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Oxidation via CYP2E1 (5-10%) - TOXIC Creates NAPQI (N-acetyl-p-benzoquinone imine)the dangerous toxic metabolite INCREASES by 80% during pregnancy NAPQI measured at 43% HIGHER in first trimester when fetal brain is most vulnerable NAPQI must be immediately neutralized by glutathione When glutathione is depleted, NAPQI causes cellular damage Crosses placenta and damages fetal brain The Perfect Storm During Pregnancy Research reveals dramatic shifts in how pregnant women metabolize acetaminophen: Safe sulfation pathway DECREASES by 33% Toxic oxidation pathway INCREASES by 80% Glutathione levels DROP by 36-87% (when you need it most) Result: 43% MORE toxic NAPQI formed in first trimester Even though glucuronidation increases, it CANNOT compensate for the massive increase in toxic metabolite production combined with dramatically reduced glutathione reserves

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doi:10.1007/s10517-018-4219-2

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doi: 10.1007/s11684-017-0575-y