Bioassay-guided isolation of anti-inflammatory and antinociceptive metabolites among three Moroccan Juniperus leaves extract supported with in vitro enzyme inhibitory assays.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as "Al'Araar" for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals. AIM OF THE STUDY: The current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays. MATERIALS AND METHODS: Firstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds. RESULTS: The results showed that acute oral administration of the extracts (300-500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 µM, respectively. CONCLUSION: J. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved.

Association of the immunity genes with type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1D) is a complicated illness marked by the death of insulin-producing pancreatic beta cells, which ultimately leads to insulin insufficiency and hyperglycemia. T lymphocytes are considered to destroy pancreatic beta cells in the etiology of T1D as a result of hereditary and environmental factors. Although the latter factors are very important causes of T1D development, this disease is very genetically predisposed, so that there is a significant genetic component to T1D susceptibility. Among the T1D-associated gene mutations, those that affect genes that encode the traditional Human Leukocyte Antigens (HLA) entail the highest risk of T1D development. Accordingly, the results of decades of genetic linkage and association studies clearly demonstrate that mutations in the HLA genes are the most associated mutations with T1D. They can therefore be used as biomarkers for prediction strategies and may even prove to be of value for personalized treatments. Other immunity-associated genetic loci, are also associated with higher T1D risk. Indeed, T1D is considered an autoimmune disease. Its prevalence is rising globally, especially among children and young people. Given the global rise of, and thus interest in, autoimmune diseases, here we present a short overview of the link between immunity, especially HLA, genes and T1D.

Attitude, perception, and feedback of graduate medical students on teaching-learning methodology in pathology courses: A call for curricular modernization in Morocco.

BACKGROUND: The difficulty of understanding the pathology courses and the student's dissatisfaction with the pathology modules is a universal problem. The principal aim of our survey was to assess the perception and satisfaction of teaching pathology by graduate medical students from nine Moroccan faculties of medicine. MATERIALS AND METHODS: This study was conducted among graduate medical students regarding their preferences in pathology teaching modalities, their satisfaction with the current lecture-based courses, their perception of pathology as a specialty, and their thoughts on whether and how such curricula should be modernized. A qualitative and comparative analysis was performed. The differences in modalities of teaching used were investigated. RESULTS: We received 274 completed surveys from graduate Moroccan medical students. Seventy-five (27.9 %) students were dissatisfied with the actual lecture-based courses. A total of 131 students (48.5%) considered that the methodology of teaching and learning used in their faculty is insufficient for learning, understanding, and memorizing pathology courses. Additionally, 233 students (86.3 %) considered that the curriculum should be modernized. The majority supported the implementation of case reports (74%), hospital-based rotation in the pathology department (68.7%), and virtual slides (60%) as the most preferred didactic methods. CONCLUSIONS: This survey based-study highlighted the limits of the current pathology teaching curriculum in Morocco, insufficiently in line with the aspirations of students. Furthermore, students' responses regarding their knowledge of the pathology laboratory functioning as well as their opinions toward considering pathology as a future career were very surprising, converging toward a huge lack of attractiveness of this discipline.

Evaluation of Antibiograms Interpretation Training Needs of Medical Biology Residents at Ibn Rochd University Hospital.

BACKGROUND: In order to determine domains with the most difficulties and plan a relevant training, the aim of this study was to assess training needs of medical biology residents at the Ibn Rochd University Hospital of Casablanca, concerning antibiograms interpretation. METHODS: A descriptive and comparative study was carried out in February 2022, with two resident groups. The first one included all residents in training in the bacteriology-virology laboratory and having spent at least 2 months. The 2nd one included residents who had validated their course (9 months). Data were collected from collective interviews and a self-administered questionnaire with a qualitative and quantitative grid analysis. RESULTS: Residents expressed needs in the three learning domains (knowledge, know-how, interpersonal skills) but they were low to moderate (scores from 0.2/4 to 2.4/4). Priority topics for training were: interpretation of observed phenotypes (5.85/8), followed by interpretative reading according to EUCAST recommendations (5.05/8). The two groups' responses were similar, except for the know-how domain of natural resistance mechanisms where the needs were greater in G1 (p = 0.008). CONCLUSIONS: In the light of these results, additional training with relevant aims should be planned.

[Evaluation of medicines price listed on the official bulletins in Morocco (2014-2019)]. / Évaluation du prix des médicaments figurant sur les bulletins officiels au Maroc (2014­2019).

OBJECTIVES: This study shows the evolution of medicines prices over the period April 2014 to September 2019 in order to provide an overview of the situation following the adoption of the new method for setting drug prices in Morocco. METHODS: The analysis concerned official bulletins relating to the Public Selling Price of drugs in Morocco published between April 2014 and September 2019 as part of a retrospective study. RESULTS: Out of a total of 7292 medicines, 35.9% were unchanged in price, 26.2% were new and 0.3% had a price increase. The decrease affected 37.7% equivalent to 2747 medicines. Of these, 38.6% decreased in price in 2014 and 84.13% had only one decrease. Medicines with a retail price of between 5 and 10 Euros were the most affected by the decrease. Decreases of less than 1% of the selling price represented 27.7% against 0.3% whose decrease exceeded 70% of the price. The largest decreases in number were recorded in 2014. Some medicines saw declines of up to 78.6%. The most affected price brackets in percentage terms were those with a retail price above 20 Euros. CONCLUSIONS: Following the adoption of the new decree on the pricing of medicines in 2013 in Morocco, several decreases were recorded and concerned all therapeutic classes. The percentages of the decreases in Moroccan Dirham as well as in percentage were very variable.

Impact of the COVID-19 pandemic on digestive cancer staging, a case series.

Introduction: The COVID-19 pandemic had an undeniable impact on the health system worldwide, this lead to a delay in the diagnosis and treatment of digestive cancers.The purpose of our study was to assess this delay and its impact on patient care. Method: Our work is a retrospective study about 165 patients that were admitted for digestive cancers at Sheik Khalifa hospital, Casablanca morocco during a 3-year period, that we divided into three. We included all the digestive adenocarcinomas (esophagus excluded) whether they were operated on or not. We excluded all other types of cancers (GIST, serous tumors …). We assessed the time between the beginning of the symptoms and the beginning of the treatment and the number of patients that were diagnosed at the complication stage. We also assessed the staging of the tumor at the moment of diagnosis and the complete surgical resection rate. Results: Among the 165 patients admitted for digestive cancer, 54,9% were males with a sex ratio of 1,22 M/F. The average age of our patients was 62,8 years varying between 25 and 86 years old and with a standard deviation of 11,8 years. Digestive cancers were diagnosed in 79 patients during period 1, 43 patients during period2, and 43 during period 3. We found a statistically significant increase in the percentage of patients with advanced cancer by 21,7% (p = 0,045) from 2019 to 2020. The delay in diagnosis (p = 0,275), percentage of cancer discovered at the stage of complication(p = 0,728), and the reduction in complete surgical resection (p = 0,177) were not statistically significant. Conclusion: Our results show an undeniable impact of the COVID-19 pandemic on the staging of digestive cancers but the impact on their care remains to be proven and needs a long-term survival follow-up.

Factors Associated With Mild Cognitive Impairment in Patients With Type 2 Diabetes: A Cohort Study.

Background Cognitive dysfunction is increasingly recognized as an important comorbidity of diabetes mellitus (DM). Objective The purpose of this study was to determine the prevalence and predictors of cognitive decline in individuals with type 2 diabetes mellitus (T2DM). Methods This cohort study included patients with type 2 diabetes mellitus aged between 40 and 75 years and with a duration of the evolution of diabetes that is greater than five years admitted in endocrinology consultation of the Sheikh Khalifa ibn Zaid Hospital in Casablanca, Morocco. For each patient, we collected clinical characteristics and biological assessments. All subjects provided screening test results as defined by the Mini-Mental State Examination (MMSE). Results We included a total of 100 patients with diabetes between May and September 2021. The median age of the patients was 65 years (interquartile range (IQR): 59-70 years), 65% were males, and the median duration of diabetes was 15 years (IQR: 9-20 years). The most common cardiovascular risk factors (CVRFs) were hypertension (72.7%) and dyslipidemia (53%). The most common complications of diabetes were peripheral neuropathy (50%), diabetic retinopathy (DR) (39%), peripheral artery disease (33%), and coronary artery disease (27%). Cognitive impairment was present in 47.5% of our patients. For the multivariate analysis, we found that the decrease in the MMSE score is associated with the increase in age (p-value = 0.004) and the occurrence of diabetic retinopathy (p-value < 0.001), dyslipidemia (p-value = 0.006), and elevated creatinine (p-value < 0.001). Conclusion It is necessary to consider the cognitive decline of patients with diabetes as one of the most important complications of this disease because of its impact on the evolution and compliance of these patients.

Knowledge, Attitude, and Practices of Moroccan Retail Pharmacists towards Veterinary Medicines.

This is the first study conducted in Morocco to assess knowledge, attitude, and practices of retail pharmacists regarding veterinary medicines. It is a cross-sectional study. Two types of multiple-choice questionnaires were distributed to pharmacists depending on whether or not they dispense veterinary medicines. A total of 143 pharmacists were involved in this study. The percentage of retail pharmacists who dispensed veterinary medicines was estimated at 23.1%. Less than half of respondents were highly satisfied regarding their knowledge of veterinary pharmacy. Besides, 39.4% of retail pharmacists were at ease giving advice in general while dispensing veterinary medicines, and 73% were knowledgeable on parasiticides. Approximately, 94% of retail pharmacists expressed their need to improve their knowledge of veterinary pharmacy. Our study also revealed that 48.5% of pharmacists dispensed veterinary medicine daily. This study demonstrated that involvement of retail pharmacists in dispensing veterinary medicines was poor. The need for training programs on veterinary pharmacy expressed by Moroccan retail pharmacists was high.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11 years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

Metro-SMHOP 01: Metronomics combination with cyclophosphamide-etoposide and valproic acid for refractory and relapsing pediatric malignancies.

BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. PATIENTS AND METHODS: From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28-day cycles with daily oral administration of cyclophosphamide (30 mg/m2 ) from days 1 to 21, together with oral etoposide (25 mg/m2 ) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. RESULTS: Ninety-eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1-18 cycles). One-year progression-free survival of our patients was 19%, and one-year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). CONCLUSION: This three-drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.

Management of gout by Moroccan rheumatologists: a Moroccan Society for Rheumatology National Survey.

To assess the modalities and current practices in gout management reported by Moroccan rheumatologists. We performed a cross-sectional online survey using a questionnaire e-mailed to 360 rheumatologists included 30 multiple-choice questions. 105 rheumatologists responded to the survey with 29% of response rate. The number of gout patients seen per month was five (3-9); they were referred in 58.7% by a general practitioner. The clinical presentation of gout patients was dominated by gout crisis in 71%, and the association gout crisis and gouty arthropathy accounted for 19% of severe forms. 40% of rheumatologists apply the 2015ACR/EULAR classification criteria. Obesity accounted for 85.7% of the associated comorbidities. The most commonly prescribed Urate-lowering therapy (ULT) was allopurinol in 81.3% (± 12). 48% of rheumatologists reported starting allopurinol at 200 mg daily and associated it with colchicine during the first 6 months by 33.3%. The determination of uric acid levels was monitoring in 76.2% every 3 months. Administration of ULT to asymptomatic hyperuricemia was found in 69.5% when patients had renal complications, while only 14.3% recommended dietary and lifestyle measures. The median duration for therapeutic education was 15 min (10, 20). In 96.2%, the education of the patient was done orally. 93.3% of rheumatologists inform their patients on how to manage a gout attack, and 96.2% on the measures of hygiene and diet has adopted. Our survey gives an insight into the elements that should be improved in the management of gout by the Moroccan rheumatologists. It highlights the need to standardize the management of gout, hence the importance of developing Moroccan recommendations on gout.

Incidence of adverse reactions caused by first-line anti-tuberculosis drugs and treatment outcome of pulmonary tuberculosis patients in Morocco.

PURPOSE: The treatment of tuberculosis is associated with a high incidence of adverse reactions with different degrees of severity. The aim of this study was to determine the incidence of adverse reactions caused by first-line anti-tuberculosis drugs and to evaluate the treatment outcome of TB patients in a large region of Morocco. METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established for data collection from clinical charts of TB patients. The study was carried out in all the 18 centers located in the Rabat-Salé-Kénitra region of Morocco where tuberculosis is treated. Adverse reactions are evaluated from the start of TB treatment until its end by a specialist clinician. The treatment outcomes are evaluated, and the definitions and classifications of these outcomes are defined according to World Health Organization guidelines. RESULTS: Among a total number of 2532 patients treated for TB, the average age is 37.3 ± 16.4 years, 10.0% of patients produced adverse reactions. 7.4% of adverse reactions are gastrointestinal, 3.7% are cutaneous, 2.0% are hepatic, 1.14% are articular, 1.07% are immunoallergic, 0.7% are neuropsychiatric, and 0.1% are ocular. The treatment outcome of TB patients is 79.1% rate for successful treatment and 15.6% for unsuccessful treatment. CONCLUSION: Adverse reactions caused by anti-TB drugs are frequent among patients with TB. These ADRs must be followed up by a closer monitoring during anti-TB treatment period. Treatment success outcome in our study is slightly lower than the success rate target of WHO of at least 85%.

Treatment outcomes of drug resistant tuberculosis patients in Morocco: multi-centric prospective study.

BACKGROUND: Drug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco. METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco. RESULTS: In our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients' age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327-14.292]). CONCLUSION: Treatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.

Eating disorders among Moroccan medical students: cognition and behavior.

INTRODUCTION AND AIM: Eating disorders (EDs) are complex, multifactorial diseases linked to biological, developmental, psychological, and sociocultural factors. Medical students are among subjects at high risk of EDs. The aim of the present investigation was to evaluate EDs among 710 Moroccan medical students with a focus on cognition and behavior related to EDs. METHODS: Sociodemographic, economic, and clinical data were collected. Validated questionnaires, such as the SCOFF (Sick, Control, One Stone, Fat, Food) questionnaire and the Eating Disorder Inventory 2 (EDI2), were administered. RESULTS: The male:female ratio was 0.53, mean age was 21±2 years, 11.1% of participants were underweight, 13.4% were overweight, and 1.8% were obese. A middle socioeconomic level was found in 84.9% of cases. The prevalence of EDs in students was 32.8% (37.6% among females and 23.7% among males) and that of weight-control behaviors 18.5%. Increased body-mass index values were significantly associated with dieting (P<0.001), fasting (P=0.044), and the use of appetite suppressants (P=0.037). CONCLUSION: It appears that the impact of EDs is high, affecting a third of medical students, with significant use of harmful weight-control behaviors. We also found that dimensions of bulimia, perfectionism, body dissatisfaction, and ineffectiveness, parts of the core of EDs, were found in future medical practitioners.

[Which place occupies the free drug sample in the prescription of the physicians in Morocco?] / Quelle place occupe l'échantillon médical gratuit dans la prescription des médecins au Maroc ?

OBJECTIVES: Do the state of affairs of the perception of free drug samples by a group of prescribers of drugs in the Morocco. METHODS: This was a cross-sectional study of 381 physicians practising in different sectors (public, private) using a self-administered anonymous questionnaire, conducted between December 2016 and March 2017. The questionnaire focused on assessing the general knowledge of prescriber on free drug sample, medical visit of medical representative of pharmaceutical laboratory, drug prescribing and free drug sample use. RESULTS: In total, 381 prescribers were interviewed. Sex M/F ratio was 0.53 with a mean age of 37.4±11.2 years exerting mainly in the public sector in urban areas. According to surveyed prescribers, the drug specialties presented as free drug sample occupied 52.1 percent of their prescription. The main interest in having the free drug sample was to help the patient at low socioeconomic level but it influences the physician's prescription. CONCLUSION: This survey puts in perspective the place of the free drug sample in the medical prescription with prescribers, in order to raise awareness about the ability of free drug sample to influence the medical prescription although it allows to help the patient low socio-economic level.

Factors associated with asthma control: MOSAR study (Multicenter Observational Study of Asthma in Rabat-Morocco).

BACKGROUND: The purpose of the study is to describe the profile of patients with asthma and to identify the signifiant risks and the protective factors associated with asthma control. METHODS: A prospective epidemiological study was conducted in three hospitals of Rabat-Morocco and included 396 patients with asthma. Differences in characteristics across the levels of asthma control were compared by the one-way analysis of variance for continuous variables, and chi-square test was used for categorical variables. The risk and protective factors associated with the asthma control levels were determined by Proportional Odds Model (POM) for bivariate and multivariate ordinal logistic regression, also expressed as Odds Ratios (OR) and 95% Confidence Intervals (95% CI). RESULTS: From 7440 patients screened by 28 physicians, 396 were included in study. 53% of the particiants sufferd controlled, 18% had partly controlled and 29% had uncontrolled asthma symptoms. A multivariate ordinal logistic regression analysis showed that having respiratory infections (AOR = 5.71), suffering from concomitant diseases (AOR = 3.36) and being allergic to animals (AOR = 2.76) were positively associated with poor control of asthma. However, adherence to treatement (AOR = 0.07), possession of health insurance (AOR = 0.41) and having more than 2 children (AOR = 0.47) were associated with good asthma control. CONCLUSION: The study established a clinical-epidemiological profile of asthmatic patients in Rabat region in Morocco. By ordinal logistic regression we found that 6 factors - respiratory infections, concomitant diseases, animals allergy, adherence to treatment, health insurance and having more than two children - were associated with asthma control.

Pregnancy outcome following in utero exposure to azathioprine: A French comparative observational study.

AIM OF THE STUDY: To evaluate whether azathioprine exposure during pregnancy increases the risk of birth defects and prematurity. METHOD: Prospective comparative observational study using the French pregnancy database TERAPPEL. To evaluate birth defects, outcomes of pregnancies exposed to azathioprine during the 1st trimester were prospectively assessed and compared to that of pregnancies exposed to another drug used for the same indications. Secondly, the rate of preterm births was compared between fetuses exposed to azathioprine at least during the third trimester and those exposed during the first trimester only. RESULTS: From 447 requests for a risk assessment for women receiving azathioprine during pregnancy, 193 pregnancies meet inclusion criteria. One hundred and twenty-four of them were exposed to azathioprine during the 1st trimester and were compared to that of 124 pregnancies exposed to another drug used for the same indication. Azathioprine use during the first trimester was not statistically associated with the risk of all birth defects ([7.3% vs. 5.4%]; [OR=1.36; 95%CI: 0.44-4.20]) nor with major birth defects (5.2% vs. 1.8% [OR=2.96; 95%CI: 0.56-15.64]). The rate of preterm births (22.5% vs. 27.3%, P=0.579) was similar regardless of the exposure period to azathioprine (at least during the third trimester or during the first trimester only). CONCLUSIONS: This study confirms that first trimester exposure to azathioprine is not associated with an elevated rate of birth defects and that the high rate of preterm births among women exposed to azathioprine is probably explained by the underlying maternal disease.