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Biomedical subjects

R F Burrows

Publications and source records attributed to R F Burrows.

At least 37 records · Page 2Linked to original sources

The prenatal identification of fetal compatibility in neonatal alloimmune thrombocytopenia using amniotic fluid and variable number of tandem repeat (VNTR) analysis.

Most severe episodes of neonatal alloimmune thrombocytopenic purpura (NATP) are caused by antiplatelet alloantibodies against the HPA-1a (PlA1) antigen. However, half of subsequent fetuses produced from a HPA-1a/b father (genotypic frequency 28%) will result in a child who is not affected. Some investigators manage NATP by confirming the fetal platelet phenotype using percutaneous umbilical cord sampling, a procedure that carries a low but real risk of fetal morbidity and mortality. More recently, physicians determine the fetal platelet antigen genotype using DNA derived from amniotic fluid or chorionic villus samples. All therapy is withdrawn for a fetus who genotypes as HPA-1b/b. However, since the fetus is the same genotype as the mother, there can be uncertainty about the origin of the genetic material and thus the validity of the fetal genotype. The inappropriate withdrawal of therapy for a erroneously genotyped fetus could be fatal, and consequently many physicians advocate fetal HPA-1 phenotyping with confirmation using percutaneous umbilical blood sampling. In this report we describe the management of two pregnancies with previously affected infants due to anti-HPA-1a alloantibodies. Both husbands were HPA-1a/b. For the current pregnancies, amniotic fluid was collected at 20 or 29 weeks of gestation, and the platelet genotype indicated that the fetuses were HPA-1b/b. The fetal origin of the amniotic fluid derived DNA was confirmed by the forensic technique of DNA profiling using variable number of tandem repeat (VNTR) analysis. All therapy was withdrawn, percutaneous umbilical blood sampling was not performed, and both women vaginally delivered healthy non-thrombocytopenic infants. The application of platelet alloantigen genotyping using DNA from amniotic fluid cells identified the HPA-1b/b fetus, and VNTR analysis confirmed that the tissue was fetal derived, thus avoiding the necessity for percutaneous umbilical blood sampling. The use of this approach in patients at risk will avoid additional investigation and treatment in approximately one-seventh of all NATP pregnancies involving the HPA-1a antigen.

Amniotic Fluid↗

Perinatal thrombocytopenia.

Maternal thrombocytopenia is common in normal pregnancies, but is a poor predictor of fetal thrombocytopenia even when the maternal thrombocytopenia is of pathologic etiology. The real risk to the fetus and the neonate is alloimmune thrombocytopenia, although identification of index cases is problematic and management of future pregnancies has not been defined.

Female↗

Fetal thrombocytopenia and its relation to maternal thrombocytopenia.

BACKGROUND: Neonates with severe thrombocytopenia can have bleeding leading to death or lifelong residual defects. The predictors, frequency, and consequences of fetal thrombocytopenia are not known, nor is it known if there are maternal clinical features that could predict fetal thrombocytopenia. METHODS: We conducted a seven-year cross-sectional study in which platelet counts were determined in newborns' umbilical-cord blood and blood obtained from their mothers at consecutive deliveries in one obstetrical unit. The relations of the umbilical-cord platelet count to maternal risk factors were determined. RESULTS: Platelet counts were determined in blood samples from 15,471 mothers and 15,932 newborn infants. The cord-blood platelet count was less than 50,000 per cubic millimeter in 19 infants (0.12 percent; 95 percent confidence interval, 0.07 to 0.19 percent), whereas the platelet count was less than 150,000 per cubic millimeter in 6.6 percent of the mothers (95 percent confidence interval, 6.2 to 7.0 percent). One infant among those born to 756 mothers with incidental thrombocytopenia, 5 infants among those born to 1414 mothers with hypertension, and 4 infants among those born to 46 mothers with idiopathic thrombocytopenic purpura had cord-blood platelet counts between 20,000 and 50,000 per cubic millimeter. Only 6 infants (0.04 percent; 95 percent confidence interval, 0.01 to 0.08 percent) had cord-blood platelet counts of less than 20,000 per cubic millimeter; all their mothers were among the 18 whose 19 fetuses were at risk for neonatal alloimmune thrombocytopenia. Two of these infants had in utero intracranial hemorrhage. In addition, 3 infants born to these 18 women had cord-blood platelet counts between 20,000 and 50,000 per cubic millimeter; there was 1 stillbirth due to intracranial hemorrhage. CONCLUSIONS: Moderate-to-severe fetal thrombocytopenia is a rare event. The only severely affected neonates with morbidity or mortality due to this condition are those born to mothers with antiplatelet alloantibodies.

Blood Platelets↗

Influence of maternal insulin-dependent diabetes mellitus on neonatal morbidity.

OBJECTIVE: To compare the neonatal morbidity rates (corrected for gestational age at delivery and method of delivery) among infants of women with insulin-dependent diabetes mellitus and those of women without diabetes. DESIGN: Historical cohort analysis. SETTING: Tertiary care centre. PATIENTS: All liveborn infants of women with insulin-dependent diabetes mellitus (IDM group) born between Jan. 1, 1980, and Dec. 31, 1989, each matched for gestational age at delivery, method of delivery and year of birth with two newborns of women without diabetes (control group). MAIN OUTCOME MEASURES: Neonatal respiratory distress, jaundice, hypoglycemia, polycythemia, hypocalcemia, intraventricular hemorrhage, seizure and macrosomia. RESULTS: There were 230 infants in the IDM group and 460 in the control group. Compared with the control group the IDM group had significantly higher incidence rates of glucose infusion (odds ratio [OR] 5.38), birth weight above the 90th percentile (OR 4.15) and neonatal jaundice (OR 1.94). No significant difference was found in the incidence rate of respiratory distress, polycythemia or hypocalcemia. The maternal serum hemoglobin A (HbA) level was not significantly related to birth weight, and neither the serum HbA level nor the presence of macrosomia was predictive of neonatal morbidity. Nearly 25% of the infants in the IDM group were born before 37 weeks' gestation; 48.2% of these were delivered early because of maternal hypertension. CONCLUSIONS: Neonatal morbidity in infants of women with diabetes is determined more by gestational age at delivery than by the maternal diabetes. Within the limits obtained in this study the degree of control of the diabetes does not seem to affect neonatal morbidity.

Adult↗

Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state.

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.

Adult↗

Cesarean section: analysis of the experience before and after the National Consensus Conference on Aspects of Cesarean Birth.

OBJECTIVE: To examine the effect of recommendations to reduce the cesarean section rate issued by the National Consensus Conference on Aspects of Cesarean Birth in 1986 on obstetric practices and to identify current patient factors that predict cesarean section. DESIGN: Descriptive retrospective cross-sectional study. SETTING: A tertiary care perinatal referral centre and a general teaching hospital with a level 2 nursery in Hamilton, Ont. PATIENTS: All patients who gave birth at the two hospitals in 1982 (4121 women) and 1990 (4431). MAIN OUTCOME MEASURES: Cesarean section rates and indications and predictors of cesarean section. RESULTS: Although a trial of vaginal delivery after cesarean section was offered 93% more often in 1990 than in 1982 (p = 0.0002), the rate of vaginal delivery increased only 2.6%, for a reduction of 8.7% in the total cesarean section rate and of 15% in the repeat cesarean section rate. The incidence rate and treatment of dystocia did not change. The rate of cesarean section for breech presentation remained unchanged, and fetal distress was rarely confirmed with pH measurement in scalp blood before cesarean section. The most important predictors of cesarean section in 1990 were previous cesarean section and labour induction. For the nulliparous women and the multiparous women with no previous cesarean section labour induction was the most important predictor. CONCLUSIONS: The rate at which patients with previous cesarean section are offered a trial of vaginal delivery has increased significantly since 1982; however, the total and repeat cesarean section rates have not decreased proportionally. Induction of labour is currently the most important correctable predictor of cesarean section. The active management of dystocia, efforts to increase the rate of vaginal breech delivery and appropriate methods to diagnose fetal distress need to be improved; such improvements should reduce the cesarean section rate further.

Adult↗

The use of an indwelling Teflon catheter for subcutaneous heparin administration during pregnancy. A randomized crossover study.

BACKGROUND: The use of subcutaneous heparin, the therapy of choice for women requiring anticoagulant prophylaxis during pregnancy, is problematic because of the discomfort produced by repeated injections. An indwelling subcutaneous Teflon catheter that can be left in place for 1 week recently became available for use as an entry port for parenteral therapy. Since the use of this catheter has the potential to overcome some of the problems of long-term heparin therapy, we decided to compare this Teflon catheter with twice-daily subcutaneous injections in women requiring heparin during pregnancy. METHODS: In a randomized, multiple-crossover study, patients alternated every 2 weeks between having heparin administered through the indwelling Teflon catheter and receiving heparin via subcutaneous injections. After each 4-week cycle, patients completed a questionnaire designed to determine their preferred method of heparin administration. The side effects, doses, and anticoagulant activity of heparin with the two delivery systems were also compared. RESULTS: Twelve patients completed one to five 4-week cycles of heparin therapy. Ten of the patients selected the Teflon catheter as the preferred route of heparin administration (P = .04) and 11 patients reported that the catheter caused less pain and bruising than twice-daily subcutaneous injections (P < .01). Five patients developed urticarial reactions at the sites of heparin injections. These reactions tended to be more severe when the Teflon catheter was used, and two women discontinued using the catheter after the first cycle because of this complication. There were no differences in heparin dose requirements or achieved activated partial thromboplastin times between the two routes of heparin administration. CONCLUSIONS: Most pregnant women in our study preferred to have subcutaneous heparin administered through an indwelling Teflon catheter rather than by twice-daily injections. Heparin given through the Teflon catheter was bioavailable and caused less local bruising than twice-daily injections. Urticarial reactions to heparin tended to be more severe with the use of the Teflon catheter and resulted in the discontinuation of the device's use in two of 12 patients.

Adult↗

A primary cytomegalovirus infection in pregnancy presenting with unusual hematologic manifestations: a case report.

A previously healthy multigravida woman presenting with pyrexia was found to be pancytopenic at 32 weeks' gestation. The leukopenia and the thrombocytopenia responded to supportive therapy. The anemia, which was Coombs' negative, continued and was associated with a drop in fibrinogen, but both eventually returned to normal with time. The isolation of the cytomegalovirus and the detection of an IgM immune response to cytomegalovirus implicated the virus as the agent responsible for the clinical manifestations. The fetus, who was well throughout the maternal illness, had no evidence of anemia or thrombocytopenia at birth; however, intrauterine infection was confirmed by isolation of the virus from the newborn's urine.

Adult↗

Pregnancy in patients with idiopathic thrombocytopenic purpura: assessing the risks for the infant at delivery.

The objective of this review is to estimate the risk of severe thrombocytopenia at birth and minor or major morbidity for the infant of a pregnancy complicated by immune thrombocytopenic purpura. English language publications on immune thrombocytopenic purpura in pregnancy from January 1980 to December 1990 were used. Manuscripts considered for infant risk assessment fulfilled the following criteria: 10 or more entrants, reported fetal platelet samples (cordocentesis, scalp sampling or cord sample at birth), and provided all infant platelet data. All other data not fulfilling these criteria are reported. The main results were 11 manuscripts reporting 288 live-born infants fulfilled the criteria enabling assessment of infant risk. There were no deaths or intracranial hemorrhages in these studies and secondary morbidity occurred in 3.5 per cent (95 per cent CI 1.4-5.6 per cent). An infant platelet count of less than 50 x 10(9) per liter was reported in 10.1 per cent (95 per cent CI 6.6-13.6 per cent) and an infant platelet count of less than 20 x 10(9) per liter occurred in 4.2 per cent (95 per cent CI 1.9-6.5 per cent). Neither cordocentesis, scalp sample, nor umbilical cord sampling at birth altered the outcome of these infants and minor morbidity occurred equally in vaginal and cesarean births. Smaller case reports (less than 10 entrants) significantly over-estimated the prevalence of severe infant thrombocytopenia and secondary morbidity. All deaths and intracranial hemorrhages were reported in manuscripts which did not specify the timing of infant platelet count determination; thus the relationship of these events to the event of birthing was unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Bias↗

Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study.

To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well-defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.

Abortion, Spontaneous↗

Venous thrombosis during pregnancy: leg and trimester of presentation.

In order to determine the relative frequencies of left and right leg venous thrombosis during pregnancy and the frequencies of venous thrombosis during the three trimesters, a cohort study of 60 consecutive patients with a first episode of venous thrombosis during pregnancy was performed. Fifty-eight women had isolated left leg thrombosis, two patients had bilateral venous thrombosis and no patient had isolated right leg venous thrombosis. Thirteen patients had venous thrombosis during the first trimester (21.7%), 28 during the second trimester (46.7%) and 19 during the third trimester (31.7%). These findings indicate that patients with symptoms in the right leg rarely have venous thrombosis. Because leg pain and swelling occur most frequently during the third trimester but venous thrombosis is relatively equally distributed during all three trimesters, patients presenting earlier during pregnancy are more likely to have venous thrombosis than patients presenting later during pregnancy.

Female↗

Thrombin regulation in mother and fetus during pregnancy.

Pregnancy is characterized by an increase in plasma concentration of several coagulants and with little or no change in plasma concentrations of inhibitors of thrombin or thrombin generation with the exception of a decrease in protein S. The net effect of these physiologic differences from nonpregnant adults is that, in vitro, thrombin generation is slightly increased in pregnancy plasma. Thrombin inhibition may be altered by the presence of circulating dermatan sulfate proteoglycan. Based on information on placental structure and function and ex vivo markers of thrombin generation, it is clear that there must be local generation of thrombin with fibrin deposition in the placenta. The roles of the alterations in the hemostatic system in regulating this increased thrombin activity remain to be elucidated. In addition, regulation of thrombin at the vessel wall of the placenta needs to be further explored, since it is likely important in preventing locally increased thrombin generation from producing systemic effects, that is, thrombosis. The fetal coagulation system is an immature, developing system, as is evident from low and gradually increasing plasma concentrations of both coagulants and inhibitors. Some of these low levels result from decreased gene expression in the immature liver. However, others (Factors II, VII and VIII) are related to other processes that remain to be determined. There is a progressive increase in the levels of these factors with increasing gestational age but most remain below adult values at term. As a result, thrombin generation and inhibition in vitro are decreased. Since bleeding and thrombotic complications are not a feature of normal fetal life, it is likely that the hemostatic system is balanced. In vivo data on thrombin generation and inhibition are lacking and the interaction of the physiologically different plasma of the fetus with the vessel wall is only now being explored.

Blood Coagulation Factors↗

False diagnosis of intestinal obstruction in a fetus with congenital chloride diarrhea.

Intestinal obstruction is often diagnosed prenatally by ultrasound, providing an opportunity for prenatal counseling, genetic investigation, and planned delivery at a perinatal center. We describe a patient with typical features of fetal bowel obstruction, who was found at birth to have congenital chloride diarrhea. A 25-year-old white woman had marked polyhydramnios; multiple dilated, fluid-filled loops of intestine were seen in the fetal abdomen on prenatal ultrasound. However, postnatally, there was no evidence of bowel obstruction. The infant girl passed large amounts of watery stools, but tolerated feeds well. A rectal biopsy showed normal ganglion cells. On the fourth day of life her serum sodium and chloride were markedly decreased, and stool chloride levels were diagnostic of congenital chloride diarrhea. She was placed on sodium chloride and potassium chloride supplements, and her serum electrolytes normalized. Congenital chloride diarrhea is a rare, inherited condition caused by an abnormality of intestinal electrolyte transport. This case illustrates that it may present prenatally with a picture similar to that seen with intestinal obstruction.

Adult↗

Use of prescription drugs in the first trimester and congenital malformations.

A prospective survey of prenatal use of prescription drugs in Tasmania yielded detailed information on drug exposure, delivery and outcome for 56,037 births from 1982 to 1989. First trimester drug use was reported by 30.9% of women, and 17.9% used only supplements of vitamins and/or minerals; 40% used alcohol during the first trimester, and 28.8% smoked cigarettes. There were 1,035 (1.85%) congenital malformations, of which 885 (85.5%) were major. The malformation rate was not significantly different in the following exposure categories: supplements only (1.62%); other pharmaceuticals (1.92%); smokers (1.88%); alcohol users (1.89%); and maternal age 35 or more years (1.95%). Adjusting for alcohol use, smoking, maternal age and diabetes mellitus, significant associations [expressed as adjusted odds ratio and 95% confidence intervals (CI)] were found between aspirin and hypospadias (3.5, 95% CI 1.4 to 8.8); dicyclomine and phocomelia (4.4, 95% CI 1.0 to 19.5); and between oral contraceptive use and pes cavus (9.7, 95% CI 2.3 to 40.4). Although significant, these associations were based on very few cases and no direct supporting evidence could be found from other data sources.

Abnormalities, Drug-Induced↗

Alloimmune neonatal thrombocytopenia associated with incidental maternal thrombocytopenia.

In this report, we describe a mother with mild incidental thrombocytopenia who delivered a severely thrombocytopenic infant having alloimmune thrombocytopenia. This coincidental association should be considered because the recognition and proper diagnosis of alloimmune neonatal thrombocytopenia is important, not only in the current pregnancy, but also in future pregnancies.

Adult↗

Low fetal risks in pregnancies associated with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura and pregnancy are commonly associated. In this article we describe our experience in the management of 61 infants born to 50 mothers with confirmed idiopathic thrombocytopenic purpura. The focus was the neonatal cord platelet count, the parameter of greatest interest to obstetricians. None of the 61 infants had morbidity or mortality as a consequence of the thrombocytopenia. Only three of 61 infants (4.9%) had a cord platelet count that was less than 50 x 10(9) per liter. Although 66% of the infants had a further fall in the platelet count after birth, in all the thrombocytopenia could readily be corrected. Neither maternal platelet count, maternal treatment with corticosteroids, maternal platelet-associated immunoglobulin G level, nor maternal splenectomy could be used to predict neonatal thrombocytopenia. Fetal scalp platelet sampling was likely to lead to an erroneous decision. The rareness of a poor neonatal outcome raises the question of whether obstetric interventions are justified for every pregnant patient with idiopathic thrombocytopenic purpura.

Female↗

Thrombocytopenia at delivery: a prospective survey of 6715 deliveries.

Thrombocytopenia occurred in 513 (7.6%) of 6715 consecutive deliveries that occurred in our hospital over a 3-year interval. The patients with thrombocytopenia could be divided into three groups. The largest group (65.1%) consisted of healthy women whose thrombocytopenia was incidentally detected. The next group of patients (13.1%) was composed of healthy women who had an obstetric or medical condition such as diabetes or premature labor. No mother or infant in either group had excessive bleeding, and no infant had a cord platelet count less than 50 x 10(9) per liter. The last group (21%) was composed of hypertensive patients and patients with immune thrombocytopenia. Two infants in this group had cord platelet counts less than 50 x 10(9) per liter, but neither had bleeding. This study indicates that incidental thrombocytopenia in an otherwise well woman at term is the most frequent type of thrombocytopenia and poses no apparent risk for mother or infant at delivery.

Female↗

Neonatal thrombocytopenia in the hypertensive disorders of pregnancy.

Infants of hypertensive mothers are at risk for a platelet count below 150 x 10(9)/L. To define this risk and assess maternal factors influencing the prevalence of neonatal thrombocytopenia, we collected cord blood samples from 520 infants of 607 consecutive hypertensive mothers with singleton pregnancies. The platelet count in cord blood from infants of hypertensive mothers was compared with that of a control normotensive population, and other comparisons were made among various maternal hypertensive groups. The rate of neonatal thrombocytopenia was 9.2% in hypertensive patients, compared with 2.2% in infants of normotensive mothers (P less than .00001). In the hypertensive group, preterm birth was the major risk factor for neonatal thrombocytopenia. Term infants of hypertensive mothers were no more likely to be thrombocytopenic than were control infants. Only two infants, both preterm, had cord platelet counts below 50 x 10(9)/L. Although obstetric interventions are not indicated, the rate of thrombocytopenia in preterm infants born to hypertensive women justifies neonatal scrutiny.

Female↗