Independent risk factors for chronic illicit substance use during pregnancy.

OBJECTIVE: We aimed to determine the incidence of chronic illicit substance use during pregnancy and to identify associated risk factors. DESIGN: A 2-year time-matched retrospective maternal quality control database (n = 4,470) analysis of parturients with chronic illicit substance use compared to controls. SETTING: A tertiary academic medical center located in a rural setting. RESULTS: The rate of chronic illicit substance use was 1.95 percent. Demographic factors associated with chronic illicit substance use in pregnancy-included lower body mass index (BMI; OR: 0.93; 95 percent CI: 0.89-0.96, p < 0.0001), higher gravidity (OR: 1.24; 95 percent CI: 1.13-1.36, p < 0.0001), higher parity (OR: 1.38; 95 percent CI: 1.22-1.57, p < 0.0001), and more live births (OR: 1.30; 95 percent CI: 1.16-1.46, p < 0.0001). A history of smoking (OR: 10.51; 95 percent CI: 5.69-19.42, p < 0.0001), alcohol use (OR: 48.98; 95 percent CI: 17.33-138.40, p < 0.0001), anxiety (OR: 1.88; 95 percent CI: 1.16-3.05, p = 0.01), depression (OR: 2.44; 95 percent CI: 1.55-3.85, p = 0.0001), transfer on admission (OR: 2.12; 95 percent CI: 1.16-3.87, p = 0.01), payor insurance (OR: 2.12, 95 percent CI: 2.10-5.04, p < 0.0001), and Apgar scores < 7 at 1 minute (OR: 0.50; 95 percent CI: 0.25-1.00, p = 0.049) were significant. Multiple variable logistic regression-revealed BMI, smoking, alcohol use, and Apgar score <7 at 1 minute as significant factors. CONCLUSIONS: Awareness of these factors can assist in identifying and treating parturients with chronic illicit substance use.

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.

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.

Increase in Cesarean Operative Time Following Institution of the 80-Hour Workweek.

BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education limited resident duty hours to 80 hours per week. More than a decade later, the effect of the limits on resident clinical competence is not fully understood. OBJECTIVE: We sought to assess the effect of duty hour restrictions on resident performance of an uncomplicated cesarean delivery. METHODS: We reviewed unlabored primary cesarean deliveries at Duke University Hospital after 34 weeks gestation, between 2003 and 2011. Descriptive statistics and linear regression were used to compare total operative time with incision to delivery time as a function of years since institution of the 80-hour workweek. Resident training level, subject body mass index, estimated blood loss, and skin closure method were controlled for in the regression model. RESULTS: We identified 444 deliveries that met study criteria. The mean (SD) total operative time in 2003-2004 was 43.3 (14.3) minutes and 59.6 (10.7) minutes in 2010-2011 (P < .001). Multivariable regression demonstrated an increase in total operative time of 1.9 min/y (P < .001) but no change in incision to delivery time (P = .05). The magnitude of increased operative time was seen among junior residents (2.0 min/y, P < .001) compared to that of senior residents (1.2 min/y, P = .06). CONCLUSIONS: Since introduction of the 2003 duty hour limits, there has been an increase of nearly 20 minutes in the time required for a routine cesarean delivery. It is unclear if the findings are due to a change in residency duty hours or to another aspect of residency training.

The effects of intermittent pneumatic compression during cesarean delivery on fibrinolysis.

OBJECTIVE: Pregnancy is associated with increased risk for thromboembolic events. Intermittent pneumatic compression (IPC) devices are the method of thromboprophylaxis in a nonpregnant population. The aim of this study was to examine the effects of IPC on markers of fibrinolysis during cesarean delivery. STUDY DESIGN: We conducted a randomized controlled trial from April 2009 to March 2010 of women undergoing scheduled elective cesarean delivery. Forty-nine women were randomized to IPCs or usual care. All participants had three blood samples obtained: (1) baseline, (2) 1 hour after randomization, and (3) 30 minutes after cesarean delivery. Tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1), and plasminogen activator inhibitor-2 (PAI-2) levels were analyzed in each sample using an enzyme-linked immunosorbent assay. Statistical analysis was performed using repeated measures two-way analysis of variance with α = 0.05. RESULTS: There was a time-dependent change in tPA, uPA, and PAI-1 levels following delivery but no difference in TAT and PAI-2 levels with time. There were no differences between women randomized to IPCs or usual care. CONCLUSION: Markers of fibrinolysis were not significantly altered by IPCs in this study of low-risk pregnant women. Further research regarding the mechanism and efficacy of IPCs in pregnant women is warranted.

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 autoantibody levels in congenital heart block and potential prophylaxis with antiinflammatory agents.

OBJECTIVE: The importance of maternal autoantibody levels in congenital heart block and elucidation of maternal factors that may reduce disease burden require further clarification. STUDY DESIGN: Pregnancies complicated by maternal anti-Ro antibodies from 2007 through 2011 were retrospectively reviewed. RESULTS: In all, 33 women were followed up throughout pregnancy. Semiquantitative maternal anti-La levels were significantly higher in pregnancies complicated by fetal heart block of any degree (median difference, 227.5; P = .04), but there was no difference in maternal anti-Ro levels. In all, 94% of fetuses maintained normal conduction when the mother was treated with hydroxychloroquine or daily prednisone therapy throughout pregnancy, compared to 59% in the untreated group (odds ratio, 0.1; P = .04). CONCLUSION: Pregnancies complicated by fetal heart block did not have higher levels of maternal anti-Ro antibodies. Maternal anti-La level may be a useful predictor of fetal heart block. Maternal treatment with either hydroxychloroquine or daily low-dose prednisone throughout pregnancy may provide a protective effect.

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 >7 days 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.

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.

Thromboembolism in pregnancy: recurrence and its prevention.

Fifteen to 25% of thromboembolic events in pregnancy are recurrent events. Women with a history of thrombosis have a three- to fourfold increased risk of recurrence when they are pregnant compared with when they are not. The risks are even higher postpartum. The rate of recurrent venous thromboembolic events without anticoagulation is 2.4% to 12.2%, whereas the rate with anticoagulation is 0% to 2.4%. Because the rates of recurrent thromboembolism can be reduced with anticoagulation, women with a history of thrombosis who are not on lifelong anticoagulation will likely require anticoagulation during pregnancy, or at least during the postpartum period. Women who are already on lifelong warfarin for the prevention of recurrent venous thromboembolism should be counseled about the teratogenic effects of warfarin and offered the opportunity to be converted to heparin before conception. During pregnancy, low-molecular-weight heparin, with fewer side effects and a longer half-life, is generally preferred over unfractionated heparin. Unfractionated heparin with its shorter half-life is generally preferred around the time of delivery. Women on antiplatelet medication for prevention of arterial thromboembolism may be converted to low-dose aspirin after conception and supplemented with low-dose heparin or low-molecular-weight heparin during pregnancy. Because current recommendations rely on case series and expert opinion, additional studies including randomized trials might enhance our ability to prevent recurrent thromboembolism in pregnancy.

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.

Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality.

OBJECTIVE: The purpose of this study was to estimate the incidence, risk factors, and mortality from pregnancy-related venous thromboembolism. STUDY DESIGN: The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the years 2000 to 2001 was queried for all pregnancy-related discharges with a diagnosis of venous thromboembolism. RESULTS: The rate of venous thromboembolism was 1.72 per 1000 deliveries with 1.1 deaths per 100,000. The risk of venous thromboembolism was 38% higher for women ages 35 and older and 64% higher for black women. Other significant risk factors included thrombophilia, lupus, heart disease, sickle cell disease, obesity, fluid and electrolyte imbalance, postpartum infection, and transfusion. The risk factor with the highest odds ratio, 51.8 (38.7-69.2) was thrombophilia. CONCLUSION: The incidence of pregnancy-related venous thromboembolism was higher than generally quoted. Women ages 35 and older, black women, and women with certain medical conditions and obstetric complications appear to be at increased risk.

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.

Anticoagulants in pregnancy.

UNLABELLED: 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.

Thrombosis, thrombophilia, and thromboprophylaxis in pregnancy.

Normal pregnancy is accompanied by changes in coagulation that have likely evolved to protect women from the bleeding challenges of miscarriage and childbirth. Consequently, pregnant women are at an increased risk of thrombosis. The most important risk factors are thrombophilia and a history of thrombosis. Most thromboses in pregnancy occur in the left lower extremity, but pelvic vein thromboses are not uncommon. Thrombophilia increases not only the risk of maternal thrombosis but also the risk of poor pregnancy outcome. All pregnant women should be asked about a personal or family history of thrombosis and the details of their obstetrical history. Some women should undergo laboratory testing, particularly those with a personal history of thrombosis or a history of poor pregnancy outcome. The purpose of testing is to help determine which women should receive anticoagulation therapy, which is used not only to treat venous thromboembolism, but also to prevent thromboembolism and reduce the risk of poor pregnancy outcome in women with thrombophilia. Low-molecular-weight heparins are preferred over unfractionated heparin because they have a longer half-life and are presumed to have fewer side effects. Their longer half-life is a disadvantage around the time of delivery when unfractionated heparin, with its shorter half-life, is easier to manage. The risk of thrombosis is higher postpartum than during pregnancy, so anticoagulation therapy is usually continued for at least 6 weeks after delivery.

Prenatal screening for thrombophilia: the background and the approach.

Coagulation is a normal response to blood vessel injury and involves the interaction of endothelium, platelets and clotting factors. Coagulation is altered by pregnancy and may be further altered by thrombophilia, an acquired or inherited predisposition to develop thrombosis. An overview of coagulation is provided as background for understanding thrombophilia. Both acquired and genetic risk factors for thrombosis are discussed. Thrombosis may affect not only the maternal circulation, but the utero-placental-fetal circulation as well. The literature documenting the association between maternal thrombosis and thrombophilia is summarized, as is the recent data linking thrombophilia and poor pregnancy outcome. An approach to screening for thrombophilia is outlined and strategies for thromboprophylaxis are provided.