Propylthiouracil (PTU) is presently considered to be the treatment of choice for hyperthyroidism in pregnancy. It is known to cross the human placenta, and therefore may affect the fetus. The major aims of this study were to evaluate the rate of major anomalies and to report the rate of fetal goitre, accompanied by hypothyroidism, in fetuses/ newborns of mothers after in utero exposure to PTU.Prospective observational controlled cohort study of PTU-exposed pregnancies of women counselled by the Israeli Teratology Information Service between the years 1994 and 2004 compared with women exposed to nonteratogens.We followed up 115 PTU-exposed pregnancies and 1141 controls. The rate of major anomalies was comparable between the groups [PTU 1/80 (1.3%), control 34/1066 (3.2%), P= 0.507]. Hypothyroidism was found in 9.5% of fetuses/neonates (56.8% of whom with goitre). Hyperthyroidism, possibly resulting from maternal disease, was found in 10.3%. Goitres prenatally diagnosed by ultrasound were successfully treated in utero by maternal dose adjustment. In most cases neonatal thyroid functions normalized during the first month of life without any treatment. Median neonatal birth weight was lower [PTU 3145 g (2655-3537) vs. control 3300 g (2968-3600), P= 0.018].PTU does not seem to be a major human teratogen. However, it could cause fetal/neonatal hypothyroidism with or without goitre. Fetal thyroid size monitoring and neonatal thyroid function tests are important for appropriate prevention and treatment.
Data suggest a large variability in the effectiveness of the orally active iron chelator, deferiprone, in inducing a sustained decrease in body iron to concentrations compatible with the avoidance of complications from iron overload. We analyzed 19 patients with thalassemia major who were undergoing long-term therapy with deferiprone (75 mg/kg/day every 8 hours). In seven of the 19 patients, hepatic iron concentration had been reduced or maintained at less than 7 mg/g of dry weight liver tissue, associated with no evidence of iron-induced toxicity (group A). In the remaining 12, hepatic iron concentration had either stabilized at higher than 7 mg/g of dry weight liver tissue, or increased to such concentrations during therapy with deferiprone (group B). We studied in these patients determinants that may explain such variability, including initial hepatic iron concentrations, compliance, transfusion index, pharmacokinetic characteristics of deferiprone, and plasma vitamin C status. Patients in group B showed significantly decreased plasma vitamin C concentrations compared with those in group A, who demonstrated normal levels (0.04 mg/dl [0.04-0.19 mg/dl] and 0.62 mg/day [0.44-1.05 mg/day], respectively; p = 0.02). A significant difference in apparent volume of distribution (Vd/F) had developed between the groups over time, with a higher Vd/F in group B (1.66 [0.681, group A] and 3.16 [0.811, group B]; p = 0.006). Group B had started with hepatic iron concentrations that were significantly higher than those of group A, a difference that became more pronounced over time. In the initial analysis, serum ferritin concentrations were also higher in group B. The two groups did not differ in the remaining factors. The initial hepatic iron concentrations predicted the slope of change in this value. Regression analysis suggested that patients with initial hepatic iron concentration of less than or equal to 7.22 mg/g of dry weight liver tissue are unlikely to further decrease while taking deferiprone 75 mg/kg/day. Vitamin C deficiency developed in patients in group B over time. Vitamin C is an important biologic cofactor that plays a role in the distribution of iron. The trend of increase in Vd/F of deferiprone over time may imply a compartment shift of iron stores to one less accessed by deferiprone. This study confirmed the effectiveness of deferiprone in heavily iron-loaded patients and provided evidence that its effectiveness decreases in proportion to liver iron load.
Lithium taken during the first trimester of pregnancy appears to increase the risk of cardiovascular anomalies in infants, although some of these anomalies resolve spontaneously. Lithium also raises the likelihood of miscarriage. On the other hand, the risk of illness recurrence is high for women who discontinue taking medication during pregnancy, and so the decision should be made on an individual basis. It is recommended that women treated with lithium during organogenesis receive fetal echocardiography and level-2 ultrasound.
The Israeli Teratogen Information Service prospectively followed up 210 pregnancies with first trimester carbamazepine exposure. Pregnancy outcome was compared with that of two overlapping controls, matched and general (n = 629), exposed to nonteratogenic agents. Our study suggests a twofold increase in the rate of major congenital anomalies (12/160 [carbamazepine] versus 18/560 [general control]; relative risk 2.24; 95% CI 1.1–4.56) and a birth weight reduction of approximately 250 g after in utero exposure to carbamazepine.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)