Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue
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 r...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
|
| Series: | Toxicology Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750020303978 |
| _version_ | 1818724467714555904 |
|---|---|
| author | Hayley R. Price Dickson Lai Hugh Kim Tricia E. Wright Michael W.H. Coughtrie Abby C. Collier |
| author_facet | Hayley R. Price Dickson Lai Hugh Kim Tricia E. Wright Michael W.H. Coughtrie Abby C. Collier |
| author_sort | Hayley R. Price |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T21:26:53Z |
| format | Article |
| id | doaj.art-14597a6d09404da39b37d3622738b44c |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-17T21:26:53Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-14597a6d09404da39b37d3622738b44c2022-12-21T21:32:01ZengElsevierToxicology Reports2214-75002020-01-01713111318Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissueHayley R. Price0Dickson Lai1Hugh Kim2Tricia E. Wright3Michael W.H. Coughtrie4Abby C. Collier5Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T1Z3, CanadaFaculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T1Z3, CanadaCentre for Blood Research, 2350 Health Sciences Mall, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Faculty of Dentistry, 2199 Wesbrook Mall, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, United States; Departments of Obstetrics, Gynecology & Women’s Health and Psychiatry, University of Hawaii Manoa, Honolulu, HI 96813, United StatesFaculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T1Z3, CanadaFaculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T1Z3, Canada; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2214750020303978NSAIDsUmbilical cordAdverse drug reactionsAnalgesicsAnalytical chemistryNeonatal health |
| spellingShingle | Hayley R. Price Dickson Lai Hugh Kim Tricia E. Wright Michael W.H. Coughtrie Abby C. Collier Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue Toxicology Reports NSAIDs Umbilical cord Adverse drug reactions Analgesics Analytical chemistry Neonatal health |
| title | Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue |
| title_full | Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue |
| title_fullStr | Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue |
| title_full_unstemmed | Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue |
| title_short | Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue |
| title_sort | detection and quantitation of non steroidal anti inflammatory drug use close to the time of birth using umbilical cord tissue |
| topic | NSAIDs Umbilical cord Adverse drug reactions Analgesics Analytical chemistry Neonatal health |
| url | http://www.sciencedirect.com/science/article/pii/S2214750020303978 |
| work_keys_str_mv | AT hayleyrprice detectionandquantitationofnonsteroidalantiinflammatorydruguseclosetothetimeofbirthusingumbilicalcordtissue AT dicksonlai detectionandquantitationofnonsteroidalantiinflammatorydruguseclosetothetimeofbirthusingumbilicalcordtissue AT hughkim detectionandquantitationofnonsteroidalantiinflammatorydruguseclosetothetimeofbirthusingumbilicalcordtissue AT triciaewright detectionandquantitationofnonsteroidalantiinflammatorydruguseclosetothetimeofbirthusingumbilicalcordtissue AT michaelwhcoughtrie detectionandquantitationofnonsteroidalantiinflammatorydruguseclosetothetimeofbirthusingumbilicalcordtissue AT abbyccollier detectionandquantitationofnonsteroidalantiinflammatorydruguseclosetothetimeofbirthusingumbilicalcordtissue |