propylthiouracil and Birth-Weight

Hyperthyroidism can occur during pregnancy and the postpartum period, and the treatment of hyperthyroidism should be considered in the preconception phase. Pregnancy has multiple normal physiologic effects on thyroid hormone, which is a separate process distinct from syndromes such as transient hyperthyroidism of hyperemesis gravidarum. The rationale regarding antithyroid drug use during different stages of pregnancy is reviewed, including the literature regarding adverse neonatal outcomes such as aplasia cutis and methimazole embryopathy in the setting of first trimester maternal methimazole use. The use of treatment modalities for hyperthyroidism during pregnancy such as surgery is also discussed. Studies of maternal, fetal, and neonatal complications of hyperthyroidism are examined in this article. Moreover, the evidence regarding antithyroid drugs, specifically methimazole and propylthiouracil, during lactation is considered. Other disease conditions that can take place during pregnancy and the postpartum period such as hyperemesis gravidarum, subclinical hyperthyroidism, gestational trophoblastic disease, and postpartum thyroiditis and their treatments are also presented.

Topics: Antithyroid Agents; Birth Weight; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Postpartum Period; Preconception Care; Pregnancy; Pregnancy Complications; Premature Birth; Propylthiouracil; Risk; Thyroid Hormones

Topics: Adolescent; Adult; Birth Weight; Female; Fetal Death; Humans; Hyperthyroidism; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones

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.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Birth Weight; Case-Control Studies; Cohort Studies; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Propylthiouracil; Ultrasonography, Prenatal

Twenty-four Rambouillet ewe lambs (average weight=43.7+/-1.2 kg, approximately 6 months of age) were used to examine the effect of thyroid suppression before the onset of puberty on serum thyroid hormones, body weights (BW), and reproductive performance. Beginning in early September, ewe lambs were randomly assigned to three treatments (n=8 lambs/treatment). All animals remained in a single pen (4 x 12 m) with access to salt, water, shade and alfalfa hay (2.5 kg per animal per day) throughout the experiment. Beginning on Day 0 (first day of treatment), all ewe lambs received daily treatments (gavage) for 15 days consisting of 0, 20, or 40 mg 6-N-propyl-2-thiouracil(PTU)/kg BW per day. Beginning on Day 15, the 20 and 40 mg treatments were lowered to 10 and 20 mg PTU/kg BW, respectively. All animals were treated for 28 days. Ovarian cyclicity was determined by twice weekly progesterone (P(4)) analysis. Thyroxine (T(4)) concentrations were similar on Day 0 (61.6, 54.8 and 56.9+/-2.5 ng/ml, P=0.17) in ewe lambs receiving 0, 20 and 40 mg PTU/kg BW, respectively. By Day 7, both PTU-treated groups had T(4) values less than 20 ng/ml (9.0 and 15.4+/-2.5 ng/ml) compared with 78.5 ng/ml in controls (P<0.01). By 7 days after termination of PTU treatment, serum T(4) had risen to 29.1 and 26.9 (+/-2.9)ng/ml in the 20/10 and 40/20 PTU groups, respectively. On Day 66, control ewes had 55.0 ng T(4)/ml compared with 43.1 and 39.0 (+/-2.6 ng/ml) for ewes in the 20/10 and 40/20 groups, respectively (linear, P<0.01). Serum triiodothyronine (T(3)) followed a similar pattern to that observed for T(4). Ewe lamb BW were similar (P>0.50) among groups throughout the treatment period. However, following the treatment, PTU-treated ewes tended (P<0.10) to weigh less than controls. Average Julian day of puberty was also similar (P>0.50) among treatments (286, 288 and 288+/-5 days; control, 20/10 and 40/20, respectively). Control ewes had a pregnancy rate of 75%, while both PTU-treated groups had pregnancy rates of 88% (P>0.20). The administration of PTU resulted in a rapid decline in serum T(4) and T(3) but neither time of puberty nor pregnancy rates were affected by lowered thyroid hormones.

Topics: Animals; Animals, Newborn; Antithyroid Agents; Birth Weight; Body Weight; Female; Male; Pregnancy; Progesterone; Propylthiouracil; Random Allocation; Reproduction; Sexual Maturation; Sheep; Thyroxine; Triiodothyronine

Primiparous, spring-calving Brahman cows (BW = 425.0 +/- 13.8 kg, body condition score [BCS] = 5.0 +/- .2 units; SEM) were used to study the effects of thyroid manipulation on weight gain, milk production, and reproduction. Nine cows served as controls. Nine cows were induced to become hypothyroid by daily ingestion of 4 mg/kg BW of 6-n-propyl-2-thiouracil (PTU). Cows were stratified to treatment 1 d after calving based on season of birth, BW, BCS, calf sex, and calf sire. The treatment period lasted for 84 d and was followed by a 56-d posttreatment period. Cow BW, BCS, and calf weight were recorded twice weekly. Milk production was estimated at 14, 28, 56, 84, 98, 112, and 140 d after calving. Weekly blood samples were obtained for analysis of triiodothyronine (T3), thyroxine (T4), and progesterone (P4). Estrus was monitored twice daily with the aid of a fertile bull equipped with a chin ball marker. Hypothyroidism was effectively induced in all PTU cows during the treatment period. The PTU cows gained more (P = .002) weight (54.6 +/- 7.6 kg) and tended (P = .06) to increase body condition (.61 +/- .17 units) more than control cows (15.7 +/- 7.6 kg; .11 +/- .17 units) during the treatment period. Control calves gained at a faster rate (.85 +/- .04 kg/d; P < .01) than PTU calves (.70 +/- .04 kg/d) during the treatment period. Milk production was lower (P < .05) in PTU cows on d 56 and 84. During posttreatment all trends were reversed, and BW, BCS, calf weight, and milk production were similar between the two groups by d 140. Reproductive performance was not affected by induction of hypothyroidism. In conclusion, induction of hypothyroidism was successful in increasing cow weight and BCS gains and suppressing milk production during the treatment period, but these changes were not successful in improving reproductive performance of primiparous Brahman cows.

Topics: Animals; Antithyroid Agents; Birth Weight; Body Composition; Cattle; Female; Hypothyroidism; Lactation; Progesterone; Propylthiouracil; Reproduction; Weight Gain

With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

Topics: Birth Weight; Carbimazole; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Growth; Humans; Infant, Newborn; Intelligence; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Rats with diets containing 0.2% propylthiouracil (PTU) throughout gestation had progeny with persistent cyanosis and high neonatal mortality. Histological and histochemical studies failed to reveal lung abnormalities in these pups. Studies of the blood of PTU-fed dams demonstrated that hemoglobin, packed cell volume, and numbers of erythrocytes were significantly reduced. In their 21-day fetal young, erythrocytopenia was accompanied by an elevated mean corpuscular volume and a reduced mean corpuscular hemoglobin concentration. Imprints of marrow from dams and of liver and spleens of the young showed normoblastic erythropoiesis. A granulocytic leucocytosis was present in the blood of the PTU-fed dams, whereas their progeny had a granulocytopenic leucopenia. Tissue concentrations of copper, zinc, manganese, magnesium and iron were determined. The most striking changes observed were the significant elevations of copper in the dams' brain, liver and kidneys. No changes in the concentration of any of the trace minerals were found in the livers of the pups. Food restriction to the dam failed to significantly alter maternal or fetal hematologic or trace element concentrations as compared with controls. It is evident that PTU, when fed to pregnant rats, has demonstrable effects on erythropoiesis, granulocytopoiesis, and maternal trace element distribution. It is not presently known whether these phenomena are interrelated.

Topics: Anemia, Macrocytic; Animals; Birth Weight; Copper; Cyanosis; Diet; Erythrocytes; Erythropoiesis; Female; Hypothyroidism; Leukocyte Count; Magnesium; Male; Manganese; Maternal-Fetal Exchange; Pregnancy; Propylthiouracil; Rats; Trace Elements; Zinc

Topics: Birth Weight; Body Weight; Digitalis Glycosides; Exophthalmos; Female; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Propylthiouracil; Tachycardia; Thyroid Function Tests

Topics: Animals; Animals, Newborn; Birth Weight; Female; Mice; Pregnancy; Pregnancy, Animal; Propylthiouracil; Secretory Rate; Thyroid Gland; Thyroxine