Could adding folic acid to salt curb Ethiopia’s sky-high rate of spinal cord deformities?

This article was originally posted on ScienceMag

Tony Magana, chief of neurosurgery at Mekelle University School of Medicine in Ethiopia’s Tigray province, confronts his country’s high prevalence of neural tube defects nearly every day. His team operates on more than 400 babies annually to repair these severe, often lethal birth malformations, in which babies can be born without brains or with their spinal cords protruding from their backs. “Probably every other day we see a child that is so bad we can’t help them,” Magana says. The holes where the spinal cord protrudes “are so big that you can’t close them.”

This month, a team of nutrition experts converged in Addis Ababa to lay groundwork for an unproven but possibly highly effective intervention: fortifying Ethiopia’s salt supply with folic acid, a synthetic form of the B vitamin folate. In the first 4 weeks of pregnancy, folate is essential to proper closure of the neural tube, which gives rise to the brain and spinal cord, and since the mid-1990s, more than 80 countries have mandated flour fortification with folic acid. Ethiopia, where fewer than one-third of people eat flour, is not among them.

Last year, a pair of studies that surveyed births at 11 public hospitals there shook the global health community. The studies—one co-authored by Magana—found that among every 10,000 births, between 126 and 131 babies suffered from neural tube defects (NTDs). That’s seven times their global prevalence and 26 times the prevalence in high-income, flour-fortifying countries such as the United States. According to Ethiopian government data, 84% of Ethiopian women of reproductive age have folate levels in their red blood cells that put them at risk of giving birth to a child with an NTD.

“These numbers from Ethiopia are some of the worst anywhere and ever,” says Marinus Koning, a retired surgeon who is founder of ReachAnother Foundation, a charity based in Bend, Oregon, that has supported the training of dozens of Ethiopian neurosurgeons in the past 10 years. “Everybody knows something needs to be done about it.”

At the invitation of the Ethiopian Ministry of Health, Koning and scientists from the United States, Canada and the Netherlands began to work with experts at the Ethiopian Public Health Institute (EPHI) to develop a plan to address the high NTD incidence. The result was an issue brief released by EPHI in May, titled “Preventing Neural Tube Defects in Ethiopia”, that recommended the government consider salt fortification.

The prospect is winning praise from affected families. “We need prevention more than any intervention,” says Beza Haile, founder of the Addis Ababa–based advocacy group HOPE-Spina Bifida and Hydrocephalus. Haile’s 4-year-old son, Hezkiel, who has an NTD, can’t talk, walk, sit, or eat, except foods that are the consistency of soft porridge.

A method of fortifying salt—spraying it with buffered folic acid solution—had already been developed by chemical engineer Levente Diosady and colleagues at the University of Toronto in Canada. The same spraying equipment used for iodization of salt, already mandated in Ethiopia to prevent intellectual disabilities and thyroid disease, can deliver the folate. “One of the main reasons this project is moving forward and there is a lot of political support for it is it requires few adaptations,” says Christine McDonald, a micronutrient scientist at Children’s Hospital Oakland Research Institute in California.

McDonald was part of the team that visited Addis Ababa this month. There, the team met with potential funders and with Hakan Kolenoğlu, chief executive of the country’s leading salt processor, SVS Salt Production PLC in Semera. Kolenoğlu on the spot promised to fortify, free of charge, 40 tons of salt for preliminary studies.

With initial funding from ReachAnother (more will be needed from other funders, the team says), researchers will test whether folate-fortified salt is stable in Ethiopian environmental conditions and whether its sensory qualities, including a slight yellowish tinge, are acceptable to Ethiopians. If the answers are encouraging, fortified salt’s effects on the gold standard measurement of folate sufficiency—red blood cell folate levels—will be put to the test in a randomized, controlled, double-blind trial of hundreds of women of reproductive age.

“There is no scientific evidence that adding [folic acid] to salt could improve the folate status of women,” says Masresha Tessema, a nutritionist at EPHI’s Food Science and Nutrition Research Directorate who was first author on the issue brief and is the Ethiopian lead on the studies. “The ministry needs evidence.”

If salt supplementation works, it could be game-changing for Ethiopia: A meta-analysis this year concluded that large-scale folic acid food fortification in low- and middle-income countries has lowered the risk of NTDs by 41%. “We have an amazing opportunity to do a lot of good,” says Kenneth Brown, the lead U.S. scientist on the team that met in Addis Ababa. Brown, an emeritus professor at the University of California, Davis, who was until recently a senior nutrition scientist at the Bill & Melinda Gates Foundation, adds: “It’s shovel ready. We know what the problem is. We know how to fix it.”

Other experts hope an Ethiopian success story could spur efforts in more than 110 other countries that don’t mandate food fortification. Says Nicholas Wald, an epidemiologist at University College London, who in a seminal 1991 paper established that taking 4 milligrams of folic acid daily, before and in early pregnancy, reduces the risk of NTDs by about 80%: “It’s a global issue of which Ethiopia is an extreme example. Loads of countries should be fortifying a staple food with folic acid and aren’t.”

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