Excretion of Antipsychotics Into the Amniotic Fluid, Umbilical Cord Blood, and Breast Milk: A Systematic Critical Review and Combined Analysis.

BACKGROUND:Antipsychotics are being increasingly prescribed during pregnancy and in the postpartum period. However, knowledge regarding the ability of antipsychotics to enter the fetal, newborn, and infant circulation presents inconsistencies. Evidence for penetration ratios in an array of matrices will contribute to further studies examining the mechanistic pathway from antipsychotic use to adverse events. METHODS:A systematic literature search of PubMed and EMBASE was performed to identify studies assessing the concentrations of antipsychotics in maternal blood (serum or plasma), amniotic fluid, umbilical cord blood, and/or breast milk. The penetration ratios were estimated by dividing the antipsychotic concentrations in the target matrix (ie, amniotic fluid, umbilical cord blood or breast milk) by the maternal concentration. Data are provided in means with ranges or SD depending on data availability. RESULTS:Forty-nine eligible studies were identified. For amniotic fluid, the penetration ratios were estimated for quetiapine, clozapine, and flupentixol, with quetiapine displaying the highest ratio (mean 0.59, range 0.09-1.70 versus 0.56, range 0.31-0.82 for clozapine and 0.24, range 0.23-0.24 for flupentixol). For umbilical cord blood, olanzapine had the highest ratio (mean 0.71 ± 0.42) followed by haloperidol (mean 0.66 ± 0.40) and paliperidone (mean 0.53, range 0.50-0.58). In case of breast milk, the highest ratio was observed for amisulpride (mean 14.42, range 11.86-19.50) followed by clozapine (mean 3.19, range 2.79-4.32) and haloperidol (mean 3.11, range 0.59-6.67). CONCLUSIONS:The ability of antipsychotics to enter the fetal, newborn, and infant circulation varies considerably among antipsychotics. Given sampling constraints of other matrices, measuring antipsychotic concentrations in maternal blood may represent the least expensive, most readily available, and reliable estimate of fetal/infant exposure.