Spina bifida (SB) occurs in one in 2000 live births and leads to lifelong and devastating physical disabilities including paraplegia, hydrocephalus, incontinence, sexual dysfunction, skeletal deformations, and mental impairment (1). Compelling experimental evidence shows that the neurological deficit associated with open SB is not entirely caused by the primary defect of neurulation, but rather that amniotic fluid causes chemical trauma that progressively damages the exposed unprotected fetal neural tissue during gestation. Timely in utero repair of SB in fetal sheep stops the ongoing spinal cord destruction and rescues neurologic function by the time of birth (2).
In late-gestation human fetuses and in neonates with SB, the neural tissue elements show severe traumatic and degenerative alterations, or there is almost complete loss of neural tissue (3). Sonographic reports of human fetuses with very large SB lesions and normal leg movements early in gestation imply that motor function is present initially and lost only later in gestation (4). We report the first successful in-utero surgical repair of open SB in an early gestation fetus.
A 27-year-old woman was referred for assessment of a 23-week gestation fetus with thoracolumbosacral SB. The lesion was first detected on a 20-week ultrasound performed because of an elevated maternal serum alpha-fetoprotein level. Serial ultrasound demonstrated good leg movements, and karyotype by amniocentesis was normal. Ultrafast fetal MRI revealed a SB lesion extending from thoracic level 11 to sacral level 1, Arnold-Chiari type II malformation, and borderline hydrocephalus (the fetal lateral ventricles measured 10 mm). The mother declined pregnancy termination and consented to surgery.
Maternal general anesthesia provided fetal anesthesia and uterine relaxation for open fetal surgery. A low transverse maternal laparotomy and vertical hysterotomy were performed (5). The cystic membrane of the SB lesion was excised, and skin flaps were developed to close the defect and protect the developing spinal cord. Amniotic fluid was replaced with warmed lactated Ringer's solution and the uterine and laparotomy wounds were closed. Postoperatively, tocolysis was maintained with magnesium sulfate intravenous infusion and indomethacin rectal suppositories, followed by terbutaline given by a subcutaneous pump. She was discharged from the hospital five days postoperatively.
At 3D-weeks gestation, preterm labor led to the cesarean-section delivery of a 1.3 kg baby boy who required a short period of ventilatory support. The mother recovered uneventfully. The baby showed excellent left leg function except for absent plantar flexion of the foot (L5Ievel). A right club foot was present, but the baby had right hip and knee flexion and extension (IA level). Postnatal MRI confirmed that the repaired SB lesion extended from Tll to S1 and revealed that the Arnold-Chiari type II malformation was no longer present and there was no hydrocephalus. He has met all developmental milestones at 12 months of age.
Neonates with thoracolumbar SB are almost invariably paraplegic and have associated hydrocephalus that requires a lifelong shunt. This case demonstrates that early gestation fetal surgical repair of severe SB can save neurological function. By arresting the neural destruction, prenatal coverage may also allow rearrangements of function due to the plasticity of the developing nervous system. In addition, the resolution of the Arnold-Chiari malformation after in utero SB repair suggests that this brain malformation is a secondary consequence of SB.
In utero SB repair may thus obviate the complications of Arnold-Chiari malformation including the need for shunt procedures after birth. Our experience with nine subsequent cases has corroborated these findings.
Adzick NS, Sutton LN, Crombleholme TM, Flake AW: Successful fetal surgery for spina bifida. Lancet 352: 675-1676, 1998. Read the abstract »
Meuli M, Meuli-Simmen C, Hutchins GM, Seller MJ, Harrison MR, Adzick NS. The spinal cord lesion in human fetuses with myelomeningocele: Implications for fetal surgery. J Pediatr Surg 1997; 32: 448-452. Read the abstract »
Meuli M, Meuli-Simmen C, Hutchins GM, Yingling CD, Hoffman KM, Harrison MR, Adzick NS. In utero surgery rescues neurological function at birth in sheep with spina bifida. Nature Medicine 1995; 1: 342-347. Read the abstract »
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