A singleton pregnancy with placental chorioangioma and hydrops fetalis complicated with mirror syndrome and ritodrine-induced side effects: a case report.

BACKGROUND: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. CASE PRESENTATION: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. CONCLUSION: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.

Mesalazine as a cause of fetal anemia and hydrops fetalis: A case report.

RATIONALE: Mesalazine and its prodrug sulfasalazine are both used for inflammatory bowel disease. Sulfasalazine has been associated with hematological side-effects such as aplastic and hemolytic anemia in patients, but also in fetuses after intrauterine exposure. To our knowledge, we describe the first case of a fetus with severe anemia, and subsequent hydrops, where this drug was found at concentrations in the fetus corresponding to those in the mother and most likely responsible for the fetal condition. PATIENT CONCERNS: A uniparous woman was referred at 31 weeks of gestation due to a hydropic fetus with massive ascites and cardiomegaly. DIAGNOSES: The patient had Crohn's disease and was thus treated with 4 g mesalazine daily. The fetus had severe anemia with an initial hemoglobin level of 51 g/L. INTERVENTIONS: The maternal medication was discontinued and four intrauterine erythrocyte transfusions were given during three weeks. Plasma samples were drawn from mother and fetus during cordocentesis for later analysis of mesalazine. OUTCOMES: A healthy baby was born after 37 full weeks of gestation. Plasma levels of mesalazine were non-conspicuous in neither mother nor fetus. The mesalazine half-life in the fetus (37 h) was half that of the mother (80 h), both considerably longer than previously reported (about 19 h). LESSONS: A causal relationship must be suspected between the fetal anemia and the maternal use of mesalazine. This fetal side-effect should be considered in pregnant women on mesalazine (and its prodrug sulfasalazine).

Dysmorphogenic effects of first trimester-equivalent ethanol exposure in mice: a magnetic resonance microscopy-based study.

BACKGROUND: The first trimester of human development and the equivalent developmental period in animal models is a time when teratogenic ethanol (EtOH) exposure induces the major structural birth defects that fall within fetal alcohol spectrum disorder (FASD). Previous FASD research employing an acute high dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive periods for a number of these defects. Extending this work, this investigation utilized high resolution magnetic resonance microscopy (MRM)-based analyses to examine the dysmorphology resulting from maternal dietary EtOH intake occurring during selected first trimester-equivalent time periods. METHODS: Female C57Bl/6J mice were acclimated to a liquid 4.8% EtOH (v/v)-containing diet, then bred while on standard chow. Dams were again provided the EtOH-containing liquid diet for a period that extended either from the beginning of gestational day (GD) 7 to the end of GD 11 or from the beginning of GD 12 to the end of GD 16. On GD 17, a subset of fetuses was selected for MRM-based analyses. Group comparisons were made for litter characteristics and gross dysmorphology, as well as whole and regional brain volumes. RESULTS: EtOH-induced stage of exposure-dependent structural brain abnormalities were observed. The GD 7 to 11 EtOH-exposed group presented with a significant decrease in cerebellar volume and an increase in septal volume, while GD 12 to 16 EtOH treatment resulted in a reduction in right hippocampal volume accompanied by enlarged pituitaries. Additionally, the GD 12 to 16 EtOH exposure caused a high incidence of edema/fetal hydrops. CONCLUSIONS: These results illustrate the teratogenic impact of maternal dietary EtOH intake occurring at time periods approximately equivalent to weeks 3 through 6 (GD 7 to 11 in mice) and weeks 7 through 12 (GD 12 to 16 in mice) of human gestation, further documenting EtOH's stage of exposure-dependent neuroteratogenic end points and highlighting the vulnerability of selected brain regions during the first trimester. Additionally they suggest that clinical attention should be paid to fetal hydrops as a likely component of FASD.

Hemodynamic assessment of indomethacin-induced fetal heart failure in high-output state.

Hemodynamic study was performed on a 32-year-old woman presenting at 27 weeks' gestation. Ultrasound revealed a single normal fetus with mild cardiomegaly, polyhydramnios, and placental chorioangioma. Doppler study showed increased middle cerebral artery peak systolic velocity, normal Tei index, and forward flow of "a" wave with normal preload in the ductus venosus. Twelve hours after initiation of indomethacin for tocolysis, frank hydrops fetalis developed rapidly. The right ventricle showed poor contractility and performance. Markedly increased preload in ductus venosus with reversed "a" wave and pulsations in the umbilical vein were demonstrated. This study suggests that indomepacin treatment in fetal high-cardiac output state should be used with extreme caution.

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

BACKGROUND: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. METHODS: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. RESULTS: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. CONCLUSIONS: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

Clinical features of the complete closure of the ductus arteriosus prenatally.

OBJECTIVE: Prenatal constriction of the ductus arteriosus associated with maternal drug ingestion was reported several decades ago. There are fewer reports of the complete closure of the ductus arteriosus; therefore, the clinical features of the latter are poorly understood. The aim of this study is to clarify the clinical features of complete ductal closure and postnatal pulmonary hypertension by performing echocardiography of the fetus. PATIENTS: We diagnosed four fetuses with complete ductal closure by performing fetal echocardiography and reviewed the prenatal and postnatal medical records of the mother and fetus. RESULTS: One mother each had bronchial asthma, ulcerative colitis, and idiopathic thrombocytopenic purpura, and they had received nonsteroidal anti-inflammatory drugs and/or corticosteroids during pregnancy. The fourth mother did not have basal disease and had not ingested any drugs. Fetal diagnosis was performed at 32-38 weeks of gestation. All fetuses had right heart dilatation with tricuspid regurgitation in the absence of any cardiac defects, and Doppler echocardiography indicated that the right ventricular pressure was elevated. Two of the fetuses had fetal hydrops, which suggested severe right heart dysfunction. All fetuses were delivered by emergent cesarean delivery. After birth, all the infants developed persistent pulmonary hypertension and required oxygen inhalation. Of these, three required mechanical ventilation, and two, nitric oxide inhalation. All infants improved within 2 weeks, and they had no neurological and cardiac complications after discharge. CONCLUSION: Right heart dilatation and severe tricuspid regurgitation in the absence of a cardiac defect in the fetus strongly suggested ductal dysfunction. Careful evaluation of ductal patency and right ventricular function can lead to precise early diagnosis and good prognosis.

Neonatal anemia and hydrops fetalis after maternal mycophenolate mofetil use.

After admitting a patient to our Neonatal Intensive Care with a severe anemia and an ear malformation, we ruled out any other cause than maternal medication use. Knowing she used mycophenolate mofetil during pregnancy, we looked for related articles. Two articles were found describing ear malformations, but no article was ever written about anemia caused by this medication. Consulting the international registers of drug effects through the National Institute for Public Health and the Environment, we found out that the anemia was never seen or reported before.

Fetal hydrops, associated with maternal propylthiouracil exposure, reversed by intrauterine therapy.

Thyroid hormone is essential for fetal neurological development. Among other etiologies, fetal hypothyroidism may be caused by maternal exposure to antithyroid drugs (ATDs). The most common presentation of fetal hypothyroidism is fetal goiter, which can cause dystocia, in addition to airway obstruction in the neonate. Intra-amniotic treatment with levothyroxine normalizes fetal thyroid status and reduces goiter size. We present a case of fetal hypothyroidism diagnosed in a patient who was treated with propylthiouracil (PTU) for Grave's disease. The fetus had marked hydrops fetalis and a large goiter. In addition, anal stenosis, vesicovaginal fistula, bilateral pyelectasia and polydactyly were diagnosed in the neonate. Intra-amniotic treatment with levothyroxine resulted in a regression of the hydrops and a reduction in the goiter size. A euthyroid, non-edematous, non-goitrous neonate was delivered. At the age of 27 months the child's psychomotor development was normal. The present case indicates that hydrops fetalis may be an unusual manifestation of fetal hypothyroidism, caused by intrauterine exposure to maternal antithyroid drugs (ATDs), and that it may be resolved by treatment with intra-amniotic levothyroxine.

Placental and fetal growth and development in late rat gestation is dependent on adrenomedullin.

Adrenomedullin is a potent, endogenous vasodilator peptide synthesized and secreted by diverse locations such as adrenal glands, lungs, kidneys, vascular smooth muscle, and endothelium. Homozygous deletion of the adrenomedullin gene is embryonic lethal. We hypothesized that adrenomedullin has an important role in placental and fetal growth and development in rat pregnancy. The current study evaluated maternal systolic blood pressure, litter size, placental and pup weight, pup mortality, and placental pathology in pregnant rats following continuous in utero exposure to an adrenomedullin antagonist. Osmotic minipumps were inserted on Gestational Day 14 to continuously deliver either adrenomedullin, adrenomedullin antagonist, or vehicle control. Systolic blood pressure was recorded daily. Pregnant rats were killed on Gestational Day 15-18, 20, and/or 22 to evaluate placental development and fetal growth. The placentas were graded for the presence of necrosis in the decidua and fetal labyrinth as well as fetal vessel development in the labyrinth. A trend toward increased systolic blood pressure was noted between Gestational Days 17 and 20 in mothers treated with adrenomedullin antagonist, but the difference was not statistically significant. Antagonism of adrenomedullin function during rat pregnancy caused fetal growth restriction, decreased placental size, gross necrosis of placental margins and amniotic membranes, histologically deficient fetal vessel development in the labyrinth, and fetal edema. Adrenomedullin contributes to angiogenesis, functions as a growth factor, and helps regulate vascular tone during rat gestation.

Varicella vaccination during early pregnancy: a cause of in utero miliary fetal tissue calcifications and hydrops?

BACKGROUND: It is the purpose of this article to describe a suspected association of inadvertent vaccination with varicella vaccine during early pregnancy with the subsequent development of in utero miliary fetal tissue calcifications and fetal hydrops detected by sonogram at 15 weeks of gestation. CASE: This is a case presentation of a pregnant patient who received varicella vaccination during the same menstrual cycle that she became pregnant, and is supplemented by a literary review. The fetus developed miliary fetal tissue calcifications and fetal hydrops detected by a targeted sonogram at 15 weeks gestation. CONCLUSION: Varicella vaccination during early pregnancy may be a cause of miliary fetal tissue calcifications and fetal hydrops.

Reversible fetal hydrops associated with indomethacin use.

BACKGROUND: Ductus arteriosus constriction is a known complication of exposure to indomethacin in utero. Nonimmune hydrops associated with indomethacin use has been reported in only six cases, all twins over 32 weeks' gestation. CASE: We present a case of fetal hydrops associated with tricuspid regurgitation and ductal constriction developing within 30 hours of instituting indomethacin tocolysis in a 28-week singleton gestation. Discontinuation of indomethacin resulted in partial resolution of these findings 72 hours later. A normal infant was delivered subsequently. CONCLUSION: Ultrasonographic screening for signs of constriction of the ductus arteriosus should be done within 48 hours of instituting indomethacin therapy at any gestational age.

Cardiovascular and pulmonary effects of betamethasone during midtrimester on fetal rats.

In order to elucidate the effects of corticosteroids on fetal hearts during midtrimester, pregnant rats were injected with a daily dose of betamethasone (1 mg/kg) from the 12th day through the 17th day of pregnancy. The fetal cardiovascular and pulmonary systems were studied on the 21st day of pregnancy (term). The treated fetuses showed the following signs of hydrops fetalis: retarded growth, pale, edematous skin, and decreased movement. The thymus and lung displayed prominent hypoplasia. The morphometry of the treated fetuses revealed: decreased right ventricle mass by 37% and decreased left ventricle mass by 29%. We concluded betamethasone had a significant effect on the developing fetal cardiovascular system, inducing hydrops fetalis. Additionally, beta-methasone caused hypoplasia of the thymus and lung.

Developmental anomalies derived from exposure of zygotes and first-cleavage embryos to mutagens.

Results of continuing studies indicate that the mouse zygote and two-cell embryo stages are a window of susceptibility in the experimental induction of congenital anomalies with certain mutagenic agents. The mechanisms by which the mutagens initiate the pathogenesis of these developmental defects are not known. However, in certain cases there is evidence that a nonconventional, perhaps epigenetic, mechanism is involved. Detailed characterization of the spectrum of anomalies induced and comparison of responses at the various stages exposed allowed classification of the mutagens generally into two groups. One group is characterized by being effective only in the early stages of zygote development and capable of producing a relatively high incidence of fetal death and hydrops. The other group affects all of the zygote stages studied as well as the two cell-embryo, but does not increase the incidence of fetal death and hydrops. Except for hydrops, chemicals in the two groups do not differ in terms of the types of anomalies present among malformed live fetuses, which bear a resemblance to a subset of common, sporadic human developmental anomalies that are of unknown etiology. This similarity raises the possibility that certain human developmental defects may have their origins in events that happen in the zygote and early pre-implantation stages.

Ductus-dependent fetal cardiac defects contraindicate indomethacin tocolysis.

The hemodynamics of critical aortic stenosis in the fetus make it a ductus-dependent cardiac defect because the ductus arteriosus supplies blood not only to the descending aorta but also to the aortic arch and coronary vessels. In utero closure of the ductus arteriosus has been reported in association with tetralogy of Fallot, truncus arteriosus, maternal use of prostaglandin inhibitors, and as idiopathic events. This is the first report of a ductus-dependent congenital heart defect (critical aortic stenosis) where treatment with indomethacin, a prostaglandin synthetase inhibitor, precipitated premature closure of the ductus and hydrops fetalis. Review of reported cases of premature closure of the ductus show that acute, in utero closure of the ductus in a fetus with limited cardiopulmonary reserves has a worse prognosis than with previously reported cardiac anomalies. This study strongly supports published concerns of increased perinatal morbidity and mortality when fetuses are exposed to prostaglandin inhibitors in utero, and shows that ductus-dependent fetal cardiac defects are contraindications to the maternal use of prostaglandin inhibitors during pregnancy.

[Prenatal diagnosis of premature closure of the ductus arteriosus with subsequent development of a non-immunologic hydrops fetalis]. / Pränatale Diagnose eines vorzeitigen Verschlusses des Ductus arteriosus mit nachfolgender Entwicklung eines nichtimmunologischen Hydrops fetalis (NIHF).

The premature closure of the ductus arteriosus (pcDA) due to maternal tocolysis with indomethacin in the 34th week of gestation was diagnosed in a twin pregnancy. The pcDA was detected using Doppler 24 hours before both fetuses developed pleural effusion. Pathologic waveforms in the fetal aorta with end-diastolic zero-flow were registered. A no-delay caesarean section with optimal neonatologic intensive care were successful for the survival of the neonates. The authors postulate, that the amount of pcDA as a cause of NIHF is higher than generally supposed. Furthermore a tocolysis with indomethacin should not be performed after the 34th week of gestation.