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Biomedical subjects

Robert M Silver

Publications and source records attributed to Robert M Silver.

14 recordsLinked to original sources
PubMed2007

Fetal death.

The death of a formed fetus is one of the most emotionally devastating events for parents and clinicians. With improved care for conditions such as RhD alloimmunization, diabetes, and preeclampsia, the rate of fetal death in the United States decreased substantially in the mid twentieth century. However, the past several decades have seen much greater reductions in neonatal death rates than in fetal death rates. As such, fetal death remains a significant and understudied problem that now accounts for almost 50% of all perinatal deaths. The availability of prostaglandins has greatly facilitated delivery options for patients with fetal death. Risk factors for fetal death include African American race, advanced maternal age, obesity, smoking, prior fetal death, maternal diseases, and fetal growth impairment. There are numerous causes of fetal death, including genetic conditions, infections, placental abnormalities, and fetal-maternal hemorrhage. Many cases of fetal death do not undergo adequate evaluation for possible causes. Perinatal autopsy and placental examination are perhaps the most valuable tests for the evaluation of fetal death. Antenatal surveillance and emotional support are the mainstays of subsequent pregnancy management. Outcomes may be improved in women with diabetes, hypertension, red cell alloimmunization, and antiphospholipid syndrome. However, there is considerable room for further reduction in the fetal death rate.

Bereavement↗
PubMed2006

Maternal morbidity associated with multiple repeat cesarean deliveries.

OBJECTIVE: Although repeat cesarean deliveries often are associated with serious morbidity, they account for only a portion of abdominal deliveries and are overlooked when evaluating morbidity. Our objective was to estimate the magnitude of increased maternal morbidity associated with increasing number of cesarean deliveries. METHODS: Prospective observational cohort of 30,132 women who had cesarean delivery without labor in 19 academic centers over 4 years (1999-2002). RESULTS: There were 6,201 first (primary), 15,808 second, 6,324 third, 1,452 fourth, 258 fifth, and 89 sixth or more cesarean deliveries. The risks of placenta accreta, cystotomy, bowel injury, ureteral injury, and ileus, the need for postoperative ventilation, intensive care unit admission, hysterectomy, and blood transfusion requiring 4 or more units, and the duration of operative time and hospital stay significantly increased with increasing number of cesarean deliveries. Placenta accreta was present in 15 (0.24%), 49 (0.31%), 36 (0.57%), 31 (2.13%), 6 (2.33%), and 6 (6.74%) women undergoing their first, second, third, fourth, fifth, and sixth or more cesarean deliveries, respectively. Hysterectomy was required in 40 (0.65%) first, 67 (0.42%) second, 57 (0.90%) third, 35 (2.41%) fourth, 9 (3.49%) fifth, and 8 (8.99%) sixth or more cesarean deliveries. In the 723 women with previa, the risk for placenta accreta was 3%, 11%, 40%, 61%, and 67% for first, second, third, fourth, and fifth or more repeat cesarean deliveries, respectively. CONCLUSION: Because serious maternal morbidity increases progressively with increasing number of cesarean deliveries, the number of intended pregnancies should be considered during counseling regarding elective repeat cesarean operation versus a trial of labor and when debating the merits of elective primary cesarean delivery. LEVEL OF EVIDENCE: II-2.

Cesarean Section, Repeat↗
PubMed2006

Preconception counseling for women with thrombophilia.

Inherited thrombophilias are a heterogeneous group of coagulation disorders that predispose individuals to thromboembolic events. This group of conditions is the major risk factor for thromboembolism during pregnancy and the puerperium. In addition, thrombophilias have been associated with several adverse obstetric events, including pregnancy loss, preeclampsia, placental abruption, and intrauterine growth restriction. An increased risk for these obstetric complications has prompted many authorities to recommend screening and treating pregnant women for thrombophilias. Optimal obstetric management, however, is controversial as thrombophilias are common and many affected individuals are asymptomatic. Indeed, pregnancy outcome in most women with thrombophilias is normal. The most commonly identified inherited thrombophilias are the factor V Leiden and prothrombin G20210A gene mutations. More rare thrombophilias include protein C and S deficiencies, antithrombin III deficiency. Although relatively common, the association between hyperhomocysteinemia and associated mutations (such as the C677 T methylenetetrahydro-folate reductase) and obstetric complications is controversial.

Factor V↗
PubMed2006

The aryl hydrocarbon receptor nuclear translocator gene polymorphism in patients with recurrent miscarriage.

OBJECTIVE: The human aryl hydrocarbon receptor nuclear translocator gene (ARNT) is crucial for embryonic development. Knockout of ARNT is embryonic lethal. We thus hypothesized that some cases of recurrent miscarriage (RM) may be due to a polymorphism in the ARNT gene. METHODS: Polymerase chain reaction was used to compare the gene frequencies of a polymorphism in codon 511 of the ARNT gene in 170 women with idiopathic RM and 105 controls. RESULTS: Using the Hardy-Weinberg equilibrium calculation, the predicted ARNT genotype frequencies for the N511/N511, N511/D511, and D511/D511 genotypes were 0, 2, and 167 respectively. The observed frequencies were 0, 2, and 168 (NS). The N/511/D511 genotype was detected in 1.2% of cases and 2.8% of controls, and the D511/D511genotype was detected in 98.8% of cases and 97.2% of controls (NS). CONCLUSIONS: In our cohort of patients, the polymorphism in codon 511 of the ARNT gene is not associated with RM.

Abortion, Habitual↗
PubMed2005

The use of cDNA microarray to identify differentially expressed labor-associated genes within the human myometrium during labor.

OBJECTIVE: Microarray technology was used to comprehensively analyze gene expression during human labor in the myometrium. STUDY DESIGN: cDNA micro-array was used to compare the transcriptomes of myometrium obtained from patients in spontaneous labor and those not in labor. Expression of four labor-specific genes was confirmed in the myometrium obtained from patients in spontaneous labor using RT-PCR, Northern blot analysis, and in-situ hybridization. RESULTS: Of the >6000 cDNAs evaluated, 56 were found to be differentially expressed during labor. The labor-specific expression of 4 genes was confirmed using RT-PCR and Northern blot analysis. The relative increased expression of thrombospondin-1 in myometrium obtained from patients in spontaneous labor was also confirmed using in-situ hybridization. CONCLUSION: cDNA microarray was used to identify 56 differentially expressed genes in myometrium obtained from patients in spontaneous labor. The up-regulation of four genes was confirmed by multiple methods. Elucidation of the role(s) of the genes identified by microarray should improve our understanding of normal labor physiology and may ultimately lead to more effective treatments for abnormal labor.

Blotting, Northern↗
PubMed2005

The factor V Leiden and the G20210A prothrombin gene mutations are rare in women with fetal death.

PROBLEM: To determine if there is an association between two commonly inherited thrombophilias, the factor V Leiden and the G20210A prothrombin mutations, and fetal death. METHOD OF STUDY: We used a case-control study design to compare the frequencies of these mutations in women with fetal death and controls. Fetal death was the intrauterine death of the conceptus > or =10 weeks gestation. Controls had one live birth, no miscarriages, and no fetal death. Results were compared using chi square analysis. RESULTS: One hundred and seventy-five cases and controls were identified. There were 4.6% of cases and 3.8% of controls heterozygous for the factor V Leiden mutation (NS), and 1.3% of cases and 1.7% of controls heterozygous for the prothrombin mutation (NS). CONCLUSION: In our population, neither the factor V Leiden nor the G20210A prothrombin mutations are associated with fetal death. Further evidence is required before routine screening for these mutations can be recommended.

Adolescent↗
PubMed2004

Maternal autoimmune diseases and immunologically induced embryonic and fetoplacental damage.

BACKGROUND: Autoimmune diseases are a group of illnesses in which autoantibodies are produced against various organs, presenting with a variety of clinical symptoms. In this review, we discuss the different aspects of autoimmune diseases in pregnancy. We also describe experimental models that help to understand the etiology and pathogenesis of the effects of this maternal disease on the developing embryo, fetus and placenta. METHODS: The possible direct effects of sera or IgG obtained from women with systemic lupus erythematosus/antiphospholipid syndrome (SLE/APS) and recurrent pregnancy loss (RPL) were examined on cultured 10.5- and 11.5-day-old rat embryos and on cultured human placental explants, as compared to sera from healthy women or synthetic medium that were used as controls. In addition, we examined the effects of the sera obtained from these women after successful treatment that allowed the birth of normal infants. RESULTS: We observed increased embryonic death and anomalies in embryos cultured on sera and IgG from SLE/APS women. Similarly, when human placental explants were cultured on these sera, trophoblastic cell growth was reduced and apoptotic rate was increased. Successful treatment also reduced the damage caused by the sera from these women in the cultured embryos and placentas. CONCLUSIONS: Our results, and the cited studies, point to the important role of the placental damage in the etiology of RPL associated with SLE/APS. Animal models, both in vivo and in vitro, as well as cultured early human placental explants can be used successfully to understand some of the pathogenic aspects of SLE/APS and RPL.

Abortion, Habitual↗
PubMed2004

Homocysteine levels in women with antiphospholipid syndrome and normal fertile controls.

OBJECTIVE: Recent studies have identified hyperhomocysteinemia as a risk factor for both recurrent pregnancy loss and thrombosis. Antiphospholipid syndrome, an autoimmune disorder, is also characterized by recurrent pregnancy loss and thrombosis. Thus, our purpose was to determine if hyperhomocysteinemia is more common in patients with APS than normal fertile controls. METHODS: Plasma, sera and whole blood were obtained from two groups of women: (1) 22 with well-characterized antiphospholipid syndrome; and (2) 41 healthy fertile controls. Levels of fasting homocysteine, vitamin B16, vitamin B12, folate and the incidence of the C677/T mutation of the methylene tetrahydrofolate reductase genotype (C677T/MTHFR) were determined. RESULTS: The proportion of individuals with hyperhomocysteinemia and fasting plasma homocysteine levels were similar in women with APS and controls. Levels of vitamin B6, vitamin B12, folate and the incidence of C677/MTHFR were also similar in the two groups. CONCLUSION: Hyperhomocyteinemia and the C677T/MTHFR mutation are not common in women with antiphospholipid syndrome. Abnormal homocysteine metabolism is unlikely to play a major role in the pathogenesis of antiphospholipid syndrome.

Adult↗
PubMed2004

Autoimmune disease in pregnancy: systemic lupus erythematosus and antiphospholipid syndrome.

Autoimmune diseases most commonly occur in women of childbearing age. Although some conditions such as ankylosing spondylitis are more common in men, over 70% of individuals with autoimmune diseases are women. This article focuses on SLE,which is often considered to be the "classic" autoimmune disease,and antiphospholipid syndrome (APS), which is associated with pregnancy loss and placental insufficiency.

Antiphospholipid Syndrome↗
PubMed2004

Poor obstetric outcome in subsequent pregnancies in women with prior fetal death.

OBJECTIVE: Patients with recurrent first-trimester spontaneous abortion have been the subject of intensive investigation. However, relatively little is known about second- and third-trimester pregnancy loss. Thus, it is difficult for clinicians to optimally counsel, evaluate, and manage women with previous unexplained fetal death. Our objective was to ascertain the outcome of subsequent pregnancies in patients with prior fetal death. METHODS: Subjects were identified from patients referred for evaluation of fetal death (occurring at >/= 10 weeks of gestation) and having at least one subsequent pregnancy. Patients with antiphospholipid antibodies were excluded. Logistic regression analysis was performed to determine the association of clinical variables with pregnancy outcome. RESULTS: Two hundred thirty subjects met inclusion criteria. Up through the time of their first fetal death, these women had a total of 721 pregnancies, resulting in 268 (37%) live births, 230 (32%) fetal deaths, and 200 (28%) spontaneous abortions. In total, these women had 839 subsequent pregnancies, resulting in 202 (24%) live births, 209 (25%) fetal deaths, and 372 (44%) spontaneous abortions. Univariate logistic regression analysis identified older age at pregnancy (P =.009, odds ratio 0.63, 95% confidence interval 0.42-1.03) and treatment with low-dose aspirin (P =.001, odds ratio 0.41, 95% confidence interval 0.25-0.68) to be associated with a decreased risk for subsequent pregnancy loss. CONCLUSION: Women with prior fetal death are at high risk for subsequent pregnancy loss and recurrent fetal death, with fewer than 25% of pregnancies resulting in surviving infants. These data underscore the need for additional research into the pathophysiology and prevention of recurrent fetal death.

Abortion, Spontaneous↗
PubMed2004

Recurrent fetal aneuploidy and recurrent miscarriage.

OBJECTIVE: Some investigators have found a high frequency of abortus aneuploidy in women with recurrent miscarriage, suggesting the possibility of recurrent aneuploidy as a cause of recurrent miscarriage. Others contend that aneuploidy is not a cause of recurrent miscarriage. The purpose of this study was to investigate the relationship between fetal aneuploidy and recurrent miscarriage by estimating whether fetal aneuploidy is more common in patients with recurrent miscarriage than in patients with sporadic miscarriage METHODS: Recurrent miscarriage cases (n = 135) included women who had a subsequent miscarriage in which an abortus karyotype was obtained. Controls (n = 150) were patients experiencing a sporadic miscarriage who had fetal karyotypes performed as part of a study to assess the utility of abortus tissue for transplantation. Karyotype analysis was performed using standard G-banding techniques. RESULTS: Abortuses from 122 cases and 133 controls were successfully karyotyped. Thirty-one (25.4%) abortuses from cases and 56 (42.1%) from controls were aneuploid (odds ratio 0.47, 95% confidence interval 0.27-0.80). Aneuploid abortuses occurred in 20% of cases and 25% of controls, aged 20-29 years, 19% of cases and 24% of controls, aged 30-34 years, 35% of cases and 47% of controls, aged 35-39 years, and 50% of both cases and controls, aged 40 years or older (not significant). Of 30 cases in whom 2 or more miscarriages were karyotyped, 3 (10%) had aneuploidy in each abortus. CONCLUSION: In our population of recurrent miscarriage patients, abortus aneuploidy occurred significantly less often than in sporadic miscarriages. The rate of aneuploidy in this study was considerably lower than reported in other studies. If recurrent aneuploidy contributes to recurrent miscarriage, it does so in only a small number of patients. LEVEL OF EVIDENCE: II-2

Abortion, Habitual↗
PubMed2003

Anticardiolipin and anti-beta2-glycoprotein-I antibodies in preeclampsia.

OBJECTIVE: To estimate whether antiphospholipid antibodies, specifically anticardiolipin and anti-beta(2)-glycoprotein-I antibodies, are associated with preeclampsia. METHODS: Plasma was prospectively obtained from four groups of pregnant women: those with 1) mild preeclampsia (n = 109); 2) severe preeclampsia (n = 134); 3) hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 57); and 4) normotensive controls (n = 100). Anticardiolipin and anti-beta(2)-glycoprotein-I levels were determined by enzyme-linked immunoassay. RESULTS: Subjects with mild preeclampsia, severe preeclampsia, and HELLP syndrome did not have significantly elevated levels of immunoglobulin G (IgG) and IgM anticardiolipin and anti-beta(2)-glycoprotein-I antibodies compared with normotensive controls (P >.05, Kruskal-Wallis). Similarly, subjects with mild preeclampsia, severe preeclampsia, and HELLP syndrome did not have a significantly higher proportion of women testing positive for each autoantibody compared with normotensive controls (chi(2)). The proportion of patients testing positive for anticardiolipin and anti-beta(2)-glycoprotein-I antibodies were similar in patients with preeclampsia developing before and after 34 weeks' gestation (chi(2)). CONCLUSION: Circulating levels of both anticardiolipin and anti-beta(2)-glycoprotein-I antibodies were not increased in patients with mild preeclampsia, severe preeclampsia, or HELLP syndrome compared with normotensive controls. Our data do not support routine testing for anticardiolipin and anti-beta(2)-glycoprotein-I antibodies in women with preeclampsia.

Adult↗
PubMed2003

The management of acardiac twins: a conservative approach.

OBJECTIVE: Optimal management of acardiac twin pregnancies is controversial. Data suggest a 50% mortality rate in the "pump" twin when the pregnancy is managed expectantly. Because of increased antenatal diagnosis, outcomes in expectantly managed cases may be better than reported. Our objective was to determine the outcome of expectantly managed acardiac twin pregnancies. STUDY DESIGN: All cases of antenatally diagnosed acardiac twins delivered in our community between 1994 and 2001 were ascertained. All were managed expectantly. Perinatal outcome of pump twins was the primary outcome variable. RESULTS: Ten cases were identified. Nine women were delivered of healthy pump twins. There was one neonatal death. The mean gestational age at delivery was 34.2 weeks. The mean weights of the pump and acardiac twins were 2279 g and 1372 g, respectively. CONCLUSION: Neonatal mortality of pump twins in antenatally diagnosed acardiac twin pregnancies may be considerably less than reported. Expectant management with close antepartum surveillance deserves consideration.

Diseases in Twins↗