Omphalocele-exstrophy of the bladder-imperforate anus-spinal defects (OEIS) complex or cloacal exstrophy (EC), describes a rare grouping of more commonly occurring component malformations [Carey et al., 1978]. The etiology is unknown, but likely heterogeneous. While postnatal identification of its associated gastrointestinal, spinal, and genitourinary systems delineates the extent and natural history of OEIS complex, prenatal findings may provide additional information regarding early detection, possible causative factors, and outcome. The purposes of this study were to: (1) present the prenatal ascertainment of OEIS complex in this series of 15 cases identified through several different sources compared to the literature, and (2) discuss the relationship of these prenatal findings to possible abnormal developmental mechanisms causing OEIS complex. These 15 cases indicate that OEIS complex may be difficult to diagnose prenatally, and that the full extent of abnormalities may not be clear until postnatal exam. Confusion with limb-body wall complex (two of our cases) and pentalogy of Cantrell (one of our cases) can occur. Anal/gastrointestinal malformations and genital ambiguity are under-ascertained. Conversely, prenatal defects may resolve postnatally, yet may provide clues for pathogenetic mechanisms. For instance, the finding of nuchal thickening in our three cases (one reported) suggests vascular/hemodynamic compromise early in embryologic development, or intrathoracic compression leading to jugular lymphatic obstruction may play a role. The association of twinning and OEIS complex suggests they may occur as early as blastogenesis. Our three sets of discordant twins also suggest a non-genetic etiology for OEIS complex of uteroplacental insufficiency. This study also indicates that OEIS complex may be more common than previously thought.