Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue
| Autor: | Michael W.H. Coughtrie, Abby C. Collier, Hugh Kim, Dickson Lai, Hayley R. Price, Tricia E. Wright |
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| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
Naproxen medicine.medical_specialty NSAIDs Health Toxicology and Mutagenesis medicine.medical_treatment Adverse drug reactions 010501 environmental sciences Toxicology 01 natural sciences Umbilical cord digestive system 03 medical and health sciences 0302 clinical medicine Diclofenac lcsh:RA1190-1270 Pregnancy medicine Adverse effect skin and connective tissue diseases lcsh:Toxicology. Poisons 0105 earth and related environmental sciences Analgesics In vitro fertilisation business.industry Ductus arteriosus closure Obstetrics Regular Article medicine.disease Ibuprofen digestive system diseases 3. Good health medicine.anatomical_structure UHPLC-MS/MS Neonatal health business Analytical chemistry 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Toxicology Reports Toxicology Reports, Vol 7, Iss, Pp 1311-1318 (2020) |
| ISSN: | 2214-7500 |
| Popis: | Highlights • Using umbilical cord, we report a prevalence of NSAID use of ∼3 % close to labour. • A novel UHPLC-MS/MS method for detecting 5 NSAIDs was developed and validated. • NSAIDs are contraindicated in first and third trimesters, but use is increasing. • Determining safe dosages of NSAIDs in pregnancy should be a priority. Background Nonsteroidal anti-inflammatory drugs are contraindicated in the third trimester of pregnancy due to negative effects including alteration of uteroplacental blood flow, premature ductus arteriosus closure, and adverse effects on the fetal kidney. However, many women are unaware of these risks, and commonly report their use in pregnancy. We aimed to determine if umbilical cord was a reliable matrix for detecting NSAID use, determine incidence of use close to labour, and uncover associations with obstetric/neonatal outcomes. Methods We developed a UHPLC-MS/MS method to simultaneously detect diclofenac, ibuprofen, indomethacin, naproxen, and salicylic acid in plasma and umbilical cord lysate. Using this method, we screened 380 lysates to determine the prevalence of NSAID use. Results were compared to the clinical outcomes in pregnancy using ICD9/10 chart codes (n = 21). Results The UHPLC-MS/MS method has excellent linearity, accuracy, and precision in solvent and plasma, but lower sensitivity in umbilical cord lysate. We report a 3 % rate of NSAID ingestion within days of labour – the pharmacokinetically-determined window for active ingestion. There were no significant differences observed for maternal, obstetric, or neonatal outcomes between the NSAID positive group (n = 11) and NSAID negative group (n = 369). Conclusions Because NSAID use in third trimester is contraindicated, even a 3% usage rate is alarmingly high. Based on UHPLC-MS/MS performance of umbilical cord lysate, 3% is likely a conservative estimate. Recent adoption of NSAIDs under clinical supervision to support in vitro fertilisation and prevent pre-eclampsia indicates future work should focus on determining safe dosages of NSAIDs and the correct therapeutic window in pregnancy. |
| Databáze: | OpenAIRE |
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