We say “drug use of interest” because one of the main difficulties in the field of substance use during pregnancy is polysubstance abuse. Most women who use drugs during pregnancy use more than one drug and this is especially true for illegal substances. Women who use cocaine or methamphetamine during pregnancy often also use tobacco, alcohol and marijuana and to a lesser extent, opiates. Among legal prenatal substance users, alcohol and tobacco are often used together. The problem of polydrug use is problematic because very little is known about how drug interactions and combinations affect fetal development and, in order to isolate the effects of a specific drug large sample sizes are needed. With a large sample size there may be enough statistical power and variability among various combinations of drugs to be able to covary or adjust the effects of the drug of interest for the effects of other drugs. However, the complexity and expense of brain imaging studies usually precludes samples that have the statistical power to adjust for covariates. For example, Rivkin35 found an initial effect for
