33.4 ETHICAL CONSIDERATIONS IN PRENATAL NUTRITIONAL INTERVENTIONS FOR SCHIZOPHRENIA

Abstract

Background: Prenatal nutrients to prevent mental illnesses are a subclass of primary prevention‐population‐wide interventions to reduce risk of illness in an entire population. The increased incidence of schizophrenia after prenatal exposure to famines, including famines where caloric intake was adequate but nutrients were not, is epidemiological indication that nutrients may have preventive effects. Prenatal folate to prevent spina bifida is the model. This intervention does not identify or target “at riskâ€� pregnancies, because incident cases of spina bifida, like mental illness, are multifactorial and unpredictable. Only 50% of women take prenatal vitamins during pregnancy, with fewer initiating folate at conception when it is most effective. Therefore, folate is added to foods consumed by the entire population to attempt to protect fetuses whose mothers do not take prenatal vitamins. Methods: Currently docosahexaenoic acid (DHA) and choline are being studied as prenatal nutrients to prevent various conditions including mental illnesses. Results: Ethical issues include balancing effectiveness in reducing the incidence for people who might have developed illness, versus the side effects and cost for the majority of the population who would never have become ill. Although the burden of mental illness falls most heavily on those who are ill, families and society as a whole are also burdened. Thus, there is some additional justification for population‐wide intervention. A similar issue is raised by immunizations: measles is fatal in newborns and influenza is harmful to fetuses, who cannot be immunized. Therefore, the population's “herd immunityâ€� is promoted by immunization campaigns, although for many people these illnesses are benign. For prevention of schizophrenia, the decades between birth and illness pose additional problems in assessing benefit, but nutrients have earlier, broader positive effects on behavior and cognition beginning in childhood, providing further justification for their use. For prenatal choline, positive effects on cognition have been recorded as long as 7 years after birth. Early childhood problems in behavior and cognition are problematic in themselves, and in some children, they are also early manifestations of schizophrenia. Broad effects raise the challenge of balancing effects on different aspects of development. DHA initiated at third trimester is effective for infantile asthma, but first trimester‐initiated DHA slightly increases the risk of ADHD. Randomized clinical trials present additional ethical challenges. The placebo group needs to have adequate nutrients, including full information and access to the nutrient under study. For the treated group, full effects will not be known for decades. The feasibility of preliminary studies to select optimal doses and gestational timing, analogous to the early Phase 2 studies of investigational drugs, is limited without immediate feedback of results to shape larger definitive trials. Thus, for many nutrients, decades of pregnancies may occur without definitive guidelines for either parents or physicians to decide whether a particular intervention is safe and effective. Conclusions: Fetal developmental problems may not inevitably presage mental illness, but neither can later interventions reverse these early defects. Therefore, improving prenatal prevention has its own ethical imperative.