The 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 Helsinki, Finland and their mothers. Healthy infants from single births, with gestational age ranging from 35 to 42 weeks, were eligible for the study.

While in the maternity ward, mothers were asked to view a list of all brands of licorice-containing confectionery available in Finland in 1998 and report the brand(s) and frequency of weekly consumption. Glycyrrhizin intake was calculated and categorized into three groups: zero-to-low (0-249 mg/week); moderate (250-499 mg/week); and high (≥ 500 mg/week). Of the mothers in the initial cohort, 75% reported zero-to-low intake; 14%, moderate intake; and 11%, high glycyrrhizin intake.

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."

―Shari Henson

References

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.