losartan-potassium and Stillbirth

Perinatal mortality has not decreased over the last two decades in pregestational diabetic pregnancies. Stillbirth rate is 4-6 times and neonatal mortality 2-4 times higher in diabetic than in non-diabetic pregnancies despite modern electronic fetal surveillance methods. Majority of late stillbirths are "unexplained", many of which are presumably caused by fetal hypoxia. Both experimental and clinical studies have shown that fetal hyperglycaemia and hyperinsulinaemia can independently cause fetal hypoxia, which ultimately can lead to fetal death. Poor glycaemic control is associated with perinatal complications. Sharp increases in amniotic fluid erythropoietin levels indicate fetal hypoxia in diabetic pregnancy. Fetal erythropoietin concentrations correlate directly with maternal HbA(1c) levels. It is therefore important to maintain near-normal glycaemic level throughout pregnancy. Measurement of amniotic fluid erythropoietin level is a new way to detect fetal hypoxia antenatally. Sufficiently large controlled studies are needed before definitive answer of the clinical utility of amniotic fluid erythropoietin measurements in diabetic pregnancies can be determined.

Topics: Amniotic Fluid; Erythropoietin; Female; Fetal Hypoxia; Glycated Hemoglobin; Humans; Infant Mortality; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Stillbirth

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