From Medscape Medical News
Laurie Barclay, MD
September 10, 2010 — Breast-feeding for less than 1 month is linked to an increased risk for type 2 diabetes, according to the results of a study reported in the September issue of the American Journal of Medicine.
"We have seen dramatic increases in the prevalence of type 2 diabetes over the last century," said lead author Eleanor Bimla Schwarz, MD, MS, from the University of Pittsburgh in Pittsburgh, Pennsylvania, in a news release.
"Diet and exercise are widely known to impact the risk of type 2 diabetes, but few people realize that breastfeeding also reduces mothers' risk of developing the disease later in life by decreasing maternal belly fat."
The goal of the study was to examine the associations between duration, exclusivity, and consistency of lactation with the risk for type 2 diabetes in a well-studied cohort of women, aged 40 to 78 years, representative of the overall population.
This cohort consisted of 2233 female members of Kaiser, a large, integrated healthcare delivery organization in California, who were enrolled in the Reproductive Risk factors for Incontinence Study at Kaiser (RRISK), between 2003 and 2008.
The investigators controlled for age, parity, race, education, hysterectomy, physical activity, tobacco and alcohol use, family history of diabetes, and body mass index using multivariable logistic regression.
Of the study sample, 1828 were mothers; more than half (56%) had breast-fed an infant for at least 1 month. Compared with nulliparous women, those who consistently breast-fed all of their children for at least 1 month had a similar adjusted risk for type 2 diabetes (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.56 - 1.81), whereas mothers who had never breast-fed an infant had greater risk (OR, 1.92; 95% CI, 1.14 - 3.27). Compared with mothers who exclusively breast-fed for 1 to 3 months, those who never exclusively breast-fed were more likely to have gone on to have type 2 diabetes (OR, 1.52; 95% CI, 1.11 - 2.10).
"Risk of type 2 diabetes increases when term pregnancy is followed by <1 month of lactation, independent of physical activity and body mass index in later life," the study authors write. "Mothers should be encouraged to exclusively breast-feed all of their infants for at least 1 month."
Limitations of this study include observational design subject to residual confounding, recall or reporting bias leading to possible misclassification of women's lactation history, and lack of data on women's level of obesity or insulin resistance at the time of pregnancy.
"Our study provides another good reason to encourage women to breastfeed their infants, at least for the infant's first month of life," said Dr. Schwarz. "Clinicians need to consider women's pregnancy and lactation history when advising women about their risk for developing type 2 diabetes."
The National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Child Health and Development supported this study. The study authors have disclosed no relevant financial relationships.
Am J Med. 2010;123:863.e1-863.e6.
Sunday, September 12, 2010
Psychological Violence During Pregnancy Linked to Postnatal Depression
From Medscape Medical News
Fran Lowry
September 9, 2010 — Psychological violence during pregnancy by an intimate partner is strongly linked to postnatal depression, independent of physical or sexual violence.
This finding, published online September 6 in The Lancet, has important implications for prevention policies because most focus only on physical violence, Ana Bernarda Ludermir, MD, from Universidade Federal de Pernambuco, Recife, Brazil, and her colleagues conclude.
"Our results have both clinical and public health implications," Dr. Ludermir told Medscape Medical News. "Interventions for victims of partner violence have included a variety of approaches, such as the use of women's empowerment protocols, referral to shelters, transitional housing, legal advice, and psychological support. However, there is still insufficient evidence on the effectiveness of such interventions in improving psychosocial health."
Most Common Form of Partner Violence
In this prospective cohort study, which was undertaken between July 2005 and December 2006 in Recife, northeastern Brazil, Dr. Ludermir and her team enrolled pregnant women aged 18 to 49 years who were in their third trimester and who were attending primary healthcare clinics.
The women were interviewed during pregnancy and after delivery. The antenatal interview was done most often at the healthcare clinic, although some were done at home at the woman's request. Most of the follow-up interviews were done at home at a median of 8.1 months (interquartile range, 5.2 – 10.2 months) after the antenatal interview.
The investigators used the Edinburgh Postnatal Depression Scale (EPDS) to assess postnatal depressive symptoms. The form of partner violence in pregnancy was assessed with a validated questionnaire.
Of the 1045 women who were included in the final analysis, 270 women (25.8%; 95% confidence interval [CI], 23.2 – 28.6) had postnatal depression.
The most common form of partner violence was psychological (28.1%; 95% CI, 4 – 31.0).
Table 1. Forms of Psychological Violence Reported by Respondents
Type of Violence No. of Women % of Women (95% CI)
Insulted you or made you feel bad about yourself 247 23.6 (21.1 – 26.3)
Belittled you or humiliated you in front of others 127 12.2 (10.2 – 14.3)
Done things to scare or intimidate you on purpose 84 8.0 (6.5 – 9.9)
Threatened to hurt you or someone you care about 81 7.8 (6.2 – 9.5)
CI = confidence interval
The frequency of psychological violence during pregnancy was positively associated with postnatal depression. Although this association was reduced after adjustment, women reporting the highest frequency of psychological violence were more than twice as likely to have postnatal depression, even after adjustment, than those who had not experienced psychological violence, the researchers report.
Psychological violence was more common than physical or sexual violence, and this is in keeping with findings from previous studies, Dr. Ludermir said. "We need to understand more about why psychological violence occurs and develop interventions to prevent it from occurring, as well as treatments to reduce its impact."
She added that prenatal care could provide an opportunity to identify women at risk. "Currently, we place emphasis, and rightly so, on preventing and treating physical violence, but psychological violence is also a serious problem, as this study shows. Interventions that might prevent psychological violence or help treat its consequences could reduce the substantial burden of postnatal depression that affects mothers, children, and the healthcare system as a whole.”
Dr. Ludermir noted that her study had some important limitations, including the use of the EPDS questionnaire to ascertain postnatal depression. "EPDS is a symptom questionnaire, and there is much debate about the appropriate criteria for defining depression and its relationship with the need for treatment," she noted. "Also, partner violence is more common in women with limited schooling and who live in poverty, so the high frequency of partner violence could reflect the characteristics of the community we studied. It is possible that violence was actually underreported because of the associated stigma and shame."
Screening Not Currently Recommended, But Should Be
In an accompanying editorial, Rachel Jewkes, MD, from the Medical Research Council, Pretoria, South Africa, writes that emotional abuse probably has a greater importance in women's mental ill-health than originally thought "and should therefore receive more attention from researchers and health services."
She adds that the high prevalence of postnatal depression reported in the study "shows the great need for improved mental healthcare."
Finally, Dr. Jewkes points out that emotional abuse screening in pregnant women is not currently recommended by official bodies, such as the American Congress of Obstetricians and Gynecologists, but suggests that it should be.
There is mounting evidence, she writes, "that guidelines should include questions about emotional abuse, as well as physical and sexual abuse. Prevention of all forms of intimate partner violence is very important for improving women's health, particularly their mental health."
Lancet. Published online September 6, 2010.
Fran Lowry
September 9, 2010 — Psychological violence during pregnancy by an intimate partner is strongly linked to postnatal depression, independent of physical or sexual violence.
This finding, published online September 6 in The Lancet, has important implications for prevention policies because most focus only on physical violence, Ana Bernarda Ludermir, MD, from Universidade Federal de Pernambuco, Recife, Brazil, and her colleagues conclude.
"Our results have both clinical and public health implications," Dr. Ludermir told Medscape Medical News. "Interventions for victims of partner violence have included a variety of approaches, such as the use of women's empowerment protocols, referral to shelters, transitional housing, legal advice, and psychological support. However, there is still insufficient evidence on the effectiveness of such interventions in improving psychosocial health."
Most Common Form of Partner Violence
In this prospective cohort study, which was undertaken between July 2005 and December 2006 in Recife, northeastern Brazil, Dr. Ludermir and her team enrolled pregnant women aged 18 to 49 years who were in their third trimester and who were attending primary healthcare clinics.
The women were interviewed during pregnancy and after delivery. The antenatal interview was done most often at the healthcare clinic, although some were done at home at the woman's request. Most of the follow-up interviews were done at home at a median of 8.1 months (interquartile range, 5.2 – 10.2 months) after the antenatal interview.
The investigators used the Edinburgh Postnatal Depression Scale (EPDS) to assess postnatal depressive symptoms. The form of partner violence in pregnancy was assessed with a validated questionnaire.
Of the 1045 women who were included in the final analysis, 270 women (25.8%; 95% confidence interval [CI], 23.2 – 28.6) had postnatal depression.
The most common form of partner violence was psychological (28.1%; 95% CI, 4 – 31.0).
Table 1. Forms of Psychological Violence Reported by Respondents
Type of Violence No. of Women % of Women (95% CI)
Insulted you or made you feel bad about yourself 247 23.6 (21.1 – 26.3)
Belittled you or humiliated you in front of others 127 12.2 (10.2 – 14.3)
Done things to scare or intimidate you on purpose 84 8.0 (6.5 – 9.9)
Threatened to hurt you or someone you care about 81 7.8 (6.2 – 9.5)
CI = confidence interval
The frequency of psychological violence during pregnancy was positively associated with postnatal depression. Although this association was reduced after adjustment, women reporting the highest frequency of psychological violence were more than twice as likely to have postnatal depression, even after adjustment, than those who had not experienced psychological violence, the researchers report.
Psychological violence was more common than physical or sexual violence, and this is in keeping with findings from previous studies, Dr. Ludermir said. "We need to understand more about why psychological violence occurs and develop interventions to prevent it from occurring, as well as treatments to reduce its impact."
She added that prenatal care could provide an opportunity to identify women at risk. "Currently, we place emphasis, and rightly so, on preventing and treating physical violence, but psychological violence is also a serious problem, as this study shows. Interventions that might prevent psychological violence or help treat its consequences could reduce the substantial burden of postnatal depression that affects mothers, children, and the healthcare system as a whole.”
Dr. Ludermir noted that her study had some important limitations, including the use of the EPDS questionnaire to ascertain postnatal depression. "EPDS is a symptom questionnaire, and there is much debate about the appropriate criteria for defining depression and its relationship with the need for treatment," she noted. "Also, partner violence is more common in women with limited schooling and who live in poverty, so the high frequency of partner violence could reflect the characteristics of the community we studied. It is possible that violence was actually underreported because of the associated stigma and shame."
Screening Not Currently Recommended, But Should Be
In an accompanying editorial, Rachel Jewkes, MD, from the Medical Research Council, Pretoria, South Africa, writes that emotional abuse probably has a greater importance in women's mental ill-health than originally thought "and should therefore receive more attention from researchers and health services."
She adds that the high prevalence of postnatal depression reported in the study "shows the great need for improved mental healthcare."
Finally, Dr. Jewkes points out that emotional abuse screening in pregnant women is not currently recommended by official bodies, such as the American Congress of Obstetricians and Gynecologists, but suggests that it should be.
There is mounting evidence, she writes, "that guidelines should include questions about emotional abuse, as well as physical and sexual abuse. Prevention of all forms of intimate partner violence is very important for improving women's health, particularly their mental health."
Lancet. Published online September 6, 2010.
Both Mothers and Fathers at Risk for Depression in First Year After Child's Birth
From Medscape Medical News
Deborah Brauser
September 9, 2010 — Although both mothers and fathers are at risk of experiencing incidences of depression by their child's 12th birthday, the highest risk is within their first year post partum, according to researchers from the United Kingdom.
"The main takeaway message for clinicians is that both parents are at risk of developing depression soon after the birth of the baby," Irwin Nazareth, PhD, MBBS, director of the Medical Research Council (MRC) General Practice Research Framework and professor of primary care at University College London, United Kingdom, told Medscape Medical News.
He noted that the UK National Institute for Clinical Excellence has recommended regular screenings for mothers for depression through the antenatal and postnatal period. However, "this should be extended to fathers so that the family is considered as a whole unit. Special attention must also be paid to young parents who have had a past history of depression and those who are socioeconomically deprived."
The study was published online September 6 in the Archives of Pediatrics and Adolescent Medicine.
Paucity of Paternal Depression Research
Although past research has shown that parental depression is associated with adverse outcomes for their children in behavior, development, and cognition, most have focused only on maternal depression, write the study authors.
"The effect of a new baby on the father has received little attention," said Dr. Nazareth. "This study was hence done to ascertain the extent of the problem and to identify those groups of fathers who were at particular risk of depression. Moreover, we believe that simultaneously studying the effect of the birth of the baby both on fathers and mothers provides us a much fuller picture of the wider effects of birth on the family unit."
He also noted that his investigative group at the MRC "has always had a special interest in mental health problems in primary care" and that this particular study resulted from 8 years of research work undertaken by lead study author Shreya Dave, PhD, MSc, BSc.
For this study, the investigators evaluated data from between 1993 and 2007 from The Health Improvement Network database, which includes information on almost 5 million primary care patients from the United Kingdom. They then identified a cohort of 86,957 mother-father-child units.
Patient records and read code entries were also assessed for unipolar depression, antidepressant prescriptions, and sociodemographic information, including follow-up data up to the child's 12th birthday.
Both Parents Experience Depression
The investigators found that 19,286 of the mothers and 8012 of the fathers had an episode of depression during the period between their child's birth up to the age of 12 years.
Of these moms, 77% experienced 1 episode of depression, 18% had 2 episodes, and 5% had 3 or more episodes. Of the depressed fathers, 83% had 1 episode, 14% had 2, and 3% had 3 or more.
The overall incidences of depression during this same period for mothers were 7.53 per 100 person-years vs 2.69 per 100 person-years for fathers.
However, the depression rates were highest for both parents during the first year after the child's birth at 13.93 per 100 person-years for mothers and 3.56 for fathers.
"What was striking in this study was the extent of the depression in fathers vs mothers and how the first year of the birth of the baby was in particular a risk period for both parents," said Dr. Nazareth.
The researchers write that in addition to such things as poor parental sleep and change in responsibilities, the high rates of depression found during the first year post partum may be partly due "to a resumption of antidepressant use following a break during pregnancy and breastfeeding."
Finally, both mothers and fathers who were between the age of 15 and 24 years at the birth of their child were significantly more likely to be depressed than parents older than 25 years, as were those who had a history of depression and were in the highest quintile for deprivation.
Dr. Nazareth noted that this link was particularly interesting. "This informs general practitioners on the need to consider closer monitoring of these at risk groups from early pregnancy and soon after."
In addition, the study authors write that future research should examine other factors potentially associated with parental depression, such as the couple's relationship quality and stressful events, as well as the effects of this depression on the child's health and development.
Awareness, Screenings Needed
"This was an interesting study that addresses an important issue that hasn't been clearly resolved in research and, in fact, has been the subject of some debate over the past 10 years," James Paulson, PhD, associate professor and clinical psychologist in the Department of Pediatrics at Eastern Virginia Medical School at Children's Hospital of the King's Daughters in Norfolk, told Medscape Medical News, when contacted for comment.
"That issue is depression in mothers during the first year post partum, which clearly has negative connotations for the family," he added. "This study works strongly in favor of the argument that depression is something that's happening in postpartum — not only in mothers but also in fathers — more than at any other time point during parenthood."
Dr. Paulson, who was not involved with this study, recently conducted a meta-analysis looking specifically at prenatal and postpartum depression in fathers.
"I thought it was great that these investigators included paternal depression in their methodology, which I think we'll find in more and more studies. This article really underscores the point that depression is happening more often in fathers."
He noted that, due to continuing stigma, men often do not admit to having depression and often do not seek help. "I also think they're less likely to recognize depression as depression when they experience it. So I think increasing awareness will really help ring that bell for more people."
Although Dr. Paulson had no concerns with this study, he said that he would have liked to have seen more about what was going on within the family and not just an exclusive focus on the individual parents.
"Turning the focus more toward the family is very important for moving this field forward, and it gives us a lot more traction in terms of what we can do for catching depression, for intervening, and for minimizing its effect on the family and the child," he explained.
"For clinicians, I think the number 1 takeaway is that when working with expecting new parents — and I think we need to start thinking about this during the pregnancy — realize that this a situation where depression is a much higher risk than it is at any other time point," concluded Dr. Paulson. "Take whatever steps are needed to screen for depression in both mothers and fathers because clearly this is a risk that occurs in both parents."
This study was funded in part through a grant from the MRC. The study authors and Dr. Paulson have disclosed no relevant financial relationships.
Arch Pediatr Adolesc Med. Published online September 6, 2010.
Deborah Brauser
September 9, 2010 — Although both mothers and fathers are at risk of experiencing incidences of depression by their child's 12th birthday, the highest risk is within their first year post partum, according to researchers from the United Kingdom.
"The main takeaway message for clinicians is that both parents are at risk of developing depression soon after the birth of the baby," Irwin Nazareth, PhD, MBBS, director of the Medical Research Council (MRC) General Practice Research Framework and professor of primary care at University College London, United Kingdom, told Medscape Medical News.
He noted that the UK National Institute for Clinical Excellence has recommended regular screenings for mothers for depression through the antenatal and postnatal period. However, "this should be extended to fathers so that the family is considered as a whole unit. Special attention must also be paid to young parents who have had a past history of depression and those who are socioeconomically deprived."
The study was published online September 6 in the Archives of Pediatrics and Adolescent Medicine.
Paucity of Paternal Depression Research
Although past research has shown that parental depression is associated with adverse outcomes for their children in behavior, development, and cognition, most have focused only on maternal depression, write the study authors.
"The effect of a new baby on the father has received little attention," said Dr. Nazareth. "This study was hence done to ascertain the extent of the problem and to identify those groups of fathers who were at particular risk of depression. Moreover, we believe that simultaneously studying the effect of the birth of the baby both on fathers and mothers provides us a much fuller picture of the wider effects of birth on the family unit."
He also noted that his investigative group at the MRC "has always had a special interest in mental health problems in primary care" and that this particular study resulted from 8 years of research work undertaken by lead study author Shreya Dave, PhD, MSc, BSc.
For this study, the investigators evaluated data from between 1993 and 2007 from The Health Improvement Network database, which includes information on almost 5 million primary care patients from the United Kingdom. They then identified a cohort of 86,957 mother-father-child units.
Patient records and read code entries were also assessed for unipolar depression, antidepressant prescriptions, and sociodemographic information, including follow-up data up to the child's 12th birthday.
Both Parents Experience Depression
The investigators found that 19,286 of the mothers and 8012 of the fathers had an episode of depression during the period between their child's birth up to the age of 12 years.
Of these moms, 77% experienced 1 episode of depression, 18% had 2 episodes, and 5% had 3 or more episodes. Of the depressed fathers, 83% had 1 episode, 14% had 2, and 3% had 3 or more.
The overall incidences of depression during this same period for mothers were 7.53 per 100 person-years vs 2.69 per 100 person-years for fathers.
However, the depression rates were highest for both parents during the first year after the child's birth at 13.93 per 100 person-years for mothers and 3.56 for fathers.
"What was striking in this study was the extent of the depression in fathers vs mothers and how the first year of the birth of the baby was in particular a risk period for both parents," said Dr. Nazareth.
The researchers write that in addition to such things as poor parental sleep and change in responsibilities, the high rates of depression found during the first year post partum may be partly due "to a resumption of antidepressant use following a break during pregnancy and breastfeeding."
Finally, both mothers and fathers who were between the age of 15 and 24 years at the birth of their child were significantly more likely to be depressed than parents older than 25 years, as were those who had a history of depression and were in the highest quintile for deprivation.
Dr. Nazareth noted that this link was particularly interesting. "This informs general practitioners on the need to consider closer monitoring of these at risk groups from early pregnancy and soon after."
In addition, the study authors write that future research should examine other factors potentially associated with parental depression, such as the couple's relationship quality and stressful events, as well as the effects of this depression on the child's health and development.
Awareness, Screenings Needed
"This was an interesting study that addresses an important issue that hasn't been clearly resolved in research and, in fact, has been the subject of some debate over the past 10 years," James Paulson, PhD, associate professor and clinical psychologist in the Department of Pediatrics at Eastern Virginia Medical School at Children's Hospital of the King's Daughters in Norfolk, told Medscape Medical News, when contacted for comment.
"That issue is depression in mothers during the first year post partum, which clearly has negative connotations for the family," he added. "This study works strongly in favor of the argument that depression is something that's happening in postpartum — not only in mothers but also in fathers — more than at any other time point during parenthood."
Dr. Paulson, who was not involved with this study, recently conducted a meta-analysis looking specifically at prenatal and postpartum depression in fathers.
"I thought it was great that these investigators included paternal depression in their methodology, which I think we'll find in more and more studies. This article really underscores the point that depression is happening more often in fathers."
He noted that, due to continuing stigma, men often do not admit to having depression and often do not seek help. "I also think they're less likely to recognize depression as depression when they experience it. So I think increasing awareness will really help ring that bell for more people."
Although Dr. Paulson had no concerns with this study, he said that he would have liked to have seen more about what was going on within the family and not just an exclusive focus on the individual parents.
"Turning the focus more toward the family is very important for moving this field forward, and it gives us a lot more traction in terms of what we can do for catching depression, for intervening, and for minimizing its effect on the family and the child," he explained.
"For clinicians, I think the number 1 takeaway is that when working with expecting new parents — and I think we need to start thinking about this during the pregnancy — realize that this a situation where depression is a much higher risk than it is at any other time point," concluded Dr. Paulson. "Take whatever steps are needed to screen for depression in both mothers and fathers because clearly this is a risk that occurs in both parents."
This study was funded in part through a grant from the MRC. The study authors and Dr. Paulson have disclosed no relevant financial relationships.
Arch Pediatr Adolesc Med. Published online September 6, 2010.
Tuesday, September 7, 2010
Surgery or Chemo First in Advanced Ovarian Cancer? New Data Fuel Debate
From Medscape Medical News
Janis C. Kelly
September 6, 2010 — Primary debulking surgery before adjuvant chemotherapy is the standard of care for patients with advanced ovarian cancer, but new data from a multinational study suggest that patients with stage IIIC or IV disease might do as well with neoadjuvant chemotherapy followed by surgery.
Lead author Ignace Vergote, MD, PhD, from Leuven University Hospitals in Belgium, told Medscape Medical News that outcomes were essentially the same in terms of overall and progression-free survival, and suggested that the neoadjuvant approach might lower the risk for postoperative death, grade 3 or 4 hemorrhage, infection, and venous complications.
Dr. Vergote emphasized that this applies only to stage IIIC and IV patients. "Primary surgery should remain the treatment of choice in patients with earlier stages of ovarian cancer," he said.
The trial was a collaborative study by researchers from the European Organization for Research and Treatment of Cancer Gynaecological Cancer Group and the National Cancer Institute of Canada Clinical Trials Group, and included researchers in Belgium, Norway, Canada, Scotland, England, the Netherlands, Italy, and Spain.
In the September 2 issue of the New England Journal of Medicine, Dr. Vergote and colleagues report data from 632 patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma. Patients were randomized to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (interval debulking surgery).
The hazard ratio for death was 0.98 for neoadjuvant chemotherapy vs primary debulking. The hazard ratio for progressive disease was 1.01.
The strongest predictor of overall survival was the complete resection of all macroscopic disease in both the primary debulking and neoadjuvant chemotherapy groups.
Residual tumor was 10 mm or less (described as optimal debulking) in 41.6% of patients in the primary debulking group and in 80.6% of patients in the neoadjuvant chemotherapy group. However, data provided in the supplementary online appendix to the paper show that complete resection was achieved in fewer than half of the patients who had tumors 10 mm or less after primary debulking, but in two thirds of those who had tumors 10 mm or less after neoadjuvant chemotherapy.
Differences by Country
There were also striking differences in surgical completeness by country. Belgium accounted for the majority of patients in the study; there was no residual disease in 62.9% of Belgian patients treated with primary debulking and in 87.3% of those treated with neoadjuvant chemotherapy.
No other country approached these results with primary debulking. Rates for no residual disease ranged from 3.9% in the Netherlands to 11.1% in Canada.
Similarly, rates for no residual disease with neoadjuvant chemotherapy ranged from 27.7% in the Netherlands to 42.9% in the United Kingdom.
Median survival was 44.98 months in patients who had no residual disease after primary debulking surgery and 27.01 months in those after neoadjuvant chemotherapy. Five-year survival was 31.31% in patients with no residual disease after primary debulking surgery and 17.52% after neoadjuvant chemotherapy.
Interestingly, median and 5-year survival were both better in patients who had some residual tumor (1 to 10 mm) after primary debulking surgery (32.26 months and 23.47%, respectively) than in those who had no residual disease after neoadjuvant chemotherapy (27.01 months and 17.52%, respectively).
Complete resection of all macroscopic disease was the strongest predictor of survival.
Adverse Events Caveat
Dr. Vergote emphasized to Medscape Medical News that this trial consisted only of patients with extensive stage IIIC or IV disease, and the outcomes should not be compared with those in patients with stage IIIB or earlier-stage ovarian carcinoma. He also noted the importance of ruling out other primary tumors (especially of gastrointestinal origin) when selecting patients for neoadjuvant chemotherapy.
The researchers concluded that "neoadjuvant chemotherapy is not inferior to primary cytoreductive surgery for patients with stage IIIC or IV ovarian carcinoma. No significant advantages of neoadjuvant therapy or primary debulking surgery were observed with respect to survival, adverse effects, quality of life, or postoperative morbidity or mortality."
Dr. Vergote later explained that although the study design did not permit a statistically valid comparison of adverse effects, the lower incidence of postoperative death, grade 3 or 4 hemorrhage, infection, and venous complications is clinically important, as is the greatly reduced operative time required after neoadjuvant chemotherapy.
Dr. Vergote said that the data also suggest that patients with very small metastases seem to do better with primary debulking surgery, whereas those with larger tumors seem to do better with neoadjuvant chemotherapy and interval debulking.
"My advice is to estimate how difficult surgery will be. For example, if the patient is 75 years old and [computed tomography] scan plus laparoscopy show extensive tumors that will require a lot of bowel resection, I would consider neoadjuvant chemotherapy rather than primary surgery," Dr. Vergote said. "It is important to be aggressive, regardless of the approach. The goal is no residual tumor, not 'less than 10 mm' residual tumor."
Operative time is another consideration. Dr. Vergote said that primary surgery in very extensive stage III or IV ovarian cancer might require 7 hours, whereas surgery for a similar patient after neoadjuvant therapy might require only 4.5 hours.
American Expert Has Concerns
Dr. Vergote suggested that the lower complete resection rates in this study, compared with data from major American cancer centers, might reflect differences in patient population, in that American series might have included patients with less extensive disease.
Robert E. Bristow, MD, director of gynecologic oncology at the University of California Irvine Medical Center in Orange, who reviewed the study for Medscape Medical News, was not completely convinced.
"The researchers are to be congratulated for completing this big, multi-institution study," Dr. Bristow said. "However, the conclusions challenge the conventional wisdom on treatment of advanced ovarian cancer. Nearly all other studies show that patients who undergo primary debulking surgery do better."
Dr. Bristow expressed concerns about the completeness of surgery in this study. He said that in the United States, generally, optimal debulking rates (less than 10 mm residual disease) are above 70% (compared with 41% in this study), and two thirds of those are complete, with no residual disease (compared with 19.2% in this study) .
"It may be that in some of the institutions in this study, the primary debulking surgery performed was not significantly different from no surgery at all," Dr. Bristow said. "This is an important study, but results are not necessarily transferable to surgical oncology clinical practice. I would like to see it replicated with participating hospitals where the optimal debulking rate is 75% or better and two thirds of those patients have no residual disease."
Dr. Vergote and Dr. Bristow have disclosed no relevant financial relationships.
Janis C. Kelly
September 6, 2010 — Primary debulking surgery before adjuvant chemotherapy is the standard of care for patients with advanced ovarian cancer, but new data from a multinational study suggest that patients with stage IIIC or IV disease might do as well with neoadjuvant chemotherapy followed by surgery.
Lead author Ignace Vergote, MD, PhD, from Leuven University Hospitals in Belgium, told Medscape Medical News that outcomes were essentially the same in terms of overall and progression-free survival, and suggested that the neoadjuvant approach might lower the risk for postoperative death, grade 3 or 4 hemorrhage, infection, and venous complications.
Dr. Vergote emphasized that this applies only to stage IIIC and IV patients. "Primary surgery should remain the treatment of choice in patients with earlier stages of ovarian cancer," he said.
The trial was a collaborative study by researchers from the European Organization for Research and Treatment of Cancer Gynaecological Cancer Group and the National Cancer Institute of Canada Clinical Trials Group, and included researchers in Belgium, Norway, Canada, Scotland, England, the Netherlands, Italy, and Spain.
In the September 2 issue of the New England Journal of Medicine, Dr. Vergote and colleagues report data from 632 patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma. Patients were randomized to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (interval debulking surgery).
The hazard ratio for death was 0.98 for neoadjuvant chemotherapy vs primary debulking. The hazard ratio for progressive disease was 1.01.
The strongest predictor of overall survival was the complete resection of all macroscopic disease in both the primary debulking and neoadjuvant chemotherapy groups.
Residual tumor was 10 mm or less (described as optimal debulking) in 41.6% of patients in the primary debulking group and in 80.6% of patients in the neoadjuvant chemotherapy group. However, data provided in the supplementary online appendix to the paper show that complete resection was achieved in fewer than half of the patients who had tumors 10 mm or less after primary debulking, but in two thirds of those who had tumors 10 mm or less after neoadjuvant chemotherapy.
Differences by Country
There were also striking differences in surgical completeness by country. Belgium accounted for the majority of patients in the study; there was no residual disease in 62.9% of Belgian patients treated with primary debulking and in 87.3% of those treated with neoadjuvant chemotherapy.
No other country approached these results with primary debulking. Rates for no residual disease ranged from 3.9% in the Netherlands to 11.1% in Canada.
Similarly, rates for no residual disease with neoadjuvant chemotherapy ranged from 27.7% in the Netherlands to 42.9% in the United Kingdom.
Median survival was 44.98 months in patients who had no residual disease after primary debulking surgery and 27.01 months in those after neoadjuvant chemotherapy. Five-year survival was 31.31% in patients with no residual disease after primary debulking surgery and 17.52% after neoadjuvant chemotherapy.
Interestingly, median and 5-year survival were both better in patients who had some residual tumor (1 to 10 mm) after primary debulking surgery (32.26 months and 23.47%, respectively) than in those who had no residual disease after neoadjuvant chemotherapy (27.01 months and 17.52%, respectively).
Complete resection of all macroscopic disease was the strongest predictor of survival.
Adverse Events Caveat
Dr. Vergote emphasized to Medscape Medical News that this trial consisted only of patients with extensive stage IIIC or IV disease, and the outcomes should not be compared with those in patients with stage IIIB or earlier-stage ovarian carcinoma. He also noted the importance of ruling out other primary tumors (especially of gastrointestinal origin) when selecting patients for neoadjuvant chemotherapy.
The researchers concluded that "neoadjuvant chemotherapy is not inferior to primary cytoreductive surgery for patients with stage IIIC or IV ovarian carcinoma. No significant advantages of neoadjuvant therapy or primary debulking surgery were observed with respect to survival, adverse effects, quality of life, or postoperative morbidity or mortality."
Dr. Vergote later explained that although the study design did not permit a statistically valid comparison of adverse effects, the lower incidence of postoperative death, grade 3 or 4 hemorrhage, infection, and venous complications is clinically important, as is the greatly reduced operative time required after neoadjuvant chemotherapy.
Dr. Vergote said that the data also suggest that patients with very small metastases seem to do better with primary debulking surgery, whereas those with larger tumors seem to do better with neoadjuvant chemotherapy and interval debulking.
"My advice is to estimate how difficult surgery will be. For example, if the patient is 75 years old and [computed tomography] scan plus laparoscopy show extensive tumors that will require a lot of bowel resection, I would consider neoadjuvant chemotherapy rather than primary surgery," Dr. Vergote said. "It is important to be aggressive, regardless of the approach. The goal is no residual tumor, not 'less than 10 mm' residual tumor."
Operative time is another consideration. Dr. Vergote said that primary surgery in very extensive stage III or IV ovarian cancer might require 7 hours, whereas surgery for a similar patient after neoadjuvant therapy might require only 4.5 hours.
American Expert Has Concerns
Dr. Vergote suggested that the lower complete resection rates in this study, compared with data from major American cancer centers, might reflect differences in patient population, in that American series might have included patients with less extensive disease.
Robert E. Bristow, MD, director of gynecologic oncology at the University of California Irvine Medical Center in Orange, who reviewed the study for Medscape Medical News, was not completely convinced.
"The researchers are to be congratulated for completing this big, multi-institution study," Dr. Bristow said. "However, the conclusions challenge the conventional wisdom on treatment of advanced ovarian cancer. Nearly all other studies show that patients who undergo primary debulking surgery do better."
Dr. Bristow expressed concerns about the completeness of surgery in this study. He said that in the United States, generally, optimal debulking rates (less than 10 mm residual disease) are above 70% (compared with 41% in this study), and two thirds of those are complete, with no residual disease (compared with 19.2% in this study) .
"It may be that in some of the institutions in this study, the primary debulking surgery performed was not significantly different from no surgery at all," Dr. Bristow said. "This is an important study, but results are not necessarily transferable to surgical oncology clinical practice. I would like to see it replicated with participating hospitals where the optimal debulking rate is 75% or better and two thirds of those patients have no residual disease."
Dr. Vergote and Dr. Bristow have disclosed no relevant financial relationships.
Monday, September 6, 2010
Acyclovir, Valacyclovir in First Trimester Not Linked to Major Birth Defects
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD
August 25, 2010 — Exposure to acyclovir or valacyclovir in the first trimester of pregnancy is not associated with an increased risk for major birth defects, according to the results of a large, population-based, historical cohort study reported in the August 25 issue of the Journal of the American Medical Association.
"Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir," write Björn Pasternak, MD, PhD, and Anders Hviid, MSc, DrMedSci, from Statens Serum Institut in Copenhagen, Denmark. "Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented."
The goal of the study was to examine associations between use of acyclovir, valacyclovir, and famciclovir during the first trimester of pregnancy and the risk for major birth defects, using a cohort of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Infants diagnosed with chromosomal abnormalities, genetic syndromes, birth defect syndromes of known cause, or congenital virus infections were excluded.
Individual-level data regarding dispensed antiviral drugs, birth defect diagnoses categorized with use of a standardized classification scheme, and potential confounders were derived from nationwide registries. The primary study endpoint was prevalence odds ratios (PORs) of any major birth defect diagnosed before age 1 year within the first year of life, by antiviral drug exposure.
A major birth defect was diagnosed in 40 (2.2%) of 1804 infants whose mothers used acyclovir, valacyclovir, or famciclovir in the first trimester and in 19,920 infants (2.4%) whose mothers were not exposed to these drugs (adjusted POR, 0.89; 95% confidence interval [CI], 0.65 - 1.22).
In the specific antiviral drugs, 32 (2.0%) of 1561 infants with first-trimester exposure to acyclovir were diagnosed with a major birth defect (adjusted POR, 0.82; 95% CI, 0.57 - 1.17), as were 7 (3.1%) of 229 infants with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56 - 2.62). Only 26 infants were exposed to famciclovir during the first trimester; of these, 1 infant (3.8%) was diagnosed with a birth defect. Although no associations between antiviral drug exposure and 13 different subgroups of birth defects were apparent in exploratory analyses, there were only a small number of exposed cases in each subgroup.
"In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects," the study authors write.
Limitations of this study include inability to capture defects diagnosed after age 1 year, exclusion of abortions, incomplete evaluation of maternal comorbidity, and possible unmeasured confounding. A major limitation is that nonadherence to the dispensed drugs would obscure teratogenic effects, if present. Because there were few exposed cases in each subgroup of major defects, teratogenic effects cannot be ruled out with certainty.
"Our study... has immediate clinical implications and may support informed decisions on safety when prescribing antivirals for herpes infections in early pregnancy," the study authors conclude. "Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient.
Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding."
Editorial: Still Some Remaining Issues
In an accompanying editorial, James L. Mills, MD, MS, and Tonia C. Carter, PhD, from the National Institutes of Health in Bethesda, Maryland, note that because of limitations, this study does not answer the key question of whether acyclovir is a teratogen.
"[This study] is helpful in demonstrating the safety of acyclovir in pregnancy, but additional strategies must be developed to resolve the remaining issues," Drs. Mills and Carter write. "At a time when the health care system in the United States is facing enormous financial challenges, it is important not to ignore any sources of data that could answer critical medical questions."
The Danish Medical Research Council and the Lundbeck Foundation supported this study. The study authors have disclosed no relevant financial relationships. The editorial work was funded by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development.
JAMA. 2010;304:859-866, 905-906.
Clinical Context
Herpes simplex and herpes zoster infections are common. More than 1% of women acquire herpes simplex during the first trimester of pregnancy. Herpes simplex is often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Individuals who experience at least 6 recurrences of genital herpes within 1 year usually require episodic or long-term suppressive treatment. The US Food and Drug Administration has classified acyclovir, valacyclovir, and famciclovir as category B drugs in pregnancy. However, the safety of these antivirals when used in the first trimester of pregnancy has been insufficiently documented.
The aim of this study was to investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk for major birth defects.
News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD
August 25, 2010 — Exposure to acyclovir or valacyclovir in the first trimester of pregnancy is not associated with an increased risk for major birth defects, according to the results of a large, population-based, historical cohort study reported in the August 25 issue of the Journal of the American Medical Association.
"Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir," write Björn Pasternak, MD, PhD, and Anders Hviid, MSc, DrMedSci, from Statens Serum Institut in Copenhagen, Denmark. "Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented."
The goal of the study was to examine associations between use of acyclovir, valacyclovir, and famciclovir during the first trimester of pregnancy and the risk for major birth defects, using a cohort of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Infants diagnosed with chromosomal abnormalities, genetic syndromes, birth defect syndromes of known cause, or congenital virus infections were excluded.
Individual-level data regarding dispensed antiviral drugs, birth defect diagnoses categorized with use of a standardized classification scheme, and potential confounders were derived from nationwide registries. The primary study endpoint was prevalence odds ratios (PORs) of any major birth defect diagnosed before age 1 year within the first year of life, by antiviral drug exposure.
A major birth defect was diagnosed in 40 (2.2%) of 1804 infants whose mothers used acyclovir, valacyclovir, or famciclovir in the first trimester and in 19,920 infants (2.4%) whose mothers were not exposed to these drugs (adjusted POR, 0.89; 95% confidence interval [CI], 0.65 - 1.22).
In the specific antiviral drugs, 32 (2.0%) of 1561 infants with first-trimester exposure to acyclovir were diagnosed with a major birth defect (adjusted POR, 0.82; 95% CI, 0.57 - 1.17), as were 7 (3.1%) of 229 infants with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56 - 2.62). Only 26 infants were exposed to famciclovir during the first trimester; of these, 1 infant (3.8%) was diagnosed with a birth defect. Although no associations between antiviral drug exposure and 13 different subgroups of birth defects were apparent in exploratory analyses, there were only a small number of exposed cases in each subgroup.
"In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects," the study authors write.
Limitations of this study include inability to capture defects diagnosed after age 1 year, exclusion of abortions, incomplete evaluation of maternal comorbidity, and possible unmeasured confounding. A major limitation is that nonadherence to the dispensed drugs would obscure teratogenic effects, if present. Because there were few exposed cases in each subgroup of major defects, teratogenic effects cannot be ruled out with certainty.
"Our study... has immediate clinical implications and may support informed decisions on safety when prescribing antivirals for herpes infections in early pregnancy," the study authors conclude. "Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient.
Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding."
Editorial: Still Some Remaining Issues
In an accompanying editorial, James L. Mills, MD, MS, and Tonia C. Carter, PhD, from the National Institutes of Health in Bethesda, Maryland, note that because of limitations, this study does not answer the key question of whether acyclovir is a teratogen.
"[This study] is helpful in demonstrating the safety of acyclovir in pregnancy, but additional strategies must be developed to resolve the remaining issues," Drs. Mills and Carter write. "At a time when the health care system in the United States is facing enormous financial challenges, it is important not to ignore any sources of data that could answer critical medical questions."
The Danish Medical Research Council and the Lundbeck Foundation supported this study. The study authors have disclosed no relevant financial relationships. The editorial work was funded by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development.
JAMA. 2010;304:859-866, 905-906.
Clinical Context
Herpes simplex and herpes zoster infections are common. More than 1% of women acquire herpes simplex during the first trimester of pregnancy. Herpes simplex is often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Individuals who experience at least 6 recurrences of genital herpes within 1 year usually require episodic or long-term suppressive treatment. The US Food and Drug Administration has classified acyclovir, valacyclovir, and famciclovir as category B drugs in pregnancy. However, the safety of these antivirals when used in the first trimester of pregnancy has been insufficiently documented.
The aim of this study was to investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk for major birth defects.
Preemies Not Born in Specialized Level III Hospitals More Likely to Die
From Medscape Medical News
Fran Lowry
August 31, 2010 — Very low birth weight (VLBW) and very preterm (VPT) infants who are born in centers that are not specially equipped or experienced to manage such births have higher rates of neonatal and predischarge death compared with similar infants who are born in highly specialized level III hospitals.
The finding, from an analysis of data from previously published studies, appears in the September issue of the Journal of the American Medical Association.
"For more than 30 years, guidelines for perinatal regionalization have recommended that [VLBW] infants be born at highly specialized hospitals, most commonly designated as level III hospitals," write Sarah Marie Lasswell, MPH, from the Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues. "Despite these recommendations, some regions continue to have large percentages of VLBW infants born in lower-level hospitals."
The aim of this study was to evaluate the relationship between hospital level and care at birth and neonatal (the first 4 weeks after birth) and predischarge mortality for VLBW infants weighing 1500 g (53 ounces) or less and for VPT infants of 32 weeks' or less gestation.
In analyzing data from 37 VLBW studies comprising 104,944 infants, the investigators found that there was a 62% increase in odds of neonatal and predischarge death for infants born in non–level III hospitals compared with those born in level III hospitals (38% vs 23%; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.44 - 1.83).
When the investigators restricted their analysis to 9 studies with higher-quality evidence comprising 46,318 infants, they noted similar results. There was a 60% increase in the odds of neonatal or predischarge mortality for VLBW infants born at non–level III hospitals compared with infants born in level III hospitals (36% vs 21%; adjusted OR, 1.60; 95% CI, 1.33 - 1.92).
Results were even worse for extremely low birth weight infants — weighing 1300 g (35 ounces) or less — born in non–level III hospitals. Those infants had an estimated 80% increase in odds of neonatal or predischarge mortality compared with infants born at level III hospitals (59% vs 32%; adjusted OR, 1.80; 95% CI, 1.31 - 2.46.)
Data from an analysis of 4 studies comprising 9300 infants showed that VPT infants born in lower-level hospitals had a 55% increase in odds of neonatal or predischarge mortality compared with infants born in level III hospitals (15% vs 17%). When only the 3 studies that were ranked as adequate and high quality were analyzed, the estimate of death was reduced to a 42% increased odds of death (7% vs 12%; adjusted OR, 1.42; 95% CI, 1.06 - 1.88).
The researchers add that meta-regression by year of publication did not reveal a change over time (slope, 0.00; P = .87).
Among the study limitations, the authors note that they excluded non-English studies and unpublished data from their meta-analysis and suggest this might be a potential source of bias in their study selection. Other potential causes of bias include inadequate definitions of hospital levels, inadequate descriptions of hospital capabilities, and variability of confounding factors among the studies.
"The results of this review confirm a primary premise on which perinatal regionalization systems are based: high risk infants have higher mortality rates when born outside hospitals with the most specialized levels of care," the authors conclude. "Although they represent less than 2% of U.S. births, 55% of infant deaths occur among VLBW infants. Strengthening perinatal regionalization systems in states with high percentages of VLBW and VPT infants born outside of level III centers could potentially save thousands of infant lives every year."
JAMA. 2010;304:992-1000.
Fran Lowry
August 31, 2010 — Very low birth weight (VLBW) and very preterm (VPT) infants who are born in centers that are not specially equipped or experienced to manage such births have higher rates of neonatal and predischarge death compared with similar infants who are born in highly specialized level III hospitals.
The finding, from an analysis of data from previously published studies, appears in the September issue of the Journal of the American Medical Association.
"For more than 30 years, guidelines for perinatal regionalization have recommended that [VLBW] infants be born at highly specialized hospitals, most commonly designated as level III hospitals," write Sarah Marie Lasswell, MPH, from the Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues. "Despite these recommendations, some regions continue to have large percentages of VLBW infants born in lower-level hospitals."
The aim of this study was to evaluate the relationship between hospital level and care at birth and neonatal (the first 4 weeks after birth) and predischarge mortality for VLBW infants weighing 1500 g (53 ounces) or less and for VPT infants of 32 weeks' or less gestation.
In analyzing data from 37 VLBW studies comprising 104,944 infants, the investigators found that there was a 62% increase in odds of neonatal and predischarge death for infants born in non–level III hospitals compared with those born in level III hospitals (38% vs 23%; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.44 - 1.83).
When the investigators restricted their analysis to 9 studies with higher-quality evidence comprising 46,318 infants, they noted similar results. There was a 60% increase in the odds of neonatal or predischarge mortality for VLBW infants born at non–level III hospitals compared with infants born in level III hospitals (36% vs 21%; adjusted OR, 1.60; 95% CI, 1.33 - 1.92).
Results were even worse for extremely low birth weight infants — weighing 1300 g (35 ounces) or less — born in non–level III hospitals. Those infants had an estimated 80% increase in odds of neonatal or predischarge mortality compared with infants born at level III hospitals (59% vs 32%; adjusted OR, 1.80; 95% CI, 1.31 - 2.46.)
Data from an analysis of 4 studies comprising 9300 infants showed that VPT infants born in lower-level hospitals had a 55% increase in odds of neonatal or predischarge mortality compared with infants born in level III hospitals (15% vs 17%). When only the 3 studies that were ranked as adequate and high quality were analyzed, the estimate of death was reduced to a 42% increased odds of death (7% vs 12%; adjusted OR, 1.42; 95% CI, 1.06 - 1.88).
The researchers add that meta-regression by year of publication did not reveal a change over time (slope, 0.00; P = .87).
Among the study limitations, the authors note that they excluded non-English studies and unpublished data from their meta-analysis and suggest this might be a potential source of bias in their study selection. Other potential causes of bias include inadequate definitions of hospital levels, inadequate descriptions of hospital capabilities, and variability of confounding factors among the studies.
"The results of this review confirm a primary premise on which perinatal regionalization systems are based: high risk infants have higher mortality rates when born outside hospitals with the most specialized levels of care," the authors conclude. "Although they represent less than 2% of U.S. births, 55% of infant deaths occur among VLBW infants. Strengthening perinatal regionalization systems in states with high percentages of VLBW and VPT infants born outside of level III centers could potentially save thousands of infant lives every year."
JAMA. 2010;304:992-1000.
Wednesday, September 1, 2010
One Third of First-Time Pregnancies Delivered by Cesarean
From Medscape Medical News
Fran Lowry
August 30, 2010 — The rate of cesarean deliveries in the United States is continuing its upward trajectory, according to a new study released today. Now accounting for 30% of all deliveries, the rate of cesarean delivery has increased 50% from 1996 to 2007 and shows no signs of diminishing.
Results of a large, retrospective, observational study conducted by the National Institute of Child Health and Human Development and National Institutes of Health, in collaboration with 12 institutions across the United States, show that:
•1 in 3 women pregnant for the first time are now being delivered by cesarean.
•Repeat cesarean after a previous caesarean delivery now accounts for one third of all cesarean deliveries.
•The rate of trial of labor after a previous cesarean is low, at 29%, and the success rate for a trial of labor has declined to 57%.
•44% of women attempting vaginal delivery had their labor induced, and their rate of cesarean delivery is twice as high as women who have spontaneous labor.
•Half of cesarean deliveries were conducted before 6 cm of cervical dilation — which is considered an early phase of labor, especially in first-time mothers — induced labor, or women who are attempting vaginal birth after cesarean delivery (VBAC).
The results were announced by lead researcher Jun Zhang, PhD, MD, from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The findings are published in the September issue of the American Journal of Obstetrics and Gynecology.
Speaking at a teleconference today, Dr. Zhang told reporters he was particularly surprised by the finding that 1 of every 3 first-time mothers are delivering via cesarean.
"This has important consequences for future pregnancies, since vaginal delivery after C-section is still thought to be somewhat risky, despite recommendations by the American College of Obstetrics and Gynecology (ACOG) to the contrary," he said.
Another surprising finding was that many cesarean deliveries are being done very early in labor, before 6 cm of dilation, Dr. Zhang added.
The study, called the Consortium on Safe Labor, was conducted to collect comprehensive information on current labor and delivery practice across the United States. It included 12 clinical centers, made up of a total of 19 hospitals, located across 9 ACOG districts. Most were university or community teaching hospitals, and only 2 were nonteaching community hospitals. They were chosen because electronic medical records were available at each institution and because they were geographically representative of all ACOG districts in the United States.
Dr. Zhang told Medscape Medical News that several factors may be driving the increase in cesarean deliveries.
"Delayed child bearing, increased maternal body mass, more twin pregnancies, and low use of vaginal birth after previous C-section, which is increasing because of 2 forces — the increasing C-section rate in first-time mothers and the decrease in VBACs. Put all these together, and it looks as if the upward trajectory may continue for a little while."
He admitted that the study has limitations. The participants are not a random sample of what is going on in the United States, and academic institutions are overrepresented in the study sample, he told Medscape Medical News.
"Although this is quite a comprehensive database, it is not totally representative of the United States population. That is one drawback."
The second is that the study is retrospective.
"We think that the quality of information we have is very good, but we still have to rely on what is recorded in the medical records. We extracted the information from the hospital database, so our data are only as good as the medical record. That is another deficiency."
Dr. Zhang said that reducing this high rate of cesarean delivery will need to focus on preventing unnecessary primary cesarean deliveries "from several aspects."
"First, we need to decrease the rate of cesarean delivery associated with a high rate of induction of labor. Cesarean section for dystocia should be avoided before active phase of labor is established, particularly in nulliparous women, induced labor, and VBAC attempts."
He added that there should be a clinically accepted indication for performing cesarean delivery. Also, physicians and patients should be educated about trial of labor in women with a previous uterine scar.
"We agree with ACOG. They have just issued guidelines that call for increased use of VBAC, and we are in accordance with this," he noted.
S. Katherine Laughon, MD, MS, a fellow and maternal–fetal medicine specialist working with Dr. Zhang, said that barriers to VBAC exist but the study was not set up to address the specific reasons why.
"Recently, there was a National Institutes of Health consensus conference on what are the barriers to women getting access to providers and to healthcare facilities that will provide the opportunity for a trial of labor after a prior cesarean section, and also what are the barriers for physicians," Dr. Laughon said. "This particular study does not address that exact question, but it is something that both clinicians and policy makers at the national level need to investigate and find answers for."
Dr. Zhang and Dr. Laughon have disclosed no relevant financial relationships.
Presented August 30, 2010, in a teleconference at the National Institutes of Health.
Am J Obstet Gynecol. Published online August 13, 2010.
Fran Lowry
August 30, 2010 — The rate of cesarean deliveries in the United States is continuing its upward trajectory, according to a new study released today. Now accounting for 30% of all deliveries, the rate of cesarean delivery has increased 50% from 1996 to 2007 and shows no signs of diminishing.
Results of a large, retrospective, observational study conducted by the National Institute of Child Health and Human Development and National Institutes of Health, in collaboration with 12 institutions across the United States, show that:
•1 in 3 women pregnant for the first time are now being delivered by cesarean.
•Repeat cesarean after a previous caesarean delivery now accounts for one third of all cesarean deliveries.
•The rate of trial of labor after a previous cesarean is low, at 29%, and the success rate for a trial of labor has declined to 57%.
•44% of women attempting vaginal delivery had their labor induced, and their rate of cesarean delivery is twice as high as women who have spontaneous labor.
•Half of cesarean deliveries were conducted before 6 cm of cervical dilation — which is considered an early phase of labor, especially in first-time mothers — induced labor, or women who are attempting vaginal birth after cesarean delivery (VBAC).
The results were announced by lead researcher Jun Zhang, PhD, MD, from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The findings are published in the September issue of the American Journal of Obstetrics and Gynecology.
Speaking at a teleconference today, Dr. Zhang told reporters he was particularly surprised by the finding that 1 of every 3 first-time mothers are delivering via cesarean.
"This has important consequences for future pregnancies, since vaginal delivery after C-section is still thought to be somewhat risky, despite recommendations by the American College of Obstetrics and Gynecology (ACOG) to the contrary," he said.
Another surprising finding was that many cesarean deliveries are being done very early in labor, before 6 cm of dilation, Dr. Zhang added.
The study, called the Consortium on Safe Labor, was conducted to collect comprehensive information on current labor and delivery practice across the United States. It included 12 clinical centers, made up of a total of 19 hospitals, located across 9 ACOG districts. Most were university or community teaching hospitals, and only 2 were nonteaching community hospitals. They were chosen because electronic medical records were available at each institution and because they were geographically representative of all ACOG districts in the United States.
Dr. Zhang told Medscape Medical News that several factors may be driving the increase in cesarean deliveries.
"Delayed child bearing, increased maternal body mass, more twin pregnancies, and low use of vaginal birth after previous C-section, which is increasing because of 2 forces — the increasing C-section rate in first-time mothers and the decrease in VBACs. Put all these together, and it looks as if the upward trajectory may continue for a little while."
He admitted that the study has limitations. The participants are not a random sample of what is going on in the United States, and academic institutions are overrepresented in the study sample, he told Medscape Medical News.
"Although this is quite a comprehensive database, it is not totally representative of the United States population. That is one drawback."
The second is that the study is retrospective.
"We think that the quality of information we have is very good, but we still have to rely on what is recorded in the medical records. We extracted the information from the hospital database, so our data are only as good as the medical record. That is another deficiency."
Dr. Zhang said that reducing this high rate of cesarean delivery will need to focus on preventing unnecessary primary cesarean deliveries "from several aspects."
"First, we need to decrease the rate of cesarean delivery associated with a high rate of induction of labor. Cesarean section for dystocia should be avoided before active phase of labor is established, particularly in nulliparous women, induced labor, and VBAC attempts."
He added that there should be a clinically accepted indication for performing cesarean delivery. Also, physicians and patients should be educated about trial of labor in women with a previous uterine scar.
"We agree with ACOG. They have just issued guidelines that call for increased use of VBAC, and we are in accordance with this," he noted.
S. Katherine Laughon, MD, MS, a fellow and maternal–fetal medicine specialist working with Dr. Zhang, said that barriers to VBAC exist but the study was not set up to address the specific reasons why.
"Recently, there was a National Institutes of Health consensus conference on what are the barriers to women getting access to providers and to healthcare facilities that will provide the opportunity for a trial of labor after a prior cesarean section, and also what are the barriers for physicians," Dr. Laughon said. "This particular study does not address that exact question, but it is something that both clinicians and policy makers at the national level need to investigate and find answers for."
Dr. Zhang and Dr. Laughon have disclosed no relevant financial relationships.
Presented August 30, 2010, in a teleconference at the National Institutes of Health.
Am J Obstet Gynecol. Published online August 13, 2010.
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