Detection of benzodiazepines and antidepressants consumption during pregnancy: Maternal hair vs. meconium

Abstract

The most common mental diseases in pregnant women are depression and anxiety disorders (estimated prevalence 6.5–12.9% and 15.6%, respectively [1] , [2] ). The drugs used in their treatment (antidepressants and benzodiazepines) can produce serious obstetric complications, as well as deleterious effects in fetal development and later in life [1] . The aim of this study was to compare maternal hair and meconium for detecting in utero drug exposure to benzodiazepines and antidepressants. Maternal hair and meconium samples were collected after delivery from 145 mother–newborn dyads. Samples were analyzed for the determination of benzodiazepines (alprazolam, clonazepam, bromazepam, diazepam, nordiazepam, lorazepam, lormetazepam, oxazepam, flunitrazepam, 7-aminoflunitrazepam, triazolam, and zolpidem), antidepressants (amitriptyline, clomipramine, fluoxetine, paroxetine, venlafaxine, citalopram), and 6 metabolites by LC-MS/MS. Hair samples were segmented in 3 segments corresponding with the 3 trimesters ( n = 99), but if the amount of hair was not enough a 8-cm segment was employed ( n = 46). Maternal hair results (LOQ = 5–20 pg/mg) and meconium Results (LOQ = 5–20 ng/g) were compared. Forty-nine hair samples (33.8%) tested positive, 23 (15.9%) for benzodiazepines (19 segmented and 4 non-segmented) and 33 (22.8%) for antidepressants (23 segmented and 10 non-segmented). Specifically, the most frequently detected compounds in hair were nordiazepam ( n = 13, > LOD-224.6 pg/mg), citalopram ( n = 11, 30.2–7166.1 pg/mg), diazepam ( n = 10, 6.6–879.5 pg/mg), amitriptyline ( n = 8, 11.3–556.5 pg/mg), and venlafaxine ( n = 8, 14.4–659.1 pg/mg). Twenty-eight meconium samples (19.3%) tested positive, 24 (16.6%) for benzodiazepines and 8 (5.5%) for antidepressants. The most frequently detect compounds in meconium were nordiazepam ( n = 16, > LOD-125.1 ng/g), diazepam ( n = 12, > LOD-68.6 ng/g), citalopram ( n = 5, > LOD-2729.5 ng/g) and its metabolite desmethylcitalopram ( n = 4, > LOD-1286.1 ng/g), and alprazolam ( n = 3, 5.7–42.2 ng/g). The overall agreement between maternal hair and meconium results was 66.9%, but this value increased to 70.2% when only the hair results corresponding with the third trimester were compared with meconium. This good agreement was due to the high percentage of negative results ( n = 84), but if only positive results were analyzed the percentage decreased to 19.7% and 42.6%, respectively. A better correlation was found between positive results in both specimens for benzodiazepines (39.1%) than antidepressants (18.2%). Moreover, when hair samples were positive in the three trimesters ( n = 15), meconium was positive in 7 cases, and in the remaining cases the concentration in hair was decreasing along pregnancy, except in one case. Surprisingly, when benzodiazepines were administrated during delivery ( n = 15), in 6 cases meconium tested positive at low concentrations (1.1–8.6 ng/g). Maternal hair was more sensitive than meconium to detect consumption during pregnancy, while meconium was able to detect consumption during the third trimester and also during delivery.