13-cis retinoic acid and neurodevelopment disorders

Abstract

13-cis retinoic acid (13-cis) is a potent teratogen that crosses the placenta and exists in equilibrium with 13-trans retinoic acid (13-trans). Compared to 13-trans, 13-cis is preferentially concentrated in the cell nucleus where it is isomerized to teratogenic 13-trans. In pregnant mothers the plasma 13-cis concentration is highest in the first 8-12 weeks of pregnancy. Neurocognitive impairment even in the absence of any physical defects has been reported to be 30%-60% of children exposed to Isotretinoin (13-cis) during the prenatal period. Genetic variability of CYP26A1 and/or CYP26B1 may be passed onto the fetus and is probably associated with increased maternal and fetal retinoid concentrations. Beta carotene crosses the placenta but may be metabolized and/or stored by the fetus differently than in adults. Measuring maternal retinoids and CYP26A1 and CYP26B1 activities may provide insight into the steep rise in neurodevelopment disorders not explained by improvement in diagnosis.

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