Psychopharmacotherapy during pregnancy: Therapeutic drug monitoring (TDM) in maternal blood, amniotic fluid and umbilical cord blood

Objectives: Treatment of psychiatric diseases during pregnancy using psychotropic drugs is complicated by the concern for the safety of the mother and the child. Aim of the study was to measure drug levels in maternal serum and to determine the penetration ratio of different psychotropic drugs into amniotic fluid and umbilical cord blood and to account for the distribution of the drugs. Methods: In a non-interventional observational study design we collected maternal blood, amniotic fluid and cord blood samples of meanwhile more than 40 mother-child pairs and analyzed the drug levels. Daily doses were correlated with maternal serum- and umbilical cord blood-concentrations, and serum levels were correlated with levels in amniotic fluid. Results: The average penetration ratio into amniotic fluid was 61.38% for sertraline, 70.83% for citalopram, 12.16% for valproic acid, 356.06% for levetiracetam, and 55.00% for lamotrigine. In umbilical cord blood, the mean ratio was 56.76% for sertraline, 54.17% for citalopram, 118.01% for valproic acid, 101.63% for levetiracetam and 86.00% for lamotrigine. Conclusion: Quantifying the extent of placental passage or knowledge about the accumulation of a drug in amniotic fluid can facilitate medication selection based on the extent of fetal drug exposure and ultimately provide insight into whether or not neonatal complications are directly related to medication exposure with measurable drug levels in amniotic fluid or fetal circulation.