Sertraline in pregnancy – Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood

Rationale: This study is the first to measure and correlate sertraline concentrations in maternal blood, amniotic fluid and umbilical cord blood and account for distribution of the drug between these three compartments.
Methods: Concentrations of sertraline were measured in six mother infant pairs at the time of delivery. Data are provided as median values, first and third quartiles as well as ranges. To account for the penetration ratio into amniotic fluid and cord blood, the concentration of sertraline in both environments was divided by the concentration in maternal serum. Daily doses were correlated with maternal serum- and umbilical cord bloodconcentrations,
and serum levels were correlated with levels in amniotic fluid.
Results: The median daily dose of sertraline was 75 mg (Q1: 43.75 mg, Q3: 100 mg; range 25–100 mg). Amniotic fluid concentrations of sertraline strongly correlated with the daily dose (r=0.833, p=0.039) while neither maternal serum concentrations nor cord blood concentrations correlated with the daily dose (p > 0.05). The median penetration ratio for sertraline into amniotic fluid was 0.57 (Q1: 0.28, Q3: 0.75; range: 0.22–0.88). The median penetration ratio into the fetal circulation, calculated on the basis of umbilical cord bloodconcentrations, was found to be 0.36 (Q1: 0.28, Q3: 0.49; range: 0.17–0.65).
Conclusions: Sertraline concentrations in amniotic fluid gave evidence that maternally administered sertraline is constantly accessible to the fetus via amniotic fluid in a manner not previously appreciated. A relatively low
penetration into fetal circulation may contribute to a sufficient safety profile of sertraline during pregnancy although in our study APGAR Scores were relatively low in three infants. Our data support the important role of therapeutic drug monitoring in maintaining the safety of pregnant women and exposed infants.