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Bu çalışmanın amacı, gebelikte makrolid maruziyeti sonrası major konjenital malformasyon, kardiak malformasyon, diğer spesifik organ malformasyonları ve advers gebelik sonuçları riskinde bir artış olup olmadığını var olan literatürün sistematik incelenmesi ve meta-analiz ile ortaya koymaktır. Prenatal dönemde makrolidlere maruz kalım ve gebelik sonuçları ile ilgili literatür taraması Haziran 2019 kadar PubMed/MEDLINE, Cochrane Central Register of Controlled Trials ve Reprotox veri tabanlarında yapıldı. Makrolidlere maruz kalmayan ve/veya non-teratojenik ilaçlara maruz kalan gebeler ve diğer antibiyotiklere maruz kalan gebeler olmak üzere iki farklı kontrol grubu belirlendi. Veriler, rastgele etki metodu kullanılarak Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) programı ile birleştirildi.Toplam 12 kohort, 4 vaka-kontrol ve 1 nested-vaka-kontrol çalışması analize dahil edildi. Kohort çalışmalarında, azitromisin maruziyeti sonrası major konjenital malformasyonlarda istatistiksel olarak anlamlı ve hafif artmış risk bulundu (OR 1,21 %95 CI 1,08-1,36) ve duyarlılık analizinde bu anlamlılık devam etti (OR 1,22 %95 CI 1,07-1,39). Vaka-kontrol çalışmalarında ise ilk trimester eritromisin maruziyeti sonrası sadece hipospadias riskini anlamlı olarak azalttığı bulundu. Diğer gebelik sonuçları incelendiğinde; tüm makrolid maruziyetinin spontan abortus ve elektif terminasyon riskini arttırdığı, canlı doğum ihtimalini azalttığı bulundu. Bu sonuçlar değerlendirilirken verilerimizin bir kısmının ham veri olması ve maternal hastalık gibi karıştırıcı faktörlerin ekarte edilememiş olması göz önüne alınmalıdır. Analiz edilen çalışmalarda makrolidler, gebelik sonuçlarını olumsuz etkileyebilecek endikasyonlarda kullanılmış olabilir. Diğer sorun kontrol gruplarımızın, hastalık şiddeti açısından uygun kontrol grupları olmamasıdır. Bu sebeple hastalık şiddeti açısından uygun şekilde eşleştirilmiş kontrollerle yapılmış ileriki çalışmalara ihtiyaç vardır. İlk trimesterde azitromisin maruziyeti olan gebeliklerde detaylı fetal ultrason önerilebilir. The aim was to determine whether gestational use of macrolides leads to an increase in rates of overall major congenital malformations, heart defects, specific organ malformations and pregnancy outcomes using systematic review and meta-analysis.A literature search regarding prenatal macrolides exposures and pregnancy outcomes from inception to Jun 2019 were conducted in PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox® databases. The pregnant women who were not exposed to macrolides and/or exposed to non-teratogenic medications and the pregnant women who were exposed to other antibiotics were defined as two different control groups. Dichotomous outcomes and reported odds ratios are combined using random-effects method in Review Manager 5.3 (Cochrane Collaboration, Oxford, UK).Twelve cohort, four case-control and one nested-case-control studies were included. Azithromycin was associated with a significant increase in rates of major congenital malformations both in primary analysis (OR 1,21 %95 CI 1,08-1,36) and sensitivity analysis (OR 1,22 %95 CI 1,07-1,39) of cohort studies. In case-control studies, first trimester erythromycin exposure was only associated with decreased in the rates of hypospadias. The significant increases in rates of spontaneous abortus and elective termination and significant decreased in rates of live birth in all macrolide analyses were found.When evaluating our results, it should be taken into consideration that confounding factors such as the disease of a mother have not been excluded. Although we excluded studies with specific indications, it is impossible to rule out confounding by indication since the included studies might still have had indications which may be associated with fetal adverse effects. In addition, pregnant women exposed to penicillins indeed may not be an appropriate disease-matched comparison group for macrolide exposure. Further studies with appropriate matched controls according to disease severity are needed. Nevertheless, a level II ultrasound may be offered following azithromycin exposure during the first trimester. 154

Congenital malformations might occur because of environmental or genetic factors, and sometimes occur because of unknown causes. Acetazolamide is a carbonic anhydrase inhibitor that is used to treat idiopathic intracranial hypertension, glaucoma, and epilepsy. The use of acetazolamide has not been recommended for pregnant women because of reported teratogenic risks. Congenital malformations, such as ectrodactyly, syndactyly, cleft lip/palate, and retarded incisor teeth development, have been reported in experimental animals. However, tooth agenesis due to the use of acetazolamide has not been reported yet. Oligodontia is a severe type of tooth agenesis involving six or more congenitally missing teeth. The causes of oligodontia are attributed to environmental factors, such as irradiation, drugs, trauma, tumors, infection, genetic factors, or a combination. There is no credible evidence of undesirable effects of acetazolamide use in human pregnancy. However, we report a case of a 12-year-old Saudi boy who was exposed to maternal acetazolamide (1,000 mg/day) for treatment of idiopathic intracranial hypertension before pregnancy, during the first trimester, and throughout the pregnancy. This treatment might have resulted in some congenital malformations, such as ectrodactyly, syndactyly, and oligodontia.