Tag: folic acid supplementation

Recommendation for Valproic Acid Restricted Use in Ethiopia

prenatal ultrasound of myelomeningocoel
Prenatal ultrasound showing fetus with lumbar myelomeningocoel

Given the already highest incidence of neural tube defects measured globally present in Ethiopia it would seem exceedingly urgent to immediately call for the cessation of use of Valproic acid, which has been shown to cause neural tube defects,  in women of child bearing age in Ethiopia except for special circumstances.

History of Valproic Acid

Valproic acid was first produced in 1882. At that time its discoverer did not imagine that would be any therapeutic use because it was thought to have no pharmacological value. Then in the 1960s it was begun to be used in France and then in the late 1970s was approved for use in the United States as a primary drug for first epilepsy and then also for migraine headaches as well as mood disorders.

Over the next thirty years, however, concerns began to be raised about the potential relationship of the drug and birth defects.  Both a joint European study and a separate French study showed that women of child bearing age taking appropriate therapeutic doses of 1000 mg a day or more had a high incidence of neural tube defects and other malformations up to seven times higher than the control population.

Valproic Acid Use in Ethiopia

The use of Valproic acid is relatively new in Ethiopia in just the last few years. A review of the treatment of epilepsy from Gondar University showed that 4.84 % of patients were using it. In addition it is being used to treat mood disorders and migraine headache to an unknown extent. The prescription of this medicine is relatively unrestricted and can be done by general practitioners and even non-physician health care providers. Unfortunately the official formulary for Ethiopia briefly mentions that pregnancy is a contraindication and suggests consideration for folic acid supplementation should be given to reduce the risks of birth defects. However a recent animal model study using chick embryos showed that supplemental folic acid for neural tube defects caused by valproic acid was not effective in prevention.

Neural Tube Defects in Ethiopia

Our research at Mekelle University looking at the incidence of neural tube defects in the Tigray region of Northern Ethiopia suggested an over all incidence of at least 130 per 10,000 births but with some locals reporting close to 300 per 10,000 births. We know from studies done by the Ethiopian Institute of Public Health that 28% of women of children bearing age throughout Ethiopia have a significant folic acid deficiency which is likely the strongest contributing factor to the high incidence of neural tube defects

Recommendations for Valproic Acid Restriction in Ethiopia

1.Given the already highest incidence of neural tube defects measured globally present in Ethiopia it would seem exceedingly urgent to call for the immediate cessation of use of Valproic acid in women of child bearing age except for situations where no other drug can be used and the patient is receiving implantable or injectable forms of birth control.

2. Prescription of Valproic acid should only be done by physician sub-specialists in neurology, neurosurgery, or psychiatry and should require extensive counseling to the patient.

3.The formulary of Ethiopia should be modified and vigorously amended to warn of the risks. Although consideration for folic supplementation is appropriate it should be clearly stated that such supplementation may not be effective in preventing birth defects.

 

Difficulties in Preventing Neural Tube Defects in Ethiopia

Ethiopian mother hold her child with lumbar myelomeningocoel

The Mekelle University Multidisciplinary Research Group for Neural Tube Defects has just published its first research paper in Brain & Development Journal July 2018, “Maternal Risk Factors Associated with Neural Tube Defects in the Tigray Region of Ethiopia”. This being the first major prospective study done on neural tube defects in Ethiopia confirmed our worst fears of a very high incidence, significantly higher than the 75 per 10,000 births seen in most of Sub-Saharan Africa. There a many challenges in how this problem can be addressed involving cultural beliefs and practices, poverty, diet diversity, supplementation, and fortification.  Unfortunately, applying a Western style solution for Ethiopia will not be so easy or likely to succeed as well.

For the past decade the development of neurosurgery in Ethiopia has witnessed the high incidence of neural tube defects including myelomeningocoel and anencephaly coming to their clinics first in Addis Ababa but now also in Mekelle, Gondar, Bahir Dar, and Oromia. Previous published reports noted incidences first of greater than 160 per 10,000 births in Addis with a more recent report of 191 per 10,000 births in Addis Ababa. The reports of up 300 per 10,000 in some areas of Tigray are higher than those reported in any other developing countries.

Research replicated in nine countries in the 1960s and 1970s showed that neural tube defects were somewhat but no totally related to lack of folic acid in the diet and that adding folic acid would significantly reduce the incidence of neural tube defects. At first attempts were made with prescribing supplementation for women of childbearing age but this did not have the desired result. The incidence really came down in Europe and the United States when the government mandated the fortification of folic acid in food staples like bread and cereals

One of the factors we identified was that a lack of diet diversity increased the risk for NTDS while increased diversity reduced it. About 65% of the diet of most Ethiopians is enjera bread made at home from teff and boiled chick peas called shiro.   Although a serving of raw chick peas has about 1000 micrograms of folic acid its likely that boiling them reduces the folic acid to basically nothing.   A similar situation exists for spinach which is often boiled and eaten during the rainy season.

Traditionally, Ethiopians avoid eating fresh vegetables and fruits as documented in our study and many previous others. In fact a study of the one hundred most elite Ethiopian runners showed that 20% had a significant folic acid deficiency which correlated with lack of dietary diversity (avoiding greens and fruit). In the countryside where the women may spend many hours a day just to get 5 gallons of water, there is not much water to spare for cleaning produce. The population fears getting diarrheal illness from such produce.

Our study showed that of more than 13,000 women interviewed who were pregnant essentially none of them had any knowledge of preconceptional nutritional needs or about neural tube defects. 

Convincing Ethiopians to take medication for invisible illness such as hypertension has proved difficult. Research in many parts of Ethiopia has shown for example that as few as 50% of those prescribed medication for hypertension actually take it. There exists underlying fears of addiction to “un-natural” substances. Will Ethiopian women be convinced to take supplementation?

Ethiopians especially the 88% who live in country side rarely buy food staples like bread but instead make their own enjera from stored teff. Currently there is only one factory in the country capable of making fortified bread but it is not functioning.

The cost of a months supply of folic acid 4 milligrams per day is about 80 birr or about $2.40 US for a single woman. Given the fact that the average family makes about 250 birr per month to support a family of six, there is little room to allow payment of this expense. There are no current domestic producers of folic acid so considerable hard foreign currency would need to be mobilized to import stock. For the government to provide this for every women of child bearing age would cost tens of millions of dollars to be added to the budget of a country which currently spends the equivalent of about $13 per capita for the 100 million population.

Ultimately addressing the issue of the high incidence of neural tube defects in Ethiopia will be requiring taking into account cultural norms and practices in such a way that changes are seen as consistent with Ethiopian culture.  Widespread public education and a major investment in folic acid purchases by the government will be necessary. This begins with the clear realization that there is a problem.