Approximately one in 1000 children born in North America is affected with spina bifida, which makes the latter one of the most common and disabling congenital defects. Due to advances in medicine and technology over the past 40 years, the predicted lifespan of a child born with this disability has improved considerably. The focus of treatment now lies in the ongoing medical and rehabilitative management of the disability, including multiple and complex neurological, surgical, orthopaedic, gastrointestinal, and urological surgical procedures, as well as long-term use of orthotic aids and mobility devices and ongoing physiotherapy regimens.
Spina bifida is one of the most common, serious malformations of human structure. At birth, it tends to be more common in girls than in boys. Additionally, the prevalence of spina bifida varies across time, by region, and by both race and ethnicity. Since the early 1980s, estimation of the prevalence of spina bifida in many industrialized countries has been complicated by the availability of prenatal diagnosis and the elective termination of some affected fetuses (Chan et al, 1993). A recognized chromosomal, teratogenic, or Mendelian malformation syndrome can be identified in a small proportion of individuals with meningomyelocoeles (Kallen & Harris, 1998). However, most affected individuals do not have an underlying malformation syndrome. The list of variables that have been implicated as risk factors for the non-syndromic form of spina bifida is long and varied, ranging from maternal consumption of blighted potatoes to a short inter-pregnancy interval. However, most of the associations that have been reported are weak and have not been replicated in subsequent studies. Consequently, only a few variables have been established, or are strongly suspected to be risk factors for spina bifida: history of previous affected pregnancy with same partner, inadequate maternal intake of folic acid, pregestational maternal diabetes, valproic acid and carbamazepine.
A family history of spina bifida or anencephaly is one of the strongest risk factors for these disorders. The risk for spina bifida or anencephaly, or both, in the siblings of affected individuals ranges from 3% to 8% and is consistently higher than that of the general population. An increase in the risk of spina bifida has also been reported for second and third degree relatives of affected individuals (Carter & Evans, 1973). One study has suggested that the risk of having a child with spina bifida or another type of neural tube defect might be increased in couples who have had a child with Down’s syndrome, and the risk of having a child with this syndrome might be increased in couples who have had a child with a neural tube defect (Barkai et al, 2003). It is apparently that additional investigation is needed to confirm or rule out any potential link between these two disorders.
It is generally accepted that inadequate intake of natural folate, or its synthetic form, folic acid, before and during early pregnancy, is associated with an increased risk of spina bifida and anencephaly. Case-control studies, randomized clinical trials, and community-based interventions with vitamin supplements have shown that the failure to consume folic acid supplements or folic acid-containing multivitamins increases the risk of having an affected child by two-fold to eight-fold (Wald et al, 2001). Moreover, the risk of having a child affected by a neural tube defect is indirectly related to both maternal folate and folic acid intake (from dietary sources and supplements) and maternal folate status. The mechanism underlying the association between neural tube defects and folate has not been established. However, folate participates in two metabolic pathways that, if disrupted, could have an adverse effect on the development of the embryo. One of these pathways is important for nucleic acid synthesis, and the other for a range of methylation reactions. Disruptions in folate metabolism can also result in raised homocysteine concentrations, which are teratogenic to the neural tube in some animal models (Wald et al, 2001).
Women with pregestational diabetes are at increased risk of having a child with spina bifida and other types of birth defects (e.g., diabetic embryopathy). In these women the risk of having a child with a malformation of the central nervous system, including spina bifida, is two-fold to tenfold higher than the risk in the general population. The mechanism underlying this teratogenic effect has not been established, but it is clearly related to the degree of maternal metabolic control. Indeed, there is evidence that the risk of congenital malformations in the offspring of diabetic women is associated with first-trimester blood glucose concentrations (assessed by glycosylated haemoglobin concentrations) (McLeod ; Ray, 2002). Whether raised glucose concentrations are directly teratogenic, or whether they serve as a marker for another teratogenic agent (e.g., ketone bodies, free oxygen radicals) is unclear.
Many anticonvulsant drugs are known teratogens. However, different anticonvulsants are associated with different constellations of malformations. An increased risk of spina bifida is associated with in-utero exposure to valproic acid or carbamazepine alone, or in combination with each other or other anticonvulsants. In infants exposed to valproic acid or carbamazepine the risk of spina bifida might be as high as 1%-2%. Women who use these drugs for indications other than epilepsy (e.g., bipolar disease, migraine, chronic pain) are also at increased risk of having a child with spina bifida if they become pregnant while taking these drugs. The mechanisms by which valproic acid and carbamazepine increase the risk of spina bifida have not been established.
Maternal serum ?-fetoprotein and ultrasound are now routinely used to identify fetuses that have or are likely to have either spina bifida or anencephaly. Positive findings from either of these two screens can be followed by amniocentesis or detailed sonography, or both. When amniocentesis is done, amniotic fluid ?-fetoprotein and acetylcholinesterase concentrations can be used to confirm the presence of an open fetal malformation and differentiate between open ventral wall defects (e.g., gastroschisis and omphalocoele) and open neural tube defects (Loft, 1990). Additionally, the fetal karyotype can be examined to rule out chromosomal anomalies. However, sonography can also be used to differentiate between ventral wall and neural tube defects, and to identify additional structural malformations that are characteristic of fetuses with chromosomal abnormalities. When a diagnosis of spina bifida is confirmed, ultrasound is used to assess spontaneous leg and foot motion, leg and spine deformities. Most fetuses with spina bifida that are not electively terminated receive no treatment until after birth. Several studies have investigated whether method of delivery influences the outcome for infants with the disorder. Anteby and Yagel (2003) concluded that, in general, there is no conclusive evidence that caesarean section improves the outcome in children with spina bifida relative to vaginal delivery. However, caesarean section might be justified for large lesions, to reduce the risk of trauma, and is done after in-utero treatment of spina bifida because the forces of labor are likely to produce a dehiscence.
Closure of the spinal lesion is usually done within 48 hours of birth. However, there are data indicating that, with antibiotics, the risk of infection does not rise until a week after birth. If there are overt signs of hydrocephalus, and imaging studies confirm the presence of ventriculomegaly, a shunt is usually placed at the same time as the lesion is closed (Charney, 1985). However, in most cases hydrocephalus is not manifest until a few days after surgical closure. Spina bifida is a disorder that might be suitable for in-utero treatment, since it is compatible with life, is associated with substantial morbidity, and is routinely detected before 20 weeks of gestation. Moreover, neurological deterioration of affected fetuses might occur during gestation. Specifically, leg movement can be seen on sonograms of some affected fetuses before 17 to 20 weeks, whereas later in gestation and in neonates there is typically some degree of deformity and paralysis (Korenromp, 1986). The lower limb movements noted early in gestation could be secondary to spinal are reflexes. However, such movements could be of cerebral origin and their absence in later gestation may be the result of neural tissue damage caused by exposure to amniotic fluid or trauma. Additionally, animal studies, in which a model for spina bifida is created by laminectomy and exposure of the spinal cord to amniotic fluid, show that function can be retained if the lesion is closed before birth (Meuli et al, 1995).
The first cases of in-utero spina bifida repair were done in 1994 with an endoscopic technique (Bruner et al, 1999) that proved unsatisfactory and was abandoned. In 1998, in-utero repair of spina bifida by hysterotomy was reported. Early experience suggested that infants treated by hysterotomy had improvement in hindbrain herniation, and possibly a diminished need for shunting relative to infants treated postnatally. It might be that in-utero treatment reduces the need for shunting by eliminating the leakage of spinal fluid that puts back-pressure on the hindbrain, such treatment allows reduction of the hindbrain hernia and relieves the obstruction of the cerebrospinal fluid outflow from the fourth ventricle.
Compared with historical controls, infants treated in utero have a lower incidence of moderate to severe hindbrain herniation and hydrocephalus requiring shunting. In a series of 50 spina bifida cases treated in utero at the Children’s Hospital of Philadelphia, reversal of hindbrain herniation was reported in all cases, and the proportion requiring shunting was less than that in historical controls (43% versus 85%) (Johnson et al, 1989). A similar proportion requiring shunting (54%) was also noted in a series of 116 spina bifida cases treated in utero at Vanderbilt University Medical Center (Bruner et al, 2004). Comparisons between infants with spina bifida who were treated in utero and historical controls are however subject to substantial bias. Infants treated in utero represent a highly selected subset of affected individuals. Additionally, the medical management of such infants might differ from that of historical controls for reasons unrelated to the in-utero repair.
Short-term and long-term survival of individuals with spina bifida has increased with improvements in medical and surgical management. The most recent population-based data indicate that 1-year survival is about 87%, and that roughly 78% of all individuals with spina bifida survive to the age of 17 years (Wong et al, 2001). Unfortunately, these individuals continue to be subject to excess morbidity and mortality into and throughout adulthood. Whether treated in utero or postnatally, individuals with spina bifida are at substantial risk for leg weakness and paralysis, sensory loss, bowel and bladder dysfunction, and orthopaedic abnormalities (e.g., clubfoot, contractures, hip dislocation, scoliosis, kyphosis). In general, the functional level of the defect corresponds to the anatomical level of the bony spinal defect as determined by radiology. However, a retrospective study published in 2002, noted that functional level was higher (worse) than the anatomic level in 48% of individuals with spina bifida, and lower than the anatomic level in 14% of individuals (Rintoul et al, 2002). Individuals with spina bifida are at risk for associated malformations of the nervous system, including hydrocephalus and Chiari II malformations.
Neonates with spina bifida should have baseline imaging studies of the central nervous system and subsequent serial head measurements to assess the velocity of head growth and the need for shunting. Orthopaedic deformities should also be treated shortly after birth, and ultrasonography and urodynamic studies should be done to assess the status of the urinary tract and provide a baseline for continuing assessment. At this age, bowel function is usually not a substantial difficulty since affected infants have the gastrocolic reflex and pass stools with most feedings. Medical care and monitoring of individuals with spina bifida is best provided by regular assessments by a multidisciplinary team. This team should be under the direction of a skilled physician with training in the care of children who have multiple disabilities, and should include a coordinator who is responsible for patient follow-up. Additional team members should include a nurse specializing in the care of children with multiple handicaps, a paediatric neurosurgeon, urologist and orthopaedic surgeon, a physical therapist, and a social worker. Other sub-specialists should be available on an as needed basis. Team members should be in direct communication with each other and with the patient’s primary care physician, who should provide routine medical care (e.g., immunizations) and continuing emotional support for the family.
As it is well known children with spina bifida have problems with perceptual and cognitive skills, particularly complex visual-spatial tasks involving figure-ground relations, form consistency, spatial memory, and the location of stimuli in space (Fletcher et al. 2000). It has been shown that children with spina bifida demonstrate preserved abilities on measures that include simple visual discrimination and simple spatial relations (Fletcher et al. 2000). For instance, Dennis et al. (2001) found that children aged 6 to 15 years with spina bifida were as adept as matched control individuals in the perception of visual illusions concerned with size, length, and area.
Various studies indicate that parents of disabled patients express a need for greater support on psychosocial aspects of their adolescents’ condition, including a desire for more anticipatory guidance in the areas of vocational/educational training, sexuality, and daily living skills (Samuelson et al, 1992). Therefore, rehabilitation professionals who serve children with spina bifida and their families should help the family by nurturing the youth through stressful periods, and by teaching family members tangible ways to strengthen adaptive functioning. Thus, while the rehabilitation team can help with the important outcomes of functional status and medical management of the condition, effective, family-centered care must also attend to the crucial developmental skill building.
Two major focuses are needed in supporting families that are coping with spina bifida: a lifelong focus and an adolescent-specific focus. In the former, rehabilitation team members must discuss autonomy skills and cognitive development early and continuously to encourage experience in decision-making appropriate for the developmental stage. In addition, it is recommended that rehabilitation professionals assess parents’ need for anticipatory guidance and resources on an ongoing basis. For optimal success, it is crucial that these interventions start early in a child’s life. For example, a toddler can be given options: which shirt to wear, what breakfast cereal to eat, or where to go for a walk. The focus on making appropriate decisions continues through the school years. Moreover, age-appropriate chores should be assigned for all children. Creativity may be needed to develop an appropriate chore for a child with mobility impairments, but the data suggest that this is critical to developing self-sufficiency (Sawin et al., 1999).
Giving the increasing incidence of spina bifida and diversity of its occurrence, the resolution to this dilemma requires two-fold approach. From the critical perspective, it is necessary to focus both on clinical research and simultaneously on the various sociological aspects of disabled patients, particularly their health status, functional status, and health-related quality of life. Simultaneously, the ability of healthcare providers to suggest preventive measures, anticipatory guidance, and wellness approaches to care for individuals with lifelong chronic illness and disability should be stimulated.