Leo R. Brancazio

Acute Myocardial Infarction in Pregnancy. A United States Population-Based Study

Background— The purpose of this study was to determine the incidence, mortality, and risk factors for pregnancy-related acute myocardial infarction in the United States. Methods and Results— The Nationwide Inpatient Sample for the years 2000 to 2002 was queried for all pregnancy-related discharges. A total of 859 discharges included a diagnosis of acute myocardial infarction, for a rate of 6.2 (95% confidence interval [CI] 3.0 to 9.4) per 100 000 deliveries. Among these, there were 44 deaths, for a case fatality rate of 5.1%. The odds of acute myocardial infarction were 30-fold higher for women aged 40 years and older than for women <20 years of age. Single independent variables that were statistically and clinically significant, including age, race, and certain medical conditions and obstetric complications, were entered into a multivariable logistic regression model. Hypertension (odds ratio [OR] 21.7, 95% CI 6.8 to 69.1), thrombophilia (OR 25.6, 95% CI 9.2 to 71.2), diabetes mellitus (OR 3.6, 95% CI 1.5 to 8.3), smoking (OR 8.4, 95% CI 5.4 to 12.9), transfusion (OR 5.1, 95% CI 2.0 to 12.7), postpartum infection (OR 3.2, 95% CI 1.2 to 10.1), and age 30 years and older remained as significant risk factors for pregnancy-related acute myocardial infarction. Black race was eliminated as a risk factor in the multivariable analysis, which suggests that the increased incidence among black women is explained by an increased prevalence of other cardiovascular risk factors. Conclusions— Although acute myocardial infarction is a rare event in women of reproductive age, pregnancy increases the risk 3- to 4-fold. Certain medical conditions and complications of pregnancy increase the risk further and are potentially modifiable risk factors.

Aspirin and reproductive outcomes.

In the late 1980s and early 1990s, researchers hypothesized that aspirin could be used to prevent or delay the onset of preeclampsia. This hypothesis was tested in numerous trials which showed limited, but positive results. Subsequently, aspirin has been used in an attempt to improve pregnancy outcomes in women who have both antiphospholipid antibodies and a history of recurrent loss, and has also been used in an attempt to improve the success of in vitro fertilization. In theory, aspirin has both positive and negative effects on reproduction. Aspirin, which suppresses cyclooxygenase, has the potential to interfere with implantation, but also has the potential to support the maintenance of pregnancy. Aspirin is prescribed with increasing frequency to reduce the risk of maternal thrombosis and reduce the risk of miscarriage and poor pregnancy outcome. Aspirin alone, however, is not considered sufficient to prevent thrombosis and even in women with the antiphospholipid syndrome, the question as to whether low-dose aspirin improves pregnancy outcomes has not been answered affirmatively. Aspirin has potential risks. Aspirin inhibits platelet function and can contribute to maternal and fetal bleeding. Aspirin crosses the placenta. Although aspirin has not been associated with other congenital anomalies, it has been associated with an increased risk of vascular disruptions, particularly gastroschisis and possibly premature closure of the ductus arteriosus. Nonetheless, large trials demonstrate low-dose aspirin’s relative safety and generally positive effects on reproductive outcomes. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall the varied reaction to low- and high-dose aspirin (ASA), and explain its biochemical roles in prostaglandin production and actions, its role in prevention and treatment of poor pregnancy outcomes, and the potential of congenital malformations and other adverse outcomes.

Low-molecular-weight heparin for thromboprophylaxis in pregnant women with mechanical heart valves.

Background. Pregnancy in a woman with a mechanical heart valve is a life-threatening situation. Due to the inability of unfractionated heparin to prevent valvular thromboses, warfarin or other vitamin K antagonists have been the preferred anticoagulants for the mother. They are, however, potentially harmful to the fetus. With the advent of low-molecular-weight heparins, clinicians were hopeful for an alternative that was safe for the fetus, but more effective than unfractionated heparin, which carries a 29–33% risk of life-threatening thromboses and a 7–15% chance of mortality. Unfortunately, fatal thromboses have occurred with low-molecular-weight heparin as well. Methods. We searched the MEDLINE database and other sources to identify cases of the use of low-molecular-weight heparin for thromboprophylaxis in women with mechanical heart valves. Results. We found 73 cases and added three of our own for a total of 76. There were 17 thrombotic events (22%). Thirteen were valve thromboses, two were strokes, and two were myocardial infarctions. There were three deaths (4%). Conclusions. While pregnant women with mechanical heart valves who receive low-molecular-weight heparin for thromboprophylaxis are at extremely high risk of life-threatening thromboses, there is no evidence that low-molecular-weight heparin is inferior to unfractionated heparin.

Anticoagulants in pregnancy.

Pregnancy is a hypercoagulable state that increases the risk of thromboembolic events. These risks may be further increased in the presence of an acquired or inherited thrombophilia. Thrombophilias have been associated with both maternal and fetal complications. The use of anticoagulants during pregnancy may reduce the risk of maternal thromboses as well as the risk of adverse pregnancy outcomes. The choice of an anticoagulant requires consideration of maternal risks, potential for teratogenicity, the underlying condition necessitating the treatment, and cost. This review examines the options for anticoagulation, the clinical situations that may warrant such treatment, and factors to be considered at delivery and during the postpartum period. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to describe the roles of acquired and inherited thrombophilia in furthering the hypercoagulable state of pregnancy, identify the potential consequences of using anticoagulants during pregnancy, and summarize the treatment options when anticoagulation is required during pregnancy.

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.

to the editor: After reading the article by Meis et al. (June 12 issue), 1 we strongly discourage practitioners from using 17 alpha-hydroxyprogesterone caproate in the care of women who have had preterm deliveries, until more investigation is done. Although initially enthusiastic about the results, which showed a risk reduction among the women who received 17 alpha-hydroxyprogesterone caproate, we were concerned about the high rate of recurrent preterm delivery among the women who received placebo. The Methods section states that the placebo was castor oil. Ricinoleic acid, the active ingredient in castor oil, is a known uterine stimulant. 2,3 Castor oil is used to induce labor. 4 We speculate that the high rate of preterm delivery in the placebo group was due to the injections of castor oil. If the study medication was given in castor oil (the authors do not say whether it was), then any beneficial effect may have been negated by the vehicle. If not, then the rate of preterm delivery among those receiving 17 alpha-hydroxyprogesterone caproate was no better than that in the historical controls. 5

Ultrasound assessment of the fetal middle cerebral artery peak systolic velocity: a comparison of the near-field versus far-field vessel

OBJECTIVE Doppler assessment of the fetal middle cerebral artery peak systolic velocity may obviate the need for more invasive procedures in the alloimmunized patient. The purpose of this study was to compare middle cerebral artery peak systolic velocity measurements in the near field and far field. STUDY DESIGN Patients between 16 and 42 weeks of gestation with normal fetuses were eligible (n=151). Peak systolic velocity measurements were obtained at the proximal portion of each middle cerebral artery at its origin in the internal carotid artery, as well as the most distal portion before its division, for a total of 4 measurements per fetus. Comparisons were made among the 4 locations and the data were analyzed using a mixed-model analysis of variance adjusted for gestational age. Results were presented using both P values and 95% CIs. P values <.05 were considered statistically significant. Where appropriate, P values and 95% CIs were adjusted using the Tukey multiple comparison procedure. A subanalysis was performed using 11 patients to assess interobserver reliability, which was calculated using the intraclass correlation coefficient (ICC). RESULTS All four measurements were obtained for 120 fetuses (79%). The mean gestational age was 27.0 weeks. Statistically significant differences were noted between distal sites (95% CI, -0.05 to 0.01; P<.01) as well as the two sites on each vessel (95% CI, 0.03-0.07 and 0.07-0.12; P<.001 for both vessels). There was no significant difference between the two proximal locations (95% CI, -0.01 to 0.03; P=0.77). CONCLUSION By which of the 2 vessels the fetal middle cerebral artery peak systolic velocity is affected is selected, as well as the location on the vessel. If the near-field proximal site cannot be interrogated, the far-field proximal site may be the best alternative.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation

INTRODUCTION The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. METHODS Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. RESULTS Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. CONCLUSIONS Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications.

Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics.

Objective: To determine if maternal serum interleukin-6 (IL-6) levels remain predictive of funisitis after completion of antibiotic administration in preterm premature rupture of membranes (PPROM). Methods: A secondary analysis of a prospective cohort study. Daily blood samples obtained from PPROM subjects were analyzed for IL-6 by enzyme-linked immunosorbent assay. Subjects (N = 39) delivered >7days post admission and were divided into those with and without funisitis. Data were analyzed using Mann–Whitney U test. Results: Maternal serum IL-6 levels obtained 24–48 hours and 48–72 hours before delivery are elevated in PPROM subjects with funisitis compared to those without funisitis (6.3 vs. 2.7 pg/ml, P < 0.03; 6.1 vs. 1.7 pg/ml, P < 0.02). Receiver operator characteristic curve revealed an IL-6 level of 1.98 pg/ml had sensitivity of 86.7%, specificity of 46.7%, positive predictive value of 61.9% and negative predictive value of 77.8%. Conclusion: This data suggests that maternal serum IL-6 levels continue to be predictive of PPROM subjects destined to develop funisitis after completion of antibiotics.

Closed-Incision Negative-Pressure Therapy in Obese Patients Undergoing Cesarean Delivery: A Randomized Controlled Trial

Background  Postcesarean wound morbidity is a costly complication of cesarean delivery for which preventative strategies remain understudied. Objective  We compared surgical site occurrences (SSOs) in cesarean patients receiving closed-incision negative-pressure therapy (ciNPT) or standard-of-care (SOC) dressing. Study Design  A single-center randomized controlled trial compared ciNPT (5–7 days) to SOC dressing (1–2 days) in obese women (body mass index [BMI] ≥ 35), undergoing cesarean delivery between 2012 and 2014. Participants were randomized 1:1 and monitored 42 ± 10 days postoperatively. The primary outcome SSOs included unanticipated local inflammation, wound infection, seroma, hematoma, dehiscence, and need for surgical or antibiotic intervention. Results  Of the 92 randomized patients, 82 completed the study. ciNPT and SOC groups had similar baseline characteristics. Mean BMI was 46.5 ± 6.5 and no treatment-related serious adverse events. Compared with SOC, the ciNPT group had fewer SSOs (7/43 [16.3%] vs. 2/39 [5.1%], respectively; p  = 0.16); significantly fewer participants with less incisional pain both at rest (39/46 [84.8%] vs. 20/46 [43.5%]; p  < 0.001) and with incisional pressure (42/46 [91.3%] vs. 25/46 [54.3%]; p  < 0.001); and a 30% decrease in total opioid use (79.1 vs. 55.9 mg morphine equivalents, p  = 0.036). Conclusion  A trend in SSO reduction and a statistically significant reduction in postoperative pain and narcotic use was observed in women using ciNPT.

Cesarean delivery among women with prolonged labor induction.

Abstract Objective: The objective of this study was to determine characteristics associated with cesarean delivery among women with labor induction lasting over 24 h. Study design: Women with live singleton pregnancies without prior cesarean delivery undergoing a labor induction lasting >24 h between September 2006 and March 2009 at Duke University Hospital were identified. Collected variables were compared between subjects by mode of delivery. A multivariate logistic regression model for the outcome cesarean delivery was constructed separately for nulliparous and parous women. Results: There were 303 women who met inclusion criteria. The overall cesarean delivery rate was 57% (n=172) and remained constant with time (P=0.15, test-for-trend). Nulliparous women having a cesarean delivery were more likely to be obese [adjusted OR (aOR) 2.00; 95% CI 1.05, 3.80] and have a larger fetus [aOR 1.11 (aOR for every 100 g increase in birthweight), 95% CI 1.03, 1.20] compared to those having a vaginal delivery. Conclusion: Increasing BMI and birthweight were independent predictors of cesarean delivery among nulliparous women with prolonged labor induction. Despite this, after 24 h of labor induction, the overall mean cesarean delivery rate remained constant at 57%, and did not change with time. Among women having a vaginal delivery following a prolonged labor induction, we saw high rates of shoulder dystocia, operative vaginal delivery and severe perineal laceration.