Maternal Licorice Consumption and Detrimental Cognitive and Psychiatric Outcomes in Children

Abstract

At critical phases of brain development, elevated concentrations of glucocorticoids are detrimental. Maintenance of low glucocorticoid levels during these periods of brain development is ensured by the action of the placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which catalyzes the rapid inactivation of maternal cortisol. A constituent of licorice, glycyrrhiza, inhibits this enzyme, thereby raising fetal glucocorticoid brain levels. In preclinical studies with rodent models, consumption of licorice was shown to have detrimental affective and cognitive effects. Licorice consumption is common among young women in several countries. A previous study in pregnant women reported that prenatal exposure to a high level of glycyrrhiza was associated with a slightly shorter duration of gestation. This study was designed to investigate whether prenatal overexposure to glucocorticoids through maternal consumption of licorice had detrimental effects on cognitive and behavioral performance and other measures of brain function in 321 Finnish children 8.1 years of age. These children had been healthy singletons delivered at 35 to 42 weeks of gestation. Cognitive function and psychiatric assessment were measured using components of several established tests including the Wechsler Intelligence Scale for Children III, the Children's Developmental Neuropsychological Assessment, the Beery Developmental Test of Visual-Motor Integration, and the Child Behavior Checklist. Compared with children of mothers who consumed 0-low glycyrrhiza (0-249 mg/wk), those of mothers who consumed high amounts (≥500 mg/wk) scored -0.38, -0.41, -0.31, and -0.34 standard deviations lower in cognitive tests evaluating vocabulary, similarities, block design, and narrative memory tests, respectively (P < 0.03). High maternal consumption of glycyrrhiza was associated with significantly increased psychiatric symptoms; these included increases in externalizing symptoms (P < 0.04) and in attention, rule-breaking and aggression problems (odds ratios, 3.43, 2.15, and 2.74, respectively, P < 0.05). These findings show that high maternal licorice consumption during pregnancy is associated with poorer cognitive performance and a number of psychiatric symptoms in offspring 8.1 years of age. The investigators recommend that pregnant woman should be advised to avoid foodstuffs containing excessive amounts of glycyrrhiza.