Thrombophilia and pregnancy complications

OBJECTIVE: This systematic review examines the strength of the association between thrombophilia and recurrent pregnancy loss and other serious obstetric complications.Study design Electronic databases and manual bibliography searches were used to identify studies evaluating the association between thrombophilia and pregnancy loss, preeclampsia, fetal growth retardation, and placental abruption. RESULTS: Thrombophilic disorders are associated with an increased risk of fetal loss in the majority of case control and cohort studies. The risk is increased throughout pregnancy, but may be higher in the second and third trimester. The common pathologic finding of placental infarction suggests unexplained fetal loss may result from uteroplacental insufficiency and thrombosis. Thrombophilic disorders are not consistently associated with preeclampsia, fetal growth retardation, or placental abruption. Preliminary data suggest prophylactic anticoagulation may improve outcome in thrombophilic women with unexplained recurrent fetal loss. CONCLUSION: Women with thrombophilia have an increased risk of pregnancy loss and possibly other serious obstetric complications, although definition of the magnitude of risk will require prospective longitudinal studies. Preliminary data suggesting prophylactic anticoagulation may improve gestational outcome provide a rationale for prospective randomized trials in thrombophilic women with unexplained recurrent fetal loss.     

Fetal interleukin-1 receptor antagonist gene polymorphism, intra-amniotic interleukin-1beta levels, and history of spontaneous abortion

OBJECTIVE: The purpose of this study was to determine whether fetal carriage of specific alleles of the polymorphic interleukin-1 receptor antagonist gene is associated with variations in intra-amniotic cytokine levels and previous pregnancy outcomes. STUDY DESIGN: Fetal cells in midtrimester amniotic fluid from 189 women were tested for interleukin-1 receptor antagonist intron 2 length polymorphisms. Concentrations of cytokines in amniotic fluid were tested by enzyme-linked immunosorbent assay. Pregnancy history data were obtained subsequently. RESULTS: Homozygosity for interleukin-1 receptor antagonist allele 1 was detected in 13 of 17 fetuses (76.5%) from women whose previous pregnancies all ended in spontaneous abortions, as compared with 33 of 74 fetuses (44.6%) from women with at least 1 previous term birth ( P = .02). Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with only 1 (5.9%) previous spontaneous abortion, as opposed to 31 pregnancies (41.9%) that were associated with a previous term delivery ( P = .004). A similar relationship between interleukin-1 receptor antagonist allele 1 and spontaneous abortions was observed when pregnancies of white women only were analyzed. Median mid trimester amniotic fluid interleukin-1beta concentrations were higher in women whose previous pregnancies ended in term deliveries (15.7 pg/mL), as opposed to women with 1 to 2 (6.4 pg/mL; P = .04) or > or =3 (4.1 pg/mL; P = .007) previous spontaneous abortions. Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with elevated intra-amniotic interleukin-1beta levels (16.2 pg/mL), as compared with interleukin-1 receptor antagonist allele 1 homozygotes (10.8 pg/mL; P = .03). CONCLUSION: Fetal carriage of interleukin-1 receptor antagonist allele 1 is associated with reduced intra-amniotic interleukin-1beta concentrations and an increased occurrence of spontaneous abortions in previous pregnancies.     

The use of prostaglandin E2 in pregnant patients with asthma

Objective

Prostaglandin E₂ is a pharmacologic agent that is used commonly in obstetrics; however, its usage in patients with asthma is unclear. The study objective was to examine pregnant patients with asthma who received prostaglandin E₂.

Study design

All pregnancies that were given prostaglandin E₂ suppositories and/or gel were recorded prospectively from January 1989 through December 2000. Those cases with a history of asthma or active asthma were analyzed for any clinical evidence of disease exacerbation after the administration of the agent. Clinical exacerbation was defined as any respiratory complaint that followed drug usage, the initiation of bronchodilator medications by patients currently not on therapy, or an increase in bronchodilator usage by patients with active disease.

Results

During the study period, 2513 patients received treatment with the cervical ripening gel, of whom 158 patients had a history of asthma or active asthma. Additionally, 536 patients were administered the 20-mg suppositories, of whom 31 patients had a history of asthma or active asthma. Thus, a total of 189 patients with a history of asthma or active asthma were exposed to prostaglandin E₂, and none of the patients had any evidence of a clinical exacerbation of the disease (0/189 cases; 95% CI, 0- 2%).

Conclusion

Based on the 95% CI of these data, the maximum risk for the development of a clinical exacerbation of asthma, if exposed to the obstetric forms of prostaglandin E₂, is ≤2%. Although all drug usage in patients with asthma should be monitored carefully, this information would support the usage of prostaglandin E₂, if obstetrically indicated, in pregnant patients with asthma.     

Pregnancy discovered after smallpox vaccination: Is vaccinia immune globulin appropriate?

Smallpox vaccination just before conception or during pregnancy can result, in rare instances, in fetal vaccinia from viral infection of the fetus. Approximately 50 cases have been documented, despite literally billions of people having been vaccinated. This live viral vaccine has a wider array of rare but serious medical side effects (eg, eczema vaccinatum, progressive vaccinia, encephalitis, myopericarditis) compared with other vaccines that are given currently to the public. In response to recent world events, the Centers for Disease Control and Prevention and the United States Department of Defense established a preoutbreak smallpox vaccination program. Because no actual outbreak has yet occurred, some investigators have proposed prophylactic treatment with vaccinia immune globulin for pregnancies that are exposed to smallpox vaccine to prevent fetal vaccinia. We review the existing medical literature to access the risks of fetal vaccinia in these pregnancies and the controversy regarding the prophylactic use of vaccinia immune globulin.     

L-Arginine erythrocyte transport in normal pregnant and preeclamptic women

OBJECTIVE: Uptake of L-arginine by the cell via amino acid transporter systems is the first step for nitric oxide (NO) production. The current study aimed to assess the total L-arginine uptake in erythrocytes of normal pregnant and preeclamptic women. STUDY DESIGN: Twenty-one normal pregnant and 21 preeclamptic women were studied. To measure total L-arginine uptake in erythrocytes, carbon 14 was used as a marker and Michaelis-Menten kinetic parameters (V(max) and K(m)) were evaluated. RESULTS: In preeclamptic women, there was a significant increase (P<.004) in the mean maximal capacity of transport in erythrocytes (V(max)=982.69 micromol/L cells/h+/-433.51) in comparison with normal pregnant women (V(max)=584.73 micromol/L cells/h+/-422.33). No significant difference was detected in the half-saturation constant (P=0.978). CONCLUSION: The transport kinetics of the NO precursor, L-arginine, is altered in erythrocytes of preeclamptic women. It is possible that abnormal L-arginine uptake may contribute to the pathophysiologic mechanisms of preeclampsia syndrome.     

Reproductive health history of lesbians: implications for care

OBJECTIVE: Parity and hormonal contraceptives modify the risk of reproductive cancers and cardiovascular disease. However, clinicians may not obtain reproductive histories from patients who self-identify as lesbian. We report lifetime pregnancy-related outcomes and hormonal contraception for 392 women who reported sexual activity with another woman in the preceding year. STUDY DESIGN: Among self-referred volunteers, previous pregnancy, pregnancy outcome, contraceptive use, and sexual identity were assessed with self-administered questionnaire. RESULTS: One in 4 subjects had been pregnant, and more than 50% of the women had used oral contraceptives (mean duration, 40 months). Sixteen percent of all subjects and 63% of those who had been pregnant previously reported having 1 or more induced abortions. The most common pregnancy outcome for women younger than 25 years was induced abortion (59% of pregnancies). Identifying as "lesbian" or "bisexual" predicted neither the duration of oral contraceptive use nor a report of induced abortion. CONCLUSION: Previous pregnancy, induced abortion, and hormonal contraceptive use are common among women who report sex with women, regardless of self-identification as lesbian.     

Obesity, obstetric complications and cesarean delivery rate--a population-based screening study

OBJECTIVE: This study was undertaken to determine whether obesity is associated with obstetric complications and cesarean delivery. METHODS: A large prospective multicenter database was studied. Subjects were divided into 3 groups: body mass index (BMI) less than 30 (control), 30 to 34.9 (obese), and 35 or greater (morbidly obese). Groups were compared by using univariate and multivariable logistic regression analyses. RESULTS: The study included 16,102 patients: 3,752 control, 1,473 obese, and 877 morbidly obese patients. Obesity and morbid obesity had a statistically significant association with gestational hypertension (odds ratios [ORs] 2.5 and 3.2), preeclampsia (ORs 1.6 and 3.3), gestational diabetes (ORs 2.6 and 4.0), and fetal birth weight greater than 4000 g (ORs 1.7 and 1.9) and greater than 4500 g (ORs 2.0 and 2.4). For nulliparous patients, the cesarean delivery rate was 20.7% for the control group, 33.8% for obese, and 47.4% for morbidly obese patients. CONCLUSION: Obesity is an independent risk factor for adverse obstetric outcome and is significantly associated with an increased cesarean delivery rate.     

Diagnostic mid trimester amniocentesis: how safe?

OBJECTIVE: Genetic mid-trimester amniocentesis is a common invasive procedure. The origin of the commonly quoted 0.5% rate of procedure-related pregnancy loss after amniocentesis is obscure and is in conflict with the only randomized prospective study that reported a procedure-related rate of loss of 1.0%. This review was performed to establish an estimate of procedure-related pregnancy loss after mid-trimester amniocentesis. The impact of placental puncture on the rate of loss and the risk of direct needle injury to the fetus were also examined. STUDY DESIGN: The National Library of Medicine database was used to identify English language reports of >1000 amniocenteses with sufficient detail and follow up data to allow the calculation of the rate of spontaneous pregnancy loss after amniocentesis but before 28 completed weeks. These reports were divided into 2 groups to assess the impact of the ultrasound technique. Group I described only preamniocentesis ultrasound evaluation; group II described primarily concurrent ultrasound needle guidance. Pregnancy loss between the 2 groups was compared. The impact of placental puncture and reported direct fetal trauma were examined. The significance of differences was tested using chi-square analysis, with significance at a probability value of < or =.05. RESULTS: Twenty-nine reports that totaled 68,119 amniocenteses were examined. In a comparison of all studies in group I with all studies in group II, there was a lower rate of loss after amniocenteses with the use of concurrent guidance (1.4%) compared with the use of preamniocentesis ultrasound evaluation (2.1%) that was significant ( P <.001). Among only the 5 controlled studies that used preamniocentesis ultrasound evaluation, the difference in rate of loss between amniocentesis patients and control subjects was 0.6% ( P =.0042; 95% CI, 0.19, 1.03), which was identical to the difference in the rate of loss of 0.6% between amniocentesis patients and control subjects from the 5 controlled studies that used concurrent ultrasound needle guidance ( P <.0001; 95% CI, 0.31, 0.90). Multiple case reports and small series of presumed fetal needle trauma were reviewed, but most of these attributed causation to the amniocentesis needle based only on circumstantial association. Two cases with direct evidence of fetal needle trauma are discussed. Finally, the rate of loss after placental puncture from among 9 reports that provided this detail was 1.4% and not different from the overall rate of loss that was noted in group II. CONCLUSION: This examination of experience with 68,119 amniocenteses from both controlled and uncontrolled studies provides a substantive basis for several conclusions: (1) Contemporary amniocentesis with concurrent ultrasound guidance in controlled studies appears to be associated with a procedure-related rate of excess pregnancy loss of 0.6% (95% CI, 0.31, 0.90). To determine the total rate of loss, this must be added to the reported natural rate of loss without amniocentesis among control patients of 1.08%. (2) The use of concurrent ultrasound guidance appears to reduce the number of punctures and the incidence of bloody fluid. Concurrent ultrasound guidance was associated with a reduced rate of loss when all studies were compared, but not among controlled studies. (3) Direct fetal needle trauma is rare, and rarely proved, but may occur more frequently than is reported because of a failure to diagnose and a failure of the consistent production of sequelae. (4) This experience does not substantiate an increased rate of pregnancy loss if placental puncture is required.     

Transplacental transmission of maternal B-cell lymphoma

We report a case of maternal malignant lymphoma transferred to the fetus during pregnancy. A 29-year-old woman developed lymphoma at 29 weeks' gestation, and her infant developed malignant lymphoma at 8 months. Immunohistochemical examinations revealed lymphoid cells of similar characteristics in the maternal, placental, and infant tissues.     

A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation

OBJECTIVE: The purpose of this study was to determine whether standard therapeutic doses of dalteparin maintain peak therapeutic levels of anticoagulation during pregnancy. STUDY DESIGN: This was a prospective trial in which 13 pregnancies that required therapeutic anticoagulation were treated with dalteparin 100 U/kg every 12 hours; peak and trough (predose) low molecular weight heparin (anti-Xa activity) levels were monitored every 2 weeks. Dosage adjustments were made to maintain peak anti-Xa activity between 0.5 and 1.0 IU/ml. Bone density and bone turnover markers were measured. RESULTS: A total of 250 peak and trough low-molecular-weight heparin (LMWH) levels were obtained. Eighty-five percent of pregnancies (11/13) required an upward dosage adjustment. Trough levels were in the therapeutic range only 9% of the time, despite the maintenance of therapeutic peak levels. Bone resorption markers and density were unchanged in singleton pregnancies. CONCLUSION: Dalteparin dosing, based on weight alone, every 12 hours is inadequate to maintain most pregnant women in the therapeutic range throughout pregnancy as measured by anti-Xa activity. Trough levels are rarely in the therapeutic range, despite maintenance of therapeutic peak levels. These notable changes in low molecular weight heparin peak may explain reported failures in pregnancy.