Possible association between different congenital abnormalities and use of different sulfonamides during pregnancy
ABSTRACT The objective of the study presented here was to check the debated human teratogenic potential of sulfonamide drugs. Five different sulfonamides such as sulfamethazine, sulfathiourea, sulfamethoxypyridazine, sulfamethoxydiazine and the combination of sulfamethazine-sulfathiourea-sulfamethoxypyridazine were differentiated. Cases with congenital abnormalities were compared with their matched controls without congenital abnormalities in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 38,151 newborn infants without any congenital abnormalities (control group), 163 (0.4%) had mothers who were treated with the sulfonamides studied during pregnancy, while of 22,843 cases with congenital abnormalities, 140 (0.6%) had mothers who were treated with the sulfonamides studied during pregnancy. The analysis of cases and matched controls indicated a higher rate of cardiovascular malformation (adjusted prevalence odds ratios [POR] with 95% CI: 3.5, 1.9-6.4) and clubfoot (adjusted POR with 95% CI: 2.6, 1.1-6.2) in infants born to mothers with sulfonamide treatment in the second and third months of pregnancy. The detailed analysis of different sulfonamides showed a possible association between cardiovascular malformations (adjusted POR with 95%; CI: 6.5, 2.6-15.9), particularly ventricular septal defect (17.1, 1.3-141.1) and sulfamethoxydiazine during the second and third months of pregnancy. In addition, a possible association was found between clubfoot and sulfathiourea, both during the entire pregnancy (adjusted POR with 95% CI: 2.3, 1.2-4.3) and in the second and third months of gestation (3.9, 1.1-13.8). Thus, maternal treatment of sulfamethoxydiazine may cause ventricular septal defect, while sulfathiourea may induce clubfoot; however, further studies are needed to verify or reject these associations.
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ABSTRACT: Daily prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) significantly decreases morbidity and mortality among people living with HIV. Some clinicians are reluctant to use TMP-SMZ in pregnant and breastfeeding HIV-infected women because of concerns about the possible teratogenicity when used in the first trimester and about its potential to induce hyperbilirubinemia near term and during early breastfeeding. We systematically reviewed evidence regarding the toxicity of TMP-SMZ prophylaxis in pregnant and breastfeeding women to help guide practice in resource-limited settings. We identified relevant literature by searching PubMed and MEDLINE via OVID, Embase, and Science Citation Index for data on hyperbilirubinemia, kernicterus, and teratogenicity associated with administration of sulfonamides and TMP-SMZ through July 2005. We also reviewed the reference lists of identified articles. Most studies demonstrated that TMP-SMZ was not associated with hyperbilirubinemia when administered to mothers during pregnancy and breastfeeding. No cases of kernicterus were reported in neonates after maternal ingestion of sulfonamides. There is mixed evidence linking ingestion of TMP-SMZ and other sulfonamides in early pregnancy to elevated risks of oral clefts, neural tube defects, and cardiovascular and urinary tract abnormalities, although some sources found that supplementation with folic acid might ameliorate this potential risk. Existing guidelines recommend that HIV-infected pregnant women receive prophylaxis, but they differ with regards to stage of disease at which to initiate treatment, need for CD4+ T-lymphocyte testing, and prophylaxis during the first trimester. Existing data indicate that the risk of serious injury to neonates from maternal use of daily TMP-SMZ prophylaxis during pregnancy and breastfeeding is small. Given the substantial benefits of TMP-SMZ prophylaxis for HIV-infected women living in resource-limited settings, this review indicates that it is safe to abide by the WHO guidelines recommending daily TMP-SMZ prophylaxis for HIV-infected pregnant women.AIDS reviews 8(1):24-36. · 4.02 Impact Factor
Article: Drug exposure in pregnant women[Show abstract] [Hide abstract]
ABSTRACT: The objectives of this paper are to describe the Hungarian case-control surveillance system of congenital abnormalities (HCCSCA), to summarize the principles of this activity and our main experiences. Among the main principles, the importance of the time factor (the first trimester concept is outdated), the differentiation of isolated and multiple manifestations of the seemingly same congenital abnormalities, noxa specificity, the separation of drugs and pregnancy supplements within medicinal products (or medicines) are stressed. After some methodological problems (recall bias, chance effect), the main experiences regarding the risk and benefit of medicines are summarized. The conclusion is that the results of our studies based on the data set of the HCCSCA showed that at present the exaggerated teratogenic risk of drugs is much more harmful for the fetus than the real teratogenic effect of some drugs themselves. Medical doctors and other experts therefore need more education to know the principles and findings of modern human teratology because it may help us to have a better balance between the risk and benefit of drug use during pregnancy.Lupus 02/2004; 13(9):740-5. DOI:10.1191/0961203303lu1095oa · 2.48 Impact Factor
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ABSTRACT: Environmental teratogenic factors (e.g. alcohol) are preventable. We focus our analysis on human teratogenic drugs which are not used frequently during pregnancy. The previous human teratogenic studies had serious methodological problems, e.g. the first trimester concept is outdated because environmental teratogens cannot induce congenital abnormalities in the first month of gestation. In addition, teratogens usually cause specific congenital abnormalities or syndromes. Finally, the importance of chemical structures, administrative routes and reasons for treatment at the evaluation of medicinal products was not considered. On the other hand, in the so-called case-control epidemiological studies in general recall bias was not limited. These biases explain that the teratogenic risk of drugs is exaggerated, while the benefit of medicine use during pregnancy is underestimated. Thus, a better balance is needed between the risk and benefit of drug treatments during pregnancy. Of course, we have to do our best to reduce the risk of teratogenic drugs as much as possible, however, it is worth stressing the preventive effect of drugs for maternal diseases (e.g. diabetes mellitus and hyperthermia) related congenital abnormalities.International journal of medical sciences 02/2005; 2(3):100-6. · 1.55 Impact Factor