Chapter 19. Fetal Therapy. Will Obs

 Chapter 19. Fetal Therapy

BS. Nguyễn Hồng Anh

Innovative treatments developed during the past three decades have dramatically altered the course o selected etal anomalies and conditions. Over time, etal interventions have become less invasive, and the number o etal centers has expanded. Te North American Fetal Terapy Network now includes 36 medical centers in the United States and Canada. Some o the etal abnormalities and conditions amenable to either medical or surgical treatment are presented here. Te management o etal anemia and thrombocytopenia is reviewed in Chapter 18, and treatment o some etal inections is discussed in Chapters 67 and 68.

MEDICAL THERAPY

Selected medications administered to the pregnant woman are transported across the placenta in concentrations high enough to treat etal conditions. Pregnancy physiology aects drug concentration, and transer depends on maternal and placental metabolism (Chap. 8, p. 145).

■ Arrhythmias

Abnormal etal cardiac rhythms are grouped into three categories: tachyarrhythmias, heart rates >180 beats per minute (bpm); bradyarrhythmias, heart rates <110 bpm; and ectopy, typically premature atrial contractions. I a etal arrhythmia is suspected, M-mode ultrasound, described in Chapter 15 (p. 294), is used to measure the atrial and ventricular rates and to clariy the relationship between atrial and ventricular beats, thereby diagnosing the type o rhythm disturbance.

Premature Atrial Contractions

I the etal heart rate is normal but the rhythm is irregular, the most common etiology is premature atrial contractions (PACs). Tese atrial ectopic beats are ound in 1 to 2 percent o uncomplicated pregnancies (Hahurij, 2011; Strasburger, 2010). PACs represent immaturity o the cardiac conduction system. Tey typically resolve later in gestation or in the neonatal period. PACs are usually an isolated nding but may be associated with redundancy o the oramen ovale ap—ormerly termed a oramen ovale aneurysm. When a PAC is conducted, an extra beat is heard with handheld Doppler. However, the premature contraction more commonly arrives at the atrioventricular node during the reractory period. Tis results in a compensatory pause, which sounds like a dropped beat. M-mode evaluation conrms the diagnosis (Fig. 15-46, p. 295).

PACs may occur as requently as every other beat, which means that the auscultated etal heart rate may be as low as 60 to 80 bpm. Known as blocked atrial bigeminy, this condition is benign and does not require treatment (Strasburger, 2010). However, monitoring the etus in labor may be challenging and necessitate cesarean delivery. M-mode ultrasound will dierentiate atrial bigeminy rom other causes o bradycardia, such as third-degree atrioventricular block. Up to 2 percent o etuses with PACs are later ound to have supraventricular tachycardia (Copel, 2000; Srinivasan, 2008). Given the importance o prompt identication and treatment o supraventricular tachyarrhythmias, pregnancies with PACs are oten monitored with etal heart rate assessment every 1 to 2 weeks until the ectopy resolves. At Parkland Hospital, we nd that auscultation with handheld Doppler is sucient or surveillance.

Tachyarrhythmias

Te two most common tachyarrhythmias are supraventricular tachycardia (SV) and atrial utter. SV is characterized by an abrupt increase in the etal heart rate to 180 to 300 bpm with 1:1 atrioventricular concordance (Fig. 19-1). Te typical range is 200 to 240 bpm. SV may develop secondary to an ectopic ocus or to an accessory atrioventricular pathway leading to a reentrant tachycardia. Atrial utter is characterized by a much higher atrial rate, generally 300 to 500 bpm, with varying degrees o atrioventricular block. As a result, the ventricular rate in a etus with atrial utter may range rom below normal to approximately 250 bpm (Fig. 19-2). In contrast, etal sinus tachycardia typically presents with a gradual heart rate rise to a rate that is only slightly above normal. With this, readily discernible causes may be maternal ever or hyperthyroidism, or rarely, etal anemia or inection.

I a etal tachyarrhythmia is identied, it is important to determine whether it is sustained—dened as present or at least

50 percent o the time. It may be necessary to monitor the

etal heart rate or 12 to 24 hours upon initial detection, and

then periodically to reassess (Srinivasan, 2008). Unsustained

or intermittent tachyarrhythmias may become sustained over

time. Although intermittent tachyarrhythmias do not generally

require treatment, close etal surveillance is warranted.

Sustained etal tachyarrhythmias with ventricular rates

exceeding 200 bpm impair ventricular lling to a degree that

the risks or developing cardiomyopathy and hydrops are signicant. With atrial utter, lack o coordinated atrioventricular contractions may urther compound this risk. Maternal

administration o antiarrhythmic agents that cross the placenta

may convert the rhythm to normal or may lower the baseline

heart rate to orestall heart ailure. Terapy can require dosages

at the upper end o the therapeutic adult range. Tereore, a

maternal electrocardiogram is obtained beore and during therapy. Monitoring o the maternal serum level may be necessary,

particularly i the dosage requires titration. I medical therapy is

successul, the medication is generally continued until delivery.

Antiarrhythmic medications most commonly used include

digoxin, ecainide, and sotalol. Teir selection depends on the

type o tachyarrhythmia and provider experience with the drug.

raditionally, digoxin was the initial preerred treatment, but

its placental transer may be poor in the setting o hydrops.

Many centers now use ecainide or sotalol as rst-line therapy

(Ekiz, 2018; van der Heijden, 2013). A second agent is needed

in more than 50 percent o cases (Jaeggi, 2011; O’Leary, 2020;

Shah, 2012). With treatment, conversion to a normal rhythm

or reduction in heart rate to a normal range occurs in 90 percent, including 80 percent o those with hydrops (Miyoshi,

2019; Ueda, 2018). SV is more likely than atrial utter to

convert to a normal rhythm. Te neonatal survival rate exceeds

90 percent (Ekman-Joelsson, 2015; Miyoshi, 2019; O’Leary,

2020; van der Heijden, 2013).

Bradyarrhythmia

Te most common etiology o etal bradycardia is congenital

heart block. Approximately 50 percent o cases occur in the setting o a structural cardiac abnormality involving the conduction system. Tese include heterotaxy, in particular left-atrial

isomerism; endocardial cushion defect; and less commonly corrected transposition of the great vessels (Srinivasan, 2008). Te

prognosis o heart block rom a structural cardiac anomaly is

extremely poor, and etal loss rates exceed 80 percent (Glatz,

2008; Strasburger, 2010).

In a structurally normal heart, 85 percent o atrioventricular block cases are caused by transplacental passage o maternal

FIGURE 19-1 Supraventricular tachycardia (SVT). This M-mode

image at 20 weeks’ gestation demonstrates an initially normal fetal

heartrate of 150 bpm. Midway through the image (arrow), the fetal

heart rate suddenly increases to 240 bpm. With SVT, there is one

atrial beat (A) for each ventricular beat (V).

FIGURE 19-2 Atrial flutter. In this M-mode image at 32 weeks’

gestation, calipers mark the ventricular rate, which is approximately

220 bpm. There are two atrial beats (A) for each ventricular beat (V),

such that the atrial rate is approximately 440 bpm with 2:1 atrioventricular block.


anti-SSA/Ro or anti-SSB/La antibodies (Buyon, 2009). Many

o these women have, or subsequently develop, systemic lupus

erythematosus or other autoimmune disease (Chap. 62, p.

1113). Te risk o third-degree heart block with Ro antibodies

is small—only approximately 2 percent. However, the risk may

reach 20 percent i a prior inant has been aected. Immunemediated congenital heart block coners a mortality rate o

nearly 20 percent, requires permanent pacing in two thirds o

surviving children, and also poses a risk or cardiomyopathy

(Brito-Zeron, 2015; Izmirly, 2011). I associated with eusions, bradyarrhythmias, or endocardial broelastosis, neonatal

status may progressively worsen ater birth.

Research has ocused on maternal corticosteroid therapy

to potentially reverse etal heart block or to orestall it. In the

PR Interval and Dexamethasone (PRIDE) study, a multicenter

trial o pregnancies with anti-SSA/Ro antibodies, Friedman

and colleagues (2008, 2009) perormed weekly etal echocardiography to assess or development o heart block. Fetal heart

block was treated with maternal oral dexamethasone, 4 mg

daily. Unortunately, therapy did not prevent progression

rom second- to third-degree block, and third-degree atrioventricular block was irreversible. In rare cases, there was a potential

benet in reversing rst-degree atrioventricular block. However, rst-degree block did not generally progress even without treatment. Similarly, a subsequent review o pregnancies

with isolated second- or third-degree etal heart block ound

that dexamethasone therapy did not aect disease progression,

need or pacemaker in the neonatal period, or overall survival

rates (Izmirly, 2016). Despite considerable enthusiasm or corticosteroid treatment, a systematic review o more than 700

pregnancies with treated etal heart block demonstrated no

improvement in etal or neonatal morbidity or mortality rates

(Michael, 2019). Tus, we do not recommend dexamethasone

use or this indication.

More recent eorts have turned to potential therapy with

hydroxychloroquine (Plaquenil), a mainstay o treatment

or systemic lupus erythematosus (Chap. 62, p. 1112). In a

review o more than 250 women with prior aected children,

early treatment with hydroxychloroquine was associated with

a signicant decrease in recurrence o congenital heart block

(Izmirly, 2012). A subsequent clinical trial ound that treatment with hydroxychloroquine was associated with a greater

than 50-percent reduction in the rate o etal heart block

(Izmirly, 2020). In each o these series, ewer than 8 percent

o children rom pregnancies treated with hydroxychloroquine

experienced heart block. Research in this area is ongoing.

Maternal terbutaline has also been given in small cohorts

with either alloimmune- or heterotaxy-mediated etal heart

block in which the etal heart rate is persistently below 56 bpm.

Te terbutaline dosage is titrated to a maternal heart rate o 95

to 115 bpm. Fetal heart rate increases o 5 to 10 bpm have been

reported, but resolution o hydrops has not been consistently

demonstrated (Cuneo, 2007, 2010).

■ Congenital Adrenal Hyperplasia

Several autosomal recessive enzyme deciencies impair etal

synthesis o cortisol rom cholesterol by the adrenal cortex,

leading to congenital adrenal hyperplasia (CAH). CAH is

the most common etiology o androgen excess in those with

46,XX disorders o sex development (Chap. 3, p. 38). Lack

o cortisol stimulates adrenocorticotrophic hormone (ACH)

secretion by the anterior pituitary, overproduction o androstenedione and testosterone, and subsequent virilization o

emale etuses. Sequelae may include ormation o labioscrotal

olds, persistence o a urogenital sinus, or even creation o a

penile urethra and scrotal sac (Fig. 15-55, p. 299).

More than 90 percent o CAH cases are caused by

21-hydroxylase deciency. Tere are two types: classic and

nonclassic. Te incidence o classic CAH approximates 1 in

15,000 births worldwide but is higher in selected populations.

Among Yupik Eskimos, the reported incidence is 1 in 300

births (Nimkarn, 2016). O those with classic CAH, 75 percent require postnatal treatment with mineralocorticoids and

glucocorticoids to prevent a salt-wasting adrenal crisis, which is

characterized by hyponatremia, dehydration, hypotension, and

even cardiovascular collapse. Te remaining 25 percent with

classic CAH have the simple virilizing type and also require

glucocorticoid supplementation. Nonclassic CAH may present

with precocious pubarche, hirsutism, or inertility. However,

aected individuals also may be asymptomatic. Te prevalence

o nonclassic CAH approximates 1 case per 200 Caucasians and

Ashkenazi Jews in the United States (Hannah-Shmouni, 2017).

As discussed in Chapter 32 (p.594), all states mandate newborn

screening or CAH.

For more than three decades, dexamethasone has been administered to the pregnant woman to suppress etal androgen overproduction and either obviate or ameliorate virilization o emale

etuses (David, 1984; New, 2012). Prenatal corticosteroid therapy is successul in most cases i initiated early and taken consistently. One metaanalysis ound that dexamethasone treatment

was associated with reduced virilization. Specically, the Prader

score, which grades genital masculinization on a scale 1 to 5,

improved by 2.3 grades (Fernandez-Balselis, 2010). Te alternative is consideration o postnatal genitoplasty, which may include

clitoroplasty, urogenital sinus surgery, and additional vaginoplasty

procedures. In a recent review, 18 percent o children treated with

eminizing genitoplasty experienced postoperative complications,

and 12 percent required urther surgery (Baskin, 2020).

Te typical preventive regimen is oral dexamethasone given

to the mother at a dosage o 20 μg/kg/d—up to 1.5 mg per

day, divided in three doses. Te critical period or external genitalia development is 7 to 12 weeks’ gestation, and treatment to

prevent virilization should be initiated by 9 weeks—before it is

known whether the fetus is aected. Because this is an autosomal

recessive condition, aected emales make up only 1 in 8 at-risk

conceptions.

Carrier parents are typically identied ater the birth o an

aected child. Molecular genetic testing is clinically available in

such cases and initially uses sequence analysis o the CYP21A2

gene, which encodes the 21-hydroxylase enzyme (Nimkarn,

2016). I this is uninormative, gene-targeted deletion/duplication analysis is perormed, and additional testing such as whole

exome sequencing may be considered (Chap. 16, p. 327).

A goal o prenatal diagnosis is to limit dexamethasone

exposure in males and in unaected emales. I both parents


are determined to be carriers, prenatal molecular genetic testing may be perormed on chorionic villi—at 10 to 12 weeks’

gestation—or on amniocytes ater 15 weeks. Determination o etal gender using cell-ree DNA (cDNA) may aid

in avoiding dexamethasone treatment. CDNA sensitivity to

detect Y-chromosome sequences is at least 95 percent when

perormed at or beyond 7 weeks (Devaney, 2011; Hill, 2011).

In the research setting, eective cDNA testing using hybridization probes anking the CYP21A2 gene has been reported as

early as 56/7 weeks’ gestation (New, 2014).

Maternal treatment with dexamethasone has become controversial. Te Endocrine Society recommends that treatment be

given only in the context o research protocols (Speiser, 2018).

It urther recommends that such protocols incorporate cDNA

screening or the Y-chromosome to avoid treatment o male

etuses. O note, i therapy is initiated shortly beore 9 weeks’

gestation, the dose o dexamethasone used is not considered

to have signicant teratogenic potential because organogenesis

o major organs has already taken place (McCullough, 2010).

Ongoing concerns ocus on the potential eects o either excess

endogenous androgens or excess exogenous dexamethasone on the

developing brain. Although maternal dexamethasone has been

used or many years to prevent virilization o emale etuses

with CAH, long-term saety data are relatively limited.

■ Congenital Cystic Adenomatoid

Malformation

Tis well-circumscribed lung mass may appear solid and echogenic or may have one or multiple variably sized cysts (Fig.

15-33, p. 288). Lesions with one or more cysts ≥5 mm are

termed macrocystic, whereas solid lesions and those with

smaller cysts are microcystic (Adzick, 1985). A small subset

o microcystic congenital cystic adenomatoid malormations

(CCAMs) may demonstrate rapid growth, generally between

18 and 26 weeks’ gestation. Te mass may become so large that

it causes mediastinal shit, which may compromise cardiac output and venous return, leading to hydrops (Cavoretto, 2008).

A CCAM-volume ratio (CVR) has been used to quantiy

size and risk or hydrops in these severe cases (Crombleholme,

2002). Tis ratio is an estimate o the CCAM volume using the

ormula or a prolate ellipse (length × width × height × π/6)

divided by the head circumerence. In a series o 40 pregnancies

with microcystic CCAM, the mean CVR was 0.5 at 20 weeks’

gestation, peaked at 1.0 by 26 weeks, and then declined sharply

beore delivery (Macardle, 2016). With a CVR exceeding 1.6,

the risk or hydrops is as high as 60 percent. However, i the

initial CVR is below 1.6, CCAM growth resulting in hydrops

develops in ewer than 2 percent o cases (Ehrenberg-Buchner,

2013; Peranteau, 2016).

A CVR threshold o 1.0 also may assist counseling. In a

series o 62 pregnancies with etal lung masses, a maximal CVR

>1.0 was associated with a 75-percent likelihood that the neonate would be symptomatic (Ehrenberg-Buchner, 2013). However, no etus with a CVR ≤1.0 subsequently required surgery

in the newborn period.

I the CVR exceeds 1.6 or i signs o hydrops develop,

corticosteroid treatment may be benecial. Regimens include

dexamethasone—6.25 mg every 12 hours or our doses, or

betamethasone—12.5 mg intramuscularly every 24 hours or

two doses. A single course o corticosteroids has been associated

with resolution o hydrops in approximately 80 percent o cases,

and 90 percent o treated etuses survived (Loh, 2012; Peranteau, 2016). Multiple courses o corticosteroids— generally

two—have been advocated or etuses with large CCAM lesions

and with persistent or worsening hydrops or ascites despite a single course o medication (Derderian, 2015; Peranteau, 2016).

Terapy or macrocystic CCAM is discussed later.

■ Thyroid Disease

Identication o etal thyroid disease is rare and is usually

prompted by sonographic detection o a etal goiter. I a goiter

is identied, determination o etal hyper- or hypothyroidism

is essential, and thyroid hormone levels should be measured in

amnionic uid or etal blood. raditionally, etal blood sampling was preerred to amniocentesis or guiding treatment,

but data are limited (Abuhamad, 1995; Ribault, 2009). Perormance o these procedures is discussed in Chapter 17 (p. 347).

Goals o therapy are correction o the physiological abnormality and diminished goiter size. Te goiter may compress the

trachea and esophagus, leading to hydramnios rom impaired

swallowing. Despite this, case reports attest to lack o airway

compromise and avorable outcomes (Blumeneld, 2013;

Machado, 2019).

Thyrotoxicosis

Maternal Graves disease may result in transplacental passage

o immunoglobulin G (IgG) thyroid-stimulating antibodies.

Untreated etal thyrotoxicosis can present with goiter, tachycardia, growth restriction, hydramnios, accelerated bone maturation, and even heart ailure and hydrops (Huel, 2009; Kieer,

2017; Peleg, 2002; van Dijk, 2018). Fetal blood sampling may

be considered to conrm the diagnosis (Duncombe, 2001;

Srisupundit, 2008). Maternal administration o antithyroid

medication may be needed, even i the woman has had prior

surgery or ablation and no longer has hyperthyroidism. I the

pregnant women develops hypothyroidism, she is treated with

supplemental levothyroxine (Hui, 2011).

Hypothyroidism

In a woman receiving medication or Graves disease, transplacental passage o methimazole or propylthiouracil may cause

fetal hypothyroidism (Bliddal, 2011). Other potential causes o

etal hypothyroidism resulting in goiter include transplacental

passage o thyroid peroxidase antibodies, etal thyroid dyshormonogenesis, and maternal consumption o iodine supplements (Agrawal, 2002; Hardley, 2018; Overcash, 2016).

Goitrous hypothyroidism may lead to hydramnios, neck

hyperextension, and delayed bone maturation. reatment

with intraamnionic levothyroxine should be considered.

Optimal dosage and requency have not been established

but have typically ranged rom 150 to 500 μg every 1 to

4 weeks (Machado, 2019; Nemescu, 2020; Ribault, 2009). I

the pregnant woman is receiving antithyroid medication, it is

generally discontinued.


SURGICAL THERAPY

Fetal surgery, also called maternal-fetal surgery, is oered or

selected congenital abnormalities in which the likelihood o

deterioration during gestation is so great that delaying treatment until ater delivery would risk etal death or substantially

greater postnatal morbidity. Fetal surgical procedures are highly

specialized interventions perormed at relatively ew centers to

treat a small number o etal conditions. Tey require extensive

preoperative counseling and multidisciplinary care. Principles

or guiding case selection are listed in Table 19-1. When considering etal surgery, the overriding concern is the saety o the

mother and etus. Accomplishing the etal goals o the procedure is secondary (Walsh, 2011).

Selected abnormalities amenable to etal surgical treatment

are shown in Table 19-2. An overview o some o these procedures, their indications, and complications is provided here to

assist with initial patient evaluation and counseling. Additional

content is also ound in Cunningham and Gilstrap’s Operative

Obstetrics, 3rd edition.

■ Open Fetal Surgery

Fetal procedures are considered open i they are accomplished

though a hysterotomy that is not perormed or the purpose o

delivery. Open procedures are perormed under general endotracheal anesthesia to suppress uterine contractions and etal

responses. Te hysterotomy is made with a stapling device, and

intraoperative ultrasound is used to avoid the placental edge and

to veriy etal position. Te stapler seals the edges o the myometrium and membranes to achieve hemostasis and avoid chorioamnion separation. Warmed uid is continuously inused into

the uterus thorough a rapid inusion device to limit cord compression. Te etus is gently manipulated to acilitate exposure,

to permit pulse oximetry monitoring, and to establish venous

access in case uids or blood are emergently needed. Te surgical procedure is then perormed, and the hysterotomy is closed.

Prophylactic antibiotics are generally administered or 24 hours.

ocolysis typically includes intravenous magnesium sulate or

24 hours and oral indomethacin or 48 hours. Cesarean delivery

is needed later in gestation and or all uture deliveries.

Risks

Open etal surgery entails signicant maternal and etal risks.

Te most recent data are rom studies o etal myelomeningocele

TABLE 19-1. Guiding Principles for Fetal Surgical Procedures

Accurate prenatal diagnosis for the defect is available, with staging if applicable

The defect appears isolated, with no evidence of other abnormality or underlying genetic syndrome that would

significantly worsen survival or quality of life

The defect results in a high likelihood of death or irreversible organ destruction, and postnatal therapy is inadequate

The procedure is technically feasible, and a multidisciplinary team is in agreement regarding the treatment plan

Maternal risks from the procedure are well documented and considered acceptable

There is comprehensive parental counseling

It is recommended that there be an animal model for the defect and procedure

Data from Deprest, 2010; Harrison, 1982; Vrecenak, 2013; Walsh, 2011.

TABLE 19-2. Selected Fetal and Placental Abnormalities

Amenable to In-Utero Procedures

Open Fetal Surgery

Congenital cystic adenomatoid malformation (CCAM)

Myelomeningocele

Pulmonary sequestration

Sacrococcygeal teratoma

Fetoscopic Surgery

Amnionic band sequence: band release

Congenital diaphragmatic hernia (CDH): fetal endoscopic

tracheal occlusion (FETO)

Congenital high airway obstruction sequence (CHAOS):

vocal cord laser

Myelomeningocele

Posterior urethral valves: cystoscopic laser

Twin-twin transfusion: laser of placental anastomoses

Percutaneous Procedures

Cardiac catheter procedures

Aortic or pulmonic valvuloplasty for stenosis

Atrial septoplasty for hypoplastic left heart with

restrictive atrial septum

Radiofrequency ablation

Twin reversed arterial perfusion (TRAP) sequence

Monochorionic twins with severe anomaly in one twin

Chorioangioma

Shunt therapy

Dominant cyst in CCAM

Thoracoamnionic shunt for pleural effusion

Vesicoamnionic shunt for bladder outlet obstruction

ExUtero Intrapartum Treatment (EXIT) Procedures

CDH after FETO

CHAOS

EXIT-to-extracorporeal membrane oxygenation (ECMO):

CDH

EXIT-to-resection: resection of fetal thoracic or mediastinal

mass

Micrognathia

Neck or airway tumors

Procedures are listed alphabetically within groupings.372 The Fetal Patient

Section 6

repair, which is the most commonly perormed procedure.

Morbidities identied in the Management o Myelomeningocele Study (MOMS) are shown in Table 19-3 (Adzick, 2011).

In a review o 26 open etal myelomeningocele cases, 15 percent experienced preterm rupture o membranes, and the mean

gestational age at delivery was 35 weeks (Pruthi, 2021). Other

potential risks include maternal sepsis and etal death during

or ollowing the procedure, particularly i hydrops is present.

Wilson and associates (2010) reviewed subsequent pregnancy

outcomes ollowing open etal surgery and reported that 14

percent o women experienced uterine rupture and 14 percent

had uterine dehiscence.

Myelomeningocele Surgery

Fetal myelomeningocele is the rst nonlethal birth deect or

which in-utero repair has been oered (Fig. 19-3). Following standard postnatal myelomeningocele repair, aected

children experience varying degrees o paralysis, bladder and

bowel dysunction, developmental delays, and brainstem dys-

unction rom the Arnold-Chiari II malormation (Chap. 15,

p. 277). Damage is postulated to result rom abnormal embryonic neurulation ollowed by exposure o neural elements to

amnionic uid throughout pregnancy (Adzick, 2010; Meuli,

1995, 1997).

In the landmark MOMS trial, Adzick and colleagues (2011)

randomized 183 pregnancies to prenatal or standard postnatal myelomeningocele repair at three centers. Criteria or trial

participation included: (1) a singleton etus at 19.0 to 25.9

weeks’ gestation; (2) an upper myelomeningocele boundary

between 1 and S1 conrmed by magnetic resonance imaging;

(3) evidence o hindbrain herniation; and (4) a normal karyotype and no evidence o a etal anomaly unrelated to the myelomeningocele. Women at risk or preterm birth or placental

abruption, those with a contraindication to etal surgery, and

women with body mass index (BMI) >35 kg/m2 were excluded.

Te MOMS trial demonstrated improved early childhood

outcomes in the prenatal surgery cohort (see able 19-3). Children who had undergone etal surgery were twice as likely to

walk independently by 30 months. Tey had signicantly less

hindbrain herniation and were only hal as likely to undergo

ventriculoperitoneal shunting by age 1 year. A primary outcome was a composite score that was derived rom the Bayley

Mental Development Index and rom the dierence between

the unctional and anatomical level o the lesion at 30 months.

Tis primary outcome was also signicantly better in the prenatal surgery group.

Despite these benets, most children who received etal

surgery were not able to ambulate independently, and nearly

30 percent were not able to ambulate at all. Prenatal surgery did not coner improvements in etal or neonatal death

rates or in the Bayley Mental Development Index score at

age 30 months. Prenatal surgery was also associated with a

small risk or placental abruption and maternal pulmonary

edema. Moreover, nearly hal were delivered beore 34 weeks,

TABLE 19-3. Benefits and Risks of Fetal Myelomeningocele Surgery versus Postnatal

Repair

Fetal Surgery

(n = 78)

Postnatal Surgery

(n = 80) p value

Benefits (Primary Outcomes)

Perinatal death or shunt by 12 monthsa 68% 98% <0.001

Shunt placement by 12 months 40% 82% <0.001

Composite developmental scorea,b 149 ± 58 123 ± 57 0.007

Hindbrain herniation (any) 64% 96% <0.001

Brainstem kinking (any) 20% 48% <0.001

Independent walking (30 months) 42% 21% 0.01

Risks

Maternal pulmonary edema 6% 0 0.03

Placental abruption 6% 0 0.03

Maternal transfusion at delivery 9% 1% 0.03

Oligohydramnios 21% 4% 0.001

Gestational age at delivery 34 ± 3 37 ± 1 <0.001

Preterm birth

<37 weeks 79% 15% <0.001

<35 weeks 46% 5%

<30 weeks 13% 0

aEach primary outcome had two components. The perinatal death components of the

primary outcomes as well as the Bayley Mental Development Index at 30 months did

not differ between the two study cohorts.

bScore derived from Bayley Mental Development Index and difference between

functional and anatomical level of lesion (30 months).

Data from Adzick, 2011.


which signicantly increased the risk or respiratory distress

syndrome (Adzick, 2011).

It is the position o the American College o Obstetricians

and Gynecologists (2017) that nondirective counseling include

the option o etal surgery or all pregnancies that meet MOMS

trial criteria. Study o etal myelomeningocele repair in women

with BMI up to 40 kg/m2 has demonstrated outcomes similar

to those in women o lower BMI (Hilton, 2019; Moldenhauer,

2020). Otherwise, MOMS trial criteria are strictly ollowed.

Outcomes o children aged 6 to 10 years who previously participated in the MOMs trial are now available (Houtrow, 2020).

Fetal surgery conerred a sustained benet in the likelihood o

independent ambulation. Nearly 30 percent o children were

able to ambulate independently, and approximately 50 percent

required ventriculoperitoneal shunt placement. Overall cognitive unction was similar between cohorts (Houtrow, 2020).

Thoracic Masses

Open etal surgery is rarely perormed or thoracic masses.

Most are small, and these have a good prognosis. Large CCAMs

are oten treated medically with a course o corticosteroids

(p. 370). A dominant cyst in a CCAM may be amenable to

drainage or shunt placement (p. 376). Similarly, an isolated

pleural eusion surrounding a pulmonary sequestration may be

amenable to drainage or shunt placement.

Fetal surgery is generally reserved or pregnancies prior to

32 weeks’ gestation in which there is a large, solid-appearing

or microcystic mass and hydrops is developing. In careully

selected cases, the survival rate ollowing open lobectomy

approximates 60 percent (Vrecenak, 2013). Use o the ex-utero

intrapartum treatment procedure in the treatment o etal lung

masses at delivery is discussed later.

Sacrococcygeal Teratoma

Te perinatal mortality rate or cases o sacrococcygeal teratoma diagnosed prenatally is 20 to 40 percent (Hedrick, 2004; Shue, 2013, Simonini, 2021). Poor prognostic actors include a solid component constituting more than 50 percent o the tumor mass and a tumor volume-to-etal weight ratio exceeding 12 percent prior to 24 weeks’ gestation (Akinkuotu, 2015).

Hydramnios is common, and hydrops may develop rom highoutput cardiac ailure, either as a consequence o tumor vascularity or secondary to bleeding within the tumor and resulting

anemia. Fetal loss rates approach 100 percent in such cases.

Mirror syndrome—maternal preeclampsia developing along

with etal hydrops—may occur in this setting (Chap. 18, p.

364).

Open etal surgery is considered only i the tumor is completely external and high cardiac output with early hydrops has developed in the second trimester (Vrecenak, 2013). However, given the poor prognosis, rapid growth beyond 27 weeks oten prompts early delivery and postnatal resection rather than open etal surgery (Baumgarten, 2019).

■ Fetoscopic Surgery

As with open etal surgeries, these procedures are perormed at highly specialized centers. Fetoscopy is perormed with beroptic endoscopes that measure 1 to 2 mm in diameter. Instruments such as lasers t through a 3- to 5-mm cannula

A B

FIGURE 19-3 Fetal myelomeningocele surgery. A. With the edges of both the laparotomy and hysterotomy incisions retracted, the skin

around the defect is incised. Subsequently, the neural placode is sharply dissected from the arachnoid membrane. B. The dural membrane

is reflected to the midline to cover the neural placode and is reapproximated using suture. In some cases a patch is needed (not shown).

The fetal skin incision is subsequently sutured. Last, hysterotomy and laparotomy are then closed. (Figures 19-3, 19-4, 19-6, and 19-8:

Reproduced with permission from Shamshirsaz AA, Ramin, SM, Belfort MA: Fetal therapy. In Yeomans ER, Hoffman BL, Gilstrap LC III, et al:

Cunningham and Gilstrap’s Operative Obstetrics, 3rd ed. New York, McGraw Hill Education, 2017.)374 The Fetal Patient

Section 6

that surrounds the endoscope. Not all etoscopic procedures

involve placing the instruments through the maternal anterior

abdominal wall. In some cases, laparotomy acilitates optimal

placement and maneuvering o the instruments or positioning

o the etus. Examples o conditions treated by etoscopy are

listed in able 19-2.

Twin-Twin Transfusion Syndrome

As discussed in Chapter 48 (p. 849), etoscopic laser ablation o placental anastomoses is the preerred management

or severe twin-twin transusion syndrome (S). It is

generally perormed between 16 and 26 weeks’ gestation or

monochorionic-diamnionic twin pregnancies with stage II to

stage IV S (Quintero, 1999; Society or Maternal-Fetal

Medicine, 2013).

A etoscope inserted into the sac o the recipient twin

is used to image the vascular equator. Te vascular equator separates the placental cotyledons that supply each twin

(Fig. 19-4). Selective laser photocoagulation involves individually

coagulating anastomoses that cross between the twins (Ville,

1995). Arteriovenous anastomoses along the placental sur-

ace o the equator are visualized with the etoscope and then

photocoagulated using a 600-μm diameter diode laser or a

400-μm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser

(Fig. 19-5). Te procedure is typically perormed under epidural analgesia. At the end, amnioreduction is perormed to

decrease the single deepest pocket o amnionic uid to below

5 cm, and antibiotics are injected into the amnionic cavity.

Unortunately, residual anastomoses remain in up to a third

o cases and may lead to S recurrence or to the development o twin anemia-polycythemia sequence (APS). Te latter is a eto-etal transusion characterized by large dierences

in hemoglobin concentrations between a pair o monochorionic

twins. With the Solomon technique, immediately ater selective photocoagulation, the laser is used to coagulate the entire

vascular equator rom one edge o the placenta to the other

(Slaghekke, 2014a). Placental dye-injection studies conrm a

signicant reduction in the number o residual anastomoses

ollowing this procedure (Ruano, 2013; Slaghekke, 2014b).

Families should have reasonable expectations o procedural

success and potential complications. Without treatment, the

perinatal mortality rate or severe S is 70 to 100 percent.

Following laser therapy, the perinatal mortality rate approximates 30 to 50 percent, and the risk or long-term neurological

handicap is 5 to 20 percent (Society or Maternal-Fetal Medicine, 2013). One series reported a double-twin survival rate

o nearly 70 percent and survival o at least one twin in more

than 90 percent o cases (Diehl, 2017). Ischemic etal brain

lesions have been identied in 2 percent o those treated by

laser and include cystic periventricular leukomalacia and grade

III or IV interventricular hemorrhage (Stirnemann, 2018).

FIGURE 19-4 Selective laser photocoagulation for twin-twin

transfusion syndrome. The fetoscope is inserted into the recipienttwin sac and positioned over the vascular equator, which lies in

between the two placental cord insertion sites. Arteriovenous

anastomoses along the placental surface are individually photocoagulated using the laser. (Reproduced with permission from Shamshirsaz AA, Ramin, SM, Belfort MA: Fetal therapy. In Yeomans ER,

Hoffman BL, Gilstrap LC III, et al: Cunningham and Gilstrap’s Operative Obstetrics, 3rd ed. New York, NY: McGraw Hill; 2017.)

A B

FIGURE 19-5 Fetoscopic photograph of laser photocoagulation for twin-twin transfusion syndrome. A. Vascular anastomoses (arrows) are shown before photocoagulation is performed. B. The ablation sites appear as blanched yellow-white areas (arrows). (Reproduced with permission from Dr. Timothy M. Crombleholme.)


Cerebral palsy has been reported in 5 percent o surviving children (Schou, 2019). Procedure-related complications include preterm prelabor rup tured membranes in up to 25 percent, placental abruption in 8 percent, vascular laceration in 3 percent, and amnionic band syndrome resulting rom laser laceration o the membranes in 3 percent. Additionally, APS complicates 16 percent o pregnancies treated with selective laser photocoagulation and 3 percent treated with the Solomon technique (Habli, 2009; Robyr, 2006; Slaghekke, 2014b). Te majority o laser-treated S pregnancies deliver beore 34 weeks’ gestation (Akkermans, 2015).

Congenital Diaphragmatic Hernia

Early attempts to treat congenital diaphragmatic hernia (CDH) used open etal surgery to reposition the liver into the abdomen. Tis unortunately kinked the umbilical vein and led to etal demise (Harrison, 1993). Knowledge that lungs normally produce uid and that etuses with upper airway obstruction develop pulmonary hyperplasia ormed the rationale or tracheal occlusion. Te idea was to “plug the lung until it grows” (Hedrick, 1994). Initial eorts ocused on occluding the trachea with an external clip (Harrison, 1993). Subsequently, a detachable silicone or latex balloon was placed within the trachea endoscopically and inated with normal saline (Fig. 19-6). Tis procedure, fetoscopic tracheal occlusion (FETO), is oered to selected pregnancies with isolated CDH in which the prognosis is otherwise poor based on the degree o etal liver herniation.

FEO uses a 3-mm operating sheath and etoscopes as small as 1 mm (Van der Veeken, 2018). Te procedure is generally perormed between 26 and 30 weeks’ gestation. Te balloon is removed ater 6 weeks or at approximately 34 weeks, either through a second etoscopic procedure or by ultrasound-guided puncture (Baschat, 2020). Fetal lamb research demonstrated that without balloon removal, the number o type II pneumocytes was markedly reduced, but that balloon removal normalized type II pneumocyte density (Flageole, 1998). Because the procedure is perormed etoscopically, vaginal delivery is not contraindicated.

In 2003, a randomized trial o the FEO procedure in pregnancies with isolated CDH, liver herniation, and lung-to-head ratio <1.4 did not identiy a benet rom etal therapy (Harrison, 2003). Survival rates 90 days ater birth were unexpectedly high—75 percent—in both groups. Tereore, the lung-tohead threshold was lowered and adjusted or gestational age in an eort to improve prediction. In a metaanalysis o more than 200 pregnancies, treatment with FEO was associated with a 13-old improvement in survival rates (Al-Maary, 2016).

FEO has also been associated with improved survival rates in right-sided CDH (Russo, 2021). Although study outcomes are promising, this procedure is currently available in the United States only through a research protocol.

Lung-to-Head Ratio. Tis imaging index was developed to improve prediction o survival in etuses with isolated let-sided CDH diagnosed beore 25 weeks’ gestation (Metkus, 1996). Te lung-to-head ratio (LHR) is a semi-quantitative estimate o the right lung area divided by the head circumerence. Investigators ound that the neonatal survival rate was 100 percent i the LHR was >1.35 and that there were no survivors i the LHR was <0.6 (Metkus, 1996). Nearly three ourths o pregnancies had values between 0.6 and 1.35, and prediction was dicult in this group because the overall survival rate approximated 60 percent. Modications to the LHR have been developed in an eort to improve prediction. Jani and colleagues (2007) derived an observed-to-expected (O/E) LHR nomogram to account or dierential growth o the head and torso across gestation.

Lung area has been measured in 3 dierent ways: (1) by tracing the lung circumerence, (2) by multiplying the longest diameter o the lung with its longest perpendicular diameter, and (3) by multiplying the anterior-posterior diameter o the at the mid-clavicular line by the perpendicular diameter at its midpoint (Jani, 2012). Te North American Fetal Terapy Network ound that reproducibility o the O/E LHR was highest when the lung circumerence was traced, but that overall interrater agreement was lower than anticipated (Abbasi, 2019).

Fetoscopic Myelomeningocele Repair

Ater publication o the MOMS trial ndings, research eorts ocused on whether maternal morbidities associated with open etal myelomeningocele repair might be mitigated i the procedure were accomplished etoscopically. Araujo Junior and associates (2016) conducted a systematic review that included 456 open cases and 84 etoscopic surgeries. Te endoscopic procedures were generally perormed by inserting instruments through the maternal abdominal wall and then through the uterine wall, with partial carbon dioxide insufation o the

FIGURE 19-6 Fetoscopic tracheal occlusion (FETO). The endoscope enters the fetal oropharynx and advances down the trachea. Inset: The balloon is inflated to occlude the trachea, and then the endoscope is removed. (Reproduced with permission from Shamshirsaz AA, Ramin, SM, Belfort MA: Fetal therapy. In Yeomans ER, Hoffman BL, Gilstrap LC III, et al: Cunningham and Gilstrap’s Operative Obstetrics, 3rd ed. New York, NY: McGraw Hill; 2017.)

Chylothorax is diagnosed i a cell count perormed on the pleural uid demonstrates that more than 80 percent o the cells are lymphocytes, and there is no evidence o inection. Pleural eusions may also orm secondary to congenital viral inection or aneuploidy, or they may be associated with a malormation such as a pulmonary sequestration. Yinon and associates (2010) reported aneuploidy in approximately 5 percent and associated anomalies in 10 percent o cases. 

ypically, the eusion is rst drained using a 22-gauge needle. Te uid may be sent or chromosomal microarray analysis, inection studies, and a cell count. I the eusion recurs, a double-pigtail shunt is placed through the etal chest wall using a trocar and cannula. For a right-sided eusion, the shunt is placed in the lower third o the chest to permit maximum expansion o the lung. I let-sided, the shunt is placed along the upper axillary line to allow the heart to return to normal position. Te overall survival rate is 70 percent, and that or hydropic etuses approximates 50 percent (Mann, 2010; Yinon, 2010). We recommend weekly surveillance ollowing shunt placement because displacement into the amnionic cavity is common. At time o delivery, the shunt must be clamped immediately to avoid neonatal pneumothorax.

A shunt may also be used drain a dominant cyst in a etus with macrocystic CCAM (Fig. 15-33, p. 288). Only rarely are such cysts large enough to coner risk or hydrops or pulmonary hypoplasia. Shunt placement may improve the survival rate to 90 percent in those without hydrops and to at least 75 percent i hydrops has developed (Litwinska, 2017).

Urinary Shunts

Vesicoamnionic shunts are oered in selected cases o etal bladder-outlet obstruction in which the amnionic uid volume is severely diminished. Lower urinary tract obstruction uterus. Te rate o maternal myometrial dehiscence or attenuation was only 1 percent ollowing endoscopy compared with 26 percent ollowing open procedures. However, etoscopy was associated with signicantly higher rates o preterm delivery beore 34 weeks—80 versus 45 percent, and o perinatal mortality—14 versus 5 percent. More recently, investigators have perormed etoscopic myelomeningocele repair but used laparotomy and exteriorization o the uterus (Belort 2017). Te proportion o inants requiring ventriculoperitoneal shunts beore age 1 year— approximately 40 percent—was similar to that with open etal surgery in the MOMS trial (Adzick, 2011; Belort, 2017).

In one series o 34 pregnancies treated with open etoscopic myelomeningocele repair, the median gestational age at delivery was 38 weeks, and 50 percent delivered vaginally (Kohn, 2018). Research is ongoing in this area.

■ Percutaneous Procedures

Tese procedures are perormed using a shunt, angioplasty catheter, radiorequency ablation needle, or bipolar cautery. Under ultrasound guidance, instruments are inserted through the maternal abdominal wall, uterine wall, and membranes to reach the amnionic cavity and etus. Risks may include preterm labor, preterm prelabor ruptured membranes, placental abruption, maternal inection, and etal injury or loss.

Thoracic Shunts

Tese shunts drain etal pleural uid into the amnionic cavity (Fig. 19-7). A large eusion may result in pulmonary hypoplasia or may cause mediastinal shit that is severe enough to result in hydrops. Te most common etiology o a primary eusion is chylothorax, which is caused by lymphatic obstruction.


FIGURE 19-7 Thoracoamnionic shunt placement. A. A large, right-sided fetal pleural effusion (asterisks) and ascites were identified at 18 weeks’ gestation. The effusion was drained but rapidly reaccumulated. The xanthochromic fluid contained 95-percent lymphocytes, consistent with chylothorax. B. A double-pigtail shunt (arrow) was inserted under ultrasound guidance. Following shunt placement, the effusion and ascites resolved


(LUO) occurs more oten in male etuses. It is most commonly caused by posterior urethral valves but may be due to anterior urethral valves, urethral atresia or stenosis, or prune belly syndrome, which is also called Eagle-Barrett syndrome. Cases in emales may be associated with complex cloacal abnormalities or the megacystis-microcolon syndrome. Ultrasound ndings include dilation o the bladder and proximal urethra, termed the “keyhole” sign, along with bladder wall thickening (Fig. 15-61, p. 301). Associated oligohydramnios beore midpregnancy leads to pulmonary hypoplasia. Unortunately, postnatal renal unction may be poor even when amnionic uid volume is normal.

Evaluation includes a careul search or associated anomalies, which may occur in 40 percent o cases, and or aneuploidy, which has been reported in 5 to 8 percent (Hayden, 1988; Hobbins, 1984; Mann, 2010). Potential candidates or therapy are etuses without other severe anomalies or genetic syndromes. Terapy is generally oered only i the etus is male because the underlying anomaly tends to be even more severe in emales. Serial bladder drainage—vesicocentesis—perormed under ultrasound guidance at approximately 48-hour intervals is used to evaluate etal urine electrolyte and protein content.

Fetal urine is normally hypotonic due to tubular resorption o sodium and chloride, whereas isotonic urine in the setting o obstruction suggests renal tubular damage. Serial assessment has been used to guide candidate selection or therapy (Table 19-4). Chromosomal microarray analysis also may be perormed on etal urine.

Vesicoamnionic shunt placement allows urine to drain rom the bladder into the amnionic cavity (Fig. 19-8). While this may prevent pulmonary hypoplasia, it does not reliably preserve renal unction, particularly i cortical cysts are visible s onographically (Ruano, 2017). Warmed lactated Ringer solution is rst inused into the amniotic cavity. Amnioinusion improves ultrasound visualization, thereby acilitating evaluation o etal anatomy and shunt placement. A small trocar and cannula are then inserted into the etal bladder. A doublepigtail catheter is used, and the shunt is placed as caudal as possible within the bladder to avoid dislodgement ater bladder decompression.

Complications include displacement o the shunt out o

the etal bladder in up to 40 percent o cases, urinary ascites

in approximately 20 percent, and even development o bowel

herniation through the abdominal wall deect—gastroschisis—

in up to 10 percent (Freedman, 2000; Mann, 2010). Preterm

delivery is common, and reported neonatal survival rates range

rom 50 to 90 percent (Biard, 2005; Walsh, 2011). A third o

A

B

FIGURE 19-8 Vesicoamnionic shunt placement. A. After amnioinfusion is performed, a trocar is inserted into the distended fetal bladder under sonographic guidance. The pigtail catheter is threaded into the trocar. B. The double-pigtail shunt has been deployed down the trocar, and the trocar has been removed. The distal end of the shunt is coiled within the fetal bladder, and the proximal end is draining into the amnionic cavity. (Reproduced with permission from Shamshirsaz AA, Ramin, SM, Belfort MA: Fetal therapy. In Yeomans ER, Hoffman BL, Gilstrap LC III, et al: Cunningham and Gilstrap’s Operative Obstetrics, 3rd ed. New York, NY: McGraw Hill; 2017.)

TABLE 19-4. Fetal Urinary Analyte Values with Bladder Outlet Obstruction


surviving children have required dialysis or renal transplantation, and almost hal have respiratory problems (Biard, 2005). In a randomized trial comparing vesicoamnionic shunt with conservative management in 31 cases, those receiving shunts

had higher survival rates. However, only two children had normal renal unction at age 2 years (Morris, 2013). Similarly, a

metaanalysis o LUO studies perormed between 1990 and

2015 ound that vesicoamnionic shunt conerred perinatal survival benet but no improvement in renal unction or survival

at age 2 years (Nassr, 2017).

Radiofrequency Ablation

With this procedure, high-requency alternating current is

used to coagulate and desiccate tissue. Radiorequency ablation

(RFA) is the avored modality or treatment o twin reversed

arterial perfusion (TRAP) sequence, also known as acardiac twin

(Chap. 48, p. 850). Without treatment, the mortality rate or

the normal or pump twin in severe RAP sequence exceeds 50

percent. Te procedure is also used or selective termination

with other monochorionic twin complications.

Under ultrasound guidance, a 17- to 19-gauge RFA needle

is directed into the base o the umbilical cord within the abdomen o the acardiac twin, and a 2-cm area o coagulation is

achieved. Color Doppler is used to veriy absent ow into the

acardius. Te procedure is generally perormed at 20 weeks’ gestation. Te neonatal survival rate o the normal or pump twin

approximates 85 percent (Cabassa, 2013; Lee, 2013; Wagata,

2016). Risks are higher or monoamnionic twin pregnancies, in

whom the survival rate is only 67 percent (Sugibayashi, 2016).

Te most common complications are preterm prelabor ruptured membranes and preterm birth.

RFA has generally been oered or RAP sequence when

the volume o the acardiac twin is large. In a series rom the

North American Fetal Terapy Network, the median size o the

acardius relative to the pump twin was 90 percent (Lee, 2013).

Considering procedure-related risks, expectant management

with close etal surveillance is oten considered i the estimated

weight o the acardius is below 50 percent o the estimated

weight o the pump twin (Jelin, 2010).

Intracardiac Catheter Procedures

Selected etal cardiac lesions may worsen during gestation,

urther complicating and even limiting options or postnatal repair. Severe narrowing o a cardiac outow tract may

result in progressive myocardial damage in utero, and a goal

o etal intervention is to permit muscle growth and preserve

ventricular unction. Tese innovative procedures include aortic valvuloplasty or critical aortic stenosis; atrial septoplasty or

hypoplastic let heart syndrome with intact interatrial septum;

and pulmonary valvuloplasty or pulmonary atresia with intact

interventricular septum.

Fetal aortic valvuloplasty is the most commonly perormed

cardiac procedure, accounting or 75 percent o cases reported

by the International Fetal Cardiac Intervention Registry

(Moon-Grady, 2015). It is oered or selected cases o critical aortic stenosis in which the let ventricle is either normal

sized or dilated. Te goal is to prevent progression to hypoplastic let heart and to permit postnatal biventricular repair.

Under sonographic guidance, an 18-gauge cannula is inserted

through uterus and etal chest wall and into the let ventricle.

Although the procedure is ideally perormed percutaneously—

through the maternal abdominal wall—laparotomy may be

needed i the etal position is unavorable. Te cannula tip is

positioned in ront o the stenotic aortic valve, and a 2.5- to

4.5-mm balloon catheter is guided into the aortic annulus and

then inated. Fetal bradycardia requiring treatment may complicate a third o cases, and hemopericardium requiring drainage aects approximately 20 percent (Patel, 2020).

In a review o 108 etuses treated with aortic valvuloplasty

rom 15 international centers, 75 percent survived until delivery, and biventricular repair was achieved in 32 percent (Patel,

2020). Friedman and coworkers (2018) rom Boston Children’s Hospital have reported improved outcomes with the

procedure in recent years. O 52 aortic valvuloplasty procedures

perormed between 2009 and 2015, nearly 90 percent resulted

in a live birth, and more than 50 percent achieved biventricular

repair. Guseh and colleagues (2020) emphasize that most children with biventricular unction still require postnatal cardiac

procedures. Te risk or neurodevelopmental impairment in

childhood appears similar to cases treated with postnatal repair

(Laraja, 2017; Moon-Grady, 2015).

Te subset o etuses with hypoplastic let heart syndrome

who also have an intact or restrictive interatrial septum have

postnatal mortality rates o nearly 80 percent (Glantz, 2007;

Jantzen, 2017). o help improve survival, etal atrial septoplasty using a percutaneous balloon catheter has been oered.

Atrial septal stent placement is oten attempted at the time o

septoplasty to ensure patency. O 47 such procedures reported

by the International Fetal Cardiac Intervention Registry, 35

percent o inants survived to hospital discharge (Jantzen,

2017). However, the 1-year survival rate was higher in those

that had successul etal cardiac intervention compared with

those that had not undergone intervention.

Fetal pulmonary valvuloplasty has been oered in cases o

pulmonary atresia with intact interventricular septum to prevent development o hypoplastic right heart syndrome and

subsequent single ventricle palliation. Te International Fetal

Cardiac Intervention Registry reported that o 58 cases o

attempted pulmonary valvuloplasty, the procedure was technically successul in 70 percent (Hogan, 2020). Tose with

successul in-utero procedures were twice as likely to achieve

biventricular repair. However, when procedure-related losses

were considered, survival to hospital discharge was similar to

those who had not received etal intervention, approximating

75 percent. Long-term benets o the procedure have yet to be

demonstrated.

■ ExUtero Intrapartum Treatment

Tis procedure allows the etus to remain perused by the placenta ater being partially delivered, so that liesaving treatment can be perormed beore completing the delivery. Te technique was rst developed to obtain an airway with etal tumors involving the oropharynx and neck and is still used or this indication (Catalano, 1992; Kelly, 1990; Langer, 1992; Shamshirsaz, 2021). An ex-utero intrapartum treatment (EXI)


procedure is perormed by a multidisciplinary team, which may include an obstetrician, maternal-etal medicine specialist, pediatric surgeon(s), pediatric otolaryngologist, pediatric cardiologist, anesthesiologists or the mother and etus, neonatologists, and specially trained nursing personnel. Components o the procedure are shown in Table 19-5 (Moldenhauer, 2013). Selected indications are listed in able 19-2. EXI is the preerred procedure or intrapartum management o large venolymphatic malormations o the neck such as the one shown in


Figure 19-9. Criteria or EXI with a cervical venolymphatic malormation include compression, deviation, or obstruction o the airway by the mass, and also involvement o the oor o the mouth (Laje, 2015). However, a review o 112 pregnancies with etal cervical venolymphatic malormations ound that only about 10 percent met these criteria. Other indications or EXI include severe micrognathia and congenital high airway obstruction sequence (CHAOS), which are discussed in Chapter 15 (Figs. 15-27 and 15-35, p. 285). 

Criteria or an EXI procedure or micrognathia include a etal jaw measurement below the 5th percentile along with indirect evidence o obstruction, such as hydramnios, an absent stomach bubble, or glossoptosis (Morris, 2009b). Case selection or EXI procedures is generally based on etal magnetic resonance imaging ndings.

In some cases, an EXI procedure has been used as a bridge to other procedures. For example, resection o large thoracic masses may be accomplished by etal thoracotomy perormed with intact placental circulation. In a series o 16 etuses with CCAM volume ratios >1.6 or hydrops, all o whom had mediastinal compression, Cass and colleagues (2013) reported that nine inants undergoing EXIT-to-resection survived. In contrast, there were no survivors with urgent postnatal surgery alone. Similarly, Moldenhauer (2013) reported that 20 o 22 newborns treated with EXI-to-resection or lung masses survived. Te EXI procedure has also been used as a bridge to extracorporeal membrane oxygenation—EXI-to-ECMO—in pregnancies with severe congenital diaphragmatic hernia. However,

TABLE 19-5. Components of the Ex-Utero Intrapartum Treatment (EXIT) Procedure Comprehensive preoperative evaluation: specialized fetal sonography, fetal echocardiography, magnetic resonance imaging, fetal karyotype if possible 

Uterine relaxation with deep general anesthesia and tocolysis

Intraoperative sonography to confirm placental margin and fetal position and to visualize vessels at planned hysterotomy site

Placement of stay-sutures followed by use of uterine stapling device to decrease hysterotomy-site bleeding

Maintenance of uterine volume during the procedure via continuous amnioinfusion of warmed physiological solution to help prevent placental separation

Delivery of the fetal head, neck, and upper torso to permit access as needed

Fetal injection of intramuscular vecuronium, fentanyl, and atropine

Fetal peripheral intravenous access, pulse oximeter, and cardiac ultrasound

Following procedure, umbilical lines placed prior to cord clamping

Uterotonic agents administered as needed


FIGURE 19-9 Ex-utero intrapartum treatment (EXIT) procedure for a venolymphatic malformation. A. Upon delivery of the head, placental circulation was maintained, and an airway was established over the course of 20 minutes by a team of pediatric subspecialists that included a surgeon, anesthesiologist, and otolaryngologist. B. Following a controlled intubation, the fetus was ready for delivery and transfer to the neonatal intensive care unit team. (Reproduced with permission from Drs. Stacey Thomas and Patricia Santiago-Muñoz.)


it has not been ound to clearly coner survival benet in such cases (Morris, 2009a; Shieh, 2017; Stoan, 2012). Counseling prior to an EXI procedure includes procedurerelated risks such as hemorrhage rom placental abruption or uterine atony, need or cesarean delivery in uture pregnancies, higher risk or subsequent uterine rupture or dehiscence, possible need or hysterectomy, and etal death or permanent neonatal disability. Compared with cesarean delivery, the EXI procedure is associated with greater blood loss, a higher incidence o wound complications, and a longer operating time (Noah, 2002; Shamshirsaz, 2019).

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