Reproductive Issues in Anorexia Nervosa

Elizabeth R Hoffman; Stephanie C Zerwas; Cynthia M Bulik


Expert Rev of Obstet Gynecol. 2011;6(4):403-414. 

In This Article

Five-year View

Prenatal nutrition status in women with anorexia nervosa is important in light of research on 'fetal programming', or the 'developmental origins of health and disease'. From a fetal programming perspective, environmental influences on fetal development during sensitive periods could significantly affect the organization of physiology and lead to long-term, and perhaps permanent, effects on the structure and functioning of organs.[114–116] Fetal environmental influences, depending on their timing and severity affect the long-term physical and mental health of offspring.

The two main processes proposed to underlie fetal programming (fetal undernutrition and overexposure to stress hormones)[117] overlap considerably with the core features of anorexia nervosa (poor nutrition and anxiety).[32] Maternal malnutrition during pregnancy is associated with increased risk for obesity, coronary heart disease, metabolic disease and stroke in adult offspring.[115,116,118] Furthermore, infants born with surrogate markers of maternal undernutrition, including low birthweight and being small for gestational age, are also at increased risk for diminished cognitive function, behavioral problems, stress reactivity and psychopathology throughout their lifespan.[114]

High levels of maternal anxiety and neuroendocrine (cortisol) indices of stress response during the prenatal period predict greater anxiety and cortisol stress response in infants, preadolescent children and young adults.[22,119–121] Poor nutrition and protein restriction during pregnancy interact with the maternal hypothalamic–pituitary–adrenal axis, which results in increased fetal exposure to maternal cortisol.[122] Thus, the synergistic effects of maternal malnutrition and anxiety due to anorexia nervosa could extend beyond the intrauterine environment and result in long-term effects on their children's wellbeing.[32] Furthermore, women with anorexia nervosa report experiencing anxiety during pregnancy related to their fear that their child may be damaged physically by their poor nutrition.[22]

Epigenetics may explain the processes by which maternal nutrition and anxiety lead to long-term effects. Epigenetics refers to any factor that affects gene expression caused by mechanisms other than the genome. Identified epigenetic mechanisms include DNA methylation, histone modification and small-interfering RNA.[123] Epigenetic modifications are thought to be dynamic and the prenatal and early postpartum period is considered a critical window.[124] Animal studies demonstrate that prenatal nutrition, specifically micronutrient deficiencies, can alter gene expression through methylation mechanisms. Micronutrients such as vitamins B2, B6, and B12, folate, methionine and choline are required for methylation of DNA.[125] If micronutrients are deficient during pregnancy, offspring are more likely to display impaired CNS development and an increased risk of obesity. These effects of malnutrition on DNA methylation extend to the human epigenome as well. Individuals whose mothers experienced the Dutch Famine early in gestation had less DNA methylation of the imprinted IGF-2 gene,[126] although their birthweight was within a normal range. Moreover, these epigenetic marks may be heritable, and risk for disease can be passed on to subsequent generations.[127] The effects are not limited just to immediate offspring but can be passed on to grandchildren.[128–131]

In the Norwegian cohort, 50% of women with anorexia nervosa reported an unplanned pregnancy,[132] and prenatal vitamin consumption prior to conception or in very early pregnancy was unlikely. Only 29% of women with anorexia nervosa took a supplement containing folic acid in the 2 months prior to conception.[37] Depending on their nutritional status before conception, women with anorexia nervosa may be at increased risk for micronutrient deficiencies that have been linked to long-term and transgenerational fetal effects. Thus, only focusing rapid weight gain in women with anorexia nervosa, with little attention to macronutrient and micronutrient quality, prior to conception and during pregnancy may be insufficient to protect against possible long-lasting fetal programming effects of a poor-quality diet.


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