Amniotic Band Syndrome

Etiology

Several proposed amniotic band syndrome etiologies exist, including intrinsic and extrinsic mechanisms. The most accepted mechanism is extrinsic, and it is theorized that early amnion rupture traps fetal parts between the amnion and chorion.[2] The cause of rupture is unknown, but it may be related to abnormal embryologic development or trauma.[3] Not all cases are associated with membrane disruption, and bands are often not visualized on prenatal ultrasound.[3]

Other proposals do not encompass the full spectrum of amniotic band syndrome but include etiologies such as local tissue developmental errors or vascular injury leading to band formation between the inflamed, hypoperfused tissue and the amnion.[4] Genetic etiologies have been explored, as rare familial and twin cases have been reported.[4] However, complete details on individual presentations are lacking, and when karyotyping was available, chromosomal studies were normal.[5][6]

Indeed, the underlying cause may be heterogeneous; however, amniotic band syndrome is not considered a hereditary or genetic condition. There is an association between invasive fetal procedures and amniotic band syndrome, referred to as post-procedural amniotic band disruption sequence. Single case reports describe amniotic band formation following routine amniocentesis and thoracoamniotic shunt placement; however, the phenomenon is more frequently documented after fetoscopic laser surgery in monozygotic twin pregnancies.[7][8][9] In case studies of twin pregnancies requiring treatment with fetoscopic laser surgery, there is an approximately 1% to 3% rate of post-procedural amniotic band disruption sequence. This risk appears to be increased when procedures are performed at earlier gestational ages, when the rates of chorion-amnion separation are higher, as the membrane layers may not be completely fused, wherein a lax amnion layer forms adhesive bands.[7]

Epidemiology

Given the broad range of clinical presentations related to amniotic band syndrome, the incidence is challenging to specify. Estimates range from 1 in 1200 to 15,000 live births.[10] Data from the European Surveillance of Congenital Anomalies registry, which includes all births, reported a prevalence of 0.53 per 10,000 births from 1980 to 2019.[4] There are no apparent sex differences. The incidence is significantly higher among stillbirths (110 in 1000), which is related to the catastrophic effects amniotic bands can have on umbilical cord constriction.[4][8][11] In a case series of nearly 30 cases, the majority of defects resulting from amniotic band syndrome involved extremities (71%), followed by umbilical cord (25%) and complex abdominal wall defects (17.9%).[3]

Pathophysiology

The effects and severity of amniotic band syndrome likely depend on where the amniotic bands exist relative to the fetus. The adverse events likely result from constricting bands or rings that disrupt normal development, crowd or tether fetal parts, and disrupt normally developed structures.[12] This results in heterogeneous phenotypes with varying severity. Smaller peripheral bands are more likely to cause extremity defects, whereas broad bands spanning the uterine cavity may lead to major consequences, including complex abdominal wall defects.[3] 

History and Physical

Amniotic band syndrome may be suspected after incidental prenatal ultrasound findings or anomalies identified postnatally. Amniotic band syndrome-related defects can be seen as early as the first trimester. This diagnosis should be considered in the setting of stillbirth, as well as unusual abdominal wall or cranial defects presenting along with limb constriction or amputation.

Prenatally, as with any congenital disability, the parental history should be reviewed for any personal or family history of congenital disabilities and teratogenic exposures. Due to the postulated mechanism of amniotic membrane disruption, the pregnant patient should also be asked about any clinical signs of membrane rupture and history of intrauterine procedures. Postnatally, in addition to the genetic and exposure histories, the neonate should undergo a complete physical examination with particular attention to the umbilical cord, digits and extremities, face, and head. Careful tracking of all defects and evaluation for gross evidence of fibrous strands is paramount.

Evaluation

Prenatally, patients should be referred to a maternal-fetal medicine consultation for a detailed anatomy ultrasound. This evaluation includes a thorough inspection of the fetal anatomy, with a specific assessment for amniotic bands. Moving the maternal patient during the ultrasound examination may unveil a fixed fetal position, which may suggest tethering or entrapment from amniotic bands. Fetal magnetic resonance imaging can be a useful complementary diagnostic tool in complex cases or for those considering intervention for amniotic band release, as ultrasound has a higher detection rate.[13]

Clinical presentation of amniotic band syndrome can be classified into 4 major categories:

• Constriction bands
• Limb defects
• Neural tube defects
• Craniofacial defects [3]

Constriction rings and limb or digital amputation are the most common findings. The amniotic bands may or may not be visible. Sonographically, amniotic bands appear as hyperechoic, thin, and linear structures. Color Doppler can be applied to demonstrate a lack of vascular flow within the suspected amniotic band. If constriction results in amputation in utero, a small remnant is produced, appropriately termed the "vestige sign."[14] Limb defects can include constriction rings, edema, absence of distal portions of 1 or more fingers and toes, clubbed feet and hands, pseudosyndactyly, contractures, and fractures. Upper extremities are affected more often.[5] If more than 1 limb is affected, the presentation is typically asymmetric. Color Doppler should be applied to all extremities of concern to evaluate perfusion proximal, at, and distal to the constriction. A grading system is used to classify the degree of limb involvement, guiding intervention.[15]

• Class 1: No signs of constriction
• Class 2a: No or mild lymphedema
• Class 2b: Severe lymphedema
• Class 3a: Abnormal distal Doppler studies
• Class 3b: No vascular flow to the extremity
• Class 4: Bowing or fracture of long bones
• Class 5: Intrauterine amputation

While less common, craniofacial abnormalities may be present, such as encephalocele, anencephaly, facial clefts, cleft lip/cleft palate, orbital involvement, and meningocele. These are often asymmetric and not along suture lines. Chest and abdominal wall defects have also been described, which include ectopia cordis, rib clefts, bowel extrusion, omphalocele, and bladder exstrophy. Spinal defects and scoliosis have been known to occur with amniotic band syndrome.[5]

Postnatally, amniotic band syndrome should be suspected in newborns with visible constrictions, amputations, and non-midline and unusually located craniofacial or body wall defects. There is frequent ocular involvement, such as microphthalmos, hypertelorism, ptosis, corneal opacities, eyelid colobomas, and lacrimal outflow obstruction.[16] Investigating the fresh fetal membranes and placenta can reveal amniotic bands, which should be examined in newborns with these findings.[8]

Treatment / Management

There are no established guidelines for managing amniotic band syndrome, and surveillance is individualized. All patients should receive counseling about identified anomalies and the possibility of additional undiagnosed abnormalities due to ultrasound's limitations in detecting all possible congenital disabilities and genetic syndromes. Pregnant individuals should continue receiving prenatal care with increased fetal surveillance, which often includes serial ultrasound evaluation of fetal growth and monitoring of affected areas. 

The in-utero intervention of fetoscopic amniotic band lysis with laser or cold scissors can potentially slow the progression of constriction effects and restore normal blood flow to the downstream structures, which may salvage an at-risk limb or prevent stillbirth in the setting of a compromised umbilical cord.[15] There is a hypothesis that fetal limb recovery may be more likely after fetal intervention than after postnatal recovery due to the plasticity of tissue healing during fetal life.(B3)

However, the efficacy of this intervention is unknown, as there are no established criteria for candidate selection and a lack of clinical studies.[17] The primary risk associated with fetoscopic band release is preterm premature rupture of membranes, which affects 51% of cases in a recent systematic review. This results in a compounded risk of preterm delivery of over 70%. More than 75% of neonates in this study had preserved function of the affected limb; however, in 21.2% of cases, the limb required amputation postnatally to allow for prostheses.[18] Additional risks include fetal injury, intrauterine bleeding, and infection. (A1)

Postnatal management includes a thorough physical examination, multidisciplinary consultation with appropriate surgical teams, and, if needed, imaging studies to determine the extent of amniotic band syndrome. Relief of constriction rings postnatally, with excision of all scarred tissue, may help salvage some limb function. Vascular comprise diagnosed postnatally may require urgent surgical intervention.

Differential Diagnosis

Due to the heterogeneous consequences of amniotic band syndrome, there is a broad differential diagnosis for this condition, which includes the following:

• Body stalk anomaly: This is often accompanied by significant scoliosis, short umbilical cord, and adherence of the abdominal wall to the placenta.[19]
• Open defects: Major organ anomalies in the setting of amniotic band syndrome are often oblique and asymmetric and in the presence of additional limb abnormalities.
  • Anencephaly: Proptotic orbits
  • Cephalocele
  • Acrania/acalvaria
  • Cleft lip
  • Gastroschisis
  • Omphaloceles
• Amniotic sheets: Normal fetal anatomy; these sheets do not entrap fetal parts
• Chorioamniotic separation: Never entraps fetal parts
• Transverse limb deficiency: Distal limb defects due to vascular insults, no visible bands present
• Skeletal dysplasia: Characteristic skeletal findings are typically seen in conjunction with abnormal fetal growth measures
• Congenital varicella syndrome: Associated with maternal infection and limb defects present in a dermatomal distribution, which is often symmetric
• Caudal regression sequence: Symmetrically affects the lower extremities
• Teratogenic effects: Eg, thalidomide requires maternal exposure and often spares the head and face
• Trisomy 18: Associated with craniofacial abnormalities and limb defects; evaluate maternal age and history of prior aneuploidy screening

Prognosis

The prognosis of a newborn affected by amniotic band syndrome depends entirely on the extent of defects, from minor cosmetic defects to lethal involvement of vital organs. Patient counseling must be tailored to the fetal and neonatal clinical presentation resulting from amniotic band syndrome, which may require discussion of the termination of pregnancy and neonatal palliative care. A multidisciplinary approach involving fetal and neonatal teams is crucial for providing insight into potential interventions, functioning, and quality of life.

Isolated constriction alone is associated with good prognoses and normal life expectancies. There is a report of a resolved case of amniotic band syndrome affecting the fetal elbow, where extremity edema was resolved, and blood flow was preserved.[1] On the contrary, umbilical cord involvement is a significant risk factor for stillbirth. In a case series, 4 out of 5 stillbirths had amniotic band syndrome involving the umbilical cord.[3] Overall, there is an increased risk of premature preterm rupture of membranes and preterm birth, which is potentiated in the presence of abdominal wall defects. If present, the mean gestational age at delivery is 33.6 weeks, and there is an increased risk of low birth weight.[3][15]

Complications

As previously mentioned, the complications related to amniotic band syndrome depend on the extent of the fetal anomalies. Obstetric complications include stillbirth, preterm premature rupture of membranes, preterm birth, and low birth weight.