Michael R. Harrison worked as a pediatric surgeon in the US throughout the late-twentieth century and performed many fetal surgeries, including one of the first successful surgeries on a fetus in utero, or while it is still in its gestational carrier’s body, also called open fetal surgery. A fetus is an organism developing inside of the uterus that is anywhere from eight weeks old to birth. Harrison hypothesized that open fetal surgery could correct developmental defects that may become fatal to the fetus at birth. After years of research, Harrison and his colleagues at the University of California, San Francisco, in San Francisco, California, performed surgery on the fetus of a woman in her seventh month of pregnancy to correct the fetus’s developmental defects. The surgery was successful, as the fetus developed into a healthy child. Harrison’s work led to advancements in fetal treatment techniques, such as a method to conduct open fetal surgery that will not harm the fetus or pregnant woman, as well as the establishment of one of the first fetal treatment centers in the US.

In 1996, Michael R. Harrison published “Fetal Surgery” in the American Journal of Obstetrics and Gynecology. In the article, Harrison describes the importance of fetal surgery and the techniques used to correct defects in fetuses. As a fetus develops in the uterus, it can develop abnormalities that may become debilitating or fatal. Harrison discusses cases that show how physicians can use fetal surgery to repair such abnormalities, including obstructions in the heart or urinary tract, or organs or muscles whose malformations impair function. Harrison states where knowledge is lacking within the field or where surgery would be inappropriate, such as in the modification of a cleft lip, which can be fixed after birth and as such does not merit the risks of surgery. In the article, Harrison provides a summary of what information existed about fetal surgeries in 1996, which helped physicians explore fetal surgery and make further advancements.

In March 1996, the National Academy of Sciences of the United States released 'Veterans and Agent Orange Update 1996: Summary and Research Highlights,' which summarized research on the health effects of Agent Orange and other herbicides used in the Vietnam War. In their 1996 report, the National Academy connects Agent Orange exposure with two health conditions: spina bifida, a birth defect that occurs when the spinal cord develops improperly, and peripheral neuropathy, a nervous system condition in which the peripheral nerves are damaged. Spina bifida was the first birth defect to linked to Agent Orange exposure. The resulting disability compensation for affected children, as a result of the conclusions in the 1996 report, marked the first time that the US Veterans Administration addressed the health outcomes of veterans' families, and not exclusively veterans themselves.

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.

Endoscopic fetoscopy is a minimally invasive surgical procedure performed during pregnancy that allows physicians to view the fetus in-utero. Physicians use endoscopic fetoscopy to evaluate, diagnose, and treat fetal abnormalities. Physicians use an endoscope, or a thin, flexible surgical device with a light attached to its end, to perform endoscopic fetoscopy procedures. In 1954, Björn Westin performed the first endoscopic fetoscopy in Sweden. Since Westin’s initial development of the procedure, interest in endoscopic fetoscopy has grown throughout the early part of the twenty-first century. In addition, the use of endoscopy has expanded beyond fetal medicine and has been introduced to other fields of medicine such as general surgery. Endoscopic fetoscopy allows surgeons to diagnose and correct fetal abnormalities that would otherwise result in fetal death before delivery or in lifelong impairment if treatment were delayed until after delivery.

In 2015, the Public Broadcasting Service, or PBS, released a three-part documentary series, Twice Born–Stories from the Special Delivery Unit, hereafter Twice Born, that follows several pregnant women and their experiences with fetal surgery. Trailblazer Studios produced the film, which predominantly features two women, although it includes the stories of many women. The two main women are pregnant with fetuses diagnosed with physical deformities. One woman’s fetus is diagnosed with spina bifida, an incomplete closure of the fetus’s spinal column. The other woman’s fetus is diagnosed with an oral teratoma, a tumor of the mouth. All the pregnant women in the series went to the Children’s Hospital of Philadelphia, or CHOP, in Philadelphia, Pennsylvania, to have in utero surgery to correct the fetus’s birth defects. Twice Born examines the benefits and risks of performing surgery on a fetus still in the pregnant woman’s uterus. Due to the popularity of PBS, the documentary reached a wide audience and brought the topic of in utero surgery to the public’s attention.

In 1984, J. David Erickson and his research team published the results of a study titled 'Vietnam Veterans' Risks for Fathering Babies with Birth Defects' that indicated that Vietnam veterans were at increased risk of fathering infants with serious congenital malformations, or birth defects. Researchers at the Centers for Disease Control (CDC) in Atlanta, Georgia, conducted the study to address Though the study's results were inconclusive, the study was one of the first to document a possible association between Vietnam War service and spina bifida, a lower back birth defect in which the spinal cord does not form properly. Later research established the links between Agent Orange exposure and various birth defects and led the US Department of Veterans Affairs to offer disability compensation for Vietnam veterans and their families who were affected by Agent Orange exposure.

In 1988, the US Centers for Disease Control published 'Health Status of Vietnam Veterans III. Reproductive Outcomes and Child Health,' which summarized part of the results of the Vietnam Experience Study commissioned by US Congress to assess the health of US Vietnam veterans. They published the article in the Journal of the American Medical Association. The most heavily used herbicide in the Vietnam, Agent Orange, had previously been found to contain a contaminant linked to birth defects in rats. By comparing the health of Vietnam War veterans exposed to Agent Orange in Vietnam to those serving elsewhere, researchers determined that veterans who served within Vietnam more frequently reported health problems for themselves and their children, but were not at increased risk of fathering children with birth defects. Later studies overturned that latter conclusion and definitively linked Agent Orange exposure to later birth defects. The article represented the first attempt by the US government to ascertain the full risk of birth defects posed by Agent Orange, which eventually culminated in 1997 when the US Veterans Administration compensating the families of Vietnam veterans for Agent Orange-related birth defects.

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.