Cranial neural tube defect after trimethoprim exposure

Abdullah, Nor Linda and Gunasekaran, Renuka and Mohd-Zin, Siti Waheeda and Lim, Bee Hui and Maniam, Pramila and Mohd-Salleh, Anis Shuhada and Thong, Meow Keong and Chik, Zamri and Nordin, Noreena and Omar, Zaliha and Engkasan, Julia Patrick and Ganesan, Dharmendra and Aiezzah, Zakaria Nurul and Ahmad-Annuar, Azlina and Abdul-Aziz, Noraishah Mydin (2018) Cranial neural tube defect after trimethoprim exposure. BMC Research Notes, 11 (1). p. 475. ISSN 1756-0500, DOI

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Objectives: The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation. Results: Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%,∗P < 0.0001), in all litters. The TELSE tablet-treated females subsequently given folic acid did not result in pregnancies despite there being evidence of possible resorption. Furthermore, after multiple rounds of mating which did not yield viable pregnancies, eventually, 2 embryos with exencephaly were harvested in a litter of 6 at 0.05% w/v pure trimethoprim once. The use of trimethoprim, a folic acid antagonist, peri-conceptionally increased the risk of exencephaly in the mouse.

Item Type: Article
Funders: High Impact Research Grant UM.C/625/1/HIR/062 and UM.C/625/1/HIR/148/2 from the University of Malaya, High Impact Research Grant UM.C/625/1/HIR/MOHE/MED/08 from the Ministry of Higher Education Malaysia, Postgraduate Grants from University of Malaya PPP PG153‑2015B and PG137‑2015A
Uncontrolled Keywords: Acne; Folic acid antagonist; Malaysia; Neural tube defects; Primary neurulation; Trimethoprim
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 14 Oct 2019 04:07
Last Modified: 14 Oct 2019 04:07

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