Utilisation des anti-infectieux chez la femme enceinte et issues indésirables de grossesse (avortement spontané, malformations congénitales et faible poids à la naissance)

Infections during pregnancy are frequent. For example, the prevalence of urinary tract infections is between 2% and 10%. A pregnant woman with asymptomatic bacteriuria is 20-30 times more likely to develop pyelonephritis, 50% more likely to have a baby with a low birth weight, and twice as likely to have a premature baby. It is therefore essential to treat pregnant maternal infections. Though antibiotics are among the most used drugs during pregnancy (20%-49%), evidence regarding its fetal safety remains limited. As such, the choice of antibiotics that should be prescribed during the first trimester of pregnancy could be a difficult task. Therefore, our aim was to assess the risk of spontaneous abortion and major congenital malformations associated with antibiotics use during pregnancy. Furthermore, it is estimated that 8-14% of low birth weight occurring in endemics regions is due to malaria. Hence, the growing role of some antibiotics such as azithromycin and trimethoprim-sulfamethoxazole in the prevention of malaria during pregnancy emerged as a potential avenue of exploration. Within the QPC, a nested case control study was conducted to evaluate the link between gestational exposure to antibiotics and the risk of spontaneous abortion. To assess the association with major congenital malformations, a cohort study was used. A meta-analysis was carried out to synthesize data on the efficacy of antimalarial drugs to reduce the risk of low birth weight Our results indicate that amoxicillin, cephalosporins and nitrofurantoin use during pregnancy were not associated with an increased risk of spontaneous abortion or major congenital malformations. In contrast, we observed a 65% and 70% increased risk of spontaneous abortion following clarithromycin and metronidazole use respectively. Trimethoprim-sulfamethoxazole, quinolones and tetracyclines exposure was also linked to more than two fold increased risk of spontaneous abortion. Doxycycline use was associated with more than a twofold increased risk of circulatory system malformation and more than a threefold increased risk of ventricular/atrial septal defect. Clindamycin exposure was associated with a 67% increased risk of musculoskeletal system malformations and 81% increased risk of ventricular/atrial septal defect This thesis also demonstrates that antimalarial were associated with a 27% reduction of the risk of low birth weight. However, this finding could be overestimate. Three doses compared to two doses of sulfadoxine-pyrimethamine was associated with a 25% reduction of the risk of low birth weight in regions where the prevalence of molecular markers of this drug did not exceed 50%.   In conclusion, health professionals should give priority to safer antibiotics such as cephalosporins, amoxicillin and nitrofurantoin for the treatment of maternal infections occurring in early pregnancy (first trimester) when possible. The use of three doses compared to two doses of sulfadoxine-pyrimethamine should be recommended by health professionals for malaria prevention during pregnancy in areas where the prevalence of molecular markers for this drug does not exceed 50%.

Keyphrases: Antibiotics, Spontaneous abortions, Congenital malformations, Low birth weight, Quebec pregnancy cohort, Nested case control, Cohort, Meta-analysis