Congenital ventricular septal defects and prenatal exposure to cyclooxygenase inhibitors

Abstract

Ventricular septal defects (VSDs) are common congenital abnormalities which have been reported to be associated with maternal fever and various environmental factors. The aim of the present study was to evaluate the effect of prenatal exposure to cyclooxygenase (COX) inhibitors on heart defects. A retrospective statistical analysis was performed using data collected in our laboratory during various teratological studies carried out on albino CRL:(WI)WUBR Wistar strain rats from 1997 to 2004. The observations were compared with concurrent and historic control data, as well as findings from other developmental toxicological studies with selective and nonselective COX-2 inhibitors. Despite the lack of significant differences in the frequency of VSDs between drug-exposed and control groups, statistical analysis by the two-sided Mantel-Haenszel test and historical control data showed a higher incidence of heart defects in offspring exposed to nonselective COX inhibitors (30.06/10,000). Unlike other specific inhibitors, aspirin (46.26/10,000) and ibuprofen (106.95/ 10,000) significantly increased the incidence of the VSD when compared with various control groups (5. 38-19.72/10,000). No significant differences in length or weight were detected between fetuses exposed to COX inhibitors and born with VSD and non-malformed offsprings. However, a statistically significant increase of fetal body length and decrease of body mass index were found in fetuses exposed to COX inhibitors when compared with untreated control. We conclude that prenatal exposure to COX inhibitors, especially aspirin and ibuprofen, increased the incidence of VSDs in rat offspring but was not related to fetal growth retardation.

Effects of acetaminophen (paracetamol) in the embryonic development of zebrafish, Danio rerio

“…Antipyretic-analgesics are an array of drugs promoted for alleviation of fever, pain and infl ammation, including (1) NSAIDs -non-steroidal anti-infl ammatory drugs and (2) PSAADs -peroxide-sensitive antipyretic and analgesic drugs (Burdan, 2004;Burdan et al, 2006;Graham and Scott, 2005). These medications are generally known as COX inhibitors as they interfere with the synthesis or the activity of cyclooxygenase (COX-1 or COX-2 or COX-3) enzymes involved in the production of prostaglandins, the ubiquitous bioactive lipid molecules (Prescott and Yost, 2002;Burdan et al, 2006;Cha et al, 2005Cha et al, , 2006.…”

“…These medications are generally known as COX inhibitors as they interfere with the synthesis or the activity of cyclooxygenase (COX-1 or COX-2 or COX-3) enzymes involved in the production of prostaglandins, the ubiquitous bioactive lipid molecules (Prescott and Yost, 2002;Burdan et al, 2006;Cha et al, 2005Cha et al, , 2006. These drugs are in use widely, and many of them are marketed as non-prescription or over-the-counter (OTC) medications (Black and Hill, 2003).…”

History and status of embryology and developmental biology at Polish Medical Faculties and Schools

“…They have shown that of the whole group of COX-inhibitors, especially the non-selective COX inhibitors significantly increase the incidence of the congenital ventricular septal defect and celosomy (gastroshisis, umbilical hernia). In addition, these studies showed, for the first time, the presence of dark chondrocytes in the rat fetal epiphyseal cartilage (Burdan et al, 2002(Burdan et al, , 2005(Burdan et al, , 2006a.…”

Organ and prenatal toxicity of nonsteroidal anti-inflammatory drugs

“…This was, however, only observed for a group of COX inhibitors, and not for a specific substance. It is worth highlighting that in the offspring of women exposed to xenobiotics, researchers observed an increased frequency of ventricular septal defects alone [5][6][7][8]. On the other hand, Torfs et al [39] have shown not only the increased prevalence of heart defects, but also of cleft lip and/or palate in the offspring of women who took COX inhibitors in pregnancy.…”