Interventions for treating cholestasis in pregnancy.

BACKGROUND: Cholestasis of pregnancy has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is unresolved, therapies have been empiric. OBJECTIVES: The objective of the review is to evaluate the effectiveness and safety of therapeutic interventions in women with a clinical diagnosis of cholestasis of pregnancy (CIP) SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE and PREMEDLINE, EMBASE, CINAHL and Current Contents. Date of last search: March 2001. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared an intervention to either a placebo or alternative treatment in women with a diagnosis of intrahepatic cholestasis of pregnancy. Trials published only as abstracts were excluded. DATA COLLECTION AND ANALYSIS: Reviewers assessed identified trials for 1) eligibility and 2) methodological quality. Attempts were made to contact authors for missing data. MAIN RESULTS: Nine RCTs involving 227 women were included but adequate data for appropriate comparisons in pruritus, bile acids or liver enzymes were not consistently reported. S-adenosylmethionine (SAMe) versus placebo (four trials, 82 women): only one trial showed significantly greater improvements in pruritus, bile salts and liver enzymes with SAMe. Ursodeoxycholic acid (UDCA) versus placebo (three trials, 56 women): in two trials a significant difference in pruritus relief was not detected. One trial observed greater reductions in bile salts and liver enzymes with UDCA. Preterm births were fewer with UDCA in one study while two studies reported no difference in fetal distress incidence. Guar gum versus placebo (one trial, 48 patients): no differences in pruritus, bile salts, or fetal/neonatal outcomes were observed. Activated charcoal versus no treatment (one trial, 20 patients): the reduction in bile salts was greater with charcoal, but no difference in pruritus relief: relative risk (RR) 9.0 95% confidence interval (CI) 0.6 - 148 or fetal/neonatal outcomes. UDCA versus SAMe (two trials, 36 patients): pruritus relief was better with UDCA in one study and with SAMe in the other. UDCA was better in reducing bile acids but not liver enzymes in one trial. UDCA + SAMe versus placebo, UDCA or SAMe (one study, eight patients/arm): UDCA + SAMe versus placebo or UDCA resulted in greater improvements in pruritus, bile salts and selected liver function assays; UDCA + SAMe versus SAMe resulted in greater improvements in bile salts and ALP only. No treatments were found to be unsafe. REVIEWER'S CONCLUSIONS: There is insufficient evidence to recommend guar gum, activated charcoal, SAMe and UDCA alone or in combination in treating women with CIP. Inconsistent and inadequate reporting of results precluded pooling the results of small studies.

Anticoagulation in pregnancy and the puerperium.

For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.

A randomised double-blind placebo controlled trial of low molecular weight heparin as prophylaxis in preventing venous thrombolic events after caesarean section: a pilot study.

OBJECTIVE: To pilot a protocol for a national multicentre randomised trial in which a low molecular weight heparin will be compared with placebo for prevention of venous thrombotic events occurring within six weeks after caesarean section. DESIGN: Double-blind randomised controlled trial. SETTING: Tertiary care centre. PARTICIPANTS: Seventy-six women having had a caesarean section, 37 in the control group and 39 in the Dalteparin group. METHODS: Consenting patients having had an emergency or elective caesarean section were commenced on study medication 6-24 hours post-operatively. The study medication, dalteparin 2,500 iu or saline, was given subcutaneously once daily for four or five days post-operatively depending on the patient's length of stay. Patients were reviewed in hospital for operative outcomes and contacted at two and six weeks post-operatively. RESULTS: Of the 141 women given information about the trial, 76 (54%) consented to participate. Follow up to six weeks was achieved in all women who were recruited. More women in the placebo arm had general anaesthesia, but otherwise the two groups had similar characteristics at randomisation. There was only one occurrence of a deep vein thrombosis during the study. This patient was in the treatment arm and the thrombosis occurred between two and six weeks post-operatively. All other outcomes were similar in the two groups. CONCLUSION: Our experience of a 26% recruitment rate, the thrombosis rate of 1.3% (95% CI 0.03-7.1%) and the contactability of all participants two and six weeks post-operatively, indicates that this study is feasible.

Platelet count may predict abnormal bleeding time among pregnant women with hypertension and preeclampsia.

BACKGROUND: Anesthesiologists often require laboratory data to estimate the bleeding risk among hypertensive pregnant women prior to administering regional anesthesia. Many rely on the bleeding time (BT) in making this determination. We examined whether the platelet count can adequately predict BT among a group of hypertensive parturients. METHODS: This retrospective subgroup analysis, taken from a cohort of 2,051 hypertensive pregnant women, comprises 87 individuals who underwent both a BT and platelet count prior to delivery. We calculated the correlation between the platelet count and BT at three platelet cut-off points with respect to prolonged BT of eight minutes or more. RESULTS: There was a significant negative correlation between platelet count at delivery and BT [r= -0.45, 95% confidence interval (CI) -0.26 to -0.60; P <0.0001]. All three platelet cut-off points had a sensitivity of less than 66% with negative predictive values below 75% for an abnormal BT. A platelet count > or =75 x 109/L [corrected] was specific for the presence of an abnormal BT (specificity 97.8%, 95% CI 91.7-100.0), with a positive predictive value of 95.5% (95% CI 83.1-100.0) and a positive likelihood ratio of 24 (95% CI 3.3-168). CONCLUSIONS: In a group of hypertensive parturients, the platelet count appears to be very specific for predicting a prolonged BT The platelet count may aid the anesthesiologist in determining the risk of bleeding from regional anesthesia. Given the study's potential for bias future research is needed to validate these findings.

MOS HIP: McMaster outcome study of hypertension in pregnancy.

BACKGROUND: The offspring of women with hypertension during pregnancy are at increased risk of low birthweight, preterm birth, diseases of prematurity and death. The risk of developing these outcomes among women with either preeclampsia or chronic hypertension, relative to those with gestational hypertension, is not known. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: A total of 1948 singleton women seen at a large tertiary care obstetrical center, whose blood pressure was greater than 140/90 mm Hg during pregnancy. The four types of hypertension were strictly defined: 864 women (44.4%) had gestational hypertension, 459 (23.6%) isolated chronic hypertension, 501 (25.7%) isolated preeclampsia, and 124 (6.4%) chronic hypertension with superimposed preeclampsia. OUTCOME MEASURES: The primary outcome of the study was a composite of the diseases of prematurity, need for assisted ventilation for greater than 1 day, or perinatal death. The secondary outcomes were each of those included in the primary endpoint, as well as admission to the neonatal ICU, small for gestational age (SGA) birthweight and preterm birth. We controlled for the effects of other maternal risk factors, such as age, parity, history of preterm delivery, cigarette smoking, pre-pregnancy weight, diabetes mellitus (DM), renal dysfunction, and current use of an antihypertensive agent or prednisone. RESULTS: For the primary composite outcome, compared to the offspring of women with gestational hypertension, the adjusted odds ratio was 1.9 (95% confidence interval 1.2 to 3.0) in the preeclamptic group and 2.0 (95% confidence interval 1.0 to 4.0) for those with chronic hypertension plus superimposed preeclampsia. Those with preeclampsia were at increased risk for small for gestational age birthweight (odds ratio 2.2, 95% confidence interval 1.5 to 3.1), as were the offspring of mothers who had chronic hypertension with superimposed preeclampsia (odds ratio 2.1, 95% confidence interval 1.2 to 3.8). Similarly, the rate of preterm birth before 32 weeks was highest among the infants of both preeclamptic mothers (28.5%; odds ratio 4.7, 95% confidence interval 2.9 to 7.6) and those with chronic hypertension and preeclampsia (30.5%; odds ratio 3.5, 95% confidence interval 1.8 to 6.7). The perinatal mortality rate was highest in the group of women with chronic hypertension plus preeclampsia (9.2%; odds ratio 3.2, 95% confidence interval 1.2 to 9.1). Other significant risk factors for the primary composite outcome included previous preterm delivery (odds ratio 2.7, 95% confidence interval 1.4 to 5.2), smoking (odds ratio 1.8, 95% confidence interval 1.1 to 3.0) and use of an antihypertensive agent during pregnancy (odds ratio 1.8, 95% confidence interval 1.2 to 2.7). Prednisone use was strongly associated with risk for perinatal death (odds ratio 4.9, 95% confidence interval 1.4 to 17.1). CONCLUSIONS: Relative to women with isolated gestational hypertension, those who develop preeclampsia, either with or without underlying chronic hypertension, experience worse perinatal outcomes. A history of previous preterm delivery and maternal smoking increase the rate preterm birth and major perinatal disease. Antihypertensive and prednisone therapy may be important risk factors for adverse perinatal events, but further research is needed to confirm these findings.

Platelet disorders in pregnancy.

Before the advent of automated cell counters, thrombocytopenia was looked for and identified after a clinical question. With automation, thrombocytopenia in pregnancy was commonly found, and with its commonality its clinical meaning went out of focus. For the majority of women, thrombocytopenia is benign and, as a marker of fetal thrombocytopenia, the value of maternal thrombocytopenia is almost non-existent.

Feto-maternal alloimmune thrombocytopenia: a literature review and statistical analysis.

Exploring prognostic factors that determine outcomes in fetomaternal alloimmune thrombocytopenia (FMAIT), a search of Medline was performed covering the years 1966 to April 1998. 376 articles were collected and reviewed; 140 articles contained the case histories of 297 mothers and 433 pregnancies that fulfilled entry criteria. More than 30 data variables were sought from these cases. The data were analysed using SPSS and Arcus Quickstat Biomedical. Nineteen different antigen incompatibilities were documented, the majority being human platelet antigen (HPA)-1a (77.3%), HPA-3a (3.5%) and HPA-5b (3.5%). The relative risk reduction (RRR) in mortality with any intervention was 57% (0.19-0.77) p = 0.009. Treatment of HPA-1a (PlA1) pregnancies with intravenous immunoglobulin (IVIG) increased the likelihood of a neurologically normal outcome, relative risk (RR) 1.68, confidence interval (1.3-2.2) p = 0.0003. Treatment of HPA-1a (PlA1) pregnancies with only antenatal complementary platelet transfusions increased the likelihood of a neurologically normal outcome, RR 1.63 (1.1-2.1) p = 0.01. Despite reviews of more than 400 cases of FMAIT, few prognostic variables are identifiable. Although IVIG appears to reduce the risk of intracranial haemorrhage (ICH), the dosage and timing of IVIG treatment was varied. This study highlights the need for standardised and directed research.

Bleeding risk and reproductive capacity among patients with factor XIII deficiency: a case presentation and review of the literature.

Factor XIII deficiency is an uncommon, inherited bleeding disorder that usually manifests in infancy or early childhood, involving both boys and girls. We present the case of a woman who had experienced two previous intracranial bleeding events, and was treated before and during her current pregnancy with factor XIII concentrate. Her pregnancy was successful, and she experienced an uncomplicated vaginal delivery. To better understand the issues surrounding bleeding, reproductive capacity, and management of factor XIII deficiency during pregnancy, we conducted a systematic literature review using MEDLINE from 1966 to December 1998. We also examined the bibliographic references from all articles, and included all cases, case reports, or case series of patients with factor XIII deficiency. We retrieved data on 117 patients from 37 articles, the majority of which had type II deficiency. Among untreated patients with type II factor XIII deficiency, the literature suggests an elevated mortality rate due to uncontrolled bleeding and intracranial hemorrhage. Because of its high degree of efficacy, the evidence supports the use of life long prophylactic therapy with at least monthly infusions of factor XIII concentrate, including during pregnancy. The opinion that women with type II factor XIII deficiency have inevitable recurrent abortions, or that men are sterile, is not well substantiated. No data were found on whether treatment alters male reproductive capacity. A policy of universal factor XIII replacement, starting in childhood, will likely enable more patients to attain reproductive status. The development of an international data registry would optimally address both bleeding risk and reproductive capacity among patients with factor XIII deficiency.

Assessing the teratogenic potential of angiotensin-converting enzyme inhibitors in pregnancy.

To assess the teratogenic potential of angiotensin-converting enzyme (ACE) inhibitors, we report on 20 prospective pregnancies and 85 identified from articles in the literature. The anomaly rate was 20.6% in small series <10 entrants (95% CI 8.7-37.9%) and 1.4% in larger series > or =10 entrants (95% CI 0.03-7.3%) p=0.0016. The most consistent anomaly seen, skull hypoplasia, along with renal dysfunction appear to be more related to prolonged or late pregnancy exposure than to first trimester exposure. There is little supportive evidence that ACE inhibitors (captopril or enalapril) are teratogenic. There seems to be no absolute reason to discontinue these 2 medications prior to pregnancy, nor to create anxiety when a patient is identified with the combination of early pregnancy and treatment with these medications. There appears to be reason to discontinue the medication in pregnancy but the adverse event rate cannot be assessed because of inadequate prospective information.

Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy.

OBJECTIVE: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. OPTIONS: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. OUTCOMES: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. EVIDENCE: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. VALUES: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. BENEFITS, HARMS AND COSTS: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. RECOMMENDATION: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. VALIDATION: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.

Report of the Canadian Hypertension Society Consensus Conference: 1. Definitions, evaluation and classification of hypertensive disorders in pregnancy.

OBJECTIVES: To provide Canadian physicians with a standard definition of hypertension in pregnancy, recommendations for laboratory investigations and tests for the assessment and management of hypertensive disorders in pregnancy, and a classification of such disorders. OPTIONS: To improve or not improve Canadian uniformity and standardization in the investigation and classification of hypertensive disorders in pregnancy. OUTCOMES: 1) Accuracy, reliability and practicality of diagnostic clinical criteria for hypertensive disorders in pregnancy. 2) Laboratory tests useful to determine severity and prognosis of disorders as measured by maternal and neonatal adverse outcomes. 3) A classification of disorders for use by Canadian physicians to facilitate uniformity and diffusion of research through a common language. EVIDENCE: Articles on hypertensive disorders in pregnancy published from 1966 to 1996, retrieved through MEDLINE search, related to definitions, tests, diagnostic criteria and classification, as well as documents on diagnosis and classification from authorities in the United States, Europe and Australia and from special interest groups. VALUES: High priority was given to the principle of preventing adverse maternal and neonatal outcomes through the provision of diagnostic criteria for severity and prognosis and through dissemination of reliable and pertinent information and research results using a common language. BENEFITS, HARMS AND COST: Higher degree of vigilance in diagnosing hypertensive disorders in pregnancy, allowing for earlier assessment and intervention, and more efficient dissemination of comparative information through common language. No harm or added cost is perceived at this time. RECOMMENDATIONS: (1) A diastolic blood pressure of 90 mm Hg or more should be the criterion for a diagnosis of hypertension in pregnancy and should trigger investigation and management. Except for very high diastolic readings (110 mm Hg or more), all diastolic readings of 90 mm Hg or more should be confirmed after 4 hours. (2) A regularly calibrated mercury sphygmomanometer, with an appropriate-sized cuff, is the instrument of choice. A rest period of 10 minutes should be allowed before taking the blood pressure. The woman should be sitting upright and the cuff positioned at the level of the heart. (3) Both Korotkoff phase IV and V sounds should be recorded, but the phase IV sound should be used for initiating clinical investigation and management. (4) A urine protein level of more than 0.3 g/d should be the criterion for a diagnosis of proteinuria; 24-hour urine collection should be the standard method for determining proteinuria. (5) Edema and weight gain should not be used as diagnostic criteria. (6) Hypertensive disorders diagnosed during pregnancy should be classified as pre-existing hypertension; gestational hypertension with or without proteinuria; pre-existing hypertension with superimposed gestational hypertension with proteinuria; and unclassifiable antenatally but final classification 42 days after delivery. VALIDATION: Except for expert opinions and reviews solicited for this project, these recommendations need to be field tested and validated in Canada. Guidelines endorsed by the Canadian Hypertension Society and the Society of Obstetricians and Gynaecologists of Canada.

A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy.

BACKGROUND: There are many health benefits associated with the use or oral contraceptives (OCs) and hormone replacement therapy (HRT), but these agents are also associated with potential health risks. OBJECTIVE: To reevaluate the current practice of withholding OCs or HRT in women with previous venous thromboembolism (VTE) by critically reviewing the evidence that the use of OCs or HRT is associated with an increased risk for VTE. METHODS: A MEDLINE literature search was performed to identify studies investigating associations between OCs and VTE or HRT and VTE. Each study was rated according to methodologic quality (level 1, low potential for bias; level 2, moderate potential for bias; level 3, high potential for bias). Results were combined across studies of similar design to determine pooled risk ratios for VTE. The results from studies investigating third-generation OCs were reported separately. RESULTS: For OC studies (n = 22), the pooled risk ratios (95% confidence intervals) in case-control studies, retrospective cohort studies, prospective cohort studies, and randomized controlled trials were 3.0 (2.6-3.4), 4.8 (2.5-7.7), 2.4 (1.6-3.5), and 1.1 (0.4-2.9), respectively. In users of third-generation OCs, the pooled risk ratio (95% confidence interval) for VTE was 5.0 (2.5-7.5). No study was rated as level 1, 6 were rated as level 2, and 16 as level 3. Methodologic limitations in these studies would tend to exaggerate the risk for VTE with OC use. For HRT studies (n = 9), the pooled risk ratios (95% confidence intervals) in case-control studies, prospective cohort studies and randomized controlled trials were 2.4 (1.7-3.5), 1.7 (1.0-2.9), and 0.7 (0.3-1.6), respectively. No study was rated as level 1, 6 were rated as level 2, and 3 as level 3. CONCLUSIONS: First, an association between OC use and VTE is likely valid, but the reported risks are probably exaggerated. We estimate that users of non-third-generation OCs have a less than 3-fold increase in the risk for VTE compared with nonusers; the risk for VTE is possibly higher with the use of third-generation OCs. Second, an association between HRT use and VTE might exist; however, further investigation is required before definitive conclusions can be made.

Pregnancy in chronic progressive external ophthalmoplegia: a case report.

The mitochondrial diseases are uncommon multisystem disorders characterized by the presence of functionally and/or structurally abnormal mitochondria. As there have been few reports of the obstetrical care of affected patients, we wish to document two pregnancies in a woman with a Chronic Progressive External Ophthalmoplegia (Kearns-Sayre-like syndrome). Both pregnancies were complicated by preterm labor and hypertension.

Thrombocytopenia in pregnancy: diagnosis, pathogenesis and management.

Maternal thrombocytopenia is a common find during pregnancy. The rapid determination of its cause can often be difficult, with the diagnosis only being made in retrospect once the course of the platelet count is known. The majority of patients with thrombocytopenia in pregnancy will have incidental thrombocytopenia of pregnancy which is of no clinical significance.

The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study.

We performed a prospective matched cohort study to investigate the effects of long-term (> 1 month) heparin therapy on lumbar spine bone density. Twenty-five women who received heparin during pregnancy, and 25 matched controls underwent dual photon absorptiometry of the lumbar spine in the post-partum period. Zero of 25 heparin-treated patients developed fractures. Heparin-treated patients had a 0.082 g/cm2 lower bone density compared to untreated controls, which is clinically and statistically significant (p = 0.0077). There were 6 matched pairs in which only the heparin-treated patient had a bone density below 1.0 g/cm2, compared to only one pair in which only the control patient had a bone density below this level (p = 0.089). The correlation coefficients of the difference in bone density in each matched pair, and the duration of heparin therapy, the mean daily dose, and the total dose of heparin were 0.042, - 0.015, and 0.021, respectively; none of these values is statistically significant. We conclude: 1) long-term heparin therapy was associated with a significant reduction in bone density, although fractures are uncommon, 2) there was no significant correlation between lumbar bone density and the dose or duration of heparin.

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.

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.

The feasibility of a control population for a randomized control trial of seizure prophylaxis in the hypertensive disorders of pregnancy.

OBJECTIVE: To document the feasibility of a control population for a randomized controlled trial, we report our experience in managing hypertensive pregnancies without seizure prophylaxis. STUDY DESIGN: An 8-year cross-sectional study in one institution was performed of all hypertensive patients. RESULTS: Of 467 patients with preeclampsia or superimposed preeclampsia managed without seizure prophylaxis, 18 had seizure activity, 3.9% (95% confidence interval 2.3% to 6.0%). There was no seizure-related maternal mortality or major morbidity, and the perinatal mortality rate after 28 gestational weeks was the same in patients with or without seizures. By logistic regression seizures were 17.4 times more likely in preeclampsia and 8.1 times more likely in chronic hypertension with superimposed preeclampsia, compared with gestational or chronic hypertension alone. CONCLUSION: The rate of seizures in patients with preeclampsia or superimposed preeclampsia managed without seizure prophylaxis was low and unassociated with an increase in maternal or perinatal mortality. A control arm is feasible in a randomized, controlled trial to address the issue of whether antiseizure medication can prevent eclampsia.