Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine.

BACKGROUND: Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. CASE REPORT: We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. CONCLUSION: Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss.

Antenatal BAY 41-2272 reduces pulmonary hypertension in the rabbit model of congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) fail to adapt at birth because of persistent pulmonary hypertension (PH), a condition characterized by excessive muscularization and abnormal vasoreactivity of pulmonary vessels. Activation of soluble guanylate cyclase by BAY 41-2272 prevents pulmonary vascular remodeling in neonatal rats with hypoxia-induced PH. By analogy, we hypothesized that prenatal administration of BAY 41-2272 would improve features of PH in the rabbit CDH model. Rabbit fetuses with surgically induced CDH at day 23 of gestation were randomized at day 28 for an intratracheal injection of BAY 41-2272 or vehicle. After term delivery (day 31), lung mechanics, right ventricular pressure, and serum NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) levels were measured. After euthanasia, lungs were processed for biological or histological analyses. Compared with untouched fetuses, the surgical creation of CDH reduced the lung-to-body weight ratio, increased mean terminal bronchial density, and impaired lung mechanics. Typical characteristics of PH were found in the hypoplastic lungs, including increased right ventricular pressure, higher serum NT-proBNP levels, thickened adventitial and medial layers of pulmonary arteries, reduced capillary density, and lower levels of endothelial nitric oxide synthase. A single antenatal instillation of BAY 41-2272 reduced mean right ventricular pressure and medial thickness of small resistive arteries in CDH fetuses. Capillary density, endothelial cell proliferation, and transcripts of endothelial nitric oxide synthase increased, whereas airway morphometry, lung growth, and mechanics remained unchanged. These results suggest that pharmacological activation of soluble guanylate cyclase may provide a new approach to the prenatal treatment of PH associated with CDH.

Antenatal maternally-administered phosphodiesterase type 5 inhibitors normalize eNOS expression in the fetal lamb model of congenital diaphragmatic hernia.

PURPOSE: Pulmonary hypertension (pHTN), a main determinant of survival in congenital diaphragmatic hernia (CDH), results from in utero vascular remodeling. Phosphodiesterase type 5 (PDE5) inhibitors have never been used antenatally to treat pHTN. The purpose of this study is to determine if antenatal PDE5 inhibitors can prevent pHTN in the fetal lamb model of CDH. METHODS: CDH was created in pregnant ewes. Postoperatively, pregnant ewes received oral placebo or tadalafil, a PDE5 inhibitor, until delivery. Near term gestation, lambs underwent resuscitations, and lung tissue was snap frozen for protein analysis. RESULTS: Mean cGMP levels were 0.53±0.11 in placebo-treated fetal lambs and 1.73±0.21 in tadalafil-treated fetal lambs (p=0.002). Normalized expression of eNOS was 82%±12% in Normal-Placebo, 61%±5% in CDH-Placebo, 116%±6% in Normal-Tadalafil, and 86%±8% in CDH-Tadalafil lambs. Normalized expression of ß-sGC was 105%±15% in Normal-Placebo, 82%±3% in CDH-Placebo, 158%±16% in Normal-Tadalafil, and 86%±8% in CDH-Tadalafil lambs. Endothelial NOS and ß-sGC were significantly decreased in CDH (p=0.0007 and 0.01 for eNOS and ß-sGC, respectively), and tadalafil significantly increased eNOS expression (p=0.0002). CONCLUSIONS: PDE5 inhibitors can cross the placental barrier. ß-sGC and eNOS are downregulated in fetal lambs with CDH. Antenatal PDE5 inhibitors normalize eNOS and may prevent in utero vascular remodeling in CDH.

[Contemporary diagnosis and therapy in women with congenital adrenal hyperplasia]. / Wspólczesna diagnostyka i terapia kobiet z wrodzonym przerostem nadnerczy.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive defect in steroidogenesis, mostly affecting 21-hydroxylase enzyme deficiency. The other seldom cortisol synthesis abnormalities include deficiencies of: 11beta-hydroxylase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxylase, 17,20-lase and 11 beta-hydroxysteroid dwehydrogenase type 1. There are three main types, depending on the clinical level of 21-hydroxylase deficiency: (1) classical form--salt-wasting CAH (2) the classical form non- salt-wasting (3) non-classical form. CAH incidence is estimated at 1/14 000-1/10 000, of which about 70% is the classic salt-wasting form. The clinical picture varies considerably depending on the form. In the classic salt-wasting CAH may develop into the a shock. In classic CAH without loss of salt dominates virilization in girls and precocious puberty in boys. A non-classical forms usually presents as hyperandrogenisation and fertility. CAH treatment is mainly based on the use of glucocorticoid therapy, and if necessary supplemented mineralocorticoids. There is also potential to consider prenatal treatment (female fetuses diagnosed as CAH) with the use of dexamethason. However this kind of treatment is related to some medical and ethical controversies.

Abrogation of maternal and fetal oxidative stress in the streptozotocin-induced diabetic rat by dietary supplements of Tinospora cordifolia.

OBJECTIVE: Diabetes during pregnancy increases the incidences of congenital anomalies, morbidity, and mortality in the mother and her fetus/newborn. Oxidative stress (OS) has been implicated to be responsible because various antioxidants have been demonstrated to be beneficial in diabetic embryopathy. In this study, we examined the propensity of Tinospora cordifolia (TC) to attenuate embryopathy and OS in pregnant diabetic rats. METHODS: Pregnant rats were rendered diabetic with streptozotocin (45 mg/kg of body weight, on gestation day 4) and fed a normal or a TC-supplemented (1% or 2%) diet. After monitoring diet intake, body weight gain, and urine output, dams were sacrificed on gestation day 20 and the markers of OS were determined in the maternal liver and the fetal brain and liver. RESULTS: Although streptozotocin induced a significant (40%) increase in embryopathy, the dietary supplements offered significant protection (63%). Interestingly, TC significantly offset the diabetes-associated OS in the maternal liver as evidenced by the lower levels of malondialdehyde (25%) and reactive oxygen species (72%) and the higher levels of glutathione (53%) and total thiols (45%). The protective effects of TC could be observed even in the fetal milieu, with higher levels of antioxidant molecules and enzymes. CONCLUSION: These data suggest that TC during pregnancy may provide significant protection against diabetes-induced OS and thus serve as an effective therapeutic supplement.

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures.

Incidental reports suggest that antenatal treatment of pyridoxine dependent seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two families with PDS are reported, both with two affected siblings. Antenatal treatment with pyridoxine was instituted during the second pregnancy in each family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively). Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12 (Family B) years of age were compared between the untreated and treated child within each family. Meconium-stained amniotic fluid was present in both first pregnancies and abnormal foetal movements were noticed in one. In the treated infants, pregnancy and birth were uncomplicated. In family A, postnatal pyridoxine supplementation prevented neonatal seizures. Both children in family A were hypotonic and started walking after 2 years of age; both had white matter changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in the antenatally untreated and treated child, respectively. The second child in family B developed seizures on the seventh day, because pyridoxine maintenance therapy had not been instituted after birth. Seizures responded rapidly to pyridoxine supplementation. MRI showed large ventricles and a mega cisterna magna. IQ was 80 and 106 in the antenatally untreated and treated child respectively. Both children had normal motor development. These results suggest that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDS.

Pediatric arrhythmias: which are the news?

Knowledge about cardiac arrhythmias has significantly improved in the last 20 years, and the improvements in diagnosis and in therapy have also had important effects on the management of pediatric arrhythmias. In this paper, the most important developments in the field of management of pediatric arrhythmias (fetal arrhythmias, genetics, pharmacological strategies, radiofrequency ablation, new technologies) as well as the remaining problems (risk stratification of some arrhythmic forms as for example Wolff-Parkinson-White and ventricular arrhythmias) will be discussed.

[Influence of intravenous ozone treatment on the level of different specificity antibodies].

Medical ozone is the universal stimulator which participates in intracellular biochemical processes. Treatment with intravenous ozone was studied in 35 women, 20 of them with gestosis Rhesus sensibility, 3--with anti-HLA antibodies, 5--pregnant with ABO sensibility, 3--with anti-sperm antibodies, and 7- with antivirus antibodies (Herpes 1,2 and CMV). As a result, ozone treatment is effective for decrease anti-erythrocyte and anti-leukocyte antibodies and other antibody levels in blood. Medical ozone has direct antiviral activity which induces long term remission and in some cases total elimination of virus from blood. Generally, ozone is a modulator of the immune system, stimulating links of humoral and cell immunity. It appeared that index of immune regulation (T-helper/T suppressor) in pregnant women was increased and level of immunoglobulins (Ig G, M, A) was within normal ranges. This work shows the results of chemical influence of ozone on the antibodies which subsequently the decreases the level of modifying immunoglobulins.

Successful management of supraventricular tachycardia in a fetus using fetal magnetocardiography.

We report a fetus at 33 weeks of gestation with supraventricular tachycardia, which was successfully managed by transplacental administration of an antiarrhythmic agent. Fetal magnetocardiography (fMCG) revealed supraventricular tachycardia of the long RP' tachycardia type. Transplacental administration of sotalol, instead of digoxin, was selected as the first-line drug, and it successfully converted supraventricular tachycardia to sinus rhythm. The diagnosis of the type of supraventricular tachycardia was confirmed by electrocardiography after birth. Sotalol was also effective after birth to maintain sinus rhythm. This case demonstrates that fMCG is potentially useful for prenatal differentiation of the type of supraventricular tachycardia and for prenatal treatment of fetal tachyarrhythmias.

[Reduction of HIV mother-to-child transmission in Colombia, two years of experience, 2003-2005]. / Reducción de la transmisión madre hijo del VIH en Colombia: dos años de experiencia nacional, 2003-2005.

INTRODUCTION: A national initiative on reduction of HIV mother-to-child-transmission is being implemented since 2003 in Colombia, including HIV counseled and voluntary testing as part of the routine antenatal care, comprehensive care with ARV treatment to HIV-positive pregnant women and their infected children, caesarian delivery, and replacement of breast milk. OBJECTIVE: To describe the achievements in the implementation of the prevention strategy of mother-to-child HIV transmission, 2003-2005. MATERIALS AND METHODS: The implementation procedures of the Project are described, as well as the coverage percentages achieved, the prevention of vertical transmission and its associated factors, and the six-month prevalence by geographical departments. The probability of transmission adjusted to the ARV treatment offered and the differences by regions are also analyzed. RESULTS: The Project was implemented in 757 municipalities (68%); diagnostic tests were performed to 200,853 pregnant women, 377 of whom were diagnosed as HIV positive (0.19%), with higher prevalences in the Caribbean region, and in the Departments of Quindio and Santander. Complete six-month follow-up after delivery was provided to 285 women and their neonates (12 of whom were HIV-positive). The probability of transmission with the use of ARV schemes during pregnancy (n=170) was 1.78% (IC 95%: 0.37-5.13%). Factors related to probability of transmission were: initial viral load > 10,000/mm3, absence of antenatal care, and late recruitment of pregnant women. No statistical differences were found between the ARV schemes used. In the Caribbean region, antenatal care was lower, and late recruitment of pregnant women was higher. CONCLUSIONS: Reduction of HIV mother-to-child-transmission is an effective preventive intervention, which also strengthens the quality of antenatal care services. Sustainability of this initiative, with nationwide coverage, must be a target for national and regional public health authorities, and for health care providers.

A study on the traditional Chinese medicine Jinyebaidu for prevention and treatment of intrauterine infection with guinea pigs cytomegalovirus.

The purpose is to study the prophylactic and therapeutic effect of the traditional Chinese Medicine (TCM)-Jinyebaidu (JYBD) to guinea pig cytomegalovirus (GPCMV) intrauterine infection. The virus-free female and male guinea pigs were screened with nest-polymerase chain reaction (N-PCR). After inbred, pregnant guinea pigs were selected and divided into 3 groups randomly: 5 guniea pigs of the blank control group were not given either GPCMV or JYBD. 31 guniea pigs of the positive control group were inoculated 1 mL (10(7) TCID50) suspension of GPCMV intraperitoneal. 10 guniea pigs of the experimental group were inoculated GPCMV firstly and then perfused stomach with JYBD for 14 days (Dosage in accordance with the modulus of the weight ratio of human to guniea pig). The effects of JYBD on the intrauterine infection of GPCMV were observed. The results showed that JYBD could decrease the maternal infection rate from 100% (31/31) to 50% (5/10) (P < 0.001), the intrauterine infection rate from 100% (72/72) to 75% (21/28) (P < 0.001), and the rate of abnormal outcome of pregnancy from 64.4% (29/45) to 25.0% (7/28) (P < 0.001), the infective symptoms being relieved. It can be concluded that traditional Chinese medicine- JYBD can prevent and treat (GPCMV intrauterine infection, and can be expected a prophylactic drug for HCMV intrauterine infection.

A study on the traditional Chinese medicine Jinyebaidu for prevention and treatment of intrauterine infection with guinea pigs cytomegalovirus / 华中科技大学学报（医学）（英德文版）

The purpose is to study the prophylactic and therapeutic effect of the traditional Chinese Medicine (TCM)-Jinyebaidu (JYBD) to guinea pig cytomegalovirus (GPCMV) intrauterine infection. The virus-free female and male guinea pigs were screened with nest-polymerase chain reaction (N-PCR). After inbred, pregnant guinea pigs were selected and divided into 3 groups randomly: 5 guniea pigs of the blank control group were not given either GPCMV or JYBD. 31 guniea pigs of the positive control group were inoculated 1 mL (10(7) TCID50) suspension of GPCMV intraperitoneal. 10 guniea pigs of the experimental group were inoculated GPCMV firstly and then perfused stomach with JYBD for 14 days (Dosage in accordance with the modulus of the weight ratio of human to guniea pig). The effects of JYBD on the intrauterine infection of GPCMV were observed. The results showed that JYBD could decrease the maternal infection rate from 100% (31/31) to 50% (5/10) (P < 0.001), the intrauterine infection rate from 100% (72/72) to 75% (21/28) (P < 0.001), and the rate of abnormal outcome of pregnancy from 64.4% (29/45) to 25.0% (7/28) (P < 0.001), the infective symptoms being relieved. It can be concluded that traditional Chinese medicine- JYBD can prevent and treat (GPCMV intrauterine infection, and can be expected a prophylactic drug for HCMV intrauterine infection.

Retinaldehyde dehydrogenase 2 (RALDH2)- independent patterns of retinoic acid synthesis in the mouse embryo.

Knockout of the murine retinoic acid (RA)-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2) gene leads to early morphogenetic defects and embryonic lethality. Using a RA-responsive reporter transgene, we have looked for RA-generating activities in Raldh2-null mouse embryos and investigated whether these activities could be ascribed to the other known RALDH enzymes (RALDH1 and RALDH3). To this end, the early defects of Raldh2(-/-) embryos were rescued through maternal dietary RA supplementation under conditions that do not interfere with the activity of the reporter transgene in WT embryos. We show that RALDH2 is responsible for most of the patterns of reporter transgene activity in the spinal cord and trunk mesodermal derivatives. However, reporter transgene activity was selectively detected in Raldh2(-/-) embryos within the mesonephric area that expresses RALDH3 and in medial-ventral cells of the spinal cord and posterior hindbrain, up to the level of the fifth rhombomere. The craniofacial patterns of RA-reporter activity were unaltered in Raldh2(-/-) mutants. Although these patterns correlated with the presence of Raldh1 andor Raldh3 transcripts in eye, nasal, and inner ear epithelia, no such correlation was found within forebrain neuroepithelium. These data suggest the existence of additional RA-generating activities in the differentiating forebrain, hindbrain, and spinal cord, which, along with RALDH1 and RALDH3, may account for the development of Raldh2(-/-) mutants once these have been rescued for early lethality.

Induction of fetal diuresis with intraamniotic furosemide increases the clearance of intraamniotic substances: An alternative therapy aimed at reducing intraamniotic meconium concentration.

BACKGROUND/PURPOSE: Contact with amniotic fluid (AF) causes intestinal damage in gastroschisis. Intraamniotic meconium has been shown to be responsible for intestinal damage, and occurrence of this damage has been shown to depend on the concentration of intraamniotic meconium. When intraamniotic meconium concentration is lowered below threshold level by exchanging AF with saline in gastroschisis, intestinal damage can be prevented. Theoretically, induction of fetal diuresis with intraamniotic furosemide may increase AF volume and fetal swallowing rate, thus, increase absorption of AF by intestines; therefore, the clearance of meconium from the AF may increase. An experimental study was planned to investigate the effects of intraamniotic diuretic injection on the clearance of intraamniotic substances. METHODS: Pregnant rabbits on the 23rd to 25th gestational day were divided into 2 groups as furosemide and control. Technetium tc99m labeled "tin colloid" was injected into the amniotic cavity, and AF sample was taken 10 minutes later. Furosemide was injected into the amniotic cavity afterwards. Two and 6 hours later, AF samples were obtained. Intestines were harvested at the end of the study. Control group received intraamniotic saline instead of furosemide. Radioactivities of the AF samples and intestines were determined by gamma counter. Clearance of the radioisotope from AF and intestinal accumulation were calculated. RESULTS: The clearance of the radioisotope from AF was increased significantly in the furosemide group (n = 10) compared with the control group (n = 8; P <.01). Gastrointestinal accumulation of the radioisotope in the furosemide group was 4-fold higher than that the control group (P <.01). CONCLUSIONS: Induction of fetal diuresis with intraamniotic furosemide accelerates the clearance of intraamniotic substances. This is probably caused by increased urinary output rate, which increases AF volume and consequently results in increased fetal swallowing of AF. In the diseases like gastroschisis and myelomeningocele, in which the contact with AF causes tissue damage, the elimination of meconium from AF in a somewhat natural manner like this method, should be studied further because it may be an alternative minimal invasive in utero treatment modality.

Treatment of spinal muscular atrophy by sodium butyrate.

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular paralysis with muscular atrophy. No effective treatment of this disorder is presently available. Studies of the correlation between disease severity and the amount of survival motor neuron (SMN) protein have shown an inverse relationship. We report that sodium butyrate effectively increases the amount of exon 7-containing SMN protein in SMA lymphoid cell lines by changing the alternative splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment of SMA-like mice resulted in increased expression of SMN protein in motor neurons of the spinal cord and resulted in significant improvement of SMA clinical symptoms. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all three types of SMA-like mice. These results suggest that sodium butyrate may be an effective drug for the treatment of human SMA patients.

Morphofunctional changes in the placenta after ozone therapy.

Macro- and microscopic aspects in the morphology of placenta after ozone therapy were studied in pregnant women with placental insufficiency and the results were compared with the control group. In the main group, the placentas were smaller and weighed less. After ozone therapy enlargement of terminal villi with true syncytiocapillary membranes was noted. A stimulating effect of ozone therapy on the growth and differentiation of terminal villi was established.

Lead poisoning and toxicokinetics in a heifer and fetus treated with CaNa2 EDTA and thiamine.

Lead (Pb) poisoning of a pregnant heifer was diagnosed based upon clinical signs (head pressing, blindness, muscle twitching) and a blood lead concentration of 1.73 ppm. Blood and urinary Pb half-lives with CaNa2 EDTA/thiamine therapy were determined to be 2.08 and 1.38 days, respectively. Many cations (Ca, Fe, Zn, Na, Cu), including Pb, were excreted at higher concentrations in urine during therapy. Blood (0.425 ppm) and liver (4.85 ppm) Pb concentrations in the fetus were 71.7% and 84.3% of the same tissue Pb concentrations of the dam, indicating a significant transfer of Pb in utero. Severe polioencephalomalacia was described in the adult, and hepatic lysosomes with metallic electron densities were present in the fetus.

[Indirect transplacental therapy of the fetus]. / Die indirekte transplazentare Therapie des Feten.

UNLABELLED: The paper is a review on the actual possibilities and indications of the transplacentar therapy of the fetus. At first some principles of the pharmacodynamics of the materno-placento-fetal unit are explained in order to enable an effective drug administration and reach therapeutic levels in the fetus. Common and less common diseases of the fetus and their therapy are exposed, such as the acceleration of lung maturation with corticosteroids, the cardioversion of tachycardias with digoxin and other antiarrhythmic drugs, the therapy of toxoplasmosis with pyrimethamine, the treatment of polyhydramnios using indomethacin, the therapy of very rare inborn errors of metabolism, the therapy of thrombocytopenia and the prevention of neural tube defects by folic acid supplementation. For these diseases the pathophysiologic background, the therapy rationale and possible side effects of therapy were exposed. Prior to an intrauterine therapy the perinatologist has to ask himself the 5 "W"- QUESTIONS: Which fetus to treat? Why to treat? When to treat? Who will treat? Way of treatment?

Fetal supraventricular tachycardia: in utero therapy with digoxin and quinidine.

Digoxin has been successfully used to treat fetal supraventricular tachycardia. When therapy with digoxin fails, alternative therapies have met with equivocal success. In this report, successful fetal therapy with maternally administered digoxin and quinidine is presented in three consecutive patients with fetal supraventricular tachycardia. The arrhythmia was eliminated in each instance. Fetal ascites, present in two fetuses, was completely reversed. Intrapartum fetal distress was not observed. The rationale of this therapy and a review of pertinent literature are also presented.