Maternal Licorice Consumption During Pregnancy and Pubertal, Cognitive, and Psychiatric Outcomes in Children.
Earlier puberty, especially in girls, is associated with physical and mental disorders. Prenatal glucocorticoid exposure influences the timing of puberty in animal models, but the human relevance of those findings is unknown. We studied whether voluntary consumption of licorice, which contains glycyrrhizin (a potent inhibitor of placental 11β-hydroxysteroid dehydrogenase type 2, the "barrier" to maternal glucocorticoids), by pregnant women was associated with pubertal maturation (height, weight, body mass index for age, difference between current and expected adult height, Tanner staging, score on the Pubertal Development Scale), neuroendocrine function (diurnal salivary cortisol, dexamethasone suppression), cognition (neuropsychological tests), and psychiatric problems (as measured by the Child Behavior Checklist) in their offspring. The children were born in 1998 in Helsinki, Finland, and examined during 2009-2011 (mean age = 12.5 (standard deviation (SD), 0.4) years; n = 378). Girls exposed to high maternal glycyrrhizin consumption (≥500 mg/week) were taller (mean difference (MD) = 0.4 SD, 95% confidence interval (CI): 0.1, 0.8), were heavier (MD = 0.6 SD, 95% CI: 0.2, 1.9), and had higher body mass index for age (MD = 0.6 SD, 95% CI: 0.2, 0.9). They were also 0.5 standard deviations (95% CI: 0.2, 0.8) closer to adult height and reported more advanced pubertal development (P < 0.04). Girls and boys exposed to high maternal glycyrrhizin consumption scored 7 (95% CI: 3.1, 11.2) points lower on tests of intelligence quotient, had poorer memory (P < 0.04), and had 3.3-fold (95% CI: 1.4, 7.7) higher odds of attention deficit/hyperactivity disorder problems compared with children whose mothers consumed little to no glycyrrhizin (≤249 mg/week). No differences in cortisol levels were found. Licorice consumption during pregnancy may be associated with harm for the developing offspring.
Katri
K
Räikkönen
Silja
S
Martikainen
Anu-Katriina
AK
Pesonen
Jari
J
Lahti
Kati
K
Heinonen
Riikka
R
Pyhälä
Marius
M
Lahti
Soile
S
Tuovinen
Karoliina
K
Wehkalampi
Sara
S
Sammallahti
Liisa
L
Kuula
Sture
S
Andersson
Johan G
JG
Eriksson
Alfredo
A
Ortega-Alonso
Rebecca M
RM
Reynolds
Timo E
TE
Strandberg
Jonathan R
JR
Seckl
Eero
E
Kajantie
D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced*; D015992:Body Mass Index; D002648:Child; D015986:Confounding Factors, Epidemiologic; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006035:Glycyrrhiza / Q000009:adverse effects*; D019695:Glycyrrhizic Acid / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007360:Intelligence / Q000187:drug effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012463:Saliva / Q000737:chemistry; D017678:Sex Distribution; D012741:Sexual Maturation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D019695:Glycyrrhizic Acid; D003907:Dexamethasone
11β-hydroxysteroid dehydrogenase type 2; ADHD; cognition; glucocorticoids; glycyrrhizin; puberty