alcohol misuse can trigger macrocytosis which discards folate. after stopping the drinking of alcohol, a time period of months is needed to rejuvenate bone marrow and recover from the macrocytosis. those who are white or hispanic have a higher risk. girls are more prone to being born with spina bifida. pathophysiology spina bifida occurs when local regions of the neural tube fail to fuse or there is failure in formation of the vertebral neural arches. neural arch formation occurs in the first month of embryonic development (often before the mother knows she is pregnant). some forms are known to occur with primary conditions that cause raised central nervous system pressure, raising the possibility of a dual pathogenesis. in normal circumstances, the closure of the neural tube occurs around the 23rd (rostral closure) and 27th (caudal closure) day after fertilization. however, if something interferes and the tube fails to close properly, a neural tube defect will occur. medications such as some anticonvulsants, diabetes, obesity, and having a relative with spina bifida can all affect the probability of neural tube malformation. extensive evidence from mouse strains with spina bifida indicates that there is sometimes a genetic basis for the condition. human spina bifida, like other human diseases, such as cancer, hypertension and atherosclerosis (coronary artery disease), likely results from the interaction of multiple genes and environmental factors. research has shown the lack of folic acid (folate) is a contributing factor in the pathogenesis of neural tube defects, including spina bifida. supplementation of the mother's diet with folate can reduce the incidence of neural tube defects by about 70%, and can also decrease the severity of these defects when they occur. it is unknown how or why folic acid has this effect. spina bifida does not follow direct patterns of heredity as do muscular dystrophy or haemophilia. studies show a woman having had one child with a neural tube defect such as spina bifida has about a 3% risk of having another affected child. this risk can be reduced with folic acid supplementation before pregnancy. for the general population, low-dose folic acid supplements are advised (0.4 mg/day). prevention there is neither a single cause of spina bifida nor any known way to prevent it entirely. however, dietary supplementation with folic acid has been shown to be helpful in reducing the incidence of spina bifida. sources of folic acid include whole grains, fortified breakfast cereals, dried beans, leaf vegetables and fruits. however it is difficult for women to get the recommended 400 micrograms of folic acid a day from unfortified foods. globally, fortified wheat flour is credited with preventing 50 thousand neural tube birth defects like spina bifida a year, but 230,000 could be prevented every year through this strategy. folate fortification of enriched grain products has been mandatory in the united states since 1998. this prevents an estimated 600 to 700 incidents of spina bifida a year in the u.s. and saves $400 - $600 million in healthcare expenses. the u.s. food and drug administration, public health agency of canada and the uk department of health and social care (dhsc) recommended amount of folic acid for women of childbearing age and women planning to become pregnant is at least 0.4 mg/day of folic acid from at least three months before conception, and continued for the first 12 weeks of pregnancy. women who have already had a baby with spina bifida or other type of neural tube defect, or are taking anticonvulsant medication, should take a higher dose of 4–5 mg/day. certain mutations in the gene vangl1 have been linked with spina bifida in some families with a history of the condition. screening open spina bifida can usually be detected during pregnancy by fetal ultrasound. increased levels of maternal serum alpha-fetoprotein (msafp) should be followed up by two tests – an ultrasound of the fetal spine and amniocentesis of the mother's amniotic fluid (to test for alpha-fetoprotein and acetylcholinesterase). afp tests are now mandated by some state laws (including california) and failure to provide them can have legal ramifications. in one case, a man born with spina bifida was awarded a $2-million settlement after court found his mother's obgyn negligent for not performing these tests. spina bifida may be associated with other malformations as in dysmorphic syndromes, often resulting in spontaneous miscarriage. in the majority of cases, though, spina bifida is an isolated malformation. genetic counseling and further genetic testing, such as amniocentesis, may be offered during the pregnancy, as some neural tube defects are associated with genetic disorders such as trisomy 18. ultrasound screening for spina bifida is partly responsible for the decline in new cases, because many pregnancies are terminated out of fear that a newborn might have a poor future quality of life. with modern medical care, the quality of life of patients has greatly improved. three-dimensional ultrasound image of the fetal spine at 21 weeks of pregnancy treatment there is no known cure for the nerve damage caused by spina bifida. standard treatment is surgery after delivery. this surgery aims to prevent further damage of the nervous tissue and to prevent infection; pediatric neurosurgeons operate to close the opening on the back. the spinal cord and its nerve roots are put back inside the spine and covered with meninges. in addition, a shunt may be surgically installed to provide a continuous drain for the excess cerebrospinal fluid produced in the brain, as happens with hydrocephalus. shunts most commonly drain into the abdomen or chest wall. pregnancy standard treatment is after delivery. there is tentative evidence about treatment for severe disease before delivery while the baby is inside the womb. as of 2014, however, the evidence remains insufficient to determine benefits and harms. treatment of spina bifida during pregnancy is not without risk. to the mother, this includes scarring of the uterus. to the baby, there is the risk of preterm birth. broadly, there are two forms of prenatal treatment. the first is open fetal surgery, where the uterus is opened and the spina bifida repair performed. the second is via fetoscopy. these techniques may be an option to standard therapy. childhood most individuals with myelomeningocele will need periodic evaluations by a variety of specialists: physiatrists coordinate the rehabilitation efforts of different therapists and prescribe specific therapies, adaptive equipment, or medications to encourage as high of a functional performance within the community as possible. orthopedists monitor growth and development of bones, muscles, and joints. neurosurgeons perform surgeries at birth and manage complications associated with tethered cord and hydrocephalus. neurologists treat and evaluate nervous system issues, such as seizure disorders. urologists to address kidney, bladder, and bowel dysfunction – many will need to manage their urinary systems with a program of catheterization. bowel management programs aimed at improving elimination are also designed. ophthalmologists evaluate and treat complications of the eyes. orthotists design and customize various types of assistive technology, including braces, crutches, walkers, and wheelchairs to aid in mobility. as a general rule, the higher the level of the spina bifida defect, the more severe the paralysis, but paralysis does not always occur. thus, those with low levels may need only short leg braces, whereas those with higher levels do best with a wheelchair, and some may be able to walk unaided. physical therapists, occupational therapists, psychologists, and speech/language pathologists aid in rehabilitative therapies and increase independent living skills. transition to adulthood although many children's hospitals feature integrated multidisciplinary teams to coordinate healthcare of youth with spina bifida, the transition to adult healthcare can be difficult because the above healthcare professionals operate independently of each other, requiring separate appointments, and communicate among each other much less frequently. healthcare professionals working with adults may also be less knowledgeable about spina bifida because it is considered a childhood chronic health condition. due to the potential difficulties of the transition, adolescents with spina bifida and their families are encouraged to begin to prepare for the transition around ages 14–16, although this may vary depending on the adolescent's cognitive and physical abilities and available family support. the transition itself should be gradual and flexible. the adolescent's multidisciplinary treatment team may aid in the process by preparing comprehensive, up-to-date documents detailing the adolescent's medical care, including information about medications, surgery, therapies, and recommendations. a transition plan and aid in identifying adult healthcare professionals are also helpful to include in the transition process. further complicating the transition process is the tendency for youths with spina bifida to be delayed in the development of autonomy, with boys particularly at risk for slower development of independence. an increased dependence on others (in particular family members) may interfere with the adolescent's self-management of health-related tasks, such as catheterization, bowel management, and taking medications. as part of the transition process, it is beneficial to begin discussions at an early age about educational and vocational goals, independent living, and community involvement. certain locations feature multidisciplinary clinics in order to offer coordinated care between specialists, such as cincinnati children's center for spina bifida. epidemiology rates of other types of spina bifida vary significantly by country from 0.1 to 5 per 1000 births. on average in developed countries it occurs in about 0.4 per 1000 births. in the united states it affected about 0.7 per 1000 births, and in india about 1.9 per 1000 births. part of this difference is believed to be due to race, with caucasians at higher risk, and part due to environmental factors. it is most common in the celtic people (12.5 per 10,000 live births), and it is rare in asians and people of african descent. in the united states, rates are higher on the east coast than on the west coast, and higher in white people (one case per 1000 live births) than in black people (0.1–0.4 case per 1000 live births). immigrants from ireland have a higher incidence of spina bifida than do natives. highest rates of the defect in the usa can be found in hispanic youth. the highest incidence rates worldwide were found in ireland and wales, where three to four cases of myelomeningocele per 1000 population have been reported during the 1970s, along with more than six cases of anencephaly (both live births and stillbirths) per 1000 population. the reported overall incidence of myelomeningocele in the british isles was 2.0–3.5 cases per 1000 births. since then, the rate has fallen dramatically with 0.15 per 1000 live births reported in 1998, though this decline is partially accounted for because some fetuses are aborted when tests show signs of spina bifida (see pregnancy screening above). history although hippocratic doctors were aware of developmental abnormalities involving the lower spine, the first person to describe a spinal spina bifida was a persian physician named al-razi (rhazes, 865–925 ad). he gave the earliest accurate account of the morbid anatomy associated with spina bifida. research 1980 – fetal surgical techniques using animal models were first developed at the university of california, san francisco by michael r. harrison, n. scott adzick and research colleagues. 1994 – a surgical model that simulates the human disease is the fetal lamb model of myelomeningocele (mmc) introduced by meuli and adzick in 1994. the mmc-like defect was surgically created at 75 days of gestation (term 145 to 150 days) by a lumbo-sacral laminectomy. approximately 3 weeks after creation of the defect a reversed latissimus dorsi flap was used to cover the exposed neural placode and the animals were delivered by cesarean section just prior term. human mmc-like lesions with similar neurological deficit were found in the control newborn lambs. in contrast, animals that underwent closure had near-normal neurological function and well-preserved cytoarchitecture of the covered spinal cord on histopathological examination. despite mild paraparesis, they were able to stand, walk, perform demanding motor test and demonstrated no signs of incontinence. furthermore, sensory function of the hind limbs was present clinically and confirmed electrophysiologically. further studies showed that this model, when combined with a lumbar spinal cord myelotomy leads to the hindbrain herniation characteristic of the chiari ii malformation and that in utero surgery restores normal hindbrain anatomy by stopping the leak of cerebrospinal fluid through the myelomeningocele lesion. surgeons at vanderbilt university, led by joseph bruner, attempted to close spina bifida in 4 human fetuses using a skin graft from the mother using a laparoscope.