Therapeutic drug monitoring (TDM) in plasma and amniotic fluid in pregnancy

Introduction: Pregnancy and the postpartum period are a time of increased risk for women to develop psychiatric disorders. Although the reproductive safety data on psychotropic drugs has expanded over the last years, there is only little information on maternal/fetal exchange of these medications and only sparse information is published on their concentrations in amniotic fluid. Method: Women treated with psychotropic drugs for different reasons underwent amniocentesis for obstetrical reasons. Concentrations of psychotropic drugs in maternal plasma and amniotic fluid were measured. A penetration-index showing the percentage of maternal drug concentration that was found in amniotic fluid was calculated. In two cases, the concentration of psychotropic drugs was also measured in umbilical cord blood shortly after delivery. Results: Concentrations of different psychotropic drugs were found in maternal plasma, amniotic fluid and umbilical cord blood in highly variable concentrations suggesting that fetal exposure is continuous and may occur through a variety of paths accounting for increased fetal exposure. Preliminary analysis of some of the acquired data revealed that the concentrations of the three anticonvulsive drugs lamotrigine, valproic acid, and clonazepam in amniotic fluid were between half and two thirds, respectively, of those in the maternal blood. Sertraline and paroxetine were not detectable in amniotic fluid despite significant levels in the maternal blood. Conclusion: These preliminary data show highly different ratios of drug penetrations into the amniotic fluid and thereby into the fetal circulation. They contribute to a better understanding of why some psychotropic drugs have more negative impacts on the unborn child e.g. in potentially leading to higher malformation rates or other neonatal symptoms such as respiratory problems, low Apgar score, hypoglycemia, or neonatal convulsions.