Endocrinology of parturition.
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Autocrine Communication↗
Biomedical subjects
Joong Shin Park
Publications and source records attributed to Joong Shin Park.
Fetal plasma cortisol and dehydroepiandrosterone sulfate concentrations in pregnancy and term parturition.
OBJECTIVE: To examine if changes in fetal plasma concentrations of cortisol or dehydroepiandrosterone sulfate (DHEAS) levels are associated with human term parturition. METHODS: Umbilical cord plasma cortisol and DHEAS concentrations were measured in 374 singleton pregnancies that delivered at term in the following six groups: group 1, cordocentesis for clinical indications before 36 weeks of gestation (n = 93); group 2, cordocentesis for clinical indications after 36 weeks of gestation (n = 9); group 3, cord blood sampling after elective cesarean section (CS) at term without labor (n = 140); group 4, cord blood sampling after CS at term with early labor (cervical dilatation < or =3 cm, n = 18); group 5, cord blood sampling after CS at term with active labor (cervical dilatation 4 cm or greater, n = 26); group 6, cord blood sampling after vaginal delivery at term (n = 88). Corticosteroids were not administered before blood collection. RESULTS: (1) Fetal plasma cortisol remained unchanged until 36 weeks of gestation and increased thereafter to term; (2) active labor was associated with a significant increase in fetal plasma cortisol; (3) fetal plasma DHEAS increased at term gestation (>36 weeks) but did not increase during active labor; (4) the cortisol/DHEAS ratio (stress index) increased with advancing gestation and with active labor at term. CONCLUSIONS. Human parturition at term is associated with an increase in fetal plasma cortisol and in the cortisol/DHEAS ratio, but not in DHEAS.
Adult↗
Angiotensinogen G(-6)A polymorphism is associated with the elevation of blood pressure in the hypertensive disorders of pregnancy.
The objective of the present study was to determine whether angiotensinogen G(-6)A polymorphism is associated with the elevation of blood pressure (BP) in the hypertensive disorders of pregnancy in Korean population. The subjects included 201 cases with the hypertensive disorders of pregnancy and 160 healthy controls. The medical records of subjects were reviewed. Cases were classified into the four subtypes (transient hypertension, preeclampsia, chronic hypertension, and preeclampsia superimposed on chronic hypertension) by the diagnostic criteria suggested by the National High Blood Pressure Education Program Working Group. Cases were also divided into the high and low BP group by the elevation of BP (diastolic BP greater than or equal to 110 mmHg). Maternal angiotensinogen G(-6)A polymorphism was determined by restriction fragment length polymorphism. Frequencies of AA genotype were significantly higher in the high than in the low BP group in the preeclampsia, superimposed preeclampsia, and the combined group (N = 201), suggesting that the angiotensinogen G(-6)A allele was significantly associated with the elevation of BP in the hypertensive disorders of pregnancy among South Korean women. The present findings imply that the elevation of BP can serve as an endophenotype for a spectrum of hypertensive conditions in pregnancy.
Analysis of Variance↗
Pregnancy outcomes in women with mechanical heart valves.
OBJECTIVE: To evaluate maternal complications and perinatal outcomes in women with mechanical heart valves treated with warfarin and heparin during pregnancy. STUDY DESIGN: A retrospective chart review was performed on 45 pregnancies in 28 women who were previously fitted with mechanical valve prostheses and treated between 1991 and 2005 at Seoul National University Hospital. Outcome parameters were maternal complications and perinatal outcomes. RESULTS: Overall, there were 27 live births (60%), 7 stillbirths (15.6%), 2 therapeutic terminations in the second trimester (4.4%), 9 first-trimester spontaneous abortions (20%) and 2 neonatal deaths after preterm delivery. After excluding 9 first-trimester spontaneous abortions and 3 pregnancies administered warfarin throughout pregnancy, there were significantly more live births among patients administered heparin only after a diagnosis of pregnancy than among those administered warfarin from the second trimester (11 of 11 vs. 13 of 22, p = 0.015). One patient with mitral valve thrombosis during heparinization in the first trimester received valve replacement surgery and then aborted. Late postpartum hemorrhage occurred in 1 patient. All stillbirths and therapeutic terminations occurred in women being administered warfarin. CONCLUSION: Warfarin use from the second trimester in combination anticoagulation regimens increases the risk of an adverse perinatal outcome.
Abortion, Spontaneous↗
An elevated maternal plasma, but not amniotic fluid, soluble fms-like tyrosine kinase-1 (sFlt-1) at the time of mid-trimester genetic amniocentesis is a risk factor for preeclampsia.
OBJECTIVE: The purpose of this study was to determine if an elevated concentration of soluble fms-like tyrosine kinase-1(sFlt-1) in maternal plasma and amniotic fluid is a risk factor for the subsequent development of preeclampsia. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of maternal plasma and amniotic fluid sFlt-1 in patients who developed preeclampsia with those who did not. The study included 32 cases with preeclampsia (18 cases: severe preeclampsia) and 128 matched controls with normal outcomes. Patients with an abnormal fetal karyotype or major anomaly, multiple pregnancies, chronic hypertension, diabetes, and renal disease were excluded. Soluble Flt-1 concentration was measured by specific immunoassay. Nonparametric techniques were used for statistical analysis. RESULTS: 1) The median maternal plasma, but not amniotic fluid, sFlt-1 concentration in patients who developed preeclampsia was significantly higher than in the control cases (maternal plasma: median 730 pg/mL, range 60-3375 pg/mL vs median 441 pg/mL, range 58-1959 pg/mL, P < .05; amniotic fluid: median 10,504 pg/mL, range 5253-38,023 pg/mL vs median 10,236 pg/mL, range 4326-87,684 pg/mL, P = .65). 2) The median plasma concentration of sFlt-1 was higher in cases of severe preeclampsia than in those with mild preeclampsia without reaching statistical significance (median 762 pg/mL, range 261-3309 pg/mL vs median 334 pg/mL, range 60-3375 pg/mL; P = .07). However, there was no significant difference in the median amniotic fluid sFlt-1 concentrations between patients with severe preeclampsia and those with mild preeclampsia (P = .45). 3) An elevated maternal plasma sFlt-1 concentration (higher than 700 pg/mL) is a risk factor for the development of preeclampsia (OR 3.9, 95% CI 1.7-8.6) and severe preeclampsia (OR 7.4, 95% CI 2.5-22.1) after genetic amniocentesis. 4) The median interval from amniocentesis to the diagnosis of preeclampsia in patients with maternal plasma sFlt-1 concentrations higher than 700 pg/mL was 117 days (range 19-154 days). CONCLUSION: An elevated concentration of sFlt-1 in maternal plasma at the time of mid-trimester amniocentesis is a risk factor for the subsequent development of preeclampsia.
Adult↗
Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia.
OBJECTIVE: Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy. This study used proteomic analysis of cerebrospinal fluid (CSF) to identify protein biomarkers characteristic of preeclampsia and related to its severity. STUDY DESIGN: CSF was collected from women diagnosed clinically with severe preeclampsia (sPE: n = 7), mild preeclampsia (mPE: n = 8), and normotensive controls (CRL: n = 8). Samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy. A discriminative proteomic biomarker profile was extracted by applying Mass Restricted analysis, and a Preeclampsia Proteomic Biomarker (PPB) score developed based on the presence or absence of four discriminatory protein peaks in individual CSF SELDI tracings. In-gel tryptic digests, Western blot analysis, on-chip immunoassays, ELISA, and spectral analysis were used to identify the biomarkers composing the PPB score. RESULTS: PPB score distinguished patients with a clinical diagnosis of sPE from mPE and CRLs. (PPB median [range]: sPE: 4 [0-4] vs mPE: 1 [0-1] vs CRL: 0 [0-0]; P < 0.001). PPB scores were unaffected by parity, magnesium seizure prophylaxis, CSF leukocyte counts, and total protein content. Proteomic identification techniques matched the discriminatory protein peaks to the alpha- and beta-hemoglobin chains. ELISA confirmed that women diagnosed clinically with sPE had significantly higher CSF hemoglobin concentrations than women with mPE or CRL (median [range]: sPE: 6.6 [0.0-10.3] microg/mL vs mPE: 0 [0-1.3] microg/mL vs CRL: 0 [0-0] microg/mL; P < 0.001). CONCLUSION: Proteomic analysis of CSF can accurately distinguish sPE from both mPE and CRL. Patients with sPE have nanomolar amounts of free hemoglobin in their CSF. Further studies are needed to confirm these observations and determine their physiologic implications.
Biomarkers↗
Maternal physiology and complications of multiple pregnancy.
Approximately 1% to 3% of all pregnancies in the United States are multiple gestations. The vast majority (97-98%) are twin pregnancies. Multiple pregnancies constitute significant risk to both mother and fetuses. Antepartum complications-including preterm labor, preterm premature rupture of the membranes, intrauterine growth restriction, intrauterine fetal demise, gestational diabetes, and preeclampsia-develop in over 80% of multiple pregnancies as compared with approximately 25% of singleton gestations. This article reviews in detail the maternal physiologic adaptations required to support a multiple pregnancy and the maternal complications that develop when these systems fail or are overwhelmed.
Female↗
Rotational forceps: should these procedures be abandoned?
Forceps delivery remains an important part of the obstetric armamentarium. When applied by practitioners skilled in their use, forceps delivery can quickly and safely deliver a fetus at risk. Unfortunately, forceps can also be an instrument of harm for the women or her infant. This is particularly true of rotational forceps. The goal of this monograph is to review in detail the indications, contraindications, technique, as well as risks and complications of forceps delivery, with particular attention to rotational forceps. We conclude by asking the question: Should rotational forceps be abandoned altogether?
Delivery, Obstetric↗
Warfarin-associated fetal intracranial hemorrhage: a case report.
A 27-yr-old woman who had been taking warfarin for 10 yr after mitral valve replacement became pregnant. After knowing her pregnancy, she received heparinization for nine weeks instead of warfarin, and took oral anticoagulant again. At 24 weeks of gestation, fetal ultrasound and MRI showed a left subdural hematoma, and the pregnancy was terminated. Subdural hematoma was demonstrated on autopsy. Fatal bleeding of the fetus is a rare complication of maternal warfarin medication, occurring mostly in the second or third trimester. There is no alternative regimen available, so that regular monitoring by fetal ultrasound and strict control of warfarin dose with regular measurement of prothrombin time are the best way to prevent intrauterine fetal death due to bleeding.
Adult↗
Percutaneous transcatheter angiographic embolization in the management of obstetric hemorrhage.
OBJECTIVE: To describe the results of percutaneous arterial embolization in the management of obstetric hemorrhage. STUDY DESIGN: From February 1992 to May 2000, 33 patients with pregnancy-related hemorrhage underwent angiographic embolization to control the hemorrhage. In all cases, hemostatic embolization was performed because of intractable hemorrhage unresponsive to conservative management. All available hospital records were reviewed and detailed, and the clinical data related to complications, clinical status, estimated blood loss and blood replacement requirements, length of time of procedure, emboli used, complications associated with the procedure and results obtained were analyzed. RESULTS: Successful embolization was achieved in 31 of 33 patients. No major complications related to embolization occurred, and 3 women subsequently became pregnant. CONCLUSION: Angiographic embolization is a safe and effective method of controlling pregnancy-related hemorrhagic complications unresponsive to conservative management and maintains reproductive ability.
Adult↗
Direct binding of AP-1 (Fos/Jun) proteins to a SMAD binding element facilitates both gonadotropin-releasing hormone (GnRH)- and activin-mediated transcriptional activation of the mouse GnRH receptor gene.
The response of pituitary gonadotropes to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GnRHR) on the cell surface, which is mediated in part at the level of gene expression. Several factors are known to affect expression of the mouse GnRHR (mGnRHR) gene, including GnRH and activin. We have previously shown that activin augments GnRH-mediated transcriptional activation of mGnRHR gene, and that region -387/-308 appears to be necessary to mediate this effect. This region contains two overlapping cis-regulatory elements of interest: GnRHR activating sequence (GRAS) and a putative SMAD-binding element (SBE). This study investigates the role of these elements and their cognate transcription factors in transactivation of the mGnRHR gene. Transfection studies confirm the presence of GnRH- and activin-response elements within -387/-308 of mGnRHR gene promoter. Competition electrophoretic mobility shift assay experiments using -335/-312 as probe and alphaT3-1 nuclear extract or SMAD, Jun, and Fos proteins demonstrate direct binding of AP-1 (Fos/Jun) protein complexes to -327/-322 and SMAD proteins to -329/-328. Further transfection studies using mutant constructs of these cis-regulatory elements confirm that both are functionally important. These data define a novel cis-regulatory element comprised of an overlapping SBE and newly characterized non-consensus AP-1 binding sequence that integrates the stimulatory transcriptional effects of both GnRH and activin on the mGnRHR gene.
3T3 Cells↗