including spontaneous abortion, stillbirth, preterm delivery, and birth defects (Hemminki et al., 1980; McDonald et al., 1987; Ahlborg et al., 1989; Savitz et al., 1989; Fenster and Coye, 1990; Restrepo et al., 1990; Goulet and Theriault, 1991; Correa-Villasenor et al., 1991; Lin et al., 1994; Nurminen et al., 1995; Blatter and Roeleveld, 1996; Blatter et al., 1996). In addition, recent studies have investigated maternal dioxin exposure and neurological development among offspring (Koopman-Esseboom et al., 1996). Another study found no association between potential Agent Orange exposure and risk of gestational trophoblastic disease among women living in Vietnam (Ha et al., 1996). The quality and results of these studies have been mixed. A major limitation of nearly all the studies is the determination of specific exposures. Many studies have defined exposure based solely on employment in agricultural occupations. Exposure to specific chemicals and other agents in these agricultural settings is usually not ascertained. Further, problems such as incomplete ascertainment of the outcome of interest, selection of inappropriate or no control groups, and failure to account for confounding factors have limited some of this work. Improvements in study design, especially exposure assessment, should allow for a more definitive evaluation of the relationship between herbicide exposure and adverse reproductive outcomes among women.

The remainder of this chapter discusses the following specific categories of reproductive effects: birth defects, fertility, stillbirth, neonatal and infant death, and low birthweight and preterm birth. For most outcomes, a brief summary of the scientific evidence in VAO and Update 1996 is presented, followed by a review of the recent scientific literature.

BIRTH DEFECTS

Background

The March of Dimes defines a birth defect as ''an abnormality of structure, function or metabolism, whether genetically determined or as the result of an environmental influence during embryonic or fetal life" (Bloom, 1981). Other terms often used interchangeably with birth defects are "congenital anomalies" and "congenital malformations." Major birth defects are usually defined as those abnormalities that are present at birth and severe enough to interfere with viability or physical well-being. Major birth defects are seen in approximately 2 to 3 percent of live births. An additional 5 percent of birth defects can be detected with follow-up through the first year of life. Given the general frequency of major birth defects of 2 to 3 percent and the number of men who served in Vietnam (2.6 million), if one assumes that they had at least one child, it has been estimated that 52,000 to 78,000 babies with birth defects have been fathered by Vietnam veterans, even in the absence of an increase due to exposure to herbicides or other toxic substances (Erickson et al., 1984a). The cause of most birth defects is



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