fetal tedavİde gÜncel durum

Doç. Dr. Gökhan YILDIRIM Kanuni Sultan Süleyman EAH

Perinatoloji Kliniği

Fetus ve eklerindeki sorunu çözmek için medikal yada cerrahi müdahale etmektir.

Son 15 yıldır ise giderek artan oranda fetal tedavi girişimleri olmaktadır.

Gelecekte çok daha yaygın ve sık olması beklenmektedir.

İlk deneyimler Rh izoimmünizasyon intrauterin transfüzyon ve amniyodrenaj

USG

Anomalilerin tanımlanması

Tanı

Perinatal sonuçlar

Fetal tedavi

Amaç:

Perinatal morbidite ve mortalite’yi önlemek / iyileştirmek

Kalıcı organ hasarlarını/Nöromorbidite’yi önlemek / azaltmak

Fetal tedavi

Medikal

Yöntemler

◦ Amniodrenaj

◦ Transfüzyon

◦ Selektif fetosid

◦ Radiofrekans

◦ Bipolar

◦ Laser

◦ Fetoskopik cerrahi

◦ Girişimsel-Cerrahi

Kapalı

Açık

◦ Laparotomi / histerotomi

MSS MMC

Pulmoner sistem Hidrotoraks Bronkopulmoner sekestrasyon CCAM Diafragm hernisi

Kalp Aritmi Ao, Pa stenozu, Fo kapanması

Üriner sistem Megasist Hidronefroz

Hematolojik sistem Anemi Trombositopeni

Endokrin sistem Guatır KAH

Fetal tedaviler: Türkiye İkiz gebelikler

◦ TTTS

◦ TRAP

◦ Selektif anomali, IUGR

Plasenta-amniotik sıvı-kordon ◦ Polihidramnios drenajı

◦ Vasa previa

◦ Amniotik band

◦ Koranjioma

Enfeksiyonlar ◦ Toxoplazma

Fetal Tümör ◦ Sakral teratom

Gen tedavisi ◦ Genetik geçişli hastalıklar

Fetal ve Neonatal Alloimmün Trombositopeni (FNAİT)

Fetal Kardiyak Disritmi

Fetal Guatr

Konjenital Adrenal Hiperplazi

• İnsidans; 1/350-1/1000 • PLT <50.000 ciddi FNAİT (%10 İKK) • Olguların %85’inde HPA-1a Ag sorumlu • HPA-1a-pozitif fetusa sahip HPA-1a-negatif kadınların yalnızca %10’unda

antikor üretilir. • HLA DRB3*0101 yokluğunda immünüzasyon nadir (NPP %99,6)

Tedavi İntra uterin trombosit tranfüzyonu IVIG, 1.0 g/kg/hafta (20 – 32. hafta arasında) Prednisone 0.5 mg/kg/gün

İntermittent ekstrasistol

Supraventriküler taşikardi

Atrial flutter

Komplet AV blok

Ventriküler taşikardi (nadir)

Tanı; M-mode, pulsed-wave ve doku Doppleri

Tedavi; SVT/atrial flutter

Yakın izlem

Anti-aritmik tedavi

Digoxin

Flecainide

Sotalol

Amiodarone

Adenosine

Atrioventiküler blok

Deksametazon/betametazon

Beta-agoistler (terbutalin, salbutamol)

Plazmaferez

Fetal pacing

• Flekainid ve digoksin SVT normal ritme çevirmede ve SVT/AF’ı daha iyi tolare edilen ventriküler hıza yavaşlatmada sotalol’dan daha etkili • İlk basamak tedavide flekainid ve digoksin düşünülebilir

SVT (114)/AF (45) 159 olgu, retrospektif , 3 merkez

Fetal Guatr

Propsil kullanan anne

%9.5 fetal hipotiroidi

%10 fetal hipertiroidi

Grave’s hastalığı

İodine eksikliği

Fetal tiroid disgenezisi, enzim defekti

İntra-amniotik 200-500 mik.gr tiroksin tedavisi, 1-2 hf ara ile

Guatr boyutu azalmakta

KAH ◦ 21-OH eksikliği, OR

◦ ACTH-Adrenal hiperplazi-androjen artışı

◦ Female fetusda virilizasyon

◦ 1.5 mg Deksametazon <7 hf , 11-14 hf CVS: male /Female- CYP21 normal Deksametazon stop

◦ %85 virilizasyonu önlüyor

Fetal Cerrahi için Kriterler

Doğru tanı ve evreleme olanaklı olmalı, diğer anomaliler dışlanmalı

Hastalığın doğal seyri ve prognozu tanımlanmış olmalı

Etkili postnatal tedavisi olmamalı

Hayvan modellerinde in-utero cerrahinin yapılabilir olduğu ve sorunun olumsuz etkilerinin geri döndürülebilir olduğu kanıtlanmalı

Girişim katı protokolleri olan ve ebeveynler bilgilendirilerek lokal etik komitelerin onayının alındığı özelleşmiş multidisipliner fetal tedavi merkezlerinde yapılmalıdır.

Kritik Aort Stenozu

Restriktif Foramen Ovale (HLHS)

Pulmoner Atrezi (İntakt Ventriküler Septum)

Koroner balon kateteri, 3-4.5 mm

18 - 19 G

Lokal / genel anestezi

Fetal ekokardiografi-USG eşliğinde

• Komplikasyonlar Fetal resüsitasyon gerektiren bradikardi (%17 – 38) Hemoperikardium (%13) Ventriküler tromboz (%15 – 20) Fetal ölüm (%8 – 13)

Balon valvuloplasti

Bakırköy EAH, 2009

Kr.Ao.Sten.

Fetal Toraks Patolojileri

Plevral Efüzyon (Hidrotoraks/Şilotoraks)

Kistik Konjenital Adenoid Malformasyon

Bronkopulmoner Sekestrasyon

Plevral Effüzyon

İzlem

Torakosentez

Plöroamniyotik şant

Plörodezis (OK-432, Streptokokus Piyogenes)

Torakoamniotik şunt, Has R, İTF

Yang YS et al., 2012

Yaşam oranları

Hidropik : % 0-67

Non-hidropik: % 33-100

Şant migrasyonu/obstrüksiyonu (%10 – 20)

Preterm erken membran rüptürü/eylem

Pulmoner Parankim Lezyonları CCAM (makrokistik/mikrokistik)

İzlem

Torakosentez

Torakoamniyotik şant

Minimal invaziv teknikler (interstisyel lazer, radyofrekans ablasyon, siyanoakrilat enjeksiyonu)

Açık fetal cerrahi (mikrokistik)

Maternal Kortikosteroid (Betametazon 12 mg, iki kez)

BPS

Sklerozan enjeksiyonu

İnterstisyel lazer koagülasyonu

CVR >1.6 ise hidrops riski yüksek

PRENATAL INTERVENTIONS FOR FETAL LUNG LESIONS 629

supply from pulmonary vessels. BPS can be diagnosedwhen a feeding systemic artery originating directly fromthe descending aorta can be identified (Sepulveda, 2009),although this occasionally proves difficult before birth.

BPS occurs in two, anatomically distinct, subtypes(Stocker, 1986). Intralobar sequestration (ILS) is locatedwithin the lung and covered by the visceral pleuraof the lung. Extralobar sequestration (ELS) is locatedoutside the normal lung and covered by its own visceralpleura. ELS can also be located below the diaphragm.Distinction between ILS and intrathoracic ELS is verydifficult prenatally.

Fetal magnetic resonance imaging (MRI) providesmore detailed imaging of the lesion and might thereforeaid in a more definite diagnosis (Hubbard et al., 1999;Levine et al., 2003; Kunisaki et al., 2007; Liu et al.,2010). Specific indications for additional MRI have notbeen described in the literature.

The amount of amniotic fluid (amniotic fluid indexor deepest vertical pocket) should be measured. Masseffect of the lesion can lead to esophageal compressioncausing impaired fetal swallowing (Adzick et al., 1985;Thorpe-Beeston and Nicolaides, 1994). This can leadto polyhydramnios. In case of polyhydramnios, cervicallength should be measured and taken into considerationwhen assessing the necessity of intervention.

Figure 1—Transverse view of the fetal chest showing a macrocysticCCAM

Figure 2—Transverse view of the fetal chest showing a microcysticCCAM

An essential part of the evaluation is a full and detailedanatomical survey of all fetal organs and structures,including echocardiography. Combined occurrence with,e.g. diaphragmatic hernia is not uncommon. The occur-rence of other anomalies in association with CCAM hasbeen reported in 10–20% of cases (Thorpe-Beeston andNicolaides, 1994; Stocker and Dehner, 2002). In BPSassociated anomalies have been reported to occur in upto 10% of cases of ILS and up to 50% of cases ofELS (Wilson et al., 2006) Cardiac evaluation may behampered by displacement of the heart. Aneuploidy hasbeen reported occasionally in fetuses with lung lesions(Laberge et al., 2001; Calvert et al., 2006), but it isnot regularly associated with isolated fetal lung lesion(Pumberger et al., 2003; Wilson et al., 2006). We dosuggest offering karyotyping, or in the near future pos-sibly array Comparative Genomic Hybridization (arrayCGH), to all women carrying a fetus with anomalies onultrasound. In fetuses with multiple congenital anoma-lies or chromosomal aberrations, the prognosis is oftenconsiderably worse. Fetal interventions are generally notoffered in this group. In the remainder of this article, wewill focus on the management of the fetus with isolatedlung lesions.

NATURAL HISTORY

The natural history of fetal lung lesions is variable.Spontaneous regression is not uncommon. CCAM/BPSgrowth generally peaks at 26–28 weeks’ gestation. Inthe weeks thereafter spontaneous regression is regularlydescribed (MacGillivray et al., 1993; Miller et al., 1996;Adzick et al., 1998). As a consequence the lesions canbe hard to find on ultrasound in the third trimester.Postnatal computed tomography or MRI can identifyto what extent the lesion is still present (Winters andEffmann, 2001; Cavoretto et al., 2008). The precisemechanism leading to spontaneous regression is notclear and may be because of outgrowing of the vascularsupply of the CCAM or to spontaneous resolution ofthe underlying bronchial obstruction (Miller et al., 1996;Adzick, 2009).

Reported rates of spontaneous regression of CCAMvary from 15 to 65% (Miller et al., 1996; Dommer-gues et al., 1997; Laberge et al., 2001; Pumberger et al.,2003; Ierullo et al., 2005; Cavoretto et al., 2008; Adz-ick, 2009) The largest published series describes sono-graphic evidence of regression in 76 of 154 CCAMs(49%)(Cavoretto et al., 2008) Spontaneous regression ofBPS is also regularly described, in up to 68% of cases(Adzick, 2009).

On the other hand, secondary physiological derange-ments can occur, mostly because of the mass effect ofthe lesion in the fetal thorax. Oesophageal compres-sion can interfere with fetal swallowing causing poly-hydramnios (Adzick et al., 1985; Thorpe-Beeston andNicolaides, 1994). The mass effect of the lesion cancause mediastinal shift and may, although surprisinglyrare, restrict lung growth causing pulmonary hypopla-sia (Sauvat et al., 2003; Davenport et al., 2004). The

Copyright ã 2011 John Wiley & Sons, Ltd. Prenat Diagn 2011; 31: 628–636.DOI: 10.1002/pd


In addition seven single cases of hydropic fetuseswith BPS treated by thoracoamniotic shunt placementhave been described (Weiner et al., 1986; Slotnick et al.,1990; Hernanz-Schulman et al., 1991; Favre et al., 1994;Salomon et al., 2003; Picone et al., 2004; Odaka et al.,2006) In one case PE reaccumulated probably because ofshunt occlusion (Weiner et al., 1986) In all other caseshydrops resolved and fetuses survived after birth.

Laser and sclerosing agents in thetreatment of CCAM and BPS

Attempts at percutaneous ablation of a microcysticCCAM in a hydropic fetus using Nd : YAG laser havebeen described four times in the literature (Fortunatoet al., 1997; Bruner et al., 2000; Davenport et al., 2004;Ong et al., 2006) In all cases a 600 mm laser fibrewas passed through the lumen of an 18G-needle afterwhich the tumour itself was photocoagulated using anNd : YAG laser. In one case (Ong et al., 2006) hydropsresolved and the fetus survived needing postnatal respi-ratory support and surgical resection the lesion. In onecase (Bruner et al., 2000) the fetus died prenatally. Inone case (Davenport et al., 2004) the fetus died 4 daysafter birth. In the last case resolution of hydrops wasdescribed but no further outcome was reported (Fortu-nato et al., 1997)

The group of Quintero reported on three cases ofCCAM complicated by fetal hydrops and treated withpercutaneous insertion of a sclerosing agent directly intothe CCAM (Bermudez et al., 2008) In all cases hydropsresolved and all fetuses were born alive. One neonatedied after 10 days because of nosocomial sepsis.

Interruption of flow in the systemic feeding vesselof a BPS has been described as a treatment option inhydropic fetuses with BPS. Successful ultrasound guidedlaser coagulation of the feeding artery of BPS usingNd : YAG laser through a 18G-needle was described byour group in 2007 and 2009 (Oepkes et al., 2007; Witloxet al., 2009). Figures 4–7 show images of the secondcase. In both cases hydrops resolved after treatmentand the fetuses survived uneventfully. In the last case,only one puncture with the 18G-needle was used first toinsert the laser fibre for coagulation of the vessel, thenfor drainage of the unilateral hydrothorax and lastly fordrainage of the polyhydramnios.

One technically successful case was performed byNicolaides, unfortunately ending in neonatal demise(Davenport et al., 2004). Ryan et al. (2003) used thesame laser technique combined with placement of athoraco-amniotic shunt in a hydropic fetus with BPS,with success. This combined procedure makes it difficultto assess which of the two interventions contributes mostto the success. Mass size reduced in both cases.

Ruano et al. (2007) described a case in which coagu-lation of the vessel was incomplete after laser therapy.The mass’s volume increased without reappearance ofhydrops. The child needed ventilatory support in theneonatal period and thoracotomy and lobectomy wereperformed.

Figure 4—Ultrasound image of a large lung lesion with PE

Figure 5—Colour Doppler showing systemic artery, thus diagnosis ofpulmonary sequestration

Figure 6—Colour Doppler after laser therapy showing absence offlow to the lung lesion

Rammos et al. (2010) described resolution of hydropsin two hydropic fetuses with BPS treated with laser. Inboth cases the feeding vessel remained open after lasertreatment. One fetus needed thoracoamniotic shuntingfor residual hydrothorax. The other child needed a thorax



supply from pulmonary vessels. BPS can be diagnosedwhen a feeding systemic artery originating directly fromthe descending aorta can be identified (Sepulveda, 2009),although this occasionally proves difficult before birth.

BPS occurs in two, anatomically distinct, subtypes(Stocker, 1986). Intralobar sequestration (ILS) is locatedwithin the lung and covered by the visceral pleuraof the lung. Extralobar sequestration (ELS) is locatedoutside the normal lung and covered by its own visceralpleura. ELS can also be located below the diaphragm.Distinction between ILS and intrathoracic ELS is verydifficult prenatally.

Fetal magnetic resonance imaging (MRI) providesmore detailed imaging of the lesion and might thereforeaid in a more definite diagnosis (Hubbard et al., 1999;Levine et al., 2003; Kunisaki et al., 2007; Liu et al.,2010). Specific indications for additional MRI have notbeen described in the literature.

The amount of amniotic fluid (amniotic fluid indexor deepest vertical pocket) should be measured. Masseffect of the lesion can lead to esophageal compressioncausing impaired fetal swallowing (Adzick et al., 1985;Thorpe-Beeston and Nicolaides, 1994). This can leadto polyhydramnios. In case of polyhydramnios, cervicallength should be measured and taken into considerationwhen assessing the necessity of intervention.

Figure 1—Transverse view of the fetal chest showing a macrocysticCCAM

Figure 2—Transverse view of the fetal chest showing a microcysticCCAM

An essential part of the evaluation is a full and detailedanatomical survey of all fetal organs and structures,including echocardiography. Combined occurrence with,e.g. diaphragmatic hernia is not uncommon. The occur-rence of other anomalies in association with CCAM hasbeen reported in 10–20% of cases (Thorpe-Beeston andNicolaides, 1994; Stocker and Dehner, 2002). In BPSassociated anomalies have been reported to occur in upto 10% of cases of ILS and up to 50% of cases ofELS (Wilson et al., 2006) Cardiac evaluation may behampered by displacement of the heart. Aneuploidy hasbeen reported occasionally in fetuses with lung lesions(Laberge et al., 2001; Calvert et al., 2006), but it isnot regularly associated with isolated fetal lung lesion(Pumberger et al., 2003; Wilson et al., 2006). We dosuggest offering karyotyping, or in the near future pos-sibly array Comparative Genomic Hybridization (arrayCGH), to all women carrying a fetus with anomalies onultrasound. In fetuses with multiple congenital anoma-lies or chromosomal aberrations, the prognosis is oftenconsiderably worse. Fetal interventions are generally notoffered in this group. In the remainder of this article, wewill focus on the management of the fetus with isolatedlung lesions.

NATURAL HISTORY

The natural history of fetal lung lesions is variable.Spontaneous regression is not uncommon. CCAM/BPSgrowth generally peaks at 26–28 weeks’ gestation. Inthe weeks thereafter spontaneous regression is regularlydescribed (MacGillivray et al., 1993; Miller et al., 1996;Adzick et al., 1998). As a consequence the lesions canbe hard to find on ultrasound in the third trimester.Postnatal computed tomography or MRI can identifyto what extent the lesion is still present (Winters andEffmann, 2001; Cavoretto et al., 2008). The precisemechanism leading to spontaneous regression is notclear and may be because of outgrowing of the vascularsupply of the CCAM or to spontaneous resolution ofthe underlying bronchial obstruction (Miller et al., 1996;Adzick, 2009).

Reported rates of spontaneous regression of CCAMvary from 15 to 65% (Miller et al., 1996; Dommer-gues et al., 1997; Laberge et al., 2001; Pumberger et al.,2003; Ierullo et al., 2005; Cavoretto et al., 2008; Adz-ick, 2009) The largest published series describes sono-graphic evidence of regression in 76 of 154 CCAMs(49%)(Cavoretto et al., 2008) Spontaneous regression ofBPS is also regularly described, in up to 68% of cases(Adzick, 2009).

On the other hand, secondary physiological derange-ments can occur, mostly because of the mass effect ofthe lesion in the fetal thorax. Oesophageal compres-sion can interfere with fetal swallowing causing poly-hydramnios (Adzick et al., 1985; Thorpe-Beeston andNicolaides, 1994). The mass effect of the lesion cancause mediastinal shift and may, although surprisinglyrare, restrict lung growth causing pulmonary hypopla-sia (Sauvat et al., 2003; Davenport et al., 2004). The


• Sağ kalım; Hidropik %68.2/Non-hidropik %87.5

Seri vezikosentez

Vesiko-amniotik şunt

Piyeloamniotik şunt

Fetal sistokopi

Renal fonksiyonlar (iyi prognoz) (güvenilirlik?)

Na < 100 mEq/L

Cl < 90 mEq/L

Osmolarite <210 osm

Beta-2 Mikroglobulin

Pyelo-amniotik şunt, Şahinoğlu Z, ZKH

Vesiko-amniotik şunt, Has R, İTF

656 J. A. DEPREST et al.

Figure 1—First description of lamb model for multiple access endoscopic in utero surgery. With permission, from Luks et al. (1994)

Figure 2—The first successful open fetal surgery at UCSF. The fetallower torso is exteriorised through the hysterotomy and the urinarytract is decompressed surgically. With permission, from Harrison(1996, chapter 5, p. 76)

never produced any urine. The team from the FetalTreatment Center team did not get discouraged by thisoutcome: the majority of patients with LUTO could besafely and effectively helped by shunt placement (Harri-son et al., 1981a,b). At that time these shunts were alsoproposed for in utero treatment of hydrocephalus untilexperimental work in fetal sheep and monkeys showedthat such a treatment was ineffective (Clewell et al.,1982). This is a good example of how, despite greatinitial enthusiasm, critical evaluation of results promptedreconsideration. The small circle of pioneers realised thatthe concept of fetal surgery was a precarious and vul-nerable one because there was too much exposure, lackof clinical evidence, ethical issues and public perception.Therefore, they set up a network for sharing information,exchanging knowledge on new techniques, discussing

treatment and frank disclosure of failures. They agreedon ethical guidelines, such as peer review publicationprior to media exposure, and standards for fetal inter-vention. They first met in 1981 in Santa Ynez (Califor-nia), where Sir William Liley was a keynote lecturer.The IFMSS was officially established 1 year later inAspen (Colorado) and drafted the ethical framework thatstill applies today (Table 1). The society founded a jour-nal, established a registry of interventions, and publisheda first report on intra-uterine shunting shortly thereafter(Manning et al., 1986). Whereas shunts were success-ful for LUTO, the group agreed at that moment on avoluntary moratorium on shunting for hydrocephalus.

LUTO can be caused by stenosis of the urethralmeatus, valves, urethral atresia, ectopic insertion of aureter or even (peri)vesical tumours. Bladder shunts areeffective for urine diversion, restoring amniotic fluidand thereby preventing pulmonary hypoplasia (recentlyreviewed by Mann et al., 2010). Whether shuntingeffectively salvages renal function is uncertain. Forthat, prior accurate assessment of renal function isrequired. An important contribution to appropriate caseselection was made by Johnson et al. (1995). Theydemonstrated the importance of serial vesicocentesis,and also reported on the long-term outcome of patients.The actual anatomical cause of LUTO proved to be animportant predictor. Posterior urethral valves do muchbetter in the long run, while babies with urethral atresiasor the Prune Belly phenotype do less well (Biard et al.,2005). Also, despite favourable prenatal renal function,up to half of the survivors still end up with chronic renalinsufficiency (Holmes et al., 2001, Clark et al., 2003).However, the self-perceived quality of life of survivorfalls within the normal range (Biard et al., 2005). Thistype of long-term information is invaluable. That studyalso emphasises the need for better prenatal anatomical


• Toplam 12 çalışma; 261 girişim (%87 VAS; 9 fetus açık cerrahi; 26 fetal sistoskopi ) (RKT yok) • Antenatal girişim perinatal sağ kalımı düzeltiyor (OR= 3,82) • İyi prognoz kriteri olan olgularda sağ kalımı düzeltiyor, ancak anlamlı değil • Kötü prognostik kritere sahip olgularda etki daha fazla

• Fetal sistoskopi vs VAS; perinatal sağ kalımda anlamlı fark yok (OR=1,49) • Fetal sistoskopi vs tedavi yok; perinatal sağ kalımda anlamlı düzelme (OR=20,51)

• 150 olgu planlanmış • Yeterli hasta toplanamadığı Için erken sonlandırıldı. Terminasyon sayısı beklenenden yüksek (68) • Her iki grup belirgin uzun ve

kısa dönem morbiditeye sahip

Konjenital Diyafragma Hernisi (FETO)

3000 gebelikte 1 Sorun pulmoner hipoplazi Postnatal cerrahide mortalite %30 26-30 hf trakeal balon 34 hf trakeal balon çıkarılıyor Lokal, lokorejyonel veya genel

anestezi

THE MAKING OF FETAL SURGERY 661

Figure 5—Survival rates of fetuses with isolated left-sided CDH depending on measurement of the observed/expected lung to head ratio (O/ELHR) measurements and liver position as in the antenatal CDH registry (Jani et al., 2006b); figure modified from Deprest et al. (2009)

alveolar type II cells (De Paepe et al., 1998) and sur-factant (O’Toole et al., 1996). The Leuven group sug-gested to limit the latter effects by reversal of TO beforebirth (plug–unplug sequence) (Flageole et al., 1998).However, functional studies still demonstrate that theresponse was better but not yet ideal (Luks et al., 2000;Davey et al., 2003). Nearly normal lung growth andmaturation was achieved in sheep by a cyclical occlu-sion protocol, that is, a 47 h occlusion period altered by1 h release, and this between 110 and 138 days (Nelsonet al., 2005). For further details on these and other stud-ies related to experimental tracheal occlusion, we refer tosome comprehensive reviews (Nelson et al., 2006; Khanet al., 2007).

CLINICAL EXPERIENCE WITH PRENATALINTERVENTION FOR CDH

The rationale for fetal surgery for CDH is that its naturalhistory can be defined, and that a subset of fetuses diein the postnatal period despite optimal care. Althoughthe latter number remains undefined, recent data indicatethat the condition is lethal in 10 to 30% of cases (Stegeet al., 2003; Javid et al., 2004; Sartoris et al., 2006;Gallot et al., 2007; Hedrick et al., 2007; Datin-Dorriereet al., 2008) (Table 5). Further, this subset must beidentifiable prior to birth. In the last decade considerableeffort has been made to validate prognostic markers thatpredict lung size and determine position of the liver. Thebest validated prognostic method in use today is thelung-to-head-ratio (LHR), which involves standardised2D-ultrasound measurement of the contralateral lung atthe four-chamber view of the heart (Jani et al., 2006a).When expressed as a proportion compared to what isexpected in a normal fetus (observed/expected LHR),this prediction is independent of gestational age (Janiet al., 2007a). Although the position of the liver iscorrelated with survival, it remains controversial thatthis is an independent variable. In Europe, we currently

use a combination of both variables to define poorprognostic groups (Figure 5). In the near future, weexpect magnetic resonance imaging (MRI) volumetryto play a more important role, because it has lessmaternal limitations and it can reliably and accuratelymeasure total rather than unilateral lung size as wellas quantifying the amount of liver herniated into thethorax (Cannie et al., 2006, 2008a,b; Jani et al., 2007b).It is also hoped that measurements of the pulmonarycirculation will be predictive of pulmonary hypertension,as this is the second most important cause of deathin CDH (Ruano et al., 2006; Sokol et al., 2006; Doneet al., 2007; Moreno-Alvarez et al., 2010).

TO was first clinically achieved by laparotomy, hys-terotomy, neck dissection and tracheal clipping (Flakeet al., 2000). In the CHOP experience, a variable lungresponse and a survival rate of 33% were observed,but four out of the five survivors had serious neuro-logical morbidity. UCSF later reported a 75% survivalrate. They related it to the use of endoscopic uterineaccess. However, this still meant uterine exposure bylaparotomy, the use of multiple cannulas and endoscopictracheal dissection and clipping (Harrison et al., 2003).An endoluminal balloon was also used as first exper-imentally described by the European group (Deprestet al., 1996b, 1998b) but clinically using a single portof 4.5 mm diameter following laparotomy for uterineexposure (Harrison et al., 2001). The first percutaneousendoluminal occlusion was reported by Quintero et al.(2000). Unfortunately, the device failed to occlude andthe baby died in the postnatal period. In Europe, theso-called Fetal Endoscopic Tracheal Occlusion—TaskForce (Figure 6) developed a clinical technique via3.3 mm percutaneous access with balloon removal ini-tially at the time of an EXIT procedure (Bouchard et al.,2002; Deprest et al., 2004; 2006). General anaesthesiawas used at first but we soon moved to regional and localanaesthesia with fetal sedation and immobilisation. Wealso reversed the occlusion in utero either by ultrasound-guided puncture or fetoscopy. This allows for vaginaldelivery, and early return of the patient to the referring


O/E LHR: < % 15, sağ kalım şansı yok O/E LHR %15-25; sağ kalım %25 O/E LHR > %15-25; sağ kalım %60 ve ↑

Lung area = Length 1 X Length 2 Lung area to Head circumference Ratio (LHR) = Lung area / Head circumference

The Lung area to Head circumference Ratio (LHR) = Lung area / Head circumference

Brezilya, 2012

Yaşam oranları ◦ FETO: %50

◦ Kontrol: %5

Yaşam oranları L: %54

R: %39

210 vaka

Çok merkezli

Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia

Primary Outcome: Survival at discharge from neonatal intensive care unit

Placebo Comparator: expectant management during pregnancy watchful waiting during pregnancy Experimental: fetal endoluminal tracheal occlusion fetoscopic balloon occlusion at 27 to 30 weeks of gestation

Estimated Enrollment: 148 Study Start Date: December 2010 Estimated Study Completion Date: October 2017 Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Nöral Tüp Defektleri

Meningomyolosel

10.000 doğumda 3.4

%10 fetal mortalite

5 yıl > %15-30 mortalite

Ağır nöromorbidite

Amaç:

Nörolojik hasar ve komplikasyonların gelişimini önlemek

Fetoskopik cerrahi, 1997 Açık fetal cerrahi, 1997 ◦ 400 vaka

Figure 1.

Open fetal repair for myelomeningocele. a) Myelomeningocele defect before repair. b) Final

skin closure of a myelomeningocele defect.

Saadai and Farmer Page 11

Clin Perinatol. Author manuscript; available in PMC 2013 June 01.

NIH-PA Author Manuscript



2011

Children’s Hospital of Philadelphia Vanderbilt University University of California, San Francisco

Box 1. Inclusion and exclusion criteria for the Management of

Myelomeningocele Study

Inclusion criteria:

1. Myelomeningocele at level T1 through S1 with hindbrain herniation.

2. Maternal age 18 years or older.

3. Gestational age at randomization of 190 to 256 weeks.

4. Normal karyotype.

Exclusion criteria:

1. Non-resident of the United States.

2. Non-singleton pregnancy.

3. Insulin-dependent pregestational diabetes.

4. Fetal anomaly not related to MMC.

5. Kyphosis in the fetus of 30 degrees or greater.

6. Current or planned cerclage or documented history of incompetent cervix.

7. Short Cervix (<20mm).

8. Placenta previa or placental abruption.

9. Body mass index 35 or greater.

10. Previous spontaneous delivery prior to 37 weeks’ gestation.

11. Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune

thrombocytopenia

12. Maternal HIV or Hepatitis B status positive.

13. Known Hepatitis C positivity.

14. Uterine anomaly such as large or multiple fibroids or müllerian duct

abnormality

15. Other maternal medical condition which is a contraindication to surgery or

general anesthesia

16. Patient does not have a support person.

17. Inability to comply with travel and follow-up requirements.

18. Patient does not meet other psychosocial criteria to handle the implications of

the trial.

19. Participation in another intervention study that influences maternal and fetal

morbidity and mortality or participation in this trial in a previous pregnancy.

20. Maternal hypertension which would increase the risk of preeclampsia or preterm

delivery.

Saadai and Farmer Page 10

Clin Perinatol . Author manuscript; available in PMC 2013 June 01.

NIH-PA Author ManuscriptNIH-PA Author Manuscript


Şant ihtiyacı azalıyor, %40 v %82 Hindbrain herniasyon azalıyor, %64 v %96 Bağımsız yürüme, %42 v %21

Polihidramnios

Plasenta-koryon-amniyon

Fetal ekstremite amputasyonu, defektleri

Amniodrenaj

Laser

Bipolar

Fetal kalp yetmezliği

Amniotik band

Preterm doğum

Koranjioma

Sakral teratom

Fetal tümörler

Açık cerrahi Laser Bipolar Radiofrekans

Fetal kalp yetmezliği

Anemi, hidrops fetalis

GELECEK

fetal tedavİde gÜncel durum

Health & Medicine