1/10. prenatal diagnosis of thyroid hormone resistance.A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor beta (TRbeta) gene. She presented with symptoms and signs of hyperthyroidism and was successfully treated with 3,5,3'-triiodothyroacetic acid (TRIAC) until the onset of pregnancy. This therapy was then discontinued in order to prevent TRIAC, a compound that crosses the placental barrier, from exerting adverse effects on normal fetal development. However, as the patient showed a recurrence of thyrotoxic features after TRIAC withdrawal, we sought to verify, by means of genetic analysis and hormone measurements, whether the fetus was also affected by RTH, in order to rapidly reinstitute TRIAC therapy, which could potentially be beneficial to both the mother and fetus. At 17 weeks gestation, fetal dna was extracted from chorionic villi and was used as a template for PCR and restriction analysis together with direct sequencing of the TRbeta gene. The results indicated that the fetus was also heterozygous for the T337A mutation. Accordingly, TRIAC treatment at a dose of 2.1 mg/day was restarted at 20 weeks gestation. The mother rapidly became euthyroid, and the fetus grew normally up to 24 weeks gestation. At 29 weeks gestation mild growth retardation and fetal goiter were observed, prompting cordocentesis. Circulating fetal TSH was very high (287 mU/L) with a markedly reduced TSH bioactivity (B/I: 1.1 /- 0.4 vs 12.7 /- 1.2), while fetal FT4 concentrations were normal (8.7 pmol/L; normal values in age-matched fetuses: 5-22 pmol/L). Fetal FT3 levels were raised (7.1 pmol/L; normal values in age-matched fetuses: <4 pmol/L), as a consequence of 100% cross-reactivity of TRIAC in the FT3 assay method. To reduce the extremely high circulating TSH levels and fetal goiter, the dose of TRIAC was increased to 3.5 mg/day. To monitor the possible intrauterine hypothyroidism, another cordocentesis was performed at 33 weeks gestation, showing that TSH levels were reduced by 50% (from 287 to 144 mU/L). Furthermore, a simultaneous ultrasound examination revealed a clear reduction in fetal goiter. After this latter cordocentesis, acute complications occured, prompting delivery by cesarean section. The female neonate was critically ill, with multiple-organ failure and respiratory distress syndrome. In addition, a small goiter and biochemical features ofhypothyroidism were noted transiently and probably related to the prematurity of the infant. At present, the baby is clinically euthyroid, without goiter, and only exhibits biochemical features of RTH. In summary, although further fetal studies in cases of RTH are necessary to determine whether elevated TSH levels with a markedly reduced bioactivity are a common finding, our data suggest transient biochemical hypothyroidism in RTH during fetal development. Furthermore, we advocate prenatal diagnosis of RTH and adequate treatment of the disease in case of maternal hyperthyroidism, to avoid fetal thyrotrope hyperplasia, reduce fetal goiter, and maintain maternal euthyroidism during pregnancy.- - - - - - - - - - ranking = 1keywords = fetal development (Clic here for more details about this article) |
2/10. Fetal pituitary negative feedback at early gestational age.We describe an early prenatal diagnosis and the successful treatment of fetal Graves' disease from transplacental transfer of maternal thyroid stimulating autoantibodies (TSAb). The diagnosis of fetal thyrotoxicosis was made by umbilical cord sampling (UBS) at 20 weeks gestation, based on suppressed TSH with elevated FT4 levels. Therapy with propylthiouracil (PTU) improved fetal thyroid function tests as well as the clinical signs of fetal Graves' disease. Three more UBS were conducted before delivery indicating persisting mild fetal hyperthyroidism. Undetectable concentrations of thyrotrophin in fetal serum in the presence of markedly elevated FT4, suggests pituitary negative feedback at as early as 20 weeks gestation. amniotic fluid thyrotrophin levels were measured at 20,24 and 26 weeks and were shown to correlate better with (elevated) maternal rather than (suppressed) fetal TSH values; therefore, we believe that amniotic fluid thyrotrophin measurement is unreliable for prediction of fetal thyroid status. Our observation is the first documentation of an intact feedback mechanism so early in fetal development and it suggests that pituitary maturation occurs earlier than previously believed.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
3/10. In utero transplantation of stem cells in humans: immunological aspects and clinical follow-up of patients.Four human fetuses were treated by transplantation of human fetal liver stem cells. Two of them had severe immunodeficiency disease and the two other ones had thalassemia major. Three of these in utero transplants were followed by engraftment. The three patients are now born: the first one is now very healthy thanks to the reconstitution of cell-mediated immunity associated with this transplant, and he lives normally at home; the two other ones, who have been more recently treated, have a significant improvement of their condition and they also live normally at home. This procedure, for the first time used in humans, has therefore demonstrated its feasibility and its efficacy: during early fetal development, foreign cells engraft readily and may result in cure or significant correction of a large variety of inherited diseases.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
4/10. Prune-belly syndrome associated with Potter (renal nonfunction) syndrome.Three fatal cases of prune-belly syndrome were associated with nonrenal features of Potter syndrome. The abdominal muscle hypoplasia is thought to be a result of large kidneys compression the developing abdominal musculature during a critical phase of fetal development. Thus, Potter syndrome and prune-belly syndrome may coexist when nonfunctioning large kidneys result in oligohydramnios. A teratogenic role of cytomegalovirus inclusion disease and other viruses is possible in the pathogenesis of these syndromes.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
5/10. Clubfeet associated with hydrocephalus: new evidence of gradual dynamic development in utero.clubfoot, a relatively frequent congenital malformation, may be associated with several genetic syndromes or other malformations, or may appear as an isolated idiopathic anomaly. We describe the intrauterine development of clubfeet subsequent and in parallel to fetal hydrocephalus formation, as followed by serial transvaginal sonographic scans at 11-16 weeks' gestation. The possibility of a causal relationship between the central nervous system malformation and the clubfeet is suggested. To the best of our knowledge, this is the first description of the dynamic, in vivo fetal development of hydrocephalus and clubfeet at 11-16 weeks' gestation.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
6/10. Prenatal stroke in a neonate heterozygous for factor v Leiden mutation.The authors report an infant with congenital hemiplegia associated to heterozygosity for factor v Leiden. Prenatal stroke in the left cerebral hemisphere was diagnosed by ultrasonography at the 28th week of pregnancy, and followed up until birth. Although neonatal neurologic examination was normal, a moderate right hemiparesis developed along the 1st months of life. Coagulation studies performed in the neonatal period and at the age of 18 months revealed activated protein c resistance due to factor v Leiden mutation (R506Q). There are some previous reports of stroke associated to this mutation in near or at term neonates, but to our knowledge this is the stroke detected at the most early stage of fetal development.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
7/10. In utero transplantation of stem cells in humans.Three human fetuses were treated by stem cell transplantation from fetal liver. Two of them had severe immunodeficiency disease and the third one had thalassemia major. All three in utero transplants were followed by engraftment. No adverse effect was seen. The three patients are now born: the first one is cured, the two other ones are still under investigation. This procedure, for the first time used in humans, is therefore shown to be an effective and safe therapy of inherited diseases, during early fetal development.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
8/10. The pathogenesis of prune belly.Three neonates were born with marked abdominal muscular laxity from three different conditions (posterior urethral valves, nonimmune ascites, and intestinal duplication); two had fetal abdominal distention by ascites documented in utero by obstetric ultrasonographic examination. Another fetus, whose abdominal distention was relieved at 21 weeks' gestation by in utero decompression of urinary obstruction, was born with only mild abdominal changes, which suggests that the "prune belly" phenotype can resolve if distention is relieved early enough. These observations suggest that the abdominal laxity in prune belly syndrome is a simple deformation secondary to abdominal stretching and distention during fetal development and is not an intrinsic generalized mesodermal abnormality.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
9/10. Hydronephrotic type of bilateral multicystic dysplastic kidney. An unusual case.25 year-old pregnant woman was admitted at week 29 of fetal development for routine ultrasonic evaluation of growth. Sonography of the fetal body revealed two cystic anechoic septated structures bilaterally. At autopsy of the stillborn neonate pathology confirmed congenital multicystic dysplastic kidney. We believe this is the first case reported.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
10/10. prenatal diagnosis of ductus venosus agenesis: a report of two cases and review of the literature.Anomalies of venous return due to absence of the ductus venosus have been described in the literature. This is a report of the prenatal diagnosis of two cases of isolated ductus venosus agenesis occurring at 20 and 37 weeks' gestation, confirmed postnatally by color-coded Doppler sonography. In both cases the hepatic veins assumed the function of the ductus venosus without compromising fetal hemodynamics or causing hydrops. In the first case, a healthy female infant was delivered at term. In the second case, a 46,XY,dup(8) (q21.1q22)[35]/47,idem, r(8)[15] karyotype was diagnosed by amniocentesis. The male newborn showed facial anomalies, a bell-shaped thorax and increased intermamillary distance. There was muscular hypotonia, delayed psychomotor development and an inspiratory stridor leading to obstructive nocturnal dyspnea. On the basis of our observations in these two cases and previous reports from animal studies, we conclude that absence of the ductus venosus may be compatible with normal fetal development without relevant disturbance of circulation and oxygenation.- - - - - - - - - - ranking = 0.5keywords = fetal development (Clic here for more details about this article) |
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