State of the Science Evaluation for Transgenerational Inheritance of Health Effects

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There is a large body of evidence indicating that early life exposures can lead to disease outcomes later in life. The effects of these exposures are thought to be limited to the exposed generation, such that subsequent generations are unaffected by the exposure history of their parents and grandparents. However, recent reports have suggested that this may not be the case, and that adverse outcomes may be carried over to multiple unexposed generations. This phenomenon is known as "transgenerational inheritance." If the effects of exposure can indeed be transmitted to subsequent generations, this would have major public health implications and therefore is it is critical to determine how widespread and robust the phenomenon.

NTP conducted a state-of-the-science or scoping review to examine the evidence for transgenerational inheritance of health effects associated with exposure to a wide range of stressors (e.g., environmental chemicals, drugs of abuse, nutrition and diet, pharmaceuticals, infectious agents, or stress) in humans and animals. The report systematically collected and categorized the literature to develop a systematic evidence map for transgenerational inheritance by broad health-effect categories, exposures, and types of evidence, and identified areas of consistency, uncertainty, data gaps, and research needs. A subset of studies were assessed for risk of bias (internal validity) to examine general bias and study quality issues for the transgenerational study design.

The scoping review found relatively few bodies of evidence where multiple studies evaluated the same exposure and the same or similar outcomes. Evidence mapping illustrated that risk of bias, having generally few studies, and heterogeneity in exposures and endpoints examined present serious limitations to available bodies of evidence for assessing transgenerational effects. Targeted research is suggested to address inconsistencies and risk of bias issues identified, and thereby establish more robust bodies of evidence to critically assess transgenerational effects—particularly by adding data on exposure-outcome pairs where there is some evidence (i.e., reproductive, metabolic, and neurological effects).