losartan-potassium and Fetal-Death

Perinatal mortality has not decreased in type 1 diabetic pregnancies during the last 30 years. Fetal deaths are five times and neonatal deaths three times higher compared with the general population. Chronic intrauterine hypoxia caused by maternal diabetes is the most likely cause of stillbirths during the last weeks of pregnancy. Both fetal hyperglycemia and hyperinsulinemia can independently cause fetal chronic hypoxia by increasing fetal oxygen consumption. Fetal chronic hypoxia can be detected antenatally by measuring amniotic fluid erythropoietin concentration. Prepregnancy visits for advice and glycemic control should be increased among diabetic women. Furthermore, pregnancy surveillance should be enhanced and therapeutic strategies changed in order to improve perinatal outcome among diabetic pregnancies.

Topics: Amniotic Fluid; Diabetes, Gestational; Erythropoietin; Female; Fetal Death; Fetal Hypoxia; Humans; Infant Mortality; Infant, Newborn; Pregnancy; Pregnancy in Diabetics; Risk Factors

Objectives To investigate mechanisms of in utero death in normally formed fetuses by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]), myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary acidic protein [GFAP]), correlated with risk factors for fetal death and placental histopathology. Methods This retrospective, observational cohort study included intrauterine deaths with transabdominal amniocentesis prior to induction of labor. Women with a normal pregnancy and an indicated amniocentesis at term were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using commercial immunoassays. Placental histopathology was reviewed, and CD15-immunohistochemistry was used. Analyte concentrations >90th centile for controls were considered "raised". Raised AF EPO, AF cTnI and AF GFAP concentrations were considered evidence of hypoxia, myocardial and brain injury, respectively. Results There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60), myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths. Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77% (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological evidence for placental dysfunction was found in 74% (43/58) of these cases. Conclusion Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be caused by cardiac arrhythmia secondary to a cardiac conduction defect.

Topics: Adult; Amniocentesis; Amniotic Fluid; Brain Injuries; Cause of Death; Erythropoietin; Female; Fetal Death; Fetal Diseases; Fetal Hypoxia; Glial Fibrillary Acidic Protein; Heart Diseases; Humans; Immunohistochemistry; Placenta; Pregnancy; Random Allocation; Retrospective Studies; Stillbirth; Troponin I; United States

To determine the in vitro stability of endogenous and recombinant erythropoietin (EPO) incubated at 37 degrees C in amniotic fluid (AF) and fetal plasma.. Endogenous and recombinant EPO in AF, fetal plasma and phosphate buffer were incubated in vitro for 21 days at 37 degrees C. Serial aliquots were analyzed for EPO and the rates of EPO decline were compared within and between groups.. Endogenous and recombinant EPO declined significantly in plasma and AF at 37 degrees C. Endogenous EPO displayed a similar linear rate of decline in AF and plasma, with nearly 70% of the initial hormone concentration remaining at 21 days. Recombinant EPO incubated in buffer did not change.. Using the rate of decline in endogenous EPO we observed, EPO levels measured in AF or plasma within 21 days of fetal demise can be extrapolated back to the level likely present at fetal death.

Topics: Amniotic Fluid; Drug Stability; Erythropoietin; Female; Fetal Blood; Fetal Death; Humans; Pregnancy; Radioimmunoassay; Recombinant Proteins; Time Factors

Increased fetal plasma erythropoietin concentration is an indicator of chronic fetal hypoxia. Amniotic fluid erythropoietin levels correlate highly significantly with fetal erythropoietin levels before labor. We studied AF erythropoietin levels after fetal death in order to determine whether this could differentiate between stillbirths from acute or chronic causes.. Amniotic fluid was obtained after fetal death for erythropoietin measurement following fetal death in 21 pregnancies. Two of the pregnancies had twins, of which one infant was born alive. All 22 stillborn fetuses had an autopsy. None had malformations. Without prior knowledge of the results of the erythropoietin analyzes, the causes of fetal death were divided into acute, chronic or unknown groups.. Eight pregnancies had an acute cause of fetal death (e.g. cord complication or placental abruption), eight pregnancies had a chronic cause (intrauterine growth restriction or erythroblastosis) and in five pregnancies the cause of fetal death could not be determined. In all eight pregnancies with an acute cause of fetal death, AF erythropoietin levels were normal (< 20 mU/mL). In contrast, six of the eight pregnancies with a chronic cause had AF erythropoietin levels above normal (range from 49.9 mU/mL to 391 mU/mL). In the five pregnancies with an unknown cause of fetal death, AF erythropoietin levels were normal in three and elevated in two.. Elevated AF erythropoietin levels, identified after fetal death, suggest that the fetus died from a chronic hypoxic event, whereas normal AF erythropoietin levels suggest that the fetus died from an acute event.

Topics: Acute Disease; Amniotic Fluid; Body Temperature; Cause of Death; Chronic Disease; Erythropoietin; Female; Fetal Death; Fetal Diseases; Humans; In Vitro Techniques; Pregnancy; Time Factors

To address whether altered erythropoietin (EPO) synthesis might be involved in prenatal pig mortality, studies were conducted to measure porcine embryonic EPO mRNA expression during early gestation (days 24-40). Three pig models differing in embryonic survival from days 24-40 were investigated: intact white crossbred gilts (INT), white crossbred gilts that were unilaterally hysterectomized-ovariectomized before puberty and whose pregnant uterus constituted a crowded environment (UHO), and prolific, intact Meishan gilts (ME). A partial cDNA for porcine EPO, developed via reverse transcription and polymerase chain reaction procedures was used to generate a 32P-labeled probe for use in Northern analyses. In an initial study, embryonic liver EPO mRNA was greatest on day 24, decreased by day 30 (P<0.01), and was barely detectable by day 40. EPO mRNA expression was not influenced by pig model. Placental EPO mRNA expression was detectable in only 4 of 53 placentae examined. In a second study at day 35 of gestation, embryonic liver EPO mRNA expression was measured in the same three pig models and in two embryos of divergent weights from each gilt. Meishan embryos had lower (P<0.01) plasma immunoassayable EPO concentrations (P=0.04) and higher survival rates (87+/-2.7%) at day 35 than did white crossbred embryos (75+/-5%). Liver EPO mRNA expression did not differ among animal models, nor did plasma EPO or tissue EPO mRNA expression differ between large and small embryos. There was no apparent relationship between embryonic development, measured as embryonic and placental size, and plasma EPO concentrations or liver EPO mRNA expression. These results indicate that at the gestational ages examined, the embryonic liver is one source of plasma erythropoietin and suggest that at the ages sampled, EPO is not a limiting factor in embryonic development.

Topics: Actins; Animals; Blotting, Northern; DNA Probes; Embryonic and Fetal Development; Erythropoietin; Female; Fetal Death; Gene Expression; Gestational Age; Glyceraldehyde-3-Phosphate Dehydrogenases; Liver; Placenta; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Species Specificity; Swine

Mice lacking suppressor of cytokine signaling 3 (SOCS3) exhibited embryonic lethality with death occurring between days 11 and 13 of gestation. At this stage, SOCS3(-/-) embryos were slightly smaller than wild type but appeared otherwise normal, and histological analysis failed to detect any anatomical abnormalities responsible for the lethal phenotype. Rather, in all SOCS3(-/-) embryos examined, defects were evident in placental development that would account for their developmental arrest and death. The placental spongiotrophoblast layer was significantly reduced and accompanied by increased numbers of giant trophoblast cells. Delayed branching of the chorioallantois was evident, and, although embryonic blood vessels were present in the labyrinthine layer of SOCS3(-/-) placentas, the network of embryonic vessels and maternal sinuses was poorly developed. Yolk sac erythropoiesis was normal, and, although the SOCS3(-/-) fetal liver was small at day 12.5 of gestation (E12.5), normal frequencies of erythroblasts and hematopoietic progenitor cells, including blast forming unit-erythroid (BFU-E) and, colony forming unit-erythroid (CFU-E) were present at both E11.5 and E12.5. Colony formation for both BFU-E and CFU-E from SOCS3(-/-) mice displayed wild-type quantitative responsiveness to erythropoietin (EPO), in the presence or absence of IL-3 or stem cell factor (SCF). These data suggest that SOCS3 is required for placental development but dispensable for normal hematopoiesis in the mouse embryo.

Topics: Animals; Base Sequence; DNA Primers; Erythropoietin; Fetal Death; Hematopoiesis; Mice; Proteins; Repressor Proteins; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Transcription Factors

The toxicity of azidothymidine (AZT) was studied in monkey dams and fetuses that were exposed to the drug over the entire gestational period. Fourteen virus-free female macaques (Macaca nemestrina) were randomly assigned to AZT or control groups. AZT animals received the drug through a gastric catheter at a dose of 1.5 mg/kg every 4 hours, which produced plasma concentrations similar to those in humans taking 500 to 600 mg/day of AZT. Control animals received water placebo, also through gastric catheter. Some animals participated in both groups. All females were mated with the same male; 41 matings produced 20 pregnancies, of which 16 were carried to term (9 in AZT females; 7 in control females). The AZT animals developed an asymptomatic macrocytic anemia, but hematologic parameters returned to normal when AZT was discontinued. Total leukocyte count decreased during pregnancy and was further affected by AZT administration. AZT-exposed infants were mildly anemic at birth. AZT caused deficits in growth, rooting and snouting reflexes, and the ability to fixate and follow near stimuli visually, but the deficits disappeared over time. These data indicate that early exposure to AZT in utero should have no irreversible adverse effects on the fetus.

Topics: Anemia; Animals; Animals, Newborn; Anti-HIV Agents; Area Under Curve; Bone Marrow; Erythrocyte Indices; Erythropoietin; Female; Fetal Death; Fetal Resorption; Fetus; Hematocrit; Hemoglobins; Leukocyte Count; Macaca nemestrina; Organ Size; Placenta; Platelet Count; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Random Allocation; Zidovudine