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One-step gestational diabetes screening doesn’t improve outcomes
according to data from a before-and-after cohort study of women in the state of Washington.
The one-step test, a 75-g 2-hour oral glucose tolerance test (OGTT), was recommended for all pregnant women in 2010, although the traditional two-step test – a 50-g screening glucose challenge test followed by a 100-g 3-hour OGTT – remains widely used, wrote Gaia Pocobelli, PhD, of Kaiser Permanente Washington Health Research Institute, Seattle, and her colleagues. “No randomized trial has been published comparing outcomes of the two approaches.”
In a study published in Obstetrics & Gynecology, the researchers compared data from 23,257 women who received prenatal care in Washington State between January 2009 and December 2014, including 8,363 women who received care before the guideline change, 4,103 who received care during a transition period, and 10,791 after the guideline change. Approximately 60% of the women received care from clinicians internal to Kaiser Permanente; 40% received care from external providers. Most (87%) of the internal clinicians switched to the one-step approach, the researchers said. Only 5% of external providers did so.
Overall, adopting the one-step approach was associated with a 41% increase in the diagnosis of GDM without improved maternal or neonatal outcomes, the researchers noted.
The incidence of GDM increased from 7% before the guideline change to 11% afterward for women seen by internal providers. For women seen by external providers, gestational diabetes incidence increased from 10% to 11%.
For women seen by internal providers, the use of insulin increased from 1% before the guideline change to 4% afterward; for women seen by external providers, use of insulin increased from 1.3% to 1.4% (change between the groups P less than .001).
In addition, women seen by internal providers were more likely to undergo induction of labor after the guideline change (25% to 29%), while labor induction decreased for women seen by external providers (31% to 29%) for a relative risk of 1.2.
Neonatal hypoglycemia increased from 1% to 2% among women seen by internal providers, but decreased slightly from 2.4% to 2.1% for women seen by external providers, for a relative risk of 1.77.
There were no significant differences between the women seen by internal and external providers in risk of primary cesarean section, large for gestational age, small for gestational age, or neonatal ICU admission.
The main limitation of the study was the potential confounding variables including maternal diet and exercise, and possible underreporting of risk factors such as smoking, the researchers noted. However, the results were strengthened by the large study population, and the results “do not suggest a benefit of adopting the one-step over the two-step approach.
“Kaiser Permanente Washington has revised [its] guidelines to return to a two-step process. We recommend that any health care system considering switching to the one-step approach incorporate a rigorous evaluation of changes in maternal and neonatal outcomes,” Dr. Pocobelli and her associates added.
Dr. Pocobelli disclosed funding from Jazz Pharmaceuticals for work unrelated to this study. The study was supported in part by a grant from the Group Health Foundation Momentum Fund.
Diabetes is a significant global public health concern, but is especially problematic for women of reproductive age because diabetes in pregnancy can cause significant health complications for the mother and baby. Gestational diabetes mellitus (GDM) affects up to 10% of pregnancies in the United States annually, and is associated with perinatal loss, operative delivery, macrosomia, hypoglycemia, respiratory distress syndrome, and metabolic derangements for the offspring. For the mother, GDM is associated with hypertensive disorders, infections, hydramnios, and increased risk for developing type 2 diabetes later in life. As the incidence of GDM continues to rise, studies examining how to reduce, manage or prevent this condition become increasingly important.
The authors’ conclusions, that adopting the one-step approach increased the number of women with diagnosed GDM but did not significantly improve maternal or neonatal outcomes, are not surprising. Since the initial publication of the Hyperglycemia and Adverse Pregnancy Outcome Study, upon which the International Association of the Diabetes in Pregnancy Study Groups based its recommendations to go to a one-step approach, much debate has ensued about the best method to diagnose GDM. Indeed, the National Institutes of Health convened a consensus panel to review the literature and determine whether the one-step approach should be universally adopted (the panel concluded that more information was needed, and that the current two-step approach should continue to be used).
As the authors concede, studies have shown conflicting results, and no large-scale randomized controlled trial has been conducted to date. However, the literature does not bear out the idea that the one-step approach is truly better. The current study, although including a significant number of women and a reasonable control group, only serves as yet another study to reinforce what has previously been published.
I would agree with the researchers’ conclusions that the one-step approach is not necessarily beneficial. Although the one-step approach may identify a subset of patients who might not otherwise be diagnosed with GDM, it still remains unclear whether the outcomes for these patients will be improved. Furthermore, additional testing, need for insulin or other oral antidiabetic medications, etc., would result in additional stress to the patient and the health care system. Based on the authors’ findings, and results of other studies, it remains to be determined if the effort (diagnosing additional patients with GDM) is justified medically, economically, or otherwise.
As ob.gyns., we must continually ask ourselves: “By not doing something, are we causing harm to our patients?” If we change the diagnostic criteria for GDM, thereby increasing the number of women with the condition who would then require additional care, medications, and, potentially, more complex decisions around timing and mode of delivery, we need to be certain that we are not doing harm. This, and other studies examining the use of the one- versus two-step approach have yet to demonstrate, unequivocally, that changing the criteria reduces harm, and, perhaps, might – unintentionally – cause more.
As the study authors and the NIH consensus panel concluded, more rigorous evaluation is needed; that is, a large, multicenter randomized controlled trial that examines not only the benefits during pregnancy but also the long-term benefits to women and their children.
E. Albert Reece, MD, PhD, MBA, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He provided commentary on the study by Pocobelli et al. Dr. Reece said he had no relevant financial disclosures.
Diabetes is a significant global public health concern, but is especially problematic for women of reproductive age because diabetes in pregnancy can cause significant health complications for the mother and baby. Gestational diabetes mellitus (GDM) affects up to 10% of pregnancies in the United States annually, and is associated with perinatal loss, operative delivery, macrosomia, hypoglycemia, respiratory distress syndrome, and metabolic derangements for the offspring. For the mother, GDM is associated with hypertensive disorders, infections, hydramnios, and increased risk for developing type 2 diabetes later in life. As the incidence of GDM continues to rise, studies examining how to reduce, manage or prevent this condition become increasingly important.
The authors’ conclusions, that adopting the one-step approach increased the number of women with diagnosed GDM but did not significantly improve maternal or neonatal outcomes, are not surprising. Since the initial publication of the Hyperglycemia and Adverse Pregnancy Outcome Study, upon which the International Association of the Diabetes in Pregnancy Study Groups based its recommendations to go to a one-step approach, much debate has ensued about the best method to diagnose GDM. Indeed, the National Institutes of Health convened a consensus panel to review the literature and determine whether the one-step approach should be universally adopted (the panel concluded that more information was needed, and that the current two-step approach should continue to be used).
As the authors concede, studies have shown conflicting results, and no large-scale randomized controlled trial has been conducted to date. However, the literature does not bear out the idea that the one-step approach is truly better. The current study, although including a significant number of women and a reasonable control group, only serves as yet another study to reinforce what has previously been published.
I would agree with the researchers’ conclusions that the one-step approach is not necessarily beneficial. Although the one-step approach may identify a subset of patients who might not otherwise be diagnosed with GDM, it still remains unclear whether the outcomes for these patients will be improved. Furthermore, additional testing, need for insulin or other oral antidiabetic medications, etc., would result in additional stress to the patient and the health care system. Based on the authors’ findings, and results of other studies, it remains to be determined if the effort (diagnosing additional patients with GDM) is justified medically, economically, or otherwise.
As ob.gyns., we must continually ask ourselves: “By not doing something, are we causing harm to our patients?” If we change the diagnostic criteria for GDM, thereby increasing the number of women with the condition who would then require additional care, medications, and, potentially, more complex decisions around timing and mode of delivery, we need to be certain that we are not doing harm. This, and other studies examining the use of the one- versus two-step approach have yet to demonstrate, unequivocally, that changing the criteria reduces harm, and, perhaps, might – unintentionally – cause more.
As the study authors and the NIH consensus panel concluded, more rigorous evaluation is needed; that is, a large, multicenter randomized controlled trial that examines not only the benefits during pregnancy but also the long-term benefits to women and their children.
E. Albert Reece, MD, PhD, MBA, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He provided commentary on the study by Pocobelli et al. Dr. Reece said he had no relevant financial disclosures.
Diabetes is a significant global public health concern, but is especially problematic for women of reproductive age because diabetes in pregnancy can cause significant health complications for the mother and baby. Gestational diabetes mellitus (GDM) affects up to 10% of pregnancies in the United States annually, and is associated with perinatal loss, operative delivery, macrosomia, hypoglycemia, respiratory distress syndrome, and metabolic derangements for the offspring. For the mother, GDM is associated with hypertensive disorders, infections, hydramnios, and increased risk for developing type 2 diabetes later in life. As the incidence of GDM continues to rise, studies examining how to reduce, manage or prevent this condition become increasingly important.
The authors’ conclusions, that adopting the one-step approach increased the number of women with diagnosed GDM but did not significantly improve maternal or neonatal outcomes, are not surprising. Since the initial publication of the Hyperglycemia and Adverse Pregnancy Outcome Study, upon which the International Association of the Diabetes in Pregnancy Study Groups based its recommendations to go to a one-step approach, much debate has ensued about the best method to diagnose GDM. Indeed, the National Institutes of Health convened a consensus panel to review the literature and determine whether the one-step approach should be universally adopted (the panel concluded that more information was needed, and that the current two-step approach should continue to be used).
As the authors concede, studies have shown conflicting results, and no large-scale randomized controlled trial has been conducted to date. However, the literature does not bear out the idea that the one-step approach is truly better. The current study, although including a significant number of women and a reasonable control group, only serves as yet another study to reinforce what has previously been published.
I would agree with the researchers’ conclusions that the one-step approach is not necessarily beneficial. Although the one-step approach may identify a subset of patients who might not otherwise be diagnosed with GDM, it still remains unclear whether the outcomes for these patients will be improved. Furthermore, additional testing, need for insulin or other oral antidiabetic medications, etc., would result in additional stress to the patient and the health care system. Based on the authors’ findings, and results of other studies, it remains to be determined if the effort (diagnosing additional patients with GDM) is justified medically, economically, or otherwise.
As ob.gyns., we must continually ask ourselves: “By not doing something, are we causing harm to our patients?” If we change the diagnostic criteria for GDM, thereby increasing the number of women with the condition who would then require additional care, medications, and, potentially, more complex decisions around timing and mode of delivery, we need to be certain that we are not doing harm. This, and other studies examining the use of the one- versus two-step approach have yet to demonstrate, unequivocally, that changing the criteria reduces harm, and, perhaps, might – unintentionally – cause more.
As the study authors and the NIH consensus panel concluded, more rigorous evaluation is needed; that is, a large, multicenter randomized controlled trial that examines not only the benefits during pregnancy but also the long-term benefits to women and their children.
E. Albert Reece, MD, PhD, MBA, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He provided commentary on the study by Pocobelli et al. Dr. Reece said he had no relevant financial disclosures.
according to data from a before-and-after cohort study of women in the state of Washington.
The one-step test, a 75-g 2-hour oral glucose tolerance test (OGTT), was recommended for all pregnant women in 2010, although the traditional two-step test – a 50-g screening glucose challenge test followed by a 100-g 3-hour OGTT – remains widely used, wrote Gaia Pocobelli, PhD, of Kaiser Permanente Washington Health Research Institute, Seattle, and her colleagues. “No randomized trial has been published comparing outcomes of the two approaches.”
In a study published in Obstetrics & Gynecology, the researchers compared data from 23,257 women who received prenatal care in Washington State between January 2009 and December 2014, including 8,363 women who received care before the guideline change, 4,103 who received care during a transition period, and 10,791 after the guideline change. Approximately 60% of the women received care from clinicians internal to Kaiser Permanente; 40% received care from external providers. Most (87%) of the internal clinicians switched to the one-step approach, the researchers said. Only 5% of external providers did so.
Overall, adopting the one-step approach was associated with a 41% increase in the diagnosis of GDM without improved maternal or neonatal outcomes, the researchers noted.
The incidence of GDM increased from 7% before the guideline change to 11% afterward for women seen by internal providers. For women seen by external providers, gestational diabetes incidence increased from 10% to 11%.
For women seen by internal providers, the use of insulin increased from 1% before the guideline change to 4% afterward; for women seen by external providers, use of insulin increased from 1.3% to 1.4% (change between the groups P less than .001).
In addition, women seen by internal providers were more likely to undergo induction of labor after the guideline change (25% to 29%), while labor induction decreased for women seen by external providers (31% to 29%) for a relative risk of 1.2.
Neonatal hypoglycemia increased from 1% to 2% among women seen by internal providers, but decreased slightly from 2.4% to 2.1% for women seen by external providers, for a relative risk of 1.77.
There were no significant differences between the women seen by internal and external providers in risk of primary cesarean section, large for gestational age, small for gestational age, or neonatal ICU admission.
The main limitation of the study was the potential confounding variables including maternal diet and exercise, and possible underreporting of risk factors such as smoking, the researchers noted. However, the results were strengthened by the large study population, and the results “do not suggest a benefit of adopting the one-step over the two-step approach.
“Kaiser Permanente Washington has revised [its] guidelines to return to a two-step process. We recommend that any health care system considering switching to the one-step approach incorporate a rigorous evaluation of changes in maternal and neonatal outcomes,” Dr. Pocobelli and her associates added.
Dr. Pocobelli disclosed funding from Jazz Pharmaceuticals for work unrelated to this study. The study was supported in part by a grant from the Group Health Foundation Momentum Fund.
according to data from a before-and-after cohort study of women in the state of Washington.
The one-step test, a 75-g 2-hour oral glucose tolerance test (OGTT), was recommended for all pregnant women in 2010, although the traditional two-step test – a 50-g screening glucose challenge test followed by a 100-g 3-hour OGTT – remains widely used, wrote Gaia Pocobelli, PhD, of Kaiser Permanente Washington Health Research Institute, Seattle, and her colleagues. “No randomized trial has been published comparing outcomes of the two approaches.”
In a study published in Obstetrics & Gynecology, the researchers compared data from 23,257 women who received prenatal care in Washington State between January 2009 and December 2014, including 8,363 women who received care before the guideline change, 4,103 who received care during a transition period, and 10,791 after the guideline change. Approximately 60% of the women received care from clinicians internal to Kaiser Permanente; 40% received care from external providers. Most (87%) of the internal clinicians switched to the one-step approach, the researchers said. Only 5% of external providers did so.
Overall, adopting the one-step approach was associated with a 41% increase in the diagnosis of GDM without improved maternal or neonatal outcomes, the researchers noted.
The incidence of GDM increased from 7% before the guideline change to 11% afterward for women seen by internal providers. For women seen by external providers, gestational diabetes incidence increased from 10% to 11%.
For women seen by internal providers, the use of insulin increased from 1% before the guideline change to 4% afterward; for women seen by external providers, use of insulin increased from 1.3% to 1.4% (change between the groups P less than .001).
In addition, women seen by internal providers were more likely to undergo induction of labor after the guideline change (25% to 29%), while labor induction decreased for women seen by external providers (31% to 29%) for a relative risk of 1.2.
Neonatal hypoglycemia increased from 1% to 2% among women seen by internal providers, but decreased slightly from 2.4% to 2.1% for women seen by external providers, for a relative risk of 1.77.
There were no significant differences between the women seen by internal and external providers in risk of primary cesarean section, large for gestational age, small for gestational age, or neonatal ICU admission.
The main limitation of the study was the potential confounding variables including maternal diet and exercise, and possible underreporting of risk factors such as smoking, the researchers noted. However, the results were strengthened by the large study population, and the results “do not suggest a benefit of adopting the one-step over the two-step approach.
“Kaiser Permanente Washington has revised [its] guidelines to return to a two-step process. We recommend that any health care system considering switching to the one-step approach incorporate a rigorous evaluation of changes in maternal and neonatal outcomes,” Dr. Pocobelli and her associates added.
Dr. Pocobelli disclosed funding from Jazz Pharmaceuticals for work unrelated to this study. The study was supported in part by a grant from the Group Health Foundation Momentum Fund.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: Increased diagnoses of gestational diabetes did not significantly improve maternal or fetal outcomes.
Major finding: Adoption of a one-step screening process for gestational diabetes increased diagnoses by 41%.
Study details: The data come from a before-and-after cohort study with a population of 23,257 women.
Disclosures: Dr. Pocobelli disclosed funding from Jazz Pharmaceuticals for work unrelated to this study. The study was supported in part by a grant from the Group Health Foundation Momentum Fund.
Source: Pocobelli G et al. Obstet Gynecol. 2018;132:859-67.
Opioid Use Disorder Numbers Among Pregnant Women Are on the Rise
The number of women with opioid use disorder (OUD) at labor and delivery more than quadrupled between 1999 and 2014, according to a first-ever multistate analysis of trends by the CDC.
Researchers found that the national prevalence rate of OUD rose from 1.5 per 1,000 delivery hospitalizations in 1999 to 6.5 in 2014. On average, the national prevalence rate grew by 0.39 cases per 1,000 each year.
The increases were significant and seen in all of the 28 states with at least 3 years of data available for analysis. The average increases were lowest in California and Hawaii and highest in Maine, New Mexico, Vermont, and West Virginia.
Opioid use disorder during pregnancy has been associated with a range of negative health outcomes, including maternal death, preterm birth, stillbirth, and neonatal abstinence syndrome (NAS).
The CDC’s recommended strategies include:
- Implementing universal substance use screening at the first prenatal visit;
- Ensuring pregnant women with OUD have access to medication-assisted therapy and related addiction services; and
- Ensuring that mothers with OUD receive adequate patient-centered postpartum care, including mental health and substance use treatment, relapse-prevention programs, and family planning services
The CDC also is supporting state-based perinatal quality cooperatives, networks of teams working to better identify women with OUD during pregnancy and to standardize care for mothers and NAS-affected infants.
The number of women with opioid use disorder (OUD) at labor and delivery more than quadrupled between 1999 and 2014, according to a first-ever multistate analysis of trends by the CDC.
Researchers found that the national prevalence rate of OUD rose from 1.5 per 1,000 delivery hospitalizations in 1999 to 6.5 in 2014. On average, the national prevalence rate grew by 0.39 cases per 1,000 each year.
The increases were significant and seen in all of the 28 states with at least 3 years of data available for analysis. The average increases were lowest in California and Hawaii and highest in Maine, New Mexico, Vermont, and West Virginia.
Opioid use disorder during pregnancy has been associated with a range of negative health outcomes, including maternal death, preterm birth, stillbirth, and neonatal abstinence syndrome (NAS).
The CDC’s recommended strategies include:
- Implementing universal substance use screening at the first prenatal visit;
- Ensuring pregnant women with OUD have access to medication-assisted therapy and related addiction services; and
- Ensuring that mothers with OUD receive adequate patient-centered postpartum care, including mental health and substance use treatment, relapse-prevention programs, and family planning services
The CDC also is supporting state-based perinatal quality cooperatives, networks of teams working to better identify women with OUD during pregnancy and to standardize care for mothers and NAS-affected infants.
The number of women with opioid use disorder (OUD) at labor and delivery more than quadrupled between 1999 and 2014, according to a first-ever multistate analysis of trends by the CDC.
Researchers found that the national prevalence rate of OUD rose from 1.5 per 1,000 delivery hospitalizations in 1999 to 6.5 in 2014. On average, the national prevalence rate grew by 0.39 cases per 1,000 each year.
The increases were significant and seen in all of the 28 states with at least 3 years of data available for analysis. The average increases were lowest in California and Hawaii and highest in Maine, New Mexico, Vermont, and West Virginia.
Opioid use disorder during pregnancy has been associated with a range of negative health outcomes, including maternal death, preterm birth, stillbirth, and neonatal abstinence syndrome (NAS).
The CDC’s recommended strategies include:
- Implementing universal substance use screening at the first prenatal visit;
- Ensuring pregnant women with OUD have access to medication-assisted therapy and related addiction services; and
- Ensuring that mothers with OUD receive adequate patient-centered postpartum care, including mental health and substance use treatment, relapse-prevention programs, and family planning services
The CDC also is supporting state-based perinatal quality cooperatives, networks of teams working to better identify women with OUD during pregnancy and to standardize care for mothers and NAS-affected infants.
Severe maternal morbidity climbs; racial disparities persist
The rate of severe maternal morbidity in the United States has climbed steadily since 2006, increasing 45% overall in the decade ending in 2015, according to a new report from the Agency for Healthcare Research and Quality that also found large ethnic and racial, geographic, and socioeconomic variation in rates of severe maternal morbidity.
The longstanding increased risk for severe maternal morbidity for black women, compared with white women, continued essentially unchanged, with black women 112%-115% more likely to experience any of 21 conditions and procedures that defined severe maternal morbidity in the report. Disparities also existed between white women and those of Hispanic or Asian/Pacific Islander origin, but those gaps are narrowing, according to the report.
“Black women, Hispanic women, and women of other races/ethnicities were overrepresented among deliveries involving severe maternal morbidity, as compared with white women,” wrote Kathryn Fingar, PhD, and her coauthors. “White women constituted a lower percentage of deliveries with any severe maternal morbidity than they did other deliveries” – 23% lower.
The 21 indicators, developed by the Centers for Disease Control and Prevention, range from conditions such as renal failure and sepsis to in-hospital procedures such as blood transfusion and hysterectomy. Women were considered to have severe maternal morbidity if any of the indicators were present, regardless of whether in-hospital death occurred.
Dr. Fingar of IBM Watson Health, Cambridge, Mass., and her collaborators summarized data from AHRQ’s Healthcare Cost and Utilization Project (H-CUP) in the statistical brief. The two most common procedures that indicate severe maternal morbidity are blood transfusion and hysterectomy, and these indicators were tracked in deliveries where women had a condition that served as one of the severe maternal morbidity indicators.
Dr. Fingar and her colleagues noted that they excluded data for the final quarter of 2015, because that is when the transition from the 9th to the 10th edition of the International Classifications of Diseases was made.
In addition to the overall increase from 101.3 to 146.6 women per 10,000 experiencing any severe maternal morbidity, the incidence of blood transfusion during a delivery hospitalization, either alone or in conjunction with other indicators, rose from 78.9 to 121.1 women per 10,000, an increase of 54%.
Showing that increased blood transfusions were a major driver of the jump in severe maternal morbidity, the composite increase in the rates of all other indicators went from 34 to 42 per delivery hospitalization, an increase of just 24%, or less than half the increase in blood transfusions.
There was significant variation in trends over time for the rates of the other indicators: acute renal failure, shock, the need for mechanical ventilation, and sepsis all increased by at least 100% (range, 104%-134%), and the rates of aneurysm increased by 99%. Rates of other indicators fell; pulmonary edema, embolism, eclampsia, myocardial infarction, cerebrovascular disorders, serious anesthesia complications, and intraoperative heart failure and arrest all declined by 25%-53% during the data-gathering period.
Looking at the data another way, 78% of cases of severe maternal morbidity in 2006 and 83% in 2015 involved a blood transfusion, making it the most common indicator. Far fewer delivery hospitalizations involved disseminated intravascular coagulation (DIC) and hysterectomy, the next most common indicators, which were seen in just 8% of cases.
Blood transfusions were most likely in women with shock (72%), amniotic fluid embolism (63%), sickle cell disease with crisis (54%), and DIC (51%).
One in three women who experienced shock during delivery had a hysterectomy, as did more than 20% of women who experienced adult respiratory distress syndrome or cardiac arrest (or ventricular fibrillation).
Women delivering at the youngest and oldest ends of the age spectrum were more likely to experience severe maternal morbidity. For women younger than 20 years of age, the rate was 206 per 10,000. In the group of women aged 40 years and over, the rate of any severe maternal morbidity was 248 per 10,000 delivery hospitalizations. Women in their 20s and 30s had rates of 136 and 143 per 10,000, respectively.
Besides race/ethnicity and age, a variety of other patient characteristics were associated with increased rates of severe maternal morbidity and mortality, with higher rates seen in women from the poorest quartile than the wealthiest (177 versus 122 per 10,000, respectively). Women with Medicaid were more likely than those with private insurance to experience severe maternal morbidity during a delivery hospitalization (175 versus 121 per 10,000, respectively).
Similarly, severe maternal morbidity was more common in safety net hospitals and in minority-serving hospitals (182 versus 128 and 176 versus 123 per 10,000, respectively) than other hospitals.
Regionally, severe maternal morbidity was most common in the Northeast and the South, at 165 and 164 per 10,000, respectively, compared with rates of 132 and 116 in the West and Midwest, respectively.
Hospital deaths per 100,000 delivery hospitalizations were 248% higher for black than white women in 2006. By the end of 2015, that figure declined modestly to 193%, with absolute rates of 19 versus 5.5 deaths per 100,000 delivery hospitalizations for black versus white women in 2006. In 2015, the absolute rates were 11 versus 4 per 100,000.
The study was conducted by the Agency for Healthcare Research and Quality. There were no reported conflicts of interest.
SOURCE: Fingar K et al. Agency for Healthcare Research and Quality Statistical Brief #243.
The data here confirm, again, that we have a crisis in maternal health care in the United States. Not only is severe maternal morbidity increasing, but disparities in outcomes between white and black women persist, such that severe maternal morbidity is twice as common among black women as it is among white women.
It’s tempting to attribute the gap to social determinants of health that are outside the control of the obstetrician-gynecologist. But education doesn’t protect black women: the New York City Department of Health and Mental Hygiene found that non-Hispanic black women with a college degree have higher rates of severe maternal morbidity than women of other race/ethnicities who never graduated high school. It’s a stark finding that’s illustrated by the heartbreaking story of Shalon Irving, a PhD epidemiologist at the Centers for Disease Control and Prevention, whose postpartum death was reported by ProPublica last winter.
One contributing factor is likely to be implicit biases that affect how well we see and hear patients who are different from us. I was mortified to see my own implicit biases when I took the Project Implicit Social Attitudes test (https://implicit.harvard.edu/implicit/). These aren’t the beliefs that we choose – they are the patterns that we absorb from our day-to-day lives. If you search Google images for “pregnancy,” “motherhood,” or “breastfeeding,” the overwhelming majority of images feature white women, whereas the phrase “welfare queen” is used to denigrate the reproduction of women of color. That’s the world we live in, and these patterns reinforce mental short cuts that are more likely to drive our behavior when we’re pressed for time, as we are every day in clinical practice. In one study in a pediatric emergency department, the busier the shift, the higher the providers’ implicit bias at the end of the shift.
We might start by looking at the images on our web sites and hanging in our offices and hospital corridors – do they look like the women we care for? Do they celebrate pregnancy and parenthood for diverse families? And how can we make sure that we pause, before we walk into a patient’s room, so that we can be fully present to her individual strengths and vulnerabilities, and tailor our care to her as an individual?
Alison Stuebe, MD, of the University of North Carolina, Chapel Hill, is medical director of lactation services and on the steering committee for Moms Rising North Carolina, the Breastfeeding Expert Work Group for the American College of Obstetricians and Gynecologists, and a board member of the Society for Maternal-Fetal Medicine. She was asked to comment on the AHRQ report by this newspaper.
The data here confirm, again, that we have a crisis in maternal health care in the United States. Not only is severe maternal morbidity increasing, but disparities in outcomes between white and black women persist, such that severe maternal morbidity is twice as common among black women as it is among white women.
It’s tempting to attribute the gap to social determinants of health that are outside the control of the obstetrician-gynecologist. But education doesn’t protect black women: the New York City Department of Health and Mental Hygiene found that non-Hispanic black women with a college degree have higher rates of severe maternal morbidity than women of other race/ethnicities who never graduated high school. It’s a stark finding that’s illustrated by the heartbreaking story of Shalon Irving, a PhD epidemiologist at the Centers for Disease Control and Prevention, whose postpartum death was reported by ProPublica last winter.
One contributing factor is likely to be implicit biases that affect how well we see and hear patients who are different from us. I was mortified to see my own implicit biases when I took the Project Implicit Social Attitudes test (https://implicit.harvard.edu/implicit/). These aren’t the beliefs that we choose – they are the patterns that we absorb from our day-to-day lives. If you search Google images for “pregnancy,” “motherhood,” or “breastfeeding,” the overwhelming majority of images feature white women, whereas the phrase “welfare queen” is used to denigrate the reproduction of women of color. That’s the world we live in, and these patterns reinforce mental short cuts that are more likely to drive our behavior when we’re pressed for time, as we are every day in clinical practice. In one study in a pediatric emergency department, the busier the shift, the higher the providers’ implicit bias at the end of the shift.
We might start by looking at the images on our web sites and hanging in our offices and hospital corridors – do they look like the women we care for? Do they celebrate pregnancy and parenthood for diverse families? And how can we make sure that we pause, before we walk into a patient’s room, so that we can be fully present to her individual strengths and vulnerabilities, and tailor our care to her as an individual?
Alison Stuebe, MD, of the University of North Carolina, Chapel Hill, is medical director of lactation services and on the steering committee for Moms Rising North Carolina, the Breastfeeding Expert Work Group for the American College of Obstetricians and Gynecologists, and a board member of the Society for Maternal-Fetal Medicine. She was asked to comment on the AHRQ report by this newspaper.
The data here confirm, again, that we have a crisis in maternal health care in the United States. Not only is severe maternal morbidity increasing, but disparities in outcomes between white and black women persist, such that severe maternal morbidity is twice as common among black women as it is among white women.
It’s tempting to attribute the gap to social determinants of health that are outside the control of the obstetrician-gynecologist. But education doesn’t protect black women: the New York City Department of Health and Mental Hygiene found that non-Hispanic black women with a college degree have higher rates of severe maternal morbidity than women of other race/ethnicities who never graduated high school. It’s a stark finding that’s illustrated by the heartbreaking story of Shalon Irving, a PhD epidemiologist at the Centers for Disease Control and Prevention, whose postpartum death was reported by ProPublica last winter.
One contributing factor is likely to be implicit biases that affect how well we see and hear patients who are different from us. I was mortified to see my own implicit biases when I took the Project Implicit Social Attitudes test (https://implicit.harvard.edu/implicit/). These aren’t the beliefs that we choose – they are the patterns that we absorb from our day-to-day lives. If you search Google images for “pregnancy,” “motherhood,” or “breastfeeding,” the overwhelming majority of images feature white women, whereas the phrase “welfare queen” is used to denigrate the reproduction of women of color. That’s the world we live in, and these patterns reinforce mental short cuts that are more likely to drive our behavior when we’re pressed for time, as we are every day in clinical practice. In one study in a pediatric emergency department, the busier the shift, the higher the providers’ implicit bias at the end of the shift.
We might start by looking at the images on our web sites and hanging in our offices and hospital corridors – do they look like the women we care for? Do they celebrate pregnancy and parenthood for diverse families? And how can we make sure that we pause, before we walk into a patient’s room, so that we can be fully present to her individual strengths and vulnerabilities, and tailor our care to her as an individual?
Alison Stuebe, MD, of the University of North Carolina, Chapel Hill, is medical director of lactation services and on the steering committee for Moms Rising North Carolina, the Breastfeeding Expert Work Group for the American College of Obstetricians and Gynecologists, and a board member of the Society for Maternal-Fetal Medicine. She was asked to comment on the AHRQ report by this newspaper.
The rate of severe maternal morbidity in the United States has climbed steadily since 2006, increasing 45% overall in the decade ending in 2015, according to a new report from the Agency for Healthcare Research and Quality that also found large ethnic and racial, geographic, and socioeconomic variation in rates of severe maternal morbidity.
The longstanding increased risk for severe maternal morbidity for black women, compared with white women, continued essentially unchanged, with black women 112%-115% more likely to experience any of 21 conditions and procedures that defined severe maternal morbidity in the report. Disparities also existed between white women and those of Hispanic or Asian/Pacific Islander origin, but those gaps are narrowing, according to the report.
“Black women, Hispanic women, and women of other races/ethnicities were overrepresented among deliveries involving severe maternal morbidity, as compared with white women,” wrote Kathryn Fingar, PhD, and her coauthors. “White women constituted a lower percentage of deliveries with any severe maternal morbidity than they did other deliveries” – 23% lower.
The 21 indicators, developed by the Centers for Disease Control and Prevention, range from conditions such as renal failure and sepsis to in-hospital procedures such as blood transfusion and hysterectomy. Women were considered to have severe maternal morbidity if any of the indicators were present, regardless of whether in-hospital death occurred.
Dr. Fingar of IBM Watson Health, Cambridge, Mass., and her collaborators summarized data from AHRQ’s Healthcare Cost and Utilization Project (H-CUP) in the statistical brief. The two most common procedures that indicate severe maternal morbidity are blood transfusion and hysterectomy, and these indicators were tracked in deliveries where women had a condition that served as one of the severe maternal morbidity indicators.
Dr. Fingar and her colleagues noted that they excluded data for the final quarter of 2015, because that is when the transition from the 9th to the 10th edition of the International Classifications of Diseases was made.
In addition to the overall increase from 101.3 to 146.6 women per 10,000 experiencing any severe maternal morbidity, the incidence of blood transfusion during a delivery hospitalization, either alone or in conjunction with other indicators, rose from 78.9 to 121.1 women per 10,000, an increase of 54%.
Showing that increased blood transfusions were a major driver of the jump in severe maternal morbidity, the composite increase in the rates of all other indicators went from 34 to 42 per delivery hospitalization, an increase of just 24%, or less than half the increase in blood transfusions.
There was significant variation in trends over time for the rates of the other indicators: acute renal failure, shock, the need for mechanical ventilation, and sepsis all increased by at least 100% (range, 104%-134%), and the rates of aneurysm increased by 99%. Rates of other indicators fell; pulmonary edema, embolism, eclampsia, myocardial infarction, cerebrovascular disorders, serious anesthesia complications, and intraoperative heart failure and arrest all declined by 25%-53% during the data-gathering period.
Looking at the data another way, 78% of cases of severe maternal morbidity in 2006 and 83% in 2015 involved a blood transfusion, making it the most common indicator. Far fewer delivery hospitalizations involved disseminated intravascular coagulation (DIC) and hysterectomy, the next most common indicators, which were seen in just 8% of cases.
Blood transfusions were most likely in women with shock (72%), amniotic fluid embolism (63%), sickle cell disease with crisis (54%), and DIC (51%).
One in three women who experienced shock during delivery had a hysterectomy, as did more than 20% of women who experienced adult respiratory distress syndrome or cardiac arrest (or ventricular fibrillation).
Women delivering at the youngest and oldest ends of the age spectrum were more likely to experience severe maternal morbidity. For women younger than 20 years of age, the rate was 206 per 10,000. In the group of women aged 40 years and over, the rate of any severe maternal morbidity was 248 per 10,000 delivery hospitalizations. Women in their 20s and 30s had rates of 136 and 143 per 10,000, respectively.
Besides race/ethnicity and age, a variety of other patient characteristics were associated with increased rates of severe maternal morbidity and mortality, with higher rates seen in women from the poorest quartile than the wealthiest (177 versus 122 per 10,000, respectively). Women with Medicaid were more likely than those with private insurance to experience severe maternal morbidity during a delivery hospitalization (175 versus 121 per 10,000, respectively).
Similarly, severe maternal morbidity was more common in safety net hospitals and in minority-serving hospitals (182 versus 128 and 176 versus 123 per 10,000, respectively) than other hospitals.
Regionally, severe maternal morbidity was most common in the Northeast and the South, at 165 and 164 per 10,000, respectively, compared with rates of 132 and 116 in the West and Midwest, respectively.
Hospital deaths per 100,000 delivery hospitalizations were 248% higher for black than white women in 2006. By the end of 2015, that figure declined modestly to 193%, with absolute rates of 19 versus 5.5 deaths per 100,000 delivery hospitalizations for black versus white women in 2006. In 2015, the absolute rates were 11 versus 4 per 100,000.
The study was conducted by the Agency for Healthcare Research and Quality. There were no reported conflicts of interest.
SOURCE: Fingar K et al. Agency for Healthcare Research and Quality Statistical Brief #243.
The rate of severe maternal morbidity in the United States has climbed steadily since 2006, increasing 45% overall in the decade ending in 2015, according to a new report from the Agency for Healthcare Research and Quality that also found large ethnic and racial, geographic, and socioeconomic variation in rates of severe maternal morbidity.
The longstanding increased risk for severe maternal morbidity for black women, compared with white women, continued essentially unchanged, with black women 112%-115% more likely to experience any of 21 conditions and procedures that defined severe maternal morbidity in the report. Disparities also existed between white women and those of Hispanic or Asian/Pacific Islander origin, but those gaps are narrowing, according to the report.
“Black women, Hispanic women, and women of other races/ethnicities were overrepresented among deliveries involving severe maternal morbidity, as compared with white women,” wrote Kathryn Fingar, PhD, and her coauthors. “White women constituted a lower percentage of deliveries with any severe maternal morbidity than they did other deliveries” – 23% lower.
The 21 indicators, developed by the Centers for Disease Control and Prevention, range from conditions such as renal failure and sepsis to in-hospital procedures such as blood transfusion and hysterectomy. Women were considered to have severe maternal morbidity if any of the indicators were present, regardless of whether in-hospital death occurred.
Dr. Fingar of IBM Watson Health, Cambridge, Mass., and her collaborators summarized data from AHRQ’s Healthcare Cost and Utilization Project (H-CUP) in the statistical brief. The two most common procedures that indicate severe maternal morbidity are blood transfusion and hysterectomy, and these indicators were tracked in deliveries where women had a condition that served as one of the severe maternal morbidity indicators.
Dr. Fingar and her colleagues noted that they excluded data for the final quarter of 2015, because that is when the transition from the 9th to the 10th edition of the International Classifications of Diseases was made.
In addition to the overall increase from 101.3 to 146.6 women per 10,000 experiencing any severe maternal morbidity, the incidence of blood transfusion during a delivery hospitalization, either alone or in conjunction with other indicators, rose from 78.9 to 121.1 women per 10,000, an increase of 54%.
Showing that increased blood transfusions were a major driver of the jump in severe maternal morbidity, the composite increase in the rates of all other indicators went from 34 to 42 per delivery hospitalization, an increase of just 24%, or less than half the increase in blood transfusions.
There was significant variation in trends over time for the rates of the other indicators: acute renal failure, shock, the need for mechanical ventilation, and sepsis all increased by at least 100% (range, 104%-134%), and the rates of aneurysm increased by 99%. Rates of other indicators fell; pulmonary edema, embolism, eclampsia, myocardial infarction, cerebrovascular disorders, serious anesthesia complications, and intraoperative heart failure and arrest all declined by 25%-53% during the data-gathering period.
Looking at the data another way, 78% of cases of severe maternal morbidity in 2006 and 83% in 2015 involved a blood transfusion, making it the most common indicator. Far fewer delivery hospitalizations involved disseminated intravascular coagulation (DIC) and hysterectomy, the next most common indicators, which were seen in just 8% of cases.
Blood transfusions were most likely in women with shock (72%), amniotic fluid embolism (63%), sickle cell disease with crisis (54%), and DIC (51%).
One in three women who experienced shock during delivery had a hysterectomy, as did more than 20% of women who experienced adult respiratory distress syndrome or cardiac arrest (or ventricular fibrillation).
Women delivering at the youngest and oldest ends of the age spectrum were more likely to experience severe maternal morbidity. For women younger than 20 years of age, the rate was 206 per 10,000. In the group of women aged 40 years and over, the rate of any severe maternal morbidity was 248 per 10,000 delivery hospitalizations. Women in their 20s and 30s had rates of 136 and 143 per 10,000, respectively.
Besides race/ethnicity and age, a variety of other patient characteristics were associated with increased rates of severe maternal morbidity and mortality, with higher rates seen in women from the poorest quartile than the wealthiest (177 versus 122 per 10,000, respectively). Women with Medicaid were more likely than those with private insurance to experience severe maternal morbidity during a delivery hospitalization (175 versus 121 per 10,000, respectively).
Similarly, severe maternal morbidity was more common in safety net hospitals and in minority-serving hospitals (182 versus 128 and 176 versus 123 per 10,000, respectively) than other hospitals.
Regionally, severe maternal morbidity was most common in the Northeast and the South, at 165 and 164 per 10,000, respectively, compared with rates of 132 and 116 in the West and Midwest, respectively.
Hospital deaths per 100,000 delivery hospitalizations were 248% higher for black than white women in 2006. By the end of 2015, that figure declined modestly to 193%, with absolute rates of 19 versus 5.5 deaths per 100,000 delivery hospitalizations for black versus white women in 2006. In 2015, the absolute rates were 11 versus 4 per 100,000.
The study was conducted by the Agency for Healthcare Research and Quality. There were no reported conflicts of interest.
SOURCE: Fingar K et al. Agency for Healthcare Research and Quality Statistical Brief #243.
FROM AN AHRQ STATISTICAL BRIEF
Key clinical point:
Major finding: Black women were over 100% more likely to experience severe maternal morbidity, compared with white women.
Study details: Statistical analysis of Healthcare Cost and Utilization Project (H-CUP) data.
Disclosures: The study was funded by the Agency for Healthcare Research and Quality. The authors reported no conflicts of interest.
Source: Fingar K et al. Agency for Healthcare Research and Quality Statistical Brief #243.
Guidelines released for perimenopausal depression
and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.
“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”
The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.
Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.
Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.
Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.
Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.
“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”
Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.
There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.
Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.
The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”
Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.
SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.
I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.
There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.
The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.
Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.
Jan Leslie Shifren, MD , is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.
I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.
There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.
The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.
Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.
Jan Leslie Shifren, MD , is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.
I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.
There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.
The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.
Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.
Jan Leslie Shifren, MD , is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.
and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.
“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”
The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.
Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.
Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.
Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.
Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.
“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”
Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.
There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.
Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.
The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”
Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.
SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.
and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.
“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”
The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.
Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.
Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.
Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.
Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.
“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”
Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.
There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.
Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.
The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”
Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.
SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.
FROM THE JOURNAL OF WOMEN’S HEALTH
Pregnancy boosts cardiac disease mortality nearly 100-fold
MUNICH – Women with cardiac disease who became pregnant had a nearly 100-fold higher mortality rate, compared with pregnant women without cardiac disease, according to the outcomes of more than 5,700 pregnancies in an international registry of women with cardiac disease.
In addition to increased mortality, women with cardiac disease who become pregnant also had a greater than 100-fold higher rate of developing heart failure, compared with pregnant women without cardiac disease.
Despite these highly elevated relative risks, the absolute rate of serious complications from pregnancy for most women with heart disease was relatively modest. The worst prognosis by far was for the 1% of women in the registry who had pulmonary arterial hypertension at the time their pregnancy began. For these women, mortality during pregnancy was about 9%, and new-onset heart failure occurred in about one third. Another subgroup showing particularly poor outcomes were women classified with WHO IV maternal cardiovascular risk by the modified World Health Organization criteria, which corresponds to having an “extremely high risk of maternal mortality or severe morbidity,” according to guidelines published in the European Heart Journal (2011 Dec 1;32[24]:3147-97).These women, constituting 7% of the registry cohort, had a 2.5% mortality rate during pregnancy and a 33% incidence of heart failure.
Across all women with cardiac disease enrolled in the registry, the incidence of death during pregnancy was 0.6% and the incidence of heart failure was 11%. Women without cardiac disease have rates of 0.007% and less than 0.1%, respectively, Jolien Roos-Hesselink, MD, said at the annual congress of the European Society of Cardiology.
“The most important message of my talk is that all patients should be counseled, not just the women at high risk, for whom pregnancy is contraindicated, but also the women at low risk,” who can have a child with relative safety, she said. “Many women [with cardiac disease] can go through pregnancy at low risk.” Counseling is the key so that women know their risk before becoming pregnant, stressed Dr. Roos-Hesselink, a cardiologist at Erasmus Medical Center in Rotterdam, the Netherlands.
Based on the observed rates of mortality and other complications, pulmonary arterial hypertension and the other cardiac conditions that define a WHO IV maternal risk classification remain contraindications for pregnancy, she said. According to the 2011 guidelines from the European Society of Cardiology for managing cardiovascular disease during pregnancy, the full list of conditions that define a WHO IV classification are the following:
- Pulmonary arterial hypertension of any cause.
- Severe systemic ventricular dysfunction (a left ventricular ejection fraction of less than 30%) or New York Heart Association functional class III or IV.
- Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
- Severe mitral stenosis or severe symptomatic aortic stenosis.
- Marfan syndrome with the aorta dilated to more than 45 mm.
- Aortic dilatation greater than 50 mm in aortic disease associated with a bicuspid aortic valve.
- Native severe coarctation.
The registry data, collected during 2007-2018, showed a clear increase in the percentage of women with WHO class IV cardiovascular disease who became pregnant and entered the registry despite the contraindication designation for that classification, rising from about 1% of enrolled women in 2008 and 2009 to more than 10% of women in 2013, 2016, and 2017. “Individualization is necessary, but all these women are at very high risk and should be counseled against pregnancy,” Dr. Roos-Hesselink said.
The Registry of Pregnancy and Cardiac Disease (ROPAC) enrolled 5,739 pregnant women at any of 138 participating centers in 53 countries including the United States. Clinicians submitted WHO classification of cardiovascular risk for 5,711 of these women. The most common risk was congenital heart disease in 57% of enrolled women, followed by valvular heart disease in 29% and cardiomyopathy in 7%. Nearly 1,200 women in the registry – about 21% of the total – had a WHO I classification, which meant that they would be expected to have no detectable increase in mortality rate during pregnancy, compared with women without cardiac disease, and either no rise in morbidity or a mild effect.
Delivery was by cesarean section in 44% of the pregnancies, roughly twice the rate in women without diagnosed cardiac disease, even though published guidelines don’t advise cesarean delivery because of cardiac disease, Dr. Roos-Hesselink said. “Cesarean sections are used too often, in my opinion,” she commented, but added that many of these women require delivery at a tertiary, specialized center.
Overall fetal mortality was 1%, nearly threefold higher than in pregnancies in women without cardiac disease, and the overall incidence of fetal and neonatal complications was especially high, at 53%, in women with pulmonary arterial hypertension. The incidence of obstetrical complications was roughly similar across the range of cardiac disease type, ranging from 16% to 24%. Premature delivery occurred in 28% of women in the high-risk WHO IV class, compared with a 13% rate among women in the WHO I class. The mortality rate was 0.2% among the WHO class I women, and their heart failure incidence was 5%.
The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.
MUNICH – Women with cardiac disease who became pregnant had a nearly 100-fold higher mortality rate, compared with pregnant women without cardiac disease, according to the outcomes of more than 5,700 pregnancies in an international registry of women with cardiac disease.
In addition to increased mortality, women with cardiac disease who become pregnant also had a greater than 100-fold higher rate of developing heart failure, compared with pregnant women without cardiac disease.
Despite these highly elevated relative risks, the absolute rate of serious complications from pregnancy for most women with heart disease was relatively modest. The worst prognosis by far was for the 1% of women in the registry who had pulmonary arterial hypertension at the time their pregnancy began. For these women, mortality during pregnancy was about 9%, and new-onset heart failure occurred in about one third. Another subgroup showing particularly poor outcomes were women classified with WHO IV maternal cardiovascular risk by the modified World Health Organization criteria, which corresponds to having an “extremely high risk of maternal mortality or severe morbidity,” according to guidelines published in the European Heart Journal (2011 Dec 1;32[24]:3147-97).These women, constituting 7% of the registry cohort, had a 2.5% mortality rate during pregnancy and a 33% incidence of heart failure.
Across all women with cardiac disease enrolled in the registry, the incidence of death during pregnancy was 0.6% and the incidence of heart failure was 11%. Women without cardiac disease have rates of 0.007% and less than 0.1%, respectively, Jolien Roos-Hesselink, MD, said at the annual congress of the European Society of Cardiology.
“The most important message of my talk is that all patients should be counseled, not just the women at high risk, for whom pregnancy is contraindicated, but also the women at low risk,” who can have a child with relative safety, she said. “Many women [with cardiac disease] can go through pregnancy at low risk.” Counseling is the key so that women know their risk before becoming pregnant, stressed Dr. Roos-Hesselink, a cardiologist at Erasmus Medical Center in Rotterdam, the Netherlands.
Based on the observed rates of mortality and other complications, pulmonary arterial hypertension and the other cardiac conditions that define a WHO IV maternal risk classification remain contraindications for pregnancy, she said. According to the 2011 guidelines from the European Society of Cardiology for managing cardiovascular disease during pregnancy, the full list of conditions that define a WHO IV classification are the following:
- Pulmonary arterial hypertension of any cause.
- Severe systemic ventricular dysfunction (a left ventricular ejection fraction of less than 30%) or New York Heart Association functional class III or IV.
- Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
- Severe mitral stenosis or severe symptomatic aortic stenosis.
- Marfan syndrome with the aorta dilated to more than 45 mm.
- Aortic dilatation greater than 50 mm in aortic disease associated with a bicuspid aortic valve.
- Native severe coarctation.
The registry data, collected during 2007-2018, showed a clear increase in the percentage of women with WHO class IV cardiovascular disease who became pregnant and entered the registry despite the contraindication designation for that classification, rising from about 1% of enrolled women in 2008 and 2009 to more than 10% of women in 2013, 2016, and 2017. “Individualization is necessary, but all these women are at very high risk and should be counseled against pregnancy,” Dr. Roos-Hesselink said.
The Registry of Pregnancy and Cardiac Disease (ROPAC) enrolled 5,739 pregnant women at any of 138 participating centers in 53 countries including the United States. Clinicians submitted WHO classification of cardiovascular risk for 5,711 of these women. The most common risk was congenital heart disease in 57% of enrolled women, followed by valvular heart disease in 29% and cardiomyopathy in 7%. Nearly 1,200 women in the registry – about 21% of the total – had a WHO I classification, which meant that they would be expected to have no detectable increase in mortality rate during pregnancy, compared with women without cardiac disease, and either no rise in morbidity or a mild effect.
Delivery was by cesarean section in 44% of the pregnancies, roughly twice the rate in women without diagnosed cardiac disease, even though published guidelines don’t advise cesarean delivery because of cardiac disease, Dr. Roos-Hesselink said. “Cesarean sections are used too often, in my opinion,” she commented, but added that many of these women require delivery at a tertiary, specialized center.
Overall fetal mortality was 1%, nearly threefold higher than in pregnancies in women without cardiac disease, and the overall incidence of fetal and neonatal complications was especially high, at 53%, in women with pulmonary arterial hypertension. The incidence of obstetrical complications was roughly similar across the range of cardiac disease type, ranging from 16% to 24%. Premature delivery occurred in 28% of women in the high-risk WHO IV class, compared with a 13% rate among women in the WHO I class. The mortality rate was 0.2% among the WHO class I women, and their heart failure incidence was 5%.
The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.
MUNICH – Women with cardiac disease who became pregnant had a nearly 100-fold higher mortality rate, compared with pregnant women without cardiac disease, according to the outcomes of more than 5,700 pregnancies in an international registry of women with cardiac disease.
In addition to increased mortality, women with cardiac disease who become pregnant also had a greater than 100-fold higher rate of developing heart failure, compared with pregnant women without cardiac disease.
Despite these highly elevated relative risks, the absolute rate of serious complications from pregnancy for most women with heart disease was relatively modest. The worst prognosis by far was for the 1% of women in the registry who had pulmonary arterial hypertension at the time their pregnancy began. For these women, mortality during pregnancy was about 9%, and new-onset heart failure occurred in about one third. Another subgroup showing particularly poor outcomes were women classified with WHO IV maternal cardiovascular risk by the modified World Health Organization criteria, which corresponds to having an “extremely high risk of maternal mortality or severe morbidity,” according to guidelines published in the European Heart Journal (2011 Dec 1;32[24]:3147-97).These women, constituting 7% of the registry cohort, had a 2.5% mortality rate during pregnancy and a 33% incidence of heart failure.
Across all women with cardiac disease enrolled in the registry, the incidence of death during pregnancy was 0.6% and the incidence of heart failure was 11%. Women without cardiac disease have rates of 0.007% and less than 0.1%, respectively, Jolien Roos-Hesselink, MD, said at the annual congress of the European Society of Cardiology.
“The most important message of my talk is that all patients should be counseled, not just the women at high risk, for whom pregnancy is contraindicated, but also the women at low risk,” who can have a child with relative safety, she said. “Many women [with cardiac disease] can go through pregnancy at low risk.” Counseling is the key so that women know their risk before becoming pregnant, stressed Dr. Roos-Hesselink, a cardiologist at Erasmus Medical Center in Rotterdam, the Netherlands.
Based on the observed rates of mortality and other complications, pulmonary arterial hypertension and the other cardiac conditions that define a WHO IV maternal risk classification remain contraindications for pregnancy, she said. According to the 2011 guidelines from the European Society of Cardiology for managing cardiovascular disease during pregnancy, the full list of conditions that define a WHO IV classification are the following:
- Pulmonary arterial hypertension of any cause.
- Severe systemic ventricular dysfunction (a left ventricular ejection fraction of less than 30%) or New York Heart Association functional class III or IV.
- Previous peripartum cardiomyopathy with any residual impairment of left ventricular function.
- Severe mitral stenosis or severe symptomatic aortic stenosis.
- Marfan syndrome with the aorta dilated to more than 45 mm.
- Aortic dilatation greater than 50 mm in aortic disease associated with a bicuspid aortic valve.
- Native severe coarctation.
The registry data, collected during 2007-2018, showed a clear increase in the percentage of women with WHO class IV cardiovascular disease who became pregnant and entered the registry despite the contraindication designation for that classification, rising from about 1% of enrolled women in 2008 and 2009 to more than 10% of women in 2013, 2016, and 2017. “Individualization is necessary, but all these women are at very high risk and should be counseled against pregnancy,” Dr. Roos-Hesselink said.
The Registry of Pregnancy and Cardiac Disease (ROPAC) enrolled 5,739 pregnant women at any of 138 participating centers in 53 countries including the United States. Clinicians submitted WHO classification of cardiovascular risk for 5,711 of these women. The most common risk was congenital heart disease in 57% of enrolled women, followed by valvular heart disease in 29% and cardiomyopathy in 7%. Nearly 1,200 women in the registry – about 21% of the total – had a WHO I classification, which meant that they would be expected to have no detectable increase in mortality rate during pregnancy, compared with women without cardiac disease, and either no rise in morbidity or a mild effect.
Delivery was by cesarean section in 44% of the pregnancies, roughly twice the rate in women without diagnosed cardiac disease, even though published guidelines don’t advise cesarean delivery because of cardiac disease, Dr. Roos-Hesselink said. “Cesarean sections are used too often, in my opinion,” she commented, but added that many of these women require delivery at a tertiary, specialized center.
Overall fetal mortality was 1%, nearly threefold higher than in pregnancies in women without cardiac disease, and the overall incidence of fetal and neonatal complications was especially high, at 53%, in women with pulmonary arterial hypertension. The incidence of obstetrical complications was roughly similar across the range of cardiac disease type, ranging from 16% to 24%. Premature delivery occurred in 28% of women in the high-risk WHO IV class, compared with a 13% rate among women in the WHO I class. The mortality rate was 0.2% among the WHO class I women, and their heart failure incidence was 5%.
The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point: Women with cardiac disease who became pregnant had substantially increased mortality and morbidity.
Major finding: Pregnancy mortality was 0.6% in women with cardiac disease versus 0.007% in women without cardiac disorders.
Study details: The ROPAC registry, which enrolled 5,739 pregnant women at any of 138 centers in 53 countries during 2007-2018.
Disclosures: The ROPAC registry is sponsored by the European Society of Cardiology. Dr. Roos-Hesselink had no disclosures.
Hormonal contraceptive use linked to leukemia risk in offspring
A nationwide cohort study found an association between a woman’s use of hormonal contraceptives and a small increased risk of nonlymphoid leukemia in her offspring.
Maternal use of hormonal contraception either during pregnancy or in the 3 months beforehand was associated with a 46% higher risk of any leukemia in the children (P = .011), compared with no use, Marie Hargreave, PhD, of the Danish Cancer Society Research Center and her coauthors reported in Lancet Oncology.
The study of 1,185,157 children born between 1996 and 2014 included data from the Danish Cancer Registry and Danish National Prescription Registry and followed children for a median of 9.3 years.
Use during pregnancy was associated with a 78% higher risk of any leukemia in the offspring (P = .070), and contraception use that stopped more than 3 months before pregnancy was associated with a 25% higher risk of any leukemia (P = .039).
The researchers estimated that maternal use of hormonal contraceptives up to and including during pregnancy would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia in Denmark from contraceptive use from 1996 to 2014.
The increased risk appeared to be limited to nonlymphoid leukemia only. The risk with recent use was more than twofold higher (HR, 2.17), compared with nonuse, and use during pregnancy was associated with a nearly fourfold increase in the risk of leukemia (HR, 3.87).
“Sex hormones are considered to be potent carcinogens, and the causal association between in-utero exposure to the oestrogen analogue diethylstilbestrol and subsequent risk for adenocarcinoma of the vagina is firmly established,” Dr. Hargreave and her colleagues wrote. “The mechanism by which maternal use of hormones increases cancer risk in children is, however, still not clear.”
Recent use of combined oral contraceptive products was associated with a more than twofold increased risk of nonlymphoid leukemia in offspring, compared with no use. However progestin-only oral contraceptives and emergency contraception did not appear to increase in the risk of lymphoid or nonlymphoid leukemia.
The association was strongest in children aged 6-10 years, which the authors suggested was likely because the incidence of nonlymphoid leukemia increases after the age of 6 years.
While acknowledging that the small increase in leukemia risk was not a major safety concern for hormonal contraceptives, the authors commented that the results suggested the intrauterine hormonal environment could be a direction for research into the causes of leukemia.
The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.
SOURCE: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
Estrogenic compounds could have a number of effects on the genomic machinery, that could in turn lead to an increased risk of leukemia in offspring. It may be that oral contraceptives cause epigenetic changes to fetal hematopoietic stem cells that lead to gene rearrangements and oxidative damage, which could then influence the risk of developing childhood leukemia.
This study opens a new avenue of investigation for a risk factor that might increase a child’s susceptibility to leukemia and is important in shedding more light on dose-response associations of exposures.
Dr. Maria S. Pombo-de-Oliveira is from the pediatric hematology-oncology research program at the Instituto Nacional de Câncer in Rio de Janeiro. These comments are adapted from an accompanying editorial (Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045[18]30509-6). Dr. Pombo-de-Oliveira reported having no conflicts of interest.
Estrogenic compounds could have a number of effects on the genomic machinery, that could in turn lead to an increased risk of leukemia in offspring. It may be that oral contraceptives cause epigenetic changes to fetal hematopoietic stem cells that lead to gene rearrangements and oxidative damage, which could then influence the risk of developing childhood leukemia.
This study opens a new avenue of investigation for a risk factor that might increase a child’s susceptibility to leukemia and is important in shedding more light on dose-response associations of exposures.
Dr. Maria S. Pombo-de-Oliveira is from the pediatric hematology-oncology research program at the Instituto Nacional de Câncer in Rio de Janeiro. These comments are adapted from an accompanying editorial (Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045[18]30509-6). Dr. Pombo-de-Oliveira reported having no conflicts of interest.
Estrogenic compounds could have a number of effects on the genomic machinery, that could in turn lead to an increased risk of leukemia in offspring. It may be that oral contraceptives cause epigenetic changes to fetal hematopoietic stem cells that lead to gene rearrangements and oxidative damage, which could then influence the risk of developing childhood leukemia.
This study opens a new avenue of investigation for a risk factor that might increase a child’s susceptibility to leukemia and is important in shedding more light on dose-response associations of exposures.
Dr. Maria S. Pombo-de-Oliveira is from the pediatric hematology-oncology research program at the Instituto Nacional de Câncer in Rio de Janeiro. These comments are adapted from an accompanying editorial (Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045[18]30509-6). Dr. Pombo-de-Oliveira reported having no conflicts of interest.
A nationwide cohort study found an association between a woman’s use of hormonal contraceptives and a small increased risk of nonlymphoid leukemia in her offspring.
Maternal use of hormonal contraception either during pregnancy or in the 3 months beforehand was associated with a 46% higher risk of any leukemia in the children (P = .011), compared with no use, Marie Hargreave, PhD, of the Danish Cancer Society Research Center and her coauthors reported in Lancet Oncology.
The study of 1,185,157 children born between 1996 and 2014 included data from the Danish Cancer Registry and Danish National Prescription Registry and followed children for a median of 9.3 years.
Use during pregnancy was associated with a 78% higher risk of any leukemia in the offspring (P = .070), and contraception use that stopped more than 3 months before pregnancy was associated with a 25% higher risk of any leukemia (P = .039).
The researchers estimated that maternal use of hormonal contraceptives up to and including during pregnancy would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia in Denmark from contraceptive use from 1996 to 2014.
The increased risk appeared to be limited to nonlymphoid leukemia only. The risk with recent use was more than twofold higher (HR, 2.17), compared with nonuse, and use during pregnancy was associated with a nearly fourfold increase in the risk of leukemia (HR, 3.87).
“Sex hormones are considered to be potent carcinogens, and the causal association between in-utero exposure to the oestrogen analogue diethylstilbestrol and subsequent risk for adenocarcinoma of the vagina is firmly established,” Dr. Hargreave and her colleagues wrote. “The mechanism by which maternal use of hormones increases cancer risk in children is, however, still not clear.”
Recent use of combined oral contraceptive products was associated with a more than twofold increased risk of nonlymphoid leukemia in offspring, compared with no use. However progestin-only oral contraceptives and emergency contraception did not appear to increase in the risk of lymphoid or nonlymphoid leukemia.
The association was strongest in children aged 6-10 years, which the authors suggested was likely because the incidence of nonlymphoid leukemia increases after the age of 6 years.
While acknowledging that the small increase in leukemia risk was not a major safety concern for hormonal contraceptives, the authors commented that the results suggested the intrauterine hormonal environment could be a direction for research into the causes of leukemia.
The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.
SOURCE: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
A nationwide cohort study found an association between a woman’s use of hormonal contraceptives and a small increased risk of nonlymphoid leukemia in her offspring.
Maternal use of hormonal contraception either during pregnancy or in the 3 months beforehand was associated with a 46% higher risk of any leukemia in the children (P = .011), compared with no use, Marie Hargreave, PhD, of the Danish Cancer Society Research Center and her coauthors reported in Lancet Oncology.
The study of 1,185,157 children born between 1996 and 2014 included data from the Danish Cancer Registry and Danish National Prescription Registry and followed children for a median of 9.3 years.
Use during pregnancy was associated with a 78% higher risk of any leukemia in the offspring (P = .070), and contraception use that stopped more than 3 months before pregnancy was associated with a 25% higher risk of any leukemia (P = .039).
The researchers estimated that maternal use of hormonal contraceptives up to and including during pregnancy would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia in Denmark from contraceptive use from 1996 to 2014.
The increased risk appeared to be limited to nonlymphoid leukemia only. The risk with recent use was more than twofold higher (HR, 2.17), compared with nonuse, and use during pregnancy was associated with a nearly fourfold increase in the risk of leukemia (HR, 3.87).
“Sex hormones are considered to be potent carcinogens, and the causal association between in-utero exposure to the oestrogen analogue diethylstilbestrol and subsequent risk for adenocarcinoma of the vagina is firmly established,” Dr. Hargreave and her colleagues wrote. “The mechanism by which maternal use of hormones increases cancer risk in children is, however, still not clear.”
Recent use of combined oral contraceptive products was associated with a more than twofold increased risk of nonlymphoid leukemia in offspring, compared with no use. However progestin-only oral contraceptives and emergency contraception did not appear to increase in the risk of lymphoid or nonlymphoid leukemia.
The association was strongest in children aged 6-10 years, which the authors suggested was likely because the incidence of nonlymphoid leukemia increases after the age of 6 years.
While acknowledging that the small increase in leukemia risk was not a major safety concern for hormonal contraceptives, the authors commented that the results suggested the intrauterine hormonal environment could be a direction for research into the causes of leukemia.
The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.
SOURCE: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
FROM LANCET ONCOLOGY
Key clinical point:
Major finding: Recent maternal hormonal contraceptive use was linked to one additional case of leukemia per 47,170 children.
Study details: Danish nationwide cohort study in 1,185,157 children.
Disclosures: The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.
Source: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
Top cancer researcher fails to disclose corporate financial ties in major research journals
This article was produced in partnership with The New York Times.
One of the world’s top breast cancer doctors failed to disclose millions of dollars in payments from drug and health care companies in recent years, omitting his financial ties from dozens of research articles in prestigious publications like the New England Journal of Medicine and the Lancet.
The researcher, José Baselga, MD, a towering figure in the cancer world, is the chief medical officer at Memorial Sloan Kettering Cancer Center in New York. He has held board memberships or advisory roles with Roche and Bristol-Myers Squibb, among other corporations; has had a stake in start-ups testing cancer therapies; and played a key role in the development of breakthrough drugs that have revolutionized treatments for breast cancer.
According to an analysis by ProPublica and the New York Times, Dr. Baselga did not follow financial disclosure rules set by the American Association for Cancer Research when he was president of the group. He also left out payments he received from companies connected to cancer research in his articles published in the group’s journal, Cancer Discovery. At the same time, he has been one of the journal’s two editors in chief.
At a conference this year and before analysts in 2017, he put a positive spin on the results of two Roche-sponsored clinical trials that many others considered disappointments, without disclosing his relationship to the company. Since 2014, he has received more than $3 million from Roche in consulting fees and for his stake in a company it acquired.
Dr. Baselga did not dispute his relationships with at least a dozen companies. In an interview, he said the disclosure lapses were unintentional.
He stressed that much of his industry work was publicly known although he declined to provide payment figures from his involvement with some biotech start-ups. “I acknowledge that there have been inconsistencies, but that’s what it is,” he said. “It’s not that I do not appreciate the importance.”
Dr. Baselga’s extensive corporate relationships – and his frequent failure to disclose them – illustrate how permeable the boundaries remain between academic research and industry, and how weakly reporting requirements are enforced by the medical journals and professional societies charged with policing them.
A decade ago, a series of scandals involving the secret influence of the pharmaceutical industry on drug research prompted the medical community to beef up its conflict-of-interest disclosure requirements. Ethicists worry that outside entanglements can shape the way studies are designed and medications are prescribed to patients, allowing bias to influence medical practice. Disclosing those connections allows the public, other scientists, and doctors to evaluate the research and weigh potential conflicts.
If leaders don’t follow the rules, then we don’t really have rules,” said Walid Gellad, MD, an of the department of medicine at the University of Pittsburgh and director of its Center for Pharmaceutical Policy and Prescribing. “It says that the rules don’t matter.”
The penalties for such ethical lapses are not severe. The cancer research group, the American Association for Cancer Research, warns authors who fill out disclosure forms for its journals that they face a 3-year ban on publishing if they are found to have financial relationships that they did not disclose. But the ban is not included in the conflict-of-interest policy posted on its website, and the group said no author had ever been barred.
Many journals and professional societies do not check conflicts and simply require authors to correct the record.
Officials at the AACR, the American Society of Clinical Oncology and the New England Journal of Medicine said they were looking into Dr. Baselga’s omissions after inquiries from the Times and ProPublica. The Lancet declined to say whether it would look into the matter.
Christine Hickey, a spokeswoman for Memorial Sloan Kettering, said that Dr. Baselga had properly informed the hospital of his outside industry work and that it was Dr. Baselga’s responsibility to disclose such relationships to entities such as medical journals. The cancer center, she said, “has a rigorous and comprehensive compliance program in place to promote honesty and objectivity in scientific research.”
Asked if he planned to correct his disclosures, Dr. Baselga asked reporters what they would recommend. In a statement several days later, he said he would correct his conflict-of-interest reporting for 17 articles, including in the New England Journal of Medicine, the Lancet, and the publication he edits, Cancer Discovery. He said that he did not believe disclosure was required for dozens of other articles detailing early stages of research.
“I have spent my career caring for cancer patients and bringing new therapies to the clinic with the goal of extending and saving lives,” Dr. Baselga said in the statement. “While I have been inconsistent with disclosures and acknowledge that fact, that is a far cry from compromising my responsibilities as a physician, as a scientist and as a clinical leader.”
The corporate imprint on cancer research
Dr. Baselga, 59, supervises clinical operations at Memorial Sloan Kettering, one of the nation’s top cancer centers and wields influence over the lives of patients and companies wishing to conduct trials there. He was paid more than $1.5 million in compensation by the cancer center in 2016, according to the hospital’s latest available tax disclosures, but that does not include his consulting or board fees from outside companies.
Many top medical researchers have ties to the for-profit health care industry, and some overlap is seen as a good thing – after all, these are the companies charged with developing the drugs, medical devices and diagnostic tests of the future.
Dr. Baselga’s relationship to industry is extensive. In addition to sitting on the board of Bristol-Myers Squibb, he is a director of Varian Medical Systems, which sells radiation equipment and for whom Memorial Sloan Kettering is a client.
In all, Dr. Baselga has served on the boards of at least six companies since 2013, positions that have required him to assume a fiduciary responsibility to protect the interests of those companies, even as he oversees the cancer center’s medical operations.
The hospital and Dr. Baselga said steps had been taken to prevent him from having a say in any business between the cancer center and the companies on whose boards he sits.
The chief executive of Memorial Sloan Kettering, Craig B. Thompson, MD, settled lawsuits several years ago that were filed by the University of Pennsylvania, Philadelphia, and an affiliated research center. They contended that he hid research conducted while he was at Penn to start a new company, Agios Pharmaceuticals, and did not share the earnings. Dr. Thompson disputed the allegations. He now sits on the board of Merck, which manufactures Keytruda, a blockbuster cancer therapy.
Ms. Hickey said the cancer center cannot fulfill its charitable mission without working with industry. “We encourage collaboration and are proud that our work has led to the approval of novel, lifesaving cancer treatments for patients around the world,” she said.
Some disclosures are required; others aren’t
After the scandals a decade ago over lack of disclosure, the federal government began requiring drug and device manufacturers to publicly disclose payments to doctors in 2013.
From August 2013 through 2017, Dr. Baselga received nearly $3.5 million from nine companies, according to the federal Open Payments database, which compiles disclosures filed by drug and device companies.
Dr. Baselga has disclosed in other forums investments and advisory roles in biotech start-ups, but he declined to provide a tally of financial interests in those firms. Companies that have not received approval from the Food and Drug Administration for their products – projects still in the testing phases – do not have to report payments they make to doctors.
Serving on boards can be lucrative. In 2017, Dr. Baselga received $260,000 in cash and stock awards to sit on Varian’s board of directors, according to the company’s corporate filings.
ProPublica and the Times analyzed Dr. Baselga’s publications in medical journals since 2013, the year he joined Memorial Sloan Kettering. He failed to disclose any industry relationships in more than 100, or about 60% of the time, a figure that has increased with each passing year. Last year, he did not list any potential conflicts in 87% of the articles that he wrote or cowrote.
Dr. Baselga compiled a color-coded list of his articles and offered a different interpretation. Sixty-two of the papers for which he did not disclose any potential conflict represented “conceptual, basic laboratory or translational work,” and did not require one, he said. Questions could be raised about others, he said, but he added that most “had no clinical nor financial implications.” That left the 17 papers he plans to correct.
Early-stage research often carries financial weight because it helps companies decide whether to move ahead with a product. In about two-thirds of Dr. Baselga’s articles that lacked details of his industry ties, one or more of his coauthors listed theirs.
In 2015, Dr. Baselga published an article in the New England Journal about a Roche-sponsored trial of one of the company’s drugs, Zelboraf. Despite his financial ties to Roche, he declared that he had “nothing to disclose.” Fourteen of his coauthors reported ties to Roche.
Dr. Baselga defended the articles, saying that “these are high-quality manuscripts reporting on important clinical trials that led to a better understanding of cancer treatments.”
The guidelines enacted by most major medical journals and professional societies ask authors and presenters to list recent financial relationships that could pose a conflict.
But much of this reporting still relies on the honor system. A study in August in the journal JAMA Oncology found that one-third of authors in a sample of cancer trials did not report all payments from the studies’ sponsors.
“We don’t routinely check because we don’t have those kind of resources,” said Rita F. Redberg, MD, the editor of JAMA Internal Medicine, who has been critical of the influence of industry on medical practice. “We rely on trust and integrity. It’s kind of an assumed part of the professional relationship.”
Jennifer Zeis, a spokeswoman for the New England Journal of Medicine, said in an email that it had now asked Dr. Baselga to amend his disclosures. She said the journal planned to overhaul its tracking of industry relationships.
The AACR said it had begun an “extensive review” of the disclosure forms submitted by Dr. Baselga.
It said that it had never barred an author from publishing, and that “such an action would be necessary only in cases of egregious, consistent violations of the rules.”
Among the most prominent relationships that Dr. Baselga has often failed to disclose is with the Swiss pharmaceutical giant Roche and its United States subsidiary Genentech.
In June 2017, at the annual meeting of the ASCO in Chicago, Dr. Baselga spoke at a Roche-sponsored investor event about study results that the company had been counting on to persuade oncologists to move patients from Herceptin – which was facing competition from cheaper alternatives – to a combination treatment involving Herceptin and a newer, more expensive drug, Perjeta.
The results were so underwhelming that Roche’s stock fell 5 % on the news. One analyst described the results as a “lead balloon,” and an editorial in the New England Journal called it a “disappointment.”
Dr. Baselga, however, told analysts that critiques were “weird” and “strange.”
This June, at the same cancer conference, Dr. Baselga struck an upbeat note about the results of a Roche trial of the drug taselisib, saying in a blog post published on the cancer center website that the results were “incredibly exciting” while conceding the side effects from the drug were high.
That same day, Roche announced it was scrapping plans to develop the drug. The news was another disappointment involving the class of drugs called PI3K inhibitors, which is a major focus of Dr. Baselga’s current research.
In neither case did Dr. Baselga reveal that his ties to Roche and Genentech went beyond serving as a trial investigator. In 2014, Roche acquired Seragon, a cancer research company in which Dr. Baselga had an ownership stake, for $725 million. Dr. Baselga received more than $3 million in 2014 and 2015 for his stake in the company, according to the federal Open Payments database.
From 2013 to 2017, Roche also paid Dr. Baselga more than $50,000 in consulting fees, according to the database.
These details were not included in the conflict-of-interest statements that are required of all presenters at the ASCO conference, although he did disclose ownership interests and consulting relationships with several other companies in the prior two years.
ASCO said it would conduct an internal review of Dr. Baselga’s disclosures and would refer the findings to a panel.
Dr. Baselga said that he played no role in the Seragon acquisition and that he had cut ties with Roche since joining the board of a competitor, Bristol-Myers, in March. As for his presentations at the ASCO meetings in the last 2 years, he said he had also noted shortcomings in the studies.
The combination of Perjeta with Herceptin was later approved by the FDA for certain high-risk patients. As for taselisib, Dr. Baselga stands by his belief that the PI3K class of drugs will be an important target for fighting cancer.
Katie Thomas covers the pharmaceutical industry for the New York Times.
This article was produced in partnership with The New York Times.
One of the world’s top breast cancer doctors failed to disclose millions of dollars in payments from drug and health care companies in recent years, omitting his financial ties from dozens of research articles in prestigious publications like the New England Journal of Medicine and the Lancet.
The researcher, José Baselga, MD, a towering figure in the cancer world, is the chief medical officer at Memorial Sloan Kettering Cancer Center in New York. He has held board memberships or advisory roles with Roche and Bristol-Myers Squibb, among other corporations; has had a stake in start-ups testing cancer therapies; and played a key role in the development of breakthrough drugs that have revolutionized treatments for breast cancer.
According to an analysis by ProPublica and the New York Times, Dr. Baselga did not follow financial disclosure rules set by the American Association for Cancer Research when he was president of the group. He also left out payments he received from companies connected to cancer research in his articles published in the group’s journal, Cancer Discovery. At the same time, he has been one of the journal’s two editors in chief.
At a conference this year and before analysts in 2017, he put a positive spin on the results of two Roche-sponsored clinical trials that many others considered disappointments, without disclosing his relationship to the company. Since 2014, he has received more than $3 million from Roche in consulting fees and for his stake in a company it acquired.
Dr. Baselga did not dispute his relationships with at least a dozen companies. In an interview, he said the disclosure lapses were unintentional.
He stressed that much of his industry work was publicly known although he declined to provide payment figures from his involvement with some biotech start-ups. “I acknowledge that there have been inconsistencies, but that’s what it is,” he said. “It’s not that I do not appreciate the importance.”
Dr. Baselga’s extensive corporate relationships – and his frequent failure to disclose them – illustrate how permeable the boundaries remain between academic research and industry, and how weakly reporting requirements are enforced by the medical journals and professional societies charged with policing them.
A decade ago, a series of scandals involving the secret influence of the pharmaceutical industry on drug research prompted the medical community to beef up its conflict-of-interest disclosure requirements. Ethicists worry that outside entanglements can shape the way studies are designed and medications are prescribed to patients, allowing bias to influence medical practice. Disclosing those connections allows the public, other scientists, and doctors to evaluate the research and weigh potential conflicts.
If leaders don’t follow the rules, then we don’t really have rules,” said Walid Gellad, MD, an of the department of medicine at the University of Pittsburgh and director of its Center for Pharmaceutical Policy and Prescribing. “It says that the rules don’t matter.”
The penalties for such ethical lapses are not severe. The cancer research group, the American Association for Cancer Research, warns authors who fill out disclosure forms for its journals that they face a 3-year ban on publishing if they are found to have financial relationships that they did not disclose. But the ban is not included in the conflict-of-interest policy posted on its website, and the group said no author had ever been barred.
Many journals and professional societies do not check conflicts and simply require authors to correct the record.
Officials at the AACR, the American Society of Clinical Oncology and the New England Journal of Medicine said they were looking into Dr. Baselga’s omissions after inquiries from the Times and ProPublica. The Lancet declined to say whether it would look into the matter.
Christine Hickey, a spokeswoman for Memorial Sloan Kettering, said that Dr. Baselga had properly informed the hospital of his outside industry work and that it was Dr. Baselga’s responsibility to disclose such relationships to entities such as medical journals. The cancer center, she said, “has a rigorous and comprehensive compliance program in place to promote honesty and objectivity in scientific research.”
Asked if he planned to correct his disclosures, Dr. Baselga asked reporters what they would recommend. In a statement several days later, he said he would correct his conflict-of-interest reporting for 17 articles, including in the New England Journal of Medicine, the Lancet, and the publication he edits, Cancer Discovery. He said that he did not believe disclosure was required for dozens of other articles detailing early stages of research.
“I have spent my career caring for cancer patients and bringing new therapies to the clinic with the goal of extending and saving lives,” Dr. Baselga said in the statement. “While I have been inconsistent with disclosures and acknowledge that fact, that is a far cry from compromising my responsibilities as a physician, as a scientist and as a clinical leader.”
The corporate imprint on cancer research
Dr. Baselga, 59, supervises clinical operations at Memorial Sloan Kettering, one of the nation’s top cancer centers and wields influence over the lives of patients and companies wishing to conduct trials there. He was paid more than $1.5 million in compensation by the cancer center in 2016, according to the hospital’s latest available tax disclosures, but that does not include his consulting or board fees from outside companies.
Many top medical researchers have ties to the for-profit health care industry, and some overlap is seen as a good thing – after all, these are the companies charged with developing the drugs, medical devices and diagnostic tests of the future.
Dr. Baselga’s relationship to industry is extensive. In addition to sitting on the board of Bristol-Myers Squibb, he is a director of Varian Medical Systems, which sells radiation equipment and for whom Memorial Sloan Kettering is a client.
In all, Dr. Baselga has served on the boards of at least six companies since 2013, positions that have required him to assume a fiduciary responsibility to protect the interests of those companies, even as he oversees the cancer center’s medical operations.
The hospital and Dr. Baselga said steps had been taken to prevent him from having a say in any business between the cancer center and the companies on whose boards he sits.
The chief executive of Memorial Sloan Kettering, Craig B. Thompson, MD, settled lawsuits several years ago that were filed by the University of Pennsylvania, Philadelphia, and an affiliated research center. They contended that he hid research conducted while he was at Penn to start a new company, Agios Pharmaceuticals, and did not share the earnings. Dr. Thompson disputed the allegations. He now sits on the board of Merck, which manufactures Keytruda, a blockbuster cancer therapy.
Ms. Hickey said the cancer center cannot fulfill its charitable mission without working with industry. “We encourage collaboration and are proud that our work has led to the approval of novel, lifesaving cancer treatments for patients around the world,” she said.
Some disclosures are required; others aren’t
After the scandals a decade ago over lack of disclosure, the federal government began requiring drug and device manufacturers to publicly disclose payments to doctors in 2013.
From August 2013 through 2017, Dr. Baselga received nearly $3.5 million from nine companies, according to the federal Open Payments database, which compiles disclosures filed by drug and device companies.
Dr. Baselga has disclosed in other forums investments and advisory roles in biotech start-ups, but he declined to provide a tally of financial interests in those firms. Companies that have not received approval from the Food and Drug Administration for their products – projects still in the testing phases – do not have to report payments they make to doctors.
Serving on boards can be lucrative. In 2017, Dr. Baselga received $260,000 in cash and stock awards to sit on Varian’s board of directors, according to the company’s corporate filings.
ProPublica and the Times analyzed Dr. Baselga’s publications in medical journals since 2013, the year he joined Memorial Sloan Kettering. He failed to disclose any industry relationships in more than 100, or about 60% of the time, a figure that has increased with each passing year. Last year, he did not list any potential conflicts in 87% of the articles that he wrote or cowrote.
Dr. Baselga compiled a color-coded list of his articles and offered a different interpretation. Sixty-two of the papers for which he did not disclose any potential conflict represented “conceptual, basic laboratory or translational work,” and did not require one, he said. Questions could be raised about others, he said, but he added that most “had no clinical nor financial implications.” That left the 17 papers he plans to correct.
Early-stage research often carries financial weight because it helps companies decide whether to move ahead with a product. In about two-thirds of Dr. Baselga’s articles that lacked details of his industry ties, one or more of his coauthors listed theirs.
In 2015, Dr. Baselga published an article in the New England Journal about a Roche-sponsored trial of one of the company’s drugs, Zelboraf. Despite his financial ties to Roche, he declared that he had “nothing to disclose.” Fourteen of his coauthors reported ties to Roche.
Dr. Baselga defended the articles, saying that “these are high-quality manuscripts reporting on important clinical trials that led to a better understanding of cancer treatments.”
The guidelines enacted by most major medical journals and professional societies ask authors and presenters to list recent financial relationships that could pose a conflict.
But much of this reporting still relies on the honor system. A study in August in the journal JAMA Oncology found that one-third of authors in a sample of cancer trials did not report all payments from the studies’ sponsors.
“We don’t routinely check because we don’t have those kind of resources,” said Rita F. Redberg, MD, the editor of JAMA Internal Medicine, who has been critical of the influence of industry on medical practice. “We rely on trust and integrity. It’s kind of an assumed part of the professional relationship.”
Jennifer Zeis, a spokeswoman for the New England Journal of Medicine, said in an email that it had now asked Dr. Baselga to amend his disclosures. She said the journal planned to overhaul its tracking of industry relationships.
The AACR said it had begun an “extensive review” of the disclosure forms submitted by Dr. Baselga.
It said that it had never barred an author from publishing, and that “such an action would be necessary only in cases of egregious, consistent violations of the rules.”
Among the most prominent relationships that Dr. Baselga has often failed to disclose is with the Swiss pharmaceutical giant Roche and its United States subsidiary Genentech.
In June 2017, at the annual meeting of the ASCO in Chicago, Dr. Baselga spoke at a Roche-sponsored investor event about study results that the company had been counting on to persuade oncologists to move patients from Herceptin – which was facing competition from cheaper alternatives – to a combination treatment involving Herceptin and a newer, more expensive drug, Perjeta.
The results were so underwhelming that Roche’s stock fell 5 % on the news. One analyst described the results as a “lead balloon,” and an editorial in the New England Journal called it a “disappointment.”
Dr. Baselga, however, told analysts that critiques were “weird” and “strange.”
This June, at the same cancer conference, Dr. Baselga struck an upbeat note about the results of a Roche trial of the drug taselisib, saying in a blog post published on the cancer center website that the results were “incredibly exciting” while conceding the side effects from the drug were high.
That same day, Roche announced it was scrapping plans to develop the drug. The news was another disappointment involving the class of drugs called PI3K inhibitors, which is a major focus of Dr. Baselga’s current research.
In neither case did Dr. Baselga reveal that his ties to Roche and Genentech went beyond serving as a trial investigator. In 2014, Roche acquired Seragon, a cancer research company in which Dr. Baselga had an ownership stake, for $725 million. Dr. Baselga received more than $3 million in 2014 and 2015 for his stake in the company, according to the federal Open Payments database.
From 2013 to 2017, Roche also paid Dr. Baselga more than $50,000 in consulting fees, according to the database.
These details were not included in the conflict-of-interest statements that are required of all presenters at the ASCO conference, although he did disclose ownership interests and consulting relationships with several other companies in the prior two years.
ASCO said it would conduct an internal review of Dr. Baselga’s disclosures and would refer the findings to a panel.
Dr. Baselga said that he played no role in the Seragon acquisition and that he had cut ties with Roche since joining the board of a competitor, Bristol-Myers, in March. As for his presentations at the ASCO meetings in the last 2 years, he said he had also noted shortcomings in the studies.
The combination of Perjeta with Herceptin was later approved by the FDA for certain high-risk patients. As for taselisib, Dr. Baselga stands by his belief that the PI3K class of drugs will be an important target for fighting cancer.
Katie Thomas covers the pharmaceutical industry for the New York Times.
This article was produced in partnership with The New York Times.
One of the world’s top breast cancer doctors failed to disclose millions of dollars in payments from drug and health care companies in recent years, omitting his financial ties from dozens of research articles in prestigious publications like the New England Journal of Medicine and the Lancet.
The researcher, José Baselga, MD, a towering figure in the cancer world, is the chief medical officer at Memorial Sloan Kettering Cancer Center in New York. He has held board memberships or advisory roles with Roche and Bristol-Myers Squibb, among other corporations; has had a stake in start-ups testing cancer therapies; and played a key role in the development of breakthrough drugs that have revolutionized treatments for breast cancer.
According to an analysis by ProPublica and the New York Times, Dr. Baselga did not follow financial disclosure rules set by the American Association for Cancer Research when he was president of the group. He also left out payments he received from companies connected to cancer research in his articles published in the group’s journal, Cancer Discovery. At the same time, he has been one of the journal’s two editors in chief.
At a conference this year and before analysts in 2017, he put a positive spin on the results of two Roche-sponsored clinical trials that many others considered disappointments, without disclosing his relationship to the company. Since 2014, he has received more than $3 million from Roche in consulting fees and for his stake in a company it acquired.
Dr. Baselga did not dispute his relationships with at least a dozen companies. In an interview, he said the disclosure lapses were unintentional.
He stressed that much of his industry work was publicly known although he declined to provide payment figures from his involvement with some biotech start-ups. “I acknowledge that there have been inconsistencies, but that’s what it is,” he said. “It’s not that I do not appreciate the importance.”
Dr. Baselga’s extensive corporate relationships – and his frequent failure to disclose them – illustrate how permeable the boundaries remain between academic research and industry, and how weakly reporting requirements are enforced by the medical journals and professional societies charged with policing them.
A decade ago, a series of scandals involving the secret influence of the pharmaceutical industry on drug research prompted the medical community to beef up its conflict-of-interest disclosure requirements. Ethicists worry that outside entanglements can shape the way studies are designed and medications are prescribed to patients, allowing bias to influence medical practice. Disclosing those connections allows the public, other scientists, and doctors to evaluate the research and weigh potential conflicts.
If leaders don’t follow the rules, then we don’t really have rules,” said Walid Gellad, MD, an of the department of medicine at the University of Pittsburgh and director of its Center for Pharmaceutical Policy and Prescribing. “It says that the rules don’t matter.”
The penalties for such ethical lapses are not severe. The cancer research group, the American Association for Cancer Research, warns authors who fill out disclosure forms for its journals that they face a 3-year ban on publishing if they are found to have financial relationships that they did not disclose. But the ban is not included in the conflict-of-interest policy posted on its website, and the group said no author had ever been barred.
Many journals and professional societies do not check conflicts and simply require authors to correct the record.
Officials at the AACR, the American Society of Clinical Oncology and the New England Journal of Medicine said they were looking into Dr. Baselga’s omissions after inquiries from the Times and ProPublica. The Lancet declined to say whether it would look into the matter.
Christine Hickey, a spokeswoman for Memorial Sloan Kettering, said that Dr. Baselga had properly informed the hospital of his outside industry work and that it was Dr. Baselga’s responsibility to disclose such relationships to entities such as medical journals. The cancer center, she said, “has a rigorous and comprehensive compliance program in place to promote honesty and objectivity in scientific research.”
Asked if he planned to correct his disclosures, Dr. Baselga asked reporters what they would recommend. In a statement several days later, he said he would correct his conflict-of-interest reporting for 17 articles, including in the New England Journal of Medicine, the Lancet, and the publication he edits, Cancer Discovery. He said that he did not believe disclosure was required for dozens of other articles detailing early stages of research.
“I have spent my career caring for cancer patients and bringing new therapies to the clinic with the goal of extending and saving lives,” Dr. Baselga said in the statement. “While I have been inconsistent with disclosures and acknowledge that fact, that is a far cry from compromising my responsibilities as a physician, as a scientist and as a clinical leader.”
The corporate imprint on cancer research
Dr. Baselga, 59, supervises clinical operations at Memorial Sloan Kettering, one of the nation’s top cancer centers and wields influence over the lives of patients and companies wishing to conduct trials there. He was paid more than $1.5 million in compensation by the cancer center in 2016, according to the hospital’s latest available tax disclosures, but that does not include his consulting or board fees from outside companies.
Many top medical researchers have ties to the for-profit health care industry, and some overlap is seen as a good thing – after all, these are the companies charged with developing the drugs, medical devices and diagnostic tests of the future.
Dr. Baselga’s relationship to industry is extensive. In addition to sitting on the board of Bristol-Myers Squibb, he is a director of Varian Medical Systems, which sells radiation equipment and for whom Memorial Sloan Kettering is a client.
In all, Dr. Baselga has served on the boards of at least six companies since 2013, positions that have required him to assume a fiduciary responsibility to protect the interests of those companies, even as he oversees the cancer center’s medical operations.
The hospital and Dr. Baselga said steps had been taken to prevent him from having a say in any business between the cancer center and the companies on whose boards he sits.
The chief executive of Memorial Sloan Kettering, Craig B. Thompson, MD, settled lawsuits several years ago that were filed by the University of Pennsylvania, Philadelphia, and an affiliated research center. They contended that he hid research conducted while he was at Penn to start a new company, Agios Pharmaceuticals, and did not share the earnings. Dr. Thompson disputed the allegations. He now sits on the board of Merck, which manufactures Keytruda, a blockbuster cancer therapy.
Ms. Hickey said the cancer center cannot fulfill its charitable mission without working with industry. “We encourage collaboration and are proud that our work has led to the approval of novel, lifesaving cancer treatments for patients around the world,” she said.
Some disclosures are required; others aren’t
After the scandals a decade ago over lack of disclosure, the federal government began requiring drug and device manufacturers to publicly disclose payments to doctors in 2013.
From August 2013 through 2017, Dr. Baselga received nearly $3.5 million from nine companies, according to the federal Open Payments database, which compiles disclosures filed by drug and device companies.
Dr. Baselga has disclosed in other forums investments and advisory roles in biotech start-ups, but he declined to provide a tally of financial interests in those firms. Companies that have not received approval from the Food and Drug Administration for their products – projects still in the testing phases – do not have to report payments they make to doctors.
Serving on boards can be lucrative. In 2017, Dr. Baselga received $260,000 in cash and stock awards to sit on Varian’s board of directors, according to the company’s corporate filings.
ProPublica and the Times analyzed Dr. Baselga’s publications in medical journals since 2013, the year he joined Memorial Sloan Kettering. He failed to disclose any industry relationships in more than 100, or about 60% of the time, a figure that has increased with each passing year. Last year, he did not list any potential conflicts in 87% of the articles that he wrote or cowrote.
Dr. Baselga compiled a color-coded list of his articles and offered a different interpretation. Sixty-two of the papers for which he did not disclose any potential conflict represented “conceptual, basic laboratory or translational work,” and did not require one, he said. Questions could be raised about others, he said, but he added that most “had no clinical nor financial implications.” That left the 17 papers he plans to correct.
Early-stage research often carries financial weight because it helps companies decide whether to move ahead with a product. In about two-thirds of Dr. Baselga’s articles that lacked details of his industry ties, one or more of his coauthors listed theirs.
In 2015, Dr. Baselga published an article in the New England Journal about a Roche-sponsored trial of one of the company’s drugs, Zelboraf. Despite his financial ties to Roche, he declared that he had “nothing to disclose.” Fourteen of his coauthors reported ties to Roche.
Dr. Baselga defended the articles, saying that “these are high-quality manuscripts reporting on important clinical trials that led to a better understanding of cancer treatments.”
The guidelines enacted by most major medical journals and professional societies ask authors and presenters to list recent financial relationships that could pose a conflict.
But much of this reporting still relies on the honor system. A study in August in the journal JAMA Oncology found that one-third of authors in a sample of cancer trials did not report all payments from the studies’ sponsors.
“We don’t routinely check because we don’t have those kind of resources,” said Rita F. Redberg, MD, the editor of JAMA Internal Medicine, who has been critical of the influence of industry on medical practice. “We rely on trust and integrity. It’s kind of an assumed part of the professional relationship.”
Jennifer Zeis, a spokeswoman for the New England Journal of Medicine, said in an email that it had now asked Dr. Baselga to amend his disclosures. She said the journal planned to overhaul its tracking of industry relationships.
The AACR said it had begun an “extensive review” of the disclosure forms submitted by Dr. Baselga.
It said that it had never barred an author from publishing, and that “such an action would be necessary only in cases of egregious, consistent violations of the rules.”
Among the most prominent relationships that Dr. Baselga has often failed to disclose is with the Swiss pharmaceutical giant Roche and its United States subsidiary Genentech.
In June 2017, at the annual meeting of the ASCO in Chicago, Dr. Baselga spoke at a Roche-sponsored investor event about study results that the company had been counting on to persuade oncologists to move patients from Herceptin – which was facing competition from cheaper alternatives – to a combination treatment involving Herceptin and a newer, more expensive drug, Perjeta.
The results were so underwhelming that Roche’s stock fell 5 % on the news. One analyst described the results as a “lead balloon,” and an editorial in the New England Journal called it a “disappointment.”
Dr. Baselga, however, told analysts that critiques were “weird” and “strange.”
This June, at the same cancer conference, Dr. Baselga struck an upbeat note about the results of a Roche trial of the drug taselisib, saying in a blog post published on the cancer center website that the results were “incredibly exciting” while conceding the side effects from the drug were high.
That same day, Roche announced it was scrapping plans to develop the drug. The news was another disappointment involving the class of drugs called PI3K inhibitors, which is a major focus of Dr. Baselga’s current research.
In neither case did Dr. Baselga reveal that his ties to Roche and Genentech went beyond serving as a trial investigator. In 2014, Roche acquired Seragon, a cancer research company in which Dr. Baselga had an ownership stake, for $725 million. Dr. Baselga received more than $3 million in 2014 and 2015 for his stake in the company, according to the federal Open Payments database.
From 2013 to 2017, Roche also paid Dr. Baselga more than $50,000 in consulting fees, according to the database.
These details were not included in the conflict-of-interest statements that are required of all presenters at the ASCO conference, although he did disclose ownership interests and consulting relationships with several other companies in the prior two years.
ASCO said it would conduct an internal review of Dr. Baselga’s disclosures and would refer the findings to a panel.
Dr. Baselga said that he played no role in the Seragon acquisition and that he had cut ties with Roche since joining the board of a competitor, Bristol-Myers, in March. As for his presentations at the ASCO meetings in the last 2 years, he said he had also noted shortcomings in the studies.
The combination of Perjeta with Herceptin was later approved by the FDA for certain high-risk patients. As for taselisib, Dr. Baselga stands by his belief that the PI3K class of drugs will be an important target for fighting cancer.
Katie Thomas covers the pharmaceutical industry for the New York Times.
Children born from ART at increased risk of developing arterial hypertension
Children born from assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection may be at risk of developing arterial hypertension due to premature vascular aging, according to a study published in the Journal of the American College of Cardiology.
In a previous study, Emrush Rexhaj, MD, director of arterial hypertension and altitude medicine at Inselspital, University Hospital, Bern, Switzerland, and his colleagues assessed vascular function in participants who were born with assisted reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); the investigators found vascular dysfunction in this patient population not “related to parental factors but to the ART procedure itself,” they said.
Dr. Rexhaj and his colleagues then reassessed vascular function in 54 participants (mean age 16.5 years old) who returned from the previous study 5 years after the initial assessment and compared the results with 43 matched patients in a control group (mean age, 17.4 years). There were no significant differences regarding body mass index, lipid, creatinine, electrolyte plasma concentrations, high-sensitive C-reactive protein, birth weight, and gestational age between children in either group, as well as no significant differences in maternal BMI, cardiovascular risk profile, and smoking status.
The investigators – with Théo A. Meister, MD, also of the university, as a joint lead author with Dr. Rexhaj – performed blinded endothelium-dependent and endothelium-independent vasodilation of the brachial artery in a supine position at room temperature and after 15 minutes of rest. They also measured carotid intima-media thickness (IMT), large artery stiffness, 24-hour ambulatory blood pressure monitoring, and short-term blood pressure variability.
“It only took five years for differences in arterial blood pressure to show,” Dr. Rexhaj stated in a press release. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”
Specifically, there was an approximately 25% reduction in flow-mediated dilation in the ART group (7%) compared with the control group (9%), which the investigators attributed to endothelial dysfunction (P less than .001). In ART patients, carotid IMT (463 mm) and carotid pulse-wave velocity (7.7 m/s) was significantly increased, compared with carotid IMT (435 mm; P less than .01) and pulse-wave velocity (7.2 m/s; P equals .033) in the control group.
With regard to arterial hypertension, 24-hour systolic blood pressure in the ART group (120 mm Hg) was “markedly” higher than in the control group (116 mm Hg; P equals .02); 24-hour diastolic blood pressure was also significantly higher in the ART group (71 mm Hg) compared with the control group (69 mm Hg; P equals .03). Investigators noted 8 of the 52 patients (15%) in the ART group met clinical criteria for arterial hypertension according to ambulatory blood pressure monitoring, compared with 1 of the 40 patients (2%) in the control group.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” Dr. Rexhaj stated in the release. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”
The investigators cited as a limitation the fact that they studied only children born from singleton births recruited from a single center, which may have a lower cardiovascular risk profile than other patient populations.
This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
SOURCE: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
Clinicians should be vigilant in detecting early cardiovascular problems in children born from ART, Larry A. Weinrauch, MD, of Harvard Medical School, Boston, and his colleagues wrote in a joint editorial comment. While the sixfold higher risk of arterial hypertension was obtained from an ambulatory blood pressure monitoring that was not repeated, the relative risk of cardiovascular problems for singleton births could be a sign that a greater risk for vascular aging exists with multiple births.
“This observation, derived from a relatively small cohort, may actually understate the importance of this problem for ART populations because higher risk populations for development of hypertension (e.g., multiple birth pregnancies) and those resulting from maternal factors of excess risk (e.g., eclampsia, chronic hypertension, diabetes, obesity) were excluded from the study,” Dr. Weinrauch and his colleagues said.
The authors cited the pediatric hypertension clinical practice guidelines of annual in-office hypertension screening after 3 years of age and noted that certain high-risk groups, such as patients with repaired aortic coarctation and chronic kidney disease, should be screened “at every health encounter.
“If adolescent hypertension risk is really sixfold higher in ART patients (and potentially subsequent generations), consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote Dr. Weinrauch and his colleagues. “Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention.”
Dr. Weinrauch is with Harvard Medical School, Marie D. Gerhard-Herman, MD, is with Brigham and Women’s Hospital, and Michael M. Mendelson, MD, is with Boston Children’s Hospital, all in Boston. These comments summarize their editorial in response to Meister et al. (J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.07.013). Dr. Gerhard-Herman is supported by the Progeria Research Foundation and Dr. Mendelson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. They reported no other relevant conflicts of interest.
Clinicians should be vigilant in detecting early cardiovascular problems in children born from ART, Larry A. Weinrauch, MD, of Harvard Medical School, Boston, and his colleagues wrote in a joint editorial comment. While the sixfold higher risk of arterial hypertension was obtained from an ambulatory blood pressure monitoring that was not repeated, the relative risk of cardiovascular problems for singleton births could be a sign that a greater risk for vascular aging exists with multiple births.
“This observation, derived from a relatively small cohort, may actually understate the importance of this problem for ART populations because higher risk populations for development of hypertension (e.g., multiple birth pregnancies) and those resulting from maternal factors of excess risk (e.g., eclampsia, chronic hypertension, diabetes, obesity) were excluded from the study,” Dr. Weinrauch and his colleagues said.
The authors cited the pediatric hypertension clinical practice guidelines of annual in-office hypertension screening after 3 years of age and noted that certain high-risk groups, such as patients with repaired aortic coarctation and chronic kidney disease, should be screened “at every health encounter.
“If adolescent hypertension risk is really sixfold higher in ART patients (and potentially subsequent generations), consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote Dr. Weinrauch and his colleagues. “Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention.”
Dr. Weinrauch is with Harvard Medical School, Marie D. Gerhard-Herman, MD, is with Brigham and Women’s Hospital, and Michael M. Mendelson, MD, is with Boston Children’s Hospital, all in Boston. These comments summarize their editorial in response to Meister et al. (J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.07.013). Dr. Gerhard-Herman is supported by the Progeria Research Foundation and Dr. Mendelson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. They reported no other relevant conflicts of interest.
Clinicians should be vigilant in detecting early cardiovascular problems in children born from ART, Larry A. Weinrauch, MD, of Harvard Medical School, Boston, and his colleagues wrote in a joint editorial comment. While the sixfold higher risk of arterial hypertension was obtained from an ambulatory blood pressure monitoring that was not repeated, the relative risk of cardiovascular problems for singleton births could be a sign that a greater risk for vascular aging exists with multiple births.
“This observation, derived from a relatively small cohort, may actually understate the importance of this problem for ART populations because higher risk populations for development of hypertension (e.g., multiple birth pregnancies) and those resulting from maternal factors of excess risk (e.g., eclampsia, chronic hypertension, diabetes, obesity) were excluded from the study,” Dr. Weinrauch and his colleagues said.
The authors cited the pediatric hypertension clinical practice guidelines of annual in-office hypertension screening after 3 years of age and noted that certain high-risk groups, such as patients with repaired aortic coarctation and chronic kidney disease, should be screened “at every health encounter.
“If adolescent hypertension risk is really sixfold higher in ART patients (and potentially subsequent generations), consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote Dr. Weinrauch and his colleagues. “Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention.”
Dr. Weinrauch is with Harvard Medical School, Marie D. Gerhard-Herman, MD, is with Brigham and Women’s Hospital, and Michael M. Mendelson, MD, is with Boston Children’s Hospital, all in Boston. These comments summarize their editorial in response to Meister et al. (J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.07.013). Dr. Gerhard-Herman is supported by the Progeria Research Foundation and Dr. Mendelson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. They reported no other relevant conflicts of interest.
Children born from assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection may be at risk of developing arterial hypertension due to premature vascular aging, according to a study published in the Journal of the American College of Cardiology.
In a previous study, Emrush Rexhaj, MD, director of arterial hypertension and altitude medicine at Inselspital, University Hospital, Bern, Switzerland, and his colleagues assessed vascular function in participants who were born with assisted reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); the investigators found vascular dysfunction in this patient population not “related to parental factors but to the ART procedure itself,” they said.
Dr. Rexhaj and his colleagues then reassessed vascular function in 54 participants (mean age 16.5 years old) who returned from the previous study 5 years after the initial assessment and compared the results with 43 matched patients in a control group (mean age, 17.4 years). There were no significant differences regarding body mass index, lipid, creatinine, electrolyte plasma concentrations, high-sensitive C-reactive protein, birth weight, and gestational age between children in either group, as well as no significant differences in maternal BMI, cardiovascular risk profile, and smoking status.
The investigators – with Théo A. Meister, MD, also of the university, as a joint lead author with Dr. Rexhaj – performed blinded endothelium-dependent and endothelium-independent vasodilation of the brachial artery in a supine position at room temperature and after 15 minutes of rest. They also measured carotid intima-media thickness (IMT), large artery stiffness, 24-hour ambulatory blood pressure monitoring, and short-term blood pressure variability.
“It only took five years for differences in arterial blood pressure to show,” Dr. Rexhaj stated in a press release. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”
Specifically, there was an approximately 25% reduction in flow-mediated dilation in the ART group (7%) compared with the control group (9%), which the investigators attributed to endothelial dysfunction (P less than .001). In ART patients, carotid IMT (463 mm) and carotid pulse-wave velocity (7.7 m/s) was significantly increased, compared with carotid IMT (435 mm; P less than .01) and pulse-wave velocity (7.2 m/s; P equals .033) in the control group.
With regard to arterial hypertension, 24-hour systolic blood pressure in the ART group (120 mm Hg) was “markedly” higher than in the control group (116 mm Hg; P equals .02); 24-hour diastolic blood pressure was also significantly higher in the ART group (71 mm Hg) compared with the control group (69 mm Hg; P equals .03). Investigators noted 8 of the 52 patients (15%) in the ART group met clinical criteria for arterial hypertension according to ambulatory blood pressure monitoring, compared with 1 of the 40 patients (2%) in the control group.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” Dr. Rexhaj stated in the release. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”
The investigators cited as a limitation the fact that they studied only children born from singleton births recruited from a single center, which may have a lower cardiovascular risk profile than other patient populations.
This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
SOURCE: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
Children born from assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection may be at risk of developing arterial hypertension due to premature vascular aging, according to a study published in the Journal of the American College of Cardiology.
In a previous study, Emrush Rexhaj, MD, director of arterial hypertension and altitude medicine at Inselspital, University Hospital, Bern, Switzerland, and his colleagues assessed vascular function in participants who were born with assisted reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); the investigators found vascular dysfunction in this patient population not “related to parental factors but to the ART procedure itself,” they said.
Dr. Rexhaj and his colleagues then reassessed vascular function in 54 participants (mean age 16.5 years old) who returned from the previous study 5 years after the initial assessment and compared the results with 43 matched patients in a control group (mean age, 17.4 years). There were no significant differences regarding body mass index, lipid, creatinine, electrolyte plasma concentrations, high-sensitive C-reactive protein, birth weight, and gestational age between children in either group, as well as no significant differences in maternal BMI, cardiovascular risk profile, and smoking status.
The investigators – with Théo A. Meister, MD, also of the university, as a joint lead author with Dr. Rexhaj – performed blinded endothelium-dependent and endothelium-independent vasodilation of the brachial artery in a supine position at room temperature and after 15 minutes of rest. They also measured carotid intima-media thickness (IMT), large artery stiffness, 24-hour ambulatory blood pressure monitoring, and short-term blood pressure variability.
“It only took five years for differences in arterial blood pressure to show,” Dr. Rexhaj stated in a press release. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”
Specifically, there was an approximately 25% reduction in flow-mediated dilation in the ART group (7%) compared with the control group (9%), which the investigators attributed to endothelial dysfunction (P less than .001). In ART patients, carotid IMT (463 mm) and carotid pulse-wave velocity (7.7 m/s) was significantly increased, compared with carotid IMT (435 mm; P less than .01) and pulse-wave velocity (7.2 m/s; P equals .033) in the control group.
With regard to arterial hypertension, 24-hour systolic blood pressure in the ART group (120 mm Hg) was “markedly” higher than in the control group (116 mm Hg; P equals .02); 24-hour diastolic blood pressure was also significantly higher in the ART group (71 mm Hg) compared with the control group (69 mm Hg; P equals .03). Investigators noted 8 of the 52 patients (15%) in the ART group met clinical criteria for arterial hypertension according to ambulatory blood pressure monitoring, compared with 1 of the 40 patients (2%) in the control group.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” Dr. Rexhaj stated in the release. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”
The investigators cited as a limitation the fact that they studied only children born from singleton births recruited from a single center, which may have a lower cardiovascular risk profile than other patient populations.
This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
SOURCE: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point:
Major finding: In the ART group, 24-hour systolic blood pressure was significantly higher than in the control group (120 mm Hg vs. 116 mm Hg), and 24-hour diastolic blood pressure was also significantly higher in the ART group compared with the control group (71 mm Hg vs. 69 mm Hg).
Study details: A reassessment of 54 children born from ART.
Disclosures: This study was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology and Mach-Gaensslen Stiftung (Schweiz). The authors reported no conflicts of interest.
Source: Meister TA et al. J Am Coll Cardiol. 2018 Sep 3. doi: 10.1016/j.jacc.2018.06.060.
Syphilis surge drives USPSTF reaffirmation of early screening for all pregnant women
Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.
The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.
The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.
Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.
“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”
The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.
The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.
The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.
Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.
In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.
The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.
“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.
The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.
SOURCE: Curry S et al. JAMA. 2018;320:911-7.
I strongly concur with the U.S. Preventive Services Task Force recommendation on early screening for syphilis infection in all pregnant women. There is benefit to screening all women for syphilis in early pregnancy given the risks of miscarriage, congenital syphilis, and maternal illness – if untreated. Additionally, in women who live in high prevalence areas or with high-risk behaviors for acquiring syphilis, testing should be performed again in the third trimester and at delivery. Also, all women with a fetal death after 20 weeks should be tested or retested if testing was done earlier in pregnancy.
Martina Badell, MD , is a maternal-fetal medicine specialist at Emory University and director of the Emory University Hospital Midtown Perinatal Center, both in Atlanta. Dr. Badell reported no relevant financial conflicts. She was asked to comment on the USPSTF recommendation.
I strongly concur with the U.S. Preventive Services Task Force recommendation on early screening for syphilis infection in all pregnant women. There is benefit to screening all women for syphilis in early pregnancy given the risks of miscarriage, congenital syphilis, and maternal illness – if untreated. Additionally, in women who live in high prevalence areas or with high-risk behaviors for acquiring syphilis, testing should be performed again in the third trimester and at delivery. Also, all women with a fetal death after 20 weeks should be tested or retested if testing was done earlier in pregnancy.
Martina Badell, MD , is a maternal-fetal medicine specialist at Emory University and director of the Emory University Hospital Midtown Perinatal Center, both in Atlanta. Dr. Badell reported no relevant financial conflicts. She was asked to comment on the USPSTF recommendation.
I strongly concur with the U.S. Preventive Services Task Force recommendation on early screening for syphilis infection in all pregnant women. There is benefit to screening all women for syphilis in early pregnancy given the risks of miscarriage, congenital syphilis, and maternal illness – if untreated. Additionally, in women who live in high prevalence areas or with high-risk behaviors for acquiring syphilis, testing should be performed again in the third trimester and at delivery. Also, all women with a fetal death after 20 weeks should be tested or retested if testing was done earlier in pregnancy.
Martina Badell, MD , is a maternal-fetal medicine specialist at Emory University and director of the Emory University Hospital Midtown Perinatal Center, both in Atlanta. Dr. Badell reported no relevant financial conflicts. She was asked to comment on the USPSTF recommendation.
Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.
The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.
The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.
Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.
“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”
The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.
The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.
The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.
Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.
In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.
The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.
“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.
The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.
SOURCE: Curry S et al. JAMA. 2018;320:911-7.
Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.
The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.
The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.
Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.
“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”
The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.
The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.
The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.
Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.
In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.
The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.
“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.
The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.
SOURCE: Curry S et al. JAMA. 2018;320:911-7.
FROM JAMA
DTC test for BRCA mutations: What to tell patients who inquire
Resources
US Food & Drug Administration. FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer genes. March 6, 2018. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm599560.htm. Accessed August 8, 2018.
US Preventive Services Task Force. Final recommendation statement: BRCA-related cancer: risk assessment, genetic counseling, and genetic testing. Available at:
https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing. Accessed August 8, 2018.
Resources
US Food & Drug Administration. FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer genes. March 6, 2018. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm599560.htm. Accessed August 8, 2018.
US Preventive Services Task Force. Final recommendation statement: BRCA-related cancer: risk assessment, genetic counseling, and genetic testing. Available at:
https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing. Accessed August 8, 2018.
Resources
US Food & Drug Administration. FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer genes. March 6, 2018. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm599560.htm. Accessed August 8, 2018.
US Preventive Services Task Force. Final recommendation statement: BRCA-related cancer: risk assessment, genetic counseling, and genetic testing. Available at:
https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing. Accessed August 8, 2018.
