Limb–body wall complex (LBWC), also known as body stalk anomaly, is a severe fetal multi-malformation syndrome characterized by a major thoracoschisis or gastroschisis, visceral herniation, severe scoliosis or kyphoscoliosis, limb deformities, craniofacial malformations, and umbilical cord abnormalities (1). As LBWC is a lethal anomaly, affected pregnancies are often terminated (2).

The reported prevalence of LBWC varies widely, with estimates ranging from 0.04 to 3.3 per 10,000 births (3–6). This variability is attributed to factors such as differing diagnostic criteria, early spontaneous abortions, pregnancy termination after diagnosis, and advances in prenatal diagnostic technologies. With the rapid development of prenatal ultrasound technology, standardized ultrasound examinations in early pregnancy (11–13⁺⁶ weeks) have been widely promoted and applied. Thus, an increasing number of LBWC cases are definitively diagnosed in early pregnancy, providing parents more time to consider and determine pregnancy outcomes. However, there is limited literature discussing the prenatal ultrasound diagnosis of LBWC. This study retrospectively summarizes the ultrasound imaging features of fetal LBWC cases, explores the pathogenesis of LBWC, and aims to offer comprehensive guidance for the prenatal diagnosis of LBWC.

We retrospectively analyzed cases of LBWC diagnosed through prenatal ultrasound at Peking Union Medical College Hospital and Xuzhou Maternity and Child Health Care Hospital between 2012 and 2023. Using the hospitals’ database search function, we identified all cases with prenatal ultrasound findings suggestive of LBWC by applying the keywords “LBWC,” “body stalk anomaly,” or “amniotic band syndrome.” Two obstetric ultrasound experts with more than 15 years of work experience independently reviewed each case, combining prenatal ultrasound images, clinical medical records, and postnatal pathological reports to confirm the diagnosis of LBWC. Consensus was reached for all included cases. The institutional review board of Peking Union Medical College Hospital approved the study and waived the need for written consent from the patients. Xuzhou Maternal and Child Health Care Hospital handled the ethical filing.

Ultrasound examinations were performed using color Doppler ultrasound diagnostic instruments (GE Voluson E10/E8, GE Healthcare; and Philips EPIQ7/IU22, Philips Healthcare) equipped with a transabdominal two-dimensional or three-dimensional convex array probe with frequency ranges of 2.0–5.0 MHz and 1.0–5.0 MHz, respectively. A transvaginal ultrasound probe with a frequency range of 4.0–8.5 MHz was also used.

All fetal ultrasound examinations were performed by certified sonographers who had obtained qualifications from the regional maternal and child health administration and followed the guidelines recommended by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). The examinations involved sequential observations of fetal cranial, facial, thoracoabdominal, spinal, limb, and cardiac development. When a suspicious thoracoabdominal wall defect was detected, particular attention was paid to detect any abnormal echogenic masses, which included an assessment of the mass location, size, morphology, content, and presence/absence of a membrane, and a thorough assessment of concomitant limb structural anomalies/position abnormalities, craniofacial deformities, and changes in spinal physiological curvature. The integrity of the amniotic sac and its relationship to the fetus were carefully inspected, along with assessments of the umbilical cord length, course, and placental insertion site, and the extraembryonic cavity. Certain cases required more detailed assessment using transvaginal ultrasound and three-dimensional ultrasound with surface rendering.

LBWC is a rare and severe malformation syndrome. The diagnostic criteria for LBWC vary across different reports (3, 8), leading to a confusing array of terms used to describe this condition (2). In the present study, we adhered to the definition proposed by Van Allen et al. (9), in which the diagnosis of LBWC is based on the presence of two out of three characteristic defects: thoracoschisis or gastroschisis with a large visceral herniation, limb defects, and exencephaly/encephalocele with facial clefts.

The etiology of LBWC remains elusive, and several competing pathophysiological theories have been proposed (6, 10, 11). In 1930, Streeter (12) proposed the intrinsic abnormal embryonic development theory, which suggests that LBWC results from a completely faulty trilaminar embryonic disc folding process along all three axes (cephalic, caudal, and lateral) during the first 4 weeks of embryonic development; this abnormal longitudinal folding results in thoracoschisis or gastroschisis. In 1965, Torpin (13) proposed the extrinsic theory, which suggests that early amniotic membrane rupture caused by direct mechanical pressure creates constriction bands that entangle the embryo, leading to severe deformities such as craniofacial defects, amputations, and body wall defects. In 1987, Van Allen et al. (9) introduced the early vascular disruption theory, which posits that a vascular disruption event occurring between the fourth and sixth weeks of gestation interrupts the normal blood supply to the developing embryo, leading to a wide range of anomalies affecting various organ systems. LBWC may also have a heterogeneous etiology, with several or all pathogenetic mechanisms being responsible in a subset of patients (14–17). In the present study, a midline cleft lip was found postnatally in one case (Figure 3d), without any associated membranous structure, thereby supporting the theory of an intrinsic cause. This finding also suggests that LBWC cannot be explained by a single mechanism and that different pathological mechanisms may arise from different phenotypes, warranting further research.

Due to the variability in clinical presentations of LBWC, different classifications have been proposed (7, 18, 19). Russo et al. (7) suggested dividing LBWC into two main phenotypes. Type I is characterized by craniofacial defects (exencephaly or cephalocele), facial clefts, cranial placental attachment, thoracoschisis, and upper limb abnormalities. Type II is characterized by thoraco-gastroschisis or gastroschisis, placento-abdominal attachments, lower limb abnormalities, urogenital anomalies, anal atresia, lumbosacral meningocele, scoliosis, and a short umbilical cord. In the present study, the higher prevalence of type II cases may reflect the greater severity of type I cases, which involve craniofacial abnormalities and often lead to early miscarriage. However, two cases in our series could not be clearly classified into either category. Sahinoglu et al. (16) have suggested that all previously proposed causative mechanisms may contribute, leading to different subgroups. They proposed a new phenotypic classification dividing LBWC into three types: type 1, a fetus with a craniofacial defect and an intact thoracoabdominal wall; type 2, a fetus with a supraumbilical, large thoracoabdominal wall defect; and type 3, a fetus with an infraumbilical abdominal wall defect with an intact thorax. Nevertheless, the majority of the proposed classifications are based on clinical interpretations of examined cases that form phenotype patterns, making it challenging to definitively classify all cases (14).

LBWC encompasses a spectrum of diseases with diverse phenotypes and varying degrees of severity. All of our cases exhibited extensive thoracoabdominal defects with visceral herniation, which are the most common and severe malformations in LBWC and the main abnormalities observed during ultrasound examinations (20). Limb anomalies have been accepted as a diagnostic criterion for LBWC (8). The rarity of upper limb anomalies in our case series can be attributed to the lower frequency of type I LBWC (21). Limb anomalies encompass a range of structural abnormalities, such as amelia, amputation, hypoplasia of all or part of a limb, and phocomelia of the pelvic limbs, and non-structural abnormalities, including simple clubfoot, arthrogryposis, ankyloses, and limb malrotation. Some authors propose that only severe limb reduction defects (amelia) should be considered as a diagnostic criterion (18, 22). However, other authors have also included minor defects, such as clubfoot, polydactyly, and oligodactyly (8, 23). As the third diagnostic key point, the cranial abnormalities observed in the present study predominantly encompassed exencephaly and encephalocele, both of which are lethal conditions that were detected during early or middle pregnancy. All 37 fetuses with LBWC in the present study displayed spinal developmental abnormalities. It is believed that aplasia or hypoplasia of the paraspinous or thoracolumbar musculature may contribute to the development of scoliosis (17). Extrusion of intra-abdominal contents and adhesion of the fetal abdomen to the placenta may result in restricted movement, causing the fetus to be in a flexed or hyperextended posture, leading to the asymmetric development of the spine.

The fetal appendages should also be carefully observed. The present study involved 23 cases with umbilical cord abnormalities, primarily characterized by a short (<10 cm) umbilical cord and a direct connection of the abdominal protrusion to the placenta (17). Umbilical cord abnormalities causing issues with the fetal blood supply may also contribute to embryonic fusion disorders. The presence of a short or absent umbilical cord and spinal abnormalities may serve as important radiological signs for diagnosing LBWC (1). Another characteristic feature of LBWC is the persistent presence of the extraembryonic coelom, manifested as a large cystic structure or fetal abdominal protrusion at the site of the abdominal wall defect, with the lower half of the body located outside the amniotic cavity. This is due to the failure of the embryo to fold along the craniocaudal and lateral axes to form a cylindrical shape (2).

The diagnosis of LBWC can typically be confirmed via prenatal ultrasound by the end of the first trimester (1, 17, 24). It is essential to conduct a comprehensive anatomical examination of the fetus while measuring nuchal translucency (25, 26). During early pregnancy, the extraembryonic coelom is relatively large, providing a clear view of intra-abdominal organs protruding into the cavity and the abdominal–placental attachment (5). Severe scoliosis can also be readily identified during the first trimester (1, 27). LBWC is accepted as a fatal anomaly and often results in intrauterine fetal demise or early neonatal death (28), making it crucial to distinguish LBWC from other potentially treatable anterior wall defects (2). Gastroschisis is characterized by a small paraumbilical defect on the right side, with the abdominal organs everted into the amniotic cavity. An omphalocele involves a supraumbilical defect with the intestinal loops and liver protruding into the umbilical cord, covered by the peritoneum and amniotic membrane. In bladder and the cloacal exstrophy, the bladder is not visible, and the bowel loops protrude between the two halves of the bladder (4). Fetuses with these malformations typically have normal umbilical cord length and usually do not have spinal and limb developmental abnormalities. However, it is challenging to differentiate between LBWC and amniotic band syndrome (ABS) due to the lack of clear diagnostic criteria (3, 14, 15). ABS is known to occur as a consequence of early amniotic membrane rupture and can present as a wide range of defects, such as craniofacial and limb malformations. Some researchers suggest that ABS and LBWC may belong to the same phenotypic spectrum with overlapping features, while others propose that LBWC is a distinct entity with the amniotic bands produced earlier (15, 29).

This study reviewed cases of LBWC in the past 12 years. Although the sample size was not large and some data were incomplete, the findings contribute to understanding the ultrasound manifestations of LBWC and to expanding the phenotypic spectrum of LBWC. Moreover, since 2018, LBWC has been increasingly detected and diagnosed before the 14th week, a trend attributed to the popularization of nuchal translucency examination. This finding also reflects the progress of ultrasound examination technology in the first trimester of pregnancy and its value in screening serious fetal structural malformations.

LBWC has characteristic ultrasonographic features and can be diagnosed in the first trimester. Accurate prenatal ultrasound assessment is essential to provide clinicians with information needed to counsel future parents about the prognosis of this anomaly.