Open Fetal Surgery - Clinical Tree

Key Points

Most fetuses with a prenatal diagnosis of a congenital abnormality can be managed expectantly. For some conditions, in utero referral is mandatory for planned delivery and management after birth.
Fetal surgery is only required for conditions that cannot await therapy after birth and when there is enough evidence that prenatal surgery partly reverses the natural course.
Open fetal surgery (OFS) is one modality to perform operations on fetuses. OFS is invasive, with maternal morbidity and an impact on the uterus in the index and future pregnancies, and it increases the risk for preterm delivery.
Open spina bifida is the only nonlethal condition operated in utero , yet it became the most frequent indication based on level I evidence. OFS improves the outcome of children with spina bifida, but it is not a cure.

Introduction

Definition

Open fetal surgery (OFS) is the type of fetal surgery that is performed via hysterotomy. It is also referred as open maternal-fetal surgery or fetal surgery by open access.

Rationale of Open Fetal Surgery for Congenital Abnormalities

Pathophysiology and Natural History

Since the introduction of ultrasound (US) and later other imaging modalities and the increased interest for congenital anomalies (CAs) and their outcomes in relation to prenatal findings, it has become possible to define the natural history of several potentially correctable CAs. Also, researchers developed appropriate animal models for the disease of interest to study both the pathophysiology as well as the surgical interventions contemplated. These studies, particularly in primates, have been used for developing the anaesthetic, tocolytic and surgical protocols for hysterotomy and OFS.

Selection Criteria for Open Fetal Surgery

Open fetal surgery is currently being offered in highly specialised multidisciplinary fetal centres for highly selected fetuses with a condition that is, without any intervention, either lethal or in which the subsequent organ function loss leads to an extremely poor quality of life after birth. The International Fetal Medicine and Surgery Society (IFMSS) defined five criteria required to justify fetal surgery ( Table 38.1 ).

TABLE 38.1

Five Criteria for Maternal-Fetal Surgery From the International Fetal Medicine and Surgery Society

Adapted Harrison MR, Filly RA, Golbus MS, et al. Fetal treatment 1982. N Engl J Med 307 (26):1651–1652, 1982.

1.
Accurate diagnosis and staging possible, with exclusion of associated anomalies

2.
Natural history of the disease is documented, and individualised prognosis is established

3.
Currently no effective postnatal therapy (i.e., improving the condition or curing it)

4.
In utero surgery proven feasible in animal models, reversing the deleterious effects of the condition

5.
Interventions performed in specialised multidisciplinary fetal treatment centres within strict protocols and approval of the local ethics committee with informed consent of the mother or parents

Indications

A Nonlethal Condition: Spina Bifida Aperta

The epidemiology, pathophysiology and natural history have been addressed in Chapter 28 . Within routine screening US programs neural tube defects should be diagnosed prenatally. An invasive fetal procedure for spina bifida aperta (SBA) seems to be justified because of the significant lifelong neurologic disabilities, the prenatal progression of findings and the experimental validation of the two-hit pathophysiology. Experimental research and early clinical experience suggest that ongoing damage to the exposed malformed spinal cord and developing brain is alleviated by prenatal repair. The Management of Myelomeningocele Study (MOMS) was a multicentre randomized controlled trial that unequivocally demonstrated that prenatal surgery for SBA improves outcome compared with standard postnatal repair. Table 38.2 displays the initial and current indications and contraindications for in utero SBA repair. Fetal surgery was shown to lessen or reverse hindbrain herniation, reduce the postnatal ventriculoperitoneal shunt rate at 1 year of age and improve neurofunctional outcome at the age of 30 months.

TABLE 38.2

Indications for Open Fetal Surgery

Indications for OFS	Type of Malformation	Rationale for In Utero Therapy	Inclusion Criteria	Exclusion Criteria
Spina bifida aperta	MMC or myeloschisis with CM	Untethering and covering of exposed malformed spinal cord to prevent or reverse functional damage to the cord and nerves Cessation of CSF leakage to prevent or reverse hydrocephaly and CM	Maternal age ≥18 yr Gestational age 19 + 0-25 + 6weeks Isolated lesion Normal karyotype Level lesion from T1–S1 Confirmed CM on prenatal US and MRI	Multiple-gestation pregnancy Uterine anomaly or corporeal uterine surgery Additional fetal anomalies unrelated to SBA (chromosomal or not) Fetal kyphosis ≥30 degrees Previous spontaneous singleton delivery at <37 wk gestation History of incompetent cervix or short cervix <20 mm by US scan Placenta previa Obesity defined by BMI ≥35 (later shifted to 40) IDP diabetes (later changed to uncontrolled) Other serious maternal medical condition Maternal-fetal Rh isoimmunisation Positive maternal HIV or haepatitis B or known haepatitis C positivity No support person to stay with the pregnant woman at the centre Psychosocial limitations Inability to comply with travel and follow-up protocols
Congenital thoracic malformations (CCAM and BPS)	Large solid lesion complicated with fetal hydrops	Prevention of fetal death Reversal of heart and great vessels compression and thus of nonimmune hydrops and cardiac failure Reversal of lung compression and thus of lung hypoplasia Reversal of oesophageal compression and thus of polyhydramnios Prevention of placentomegaly and maternal mirror syndrome	Isolated lesion Fetal hydrops <32 wk of gestation No dominant cyst CVR >1.6	Multiple-gestation pregnancy Chromosomal abnormality Other significant anatomic abnormalities Placentomegaly Maternal mirror syndrome Short cervix History of heavy cigarette smoking Maternal psychosocial difficulties Other maternal medical risk factors
Sacrococcygeal teratoma	Large, fast-growing solid lesion complicated with fetal hydrops	Prevention of fetal death Cessation of vascular steal phenomenon, reversing high-output cardiac failure Reversal of mass effect	Isolated lesion Type I or II (more external forms) Fetal hydrops Progressive evolution of high output cardiac failure <28 wk of gestation	Multiple-gestation pregnancy Chromosomal abnormality Other significant anatomic abnormalities Placentomegaly Maternal mirror syndrome Short cervix History of heavy cigarette smoking Maternal psychosocial difficulties Other maternal medical risk factors

BMI, Body mass index; BPS, bronchopulmonary sequestration; CCAM, congenital cystic adenomatoid; CM, Chiari II malformation; CSF, cerebrospinal fluid; CVR, cystic adenomatoid malformation volume ratio; HIV, human immunodeficiency virus; IDP, insulin-dependent pregestational; MMC, myelomeningocele; MOMS, Management of Myelomeningocele Study; MRI, magnetic resonance imaging; OFS, open fetal surgery; SBA, spina bifida aperta; US, ultrasonography.

Lethal Conditions

Congenital Thoracic Malformations Complicated With Fetal Hydrops

Congenital thoracic malformations (CTMs) are a heterogeneous group of rare disorders that may involve the airways or lung parenchyma. As an accurate pathological prenatal diagnosis is not possible; a detailed prenatal description of the appearance of the lesion is sufficient and should follow the new CTM classification and nomenclature (see Chapter 30 ). This section focuses on the two most frequent CTMs that are also amenable to OFS: congenital cystic adenomatoid malformation (CCAM) and its related malformation, bronchopulmonary sequestration (BPS). It is important to realise that the exact nature of the condition (or their combination) may only be possible after resection. In fact, lung parenchymal malformations, although superficially heterogeneous in appearance, have significant overlap and seem to share a common embryologic origin. According to the European Surveillance of Congenital Anomalies (EUROCAT) registry, the prevalence of CTM between 2008 and 2012 was 4.13 per 10,000 live births. Among the CTMs, the estimated prevalence of CCAM was 1.05 per 10,000 live births, that is, about one quarter of all CTMs. The exact prevalence of BPS is unknown and probably lower than for CCAM. CTMs may spontaneously regress before birth; the ones that deteriorate in utero and may even lead to fetal death are of relevance to this chapter (see Table 38.2 ).

Congenital Cystic Adenomatoid Malformation

Congenital cystic adenomatoid malformation is a benign cystic intrapulmonary nonfunctioning lung mass that is usually localised in one lobe of the lung and mainly unilateral. CCAM contains cysts ranging from smaller than 1 mm to larger than 10 cm in diameter. Most CCAMs derive their blood supply from the pulmonary circulation. CCAM is histologically characterised by an overgrowth of terminal respiratory bronchioles that form cysts and lack normal alveoli. Many pathologists consider it a hamartoma (i.e., a developmental abnormality with excess of one or several tissue components). Although nonfunctional for normal gas exchange, CCAM parenchyma has connections with the tracheobronchial tree as evidenced by air trapping that can develop during postnatal resuscitative efforts. There are different prenatal classifications; however, postnatally, typically four Stocker types (I–IV) are described.

Congenital cystic adenomatoid malformation growth usually reaches a plateau by 28 weeks of gestation and may even nearly disappear by birth. Others may cause fetal hydrops and in utero death. The impact on normal lung development and postnatal function has not been properly studied. Prenatally, the size of the lesion, the cyst size, the growth and perfusion and the secondary signs have all been used to describe the severity of the impact on the fetus. In general, fetal hydrops is the single accepted criterion for fetal therapy. A CCAM volume ratio (CVR) (CCAM volume by sonographic measurement using the formula for an ellipse, length × height × width × 0.52 divided by head circumference to correct for differences in fetal size) greater than1.6 has been shown to predict hydrops in 80% of fetuses with CCAM.

Bronchopulmonary Sequestration

Bronchopulmonary sequestration is defined as a nonfunctioning lung mass that receives a systemic blood supply rather than from a branch of the pulmonary artery. It belongs to the spectrum of congenital foregut malformations arising as an aberrant outpouching from the developing foregut. BPS is believed to be aberrantly located pulmonary mesenchyma that develops apart from the normal lung.

Bronchopulmonary sequestration is classified into intralobar and extralobar forms. The extralobar (25%) form consists of pulmonary tissue located outside the lung and enveloped in its own pleura without communication with the normal tracheobronchial tree. Around 90% are supradiaphragmatic and 10% infradiaphragmatic, usually left suprarenal. The intralobar form is found within the normal lung tissue with or without communication.

Other Rarer Lethal Conditions

We will not discuss these even rarer indications, some of which have been operated in utero :

Hybrid lesions (CCAM and BPS)
Bronchogenic and enteric cysts
Mediastinal cystic teratoma
Congenital lobar emphysema
Haemangioma
Bronchial atresia
Pulmonary leiomyofibroma
Intrathoracic gastric duplication cyst

Sacrococcygeal Teratoma With Hydrops Fetalis

Sacrococcygeal teratoma (SCT) is the most common tumour of newborns with a prevalence of about 0.37 to 0.93 per 10,000 live births. SCT is uniformly attached to the coccyx and has been classified into four types (I–IV) by the relative amounts of intrapelvic and external tumour. SCTs presenting postnatally have excellent long-term outcomes; conversely, prenatally diagnosed SCTs have a significant perinatal mortality ranging from 25% to 37%. Death occurs mainly in fetuses with fast-growing, solid and highly vascularised teratomas that lead to high-output cardiac failure or haemorrhage. The pathophysiological mechanism behind this is explained by the ‘vascular steal’ from the placenta and the fetus and by the mass effect :

1.
SCT acts as a large arteriovenous malformation that deviates high volumes of blood from the fetus and the placenta. Also, bleeding inside the tumour can cause anaemia. The consequence is high-output cardiac failure, which can then lead to placentomegaly, hydrops fetalis, intrauterine fetal demise, preterm birth and neonatal death. This may also cause Ballantyne syndrome (maternal mirror syndrome), which is a dangerous maternal complication.
2.
SCT compresses the abdominal and thoracic organs, leading to polyhydramnios (oesophageal and gastric compression) inducing uterine irritability, premature rupture of the membranes (PPROM) and preterm delivery. The tumour may also have an effect on nearby organs, such as obstructive uropathy. Dystocia in undiagnosed large masses is frequently associated with traumatic tumour rupture and haemorrhage during delivery, which is usually fatal.

Assessment of tumour size, growth rate and fetal cardiac function by fetal imaging allows the identification of fetuses at particular risk for decompensation. Ultrafast fetal magnetic resonance imaging (MRI) is superior to US in delineating the intrapelvic extent of the tumour, yet this does not contribute to the indication for fetal surgery. The currently accepted indications for OFS for this condition are detailed in Table 38.2 .

Surgical Technique

Pre- and Intraoperative Management

Open fetal surgery is recommended to take place in tertiary medical centres that have a multidisciplinary team experienced with the anaesthetic and surgical techniques described later; familiar with the management of the potential postoperative complications such as amniotic fluid leakage, fetal membrane separation and preterm labour; and with proven track record of managing the condition of interest postnatally. Any candidate OFS centres should follow a specific training with expert centres. We did so in a mixed training model, in-house training by physicians familiar with OFS, as well as exported training (i.e., short stay of selected team members at a large volume OFS centre). We performed our first five local surgeries under direct supervision.

Preoperative Management

A multidisciplinary OFS team of specialists will perform a complete prenatal evaluation and counselling of the parents. Surgery should not proceed until full informed consent is obtained. The maternal-fetal evaluation includes detailed prenatal US to confirm the diagnosis and severity and exclude other abnormalities as well as technical aspects such as placental location and maternal assessment. A fetal echocardiogram is mandatory to measure the haemodynamic impact of the condition while also ruling out congenital heart defects. Ultrafast fetal MRI today seems to be standard of care for most conditions eligible for fetal surgery. If no genetic testing was done yet, this should be undertaken first. Moreover, the expectant mothers undergo psychological evaluations and extensive counselling on the postnatal impact of the condition as well as that of OFS. Any nonmedical, socioeconomic issues should also be discussed and when necessary dealt with. Some centres organise a consult with the whole multidisciplinary team present.

Intraoperative Management

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here