Multivitamin supplementation is very important in pregnancy. In addition to being an important requirement for the mother and the fetus, its roll in minimizing the incidence of congenital anomalies is well-known. Vitamin supplementation reduces the risk of the fetus developing cardiovascular and urinary tract defects and oral clefts in addition to neural tube defects (NTDs); but these have to be started before conception. These have been borne out by observational studies and the experimental data showing folic acid antagonists administered in the periconceptional period cause congenital anomalies. The drugs, which are dihydrofolate reductase inhibitors, are well-known to cause defects in the neural tube. Methotrexate, antiepileptics, and trimethoprim are the well-known culprits.
The link between folate deficiency and NTDs was suspected as early as 1964. Animal experiments, clinical, and epidemiologic data confirmed this.
Among women who take periconceptional folate, the incidence of NTDs was 0.9 per 1000 as opposed to the group who did not; the incidence was 3.5 per 1000.
The recommendation is to start folate at least one menstrual cycle before conception and to be continued at least till the tenth week of pregnancy.
The recommended dose for women at low risk is 0.4 mg/day of folic acid supplementation and the dose increases to 4 mg/day in those who are at risk. Both multivitamin medication and dietary supplementation have been advocated. Folic acid is a synthetic form of folate and is more stable and has greater bioavailability than the folate. One milligram of folate in food is equivalent to 0.5 mg of folic acid in food supplement.
The two main instances that result in failure of folate ingestion are unplanned pregnancy and ignorance of the role of folate.
So what can we do? Increase the awareness of the role of folate and recommend dietary supplementation in all women who can conceive.
But what has to be understood is the fact that factors other than folate insufficiency can cause NTDs. Some of the risk factors that have been enumerated are as follows: earlier pregnancy where there was a NTD, partner with NTD, diabetes mellitus, obesity, anticonvulsant medication, relative with NTD, exposure to pesticides, radiation, lead, anesthetic agents, and tobacco smoke.
Most of the NTDs occur in women with no prior history (family or personal) of NTD. This brings up the fact that NTDs are not wholly preventable by folate alone, since other factors are at play too.
Many loose ends have to be tied up in this issue. The issue of fortification vs supplementation is still unanswered. Folate usage is not without side effects, its association with cardiovascular diseases is well- known.
Great service can be done by educating women in the child-bearing age and probably this will be the significant factor in reducing the incidence of NTDs.
Further Readings
Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608-14.
Milunsky A, Jick H, Jick SS, Bruell CL, MacLaughlin DS, Rothman KJ, et al. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. JAMA 1989;262:2847-52.
Dunlap B, Shelke K, Salem SA, Keith LG. Folic acid and human reproduction-ten important issues for clinicians. J Exp Clin Assist Reprod 2011;8:2.
Heseker HB, Mason JB, Selhub J, Rosenberg IH, Jacques PF. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid. Br J Nutr 2009;102:173-80.
Cohen AR, Robinson S. Early management of myelomeningocele. in Pediatric Neurosurgery. 4thed. WB Saunders Company; 2001. p. 241-61.