Limb body wall complex

Limb-body wall complex (LBWC) is a complex anomaly of the body wall with associated limb and visceral abnormalities [1]. LBWC is also known as body stalk anomaly. 

Q79.59—congenital malformations of the abdominal wall

The incidence of LBWC in the literature varies from 1 in 14,000 to 1 in 22,000 pregnancies. Most cases have an early prenatal diagnosis and result in termination of pregnancy [1-5].  The incidence of LBWC at birth is 0.2—0.3 per 10,000 births due to loss from termination of pregnancy and intrauterine fetal demise in continuing pregnancies [1].

The exact pathogenesis of the condition is complex and remains unclear although various models have been proposed [1-6]. The most documented theories include the extrinsic (amnion rupture, vascular disruption) and intrinsic (embryonic mal-development) theories [5,6].  

Extrinsic theories include amniotic rupture and vascular disruption. In amniotic rupture it is thought that early damage to the amnion before obliteration of the coelomic cavity leads to the formation of fibrous bands from the chorionic surface [4-6].  These bands then entrap various body parts and/or the umbilical cord, resulting in complex malformations, amputation and clefting [4,5]. In the vascular disruption theory, it is proposed that early generalised ischemia from weeks 4-6 gestation results in failure of ventral body wall closure and persistence of the extra-embryonic coelomic cavity. This then leads to visceral herniation and necrosis. Adhesions form between the necrotic viscera and the amnion leading to band formation and organ entrapment [1-6]. 

The intrinsic theory, or embryonic mal-development theory, describes disruption to the cephalic, caudal and lateral folds in the 5th week of gestation.  This causes visceral organ herniation and malformation depending on the location of the aberrant folding.  In LBWC there can be disruption to all four folding processes [2,3].  

The etiology of LBWC is unknown. 

Fetuses affected by LBWC usually have normal karyotype. Some studies, however, have shown an association with placental trisomy 16 or maternal uniparental disomy 16. More recently, genes involved in abnormal lateral folding of the fetus have been implicated [7,8].  

Drug use with vasoconstrictive agents including cocaine in early pregnancy are thought to compromise embryonic blood flow and support the vascular disruption pathway to developing LBWC anomalies [5,7,8].
 
Abdominal trauma has also been suggested in some case reports to precipitate amnion rupture and result in widespread fibrous band formation [5].

LBWC is thought to be a sporadic abnormality with a very low risk of recurrence in subsequent pregnancies (<0.2%) . There is no known correlation with parental age or fetal sex [1,5,8].

The majority of cases of LBWC can be diagnosed by the late first trimester with some cases detectable from eight weeks gestation [9,10]. No clear diagnostic criteria for LBWC exists, however most classification systems in the literature include a combination of at least two of the following abnormalities: craniofacial defects, limb abnormalities and abdominal wall defects [1-5, 9].

Ultrasound features for LBWC vary from case to case.  In the early first trimester the most commonly described abnormalities may not be discernable, however the following findings may support the diagnosis: the entire fetus or portion of the fetus may be seen outside of the amniotic cavity, the amniotic membrane may be normal or appear ruptured, or the normal umbilical cord may not be seen as demonstrated by an abnromally elevated crown-rump-length to umbilical cord length ratio (the normal ratio is 1:1) [9,10]. 

By the late first trimester (11-13 week scan) additional findings commonly include an increased nuchal translucency with or without body edema [10]. The abdominal contents may be seen beyond the amniotic membrane. Commonly there is a very short or absent umbilical cord and the fetus appears “stuck” to the placenta in the thoraco-abdominal region. Severe kyphoscoliosis is commonly identified, and limb defects are commonly seen. Some early cases also demonstrate that the heart is outside the chest cavity. 

In the first trimester it is quite important to use transvaginal scanning to confirm abnormalities. In addition, 3D imaging may improve understanding of anatomic relationships and improve image resolution as well as demonstrating abnormalities to the parents [12]. 

A series of 4 cases published in 2011 demonstrated the usefulness of 3D sonography to identify LBWC in the first trimester. The authors used multiplanar assessment and paralell shifting to determine the precise anatomic locations of fetal structure and their relationship to the amniotic cavity [11,12].  In this series, 3D sonography was also superior to 2D techniques in differentiating between LBWC and other malformations such as a simple omphalocele at early gestations (<12 weeks), while the use of 3D surface rendering improved delineation of lower limb abnormalities [10,11]. 

In the second and third trimester, the more characteristic findings associated with LBWC can be identified using ultrasound. These include: large thoraco-abdominal wall defect without a covering membrane, an absent or very short umbilical cord with vessels seen coursing from the placental surface to the fetal torso, scoliosis, limb defects (clubfoot, arthrogryposis, polydactyly, syndactyly, absent limbs or digits), cranio-facial defects (encephalocele, exencephaly, facial defects) and oligohydramnios [1,5,11,12]. 

To assist in making the diagnosis it is advisable to observe the fetus over time and to scan the patient in multiple positions to demonstrate that the fetus is in a fixed position or has attachments to surrounding structures such as the placenta [1,5,11]. The umbilical cord length can be evaluated using colour Doppler and colour Doppler can be used to distinguish between cord and fibrous connections [11].  Colour Doppler is also useful to course the renal arteries, hepatic vessels and iliac bifurcations in order to determine visceral anatomic relationships and clarify the origin or arrangement of herniated viscera [5,12]. 

The ultrasound features of LBWC overlap with other diagnoses involving abdominal wall defects including gastroschisis, omphalocele, Pentalogy of Cantrell, cloacal exstrophy and amniotic band syndrome. 

In gastroschisis the bowel herniates through a paramedian abdominal wall defect that is usually to the right of the cord insertion [12,13]. The umbilical cord insertion is normal.  The herniating bowel loops do not have a membranous covering and remain free floating within the amniotic fluid without becoming adherent other structures such as the placenta [12,13]. Fetal movements are unrestricted and gastroschisis is usually an isolated finding [12] (See VISUOG Chapter on Gastroschisis).

An omphalocele results from a midline abdominal wall defect.  Herniated contents can be variable and may include bowel, liver and other viscera with a double layered membranous covering composed of amnion externally and peritoneum internally [13]. The umbilical cord inserts into the covering membrane, not directly on the abdominal wall, however the cord remains free floating within the amniotic fluid and has normal length [12,13]. In contrast to LBWC, the herniated contents within the omphalocele remain contained within the membranous sac and do not adhere to surrounding structures [13]. Similarly, omphaloceles are not usually associated with spine and limb abnormalities [12,13] (See VISUOG Chapter on Omphalocele). 

In cloacal exstrophy and the OEIS complex there is a lower midline abdominal wall defect that results in herniation of all the strucutres derived from the cloaca (i.e. rectum, bladder and lower genitourinary tract) [12]. These defects begin consist of a more extensive abdominal wall defect extending inferiorly towards the pubis. Bowel can be seen herniating between the bladder halves creating an ‘elephant trunk’ appearance and the anal dimple is often absent. Associated lumbosacral and genitourinary abnormalities are found in up to 60% of cases [12].  Differentiating features from LBWC include an absent bladder, umbilical cord length and mobility, non adherence of herniated organs to the placenta or uterine wall and overall fetal mobility [12,14].  In LBWC the bladder is often present within the abdominal cavity, the fetus assumes a more fixed position and the umbilical cord is shortened or absent [1,12] (See VISUOG Chapter on Cloacal Exstrophy).

In Pentalogy of Cantrell there is a combination of congenital heart disease (typically septal defects, tetralogy of Fallot, left ventricular diverticulum and Ebstein malformation), defects in the lower sternum, anterior diaphragm, diaphragmatic pericardium and supraumbilical abdominal wall [12,15]. Omphaloceles of the upper abdominal wall resultsing in ectopia cordis are seen in 63% of cases while 30% of cases are associated with facial defects, central nervous system abnormalities (exencephaly, encephalocele, spina bifida) and musculoskeletal anomalies [15]. The abnormality exists on a spectrum:  mild cases display isolated or few abnormalities whilst more complex presentations display multiple anomalies that may or may not be lethal [15]. The latter can be challgenging to differentiate from LBWC, particularly in early gestation. The main distinguishing features include the length and mobility of the umbilical cord and fetal mobility [15] (See VISUOG Chapter—Chest: other conditions).

Amniotic Band Syndrome is caused by intra-cavitary fibrous bands that form from the amniotic surface and entangle and deform fetal parts [12].  The syndrome has considerable overlap with LBWC especially if linear ‘slash defects’ occur along the torso or abdomen causing abdominoschisis and thoracoschisis. In amniotic band syndrome fetal movements may be less restricted and limb amputations are more common [1,4,12]. Differentiation from LBWC depends on demonstration of a normal umbilical cord [12]. 

Additional abnormalities are present in all cases. Due to the highly distorted anatomic structures, not all abnormlaities will able to be identified. Abnormalities which have been reported include ectopia cordis, congenital diaphragmatic hernias or absent diaphragms, renal anomalies (hydronephrosis, agenesis, cystic dysplasia), bowel atresia, scoliosis, facial clefts, cephaloceles and limb anomalies [1-4, 9-12].  

LBWC has also been associated with placenta previa and placenta accreta [3], A careful look at the placenta for abnormal placentation is suggested. (See VISUOG chapter on Placenta Accreta Spectrum). 

Conditions such as LBWC strongly support the argument for first trimester ultrasound screening. Due to the severity of the anomalies associated with LBWC, the majority of cases of LBWC can be identified at the time of the first trimester structural survey [1,5,10]. Early diagnosis is helpful for prenatal counselling and pregnancy management as the diagnosis can be made with certainty in the first trimester, and the condition is lethal [1,5,10]. In most cases the fetus demonstrates normal chromosomes hence diagnostic testing with chorion villus sampling or amniocentesis is not necessary [7,8].  However in some case reports there have been instances of both de-novo and inherited mutations in the genes responsible for lateral and caudal folding which may support consideration for invasive testing [7,8]. 

Due to the extensive multi-organ involvement and major midline defects associated with LBWC all cases are lethal [1-5]. More than 60 percent of fetuses with LBWC die in-utero in the preterm period when pregnancies are continued [1-5].   Of those who survive until delivery, most do not survive labor or die shortly after birth [1-5]. 

Parents should be counselled about the lethal nature of the diagnosis. Invasive testing is not typically necessary since most fetuses have normal chromosomes, and the recurrence risk is low [6-8]. Pregnancy termination should be offered based on local laws [5,16-18].  Should parents be committed to the pregnancy, further ultrasound examinations may be helpful to help parents understand the structural malformations which are present [16-18]. A multidisciplinary  Perinatal Bereavement team, if available, may be helpful [5]. Antenatal consultation with the neonatology or pediatric team to discuss comfort care measures may also be helpful [16-18].

Vaginal birth is desirable due to the lethal nature of the diagnosis with cesarean birth reserved for the usual obstetric reasons [16-18]. Parents should be aware that the baby may die intrapartum. There have been case reports of labor dystocia due to fetal malposition, uterine rupture and placenta accreta spectrum which may require cesarean delivery [16-18]. Last, there are some patients who may request cesarean delivery in order to hold a live-born baby—in these cases neonatal care should include comfort care support [16-18]. 

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