Obstetrics

A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.

The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.

MattZ90/Thinkstock.com

A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.

The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.

MattZ90/Thinkstock.com

A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.

The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.

MattZ90/Thinkstock.com

ATLANTA – Physicians are falling short on syphilis testing in both the prenatal period and at the time of delivery, suggest the findings of a study examining insurance claims from nearly 10,000 women who experienced stillbirths.

Overall, less than 10% of women in the study were tested for syphilis following a stillbirth delivery, while less than two-thirds of women who experienced a stillbirth had received prenatal syphilis testing.

jarun011/Thinkstock

[email protected]

ATLANTA – Physicians are falling short on syphilis testing in both the prenatal period and at the time of delivery, suggest the findings of a study examining insurance claims from nearly 10,000 women who experienced stillbirths.

Overall, less than 10% of women in the study were tested for syphilis following a stillbirth delivery, while less than two-thirds of women who experienced a stillbirth had received prenatal syphilis testing.

jarun011/Thinkstock

[email protected]

ATLANTA – Physicians are falling short on syphilis testing in both the prenatal period and at the time of delivery, suggest the findings of a study examining insurance claims from nearly 10,000 women who experienced stillbirths.

Overall, less than 10% of women in the study were tested for syphilis following a stillbirth delivery, while less than two-thirds of women who experienced a stillbirth had received prenatal syphilis testing.

jarun011/Thinkstock

[email protected]

Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.

The search for information

The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.

Purestock/Thinkstock

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

Learning the lessons of the past

During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.

Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.

Moving toward personalized medicine

Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.

As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

Perception of risk

Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.

While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.

Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.

Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.

The search for information

The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.

Purestock/Thinkstock

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

Learning the lessons of the past

During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.

Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.

Moving toward personalized medicine

Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.

As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

Perception of risk

Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.

While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.

Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.

Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.

The search for information

The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.

Purestock/Thinkstock

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

Learning the lessons of the past

During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.

Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.

Moving toward personalized medicine

Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.

As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

Perception of risk

Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.

While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.

Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.

Cesarean delivery is now the most commonly performed major operation in hospitals across the United States. Approximately 30% of the 4 million deliveries that occur each year are by cesarean. Endometritis and wound infection (superficial and deep surgical site infection) are the most common postoperative complications of cesarean delivery. These 2 infections usually can be treated in a straightforward manner with antibiotics or surgical drainage. In some cases, however, they can lead to serious sequelae, such as pelvic abscess, septic pelvic vein thrombophlebitis, and wound dehiscence/evisceration, thereby prolonging the patient’s hospitalization and significantly increasing medical expenses.

Accordingly, in the past 50 years many investigators have proposed various specific measures to reduce the risk of postcesarean infection. In this article, we critically evaluate 2 of these major interventions: methods of skin preparation and administration of prophylactic antibiotics. In part 2 of this series next month, we will review the evidence regarding preoperative bathing with an antiseptic, preoperative vaginal cleansing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.

CASE Cesarean delivery required for nonprogressing labor

A 26-year-old obese primigravid woman, body mass index (BMI) 37 kg m², at 40 weeks’ gestation has been in labor for 20 hours. Her membranes have been ruptured for 16 hours. Her cervix is completely effaced and is 7 cm dilated. The fetal head is at −1 cm station. Her cervical examination findings have not changed in 4 hours despite adequate uterine contractility documented by intrauterine pressure catheter. You are now ready to proceed with cesarean delivery, and you want to do everything possible to prevent the patient from developing a postoperative infection.

What are the best practices for postcesarean infection prevention in this patient?

Skin preparation

Adequate preoperative skin preparation is an important first step in preventing post‑ cesarean infection.

How should you prepare the patient’s skin for surgery?

Two issues to address when preparing the abdominal wall for surgery are hair removal and skin cleansing. More than 40 years ago, Cruse and Foord definitively answered the question about hair removal.¹ In a landmark cohort investigation of more than 23,000 patients having many different types of operative procedures, they demonstrated that shaving the hair on the evening before surgery resulted in a higher rate of wound infection than clipping the hair, removing the hair with a depilatory cream just before surgery, or not removing the hair at all.

Three recent investigations have thoughtfully addressed the issue of skin cleansing. Darouiche and colleagues conducted a prospective, randomized, multicenter trial comparing chlorhexidine-alcohol with povidone-iodine for skin preparation before surgery.² Their investigation included 849 patients having many different types of surgical procedures, only a minority of which were in obstetric and gynecologic patients. They demonstrated fewer superficial wound infections in patients in the chlorhexidine-alcohol group (4.2% vs 8.6%, P = .008). Of even greater importance, patients in the chlorhexidine-alcohol group had fewer deep wound infections (1% vs 3%, P = .005).

Ngai and co-workers recently reported the results of a randomized controlled trial (RCT) in which women undergoing nonurgent cesarean delivery had their skin cleansed with povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions.³ The overall rate of surgical site infection was just 4.3%. The 3 groups had comparable infection rates and, accordingly, the authors were unable to conclude that one type of skin preparation was superior to the other.

The most informative recent investigation was by Tuuli and colleagues, who evaluated 1,147 patients having cesarean delivery assigned to undergo skin preparation with either chlorhexidine-alcohol or iodine-alcohol.⁴ Unlike the study by Ngai and co-workers, in this study approximately 40% of the patients in each treatment arm had unscheduled, urgent cesarean deliveries.^3,4 Overall, the rate of infection in the chlorhexidine-alcohol group was 4.0% compared with 7.3% in the iodine-alcohol group (relative risk [RR], 0.55; 95% confidence interval [CI], 0.34–0.90, P = .02).

What the evidence says

Based on the evidence cited above, we advise removing hair at the incision site with clippers or depilatory cream just before the start of surgery. The abdomen should then be cleansed with a chlorhexidine-alcohol solution (Level I Evidence, Level 1A Recommendation; TABLE).

Antibiotic prophylaxis

Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.

Should you give the patient prophylactic antibiotics?

Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met⁵:

1. the surgical site is inevitably contaminated with bacteria
2. in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
3. operative site infections have the potential to lead to serious, potentially life-threatening sequelae.

Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.⁶

In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.⁵ Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.

When should you administer antibiotics: Before the surgical incision or after cord clamping?

More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.⁷ Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.

Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.

Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.⁸ However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).⁹ Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.

In 2007, Sullivan and colleagues challenged this long-standing practice.¹⁰ In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.

Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.^10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.⁷

Which antibiotic(s) should you administer for prophylaxis, and how many doses?

In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.⁵ The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.

Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.

Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.¹³ In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.¹⁴ In both of these investigations, the antibiotics were administered after cord clamping.

In a subsequent report, Ward and Duff¹⁵ showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.^13,14

Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.¹⁶ This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.

What the evidence says

We conclude that all patients, even those having a scheduled cesarean before the onset of labor or ruptured membranes, should receive prophylactic antibiotics in a single dose administered preoperatively rather than after cord clamping (Level I Evidence, Level 1A Recommendation; TABLE). In high-risk populations (eg, women in labor with ruptured membranes who are having an urgent cesarean), for whom the baseline risk of infection is high, administer the combination of cefazolin plus azithromycin in lieu of cefazolin alone (Level I Evidence, Level 1A Recommendation; TABLE).

If the patient has a history of an immediate hypersensitivity reaction to beta-lactam antibiotics, we recommend the combination of clindamycin (900 mg) plus gentamicin (1.5 mg/kg) as a single infusion prior to surgery. We base this recommendation on the need to provide reasonable coverage against a broad range of pathogens. Clindamycin covers gram-positive aerobes, such as staphylococci species and group B streptococci, and anaerobes; gentamicin covers aerobic gram-negative bacilli. A single agent, such as clindamycin or metronidazole, does not provide the broad-based coverage necessary for effective prophylaxis (Level III Evidence, Level 1C Recommendation; TABLE).

If the patient is overweight or obese, should you modify the antibiotic dose?

The prevalence of obesity in the United States continues to increase. One-third of all US reproductive-aged women are obese, and 6% of women are extremely obese.¹⁷ Obesity increases the risk of postcesarean infection 3- to 5- fold.¹⁸ Because both pregnancy and obesity increase the total volume of a drug’s distribution, achieving adequate antibiotic tissue concentrations may be hindered by a dilutional effect. Furthermore, pharmacokinetic studies consistently have shown that the tissue concentration of an antibiotic—which, ideally, should be above the minimum inhibitory concentration (MIC) for common bacteria—determines the susceptibility of those tissues to infection, regardless of whether the serum concentration of the antibiotic is in the therapeutic range.¹⁹

These concerns have led to several recent investigations evaluating different doses of cefazolin for obese patients. Pevzner and colleagues conducted a prospective cohort study of 29 women having a scheduled cesarean delivery.²⁰ The patients were divided into 3 groups: lean (BMI <30 kg m²), obese (BMI 30.0–39.9 kg m²), and extremely obese (BMI >40 kg m²). All women received a 2-g dose of cefazolin 30 to 60 minutes before surgery. Cefazolin concentrations in adipose tissue obtained at the time of skin incision were inversely proportional to maternal BMI (r, −0.67; P<.001). All specimens demonstrated a therapeutic concentration (>1 µg/g) of cefazolin for gram-positive cocci, but 20% of the obese women and 33% of the extremely obese women did not achieve the MIC (>4 µg/g) for gram-negative bacilli (P = .29 and P = .14, respectively). At the time of skin closure, 20% of obese women and 44% of extremely obese women did not have tissue concentrations that exceeded the MIC for gram-negative bacteria.

Swank and associates conducted a prospective cohort study that included 28 women.¹⁸ They demonstrated that, after a 2-g dose of cefazolin, only 20% of the obese women (BMI 30–40 kg m²) and 0% of the extremely obese women (BMI >40 kg m²) achieved an adipose tissue concentration that exceeded the MIC for gram-negative rods (8 µg/mL). However, 100% and 71.4%, respectively, achieved such a tissue concentration after a 3-g dose. When the women were stratified by actual weight, there was a statistically significant difference between those who weighed less than 120 kg and those who weighed more than 120 kg. Seventy-nine percent of the former had a tissue concentration of cefazolin greater than 8 µg/mL compared with 0% of the women who weighed more than 120 kg. Based on these observations, the authors recommended a 3-g dose of cefazolin for women who weigh more than 120 kg.

In a double-blind RCT with 26 obese women (BMI ≥30 kg m²), Young and colleagues demonstrated that, at the time of hysterotomy and fascial closure, significantly higher concentrations of cefazolin were found in the adipose tissue of obese women who received a 3-g dose of antibiotic compared with those who received a 2-g dose.²¹ However, all concentrations of cefazolin were consistently above the MIC of cefazolin for gram-positive cocci (1 µg/g) and gram-negative bacilli (4 µg/g). Further, Maggio and co-workers conducted a double-blind RCT comparing a 2-g dose of cefazolin versus a 3-g dose in 57 obese women (BMI ≥30 kg m²).²² They found no statistically significant difference in the percentage of women who had tissue concentrations of cefazolin greater than the MIC for gram-positive cocci (8 µg/g). All samples were above the MIC of cefazolin for gram-negative bacilli (2 µg/g). Based on these data, these investigators did not recommend increasing the dose of cefazolin from 2 g to 3 g in obese patients.^21,22

The studies discussed above are difficult to compare for 3 reasons. First, each study used a different MIC of cefazolin for both gram-positive and gram-negative bacteria. Second, the authors sampled different maternal tissues or serum at varying times during the cesarean delivery. Third, the studies did not specifically investigate, or were not powered sufficiently to address, the more important clinical outcome of surgical site infection. In a recent historical cohort study, Ward and Duff were unable to show that increasing the dose of cefazolin to 2 g in all women with a BMI <30 kg m² and to 3 g in all women with a BMI >30 kg m² reduced the rate of endometritis and wound infection below the level already achieved with combined prophylaxis with cefazolin (1 g) plus azithromycin (500 mg).¹⁵

Sutton and colleagues recently assessed the pharmacokinetics of azithromycin when used as prophylaxis for cesarean delivery.²³ They studied 30 women who had a scheduled cesarean delivery and who received a 500-mg intravenous dose of azithromycin that was initiated 15, 30, or 60 minutes before the surgical incision and then infused over 1 hour. They obtained maternal plasma samples multiple times during the first 8 hours after surgery. They also obtained samples of amniotic fluid, placenta, myometrium, adipose tissue, and umbilical cord blood intraoperatively. The median concentration of azithromycin in adipose tissue was 102 ng/g, which is below the MIC₅₀ for Ureaplasma species (250 ng/mL). The median concentration in myometrial tissue was 402 ng/g. The concentration in maternal plasma consistently exceeded the MIC₅₀ for Ureaplasma species.

What the evidence says

All women, regardless of weight, who will undergo cesarean delivery should receive a 2-g dose of cefazolin (Level II Evidence, Level 1B Recommendation; TABLE).If azithromycin is used in combination with cefazolin, an intravenous dose of 500 mg appears to provide adequate concentrations in serum and myometrium, but probably not in adipose tissue. More information is needed before we can make a firm recommendation about weight-based dosing of azithromycin.

CASE Resolved

For the 26-year-old obese laboring patient about to undergo cesarean delivery, reasonable steps for prevention of infection include removing the hair at the incision site with clippers or depilatory cream immediately prior to the start of surgery; cleansing the abdomen with a chlorhexidine-alcohol solution; and administering cefazolin (2 g) plus azithromycin (500 mg) preoperatively.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Cesarean delivery is now the most commonly performed major operation in hospitals across the United States. Approximately 30% of the 4 million deliveries that occur each year are by cesarean. Endometritis and wound infection (superficial and deep surgical site infection) are the most common postoperative complications of cesarean delivery. These 2 infections usually can be treated in a straightforward manner with antibiotics or surgical drainage. In some cases, however, they can lead to serious sequelae, such as pelvic abscess, septic pelvic vein thrombophlebitis, and wound dehiscence/evisceration, thereby prolonging the patient’s hospitalization and significantly increasing medical expenses.

Accordingly, in the past 50 years many investigators have proposed various specific measures to reduce the risk of postcesarean infection. In this article, we critically evaluate 2 of these major interventions: methods of skin preparation and administration of prophylactic antibiotics. In part 2 of this series next month, we will review the evidence regarding preoperative bathing with an antiseptic, preoperative vaginal cleansing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.

CASE Cesarean delivery required for nonprogressing labor

A 26-year-old obese primigravid woman, body mass index (BMI) 37 kg m², at 40 weeks’ gestation has been in labor for 20 hours. Her membranes have been ruptured for 16 hours. Her cervix is completely effaced and is 7 cm dilated. The fetal head is at −1 cm station. Her cervical examination findings have not changed in 4 hours despite adequate uterine contractility documented by intrauterine pressure catheter. You are now ready to proceed with cesarean delivery, and you want to do everything possible to prevent the patient from developing a postoperative infection.

What are the best practices for postcesarean infection prevention in this patient?

Skin preparation

Adequate preoperative skin preparation is an important first step in preventing post‑ cesarean infection.

How should you prepare the patient’s skin for surgery?

Two issues to address when preparing the abdominal wall for surgery are hair removal and skin cleansing. More than 40 years ago, Cruse and Foord definitively answered the question about hair removal.¹ In a landmark cohort investigation of more than 23,000 patients having many different types of operative procedures, they demonstrated that shaving the hair on the evening before surgery resulted in a higher rate of wound infection than clipping the hair, removing the hair with a depilatory cream just before surgery, or not removing the hair at all.

Three recent investigations have thoughtfully addressed the issue of skin cleansing. Darouiche and colleagues conducted a prospective, randomized, multicenter trial comparing chlorhexidine-alcohol with povidone-iodine for skin preparation before surgery.² Their investigation included 849 patients having many different types of surgical procedures, only a minority of which were in obstetric and gynecologic patients. They demonstrated fewer superficial wound infections in patients in the chlorhexidine-alcohol group (4.2% vs 8.6%, P = .008). Of even greater importance, patients in the chlorhexidine-alcohol group had fewer deep wound infections (1% vs 3%, P = .005).

Ngai and co-workers recently reported the results of a randomized controlled trial (RCT) in which women undergoing nonurgent cesarean delivery had their skin cleansed with povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions.³ The overall rate of surgical site infection was just 4.3%. The 3 groups had comparable infection rates and, accordingly, the authors were unable to conclude that one type of skin preparation was superior to the other.

The most informative recent investigation was by Tuuli and colleagues, who evaluated 1,147 patients having cesarean delivery assigned to undergo skin preparation with either chlorhexidine-alcohol or iodine-alcohol.⁴ Unlike the study by Ngai and co-workers, in this study approximately 40% of the patients in each treatment arm had unscheduled, urgent cesarean deliveries.^3,4 Overall, the rate of infection in the chlorhexidine-alcohol group was 4.0% compared with 7.3% in the iodine-alcohol group (relative risk [RR], 0.55; 95% confidence interval [CI], 0.34–0.90, P = .02).

What the evidence says

Based on the evidence cited above, we advise removing hair at the incision site with clippers or depilatory cream just before the start of surgery. The abdomen should then be cleansed with a chlorhexidine-alcohol solution (Level I Evidence, Level 1A Recommendation; TABLE).

Antibiotic prophylaxis

Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.

Should you give the patient prophylactic antibiotics?

Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met⁵:

1. the surgical site is inevitably contaminated with bacteria
2. in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
3. operative site infections have the potential to lead to serious, potentially life-threatening sequelae.

Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.⁶

In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.⁵ Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.

When should you administer antibiotics: Before the surgical incision or after cord clamping?

More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.⁷ Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.

Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.

Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.⁸ However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).⁹ Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.

In 2007, Sullivan and colleagues challenged this long-standing practice.¹⁰ In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.

Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.^10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.⁷

Which antibiotic(s) should you administer for prophylaxis, and how many doses?

In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.⁵ The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.

Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.

Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.¹³ In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.¹⁴ In both of these investigations, the antibiotics were administered after cord clamping.

In a subsequent report, Ward and Duff¹⁵ showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.^13,14

Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.¹⁶ This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.

What the evidence says

We conclude that all patients, even those having a scheduled cesarean before the onset of labor or ruptured membranes, should receive prophylactic antibiotics in a single dose administered preoperatively rather than after cord clamping (Level I Evidence, Level 1A Recommendation; TABLE). In high-risk populations (eg, women in labor with ruptured membranes who are having an urgent cesarean), for whom the baseline risk of infection is high, administer the combination of cefazolin plus azithromycin in lieu of cefazolin alone (Level I Evidence, Level 1A Recommendation; TABLE).

If the patient has a history of an immediate hypersensitivity reaction to beta-lactam antibiotics, we recommend the combination of clindamycin (900 mg) plus gentamicin (1.5 mg/kg) as a single infusion prior to surgery. We base this recommendation on the need to provide reasonable coverage against a broad range of pathogens. Clindamycin covers gram-positive aerobes, such as staphylococci species and group B streptococci, and anaerobes; gentamicin covers aerobic gram-negative bacilli. A single agent, such as clindamycin or metronidazole, does not provide the broad-based coverage necessary for effective prophylaxis (Level III Evidence, Level 1C Recommendation; TABLE).

If the patient is overweight or obese, should you modify the antibiotic dose?

The prevalence of obesity in the United States continues to increase. One-third of all US reproductive-aged women are obese, and 6% of women are extremely obese.¹⁷ Obesity increases the risk of postcesarean infection 3- to 5- fold.¹⁸ Because both pregnancy and obesity increase the total volume of a drug’s distribution, achieving adequate antibiotic tissue concentrations may be hindered by a dilutional effect. Furthermore, pharmacokinetic studies consistently have shown that the tissue concentration of an antibiotic—which, ideally, should be above the minimum inhibitory concentration (MIC) for common bacteria—determines the susceptibility of those tissues to infection, regardless of whether the serum concentration of the antibiotic is in the therapeutic range.¹⁹

These concerns have led to several recent investigations evaluating different doses of cefazolin for obese patients. Pevzner and colleagues conducted a prospective cohort study of 29 women having a scheduled cesarean delivery.²⁰ The patients were divided into 3 groups: lean (BMI <30 kg m²), obese (BMI 30.0–39.9 kg m²), and extremely obese (BMI >40 kg m²). All women received a 2-g dose of cefazolin 30 to 60 minutes before surgery. Cefazolin concentrations in adipose tissue obtained at the time of skin incision were inversely proportional to maternal BMI (r, −0.67; P<.001). All specimens demonstrated a therapeutic concentration (>1 µg/g) of cefazolin for gram-positive cocci, but 20% of the obese women and 33% of the extremely obese women did not achieve the MIC (>4 µg/g) for gram-negative bacilli (P = .29 and P = .14, respectively). At the time of skin closure, 20% of obese women and 44% of extremely obese women did not have tissue concentrations that exceeded the MIC for gram-negative bacteria.

Swank and associates conducted a prospective cohort study that included 28 women.¹⁸ They demonstrated that, after a 2-g dose of cefazolin, only 20% of the obese women (BMI 30–40 kg m²) and 0% of the extremely obese women (BMI >40 kg m²) achieved an adipose tissue concentration that exceeded the MIC for gram-negative rods (8 µg/mL). However, 100% and 71.4%, respectively, achieved such a tissue concentration after a 3-g dose. When the women were stratified by actual weight, there was a statistically significant difference between those who weighed less than 120 kg and those who weighed more than 120 kg. Seventy-nine percent of the former had a tissue concentration of cefazolin greater than 8 µg/mL compared with 0% of the women who weighed more than 120 kg. Based on these observations, the authors recommended a 3-g dose of cefazolin for women who weigh more than 120 kg.

In a double-blind RCT with 26 obese women (BMI ≥30 kg m²), Young and colleagues demonstrated that, at the time of hysterotomy and fascial closure, significantly higher concentrations of cefazolin were found in the adipose tissue of obese women who received a 3-g dose of antibiotic compared with those who received a 2-g dose.²¹ However, all concentrations of cefazolin were consistently above the MIC of cefazolin for gram-positive cocci (1 µg/g) and gram-negative bacilli (4 µg/g). Further, Maggio and co-workers conducted a double-blind RCT comparing a 2-g dose of cefazolin versus a 3-g dose in 57 obese women (BMI ≥30 kg m²).²² They found no statistically significant difference in the percentage of women who had tissue concentrations of cefazolin greater than the MIC for gram-positive cocci (8 µg/g). All samples were above the MIC of cefazolin for gram-negative bacilli (2 µg/g). Based on these data, these investigators did not recommend increasing the dose of cefazolin from 2 g to 3 g in obese patients.^21,22

The studies discussed above are difficult to compare for 3 reasons. First, each study used a different MIC of cefazolin for both gram-positive and gram-negative bacteria. Second, the authors sampled different maternal tissues or serum at varying times during the cesarean delivery. Third, the studies did not specifically investigate, or were not powered sufficiently to address, the more important clinical outcome of surgical site infection. In a recent historical cohort study, Ward and Duff were unable to show that increasing the dose of cefazolin to 2 g in all women with a BMI <30 kg m² and to 3 g in all women with a BMI >30 kg m² reduced the rate of endometritis and wound infection below the level already achieved with combined prophylaxis with cefazolin (1 g) plus azithromycin (500 mg).¹⁵

Sutton and colleagues recently assessed the pharmacokinetics of azithromycin when used as prophylaxis for cesarean delivery.²³ They studied 30 women who had a scheduled cesarean delivery and who received a 500-mg intravenous dose of azithromycin that was initiated 15, 30, or 60 minutes before the surgical incision and then infused over 1 hour. They obtained maternal plasma samples multiple times during the first 8 hours after surgery. They also obtained samples of amniotic fluid, placenta, myometrium, adipose tissue, and umbilical cord blood intraoperatively. The median concentration of azithromycin in adipose tissue was 102 ng/g, which is below the MIC₅₀ for Ureaplasma species (250 ng/mL). The median concentration in myometrial tissue was 402 ng/g. The concentration in maternal plasma consistently exceeded the MIC₅₀ for Ureaplasma species.

What the evidence says

All women, regardless of weight, who will undergo cesarean delivery should receive a 2-g dose of cefazolin (Level II Evidence, Level 1B Recommendation; TABLE).If azithromycin is used in combination with cefazolin, an intravenous dose of 500 mg appears to provide adequate concentrations in serum and myometrium, but probably not in adipose tissue. More information is needed before we can make a firm recommendation about weight-based dosing of azithromycin.

CASE Resolved

For the 26-year-old obese laboring patient about to undergo cesarean delivery, reasonable steps for prevention of infection include removing the hair at the incision site with clippers or depilatory cream immediately prior to the start of surgery; cleansing the abdomen with a chlorhexidine-alcohol solution; and administering cefazolin (2 g) plus azithromycin (500 mg) preoperatively.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Cesarean delivery is now the most commonly performed major operation in hospitals across the United States. Approximately 30% of the 4 million deliveries that occur each year are by cesarean. Endometritis and wound infection (superficial and deep surgical site infection) are the most common postoperative complications of cesarean delivery. These 2 infections usually can be treated in a straightforward manner with antibiotics or surgical drainage. In some cases, however, they can lead to serious sequelae, such as pelvic abscess, septic pelvic vein thrombophlebitis, and wound dehiscence/evisceration, thereby prolonging the patient’s hospitalization and significantly increasing medical expenses.

Accordingly, in the past 50 years many investigators have proposed various specific measures to reduce the risk of postcesarean infection. In this article, we critically evaluate 2 of these major interventions: methods of skin preparation and administration of prophylactic antibiotics. In part 2 of this series next month, we will review the evidence regarding preoperative bathing with an antiseptic, preoperative vaginal cleansing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.

CASE Cesarean delivery required for nonprogressing labor

A 26-year-old obese primigravid woman, body mass index (BMI) 37 kg m², at 40 weeks’ gestation has been in labor for 20 hours. Her membranes have been ruptured for 16 hours. Her cervix is completely effaced and is 7 cm dilated. The fetal head is at −1 cm station. Her cervical examination findings have not changed in 4 hours despite adequate uterine contractility documented by intrauterine pressure catheter. You are now ready to proceed with cesarean delivery, and you want to do everything possible to prevent the patient from developing a postoperative infection.

What are the best practices for postcesarean infection prevention in this patient?

Skin preparation

Adequate preoperative skin preparation is an important first step in preventing post‑ cesarean infection.

How should you prepare the patient’s skin for surgery?

Two issues to address when preparing the abdominal wall for surgery are hair removal and skin cleansing. More than 40 years ago, Cruse and Foord definitively answered the question about hair removal.¹ In a landmark cohort investigation of more than 23,000 patients having many different types of operative procedures, they demonstrated that shaving the hair on the evening before surgery resulted in a higher rate of wound infection than clipping the hair, removing the hair with a depilatory cream just before surgery, or not removing the hair at all.

Three recent investigations have thoughtfully addressed the issue of skin cleansing. Darouiche and colleagues conducted a prospective, randomized, multicenter trial comparing chlorhexidine-alcohol with povidone-iodine for skin preparation before surgery.² Their investigation included 849 patients having many different types of surgical procedures, only a minority of which were in obstetric and gynecologic patients. They demonstrated fewer superficial wound infections in patients in the chlorhexidine-alcohol group (4.2% vs 8.6%, P = .008). Of even greater importance, patients in the chlorhexidine-alcohol group had fewer deep wound infections (1% vs 3%, P = .005).

Ngai and co-workers recently reported the results of a randomized controlled trial (RCT) in which women undergoing nonurgent cesarean delivery had their skin cleansed with povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions.³ The overall rate of surgical site infection was just 4.3%. The 3 groups had comparable infection rates and, accordingly, the authors were unable to conclude that one type of skin preparation was superior to the other.

The most informative recent investigation was by Tuuli and colleagues, who evaluated 1,147 patients having cesarean delivery assigned to undergo skin preparation with either chlorhexidine-alcohol or iodine-alcohol.⁴ Unlike the study by Ngai and co-workers, in this study approximately 40% of the patients in each treatment arm had unscheduled, urgent cesarean deliveries.^3,4 Overall, the rate of infection in the chlorhexidine-alcohol group was 4.0% compared with 7.3% in the iodine-alcohol group (relative risk [RR], 0.55; 95% confidence interval [CI], 0.34–0.90, P = .02).

What the evidence says

Based on the evidence cited above, we advise removing hair at the incision site with clippers or depilatory cream just before the start of surgery. The abdomen should then be cleansed with a chlorhexidine-alcohol solution (Level I Evidence, Level 1A Recommendation; TABLE).

Antibiotic prophylaxis

Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.

Should you give the patient prophylactic antibiotics?

Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met⁵:

1. the surgical site is inevitably contaminated with bacteria
2. in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
3. operative site infections have the potential to lead to serious, potentially life-threatening sequelae.

Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.⁶

In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.⁵ Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.

When should you administer antibiotics: Before the surgical incision or after cord clamping?

More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.⁷ Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.

Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.

Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.⁸ However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).⁹ Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.

In 2007, Sullivan and colleagues challenged this long-standing practice.¹⁰ In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.

Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.^10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.⁷

Which antibiotic(s) should you administer for prophylaxis, and how many doses?

In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.⁵ The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.

Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.

Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.¹³ In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.¹⁴ In both of these investigations, the antibiotics were administered after cord clamping.

In a subsequent report, Ward and Duff¹⁵ showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.^13,14

Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.¹⁶ This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.

What the evidence says

We conclude that all patients, even those having a scheduled cesarean before the onset of labor or ruptured membranes, should receive prophylactic antibiotics in a single dose administered preoperatively rather than after cord clamping (Level I Evidence, Level 1A Recommendation; TABLE). In high-risk populations (eg, women in labor with ruptured membranes who are having an urgent cesarean), for whom the baseline risk of infection is high, administer the combination of cefazolin plus azithromycin in lieu of cefazolin alone (Level I Evidence, Level 1A Recommendation; TABLE).

If the patient has a history of an immediate hypersensitivity reaction to beta-lactam antibiotics, we recommend the combination of clindamycin (900 mg) plus gentamicin (1.5 mg/kg) as a single infusion prior to surgery. We base this recommendation on the need to provide reasonable coverage against a broad range of pathogens. Clindamycin covers gram-positive aerobes, such as staphylococci species and group B streptococci, and anaerobes; gentamicin covers aerobic gram-negative bacilli. A single agent, such as clindamycin or metronidazole, does not provide the broad-based coverage necessary for effective prophylaxis (Level III Evidence, Level 1C Recommendation; TABLE).

If the patient is overweight or obese, should you modify the antibiotic dose?

The prevalence of obesity in the United States continues to increase. One-third of all US reproductive-aged women are obese, and 6% of women are extremely obese.¹⁷ Obesity increases the risk of postcesarean infection 3- to 5- fold.¹⁸ Because both pregnancy and obesity increase the total volume of a drug’s distribution, achieving adequate antibiotic tissue concentrations may be hindered by a dilutional effect. Furthermore, pharmacokinetic studies consistently have shown that the tissue concentration of an antibiotic—which, ideally, should be above the minimum inhibitory concentration (MIC) for common bacteria—determines the susceptibility of those tissues to infection, regardless of whether the serum concentration of the antibiotic is in the therapeutic range.¹⁹

These concerns have led to several recent investigations evaluating different doses of cefazolin for obese patients. Pevzner and colleagues conducted a prospective cohort study of 29 women having a scheduled cesarean delivery.²⁰ The patients were divided into 3 groups: lean (BMI <30 kg m²), obese (BMI 30.0–39.9 kg m²), and extremely obese (BMI >40 kg m²). All women received a 2-g dose of cefazolin 30 to 60 minutes before surgery. Cefazolin concentrations in adipose tissue obtained at the time of skin incision were inversely proportional to maternal BMI (r, −0.67; P<.001). All specimens demonstrated a therapeutic concentration (>1 µg/g) of cefazolin for gram-positive cocci, but 20% of the obese women and 33% of the extremely obese women did not achieve the MIC (>4 µg/g) for gram-negative bacilli (P = .29 and P = .14, respectively). At the time of skin closure, 20% of obese women and 44% of extremely obese women did not have tissue concentrations that exceeded the MIC for gram-negative bacteria.

Swank and associates conducted a prospective cohort study that included 28 women.¹⁸ They demonstrated that, after a 2-g dose of cefazolin, only 20% of the obese women (BMI 30–40 kg m²) and 0% of the extremely obese women (BMI >40 kg m²) achieved an adipose tissue concentration that exceeded the MIC for gram-negative rods (8 µg/mL). However, 100% and 71.4%, respectively, achieved such a tissue concentration after a 3-g dose. When the women were stratified by actual weight, there was a statistically significant difference between those who weighed less than 120 kg and those who weighed more than 120 kg. Seventy-nine percent of the former had a tissue concentration of cefazolin greater than 8 µg/mL compared with 0% of the women who weighed more than 120 kg. Based on these observations, the authors recommended a 3-g dose of cefazolin for women who weigh more than 120 kg.

In a double-blind RCT with 26 obese women (BMI ≥30 kg m²), Young and colleagues demonstrated that, at the time of hysterotomy and fascial closure, significantly higher concentrations of cefazolin were found in the adipose tissue of obese women who received a 3-g dose of antibiotic compared with those who received a 2-g dose.²¹ However, all concentrations of cefazolin were consistently above the MIC of cefazolin for gram-positive cocci (1 µg/g) and gram-negative bacilli (4 µg/g). Further, Maggio and co-workers conducted a double-blind RCT comparing a 2-g dose of cefazolin versus a 3-g dose in 57 obese women (BMI ≥30 kg m²).²² They found no statistically significant difference in the percentage of women who had tissue concentrations of cefazolin greater than the MIC for gram-positive cocci (8 µg/g). All samples were above the MIC of cefazolin for gram-negative bacilli (2 µg/g). Based on these data, these investigators did not recommend increasing the dose of cefazolin from 2 g to 3 g in obese patients.^21,22

The studies discussed above are difficult to compare for 3 reasons. First, each study used a different MIC of cefazolin for both gram-positive and gram-negative bacteria. Second, the authors sampled different maternal tissues or serum at varying times during the cesarean delivery. Third, the studies did not specifically investigate, or were not powered sufficiently to address, the more important clinical outcome of surgical site infection. In a recent historical cohort study, Ward and Duff were unable to show that increasing the dose of cefazolin to 2 g in all women with a BMI <30 kg m² and to 3 g in all women with a BMI >30 kg m² reduced the rate of endometritis and wound infection below the level already achieved with combined prophylaxis with cefazolin (1 g) plus azithromycin (500 mg).¹⁵

Sutton and colleagues recently assessed the pharmacokinetics of azithromycin when used as prophylaxis for cesarean delivery.²³ They studied 30 women who had a scheduled cesarean delivery and who received a 500-mg intravenous dose of azithromycin that was initiated 15, 30, or 60 minutes before the surgical incision and then infused over 1 hour. They obtained maternal plasma samples multiple times during the first 8 hours after surgery. They also obtained samples of amniotic fluid, placenta, myometrium, adipose tissue, and umbilical cord blood intraoperatively. The median concentration of azithromycin in adipose tissue was 102 ng/g, which is below the MIC₅₀ for Ureaplasma species (250 ng/mL). The median concentration in myometrial tissue was 402 ng/g. The concentration in maternal plasma consistently exceeded the MIC₅₀ for Ureaplasma species.

What the evidence says

All women, regardless of weight, who will undergo cesarean delivery should receive a 2-g dose of cefazolin (Level II Evidence, Level 1B Recommendation; TABLE).If azithromycin is used in combination with cefazolin, an intravenous dose of 500 mg appears to provide adequate concentrations in serum and myometrium, but probably not in adipose tissue. More information is needed before we can make a firm recommendation about weight-based dosing of azithromycin.

CASE Resolved

For the 26-year-old obese laboring patient about to undergo cesarean delivery, reasonable steps for prevention of infection include removing the hair at the incision site with clippers or depilatory cream immediately prior to the start of surgery; cleansing the abdomen with a chlorhexidine-alcohol solution; and administering cefazolin (2 g) plus azithromycin (500 mg) preoperatively.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

John M. Thorp Jr, MD, McAllister Distinguished Professor, Division Director, General Obstetrics and Gynecology, Vice Chair of Research, Department of Ob-Gyn, University of North Carolina Schools of Medicine and Public Health, Chapel Hill.

Five years ago one of our interns operating with the director of labor and delivery challenged him as to why we were not using evidenced-based surgical techniques for cesarean delivery. Bruised by the formidable (and at times misleading) club of “evidence-based medicine” that is held as sacrosanct by the modern obstetrician, the director responded to the charge by researching a systematic review on abdominal delivery that amalgamated studies of poor quality with precious few trials. He unilaterally decided that we needed an opening in the transparent portion of the drape overlying the incision site so that we might use “evidence” to prevent operative site infection. The end result: No change in the incidence of wound infections, and adhesive drapes that did not adhere well, thereby displacing the effluent of amniotic fluid and blood that are part of a cesarean delivery back into the first assistant’s socks, shoes, and clothing. It was as if the clock had been turned back to my early years as an attending when we had cloth drapes. So much for having an evidence-based protocol. I was thus elated at reading the results of the CORONIS trial.

Details of the study

The CORONIS trial, in which investigators randomly assigned almost 16,000 women from 7 countries (Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan), used a sophisticated factorial design and followed up 13,153 (84%) of the women for 3 years. The investigators tested an array of technical questions about 5 intervention pairs used during abdominal delivery and reported the main outcomes of interest for each intervention, including:

• blunt versus sharp abdominal entry—no evidence of a difference in risk of abdominal hernias (adjusted risk ratio [RR], 0.66; 95% confidence interval [CI], 0.39–1.11)
• exteriorization of the uterus versus intra-abdominal repair—no evidence of a difference in risk of infertility (RR, 0.91; 95% CI, 0.71–1.18) or of ectopic pregnancy (RR, 0.50; CI, 0.15–1.66)
• single- versus double-layer closure of the uterus—no evidence of a difference in maternal death (RR, 0.78; 95% CI, 0.46–1.32) or a composite of pregnancy complications (RR, 1.20; 95% CI, 0.75–1.90)
• closure versus nonclosure of the peritoneum—no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions, such as infertility (RR, 0.8; 95% CI, 0.61–1.06)
• chromic catgut versus polyglactin-910 sutures—no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (RR, 3.05; 95% CI, 0.32–29.29).

Strengths and limitations. The CORONIS trial included a large number of participants and had comprehensive follow-up, a rigorous data collection process, and the participation of many countries. The trial’s participating centers, however, were mostly large referral hospitals with high research interest; adverse outcomes might have been higher in other settings. As well, a lower incidence of subsequent pregnancy among participants limited the study’s power to detect differences in outcomes between the intervention pairs.

Conclusions. None of the alternative techniques produced any real benefits despite syntheses-suggested benefit reported in systematic reviews. Surgeon preference for cesarean delivery techniques likely will continue to guide clinical practice along with economic and institution factors.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

John M. Thorp Jr, MD, McAllister Distinguished Professor, Division Director, General Obstetrics and Gynecology, Vice Chair of Research, Department of Ob-Gyn, University of North Carolina Schools of Medicine and Public Health, Chapel Hill.

Five years ago one of our interns operating with the director of labor and delivery challenged him as to why we were not using evidenced-based surgical techniques for cesarean delivery. Bruised by the formidable (and at times misleading) club of “evidence-based medicine” that is held as sacrosanct by the modern obstetrician, the director responded to the charge by researching a systematic review on abdominal delivery that amalgamated studies of poor quality with precious few trials. He unilaterally decided that we needed an opening in the transparent portion of the drape overlying the incision site so that we might use “evidence” to prevent operative site infection. The end result: No change in the incidence of wound infections, and adhesive drapes that did not adhere well, thereby displacing the effluent of amniotic fluid and blood that are part of a cesarean delivery back into the first assistant’s socks, shoes, and clothing. It was as if the clock had been turned back to my early years as an attending when we had cloth drapes. So much for having an evidence-based protocol. I was thus elated at reading the results of the CORONIS trial.

Details of the study

The CORONIS trial, in which investigators randomly assigned almost 16,000 women from 7 countries (Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan), used a sophisticated factorial design and followed up 13,153 (84%) of the women for 3 years. The investigators tested an array of technical questions about 5 intervention pairs used during abdominal delivery and reported the main outcomes of interest for each intervention, including:

• blunt versus sharp abdominal entry—no evidence of a difference in risk of abdominal hernias (adjusted risk ratio [RR], 0.66; 95% confidence interval [CI], 0.39–1.11)
• exteriorization of the uterus versus intra-abdominal repair—no evidence of a difference in risk of infertility (RR, 0.91; 95% CI, 0.71–1.18) or of ectopic pregnancy (RR, 0.50; CI, 0.15–1.66)
• single- versus double-layer closure of the uterus—no evidence of a difference in maternal death (RR, 0.78; 95% CI, 0.46–1.32) or a composite of pregnancy complications (RR, 1.20; 95% CI, 0.75–1.90)
• closure versus nonclosure of the peritoneum—no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions, such as infertility (RR, 0.8; 95% CI, 0.61–1.06)
• chromic catgut versus polyglactin-910 sutures—no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (RR, 3.05; 95% CI, 0.32–29.29).

Strengths and limitations. The CORONIS trial included a large number of participants and had comprehensive follow-up, a rigorous data collection process, and the participation of many countries. The trial’s participating centers, however, were mostly large referral hospitals with high research interest; adverse outcomes might have been higher in other settings. As well, a lower incidence of subsequent pregnancy among participants limited the study’s power to detect differences in outcomes between the intervention pairs.

Conclusions. None of the alternative techniques produced any real benefits despite syntheses-suggested benefit reported in systematic reviews. Surgeon preference for cesarean delivery techniques likely will continue to guide clinical practice along with economic and institution factors.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

John M. Thorp Jr, MD, McAllister Distinguished Professor, Division Director, General Obstetrics and Gynecology, Vice Chair of Research, Department of Ob-Gyn, University of North Carolina Schools of Medicine and Public Health, Chapel Hill.

Five years ago one of our interns operating with the director of labor and delivery challenged him as to why we were not using evidenced-based surgical techniques for cesarean delivery. Bruised by the formidable (and at times misleading) club of “evidence-based medicine” that is held as sacrosanct by the modern obstetrician, the director responded to the charge by researching a systematic review on abdominal delivery that amalgamated studies of poor quality with precious few trials. He unilaterally decided that we needed an opening in the transparent portion of the drape overlying the incision site so that we might use “evidence” to prevent operative site infection. The end result: No change in the incidence of wound infections, and adhesive drapes that did not adhere well, thereby displacing the effluent of amniotic fluid and blood that are part of a cesarean delivery back into the first assistant’s socks, shoes, and clothing. It was as if the clock had been turned back to my early years as an attending when we had cloth drapes. So much for having an evidence-based protocol. I was thus elated at reading the results of the CORONIS trial.

Details of the study

The CORONIS trial, in which investigators randomly assigned almost 16,000 women from 7 countries (Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan), used a sophisticated factorial design and followed up 13,153 (84%) of the women for 3 years. The investigators tested an array of technical questions about 5 intervention pairs used during abdominal delivery and reported the main outcomes of interest for each intervention, including:

• blunt versus sharp abdominal entry—no evidence of a difference in risk of abdominal hernias (adjusted risk ratio [RR], 0.66; 95% confidence interval [CI], 0.39–1.11)
• exteriorization of the uterus versus intra-abdominal repair—no evidence of a difference in risk of infertility (RR, 0.91; 95% CI, 0.71–1.18) or of ectopic pregnancy (RR, 0.50; CI, 0.15–1.66)
• single- versus double-layer closure of the uterus—no evidence of a difference in maternal death (RR, 0.78; 95% CI, 0.46–1.32) or a composite of pregnancy complications (RR, 1.20; 95% CI, 0.75–1.90)
• closure versus nonclosure of the peritoneum—no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions, such as infertility (RR, 0.8; 95% CI, 0.61–1.06)
• chromic catgut versus polyglactin-910 sutures—no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (RR, 3.05; 95% CI, 0.32–29.29).

Strengths and limitations. The CORONIS trial included a large number of participants and had comprehensive follow-up, a rigorous data collection process, and the participation of many countries. The trial’s participating centers, however, were mostly large referral hospitals with high research interest; adverse outcomes might have been higher in other settings. As well, a lower incidence of subsequent pregnancy among participants limited the study’s power to detect differences in outcomes between the intervention pairs.

Conclusions. None of the alternative techniques produced any real benefits despite syntheses-suggested benefit reported in systematic reviews. Surgeon preference for cesarean delivery techniques likely will continue to guide clinical practice along with economic and institution factors.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

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ROME – It’s fortunate that pregnancy-associated acute MIs are infrequent, because the associated in-hospital mortality is markedly higher than in similar-age nonchildbearing women, Reza Masoomi, MD, said at the annual congress of the European Society of Cardiology.

One likely contributor to the disparity in outcome is that current management appears to feature underutilization of percutaneous intervention in women who experience pregnancy-associated MI, according to Dr. Masoomi of the University of Kansas in Kansas City.

He presented an analysis of the U.S. National Inpatient Sample database for the years 2008-2012. The NIS is a nationally representative sample of hospitalizations drawn from all of the country’s nonfederal acute-care hospitals.

A total of 55,315 hospitalizations with a discharge diagnosis of acute MI were recorded in women aged 15-54 years during the study years, of which 453 involved an ante- or postpartum MI. Extrapolating from those figures, nearly 262,000 women aged 15-54 years across the U.S. had an acute MI during the study years, of whom an estimated 2,153 experienced a pregnancy-associated MI.

In-hospital mortality among women with peripregnancy MI was 7.2%, significantly higher than the 5.2% rate in women who weren’t pregnant.

Women with peripregnancy MI had a significantly higher rate of ST-elevation MI (STEMI) than did nonpregnant women with MI in their reproductive years, by a margin of 35.3% to 32.8%. They were younger, too: an average age of 34.9 years, compared with 47.3 years in nonpregnant patients with an MI. Nearly two-thirds of women with peripregnancy MI were nonwhite, compared with 47.3% of the comparison group.

Regardless of whether women with peripregnancy MI had a STEMI or non-STEMI, they had significantly lower rates of diagnostic coronary angiography and percutaneous intervention. They were also far less likely to receive drug-eluting stents.

Diagnostic coronary angiography was performed in 59% of women with pregnancy-associated STEMI, compared with 73% of nonpregnant women with a STEMI. Only 34% of patients with peripregnancy STEMI underwent PCI, compared with 61% of nonpregnant women with a STEMI. Drug-eluting stents were implanted in 12% of peripregnancy STEMI patients and in 35% of nonpregnant patients. In contrast, 10% of patients with a pregnancy-related STEMI underwent coronary artery bypass surgery, compared with 5% of nonpregnant women with a STEMI.

The PCI rate among women with a peripregnancy non-STEMI was 7.8%, compared with 28.7% in nonpregnant women with a non-STEMI. However, CABG was utilized less frequently in the peripregnancy non-STEMI group, by a margin of 4.4% to 5.9%.

Dr. Masoomi reported having no financial conflicts regarding his study.
 

[email protected]
 

ROME – It’s fortunate that pregnancy-associated acute MIs are infrequent, because the associated in-hospital mortality is markedly higher than in similar-age nonchildbearing women, Reza Masoomi, MD, said at the annual congress of the European Society of Cardiology.

One likely contributor to the disparity in outcome is that current management appears to feature underutilization of percutaneous intervention in women who experience pregnancy-associated MI, according to Dr. Masoomi of the University of Kansas in Kansas City.

He presented an analysis of the U.S. National Inpatient Sample database for the years 2008-2012. The NIS is a nationally representative sample of hospitalizations drawn from all of the country’s nonfederal acute-care hospitals.

A total of 55,315 hospitalizations with a discharge diagnosis of acute MI were recorded in women aged 15-54 years during the study years, of which 453 involved an ante- or postpartum MI. Extrapolating from those figures, nearly 262,000 women aged 15-54 years across the U.S. had an acute MI during the study years, of whom an estimated 2,153 experienced a pregnancy-associated MI.

In-hospital mortality among women with peripregnancy MI was 7.2%, significantly higher than the 5.2% rate in women who weren’t pregnant.

Women with peripregnancy MI had a significantly higher rate of ST-elevation MI (STEMI) than did nonpregnant women with MI in their reproductive years, by a margin of 35.3% to 32.8%. They were younger, too: an average age of 34.9 years, compared with 47.3 years in nonpregnant patients with an MI. Nearly two-thirds of women with peripregnancy MI were nonwhite, compared with 47.3% of the comparison group.

Regardless of whether women with peripregnancy MI had a STEMI or non-STEMI, they had significantly lower rates of diagnostic coronary angiography and percutaneous intervention. They were also far less likely to receive drug-eluting stents.

Diagnostic coronary angiography was performed in 59% of women with pregnancy-associated STEMI, compared with 73% of nonpregnant women with a STEMI. Only 34% of patients with peripregnancy STEMI underwent PCI, compared with 61% of nonpregnant women with a STEMI. Drug-eluting stents were implanted in 12% of peripregnancy STEMI patients and in 35% of nonpregnant patients. In contrast, 10% of patients with a pregnancy-related STEMI underwent coronary artery bypass surgery, compared with 5% of nonpregnant women with a STEMI.

The PCI rate among women with a peripregnancy non-STEMI was 7.8%, compared with 28.7% in nonpregnant women with a non-STEMI. However, CABG was utilized less frequently in the peripregnancy non-STEMI group, by a margin of 4.4% to 5.9%.

Dr. Masoomi reported having no financial conflicts regarding his study.
 

[email protected]
 

ROME – It’s fortunate that pregnancy-associated acute MIs are infrequent, because the associated in-hospital mortality is markedly higher than in similar-age nonchildbearing women, Reza Masoomi, MD, said at the annual congress of the European Society of Cardiology.

One likely contributor to the disparity in outcome is that current management appears to feature underutilization of percutaneous intervention in women who experience pregnancy-associated MI, according to Dr. Masoomi of the University of Kansas in Kansas City.

He presented an analysis of the U.S. National Inpatient Sample database for the years 2008-2012. The NIS is a nationally representative sample of hospitalizations drawn from all of the country’s nonfederal acute-care hospitals.

A total of 55,315 hospitalizations with a discharge diagnosis of acute MI were recorded in women aged 15-54 years during the study years, of which 453 involved an ante- or postpartum MI. Extrapolating from those figures, nearly 262,000 women aged 15-54 years across the U.S. had an acute MI during the study years, of whom an estimated 2,153 experienced a pregnancy-associated MI.

In-hospital mortality among women with peripregnancy MI was 7.2%, significantly higher than the 5.2% rate in women who weren’t pregnant.

Women with peripregnancy MI had a significantly higher rate of ST-elevation MI (STEMI) than did nonpregnant women with MI in their reproductive years, by a margin of 35.3% to 32.8%. They were younger, too: an average age of 34.9 years, compared with 47.3 years in nonpregnant patients with an MI. Nearly two-thirds of women with peripregnancy MI were nonwhite, compared with 47.3% of the comparison group.

Regardless of whether women with peripregnancy MI had a STEMI or non-STEMI, they had significantly lower rates of diagnostic coronary angiography and percutaneous intervention. They were also far less likely to receive drug-eluting stents.

Diagnostic coronary angiography was performed in 59% of women with pregnancy-associated STEMI, compared with 73% of nonpregnant women with a STEMI. Only 34% of patients with peripregnancy STEMI underwent PCI, compared with 61% of nonpregnant women with a STEMI. Drug-eluting stents were implanted in 12% of peripregnancy STEMI patients and in 35% of nonpregnant patients. In contrast, 10% of patients with a pregnancy-related STEMI underwent coronary artery bypass surgery, compared with 5% of nonpregnant women with a STEMI.

The PCI rate among women with a peripregnancy non-STEMI was 7.8%, compared with 28.7% in nonpregnant women with a non-STEMI. However, CABG was utilized less frequently in the peripregnancy non-STEMI group, by a margin of 4.4% to 5.9%.

Dr. Masoomi reported having no financial conflicts regarding his study.
 

[email protected]
 

There were 54 new cases of pregnant women with laboratory evidence of Zika virus in the 50 states and the District of Columbia reported during the week ending Oct. 20 – the largest weekly increase in a month, according to the Centers for Disease Control and Prevention.

The number of cases reported in the U.S. territories, 100, was lower for the second week in a row, however, so the U.S. total for the week was a fairly average 154. The total number of pregnant women with laboratory evidence of Zika virus infection is now 2,980 for the year: 953 in the states/D.C. and 2,027 in the territories, the CDC reported.

[email protected]

There were 54 new cases of pregnant women with laboratory evidence of Zika virus in the 50 states and the District of Columbia reported during the week ending Oct. 20 – the largest weekly increase in a month, according to the Centers for Disease Control and Prevention.

The number of cases reported in the U.S. territories, 100, was lower for the second week in a row, however, so the U.S. total for the week was a fairly average 154. The total number of pregnant women with laboratory evidence of Zika virus infection is now 2,980 for the year: 953 in the states/D.C. and 2,027 in the territories, the CDC reported.

[email protected]

There were 54 new cases of pregnant women with laboratory evidence of Zika virus in the 50 states and the District of Columbia reported during the week ending Oct. 20 – the largest weekly increase in a month, according to the Centers for Disease Control and Prevention.

The number of cases reported in the U.S. territories, 100, was lower for the second week in a row, however, so the U.S. total for the week was a fairly average 154. The total number of pregnant women with laboratory evidence of Zika virus infection is now 2,980 for the year: 953 in the states/D.C. and 2,027 in the territories, the CDC reported.

[email protected]

The U.S. Preventive Services Task Force (USPSTF) has issued a B-level recommendation for interventions given during pregnancy and after birth to support breastfeeding.

The Task Force cites “adequate” evidence that breastfeeding provides substantial health benefits for children and moderate health benefits for women. While they found evidence to support individual-level interventions, such as education and psychosocial support, system-level interventions were not shown to be effective. The recommendation appears online in JAMA (2016 Oct 25;316[16]:1688-93).

The recommendation updates a previous one issued in 2008, in which the USPSTF also recommended breastfeeding support interventions with a grade of B. The new recommendation is based on a review of 43 studies of individual-level primary care interventions in support of breastfeeding, and nine system-level interventions. The authors evaluated the available evidence on breastfeeding initiation, duration, and exclusivity, as well as breastfeeding’s effects on child and maternal health outcomes. They determined that support from a professional lactation consultant or a peer group was effective in producing any or exclusive breastfeeding, while systemwide interventions, such as the World Health Organization’s Baby-Friendly Hospital Initiative offered inconsistent benefits. The evidence review was also published in JAMA (2016;316[16]:1694-1705).

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[email protected]

On Twitter @whitneymcknight

The U.S. Preventive Services Task Force (USPSTF) has issued a B-level recommendation for interventions given during pregnancy and after birth to support breastfeeding.

The Task Force cites “adequate” evidence that breastfeeding provides substantial health benefits for children and moderate health benefits for women. While they found evidence to support individual-level interventions, such as education and psychosocial support, system-level interventions were not shown to be effective. The recommendation appears online in JAMA (2016 Oct 25;316[16]:1688-93).

The recommendation updates a previous one issued in 2008, in which the USPSTF also recommended breastfeeding support interventions with a grade of B. The new recommendation is based on a review of 43 studies of individual-level primary care interventions in support of breastfeeding, and nine system-level interventions. The authors evaluated the available evidence on breastfeeding initiation, duration, and exclusivity, as well as breastfeeding’s effects on child and maternal health outcomes. They determined that support from a professional lactation consultant or a peer group was effective in producing any or exclusive breastfeeding, while systemwide interventions, such as the World Health Organization’s Baby-Friendly Hospital Initiative offered inconsistent benefits. The evidence review was also published in JAMA (2016;316[16]:1694-1705).

Thinkstock

[email protected]

On Twitter @whitneymcknight

The U.S. Preventive Services Task Force (USPSTF) has issued a B-level recommendation for interventions given during pregnancy and after birth to support breastfeeding.

The Task Force cites “adequate” evidence that breastfeeding provides substantial health benefits for children and moderate health benefits for women. While they found evidence to support individual-level interventions, such as education and psychosocial support, system-level interventions were not shown to be effective. The recommendation appears online in JAMA (2016 Oct 25;316[16]:1688-93).

The recommendation updates a previous one issued in 2008, in which the USPSTF also recommended breastfeeding support interventions with a grade of B. The new recommendation is based on a review of 43 studies of individual-level primary care interventions in support of breastfeeding, and nine system-level interventions. The authors evaluated the available evidence on breastfeeding initiation, duration, and exclusivity, as well as breastfeeding’s effects on child and maternal health outcomes. They determined that support from a professional lactation consultant or a peer group was effective in producing any or exclusive breastfeeding, while systemwide interventions, such as the World Health Organization’s Baby-Friendly Hospital Initiative offered inconsistent benefits. The evidence review was also published in JAMA (2016;316[16]:1694-1705).

Thinkstock

[email protected]

On Twitter @whitneymcknight

The total number of pregnant women in the United States and its territories with laboratory evidence of Zika infection rose by 142 for the week ending Oct. 13 – the smallest increase since early September, according to the Centers for Disease Control and Prevention.

There were 121 new cases of Zika virus infection in pregnant women reported in the U.S. territories and 21 new cases in the states and the District of Columbia, bringing the corresponding totals for the year to 1,927 cases in the territories and 899 in the states/D.C. – a total of 2,826 pregnant women with Zika in the United States, the CDC reported Oct. 20.

[email protected]

The total number of pregnant women in the United States and its territories with laboratory evidence of Zika infection rose by 142 for the week ending Oct. 13 – the smallest increase since early September, according to the Centers for Disease Control and Prevention.

There were 121 new cases of Zika virus infection in pregnant women reported in the U.S. territories and 21 new cases in the states and the District of Columbia, bringing the corresponding totals for the year to 1,927 cases in the territories and 899 in the states/D.C. – a total of 2,826 pregnant women with Zika in the United States, the CDC reported Oct. 20.

[email protected]

The total number of pregnant women in the United States and its territories with laboratory evidence of Zika infection rose by 142 for the week ending Oct. 13 – the smallest increase since early September, according to the Centers for Disease Control and Prevention.

There were 121 new cases of Zika virus infection in pregnant women reported in the U.S. territories and 21 new cases in the states and the District of Columbia, bringing the corresponding totals for the year to 1,927 cases in the territories and 899 in the states/D.C. – a total of 2,826 pregnant women with Zika in the United States, the CDC reported Oct. 20.

[email protected]