Folic acid: the strongest evidence in this whole section
One of the very few things where the answer is simple and the trial evidence is real.
Almost everything in this guide comes with a caveat. This does not.
In a randomized trial of women planning a pregnancy, a daily multivitamin containing 0.8 mg of folic acid, started at least one month before conception, produced six neural tube defects in the 2,052 control pregnancies and none in the 2,104 vitamin pregnancies. All congenital malformations together fell from 22.9 per 1,000 to 13.3 per 1,000.
In a separate randomized trial of 1,817 women who had already had a pregnancy affected by a neural tube defect, folic acid cut recurrence by 72%: 6 affected pregnancies in the folic acid groups against 21 in the others (relative risk 0.28, 95% confidence interval 0.12 to 0.71). The other vitamins tested showed no significant protective effect.
The Task Force's evidence review found no statistically significant harms across twelve observational studies covering 1.24 million people.
Start before you conceive, not when the test is positive. The neural tube closes in the first four weeks after conception, often before a woman knows she is pregnant. That is the entire reason this is a preconception recommendation rather than a prenatal one.