Exposure to Non-Steroidal Anti-Inflammatory Drugs during Pregnancy and the Risk of Selected Birth Defects: A Prospective Cohort Study

Contains fulltext : 97906.pdf (publisher's version ) (Open Access)BACKGROUND: Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs. METHODS AND FINDINGS: We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0-12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4-1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9-15.7). CONCLUSIONS: Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded

Congenital ventricular septal defects and prenatal exposure to cyclooxygenase inhibitors

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

Prenatal and nutritional influences on skeletal development: lessons from animal studies

It is now well established that the onset of adult diseases such as heart disease, stroke, type 2 diabetes and hypertension are linked to an adverse uterine growth environment, in particular through maternal nutrition, during development of the individual. The geographical distribution of the incidence rate of heart disease is similar to that of osteoporosis. This may indicate a link between maternal nutrition during pregnancy and the subsequent risk of developing osteoporosis in the offspring. This review summarises what we know to date, from animal models, about maternal nutrition and the subsequent alterations in the offspring’s skeletal structure

Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, and para -methoxyamphetamine-induced hyperthermia

The original publication is available at www.springerlink.comRationale: Cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), and para-methoxyamphetamine (PMA) disrupt normal thermoregulation in humans, with PMA being associated with more severe cases of hyperthermia. Harm minimization advice on how to prevent overheating depends on appropriate thermoregulatory behavior by drug users. Objectives: The purpose of the current study was to establish dose–response relationships for the effects of a number of commonly used illicit stimulants and investigate the behavioral response to increased core temperature. Materials and methods Sprague-Dawley rats with telemetry implants were administered either saline or 4, 12, 26, 40 or 80 μmol/kg of cocaine, methamphetamine, MDMA, or PMA and confined to an ambient temperature of 30°C for 30 min, before being able to choose their preferred temperature on a thermally graded runway (11-41°C). Results: The increased core temperature caused by administration of cocaine, methamphetamine, and MDMA treatment led to the animals seeking the cool end of the runway to correct their core temperature, although this did not occur in PMA-treated rats. The order of potency for increasing core temperature was methamphetamine >PMA = MDMA> cocaine. This differed to the slopes of the dose–response curves where MDMA and PMA showed the steepest slope for the doses used followed by methamphetamine then cocaine. Conclusions: These results suggest that behavioral aspects of thermoregulation are important in assessing the potential of individual drugs to cause harmful increases in core temperature.Emily Joy Jaehne, Abdallah Salem and Rodney James Irvin