Sprayed extensively by the US military in Vietnam, Agent Orange contained a dioxin contaminant later found to be toxic to humans. Despite reports by Vietnamese citizens and Vietnam War veterans of increased rates of stillbirths and birth defects in their children, studies in the 1980s showed conflicting evidence for an association between the two. In 1996, the US National Academy of Sciences reported that there was evidence that suggested dioxin and Agent Orange exposure caused spina bifida, a birth defect in which the spinal cord develops improperly. The US Department of Veterans Affairs' subsequent provision of disability compensation for spina bifida-affected children marked the US government's first official acknowledgement of a link between Agent Orange and birth defects. By 2016, spina bifida and related neural tube defects were the only birth defects associated with Agent Orange.

Spina bifida is a birth defect that affects the spines of developing fetuses and infants, and research in the 20th century indicated that chemicals in the herbicide Agent Orange likely lead to the birth defect. People with spina bifida can have nerve damage, paralysis, and mental disabilities. During the Vietnam War in the 1960s, the US military employed Agent Orange and other herbicides to destroy enemy crops and forest cover until 1970. Though studies of the link between Agent Orange exposure and birth defects were at first inconclusive, in 1995 the US National Academy of Sciences concluded that one birth defect, spina bifida, was associated with paternal Agent Orange exposure. Spina bifida was, by the twenty-first century, the only birth defect that the US Veterans Administration connected to Agent Orange exposure.

From 1993 to 1995 researchers led by Robert J. Berry from the US Centers for Disease Control headquartered in Atlanta, Georgia, and Zhu Li from Beijing Medical University in Beijing, China, conducted a collaborative study in China on the prevention of neural tube defects or NTDs using folic acid supplements. NTDs are birth defects in which openings in the spinal cord or the brain that occur during early development remain after birth. Neural-tube formation occurs in early pregnancy, often before a woman knows she is pregnant and therefore before she has begun taking prenatal vitamins. The researchers presented their findings in the article “Prevention of the Neural Tube Defects with Folic Acid in China” published in 1999 in The New England Journal of Medicine. The researchers from The China-US study found that women who took folic acid in the periconceptional period, or the time before conception through the first twenty-eight days after conception, reduced the occurrence of NTDs.