From MedscapeCME Clinical Briefs
News Author: Pam Harrison
CME Author: Laurie Barclay, MD
March 3, 2010 — Targeted acupuncture may offer women with major depression a safe and effective alternative to antidepressant medication, new research suggests.
Investigators at Stanford University School of Medicine in California found that women with major depressive disorder treated with depression-specific acupuncture had a 63% response rate after 12 sessions compared with a 44.3% response rate in 2 combined control groups who were treated with either acupuncture not known to help alleviate depressive symptoms or Swedish massage.
"Pregnancy just by its nature can bring out some underlying psychiatric and emotional issues ... but treatment of depression during pregnancy is critically important so that a woman can maintain her sense of well being and take good care of herself, her fetus and, someday, her child," study coauthor Deirdre Lyell, MD, Stanford University School of Medicine, said in a statement.
Led by Rachel Manber, PhD, the study was published in the March issue of Obstetrics & Gynecology.
Response Rates Significantly Higher
For the study, investigators randomized 150 women whose pregnancies were between 12 and 30 weeks of gestation and who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depressive disorder and who scored at least 14 on the 17-item Hamilton Rating Scale for Depression.
Of the 141 women who eventually entered the study, 52 received depression-specific acupuncture, 49 received control acupuncture, and 49 others received Swedish massage.
Treatments were provided twice a week for the first 4 weeks and then weekly thereafter for 4 additional weeks, with each session lasting about 25 minutes.
The investigators found that response rates were significantly higher in women who received depression-specific acupuncture than for either control group. Response rates in women randomized to the 2 control interventions did not differ significantly from each other at 37.5% for the control acupuncture group vs 50% for the massage group.
On the other hand, remission rates did not differ significantly between women who received depression-specific acupuncture at 34.8% and the combined control groups at 29.5%. They also did not differ between those assigned to the control acupuncture group at 27.5% or the massage group at 31.2%.
Thirty-three of the study participants discontinued treatment before the study endpoint, 30% of them for reasons related to the pregnancy. Some women in both acupuncture groups reported transient discomfort at the point of needle insertion, and 1 woman experienced bleeding at the needle site.
Significantly fewer women who received massage reported any adverse effects compared with the 2 acupuncture groups.
Clinically Meaningful
The study authors point out that the benefits observed with depression-specific acupuncture can be considered "clinically meaningful" when assessed in a broader context of depression studies.
Although there are no randomized controlled trials of antidepressants being used during pregnancy, 1 randomized controlled trial found that interpersonal psychotherapy produced a 52% reduction in Hamilton Rating Scale for Depression scores and a 19% remission rate after 16 weeks of therapy, to which the currently study compares very favorably.
According to the study, antidepressant use during pregnancy doubled between 1999 and 2003, but many women are reluctant to take these medications because of safety concerns. In fact, in this particular study, 94% of the women involved expressed reluctance to take an antidepressant because of their pregnancy.
"Because there’s this concern about medication among pregnant women and their physicians, it’s important to find an alternative," said Dr. Manber.
Results from this study therefore suggest that this standardized acupuncture protocol could be considered a "viable treatment option" for depression during pregnancy, the investigators conclude.
Michael Thase, MD, University of Pennsylvania School of Medicine, cautions that findings from this study are preliminary, although they suggest that depression-specific acupuncture may have value in major depressive disorder in this patient population.
On the other hand, another study assessing depression-specific acupuncture in a broader population of men and women with major depressive disorder failed to find a significant effect from the modality, so evidence supporting acupuncture for the treatment of major depressive disorder is not consistent.
"Still there is reason to be cautious when prescribing antidepressants in pregnancy, and one has to weigh the pros and cons of using an antidepressant on an individual basis,” he told Medscape Psychiatry.
"If these promising findings are confirmed, it would be good to have another option to complement the focused forms of psychotherapy which are currently used for antenatal depression," he added.
The study was funded by the Agency for Healthcare Research and Quality. The study authors and Dr. Thase have disclosed no relevant financial relationships.
Obstet Gynecol. 2010;115:511-520.
Clinical Context
Major depressive disorder may occur in up to 14% of pregnant women, possibly in response to hormonal fluctuations or anticipated lifestyle changes. Depression during pregnancy has been associated with poor birth outcomes and postpartum depression. Untreated depression during pregnancy may harm the mother as well as the baby, particularly if the mother neglects prenatal care or engages in self-destructive behavior.
Although the use of antidepressants during pregnancy doubled between 1999 and 2003, many depressed women are unwilling to take these medications while pregnant because of safety issues. It is therefore important to find a nonpharmacologic, safe yet effective treatment option for depression during pregnancy. Previous studies have shown that acupuncture is an effective treatment of depression in the general population.
Study Highlights
The goal of this randomized controlled trial was to estimate the efficacy of acupuncture for depression during pregnancy.
The study sample consisted of 150 pregnant women between 12 and 30 weeks of gestation who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depressive disorder.
Participants were randomly assigned to receive either depression-specific acupuncture (n = 52) or 1 of 2 active controls: control acupuncture (n = 49) or Swedish massage (n = 49).
All treatments were standardized and lasted 8 weeks (12 sessions).
Junior acupuncturists blinded to treatment assignment needled participants at points prescribed by senior acupuncturists.
The main study endpoint was the Hamilton Rating Scale for Depression, performed by blinded raters at baseline and after 4 and 8 weeks of treatment.
Response rate was defined as having at least a 50% reduction in symptoms.
Analysis of continuous data was by intent-to-treat, with use of mixed-effects models.
Rate of decrease in symptom severity was greater in women who received depression-specific acupuncture vs the combined controls (d = 0.39; 95% confidence interval [CI], −1.31 to 1.65; P < .05) or control acupuncture group alone (P < .05; Cohen's-d = 0.46; 95% CI, −1.24 to 2.31).
In women who received depression-specific acupuncture, response rate (63.0%) was also significantly greater vs the combined controls (44.3%; P < .05; number needed to treat, 5.3; 95% CI, 2.8 - 75.0) and control acupuncture group (37.5%; P < .05; number needed to treat, 3.9; 95% CI, 2.2 - 19.8).
The control groups were not significantly different in symptom reduction and response rates (control acupuncture, 37.5% vs massage, 50.0%).
Rates of adverse events were not significantly different for the 3 treatment groups
Acupuncture-related adverse effects included transient discomfort at the point of needle insertion (7 participants in the control acupuncture group and 14 in the depression-specific acupuncture group) and bleeding at the needling site (1 in the depression-specific acupuncture group).
Massage-related adverse effects included transient discomfort in 5 participants.
None of these adverse effects resulted in study discontinuation.
The investigators concluded that the short acupuncture protocol tested in this study yielded symptom reduction and a response rate similar to those seen with standard depression treatments of similar length.
Study limitations include limited generalizability of the results because of the high education and socioeconomic status, predominance of Caucasians (67%), and exclusion of comorbid mental and medical disorders.
In addition, the massage therapy provided in this study was shorter vs standard practice.
Clinical Implications
Depression during pregnancy is responsive to treatment with a short acupuncture protocol, which could be a viable treatment option for depressed pregnant women. Rate of decrease in symptom severity was greater in women who received depression-specific acupuncture vs the combined controls or control acupuncture group alone.
Response rate (≥ 50% reduction in symptoms) was 63.0% in women who received depression-specific acupuncture, which was significantly greater vs the combined controls (44.3%) and control acupuncture alone (37.5%). Response rate with depression-specific acupuncture was similar to those seen with standard depression treatments of similar length.
Sunday, March 28, 2010
Friday, March 26, 2010
Palpable Breast Cancers More Common in Women Not Having Annual Mammography
From Medscape Medical News
Laurie Barclay, MD
March 26, 2010 — Palpable breast cancers are more common in women not having annual mammography, according to the results of a study reported in the March issue of the Journal of the American College of Surgeons.
Despite the frequent use of screening mammography, 43% of breast cancers presented symptomatically or as a palpable mass.
"This study confirms the importance of participation in screening mammography, since a palpable presentation was least common in women undergoing mammographic screening at the recommended interval of 1 year," senior author Amy C. Degnim, MD, FACS, associate professor of surgery at the Mayo Clinic in Rochester, Minnesota, told Medscape Ob/Gyn & Women's Health.
"In addition, this study sheds light on the possible impact of reduced breast cancer screening with mammography for women between [the ages of] 40 and 49 [years], as recently recommended by the US Preventive Services Task Force [USPSTF].
Lastly, this study shows that some cancers are still detected by breast self examination [BSE] and by clinical breast examination [CBE] by a healthcare provider, so there is still a role to be defined for these techniques in detecting breast cancer."
A study by the Commission on Cancer in the 1990s showed that the percentage of breast cancer patients presenting with palpable masses decreased from over 70% in 1983 to 44% in 1990, which may be attributable to the increasing use of screening mammography. Before the present study, however, few data have been published since 1990.
Breast Cancer Screening Recommendations
The new findings fuel the controversy over breast cancer screening recommendations. On November 17, 2009, the USPSTF issued new breast cancer screening guidelines recommending against routine mammography screening for women younger than age 50 years and for stopping screening at age 74 years. On the basis of current evidence, the USPSTF also could not determine the additional benefits and harms of CBE beyond screening mammography in women 40 years or older and recommended against teaching BSE.
"[Our] study demonstrates that the recent USPSTF recommendations should be taken with caution," Dr. Degnim said.
After widespread objections to the USPSTF guidelines by the American Cancer Society (ACS), the American College of Radiology (ACR), and others, the ACR and the Society of Breast Imaging jointly issued new recommendations in January 2010.
These guidelines on the use of imaging modalities for breast cancer screening suggest that women at average risk of developing breast cancer should begin annual mammography screening at age 40 years.
"Compared with detection by mammography, palpable breast cancer is larger, more likely to have metastasized, and have worse prognosis and worse survival," Robert A. Smith, PhD, ACS director of cancer screening, told Medscape Ob/Gyn & Women's Health.
"Mammography is the single best tool we have for the detection of breast cancer when it is small, has not spread, and when treatment options are greatest."
"Women with palpable tumors have larger tumor sizes and more advanced stage at presentation," Dr. Degnim agreed. "They also have worse breast cancer–specific survival than those with mammographically detected cancers, even when adjustments are made to compare women with similar tumor size and nodal stage."
Study Findings
The goal of the present study was to determine the method of cancer detection and frequency of screening mammography in women undergoing breast cancer surgery in 2000, using an institutional surgical breast cancer database from the Mayo Clinic. The investigators reviewed medical records to evaluate presentation at time of diagnosis and to characterize it either as "palpable" if the woman presented with a breast complaint or if a new mass was identified on examination or as "screening" if breast cancer was detected on screening mammography.
Dates of prior mammography screening were also recorded, and patients whose cancer was detected by mammogram were compared with those whose tumors were detected by BSE or CBE. Of 592 breast cancers detected, 335 (57%) were identified on screening, 255 (43%) were characterized as palpable, and in 2 patients (<1%), the method of cancer detection was unknown.
In women with a palpable mass, the size of the tumor was significantly larger than in women in whom cancer was detected by mammography (2.6 vs 1.5 cm; P < .0001). Patients with palpable presentation were younger than those with screen-detected cancer (mean age, 57 vs 62 years; P < .0001).
"The study findings are consistent with what is known about the advantage of mammography in detecting breast cancer before it has reached a size when it is palpable; that is, the screen-detected cancers were smaller than the palpable cancers," Dr. Smith said. "The cancers detected on mammography also were less likely to be advanced; that is, not having spread to the axillary lymph nodes. The findings also show that some women will, inevitably, be diagnosed with a palpable tumor before they are due for their next mammogram."
At least 1 prior screening mammogram was documented in 481 women (81%), although most screenings were performed less frequently than once annually. Compared with women who had previous mammography, those who had no previous screening mammography were more likely to have cancer present as palpable (67% vs 39%; P = .0002).
"We know that mammography does not pick up every breast cancer, however we were surprised at how often breast cancer was detected by a palpable mass," coauthor Judy Boughey, MD, FACS, an assistant professor of surgery at Mayo Clinic, said in a news release. "Presentation as a palpable mass was more frequent in those women who had not had a mammogram in the prior 12 months. This finding is even more concerning when you consider the recent recommendations for decreasing the use of mammography because it would result in an even greater proportion of breast cancers being detected by palpation and therefore at more advanced stages."
On the basis of their findings, the study authors concluded that despite the frequent use of screening mammography, 43% of breast cancers presented as a palpable mass or otherwise symptomatic presentation, whereas 57% were detected by mammography. Women who had not had mammography were more likely to present with palpable tumors.
Carol H. Lee, MD, radiologist from the Memorial Sloan-Kettering Cancer Center in New York City, and chair of the ACR Breast Imaging Commission, told Medscape Ob/Gyn & Women's Health that these findings were "not particularly surprising."
"The cancers found by screening were smaller, and it is known that smaller, lower-stage cancers are associated with a better prognosis," Dr. Lee said. "In addition, for cancers of similar size, those that are not palpable cancers have been shown to have a better outcome. In my opinion, this study emphasizes the importance of both screening mammography and BSE and underscores the potential damage that might occur if the USPSTF guidelines are widely followed in terms of delay in breast cancer diagnosis."
Study Strengths and Limitations
"A strength of this study is that it evaluates the frequency of palpable presentation of breast cancer in the modern era, during a time in which screening mammography was widely used, so this is likely very reflective of the current pattern of how breast cancers are discovered," Dr. Degnim said. "Another strength of this study is that the method of presentation could be determined for the vast majority of patients from the medical records, whereas this detailed information is usually not available in large national databases."
"[This study] is informative about the recent screening experience of women with a palpable mass vs those whose breast cancer was detected on mammography, and the tumor characteristics of each group," Dr. Smith said. "It also is informative about the mode of detection among women who had a palpable breast cancer, although there may be a lack of precision between categories of [BSE], incidental breast cancer detection, and 'found by patient, but method unspecified.' "
However, Dr. Smith also noted that the findings are not generalizable to the larger population of women beyond those presenting to the Mayo Clinic in Rochester for breast cancer surgery in 2000, and that the study depended on retrospective chart review for evidence of frequency and data of prior screening.
The study authors agree that these factors limitgeneralizability and also note that the study was set at a tertiary referral center, where patients might be more likely to present with palpable or more advanced tumors, and that the study population was almost exclusively white. These data were from 2000, when only film mammography was used, whereas the current practice is to use digital mammography.
"This study is a case series; it does not appear to be designed to study associations or causalities, and therefore the authors' conclusions are not appropriate because the results are calculated based on events (ie, mammogram vs SBE) that occurred in their cases," Miriam Alexander, MD, MPH, director, General Preventive Medicine Residency, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, told Medscape Ob/Gyn & Women's Health when asked for independent comment. "They were not able to use any measures of association such as odds ratios or relative risks, as this was not a case-control or cohort study or a clinical trial. I do not believe there are epidemiological or statistically valid conclusions that can be drawn from their results; they can only fairly report their results as observations of occurrence."
"I do not believe that studies like this would be considered by the USPSTF in evaluating whether the evidence is supportive, not supportive, or insufficient for screening tests such as mammography or SBE," Dr. Alexander said. "Unfortunately, there are no conclusions that can be drawn from this study as to the use of mammography or SBE for screening. Therefore, I cannot see that there are any clinical implications for changing screening recommendations based on this study."
Research Recommendations
In terms of additional research, Dr. Lee recommended continuing to develop more sensitive imaging methods to detect early breast cancer.
"The study implications remain valid for clinical practice today, since there have not been dramatic changes in participation in screening mammography over the last 10 years," Dr. Degnim said. "Further research is needed to evaluate whether this finding remains true in 2010 and in community-based healthcare settings."
Dr. Smith pointed out that we need to learn more about the duration of time between the first detection of a palpable mass and when women report symptoms to their physician. Although he believes this time is shorter today than in 2000, he suggests that factors contributing to the detection of palpable breast cancer and either quick reporting or delay need to be better understood.
"I do not believe that the results of this study should contribute to clinicians' decision making," Dr. Alexander said. "It is totally appropriate and necessary to continue our quest to minimize the human burden of suffering from breast cancer, but I would not recommend that further research be undertaken along these lines if our goal is to correctly identify and treat significant disease on a population basis.
"If we want to appropriately identify breast cancer from other breast anomalies, and if we want to correctly identify breast cancers that need treating to prevent morbidity and mortality, we should do research to develop tests or methodologies that meet all the criteria for excellent screening tests," Dr. Alexander continued. "There are multiple study designs that could then be employed to demonstrate the strength of the association between the screening test in question and the reduction in disease or its severity or progression, depending on the goals of the researchers."
Detection by BSE
Among the 255 patients with palpable or otherwise symptomatic presentations, 86% of the cancers were found by the patient either incidentally or during BSE, and the remaining 14% were detected during CBE by a physician or other healthcare provider.
"Because we don't know what proportion of women in the sample actually performed routine BSE, we can't conclude anything about the performance of BSE in detecting palpable tumors, nor did the authors report the relative sizes of the palpable tumors that fell into each group," Dr. Smith said. "The finding that CBE accounted for a very small proportion of the detected palpable breast cancers is consistent with recent literature [and]...is consistent with the observation that most women don't practice regular BSE. The ACS does not recommend for or against routine BSE but does emphasize the importance of maintaining a heightened sense of awareness about the presence or absence of breast symptoms."
Clinical Implications
The study authors note that their findings reaffirm the importance of participating in regular screening mammography, because this was associated with a decreased frequency of palpable presentation that was lowest among those women screened at the recommended annual interval. They also suggest that their findings confirm that both BSE and CBE still play a role in detecting breast cancer.
Dr. Smith noted that 71% to 75% of breast cancers diagnosed in the period between 11 and 24 months were detected by mammography screening, which highlights the greater advantage of annual screening vs biennial screening.
"Breast cancers are missed due to human error or because of the limitations of the exam in women with significant breast density," he said. "However, [the study findings] are consistent with the observation that there is a greater likelihood of detecting a palpable tumor the longer the duration from the previous mammogram, but also that mammography is not perfect and that some breast cancers will arise in the period between normal screening exams."
When asked how findings from this study affect ACS' position concerning the recent USPSTF recommendations regarding screening mammography, BSE, and CBE, Dr. Smith responded, "There is clear evidence that mammography saves lives in women 40 years of age and older. As these data show, women at all ages who were detected with a palpable mass were more likely to have a more advanced breast cancer compared with women with breast cancer detected by screening."
Although a higher proportion of women between ages 40 to 49 years were diagnosed with a palpable mass (58% vs 42%), a majority of women older than 40 years who had never had a previous mammogram were between the ages of 40 and 49 years. Dr. Smith noted that among women with prior screening, the risk of being diagnosed with a palpable tumor may have been more similar in younger and older women.
The study showed that a sizeable percentage of breast cancers occurred in women in their 40s (namely, 19%), leading the study authors to state that "Without screening mammography in this age group, at least 48 of these 115 cancers would have been missed, and many more would likely have been missed if both CBE and [BSE] were also omitted."
"In this instance, 'missed' means that these women would have been diagnosed with palpable breast cancer, had worse prognosis, fewer treatment options, and most likely poorer survival," Dr. Smith concluded. "Although ACS recommends routine CBE, we recognize its diminishing contribution to the detection of palpable breast cancer as routine mammography and a heightened sense of awareness account for most breast cancer detection."
Dr. Degnim and the other study authors and experts have disclosed no relevant financial relationships.
J Am Coll Surg. 2010;210:314-318. Abstract
Laurie Barclay, MD
March 26, 2010 — Palpable breast cancers are more common in women not having annual mammography, according to the results of a study reported in the March issue of the Journal of the American College of Surgeons.
Despite the frequent use of screening mammography, 43% of breast cancers presented symptomatically or as a palpable mass.
"This study confirms the importance of participation in screening mammography, since a palpable presentation was least common in women undergoing mammographic screening at the recommended interval of 1 year," senior author Amy C. Degnim, MD, FACS, associate professor of surgery at the Mayo Clinic in Rochester, Minnesota, told Medscape Ob/Gyn & Women's Health.
"In addition, this study sheds light on the possible impact of reduced breast cancer screening with mammography for women between [the ages of] 40 and 49 [years], as recently recommended by the US Preventive Services Task Force [USPSTF].
Lastly, this study shows that some cancers are still detected by breast self examination [BSE] and by clinical breast examination [CBE] by a healthcare provider, so there is still a role to be defined for these techniques in detecting breast cancer."
A study by the Commission on Cancer in the 1990s showed that the percentage of breast cancer patients presenting with palpable masses decreased from over 70% in 1983 to 44% in 1990, which may be attributable to the increasing use of screening mammography. Before the present study, however, few data have been published since 1990.
Breast Cancer Screening Recommendations
The new findings fuel the controversy over breast cancer screening recommendations. On November 17, 2009, the USPSTF issued new breast cancer screening guidelines recommending against routine mammography screening for women younger than age 50 years and for stopping screening at age 74 years. On the basis of current evidence, the USPSTF also could not determine the additional benefits and harms of CBE beyond screening mammography in women 40 years or older and recommended against teaching BSE.
"[Our] study demonstrates that the recent USPSTF recommendations should be taken with caution," Dr. Degnim said.
After widespread objections to the USPSTF guidelines by the American Cancer Society (ACS), the American College of Radiology (ACR), and others, the ACR and the Society of Breast Imaging jointly issued new recommendations in January 2010.
These guidelines on the use of imaging modalities for breast cancer screening suggest that women at average risk of developing breast cancer should begin annual mammography screening at age 40 years.
"Compared with detection by mammography, palpable breast cancer is larger, more likely to have metastasized, and have worse prognosis and worse survival," Robert A. Smith, PhD, ACS director of cancer screening, told Medscape Ob/Gyn & Women's Health.
"Mammography is the single best tool we have for the detection of breast cancer when it is small, has not spread, and when treatment options are greatest."
"Women with palpable tumors have larger tumor sizes and more advanced stage at presentation," Dr. Degnim agreed. "They also have worse breast cancer–specific survival than those with mammographically detected cancers, even when adjustments are made to compare women with similar tumor size and nodal stage."
Study Findings
The goal of the present study was to determine the method of cancer detection and frequency of screening mammography in women undergoing breast cancer surgery in 2000, using an institutional surgical breast cancer database from the Mayo Clinic. The investigators reviewed medical records to evaluate presentation at time of diagnosis and to characterize it either as "palpable" if the woman presented with a breast complaint or if a new mass was identified on examination or as "screening" if breast cancer was detected on screening mammography.
Dates of prior mammography screening were also recorded, and patients whose cancer was detected by mammogram were compared with those whose tumors were detected by BSE or CBE. Of 592 breast cancers detected, 335 (57%) were identified on screening, 255 (43%) were characterized as palpable, and in 2 patients (<1%), the method of cancer detection was unknown.
In women with a palpable mass, the size of the tumor was significantly larger than in women in whom cancer was detected by mammography (2.6 vs 1.5 cm; P < .0001). Patients with palpable presentation were younger than those with screen-detected cancer (mean age, 57 vs 62 years; P < .0001).
"The study findings are consistent with what is known about the advantage of mammography in detecting breast cancer before it has reached a size when it is palpable; that is, the screen-detected cancers were smaller than the palpable cancers," Dr. Smith said. "The cancers detected on mammography also were less likely to be advanced; that is, not having spread to the axillary lymph nodes. The findings also show that some women will, inevitably, be diagnosed with a palpable tumor before they are due for their next mammogram."
At least 1 prior screening mammogram was documented in 481 women (81%), although most screenings were performed less frequently than once annually. Compared with women who had previous mammography, those who had no previous screening mammography were more likely to have cancer present as palpable (67% vs 39%; P = .0002).
"We know that mammography does not pick up every breast cancer, however we were surprised at how often breast cancer was detected by a palpable mass," coauthor Judy Boughey, MD, FACS, an assistant professor of surgery at Mayo Clinic, said in a news release. "Presentation as a palpable mass was more frequent in those women who had not had a mammogram in the prior 12 months. This finding is even more concerning when you consider the recent recommendations for decreasing the use of mammography because it would result in an even greater proportion of breast cancers being detected by palpation and therefore at more advanced stages."
On the basis of their findings, the study authors concluded that despite the frequent use of screening mammography, 43% of breast cancers presented as a palpable mass or otherwise symptomatic presentation, whereas 57% were detected by mammography. Women who had not had mammography were more likely to present with palpable tumors.
Carol H. Lee, MD, radiologist from the Memorial Sloan-Kettering Cancer Center in New York City, and chair of the ACR Breast Imaging Commission, told Medscape Ob/Gyn & Women's Health that these findings were "not particularly surprising."
"The cancers found by screening were smaller, and it is known that smaller, lower-stage cancers are associated with a better prognosis," Dr. Lee said. "In addition, for cancers of similar size, those that are not palpable cancers have been shown to have a better outcome. In my opinion, this study emphasizes the importance of both screening mammography and BSE and underscores the potential damage that might occur if the USPSTF guidelines are widely followed in terms of delay in breast cancer diagnosis."
Study Strengths and Limitations
"A strength of this study is that it evaluates the frequency of palpable presentation of breast cancer in the modern era, during a time in which screening mammography was widely used, so this is likely very reflective of the current pattern of how breast cancers are discovered," Dr. Degnim said. "Another strength of this study is that the method of presentation could be determined for the vast majority of patients from the medical records, whereas this detailed information is usually not available in large national databases."
"[This study] is informative about the recent screening experience of women with a palpable mass vs those whose breast cancer was detected on mammography, and the tumor characteristics of each group," Dr. Smith said. "It also is informative about the mode of detection among women who had a palpable breast cancer, although there may be a lack of precision between categories of [BSE], incidental breast cancer detection, and 'found by patient, but method unspecified.' "
However, Dr. Smith also noted that the findings are not generalizable to the larger population of women beyond those presenting to the Mayo Clinic in Rochester for breast cancer surgery in 2000, and that the study depended on retrospective chart review for evidence of frequency and data of prior screening.
The study authors agree that these factors limitgeneralizability and also note that the study was set at a tertiary referral center, where patients might be more likely to present with palpable or more advanced tumors, and that the study population was almost exclusively white. These data were from 2000, when only film mammography was used, whereas the current practice is to use digital mammography.
"This study is a case series; it does not appear to be designed to study associations or causalities, and therefore the authors' conclusions are not appropriate because the results are calculated based on events (ie, mammogram vs SBE) that occurred in their cases," Miriam Alexander, MD, MPH, director, General Preventive Medicine Residency, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, told Medscape Ob/Gyn & Women's Health when asked for independent comment. "They were not able to use any measures of association such as odds ratios or relative risks, as this was not a case-control or cohort study or a clinical trial. I do not believe there are epidemiological or statistically valid conclusions that can be drawn from their results; they can only fairly report their results as observations of occurrence."
"I do not believe that studies like this would be considered by the USPSTF in evaluating whether the evidence is supportive, not supportive, or insufficient for screening tests such as mammography or SBE," Dr. Alexander said. "Unfortunately, there are no conclusions that can be drawn from this study as to the use of mammography or SBE for screening. Therefore, I cannot see that there are any clinical implications for changing screening recommendations based on this study."
Research Recommendations
In terms of additional research, Dr. Lee recommended continuing to develop more sensitive imaging methods to detect early breast cancer.
"The study implications remain valid for clinical practice today, since there have not been dramatic changes in participation in screening mammography over the last 10 years," Dr. Degnim said. "Further research is needed to evaluate whether this finding remains true in 2010 and in community-based healthcare settings."
Dr. Smith pointed out that we need to learn more about the duration of time between the first detection of a palpable mass and when women report symptoms to their physician. Although he believes this time is shorter today than in 2000, he suggests that factors contributing to the detection of palpable breast cancer and either quick reporting or delay need to be better understood.
"I do not believe that the results of this study should contribute to clinicians' decision making," Dr. Alexander said. "It is totally appropriate and necessary to continue our quest to minimize the human burden of suffering from breast cancer, but I would not recommend that further research be undertaken along these lines if our goal is to correctly identify and treat significant disease on a population basis.
"If we want to appropriately identify breast cancer from other breast anomalies, and if we want to correctly identify breast cancers that need treating to prevent morbidity and mortality, we should do research to develop tests or methodologies that meet all the criteria for excellent screening tests," Dr. Alexander continued. "There are multiple study designs that could then be employed to demonstrate the strength of the association between the screening test in question and the reduction in disease or its severity or progression, depending on the goals of the researchers."
Detection by BSE
Among the 255 patients with palpable or otherwise symptomatic presentations, 86% of the cancers were found by the patient either incidentally or during BSE, and the remaining 14% were detected during CBE by a physician or other healthcare provider.
"Because we don't know what proportion of women in the sample actually performed routine BSE, we can't conclude anything about the performance of BSE in detecting palpable tumors, nor did the authors report the relative sizes of the palpable tumors that fell into each group," Dr. Smith said. "The finding that CBE accounted for a very small proportion of the detected palpable breast cancers is consistent with recent literature [and]...is consistent with the observation that most women don't practice regular BSE. The ACS does not recommend for or against routine BSE but does emphasize the importance of maintaining a heightened sense of awareness about the presence or absence of breast symptoms."
Clinical Implications
The study authors note that their findings reaffirm the importance of participating in regular screening mammography, because this was associated with a decreased frequency of palpable presentation that was lowest among those women screened at the recommended annual interval. They also suggest that their findings confirm that both BSE and CBE still play a role in detecting breast cancer.
Dr. Smith noted that 71% to 75% of breast cancers diagnosed in the period between 11 and 24 months were detected by mammography screening, which highlights the greater advantage of annual screening vs biennial screening.
"Breast cancers are missed due to human error or because of the limitations of the exam in women with significant breast density," he said. "However, [the study findings] are consistent with the observation that there is a greater likelihood of detecting a palpable tumor the longer the duration from the previous mammogram, but also that mammography is not perfect and that some breast cancers will arise in the period between normal screening exams."
When asked how findings from this study affect ACS' position concerning the recent USPSTF recommendations regarding screening mammography, BSE, and CBE, Dr. Smith responded, "There is clear evidence that mammography saves lives in women 40 years of age and older. As these data show, women at all ages who were detected with a palpable mass were more likely to have a more advanced breast cancer compared with women with breast cancer detected by screening."
Although a higher proportion of women between ages 40 to 49 years were diagnosed with a palpable mass (58% vs 42%), a majority of women older than 40 years who had never had a previous mammogram were between the ages of 40 and 49 years. Dr. Smith noted that among women with prior screening, the risk of being diagnosed with a palpable tumor may have been more similar in younger and older women.
The study showed that a sizeable percentage of breast cancers occurred in women in their 40s (namely, 19%), leading the study authors to state that "Without screening mammography in this age group, at least 48 of these 115 cancers would have been missed, and many more would likely have been missed if both CBE and [BSE] were also omitted."
"In this instance, 'missed' means that these women would have been diagnosed with palpable breast cancer, had worse prognosis, fewer treatment options, and most likely poorer survival," Dr. Smith concluded. "Although ACS recommends routine CBE, we recognize its diminishing contribution to the detection of palpable breast cancer as routine mammography and a heightened sense of awareness account for most breast cancer detection."
Dr. Degnim and the other study authors and experts have disclosed no relevant financial relationships.
J Am Coll Surg. 2010;210:314-318. Abstract
Thursday, March 25, 2010
Incontinence After Childbirth May Last Years
From WebMD Health News
Jennifer Warner
March 25, 2010 — Problems with anal incontinence following childbirth may linger long after childbirth and hurt women’s quality of life and ability to care for their child, a new study finds.
In a previous study, about 38% of women reported new onset of at least one anal incontinence symptom -- such as gas or involuntary passing of stool -- in the 3-6 month period after delivery.
The new study shows that some women may experience bouts of anal incontinence two years after childbirth. More than half of these women are frustrated by their condition, and more than a quarter say it negatively affects their emotional health.
In addition, researchers say nearly one in five mothers with anal incontinence say the condition hinders her ability to care for her child.
“The postpartum period is an important time for parent-child bonding,” researcher Jaime Lo, MD, of the University of Utah, Salt Lake City, and colleagues write in Obstetrics & Gynecology.
“The development of anal incontinence postpartum may have important ramifications for both maternal and child health because it may affect a mother’s ability to care for her child emotionally and physically.”
Postpartum Incontinence Affects Quality of LIfe
In the study, researchers surveyed 1,247 women in Utah who experienced anal incontinence at least once in the two years following childbirth.
The results showed that 68% reported anal incontinence symptoms six months after childbirth, and 45% had symptoms 12 months following childbirth. By two years after childbirth, 28% of women still reported bouts of anal incontinence.
More than half of women with anal incontinence also reported symptoms of urinary incontinence.
Researchers found anal incontinence after childbirth had a significant impact on women’s quality of life in several ways. For example:
22% of women with anal incontinence felt their condition negatively affected their physical recreation.
12% said anal incontinence negatively affected their entertainment activities.
13% said their anal incontinence got in the way of any travel longer than half an hour.
Women with severe anal incontinence symptoms were four to seven times more likely to report negative quality of life than women with mild symptoms.
Researchers say despite persistent symptoms and negative quality of life, few women report their anal incontinence symptoms to their health care provider.
The results suggest that about 80,000 women (2% of births) each year in the United States may have persistent long-term anal incontinence related to childbirth. But only 8,000 will report these symptoms to their health care providers.
Treatment for anal incontinence frequently involves a combination of medication, biofeedback, and exercise. Surgery is also an option.
SOURCES:
Lo, J. Obstetrics & Gynecology, April 2010; vol 115: pp 809-814.
Jennifer Warner
March 25, 2010 — Problems with anal incontinence following childbirth may linger long after childbirth and hurt women’s quality of life and ability to care for their child, a new study finds.
In a previous study, about 38% of women reported new onset of at least one anal incontinence symptom -- such as gas or involuntary passing of stool -- in the 3-6 month period after delivery.
The new study shows that some women may experience bouts of anal incontinence two years after childbirth. More than half of these women are frustrated by their condition, and more than a quarter say it negatively affects their emotional health.
In addition, researchers say nearly one in five mothers with anal incontinence say the condition hinders her ability to care for her child.
“The postpartum period is an important time for parent-child bonding,” researcher Jaime Lo, MD, of the University of Utah, Salt Lake City, and colleagues write in Obstetrics & Gynecology.
“The development of anal incontinence postpartum may have important ramifications for both maternal and child health because it may affect a mother’s ability to care for her child emotionally and physically.”
Postpartum Incontinence Affects Quality of LIfe
In the study, researchers surveyed 1,247 women in Utah who experienced anal incontinence at least once in the two years following childbirth.
The results showed that 68% reported anal incontinence symptoms six months after childbirth, and 45% had symptoms 12 months following childbirth. By two years after childbirth, 28% of women still reported bouts of anal incontinence.
More than half of women with anal incontinence also reported symptoms of urinary incontinence.
Researchers found anal incontinence after childbirth had a significant impact on women’s quality of life in several ways. For example:
22% of women with anal incontinence felt their condition negatively affected their physical recreation.
12% said anal incontinence negatively affected their entertainment activities.
13% said their anal incontinence got in the way of any travel longer than half an hour.
Women with severe anal incontinence symptoms were four to seven times more likely to report negative quality of life than women with mild symptoms.
Researchers say despite persistent symptoms and negative quality of life, few women report their anal incontinence symptoms to their health care provider.
The results suggest that about 80,000 women (2% of births) each year in the United States may have persistent long-term anal incontinence related to childbirth. But only 8,000 will report these symptoms to their health care providers.
Treatment for anal incontinence frequently involves a combination of medication, biofeedback, and exercise. Surgery is also an option.
SOURCES:
Lo, J. Obstetrics & Gynecology, April 2010; vol 115: pp 809-814.
Tuesday, March 23, 2010
Aspiration of Breast Lumps Reviewed
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
03/09/2010;
March 9, 2010 — A review in the March 1 issue of the Canadian Medical Association Journal (CMAJ) describes an "in-office" approach for immediate evaluation of women who present to their family physician with a breast lump.
"As a family physician and a GP [general practice] oncologist who specializes in breast disease, I know how important it is to quickly evaluate breast lumps and reassure women who have benign cysts," lead author Ruth E. Heisey, MD, from University of Toronto, the Princess Margaret Hospital and the Women's College Hospital in Toronto, Ontario, Canada, said in a news release.
"Because 10% of malignant lesions in young women have features consistent with a fibroadenoma, new palpable masses in women of any age should be thoroughly evaluated," Dr. Heisey and coauthor David R. McCready, MD, MSc, also from the University of Toronto, write. "Cysts account for about 25% of all breast lumps and are common in premenopausal women over 35 years of age and uncommon in postmenopausal women unless they have received hormone therapy. In this article, we review an approach to the initial management of palpable breast lumps and describe several techniques for breast lump aspiration in the outpatient setting."
Women who have a breast lump and features suggesting cancer should be referred to a breast surgeon and immediately undergo mammography, ultrasonography, and core biopsy. These features include hard, irregular mass fixed to the skin; palpable ipsilateral lymph nodes; or a puckered "peau d'orange" appearance of the skin.
The family physician can begin in-office workup and management of a palpable breast lump not clinically suspicious for malignant disease. The lump should be aspirated with a fine needle because differentiating cystic from solid lesions using palpation alone can be difficult, and imaging may involve wait time, causing unnecessary anxiety for the patient. However, ultrasound is an alternative initial option to distinguish cystic from solid lumps.
Women with breast implants and those receiving anticoagulant therapy should not undergo aspiration in the family physician's office. When aspiration is performed, a local anesthetic is not needed.
A simple cyst is diagnosed when aspiration yields nonbloody fluid, and the lump completely disappears. Using clock position and distance from the nipple, the physician should precisely document the cyst's location in the breast, and the fluid may be discarded.
However, women should be referred to a surgeon if aspiration yields bloody fluid, if the lump does not disappear completely, or if the lump recurs. In these cases, the aspirate should be sent for pathologic examination by a skilled cytopathologist.
When fine-needle insertion indicates that the breast lump is solid, the needle may be removed without further aspiration, or an aspiration biopsy may be performed and the specimen sent for cytopathologic analysis.
Complications of aspiration may include local discomfort; bruising caused by blood vessel puncture; transient vasovagal reaction; or, uncommonly, a pneumothorax, which can be avoided by moving a lesion close to the chest wall over a rib before aspiration. However, immediate inspiratory and expiratory chest radiographs are indicated if air is drawn into the syringe.
Aspiration is not associated with higher rate of false-positive mammography results if the radiologist is informed about the aspiration site, nor is there any evidence that needle biopsy will cause malignant lesions to spread. Most cancers are diagnosed before surgery by needle or core biopsy.
Women who have a simple cyst should be seen in 6 to 8 weeks to be evaluated for recurrence, which, if present, mandates ultrasonography, mammography, or both, as well as surgical referral. No additional workup is needed for cysts that do not recur.
Women with solid lesions require imaging and surgical referral. Ultrasonography only is recommended for women younger than 30 years, whereas women at least 30 years old should have both mammography and ultrasonography studies.
To ensure concordance between clinical findings and the results of imaging and cytopathologic evaluation of solid breast lumps, triple assessment is recommended (examination, imaging, and aspiration).
Some clinicians opt to defer cytopathologic testing of palpable lumps presumed to be fibroadenomas, but this strategy may result in some breast cancers being missed in young women. Most delays in diagnosing breast cancer in this group occur as a result of falsely reassuring clinical or imaging findings.
"Aspiration of a palpable breast lump allows immediate reassurance for women with breast cysts and timely investigation and referral for women with solid masses," the review authors conclude. "If the lump is a cyst, the aspirated fluid may be discarded provided the fluid is not bloody and the lump disappears. If the lump is solid, triple assessment (clinical examination, breast imaging and fine-needle aspiration cytologic assessment) is warranted."
The review authors have disclosed no financial relationships.
CMAJ. Published online March 1, 2010.
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
03/09/2010;
March 9, 2010 — A review in the March 1 issue of the Canadian Medical Association Journal (CMAJ) describes an "in-office" approach for immediate evaluation of women who present to their family physician with a breast lump.
"As a family physician and a GP [general practice] oncologist who specializes in breast disease, I know how important it is to quickly evaluate breast lumps and reassure women who have benign cysts," lead author Ruth E. Heisey, MD, from University of Toronto, the Princess Margaret Hospital and the Women's College Hospital in Toronto, Ontario, Canada, said in a news release.
"Because 10% of malignant lesions in young women have features consistent with a fibroadenoma, new palpable masses in women of any age should be thoroughly evaluated," Dr. Heisey and coauthor David R. McCready, MD, MSc, also from the University of Toronto, write. "Cysts account for about 25% of all breast lumps and are common in premenopausal women over 35 years of age and uncommon in postmenopausal women unless they have received hormone therapy. In this article, we review an approach to the initial management of palpable breast lumps and describe several techniques for breast lump aspiration in the outpatient setting."
Women who have a breast lump and features suggesting cancer should be referred to a breast surgeon and immediately undergo mammography, ultrasonography, and core biopsy. These features include hard, irregular mass fixed to the skin; palpable ipsilateral lymph nodes; or a puckered "peau d'orange" appearance of the skin.
The family physician can begin in-office workup and management of a palpable breast lump not clinically suspicious for malignant disease. The lump should be aspirated with a fine needle because differentiating cystic from solid lesions using palpation alone can be difficult, and imaging may involve wait time, causing unnecessary anxiety for the patient. However, ultrasound is an alternative initial option to distinguish cystic from solid lumps.
Women with breast implants and those receiving anticoagulant therapy should not undergo aspiration in the family physician's office. When aspiration is performed, a local anesthetic is not needed.
A simple cyst is diagnosed when aspiration yields nonbloody fluid, and the lump completely disappears. Using clock position and distance from the nipple, the physician should precisely document the cyst's location in the breast, and the fluid may be discarded.
However, women should be referred to a surgeon if aspiration yields bloody fluid, if the lump does not disappear completely, or if the lump recurs. In these cases, the aspirate should be sent for pathologic examination by a skilled cytopathologist.
When fine-needle insertion indicates that the breast lump is solid, the needle may be removed without further aspiration, or an aspiration biopsy may be performed and the specimen sent for cytopathologic analysis.
Complications of aspiration may include local discomfort; bruising caused by blood vessel puncture; transient vasovagal reaction; or, uncommonly, a pneumothorax, which can be avoided by moving a lesion close to the chest wall over a rib before aspiration. However, immediate inspiratory and expiratory chest radiographs are indicated if air is drawn into the syringe.
Aspiration is not associated with higher rate of false-positive mammography results if the radiologist is informed about the aspiration site, nor is there any evidence that needle biopsy will cause malignant lesions to spread. Most cancers are diagnosed before surgery by needle or core biopsy.
Women who have a simple cyst should be seen in 6 to 8 weeks to be evaluated for recurrence, which, if present, mandates ultrasonography, mammography, or both, as well as surgical referral. No additional workup is needed for cysts that do not recur.
Women with solid lesions require imaging and surgical referral. Ultrasonography only is recommended for women younger than 30 years, whereas women at least 30 years old should have both mammography and ultrasonography studies.
To ensure concordance between clinical findings and the results of imaging and cytopathologic evaluation of solid breast lumps, triple assessment is recommended (examination, imaging, and aspiration).
Some clinicians opt to defer cytopathologic testing of palpable lumps presumed to be fibroadenomas, but this strategy may result in some breast cancers being missed in young women. Most delays in diagnosing breast cancer in this group occur as a result of falsely reassuring clinical or imaging findings.
"Aspiration of a palpable breast lump allows immediate reassurance for women with breast cysts and timely investigation and referral for women with solid masses," the review authors conclude. "If the lump is a cyst, the aspirated fluid may be discarded provided the fluid is not bloody and the lump disappears. If the lump is solid, triple assessment (clinical examination, breast imaging and fine-needle aspiration cytologic assessment) is warranted."
The review authors have disclosed no financial relationships.
CMAJ. Published online March 1, 2010.
Friday, March 19, 2010
Eating During Labor
From Medscape Ob/Gyn & Women's Health
Maria I. Rodriguez, MD
Posted: 03/10/2010
Oral intake during labor was identified in the 1940s as a risk factor for gastric aspiration with general anesthesia.
Since that time, restrictions have been placed on the diets of women in labor. At one time, all women in labor were restricted to ice chips in order to reduce the risk for pulmonary aspiration in the small proportion of patients who may require general anesthesia.
With improvements in obstetric anesthesia over subsequent decades, this approach has come under criticism.
Although the physiology of pregnancy does increase a woman's risk for aspiration as a result of delayed gastric emptying, pulmonary aspiration is rare.
Restriction of food and liquid for low-risk women in labor is felt to be potentially harmful by advocates. They cite concern that hunger may exacerbate fatigue and cause psychological stress.
Wide differences exist in the management of caloric intake during labor, varying dramatically by institution and country.Approaches range from "ice chips only" to a liberal diet for women at low risk of needing anesthesia.
New evidence exists to help guide management, although the outcome of pulmonary aspiration is so rare that it is not possible to include it as a study endpoint.
A Cochrane review of 5 randomized, controlled trials involving 3130 women in active labor was published recently. The investigators sought to determine the potential for harm or benefit of fluid or food intake during labor. Singata and colleagues identified 5 studies of sufficient quality to include in their meta- analysis.
All studies included women in active labor who were deemed to be at low risk of needing a general anesthetic. One study looked at complete restriction vs giving women the freedom to eat and drink at will. Two studies looked at allowing water only compared with giving women specific fluids and foods.An additional 2 studies looked at giving water only vs giving women carbohydrate drinks.
Primary outcomes included cesarean delivery, operative vaginal birth, and a 5-minute Apgar score of < 7. Secondary outcomes were duration of labor and maternal nausea or emesis.No statistically significant differences were identified in any primary or secondary outcome.Patient preferences were not considered in this meta-analysis. This level-1 evidence suggests that there is no justification for restriction of access to fluids during labor in low-risk women.
Critical to interpretation of these studies and application of the findings to practice is consideration of what it means to be "low risk."
Exclusion criteria for these studies varied but commonly included preterm labor, multiple gestation, breech position, intent to use analgesia during labor, and "any medical or obstetrical condition increasing risk for instrumental delivery or cesarean."These results may be less generalizable to hospitals with a high rate of cesarean delivery or epidural anesthesia.
In 2007, the American Society of Anesthesiologists updated their obstetric anesthesia guidelines with respect to oral intake during labor.
Their panel of experts agreed that permitting intake of clear liquids during labor for uncomplicated parturients does not increase risk for maternal harm.
The committee, however, highlighted the need for case-by-case consideration for individuals who had additional risk factors for aspiration, such as obesity, diabetes, or a difficult airway.
Obstetric considerations that increase the likelihood of intervention must also be taken into account. The American Congress of Obstetricians and Gynecologists concurs with permitting a modest intake of clear liquids during labor for low-risk patients.
In addition, they advise against ingestion of solid food during labor because no evidence supports a safe time period for such consumption.
This evidence provides an opportunity for reevaluation of our practices toward oral intake in women during labor, and suggests that patient preference should guide oral intake of fluids in low-risk women.
Care should be taken to consider the incidence of cesarean delivery and anesthesia use at a specific hospital when applying these results to one's own practice.
This issue also reminds us of the necessity of close communication between obstetricians and anesthesiologists in individualizing patient care.
Maria I. Rodriguez, MD
Posted: 03/10/2010
Oral intake during labor was identified in the 1940s as a risk factor for gastric aspiration with general anesthesia.
Since that time, restrictions have been placed on the diets of women in labor. At one time, all women in labor were restricted to ice chips in order to reduce the risk for pulmonary aspiration in the small proportion of patients who may require general anesthesia.
With improvements in obstetric anesthesia over subsequent decades, this approach has come under criticism.
Although the physiology of pregnancy does increase a woman's risk for aspiration as a result of delayed gastric emptying, pulmonary aspiration is rare.
Restriction of food and liquid for low-risk women in labor is felt to be potentially harmful by advocates. They cite concern that hunger may exacerbate fatigue and cause psychological stress.
Wide differences exist in the management of caloric intake during labor, varying dramatically by institution and country.Approaches range from "ice chips only" to a liberal diet for women at low risk of needing anesthesia.
New evidence exists to help guide management, although the outcome of pulmonary aspiration is so rare that it is not possible to include it as a study endpoint.
A Cochrane review of 5 randomized, controlled trials involving 3130 women in active labor was published recently. The investigators sought to determine the potential for harm or benefit of fluid or food intake during labor. Singata and colleagues identified 5 studies of sufficient quality to include in their meta- analysis.
All studies included women in active labor who were deemed to be at low risk of needing a general anesthetic. One study looked at complete restriction vs giving women the freedom to eat and drink at will. Two studies looked at allowing water only compared with giving women specific fluids and foods.An additional 2 studies looked at giving water only vs giving women carbohydrate drinks.
Primary outcomes included cesarean delivery, operative vaginal birth, and a 5-minute Apgar score of < 7. Secondary outcomes were duration of labor and maternal nausea or emesis.No statistically significant differences were identified in any primary or secondary outcome.Patient preferences were not considered in this meta-analysis. This level-1 evidence suggests that there is no justification for restriction of access to fluids during labor in low-risk women.
Critical to interpretation of these studies and application of the findings to practice is consideration of what it means to be "low risk."
Exclusion criteria for these studies varied but commonly included preterm labor, multiple gestation, breech position, intent to use analgesia during labor, and "any medical or obstetrical condition increasing risk for instrumental delivery or cesarean."These results may be less generalizable to hospitals with a high rate of cesarean delivery or epidural anesthesia.
In 2007, the American Society of Anesthesiologists updated their obstetric anesthesia guidelines with respect to oral intake during labor.
Their panel of experts agreed that permitting intake of clear liquids during labor for uncomplicated parturients does not increase risk for maternal harm.
The committee, however, highlighted the need for case-by-case consideration for individuals who had additional risk factors for aspiration, such as obesity, diabetes, or a difficult airway.
Obstetric considerations that increase the likelihood of intervention must also be taken into account. The American Congress of Obstetricians and Gynecologists concurs with permitting a modest intake of clear liquids during labor for low-risk patients.
In addition, they advise against ingestion of solid food during labor because no evidence supports a safe time period for such consumption.
This evidence provides an opportunity for reevaluation of our practices toward oral intake in women during labor, and suggests that patient preference should guide oral intake of fluids in low-risk women.
Care should be taken to consider the incidence of cesarean delivery and anesthesia use at a specific hospital when applying these results to one's own practice.
This issue also reminds us of the necessity of close communication between obstetricians and anesthesiologists in individualizing patient care.
Stress During Pregnancy Linked to Higher Risk for Asthma in Offspring
From Medscape Medical News
Laurie Barclay, MD
March 18, 2010 — Maternal stress during pregnancy is linked to a higher risk for asthma in the offspring, according to the results of a prospective study reported online March 18 in the American Journal of Respiratory and Critical Care Medicine.
"This is the first study in humans to show that increased stress experienced during pregnancy in these urban, largely minority women, is associated with different patterns of cord blood cytokine production to various environmental stimuli, relative to babies born to lower-stressed mothers," lead author Rosalind Wright, MD, MPH, associate physician at Brigham and Women's Hospital in Boston, Massachusetts, said in a news release.
In the Urban Environment and Childhood Asthma Study, the investigators evaluated associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses among 557 families in Boston; Baltimore, Maryland; New York City; St. Louis, Missouri, and other cities. Each child had a parent with history of asthma or allergy.
Prenatal maternal stress was defined as financial hardship, Difficult Life Circumstances (a 26-item survey to assess particular life stressors occurring within the previous 6 months; eg, domestic violence), community violence, and/or stressful neighborhood/block and housing conditions. A composite cumulative stress indicator was created using factor analysis to produce latent variables representing 3 contexts (individual stressors, housing and neighborhood problems).
CBMCs were incubated with innate stimuli (lipopolysaccharide, Poly I:C, CpG, peptidoglycan [PG]), adaptive stimuli (tetanus, dust mite, cockroach), respiratory syncytial virus, phytohemagglutinin, or medium alone. Multiplex enzyme-linked immunosorbent assays were used to measure cytokines. After adjustment for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, prenatal smoking, and birth weight for gestational age, associations among increasing cumulative stress and cytokine responses were evaluated with linear regression.
Among the study cohort, 71% of mothers were black and 19% were Latino, and 69% had an income less than $15,000. Mothers with the highest cumulative stress tended to be older and were more likely to have asthma and to deliver lower–birth weight infants. Higher levels of prenatal stress were associated with increased interleukin 8 production after microbial stimuli (CpG, PIC, PG) and increased tumor necrosis factor-alpha production to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was related to higher interleukin 13 levels after dust mite stimulation and lower levels of phytohemagglutinin-induced gamma-interferon.
"The cytokine patterns seen in the higher stress groups, which are an indication of how the child's immune system is functioning at birth, may be a marker of increased risk for developing asthma and allergy as they get older," Dr. Wright said. "For example, while the debate continues as to whether primary sensitization to allergens begins before birth, these findings suggest the possibility that prenatal stress may enhance the neonates' response to inhalant antigens, specifically those antigens that the fetus is likely to encounter more directly in utero, like dust mite."
On the basis of these findings, the study authors concluded that prenatal stress was associated with altered innate and adaptive immune responses in CBMCs, and that stress-induced perinatal immunomodulation may affect the expression of allergic disease in these children.
"The current findings suggest that psychological stress is involved in programming of the infant immune response and that this influence begins during pregnancy," said Dr. Wright. "As these infants mature, we will learn how these factors manifest later in terms of the development of asthma and allergy."
Limitations of this study include the possibility that some relationships were observed by chance because of multiple comparisons, in addition to variability and noise in the cytokine assays.
Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and from the National Center for Research Resources, National Institutes of Health, supported this study and Dr. Wright.
Am J Respir Crit Care Med. Published online March 18, 2010.
Laurie Barclay, MD
March 18, 2010 — Maternal stress during pregnancy is linked to a higher risk for asthma in the offspring, according to the results of a prospective study reported online March 18 in the American Journal of Respiratory and Critical Care Medicine.
"This is the first study in humans to show that increased stress experienced during pregnancy in these urban, largely minority women, is associated with different patterns of cord blood cytokine production to various environmental stimuli, relative to babies born to lower-stressed mothers," lead author Rosalind Wright, MD, MPH, associate physician at Brigham and Women's Hospital in Boston, Massachusetts, said in a news release.
In the Urban Environment and Childhood Asthma Study, the investigators evaluated associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses among 557 families in Boston; Baltimore, Maryland; New York City; St. Louis, Missouri, and other cities. Each child had a parent with history of asthma or allergy.
Prenatal maternal stress was defined as financial hardship, Difficult Life Circumstances (a 26-item survey to assess particular life stressors occurring within the previous 6 months; eg, domestic violence), community violence, and/or stressful neighborhood/block and housing conditions. A composite cumulative stress indicator was created using factor analysis to produce latent variables representing 3 contexts (individual stressors, housing and neighborhood problems).
CBMCs were incubated with innate stimuli (lipopolysaccharide, Poly I:C, CpG, peptidoglycan [PG]), adaptive stimuli (tetanus, dust mite, cockroach), respiratory syncytial virus, phytohemagglutinin, or medium alone. Multiplex enzyme-linked immunosorbent assays were used to measure cytokines. After adjustment for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, prenatal smoking, and birth weight for gestational age, associations among increasing cumulative stress and cytokine responses were evaluated with linear regression.
Among the study cohort, 71% of mothers were black and 19% were Latino, and 69% had an income less than $15,000. Mothers with the highest cumulative stress tended to be older and were more likely to have asthma and to deliver lower–birth weight infants. Higher levels of prenatal stress were associated with increased interleukin 8 production after microbial stimuli (CpG, PIC, PG) and increased tumor necrosis factor-alpha production to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was related to higher interleukin 13 levels after dust mite stimulation and lower levels of phytohemagglutinin-induced gamma-interferon.
"The cytokine patterns seen in the higher stress groups, which are an indication of how the child's immune system is functioning at birth, may be a marker of increased risk for developing asthma and allergy as they get older," Dr. Wright said. "For example, while the debate continues as to whether primary sensitization to allergens begins before birth, these findings suggest the possibility that prenatal stress may enhance the neonates' response to inhalant antigens, specifically those antigens that the fetus is likely to encounter more directly in utero, like dust mite."
On the basis of these findings, the study authors concluded that prenatal stress was associated with altered innate and adaptive immune responses in CBMCs, and that stress-induced perinatal immunomodulation may affect the expression of allergic disease in these children.
"The current findings suggest that psychological stress is involved in programming of the infant immune response and that this influence begins during pregnancy," said Dr. Wright. "As these infants mature, we will learn how these factors manifest later in terms of the development of asthma and allergy."
Limitations of this study include the possibility that some relationships were observed by chance because of multiple comparisons, in addition to variability and noise in the cytokine assays.
Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and from the National Center for Research Resources, National Institutes of Health, supported this study and Dr. Wright.
Am J Respir Crit Care Med. Published online March 18, 2010.
Friday, March 12, 2010
Is Postmastectomy Radiation Necessary for All Breast Cancer Patients?
From Medscape Medical News
Roxanne Nelson
March 11, 2010 — Some women with early-stage breast cancer that has spread to only 1 lymph node might not derive a benefit from postmastectomy radiation, according to new data presented during the plenary session at the Society of Surgical Oncology (SSO) Annual Cancer Symposium in St. Louis, Missouri.
Researchers from the University of Texas M.D. Anderson Cancer Center in Houston found that after surgery, adjuvant chemotherapy, and/or hormonal therapy, the risk for local regional recurrence rates were extremely low for patients with T1 and T2 breast cancer with 0 to 3 positive lymph nodes.
At a median follow-up of 94 months (95% confidence interval [CI], 88 to 94), local regional recurrence occurred in only 2.13% (n = 22) of the total number of patients in the study. There was also no statistical difference in the recurrence rates between patients with 1 lymph node metastasis and those with no nodal involvement (3.3% vs 2.1%).
Radiation is indicated for women after a lumpectomy because it reduces the recurrence rate, but the data are less clear after mastectomy, explained senior author Henry Kuerer, MD, PhD. professor and training program director in M.D. Anderson's Department of Surgical Oncology.
Data Could Be Outdated
"We have long-term data, but they are old data," he told Medscape Oncology in an interview. "They are from randomized studies that were conducted in the 1960s to 1980s, and the rates of local regional recurrence were high in these women. A benefit was seen with radiation."
Dr. Kuerer pointed out that in 2005, a meta-analysis of trials conducted in the 1960s to 1980s showed that there was a 66% reduction in locoregional recurrence in women who received postmastectomy radiation, compared with no radiation. The analysis also showed a small survival benefit associated with radiation therapy.
These findings led to a shift in clinical practice, and the National Comprehensive Cancer Network altered their guidelines in 2007 to suggest that stage I and II breast cancer patients with 1 to 3 lymph node metastases "strongly consider" radiation after mastectomy.
The overall 5- and 10-year recurrence rates in those studies ranged from 20% to 25%, which are much higher than what is currently observed, said Dr. Kuerer. "We have not seen that in our own clinical practice."
We have better screening, better detection, better surgical techniques.
In the decades since those studies were conducted, Dr. Kuerer explained, much has changed in the treatment and diagnosis of breast cancer. "We have better screening, better detection, better surgical techniques, and we now have therapies that didn't exist when these early studies were done," he said. "Pathology has also improved, and more extensive examination of lymph nodes is now conducted."
Radiotherapy after mastectomy is effective at decreasing the chances of local regional recurrence in patients with lymph node spread in more than 4 nodes, and where the risk for recurrence is greater than 15%. "The benefit of radiation therapy in this case clearly outweighs the risk, and can offer a survival advantage," he said.
But the use of radiation in patients with early-stage breast cancer with only 1 to 3 positive nodes has been a "hot topic of debate" within the cancer community, Dr. Kuerer explained.
Low Recurrence Rates
The goal of this study was to determine the present-day rates of local regional recurrence to better gauge the potential benefit of postmastectomy radiation in this particular subpopulation of breast cancer patients. Dr. Kuerer and his colleagues conducted a retrospective study in which they evaluated the clinical and pathological factors of 1022 stage I or II breast cancer patients who received a mastectomy at M.D. Anderson between 1997 and 2002.
The median patient age was 55 years and, within this group, 79% had T1 and 21% had T2 tumors. The majority of patients (74%) had no lymph node metastasis, but 26% had 1 to 3 positive nodes. None of the patients in the study received postmastectomy radiation therapy or neoadjuvant therapy, and 77% received adjuvant chemotherapy and/or hormonal therapy.
Node Status and Rates of Local Regional Recurrence (LRR) Number of
Positive Nodes n (%) 5-Year LRR 10-Year LRR
0 753 (74) 1.2% 2.4%
1 180 (18) 2.4% 3.2%
2 69 (7) 3.1% 6.7%
3 21 (2) N/A N/A
There were too few patients in the study with 3 positive nodes to determine rates. Patients who were younger than 40 years, who had T2 tumors with nodal metastasis, and who had estrogen-receptor negative tumors had significantly higher chances of local regional recurrence (P < .01).
"I think that our study should have an impact on how women with early-stage disease and 1 positive lymph node are treated," said Dr. Kuerer, although he cautioned that treatment decisions must always be based on the individual patient.
Monica Morrow, MD, chief of the breast service in the Department of Surgery at Memorial Sloan-Kettering Cancer Center in New York City, doesn't believe that current practice should change just yet.
"The question asked in this study — what is the rate of local recurrence after mastectomy in patients receiving modern systemic therapy and high-quality surgery — is an important one," said Dr. Morrow, who moderated the plenary session at the SSO symposium. However, "this study cannot be used as evidence that radiation therapy can be eliminated, because this was a very selected group of patients."
This study should stimulate other more inclusive studies, but should not be regarded as practice-changing.
She told Medscape Oncology that there were many more patients who received treatment during the same time period, and who received radiation therapy and neoadjuvant chemotherapy, or both. "We don't have any information on how the group who didn't get radiation therapy compares or what percentage of patients they were," she explained. "So this study should stimulate other more inclusive studies, but should not be regarded as practice-changing."
Dr. Kuerer agreed that more studies are needed, and pointed to the international randomized SUPREMO trial, which is currently enrolling patients. The trial is designed to evaluate the role of chest-wall radiation therapy after mastectomy in women who are at intermediate risk for locoregional recurrence, with 1 to 3 involved lymph nodes.
"However," he said, "it may be a decade before we have that information."
Society of Surgical Oncology's Annual Cancer Symposium: Abstract 47. Presented March 6, 2010.
Roxanne Nelson
March 11, 2010 — Some women with early-stage breast cancer that has spread to only 1 lymph node might not derive a benefit from postmastectomy radiation, according to new data presented during the plenary session at the Society of Surgical Oncology (SSO) Annual Cancer Symposium in St. Louis, Missouri.
Researchers from the University of Texas M.D. Anderson Cancer Center in Houston found that after surgery, adjuvant chemotherapy, and/or hormonal therapy, the risk for local regional recurrence rates were extremely low for patients with T1 and T2 breast cancer with 0 to 3 positive lymph nodes.
At a median follow-up of 94 months (95% confidence interval [CI], 88 to 94), local regional recurrence occurred in only 2.13% (n = 22) of the total number of patients in the study. There was also no statistical difference in the recurrence rates between patients with 1 lymph node metastasis and those with no nodal involvement (3.3% vs 2.1%).
Radiation is indicated for women after a lumpectomy because it reduces the recurrence rate, but the data are less clear after mastectomy, explained senior author Henry Kuerer, MD, PhD. professor and training program director in M.D. Anderson's Department of Surgical Oncology.
Data Could Be Outdated
"We have long-term data, but they are old data," he told Medscape Oncology in an interview. "They are from randomized studies that were conducted in the 1960s to 1980s, and the rates of local regional recurrence were high in these women. A benefit was seen with radiation."
Dr. Kuerer pointed out that in 2005, a meta-analysis of trials conducted in the 1960s to 1980s showed that there was a 66% reduction in locoregional recurrence in women who received postmastectomy radiation, compared with no radiation. The analysis also showed a small survival benefit associated with radiation therapy.
These findings led to a shift in clinical practice, and the National Comprehensive Cancer Network altered their guidelines in 2007 to suggest that stage I and II breast cancer patients with 1 to 3 lymph node metastases "strongly consider" radiation after mastectomy.
The overall 5- and 10-year recurrence rates in those studies ranged from 20% to 25%, which are much higher than what is currently observed, said Dr. Kuerer. "We have not seen that in our own clinical practice."
We have better screening, better detection, better surgical techniques.
In the decades since those studies were conducted, Dr. Kuerer explained, much has changed in the treatment and diagnosis of breast cancer. "We have better screening, better detection, better surgical techniques, and we now have therapies that didn't exist when these early studies were done," he said. "Pathology has also improved, and more extensive examination of lymph nodes is now conducted."
Radiotherapy after mastectomy is effective at decreasing the chances of local regional recurrence in patients with lymph node spread in more than 4 nodes, and where the risk for recurrence is greater than 15%. "The benefit of radiation therapy in this case clearly outweighs the risk, and can offer a survival advantage," he said.
But the use of radiation in patients with early-stage breast cancer with only 1 to 3 positive nodes has been a "hot topic of debate" within the cancer community, Dr. Kuerer explained.
Low Recurrence Rates
The goal of this study was to determine the present-day rates of local regional recurrence to better gauge the potential benefit of postmastectomy radiation in this particular subpopulation of breast cancer patients. Dr. Kuerer and his colleagues conducted a retrospective study in which they evaluated the clinical and pathological factors of 1022 stage I or II breast cancer patients who received a mastectomy at M.D. Anderson between 1997 and 2002.
The median patient age was 55 years and, within this group, 79% had T1 and 21% had T2 tumors. The majority of patients (74%) had no lymph node metastasis, but 26% had 1 to 3 positive nodes. None of the patients in the study received postmastectomy radiation therapy or neoadjuvant therapy, and 77% received adjuvant chemotherapy and/or hormonal therapy.
Node Status and Rates of Local Regional Recurrence (LRR) Number of
Positive Nodes n (%) 5-Year LRR 10-Year LRR
0 753 (74) 1.2% 2.4%
1 180 (18) 2.4% 3.2%
2 69 (7) 3.1% 6.7%
3 21 (2) N/A N/A
There were too few patients in the study with 3 positive nodes to determine rates. Patients who were younger than 40 years, who had T2 tumors with nodal metastasis, and who had estrogen-receptor negative tumors had significantly higher chances of local regional recurrence (P < .01).
"I think that our study should have an impact on how women with early-stage disease and 1 positive lymph node are treated," said Dr. Kuerer, although he cautioned that treatment decisions must always be based on the individual patient.
Monica Morrow, MD, chief of the breast service in the Department of Surgery at Memorial Sloan-Kettering Cancer Center in New York City, doesn't believe that current practice should change just yet.
"The question asked in this study — what is the rate of local recurrence after mastectomy in patients receiving modern systemic therapy and high-quality surgery — is an important one," said Dr. Morrow, who moderated the plenary session at the SSO symposium. However, "this study cannot be used as evidence that radiation therapy can be eliminated, because this was a very selected group of patients."
This study should stimulate other more inclusive studies, but should not be regarded as practice-changing.
She told Medscape Oncology that there were many more patients who received treatment during the same time period, and who received radiation therapy and neoadjuvant chemotherapy, or both. "We don't have any information on how the group who didn't get radiation therapy compares or what percentage of patients they were," she explained. "So this study should stimulate other more inclusive studies, but should not be regarded as practice-changing."
Dr. Kuerer agreed that more studies are needed, and pointed to the international randomized SUPREMO trial, which is currently enrolling patients. The trial is designed to evaluate the role of chest-wall radiation therapy after mastectomy in women who are at intermediate risk for locoregional recurrence, with 1 to 3 involved lymph nodes.
"However," he said, "it may be a decade before we have that information."
Society of Surgical Oncology's Annual Cancer Symposium: Abstract 47. Presented March 6, 2010.
Thursday, March 11, 2010
Vaginal Birth After Cesarean Delivery
From Medscape Medical News
Draft NIH Consensus Statement Released
Laurie Barclay, MD
March 10, 2010 — An independent expert panel released today a draft consensus statement on vaginal birth after cesarean delivery (VBAC) at the close of a 3-day conference.
The National Institutes of Health (NIH) Consensus Development Conference on Vaginal Birth After Cesarean (VBAC): New Insights, was held from March 8-10 in Bethesda, Maryland. When choosing VBAC or repeat cesarean delivery, parents' preferences and risk factors should be carefully considered, the panel said.
VBAC was not generally accepted as a viable option until the 1980s. VBAC rates in the United States have increased steadily until they reached 28% in 1996, but they have consistently decreased since 1996, despite a steady increase in the rates of repeat cesarean delivery.
The current overall cesarean delivery rate is 31%, whereas the VBAC rate is less than 10%.
"The exact causes of these shifts are not known and are likely multifactorial," Catherine Y. Spong, MD, chief, and Caroline Signore, MD, medical officer, Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, told Medscape Ob/Gyn & Women's Health.
"On one hand, the VBAC rate peaked in the mid-1990s, and then there was the publication of some studies that suggested increased risk with VBAC vs a repeat cesarean; at the same time, there was the malpractice crisis, especially in obstetrics, and the [American Congress of Obstetricians and Gynecologists] guidelines were modified to require that a physician capable of performing an emergency cesarean is immediately available through active labor. These events may have started the decline in VBAC utilization," Dr. Spong explained.
The panel noted that pregnant women, even those at low risk for complications, currently have limited access to clinicians and facilities capable of and willing to offer a trial of labor after previous cesarean delivery.
"Many women bemoan the fact that they have not had access to a trial of labor after prior cesarean section," Consensus Development Panel Chair F. Gary Cunningham, MD, Beatrice and Miguel Elias Distinguished Chair in Obstetrics and Gynecology at the University of Texas Southwestern Medical Center at Dallas, said during a telebriefing held after the conference.
The consensus conference aimed to explore the reasons underlying the changing practice patterns resulting in lower rates of VBAC, to clarify the clinical risks and benefits of both types of delivery procedures, and to describe the interaction of these risks with legal, ethical, and economic forces affecting clinician and patient choices regarding VBAC.
"A frequently cited concern [about VBAC] is the concern of safety — specifically the risk of uterine rupture, along with other risks," Dr. Spong and Dr. Signore said.
"In addition, there are nonclinical factors, including hospital practices and physician practices, professional society guidelines, medicolegal concerns, personal preferences of patients and clinicians, insurance policies, and economic considerations."
VBAC a Reasonable Option for Many
Despite the lack of widespread availability, a trial of labor is a reasonable option for many women with a previous cesarean delivery, and it is successful in nearly 75% of cases, the panel concluded.
Women in whom VBAC may be considered are those with 1 prior cesarean section, a single low transverse incision, singleton gestation, and no medical or obstetrical complicating conditions.
Data to support the safety of VBAC in women not meeting these criteria are lacking. Age itself does not preclude VBAC, but the rates of large babies, hypertension, diabetes, and dysfunctional labor are higher in older women.
Maternal mortality is lower for women who have a trial of labor, regardless of whether the baby is ultimately delivered vaginally or by cesarean section.
However, women who have an unsuccessful trial of labor and undergo repeat cesarean delivery have higher morbidity rates than those who have a successful VBAC.
Further complicating decision-making regarding VBAC is that benefits for the mother may come at the price of increased risks for the baby, and vice versa.
Although hysterectomy rates are similar for both forms of delivery, risk for uterine rupture is higher in women who have a trial of labor. VBAC has been linked to reduced abnormalities of placental growth and position in subsequent pregnancies. However, high-quality evidence about medical and nonmedical risk factors is limited or lacking.
"In general, there are short- and long-term risks and benefits for both the mother and the baby that need to be considered," Dr. Spong and Dr. Signore said. "Basically, they include — for the mother — risks of uterine rupture, transfusion and hemorrhage, operative risks including injury to the bowel and bladder, hysterectomy, death, infection, problems with placentation in subsequent pregnancies, [and] possible risk of stillbirth and ectopic pregnancies. For the baby, the risks include transition problems for the newborn, respiratory distress, neonatal encephalopathy and hypoxic ischemic encephalopathy, death, and brachial plexus injury."
Current VBAC Guidelines Should be Reassessed
The panel recommended that current VBAC guidelines from professional societies be reassessed, particularly the recommendation for "immediate availability" of surgical and anesthesia personnel before a trial of labor can be offered.
According to 2 recent surveys of hospital administrators, 30% of hospitals no longer offer a trial of labor or VBAC services because they could not meet the immediate availability standard suggested by the American College of Obstetricians and Gynecologists and the American Society of Anesthesiologists guidelines. However, the panel found no evidence that outcomes were improved by the immediate availability of surgical and anesthesia personnel.
" 'Nonmedical' factors affecting VBAC utilization [were also] considered at the conference, based on talks by expert presenters," Dr. Spong and Dr. Signore said. "The panel [considered], for example, the influence of hospital administrative policies, healthcare expenditures, resource utilization, the threat of malpractice litigation and the associated financial ramifications (insurance premiums, settlements and awards), the impact of professional society recommendations and standards, the role of maternal and provider preferences, understanding how risk is communicated and understood, the medical ethics of choice and access to childbirth options, and availability of surgical and anesthesiology staff."
Other Recommendations
Other recommendations of the panel are that malpractice concerns be addressed and that additional research be performed to better understand the medical and nonmedical factors that affect decision making for women with previous cesarean deliveries. Also needed are clear, evidence-based risk assessment tools to facilitate the decision-making process from early pregnancy through delivery, considering individual risk factors as well as maternal values and preferences.
"All women who have had a prior cesarean section should talk to their provider about VBAC and reassess the safety of a trial of labor," panel member Emily Spencer Lukacz, MD, MAS, associate professor of clinical reproductive medicine at the University of California–San Diego, said during the telebriefing.
Some women prefer to attempt a trial of labor because they would like their partner to be involved in the delivery, they perceive labor and vaginal delivery as deeply empowering, and/or they believe it will enhance maternal–infant bonding, breast-feeding, and recovery. In contrast, preferences favoring planned cesarean delivery include scheduling convenience, avoidance of labor pain or possible emergency cesarean section, and/or desire for surgical sterilization at the time of delivery.
The panels hopes the conference findings will have important implications for health services planning as well as for informed clinical decisions. The panel strongly urged policymakers and healthcare providers to collaborate in developing and implementing appropriate strategies to address and alleviate malpractice concerns.
"Pregnancy is something of a risky endeavor," concluded Carol J. Rowland Hogue, PhD, MPH, Jules & Uldeen Terry Professor of Maternal and Child Health at Emory University in Atlanta, Georgia. "Problems occur irrespective of the mode of delivery.... It's a tradeoff between making the pregnancy as safe as possible for the mother and making the pregnancy as safe as possible for the baby."
The statement issued by the impartial, independent Consensus Development Conference panel synthesized their evaluation of the available evidence from a systematic literature review prepared through the Agency for Healthcare Research and Quality Evidence-Based Practice Centers program by the Oregon Evidence-Based Practice Center. The panel included 15 experts in obstetrics and gynecology, urogynecology, maternal and fetal medicine, pediatrics, midwifery, clinical pharmacology, medical ethics, internal medicine, family medicine, perinatal and reproductive psychiatry, anesthesiology, nursing, biostatistics, epidemiology, healthcare regulation, and risk management, and a public representative.
The panel also considered evidence from expert presentations and audience input at the conference to provide a basis for informed patient and clinician decisions concerning VBAC. The statement also includes specific recommendations for future research.
The draft consensus statement is available on the NIH Consensus Development Program Web site.
NIH Consensus Development Conference on (VBAC): New Insights. March 8-10, 2010.
Draft NIH Consensus Statement Released
Laurie Barclay, MD
March 10, 2010 — An independent expert panel released today a draft consensus statement on vaginal birth after cesarean delivery (VBAC) at the close of a 3-day conference.
The National Institutes of Health (NIH) Consensus Development Conference on Vaginal Birth After Cesarean (VBAC): New Insights, was held from March 8-10 in Bethesda, Maryland. When choosing VBAC or repeat cesarean delivery, parents' preferences and risk factors should be carefully considered, the panel said.
VBAC was not generally accepted as a viable option until the 1980s. VBAC rates in the United States have increased steadily until they reached 28% in 1996, but they have consistently decreased since 1996, despite a steady increase in the rates of repeat cesarean delivery.
The current overall cesarean delivery rate is 31%, whereas the VBAC rate is less than 10%.
"The exact causes of these shifts are not known and are likely multifactorial," Catherine Y. Spong, MD, chief, and Caroline Signore, MD, medical officer, Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, told Medscape Ob/Gyn & Women's Health.
"On one hand, the VBAC rate peaked in the mid-1990s, and then there was the publication of some studies that suggested increased risk with VBAC vs a repeat cesarean; at the same time, there was the malpractice crisis, especially in obstetrics, and the [American Congress of Obstetricians and Gynecologists] guidelines were modified to require that a physician capable of performing an emergency cesarean is immediately available through active labor. These events may have started the decline in VBAC utilization," Dr. Spong explained.
The panel noted that pregnant women, even those at low risk for complications, currently have limited access to clinicians and facilities capable of and willing to offer a trial of labor after previous cesarean delivery.
"Many women bemoan the fact that they have not had access to a trial of labor after prior cesarean section," Consensus Development Panel Chair F. Gary Cunningham, MD, Beatrice and Miguel Elias Distinguished Chair in Obstetrics and Gynecology at the University of Texas Southwestern Medical Center at Dallas, said during a telebriefing held after the conference.
The consensus conference aimed to explore the reasons underlying the changing practice patterns resulting in lower rates of VBAC, to clarify the clinical risks and benefits of both types of delivery procedures, and to describe the interaction of these risks with legal, ethical, and economic forces affecting clinician and patient choices regarding VBAC.
"A frequently cited concern [about VBAC] is the concern of safety — specifically the risk of uterine rupture, along with other risks," Dr. Spong and Dr. Signore said.
"In addition, there are nonclinical factors, including hospital practices and physician practices, professional society guidelines, medicolegal concerns, personal preferences of patients and clinicians, insurance policies, and economic considerations."
VBAC a Reasonable Option for Many
Despite the lack of widespread availability, a trial of labor is a reasonable option for many women with a previous cesarean delivery, and it is successful in nearly 75% of cases, the panel concluded.
Women in whom VBAC may be considered are those with 1 prior cesarean section, a single low transverse incision, singleton gestation, and no medical or obstetrical complicating conditions.
Data to support the safety of VBAC in women not meeting these criteria are lacking. Age itself does not preclude VBAC, but the rates of large babies, hypertension, diabetes, and dysfunctional labor are higher in older women.
Maternal mortality is lower for women who have a trial of labor, regardless of whether the baby is ultimately delivered vaginally or by cesarean section.
However, women who have an unsuccessful trial of labor and undergo repeat cesarean delivery have higher morbidity rates than those who have a successful VBAC.
Further complicating decision-making regarding VBAC is that benefits for the mother may come at the price of increased risks for the baby, and vice versa.
Although hysterectomy rates are similar for both forms of delivery, risk for uterine rupture is higher in women who have a trial of labor. VBAC has been linked to reduced abnormalities of placental growth and position in subsequent pregnancies. However, high-quality evidence about medical and nonmedical risk factors is limited or lacking.
"In general, there are short- and long-term risks and benefits for both the mother and the baby that need to be considered," Dr. Spong and Dr. Signore said. "Basically, they include — for the mother — risks of uterine rupture, transfusion and hemorrhage, operative risks including injury to the bowel and bladder, hysterectomy, death, infection, problems with placentation in subsequent pregnancies, [and] possible risk of stillbirth and ectopic pregnancies. For the baby, the risks include transition problems for the newborn, respiratory distress, neonatal encephalopathy and hypoxic ischemic encephalopathy, death, and brachial plexus injury."
Current VBAC Guidelines Should be Reassessed
The panel recommended that current VBAC guidelines from professional societies be reassessed, particularly the recommendation for "immediate availability" of surgical and anesthesia personnel before a trial of labor can be offered.
According to 2 recent surveys of hospital administrators, 30% of hospitals no longer offer a trial of labor or VBAC services because they could not meet the immediate availability standard suggested by the American College of Obstetricians and Gynecologists and the American Society of Anesthesiologists guidelines. However, the panel found no evidence that outcomes were improved by the immediate availability of surgical and anesthesia personnel.
" 'Nonmedical' factors affecting VBAC utilization [were also] considered at the conference, based on talks by expert presenters," Dr. Spong and Dr. Signore said. "The panel [considered], for example, the influence of hospital administrative policies, healthcare expenditures, resource utilization, the threat of malpractice litigation and the associated financial ramifications (insurance premiums, settlements and awards), the impact of professional society recommendations and standards, the role of maternal and provider preferences, understanding how risk is communicated and understood, the medical ethics of choice and access to childbirth options, and availability of surgical and anesthesiology staff."
Other Recommendations
Other recommendations of the panel are that malpractice concerns be addressed and that additional research be performed to better understand the medical and nonmedical factors that affect decision making for women with previous cesarean deliveries. Also needed are clear, evidence-based risk assessment tools to facilitate the decision-making process from early pregnancy through delivery, considering individual risk factors as well as maternal values and preferences.
"All women who have had a prior cesarean section should talk to their provider about VBAC and reassess the safety of a trial of labor," panel member Emily Spencer Lukacz, MD, MAS, associate professor of clinical reproductive medicine at the University of California–San Diego, said during the telebriefing.
Some women prefer to attempt a trial of labor because they would like their partner to be involved in the delivery, they perceive labor and vaginal delivery as deeply empowering, and/or they believe it will enhance maternal–infant bonding, breast-feeding, and recovery. In contrast, preferences favoring planned cesarean delivery include scheduling convenience, avoidance of labor pain or possible emergency cesarean section, and/or desire for surgical sterilization at the time of delivery.
The panels hopes the conference findings will have important implications for health services planning as well as for informed clinical decisions. The panel strongly urged policymakers and healthcare providers to collaborate in developing and implementing appropriate strategies to address and alleviate malpractice concerns.
"Pregnancy is something of a risky endeavor," concluded Carol J. Rowland Hogue, PhD, MPH, Jules & Uldeen Terry Professor of Maternal and Child Health at Emory University in Atlanta, Georgia. "Problems occur irrespective of the mode of delivery.... It's a tradeoff between making the pregnancy as safe as possible for the mother and making the pregnancy as safe as possible for the baby."
The statement issued by the impartial, independent Consensus Development Conference panel synthesized their evaluation of the available evidence from a systematic literature review prepared through the Agency for Healthcare Research and Quality Evidence-Based Practice Centers program by the Oregon Evidence-Based Practice Center. The panel included 15 experts in obstetrics and gynecology, urogynecology, maternal and fetal medicine, pediatrics, midwifery, clinical pharmacology, medical ethics, internal medicine, family medicine, perinatal and reproductive psychiatry, anesthesiology, nursing, biostatistics, epidemiology, healthcare regulation, and risk management, and a public representative.
The panel also considered evidence from expert presentations and audience input at the conference to provide a basis for informed patient and clinician decisions concerning VBAC. The statement also includes specific recommendations for future research.
The draft consensus statement is available on the NIH Consensus Development Program Web site.
NIH Consensus Development Conference on (VBAC): New Insights. March 8-10, 2010.
Wednesday, March 10, 2010
Feeding Challenges in the Late Preterm Infant
From Neonatal Network
Karen Cleaveland, MSN, APRN, NNP-BC
Abstract
A late preterm infant is defined as one born between 34 and 36 6/7 weeks of completed gestation. The rate of late preterm births has risen 18 percent since the late 1990s. Data are beginning to emerge concerning morbidity rates and the risks these newborns face with regard to feeding difficulties, temperature instability, hypoglycemia, and hyperbilirubinemia.
Feeding challenges place these vulnerable infants at risk for prolonged hospital stays and readmission after discharge. To better address the unique needs of late preterm infants, providers should establish individual feeding orders. This article offers research-based suggestions for caring for these infants in the newborn nursery and the postpartum unit as well as parent teaching guidelines.
Introduction
Late preterm infants represent the most rapidly growing segment of preterm births in the U.S., accounting for 72 percent of the 12.7 percent preterm birth rate in 2005. This population of preterm infants is often cared for within the general newborn setting using the feeding guidelines for healthy term infants.
The staff of the newborn nursery often regards these infants as being term because they are usually of normal size and have a more mature appearance than preterm infants born after shorter gestations.
Compared with term infants, however, late preterm infants are at higher risk for excessive weight loss, feeding intolerance, hyperbilirubinemia, hypoglycemia, hypothermia, respiratory distress, apnea of prematurity, and a weak suck.
And, because of the increased risks these infants face, they also have higher morbidity and mortality than term infants. It is therefore necessary to recognize and treat this late preterm infant population with its own feeding and care guidelines instead of using guidelines for term infants. It is also vital to formulate a specific set of discharge planning teaching guidelines for them.
Feeding Challenges
Feeding challenges in the late preterm infant have been shown to be related to immature sucking and swallowing reflexes, which lead to improper latch-on for the breastfeeding infant as well as inadequate intake in the bottle-feeding infant.
As noted earlier, sucking, swallowing, and breathing must synchronize smoothly and effectively, with highly accurate timing and coordination, for safe and efficient oral feeding.[11]
Late preterm infants often have fewer awake-alert periods and less postural stability than their full-term counterparts, which often results in inadequate caloric intake. Decreased feeding combined with low energy stores and high energy demands place these infants at risk for inadequate hydration.
Health care providers and mothers may assume that the infant has ingested an adequate volume of milk when he falls asleep at the breast, when in reality the infant has exceeded his energy stores and has shut down without adequate caloric intake. Parents need to be educated regarding their infant's feeding cues, sleep-wake cycles, and how to promote postural stability.
Behaviors such as rooting, mouthing, and finger sucking indicate feeding readiness. Ensuring that the hips are flexed and the head and neck are aligned with the trunk provides appropriate postural stability, improving feeding success in the late preterm infant.
Immature brain development in late preterm infants is often overlooked because they are considered stable compared with extremely low birth weight premature infants. During the final few weeks of gestation, movements become smoother, oral motor skills more coordinated, and states of alertness more predictable.
This relates directly to why late preterm infants fail at feeding when they are discharged without the proper instructions being given to their caregivers. It is necessary that the nursing staff and parents, as well as the pediatric providers, receive education in achieving safe and effective oral feedings in late preterm infants.
The medical issues described earlier also make late preterm infants more susceptible to having a decreased state of arousal as well as poor endurance, resulting in early fatigue during feeding.
Karen Cleaveland, MSN, APRN, NNP-BC
Abstract
A late preterm infant is defined as one born between 34 and 36 6/7 weeks of completed gestation. The rate of late preterm births has risen 18 percent since the late 1990s. Data are beginning to emerge concerning morbidity rates and the risks these newborns face with regard to feeding difficulties, temperature instability, hypoglycemia, and hyperbilirubinemia.
Feeding challenges place these vulnerable infants at risk for prolonged hospital stays and readmission after discharge. To better address the unique needs of late preterm infants, providers should establish individual feeding orders. This article offers research-based suggestions for caring for these infants in the newborn nursery and the postpartum unit as well as parent teaching guidelines.
Introduction
Late preterm infants represent the most rapidly growing segment of preterm births in the U.S., accounting for 72 percent of the 12.7 percent preterm birth rate in 2005. This population of preterm infants is often cared for within the general newborn setting using the feeding guidelines for healthy term infants.
The staff of the newborn nursery often regards these infants as being term because they are usually of normal size and have a more mature appearance than preterm infants born after shorter gestations.
Compared with term infants, however, late preterm infants are at higher risk for excessive weight loss, feeding intolerance, hyperbilirubinemia, hypoglycemia, hypothermia, respiratory distress, apnea of prematurity, and a weak suck.
And, because of the increased risks these infants face, they also have higher morbidity and mortality than term infants. It is therefore necessary to recognize and treat this late preterm infant population with its own feeding and care guidelines instead of using guidelines for term infants. It is also vital to formulate a specific set of discharge planning teaching guidelines for them.
Feeding Challenges
Feeding challenges in the late preterm infant have been shown to be related to immature sucking and swallowing reflexes, which lead to improper latch-on for the breastfeeding infant as well as inadequate intake in the bottle-feeding infant.
As noted earlier, sucking, swallowing, and breathing must synchronize smoothly and effectively, with highly accurate timing and coordination, for safe and efficient oral feeding.[11]
Late preterm infants often have fewer awake-alert periods and less postural stability than their full-term counterparts, which often results in inadequate caloric intake. Decreased feeding combined with low energy stores and high energy demands place these infants at risk for inadequate hydration.
Health care providers and mothers may assume that the infant has ingested an adequate volume of milk when he falls asleep at the breast, when in reality the infant has exceeded his energy stores and has shut down without adequate caloric intake. Parents need to be educated regarding their infant's feeding cues, sleep-wake cycles, and how to promote postural stability.
Behaviors such as rooting, mouthing, and finger sucking indicate feeding readiness. Ensuring that the hips are flexed and the head and neck are aligned with the trunk provides appropriate postural stability, improving feeding success in the late preterm infant.
Immature brain development in late preterm infants is often overlooked because they are considered stable compared with extremely low birth weight premature infants. During the final few weeks of gestation, movements become smoother, oral motor skills more coordinated, and states of alertness more predictable.
This relates directly to why late preterm infants fail at feeding when they are discharged without the proper instructions being given to their caregivers. It is necessary that the nursing staff and parents, as well as the pediatric providers, receive education in achieving safe and effective oral feedings in late preterm infants.
The medical issues described earlier also make late preterm infants more susceptible to having a decreased state of arousal as well as poor endurance, resulting in early fatigue during feeding.
Friday, March 5, 2010
Asthma Severity Remains Stable in Pregnant Women Continuing Their Medication
From Medscape Medical News
Laurie Barclay, MD
March 5, 2010 — Asthma severity during pregnancy is similar to severity in the previous year if women continue to take their prescribed medication but is more severe if they discontinue it, according to the results of a study reported in the March issue of Obstetrics & Gynecology.
"Early investigators suggested a rule of thirds: in one third of women, asthma improves during pregnancy; in one third, asthma becomes worse; and in one third it remains the same," write Kathleen Belanger, PhD, from Yale University School of Public Health in New Haven, Connecticut, and colleagues. "However, assessment of improvement has often been subjective, and exacerbations have been measured by hospitalizations and emergency department visits. No studies have used the more common clinical endpoints of symptoms and medication use to assess exacerbation during pregnancy."
The goal of this study was to assess the effect of patient-related or treatment-related factors on asthma severity during pregnancy among women recruited before 24 weeks of gestation through private obstetricians and hospital clinics.
In-person and telephone interviews allowed gathering of symptom and medication data. Of 872 women with physician-diagnosed asthma, 686 had active asthma; of these, 641 women with complete data were analyzed. Changes in asthma severity, measured by the Global Initiative for Asthma, were evaluated during each month of pregnancy with use of cumulative logistic regression models for repeated measures.
Prepregnancy asthma severity and use of medication according to Global Initiative for Asthma guidelines significantly and profoundly affected the course of asthma.
No other factors analyzed were significant risk factors for clinically meaningful changes in asthma severity, defined as a 1-step change in the Global Initiative for Asthma category. These included race, age, atopic status, body mass index (BMI), parity, fetal sex, and smoking.
The most benefit from appropriate treatment was observed in women with milder asthma, with a 62% decreased risk for worsening asthma among those with intermittent asthma (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.23 - 0.64) and a 52% decreased risk among those with mild persistent asthma (OR, 0.48; 95% CI, 0.28 - 0.84). The gestational month or trimester was not consistently associated with changes in asthma severity.
"Asthma severity during pregnancy is similar to severity in the year before pregnancy, provided patients continue to use their prescribed medication," the study authors write.
"If women discontinue medication, even mild asthma is likely to become significantly more severe."
Limitations of this study include failure to directly measure lung function; and collection of symptom and medication data by interview, which could result in recall errors.
"Recent research indicates that the fetus may experience significant risk from exacerbations of asthma in the mother," the study authors conclude.
"The American College of Obstetricians and Gynecologists (the College) recommends continuation of medication for the health of both mother and fetus. The current paper provides empirical support for the College guidelines: exacerbations during pregnancy are best prevented when the mother uses asthma medication appropriate to her level of symptoms."
The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.
Obstet Gynecol. 2010;115:559-567. Abstract
Laurie Barclay, MD
March 5, 2010 — Asthma severity during pregnancy is similar to severity in the previous year if women continue to take their prescribed medication but is more severe if they discontinue it, according to the results of a study reported in the March issue of Obstetrics & Gynecology.
"Early investigators suggested a rule of thirds: in one third of women, asthma improves during pregnancy; in one third, asthma becomes worse; and in one third it remains the same," write Kathleen Belanger, PhD, from Yale University School of Public Health in New Haven, Connecticut, and colleagues. "However, assessment of improvement has often been subjective, and exacerbations have been measured by hospitalizations and emergency department visits. No studies have used the more common clinical endpoints of symptoms and medication use to assess exacerbation during pregnancy."
The goal of this study was to assess the effect of patient-related or treatment-related factors on asthma severity during pregnancy among women recruited before 24 weeks of gestation through private obstetricians and hospital clinics.
In-person and telephone interviews allowed gathering of symptom and medication data. Of 872 women with physician-diagnosed asthma, 686 had active asthma; of these, 641 women with complete data were analyzed. Changes in asthma severity, measured by the Global Initiative for Asthma, were evaluated during each month of pregnancy with use of cumulative logistic regression models for repeated measures.
Prepregnancy asthma severity and use of medication according to Global Initiative for Asthma guidelines significantly and profoundly affected the course of asthma.
No other factors analyzed were significant risk factors for clinically meaningful changes in asthma severity, defined as a 1-step change in the Global Initiative for Asthma category. These included race, age, atopic status, body mass index (BMI), parity, fetal sex, and smoking.
The most benefit from appropriate treatment was observed in women with milder asthma, with a 62% decreased risk for worsening asthma among those with intermittent asthma (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.23 - 0.64) and a 52% decreased risk among those with mild persistent asthma (OR, 0.48; 95% CI, 0.28 - 0.84). The gestational month or trimester was not consistently associated with changes in asthma severity.
"Asthma severity during pregnancy is similar to severity in the year before pregnancy, provided patients continue to use their prescribed medication," the study authors write.
"If women discontinue medication, even mild asthma is likely to become significantly more severe."
Limitations of this study include failure to directly measure lung function; and collection of symptom and medication data by interview, which could result in recall errors.
"Recent research indicates that the fetus may experience significant risk from exacerbations of asthma in the mother," the study authors conclude.
"The American College of Obstetricians and Gynecologists (the College) recommends continuation of medication for the health of both mother and fetus. The current paper provides empirical support for the College guidelines: exacerbations during pregnancy are best prevented when the mother uses asthma medication appropriate to her level of symptoms."
The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.
Obstet Gynecol. 2010;115:559-567. Abstract
Thursday, March 4, 2010
High Plasma Folate Levels in Pregnancy May Increase Asthma Risk for Offspring
From Medscape Medical News
Deborah Brauser
March 4, 2010 (New Orleans, Louisiana) — Children of mothers with high plasma folate levels during pregnancy appear to have an increased risk of developing asthma by the age of 3 years, according to a sampling from the Norwegian Mother and Child Cohort (NMCC) study presented in a poster session here at the American Academy of Allergy, Asthma and Immunology 2010 Annual Meeting.
"Norway provides a unique opportunity to address the question of possible deleterious consequences of high folate intake during pregnancy because the food supply there is not fortified with folates,"
"It's one of the few places where you can look at whether the supplementation, which is clearly good from the point of view of decreasing birth defects, could potentially also have some adverse effects,"
Recent Studies Question Folic Effects
Previous research has consistently shown that the periconceptional intake of folic acid reduces the risk for neural tube defects in infants, leading to the increased use of these supplements and to the fortification of foods with folic acid in the United States and other countries.
However, a recent study showed that high dietary supplementation with folic acid and other methyl donors in pregnant mice led to allergic asthma phenotypes, through epigenetic changes, in offspring.
In another study recently conducted by Dr. London's research team, an association was found between folate supplements used during early pregnancy and an increased risk for respiratory disease in children up to the age of 18 months.
For this study, they examined data on 507 mothers from the population-based NMCC who had plasma folate levels measured during their second trimester of pregnancy, and who had children with asthma at the age of 3 years. The folate levels of 1455 mothers of healthy controls were also measured.
"The age of 3 isn't a perfect phenotype because that's early to diagnose asthma, but that was the age that the kids were at the time of the study," explained Dr. London.
A Linear Increase Found
Results showed that mothers in the top quintile of plasma folate had children with an increased risk for asthma at age 3 (adjusted odds ratio [OR], 1.66; 95% confidence interval [CI], 1.16 - 2.37), relative to mothers in the bottom quintile.
In addition, the investigators found "a trend of linear increase across quintiles" (P = 0.007). Children of mothers with folate levels between the 70th and 95th percentiles had an OR of 1.34 (95% CI, 1.03 - 1.73), whereas children of mothers with levels above the 95th percentile had an OR of 1.44 (95% CI, 1.08-1.93).
"In other words, as the mother's folate level increased, so did the risk of asthma in their child," said Dr. London.
"Overall, this study showed small effects, but it definitely doesn't mean that people shouldn't use folates," she noted. "It just raises the possibility that, as a population, maybe we're reaching folate repletion. It's also possible that there could be a double-edged sword to folate supplementation; certainly it's looking like that may be the case in some cancer studies. However, at this stage, I wouldn't want to be quoted as saying that we should rethink how much folate people are getting."
The investigators next plan to follow-up with these children to "an age when asthma can be more reliably diagnosed," and through to age 7. They've received funding to assess the epigenetic effects of folate supplementation. "In these women, we're going to be looking at cord blood DNA, and looking at whether the patterns of methylation are different according to folate levels and asthma status in the child," explained Dr. London.
Caution Urged
"The findings were consistent with literature from animal models where folic acid could possibly lead to a higher risk for asthma," said Juan Celedón, MD, DrPH, associate professor of medicine at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts.
"However, I think that there are some cautions with this study," added Dr. Celedón, who was not involved in the research. "First, you can't diagnose asthma until the age of 6, so further follow-up of those kids is needed. Second, they did not measure any objective markers of allergy. And third, they didn't show a mechanism. All that said, the findings are very intriguing,"
"We just need to be very cautious in this area," he told Medscape Allergy & Clinical Immunology. "A woman takes folic acid to protect against neural tube defects and it's been very, very effective for that. I think we need to be extraordinarily careful and need to assess this thoroughly before we can begin to make any recommendations [for] current practice in regard to changing or even reducing folic acid during pregnancy."
This study was funded by the Norwegian Research Council. The NMCC study was funded by the Norwegian Ministry of Health and a grant from the National Institute of Environmental Health Sciences/National Institutes of Health. Dr. London and Dr. Celedón have disclosed no relevant financial relationships.
American Academy of Allergy, Asthma and Immunology (AAAAI) 2010 Annual Meeting: Abstract 505. Presented February 28, 2010.
Deborah Brauser
March 4, 2010 (New Orleans, Louisiana) — Children of mothers with high plasma folate levels during pregnancy appear to have an increased risk of developing asthma by the age of 3 years, according to a sampling from the Norwegian Mother and Child Cohort (NMCC) study presented in a poster session here at the American Academy of Allergy, Asthma and Immunology 2010 Annual Meeting.
"Norway provides a unique opportunity to address the question of possible deleterious consequences of high folate intake during pregnancy because the food supply there is not fortified with folates,"
"It's one of the few places where you can look at whether the supplementation, which is clearly good from the point of view of decreasing birth defects, could potentially also have some adverse effects,"
Recent Studies Question Folic Effects
Previous research has consistently shown that the periconceptional intake of folic acid reduces the risk for neural tube defects in infants, leading to the increased use of these supplements and to the fortification of foods with folic acid in the United States and other countries.
However, a recent study showed that high dietary supplementation with folic acid and other methyl donors in pregnant mice led to allergic asthma phenotypes, through epigenetic changes, in offspring.
In another study recently conducted by Dr. London's research team, an association was found between folate supplements used during early pregnancy and an increased risk for respiratory disease in children up to the age of 18 months.
For this study, they examined data on 507 mothers from the population-based NMCC who had plasma folate levels measured during their second trimester of pregnancy, and who had children with asthma at the age of 3 years. The folate levels of 1455 mothers of healthy controls were also measured.
"The age of 3 isn't a perfect phenotype because that's early to diagnose asthma, but that was the age that the kids were at the time of the study," explained Dr. London.
A Linear Increase Found
Results showed that mothers in the top quintile of plasma folate had children with an increased risk for asthma at age 3 (adjusted odds ratio [OR], 1.66; 95% confidence interval [CI], 1.16 - 2.37), relative to mothers in the bottom quintile.
In addition, the investigators found "a trend of linear increase across quintiles" (P = 0.007). Children of mothers with folate levels between the 70th and 95th percentiles had an OR of 1.34 (95% CI, 1.03 - 1.73), whereas children of mothers with levels above the 95th percentile had an OR of 1.44 (95% CI, 1.08-1.93).
"In other words, as the mother's folate level increased, so did the risk of asthma in their child," said Dr. London.
"Overall, this study showed small effects, but it definitely doesn't mean that people shouldn't use folates," she noted. "It just raises the possibility that, as a population, maybe we're reaching folate repletion. It's also possible that there could be a double-edged sword to folate supplementation; certainly it's looking like that may be the case in some cancer studies. However, at this stage, I wouldn't want to be quoted as saying that we should rethink how much folate people are getting."
The investigators next plan to follow-up with these children to "an age when asthma can be more reliably diagnosed," and through to age 7. They've received funding to assess the epigenetic effects of folate supplementation. "In these women, we're going to be looking at cord blood DNA, and looking at whether the patterns of methylation are different according to folate levels and asthma status in the child," explained Dr. London.
Caution Urged
"The findings were consistent with literature from animal models where folic acid could possibly lead to a higher risk for asthma," said Juan Celedón, MD, DrPH, associate professor of medicine at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts.
"However, I think that there are some cautions with this study," added Dr. Celedón, who was not involved in the research. "First, you can't diagnose asthma until the age of 6, so further follow-up of those kids is needed. Second, they did not measure any objective markers of allergy. And third, they didn't show a mechanism. All that said, the findings are very intriguing,"
"We just need to be very cautious in this area," he told Medscape Allergy & Clinical Immunology. "A woman takes folic acid to protect against neural tube defects and it's been very, very effective for that. I think we need to be extraordinarily careful and need to assess this thoroughly before we can begin to make any recommendations [for] current practice in regard to changing or even reducing folic acid during pregnancy."
This study was funded by the Norwegian Research Council. The NMCC study was funded by the Norwegian Ministry of Health and a grant from the National Institute of Environmental Health Sciences/National Institutes of Health. Dr. London and Dr. Celedón have disclosed no relevant financial relationships.
American Academy of Allergy, Asthma and Immunology (AAAAI) 2010 Annual Meeting: Abstract 505. Presented February 28, 2010.
Children of Psychiatrically Ill Parents at Risk for Mental Disorders
From Medscape Medical News
Allison Gandey
March 4, 2010 — Children of 2 parents with schizophrenia or bipolar disorder are more likely to develop these or other mental disorders, a new national study shows.
Young people with both parents diagnosed as having schizophrenia were 27% more likely to develop the illness.
The risk of bipolar disorder was similar at almost 25%.
In contrast, people with only 1 parent with a psychiatric illness were much less likely to develop mental disorders. Just 7% of those with a parent with schizophrenia developed the disease.
Only 4% of people with 1 parent with bipolar disorder had the disorder.
The population-based study of 2.7 million people in Denmark is published in the March issue of Archives of General Psychiatry.
Irving Gottesman has been a leader in psychiatric genetic epidemiology for many decades.
"I think we set a world record in terms of the number of parent couples we looked at," lead investigator Irving Gottesman, PhD, from the University of Minnesota Medical School in Minneapolis, said during an interview. "Our cohort included 196 couples with 270 offspring — this is very large," he said.
"Irving Gottesman has been a leader in psychiatric genetic epidemiology for many decades," James Potash, MD, from Johns Hopkins University in Baltimore, Maryland, told Medscape Psychiatry.
"This gigantic study gives us hard numbers to help assess risk," he said.
Large Study
The research team linked data from the Danish civil registration system to the Danish psychiatric central register. Investigators wanted to determine the risk of schizophrenia, bipolar disorder, unipolar depressive disorder, or any diagnosis.
The risk for any psychiatric disorder in offspring with both parents with schizophrenia was close to 68%. For 2 parents with bipolar disorder, the risk was 44%.
During an interview, Dr. Gottesman acknowledged the increased risk, but he also pointed to the high numbers that suggest no diagnosis at all.
"This is something that was cut from the paper because there wasn't enough space to elaborate, but if you do the math and follow the numbers through, you will see high rates with no later diagnosis," he said.
For children with both parents with schizophrenia, the chance of no diagnosis was 73%. For children with both parents with bipolar disorder, the rate was 75%.
"This is good news for many people," Dr. Gottesman said.
Weighing the Risk
Dr. Potash said he agrees that most offspring will not be diagnosed as having mental disorders. "The risk is certainly higher, but many won't become ill." He also points out that this study is consistent with previous work.
"For the practicing clinician," Dr. Gottesman said, "I think this paper speaks to the importance of taking a careful family history."
He notes the many challenges of the intake interview — particularly when it comes to discussing psychiatric health. "People are often embarrassed about mental disorders and keep them secret. Not everyone in a family will necessarily know."
Dr. Gottesman points out that it can be helpful to ask related questions about alcohol and drug use, including more subtle questions about weekly consumption.
Arch Gen Psychiatry. 2010;67:252-257.
Allison Gandey
March 4, 2010 — Children of 2 parents with schizophrenia or bipolar disorder are more likely to develop these or other mental disorders, a new national study shows.
Young people with both parents diagnosed as having schizophrenia were 27% more likely to develop the illness.
The risk of bipolar disorder was similar at almost 25%.
In contrast, people with only 1 parent with a psychiatric illness were much less likely to develop mental disorders. Just 7% of those with a parent with schizophrenia developed the disease.
Only 4% of people with 1 parent with bipolar disorder had the disorder.
The population-based study of 2.7 million people in Denmark is published in the March issue of Archives of General Psychiatry.
Irving Gottesman has been a leader in psychiatric genetic epidemiology for many decades.
"I think we set a world record in terms of the number of parent couples we looked at," lead investigator Irving Gottesman, PhD, from the University of Minnesota Medical School in Minneapolis, said during an interview. "Our cohort included 196 couples with 270 offspring — this is very large," he said.
"Irving Gottesman has been a leader in psychiatric genetic epidemiology for many decades," James Potash, MD, from Johns Hopkins University in Baltimore, Maryland, told Medscape Psychiatry.
"This gigantic study gives us hard numbers to help assess risk," he said.
Large Study
The research team linked data from the Danish civil registration system to the Danish psychiatric central register. Investigators wanted to determine the risk of schizophrenia, bipolar disorder, unipolar depressive disorder, or any diagnosis.
The risk for any psychiatric disorder in offspring with both parents with schizophrenia was close to 68%. For 2 parents with bipolar disorder, the risk was 44%.
During an interview, Dr. Gottesman acknowledged the increased risk, but he also pointed to the high numbers that suggest no diagnosis at all.
"This is something that was cut from the paper because there wasn't enough space to elaborate, but if you do the math and follow the numbers through, you will see high rates with no later diagnosis," he said.
For children with both parents with schizophrenia, the chance of no diagnosis was 73%. For children with both parents with bipolar disorder, the rate was 75%.
"This is good news for many people," Dr. Gottesman said.
Weighing the Risk
Dr. Potash said he agrees that most offspring will not be diagnosed as having mental disorders. "The risk is certainly higher, but many won't become ill." He also points out that this study is consistent with previous work.
"For the practicing clinician," Dr. Gottesman said, "I think this paper speaks to the importance of taking a careful family history."
He notes the many challenges of the intake interview — particularly when it comes to discussing psychiatric health. "People are often embarrassed about mental disorders and keep them secret. Not everyone in a family will necessarily know."
Dr. Gottesman points out that it can be helpful to ask related questions about alcohol and drug use, including more subtle questions about weekly consumption.
Arch Gen Psychiatry. 2010;67:252-257.
Monday, March 1, 2010
Maternal Physical Characteristics, Lifestyle Habits Predict Early Fetal Growth
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
CME Released: 02/18/2010; Valid for credit through 02/18/2011
February 18, 2010 — Maternal physical characteristics and lifestyle habits are independently associated with early fetal growth, according to the results of a study reported in the February 10 issue of the Journal of the American Medical Association.
"Adverse environmental exposures lead to developmental adaptations in fetal life," write Dennis O. Mook-Kanamori, MD, MSc, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues. "The influences of maternal physical characteristics and lifestyle habits on first trimester fetal adaptations and the postnatal consequences are not known."
The goal of this study was to determine the risk factors and outcomes associated with first-trimester growth restriction. In Rotterdam, the Netherlands, between 2001 and 2005, a total of 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle were enrolled. The investigators evaluated associations of maternal physical characteristics and lifestyle habits with first-trimester fetal growth, and then subsequently looked at the associations of first-trimester fetal growth restriction with the risks for adverse birth outcomes and postnatal growth acceleration until age 2 years.
Between gestational ages of 10 weeks 0 days and 13 weeks 6 days, an ultrasound study was performed to measure first-trimester fetal growth based on crown-to-rump length. Primary study endpoints included preterm birth, defined as gestational age of less than 37 weeks; low birth weight (< 2500 g); and small size for gestational age (lowest fifth birth centile); as well as postnatal growth measured until age 2 years.
Maternal age was positively associated with first-trimester fetal crown-to-rump length, based on multivariate analysis (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 -1.18 per SD score increase). Factors associated with a shorter crown-to-rump length were higher diastolic blood pressure and higher hematocrit level (differences, −0.40 mm; 95% CI, −0.74 to −0.06 and −0.52 mm; 95% CI, −0.90 to −0.14 per SD increase, respectively).
Shorter fetal crown-to-rump lengths were reported for mothers who both smoked and did not use folic acid supplements vs mothers who were nonsmokers and optimal users of folic acid supplements (difference, −3.84 mm; 95% CI, −5.71 to −1.98).
Compared with normal first-trimester fetal growth, adverse outcomes associated with first-trimester growth restriction included preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 - 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 - 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 - 4.25).
For each SD decrease in first-trimester fetal crown-to-rump length, there was a postnatal growth acceleration until age 2 years (SD score increase, 0.139 per 2 years; 95% CI, 0.097 - 0.181).
"Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth," the study authors write. "First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood....Further studies are needed to assess the associations of first-trimester growth variation on the risks of disease in later childhood and adulthood."
Limitations of this study include possible misclassification of gestational age because of inability to measure the timing of ovulation and implantation, and possible recall bias confounding dating of the last menstrual period.
In an accompanying editorial, Gordon C.S. Smith, MD, PhD, from the University of Cambridge in Cambridge, United Kingdom, notes that this study adds to the body of evidence suggesting that growth and placental function in the first trimester of pregnancy significantly affect fetal and infant growth.
"Hence, complications of late pregnancy may, at least for some women, already be determined in the first 3 months postconception, even before a woman has sought prenatal care," Dr. Smith writes. "The multiple associations described suggest that combined ultrasonic and biochemical screening in early pregnancy may be able to identify women at high risk of complications in late pregnancy. The challenges for future research are to produce robust screening tests with acceptable levels of detection and prediction, and to identify interventions that are effective in improving outcome when a pregnancy has been identified as high risk."
The first phase of the Generation R Study was supported financially by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research. One of the study authors (Dr. Jaddoe) has received funding from the Netherlands Organization for Health Research. The other study authors have disclosed no relevant financial relationships.
Dr. Smith reports that he has been a member of preterm labor advisory boards for GlaxoSmithKline. Funding for his editorial was provided by Cambridge National Institute for Health (NHS) Research Biomedical Research Centre, Cambridge University Hospitals, NHS Foundation Trust.
JAMA. 2010;303:527-534, 561-562. Abstract
Clinical Context
Human growth and development rates are highest in the first trimester of pregnancy, and first-trimester crown-to-rump length is used as a dating method in obstetrics and as an assessment of fetal growth. However, the relationship between fetal growth restriction in the first trimester and pregnancy and postnatal outcomes is still unknown.
This is a population-based, prospective cohort study to examine the association between maternal characteristics and lifestyle habits and first-trimester crown-to-rump length, and the association between growth restriction and neonatal and postnatal outcomes to 2 years.
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
CME Released: 02/18/2010; Valid for credit through 02/18/2011
February 18, 2010 — Maternal physical characteristics and lifestyle habits are independently associated with early fetal growth, according to the results of a study reported in the February 10 issue of the Journal of the American Medical Association.
"Adverse environmental exposures lead to developmental adaptations in fetal life," write Dennis O. Mook-Kanamori, MD, MSc, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues. "The influences of maternal physical characteristics and lifestyle habits on first trimester fetal adaptations and the postnatal consequences are not known."
The goal of this study was to determine the risk factors and outcomes associated with first-trimester growth restriction. In Rotterdam, the Netherlands, between 2001 and 2005, a total of 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle were enrolled. The investigators evaluated associations of maternal physical characteristics and lifestyle habits with first-trimester fetal growth, and then subsequently looked at the associations of first-trimester fetal growth restriction with the risks for adverse birth outcomes and postnatal growth acceleration until age 2 years.
Between gestational ages of 10 weeks 0 days and 13 weeks 6 days, an ultrasound study was performed to measure first-trimester fetal growth based on crown-to-rump length. Primary study endpoints included preterm birth, defined as gestational age of less than 37 weeks; low birth weight (< 2500 g); and small size for gestational age (lowest fifth birth centile); as well as postnatal growth measured until age 2 years.
Maternal age was positively associated with first-trimester fetal crown-to-rump length, based on multivariate analysis (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 -1.18 per SD score increase). Factors associated with a shorter crown-to-rump length were higher diastolic blood pressure and higher hematocrit level (differences, −0.40 mm; 95% CI, −0.74 to −0.06 and −0.52 mm; 95% CI, −0.90 to −0.14 per SD increase, respectively).
Shorter fetal crown-to-rump lengths were reported for mothers who both smoked and did not use folic acid supplements vs mothers who were nonsmokers and optimal users of folic acid supplements (difference, −3.84 mm; 95% CI, −5.71 to −1.98).
Compared with normal first-trimester fetal growth, adverse outcomes associated with first-trimester growth restriction included preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 - 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 - 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 - 4.25).
For each SD decrease in first-trimester fetal crown-to-rump length, there was a postnatal growth acceleration until age 2 years (SD score increase, 0.139 per 2 years; 95% CI, 0.097 - 0.181).
"Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth," the study authors write. "First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood....Further studies are needed to assess the associations of first-trimester growth variation on the risks of disease in later childhood and adulthood."
Limitations of this study include possible misclassification of gestational age because of inability to measure the timing of ovulation and implantation, and possible recall bias confounding dating of the last menstrual period.
In an accompanying editorial, Gordon C.S. Smith, MD, PhD, from the University of Cambridge in Cambridge, United Kingdom, notes that this study adds to the body of evidence suggesting that growth and placental function in the first trimester of pregnancy significantly affect fetal and infant growth.
"Hence, complications of late pregnancy may, at least for some women, already be determined in the first 3 months postconception, even before a woman has sought prenatal care," Dr. Smith writes. "The multiple associations described suggest that combined ultrasonic and biochemical screening in early pregnancy may be able to identify women at high risk of complications in late pregnancy. The challenges for future research are to produce robust screening tests with acceptable levels of detection and prediction, and to identify interventions that are effective in improving outcome when a pregnancy has been identified as high risk."
The first phase of the Generation R Study was supported financially by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research. One of the study authors (Dr. Jaddoe) has received funding from the Netherlands Organization for Health Research. The other study authors have disclosed no relevant financial relationships.
Dr. Smith reports that he has been a member of preterm labor advisory boards for GlaxoSmithKline. Funding for his editorial was provided by Cambridge National Institute for Health (NHS) Research Biomedical Research Centre, Cambridge University Hospitals, NHS Foundation Trust.
JAMA. 2010;303:527-534, 561-562. Abstract
Clinical Context
Human growth and development rates are highest in the first trimester of pregnancy, and first-trimester crown-to-rump length is used as a dating method in obstetrics and as an assessment of fetal growth. However, the relationship between fetal growth restriction in the first trimester and pregnancy and postnatal outcomes is still unknown.
This is a population-based, prospective cohort study to examine the association between maternal characteristics and lifestyle habits and first-trimester crown-to-rump length, and the association between growth restriction and neonatal and postnatal outcomes to 2 years.
Older Maternal Age Linked to Increased Risk for Autism in Children
From MedscapeCME Clinical Briefs
News Author: Caroline Cassels
CME Author: Hien T. Nghiem, MD
February 16, 2010 — Advanced maternal age significantly increases the risk of having a child with autism irrespective of paternal age, a large population-based study suggests.
The research, conducted by investigators at UC Davis Health System, Sacramento, California, shows that the incremental risk of having a child with autism increased by 18% for every 5-year increase in maternal age.
"These data show that the risk of having a child with full-syndrome autism increases with maternal age, but increased risk from advancing paternal age primarily occurs among younger mothers (<30)," the researchers, led by senior investigator Irva-Hertz-Picciotto, PhD, MPH, write.
According to lead study author Janie Shelton, a doctoral student, the study challenges the hypothesis that the father's age is a key factor in increasing autism risk.
"It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older and the mother is under 30 years old.
Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism," Ms. Shelton said in a statement.
The study was published online February 8 in Autism Research.
According to the study, previous research on autism and paternal age have yielded conflicting results on whether mothers, fathers, or both contribute to an increased risk for autism in children.
To determine the independent or dependent effect from each parent, the researchers gathered electronic records for all births in California between January 1, 1990, and December 31, 1999. The records incorporated detailed demographic information, including the age of both parents.
To identify which children would subsequently develop autism, the investigators obtained electronic records identifying children born during the study period who later received an autism diagnosis from California's Department of Developmental Services. For the study, autism was defined as a diagnosis of full-syndrome autism at a California regional center.
The final study sample included 4.9 million births and 12,159 cases of autism. The researchers report that for older mothers there was a stepwise progression in the risk of having a child who would later be diagnosed as having autism, irrespective of the father's age.
"We demonstrate that advancing maternal age increases the risk of autism independent of father's age, while advancing father's age increases the risk of autism primarily for mothers under 30. Among mothers over 30, we observed a small increased risk only among fathers 40+; even at the highest age group, the increase was smaller and less precise than that for fathers 30-34 among younger mothers," the researchers write.
At this point, the reason parental age influences autism risk is not clear. "We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so we can begin to design interventions," Dr. Hertz-Picciotto said in a statement.
The study authors have disclosed no relevant financial relationships.
Autism Res. Published online February 8, 2010.
Clinical Context
In recent decades, the diagnosis of autism has increased. Autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years. Between 1990 and 2001, there has been a 7-fold increase in cumulative incidence observed among 5-year-olds in California. Known factors can explain this finding such as changes in the diagnostic criteria and a shift towards younger age at diagnosis. Studies have linked advancing parental age as a risk factor for autism. However, reports on autism and parental age have yielded conflicting results on whether mothers, fathers, or both, contribute to increased risk.
The aim of this study was to analyze restricted strata of parental age in a 10-year California birth cohort to determine the independent or dependent effect from each parent.
Study Highlights
To establish the cohort of this study, the investigators linked autism cases from California Department of Developmental Services records to state birth files (1990-1999). Subsequently, only singleton births with complete data on parental age and education were included (n = 4,947,935; cases = 12,159).
The net effects of maternal and paternal age on the risk for autism after adjustment for potential confounders were modeled by logistic regression, with the parental age terms specified either as continuous or categoric.
aORs for the effects of advancing paternal (maternal) age were also estimated with use of stratified multivariate logistic regression in strata defined by narrow (5-year) maternal (paternal) age groups.
The covariates adjusted in all models were parental education, year of child's birth, race or ethnicity of mother and father, mother's parity, and insurance payment.
Results demonstrated that children with autism were more likely than control subjects to be men, to have older parents, and to be either non-Hispanic white or Asian vs children without autism.
In multivariate logistic regression models, advancing maternal age increased the risk for autism monotonically regardless of the paternal age.
Compared with mothers aged 25 to 29 years, the aOR for mothers older than 40 years was 1.51 (95% CI, 1.35 - 1.70) vs mothers younger than 25 years (aOR, 1.77; 95% CI, 1.56 - 2.00).
In contrast, autism risk was associated with advancing paternal age (> 40 years), primarily among mothers younger than 30 years (aOR, 1.59; 95% CI, 1.37 - 1.85) vs the reference group of fathers aged 25 to 29 years (aOR, 0.76; 95% CI, 0.70 - 0.82).
Among mothers 30 years and older, the aOR was 1.13 (95% CI, 1.01 - 1.27) for fathers 40 years and older vs fathers aged 25 to 29 years, almost identical to the aOR for fathers younger than 25 years.
Based on the first examination of heterogeneity in parental age effects, it appears that a women's risk of delivering a child who develops autism increases throughout her reproductive years, whereas the father's age (> 40 years) confers an increased risk for autism when the mother is younger than 30 years but has limited effect when the mother is older than 30 years.
Additionally, the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California between 1990 and 1999.
Clinical Implications
According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years.
The risk of having a child with autism increases with older maternal age, but the increased risk from advancing paternal age occurs when the mother is younger (age < 30 years).
News Author: Caroline Cassels
CME Author: Hien T. Nghiem, MD
February 16, 2010 — Advanced maternal age significantly increases the risk of having a child with autism irrespective of paternal age, a large population-based study suggests.
The research, conducted by investigators at UC Davis Health System, Sacramento, California, shows that the incremental risk of having a child with autism increased by 18% for every 5-year increase in maternal age.
"These data show that the risk of having a child with full-syndrome autism increases with maternal age, but increased risk from advancing paternal age primarily occurs among younger mothers (<30)," the researchers, led by senior investigator Irva-Hertz-Picciotto, PhD, MPH, write.
According to lead study author Janie Shelton, a doctoral student, the study challenges the hypothesis that the father's age is a key factor in increasing autism risk.
"It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older and the mother is under 30 years old.
Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism," Ms. Shelton said in a statement.
The study was published online February 8 in Autism Research.
According to the study, previous research on autism and paternal age have yielded conflicting results on whether mothers, fathers, or both contribute to an increased risk for autism in children.
To determine the independent or dependent effect from each parent, the researchers gathered electronic records for all births in California between January 1, 1990, and December 31, 1999. The records incorporated detailed demographic information, including the age of both parents.
To identify which children would subsequently develop autism, the investigators obtained electronic records identifying children born during the study period who later received an autism diagnosis from California's Department of Developmental Services. For the study, autism was defined as a diagnosis of full-syndrome autism at a California regional center.
The final study sample included 4.9 million births and 12,159 cases of autism. The researchers report that for older mothers there was a stepwise progression in the risk of having a child who would later be diagnosed as having autism, irrespective of the father's age.
"We demonstrate that advancing maternal age increases the risk of autism independent of father's age, while advancing father's age increases the risk of autism primarily for mothers under 30. Among mothers over 30, we observed a small increased risk only among fathers 40+; even at the highest age group, the increase was smaller and less precise than that for fathers 30-34 among younger mothers," the researchers write.
At this point, the reason parental age influences autism risk is not clear. "We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so we can begin to design interventions," Dr. Hertz-Picciotto said in a statement.
The study authors have disclosed no relevant financial relationships.
Autism Res. Published online February 8, 2010.
Clinical Context
In recent decades, the diagnosis of autism has increased. Autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years. Between 1990 and 2001, there has been a 7-fold increase in cumulative incidence observed among 5-year-olds in California. Known factors can explain this finding such as changes in the diagnostic criteria and a shift towards younger age at diagnosis. Studies have linked advancing parental age as a risk factor for autism. However, reports on autism and parental age have yielded conflicting results on whether mothers, fathers, or both, contribute to increased risk.
The aim of this study was to analyze restricted strata of parental age in a 10-year California birth cohort to determine the independent or dependent effect from each parent.
Study Highlights
To establish the cohort of this study, the investigators linked autism cases from California Department of Developmental Services records to state birth files (1990-1999). Subsequently, only singleton births with complete data on parental age and education were included (n = 4,947,935; cases = 12,159).
The net effects of maternal and paternal age on the risk for autism after adjustment for potential confounders were modeled by logistic regression, with the parental age terms specified either as continuous or categoric.
aORs for the effects of advancing paternal (maternal) age were also estimated with use of stratified multivariate logistic regression in strata defined by narrow (5-year) maternal (paternal) age groups.
The covariates adjusted in all models were parental education, year of child's birth, race or ethnicity of mother and father, mother's parity, and insurance payment.
Results demonstrated that children with autism were more likely than control subjects to be men, to have older parents, and to be either non-Hispanic white or Asian vs children without autism.
In multivariate logistic regression models, advancing maternal age increased the risk for autism monotonically regardless of the paternal age.
Compared with mothers aged 25 to 29 years, the aOR for mothers older than 40 years was 1.51 (95% CI, 1.35 - 1.70) vs mothers younger than 25 years (aOR, 1.77; 95% CI, 1.56 - 2.00).
In contrast, autism risk was associated with advancing paternal age (> 40 years), primarily among mothers younger than 30 years (aOR, 1.59; 95% CI, 1.37 - 1.85) vs the reference group of fathers aged 25 to 29 years (aOR, 0.76; 95% CI, 0.70 - 0.82).
Among mothers 30 years and older, the aOR was 1.13 (95% CI, 1.01 - 1.27) for fathers 40 years and older vs fathers aged 25 to 29 years, almost identical to the aOR for fathers younger than 25 years.
Based on the first examination of heterogeneity in parental age effects, it appears that a women's risk of delivering a child who develops autism increases throughout her reproductive years, whereas the father's age (> 40 years) confers an increased risk for autism when the mother is younger than 30 years but has limited effect when the mother is older than 30 years.
Additionally, the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California between 1990 and 1999.
Clinical Implications
According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years.
The risk of having a child with autism increases with older maternal age, but the increased risk from advancing paternal age occurs when the mother is younger (age < 30 years).
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