HARM WORKSHEET Citation: Treatment of Graves Disease with Antithyroid Dr !s in the "irst Trimester of #re!

nan$y and the #reva%en$e of Con!enita% Ma%formation Are the res %ts of this harm st dy va%id& Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause? 'es( We reviewed the cases of women with Graves disease who became pregnant. The Pregnancy outcomes of !"" women were #nown, and there were $% ! live births. &&' alone had been used to treat (") of the women, and ($!* women had been treated with PT+ alone. The ), $ women who had received no medication for the treatment of Graves disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The anti thyroid drugs were evaluated for associations with congenital malformations. Cant te%%(

Were treatments-exposures and clinical outcomes measured in the same ways in both groups .was the assessment of outcomes either ob/ective or blinded to exposure0? Was the follow1up of study patients complete and long enough?

'es( We reviewed the cases of %"( women with Graves disease who became pregnant between 2anuary (, (%%%, and 3ecember 4(, ),(,, and the pregnancy outcome of !"" .%!50 women was #nown.

3o the results satisfy some 6diagnostic tests for causation7? 's it clear that the exposure preceded the 'es( onset of the outcome? 'n utero exposure to &&' during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly 's there a dose1response gradient? )o( The dosage of the antithyroid drug did not differ significantly according to whether or not the mothers delivered a child with a congenital malformation8 &&' group,P9,.(4: PT+ group,P9,.*". 's there positive evidence from a 'es( 6dechallenge1rechallenge7 study? ;vidence regarding the impact of antithyroid drugs on pregnancy outcomes remains inconclusive. <everal case reports have suggested that PT+ may be safer than &&' during pregnancy because of the occurrence of congenital malformations associated with the use of &&' during pregnancy .aplasia cutis congenita, choanal atresia, and intestinal anomalies0. =owever, a casual relationship between &&' and malformations cannot be excluded. 't has been suggested that thyrotoxicosis might it self be a teratogen because fetal loss and intrauterine growth retardation have been observed in untreated hyperthyroid pregnant women. 's the association consistent from study to 'es( study? 'n a recent study in ),(,, >lementi et al. investigated the use of &&'->&? and PT+ for associations with congenital malformations and found that prenatal exposure to &&'->&? was significantly associated with choanal atresia, omphalocele, and total situs inversus and-or dextrocardia 3oes the association ma#e biological Cant te%% sense?

Are the va%id res %ts from this harm st dy im*ortant& The mothers treated with &&' during pregnancy had higher odds of giving birth to an infant with a congenital malformation .@A 9 ).)*: %$5 >', (.$"B4.44: P9,.,,,)0. @n the other hand, no in1creased ris# of giving birth to an infant with a congenital malformationwas found among themothers treatedwith PT+ .@A 9 ,. : %$5 >', ,."(B(.,4: P9,.,!%0. The results indicated that exposure to &&' during the first trimester of pregnancy increases the ris# of giving birth to an infant with a congenital malformation. 't seems preferable to treat Graves disease with PT+ because it appears to be safer touse in the fertile period. Sho %d these va%id+ *otentia%%y im*ortant res %ts $han!e the treatment of yo r *atient& 's your patient so different from those in the study that its results dont apply? What are your patients ris#s of the adverse event? To calculate the CC= .number of patients you need to treat to harm one of them0 for any odds ratio .@A0 and your patients expected event rate for this adverse event if they were not exposed to this treatment .P;;A08 CC= 9 (- DA' 9 (- .;;A1>;A0 What are your patients preferences, concerns and expectations from this treatment? We can apply the result of this study in patient here because there is no much different characteristics of mother in this study and in patient here. >;A 9 ),(5 ;;A .&&'0 9 ",(5 ;;A .PT+0 9 (,%5 CC= .&&'0 9 (-.;;A .&&'0 1 >;A0 9 (-.",(1),(0 9 (-) 5 9 $, 2adi. Perlu mengobati $, orang dengan &&' untu# munculnya ( bayi dengan malformasi #ongenital The patient preferences, concern and expectation from this treatment in this study is patient with Graves disease can choose the anti thyroid drugs for treatment graves disease in their first trimester of pregnancy. 't seems, preferable to treat Graves disease with PT+ because it appears to be safer to use in the fertile period, because exposure with &&' during the first trimester of pregnancy increased the ris# of congenital anomalies, including the ris# of the rare anomalies aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

What alternative treatments are available?

'n the first trimester of pregnancy, PT+ is safer than &&' to treatment Graves disease, because exposure with &&' during the first trimester of pregnancy increased the ris# of congenital anomalies, including the ris# of the rare anomalies aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.