Medically assisted procreation significantly contributes to an increase in twin pregnancies. One of the major factors contributing to more twin births is the use of fertility treatments. Twin pregnancy is not without a risk for fetal organ development and the health outcome of new-borns, children, and adults. Multiple pregnancies are associated with an increased risk of developmental complications, such as perinatal mortality, premature births, and low birth weight. Oxidative stress is involved in pregnancy disorders such as abortion, intrauterine growth retardation, and prenatal mortality. The link between oxidative stress and prenatal development, poorly perceived in the medical community, is a major problem in human reproductive medicine and health outcomes. The sex-based considerations and analyses are also, often neglected in biomedical research. In addition, fetal sexual dimorphism in antioxidant pathways following intrauterine exposure to environmental pollutants has not been explored. This is an important area of research because sexually dimorphic antioxidant adaptive responses to early life exposure-induced oxidative stress may have long-term effects on offspring health outcome and increase the risk of non-communicable diseases in men and women. This concept is useful, since it may open the avenue to develop antenatal antioxidant therapeutic strategies to developmental disorders and complications related to multiple pregnancies, and in association with acute or chronic environmental exposure. This article reviews the status of research, supporting data, possible pathogenic mechanisms, and future perspectives in the proposed area. Birth Defects Research (Part C) 108:351-364, 2016. (c) 2016 Wiley Periodicals, Inc.