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Decades ago, when David Barker1 introduced the developmental origins of health and disease (DOHaD) conceptual model and later demonstrated that the prenatal period is relevant for future well-being, he could not have envisioned that fetal brain imaging would substantiate his claims or that maternal stress would be a potent prenatal exposure affecting health outcomes. Barker’s focus was inadequate maternal nutrition, to which he hypothesized fetuses adapt, resulting in programmed changes in physiology and metabolism that contribute to disease risk in adulthood, including coronary heart disease and the related disorders stroke, diabetes, and hypertension.1 Briefly, lower birth weight, which was viewed as a proxy for nonoptimal maternal nutrition, was found to be associated with increased risk for coronary heart disease years later.1 When the DOHaD approach was applied to national health records from the World War II–era Dutch Famine and neurodevelopment was added as a disease outcome—showing, for example, far higher rates of schizophrenia in men who had been in utero during the famine rather than the months before or after it—maternal stress was not considered as an additional exposure factor.2 In the 21st century, DOHaD researchers pivoted, ultimately establishing stress, depression, and anxiety as maternal experiences affecting child prenatal and future development, although to be sure, much of this research was based on maternal report of child outcomes such that the mother was both the source of the independent variable (mood state in pregnancy, often associated with postpartum mood state) and dependent variable (child temperament and emotional or behavioral symptoms) years later.3 Wu et al3 build on prior DOHaD research4 to make substantial contributions to prenatal programming science, with implications for ways to transform the prenatal care ecosystem for 2generation impact. Wu et al3 have 4 key findings. First, higher self-reported perceived stress during pregnancy was inversely associated with the cognitive development domain of the Bayley Scales of Infant Development administered by a licensed psychologist at 18 months old. Second, the volume of the left hippocampus imaged months earlier during gestation accounted for 11% of this association. Third, other characteristics of fetal brain development were associated with 18-month-old development; specifically, local gyrification index was inversely associated with competence, and sulcal depth was inversely associated with infant social-emotional development and competence. Wu et al3 indicate that their prior work4 showed that maternal distress is associated with gyrification and sulcal depth, thus suggesting that maternal mental health affects the fetal brain and child outcomes. Fourth, perceived stress during pregnancy was positively associated with parenting stress at 18 months post partum. This study by Wu et al3 incorporates cutting-edge neuroscience into DOHaD neurodevelopmental research by directly assessing fetal brain development and showing that it mediates the association between maternal prenatal stress and child cognition and is relevant to other domains of functioning nearly 2 years later. A key outcome associated with maternal stress, cognitive functioning at 18 months, is observer based, consistent with other recent findings5 that strengthen the rigor of DOHaD research using maternal prenatal mood as an exposure variable. Finally, with the positive associations between prenatal and postnatal distress, Wu et al3 control for postnatal parenting stress in their models, elegantly isolating prenatal stress as the active agent in + Related article