| ||25 ||IUT 27, 28, 29 ||Classical C section || |
| || ||Delivery 29 wk || ||Lau et al98 |
| || ||NND || || |
|Embolization ||24 ||PROM 26 wk ||C section || |
| || ||NND || ||Lau et al99 |
|Alcohol ||30 ||Ablation surface vessel || || |
| || ||Vaginal delivery 32 wk || ||Wanapirak et al100 |
| || ||LB || || |
|Alcohol ||25/26 ||Chorioangioma injection || || |
| || ||Vaginal delivery 28 wk || ||Deren et al101 |
| || ||LB || || |
Umbilical cord lesions are uncommon, but ultrasound will usually allow prenatal diagnosis. Hemangiomas of the umbilical cord are typically seen as fusiform swellings in the cord with an angiomatous nodule and edematous Wharton jelly. The hemagioma location is usually close to the placental cord insertion site. Ultrasound-guided decompression of the cystic portion of the hemangioma has been used in the third trimester to improve umbilical Doppler flow, and to prevent fetal malpresentation and dystocia, and minimize the risk of cyst rupture. This decompression management allowed a vaginal delivery to occur safely.
Quality of Evidence III
Strength of Recommendation B
Evaluation of the fetus to determine the origin and pathology of the abdominal/pelvic cystic structure
Ultrasound guidance for ovarian cyst decompression with size greater than 50 mm to prevent ovarian torsion
Ultrasound surveillance for cysts less than 50 mm or those that have undergone decompression
Postnatal evaluation of the neonatal ovarian pathology to determine appropriate management
Ovarian cysts are a common abdominal mass in female fetuses with an estimated incidence of 1 in 2600 fetuses.102,103 The cysts develop due to fetal follicle-stimulating hormone (FSH), maternal estrogens, and human placental chorionic gonadotropin (hCG) stimulation. Other obstetrical complications associated with increased hCG production (maternal diabetes, preeclampsia, rhesus sensitization) have an increased incidence of ovarian cysts. Ultrasound criteria for a probable ovarian cyst are female gender, fetal pelvic location, cystic appearance (simple, complex), and no peristalsis. Simple cysts are anechoic with no internal debris or septations. Complex cysts have internal echos, septations, and debris. Meta-analysis has identified 420 fetuses with ovarian cysts (1984 to 2005). In 50% of the cases, the cyst regressed spontaneously, while 35% of cysts were complicated by torsion and intracystic hemorrhage. Cysts less than 50 mm regressed spontaneously in 98%. Cysts greater than 50 mm resulted in a complicated course in 93% and direct recommendations to consider decompression of the cyst by ultrasound-guided needle aspiration to prevent ovarian torsion. Following the aspiration, spontaneous regression was observed in 89%. Prenatal aspiration appears to be effective and safe. Cysts with an ultrasound appearance of torsion that persist postnatally require surgical evaluation. The neonatal outcomes following a protocol of prenatal serial ultrasound without in utero cyst aspiration and early postnatal ultrasound scan are reported.103 Neonatal surgery was indicated for complex-appearing cysts regardless of size, and for simple cysts greater than 20 mm. The median gestational age at prenatal detection was 33 weeks with a median size of 40 mm, and 18% had a complex appearance. At the time of neonatal surgery, 56% of the cysts were found to have undergone torsion, 6% were hemorrhagic, and 38% were uncomplicated. This report confirms the high risk of fetal/neonatal ovarian loss with large fetal ovarian cysts. Additional reasons for cyst aspiration (other than torsion risk reduction) are analysis of cyst fluid to confirm ovarian hormonal status and to decrease fetal abdominal dystocia at delivery with very large cysts. Arguments against the cyst aspiration are risks of bleeding, infection, and spread of malignancy. The evidence-based management plan for prenatally diagnosed ovarian cysts is not well defined and may require a multicenter RCT to establish the optimal risk:benefit outcome algorithm.
Multifetal Reduction (MFR) and Selective Termination
Quality of Evidence III
Strength of Recommendation B
Late first trimester/early second trimester evaluation for gestational age, fetal number, placental chorionicity, and uterine position
Ultrasound guidance for chorionic villus sampling (CVS) genetic testing of each fetus prior to reduction
Ultrasound guidance for directing the needle into the fetal thorax for the potassium chloride (KCl) injection
Following the procedure, evaluation of the remaining fetuses for viability and complications
These ultrasound-guided techniques have been used to improve the pregnancy outcomes in higher-order multiples (triplets or more) and monochorionic twinning pathology with significant morbidity/mortality discordant birth defects.104 Changes in MFR procedures have been reported for the technique, which has been available for over 20 years. A series of 2000 patients who had undergone MFR showed evolving trends with the procedure, reflecting the changes in assisted reproductive techniques and patient demographics. MFR trends have moved toward reduction of higher-order multiples to a singleton, reduction from twins to a singleton, and a strong preference for prenatal diagnosis by CVS prior to the MFR. The MFR technique uses a transabdominal injection of potassium chloride into the region of the fetal thorax under ultrasound guidance. The CVS technique is an ultrasound-guided transabdominal technique to obtain placental chorionic tissue for chromosomal and genetic analysis of each fetus prior to reduction selection. An ethical/clinical debate surrounds the use and consequences of assisted reproductive technology due to the increased incidence of multiple gestations, monochorionic twinning, and fetal anomalies. The background rate of fetal anomalies may be higher in the infertility population, but this finding is only revealed with the assisted reproductive conceived pregnancies.
Other Case Reports of Ultrasound-Guided Fetal Therapy Techniques
Quality of Evidence IV
Strength of Recommendation C
Fetal evaluation to determine the anatomical location of the pathology
Ultrasound guidance for selected fetal therapy
A 25-week fetus was identified to have a 50 × 40 mm cystic tumor originating from the sublingual area and protruding from the mouth.105 The cystic tumor (60 × 60 mm) was decompressed by ultrasound-guided percutaneous needle aspiration at 26 weeks. The aspirated fluid was found to have amylase levels consistent with a ranula (salivary gland tumor). Fetal maxillary movements were observed after decompression of the cystic mass. This decompression allowed a full-term vaginal delivery of 2840-g female with an oral mass of 60 × 70 mm. Definitive surgery was completed at 25 days of life with surgical excision of the salivary gland cyst and tongue reconstruction. This decompression technique could be used in conjunction with an EXIT delivery to secure the neonatal airway/trachea, dependent on the tumor location or size due to the risk of neonatal airway obstruction.