Räikkönen K, Pesonen A-K, Heinonen K, et al. Maternal licorice consumption and detrimental cognitive and psychiatric outcomes in children. Am J Epidemiol. 2009 Nov 1;170(9): 1137-1146.
Glucocorticoids are essential for brain development; however, elevated levels are detrimental, affecting neuronal division, maturation, migration, interactions, and apoptosis.1 In utero, overexposure to glucocorticoids may later cause detrimental effects in children as they develop. Normally, fetal cortisol levels are two to 10 times lower than maternal levels.2 Glycyrrhizin [consistently misrepresented in the article as "glycyrrhiza"], a constituent of licorice (Glycyrrhiza glabra), inhibits the feto-placental 11beta-hydroxysteroid dehydrogenase type 2 enzymatic "barrier" to higher maternal levels of cortisol. These authors studied whether prenatal exposure to glycyrrhizin in licorice exerts detrimental effects on cognitive performance and psychiatric symptoms in young Finnish children.
children initially were part of a random, population-based urban cohort of
1,049 infants born between March 1, 1998, and November 30, 1998, in
the maternity ward, mothers were asked to view a list of all brands of
licorice-containing confectionery available in
No differences were noted in prenatal, perinatal, or maternal characteristics, or birth weight, birth anthropometry, or gestation length among the three groups.
In 2006, children and their parents were invited to participate in a follow-up study to examine physical and psychological development of the children. Of the initial cohort, 922 (87%) could be contacted. Of those, a subsample was invited for follow-up. All 89 children belonging to the group prenatally exposed to high levels of glycyrrhizin in licorice were invited; 64 participated. Of the 271 children exposed to zero-to-low glycyrrhizin levels, 211 participated. Of the 54 invited children exposed to moderate glycyrrhizin levels, 46 participated. After cancellations and exclusions, data on psychiatric symptoms were gathered for 298 children, and cognitive data were gathered on 309 children.
The study used a neuropsychological test battery including vocabulary, similarities, block design, and symbol search subtests of the Wechsler Intelligence Scale for Children III, the Beery Developmental Test of Visual-Motor Integration, and the narrative memory subtest of A Developmental Neuropsychological Assessment for the children. The mothers completed the Child Behavior Checklist, which screens for emotional, social, and behavioral problems.
The authors report that children of mothers who consumed high amounts of glycyrrhizin in licorice confections performed significantly more poorly in the cognitive tests than did those of mothers consuming zero-to-low amounts. Children of mothers in the high consumption group scored -0.38 standard deviations (SDs) lower in vocabulary, -0.41 SDs lower in similarities, -0.31 SDs lower in block design, and -0.34 SDs lower in narrative memory tests (P ≤ 0.03). No differences were reported between the moderate-exposure group and the zero-to-low group in any cognitive test result (P > 0.52).
The authors further report that children of mothers who consumed high amounts of glycyrrhizin scored significantly higher in externalizing symptoms, even after adjustment for covariates (0.40 SD, 95% confidence interval [CI], 0.11-0.69; P = 0.008; fully adjusted P = 0.02) and total behavioral problems (0.45 SD, 95% CI, 0.16-0.74; P = 0.002; fully adjusted P = 0.003), than did offspring of mothers consuming zero-to-low amounts. Also after adjusting for covariates, their risk of borderline clinically significant externalizing symptoms, rule-breaking behavior problems, attention problems, aggressive behavior problems, attention deficit hyperactivity disorder, and somatic complaints increased significantly (P < 0.05). The moderate-exposure group did not differ from the zero-to-low group regarding psychiatric symptoms (P > 0.08).
The authors explain the enzymatic inhibition and other possible mechanisms by which the consumption of glycyrrhizin in licorice might affect fetal brain development. They conclude that "high maternal licorice consumption during pregnancy is associated with poorer cognitive performance and with externalizing symptoms and attention problems in offspring 8.1 years of age."
1Seckl JR, Meaney MJ. Glucocorticoid programming. Ann N Y Acad Sci. 2004;1032:63-84.
2Blasco MJ, López Bernal A, Turnbull AC. 11 beta-Hydroxy-steroid dehydrogenase activity of the human placenta during pregnancy. Horm Metab Res. 1986;18(19):638-641.