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Intrauterine fetal demise affects between 0.4-0.8% of pregnancies worldwide. This significant adverse pregnancy outcome continues to be poorly understood. In utero exposure to substances increases the risk of stillbirth to varying degrees according to the type of substance and degree of exposure. The aim of this qualitative narrative review is to investigate common biologic relationships between stillbirth and maternal substance use.Methods:   A PubMed literature search was conducted to query the most commonly used substances and biologic mechanisms of stillbirth. Search terms included “stillbirth,” “intrauterine fetal demise,” “placenta,” “cocaine,” “tobacco,” “alcohol,” “methamphetamines,” “opioids/ opiates,” and “cannabis.”Results:   There are very few studies identifying a direct link between substance use and stillbirth. Several studies demonstrate associations with placental lesions of insufficiency including poor invasion, vasoconstriction, and sequestration of toxic substances that inhibit nutrient transport. Restricted fetal growth is the most common finding in pregnancies complicated by all types of substance use.Discussion:   More research is needed to understand the biologic mechanisms of stillbirth. Such knowledge will be foundational to understanding how to prevent and treat the adverse effects of substances during pregnancy.

Investigating Mechanisms of Stillbirth in the Setting of Prenatal Substance Use