Riesgo teratogénico de la exposición prenatal a hipertiroidismo tratadocon antitiroideos: un estudio caso-control^ies

Prenatal exposition to antithyroid drugs, propylthiouracil (PTU) and methimazole (MMI), specially the latest, have been associated to teratogenic risk, but information is not conclusive yet. Our aim was to evaluate the association of antithyroid drugs with congenital malformations using a case control study with data from the Estudio Colaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC). We evaluated 43 major isolated malformations and two combinations of malformations in 65.731 malformed patients and 110.814 healthy controls. In order to avoid the possible biases the analysis was performed by three groups of controls: a) a group without malformations b) a case-affected control group with a different malformation c) a case-affected control group with a different malformation and exposed to any drugs. The study was done with paired controls (by hospital and year) 1 to 4 and then with the total of controls. The only isolated malformation that showed association was atresia of esophagus. The following combinations also showed association: 1) esophageal atresia or choanal atresia 2) esophageal atresia or choanal atresia or omphalocele. An adjustment was performed by logistic regression considering the mother variables (age, parity and education), OR was calculated for the three groups of controls (healthy, malformed and exposed malformed). Results were: esophageal atresia OR=12.97 (CI95 %: 3.93-42.72), OR=6.00 (CI95 %:1.84-19.55) and OR=5.37 (CI95 %:1.63 - 17.60); esophageal atresia or choanal atresia OR=19.22 (CI95 %:7.41-49.82), OR=6.00 (CI95 %:1.84-19.55) and OR=7.97 (CI95 %:3.09 - 20.52); esophageal atresia or choanal atresia or omphalocele OR=12.67 (CI95 %:5.24 - 30.60), OR=5.86 (CI95 %:2.46 - 13.96) and OR=5.04 (CI95 %: 2.11-12.05). All the cases with the associated malformations were exposed only to MMI. Although future studies will be necessary to confirm these findings, our results help to define a picture of MMI embryopathy and support worldwide recommendations in regard to avoiding the use of this drug during pregnancy and its replacement by another alternative drug.