Women's Health

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized crossover trial reveals.

The research was published recently in Diabetes Care.

Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.

Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.

“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.

“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.
 

Prolonged lack of sleep may accelerate diabetes progression

Dr. St-Onge added, “If that’s sustained over time, it is possible that prolonged insufficient sleep among individuals with prediabetes could accelerate the progression to type 2 diabetes.”

Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”

The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.

Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.

Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”

Joslin Diabetes Center

A version of this article appeared on Medscape.com.

Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized crossover trial reveals.

The research was published recently in Diabetes Care.

Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.

Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.

“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.

“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.
 

Prolonged lack of sleep may accelerate diabetes progression

Dr. St-Onge added, “If that’s sustained over time, it is possible that prolonged insufficient sleep among individuals with prediabetes could accelerate the progression to type 2 diabetes.”

Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”

The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.

Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.

Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”

Joslin Diabetes Center

A version of this article appeared on Medscape.com.

Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized crossover trial reveals.

The research was published recently in Diabetes Care.

Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.

Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.

“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.

“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.
 

Prolonged lack of sleep may accelerate diabetes progression

Dr. St-Onge added, “If that’s sustained over time, it is possible that prolonged insufficient sleep among individuals with prediabetes could accelerate the progression to type 2 diabetes.”

Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”

The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.

Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.

Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”

Joslin Diabetes Center

A version of this article appeared on Medscape.com.

In 2022, two colleagues from Johns Hopkins University, Baltimore, Bhuchitra Singh, MD, MPH, MS, MBA, and James Segars Jr., MD, reviewed the available literature to evaluate the effectiveness of newer minimally invasive therapies in reducing bleeding and improving the quality of life and control of symptoms linked to uterine fibroids. 

Their goal, according to Dr. Segars, a professor of obstetrics and gynecology and director of the division of women’s health research at Johns Hopkins, was to help guide clinicians and patients in making decisions about the use of the newer therapies, including radiofrequency ablation and ultrasound-guided removal of lesions. 

But he and Dr. Singh, the director of clinical research at the Howard W. and Georgeanna Seegar Jones Laboratory of Reproductive Sciences and Women’s Health Research, were surprised by their findings. “The outcomes were relatively the same,” Dr. Segars said. “All of the modalities lead to significant reduction in bleeding and other fibroid-related symptoms.” 

The data on long-term complications and risk for recurrence are sparse for some of the newer approaches, and not enough high-quality long-term studies have been conducted for the Food and Drug Administration to approve them as fertility-sparing treatments.

But perhaps, the biggest challenge now is to ensure that women can take advantage of these newer therapies, with large gaps in both the diagnosis of fibroids and geographic access to minimally invasive treatments.
 

A widespread condition widely underdiagnosed 

Uterine fibroids occur in most women (the incidence rises with age) and can be found in up to 70% of women by the time they reach menopause. Risk factors include family history, increasing interval since last birth, hypertension, and obesity. Increasing parity and use of oral contraceptives are protective.

But as many as 50% of cases go undiagnosed, and one reason for this is the failure of clinicians to dig deeply enough into women’s menstrual histories to diagnose fibroids. 

“The most common cause of anemia is heavy menstrual bleeding,” said Shannon Laughlin-Tommaso, MD, MPH, a professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minn. She frequently sees patients who have already undergone colonoscopy to work-up the source of their anemia before anyone suspects that fibroids are the culprit. 

“When women tell us about their periods, what they’ve been told is normal [bleeding] – or what they’ve always had and considered normal – is actually kind of on the heavier spectrum,” she said. 

Ideally, treatment for uterine fibroids would fix abnormally prolonged or heavy menstrual bleeding, relieve pain, and ameliorate symptoms associated with an enlarged uterus, such as pelvic pressure, urinary frequency, and constipation. And the fibroids would never recur.

By those measures, hysterectomy fits the bill: Success rates in relieving symptoms are high, and the risk for recurrence is zero. But the procedure carries significant drawbacks: short-term complications of surgery, including infection, bleeding, and injury to the bowels and bladder along with potential long-term risks for cardiovascular disease, cancer, ovarian failure and premature menopause, depression, and decline in cognitive function. Those factors loom even larger for women who still hope to have children. 

For that reason, the American College of Obstetricians and Gynecologists recommends myomectomy, or surgical removal of individual fibroids, for women who desire uterine preservation or future pregnancy. And the literature here is solid, according to Dr. Singh, who found that 95% of myomectomy patients achieved control of their bleeding symptoms, whether it was via laparoscopy, hysteroscopy, or laparotomy. Up to 40% of women may develop new fibroids, or leiomyomas, within 3 years, although only 12.2% required a second surgery up to after 5 years. 

But myomectomy is invasive, requiring general anesthesia, incisions in the uterus, and stitches to close the organ. 

Newer techniques have emerged that can effectively treat symptoms of fibroids without requiring surgery. Uterine artery embolization (UAE), which involves passing a catheter into the femoral artery, or laparoscopic uterine artery occlusion can be used to cut off the blood supply of the fibroid. Other techniques, including focused ultrasound surgery and radiofrequency ablation (RFA), use various forms of energy to heat and ablate fibroids. The latter two can be performed in outpatient settings and often without general anesthesia.

Approved for use in 1994, UAE has the most data available, with reduction in the volume of fibroids and uterine tissue lasting up to 5 years, and rates of reintervention of 19%-38% between 2 and 5 years after the procedure. Dr. Singh’s review found that 79%-98.5% of recipients of the procedure reported declines in bleeding that persisted for several years, which is comparable to myomectomy. Quality of life and pain scores also showed good improvement, with follow-up in the different studies ranging from 12 months to over 5 years, the analysis showed.

UAE does have its drawbacks. In rare cases, embolization can deprive the entire uterus and ovaries of blood, which can cause ovarian dysfunction and potentially result in premature menopause, although this outcome is most common in women who are older than 45 years. The procedure can often also be painful enough that overnight hospitalization is required.

Focused ultrasound surgeries, which include magnetic resonance–guided focused ultrasound surgery (MRgFUS) and high-intensity focused ultrasound (HIFU), were approved by the FDA in 2004. Focused ultrasound waves pass through the abdominal wall and produce significant heating, causing a burn that destroys the targeted tissue without damaging surrounding tissue. As with UAE, improvements in fibroid-associated bleeding and measures of quality of life were similar to those after myomectomy up to 3 years later.

But Dr. Singh noted that both focused ultrasound and RFA can damage the skin or internal organs. “[As] always with the thermal interventions, there is the probability of skin as well as internal organs that might get the thermal energy if it’s not focused correctly on to the fibroid itself,” he said. In addition, MRgFUS is not an option for women who are not good candidates to undergo an MRI, such as those with claustrophobia or pacemakers.

Also, with focus ultrasound and RFA, “we do worry about that fibroid getting blood flow back,” which can lead to recurrence of heavy menstrual bleeding, Dr. Laughlin-Tommaso noted. 

Although data on RFA are limited to 12 months of follow-up, most women reported meaningful reductions in bleeding symptoms. Longer follow-up has been reported for bleeding symptoms after MRgFUS, with similar results up to 3 years later. 

For Leslie Hansen-Lindner, MD, chief of obstetrics and gynecology at Atrium Health in Charlotte, N.C., choosing the right procedure starts with a patient-centered conversation weighing the pros and cons of the options and the woman’s goals. 

“Is their goal to reduce the size and impact of their fibroid, bleed less, and have a better quality of life on their period?” Dr. Hansen-Lindner said. “Or is their goal to have the entire fibroid removed?” 

If the former, an RFA is appealing to many women. If the latter, laparoscopic or mini-laparotomy myomectomy might be a better choice. Although fewer than 10% of patients require surgical reintervention at 3 years of follow-up for RFA, myomectomy has more consistent long-term evidence showing that fewer women require re-intervention and preserve their fertility, she added. 

Age also plays a role in the decision: The closer a woman is to menopause, the less likely she is to experience a recurrence, so a less-invasive procedure is preferable. But for younger women hoping to become pregnant, the lower risk for recurrence and good prognosis for future fertility might sway the choice toward myomectomy.

The first laparoscopic RFA procedures were approved for uterine fibroids in 2012. Dr. Hansen-Lindner is a proponent of transcervical fibroid ablation (TFA), a newer RFA procedure that the FDA approved in 2018. Performed through the cervix, TFA requires no incisions and can generally be done without general anesthesia. Eligible candidates would be any woman with symptomatic fibroids, such as heavy menstrual bleeding, pain, or bulk symptoms. The contraindications are few.

“It’s going to come down to size and location of fibroids, and whether or not they would be accessible by the TFA,” Dr. Hansen-Lindner said. “I have to make sure that there isn’t a fibroid blocking their cervix and that the fibroids are accessible with this device.” 

TFA also is not suitable for removing most submucosal lesions, which typically must be removed by hysteroscopic myomectomy. Dr. Hansen-Lindner said that she often uses TFA in conjunction with hysteroscopic myomectomy for this scenario. Although data on pregnancy after RFA (including TFA), MRgFUS, and HIFU are lacking, Gynesonics, the manufacturer of the Sonata System (the device that delivers radiofrequency energy to shrink the fibroid) has documented 79 pregnancies among the 2,200 women who have undergone TFA in the United States since 2018.
 

Disparities hampering care

Uterine fibroids are a particular problem for Black women, whose symptoms are more likely to be ignored by clinicians, according to Jodie Katon, PhD, a core investigator at the Veterans Affairs Greater Los Angeles Center for the Study of Healthcare Innovation, Implementation and Policy. Dr. Katon cited studies in which Black women interviewed about their experiences reported a consistent theme: Clinicians dismissed their symptoms, told them these were nothing to worry about, and advised them to lose weight. Those interactions not only delayed diagnosis among Black women but also led many of them to mistrust clinicians and avoid the health care system altogether.

The failure of clinicians to take their complaints seriously is just one of the disparities affecting Black women. In reviewing the literature, Dr. Laughlin-Tommaso, who also serves as the associate dean for Education Diversity, Equity, and Inclusion at the Mayo Clinic, found that African American women experience two to three times the risk for fibroids, compared with White women, as well as earlier onset and more severe disease, as measured by number and size of the lesions. 

According to Dr. Katon, the etiology of fibroids is still poorly understood. “What we do know is that Black women are disproportionately exposed to a variety of factors that we have shown through observational studies are associated with increased risk of development of uterine fibroids.” 

The list includes factors like stress; interpersonal racism; early age at menarche; various indicators of poor diets, such as vitamin D deficiency; the use of certain beauty products, specifically hair straighteners; as well as exposure to air pollution and other environmental toxins.

Laughlin-Tommaso also pointed to historical disparities in management, citing a doubled risk for hysterectomy for Black women in a study published in 2007 despite survey data suggesting that Black women report being more interested in uterine-preserving therapies rather than a hysterectomy.
 

Breaking down barriers of access to new treatments

Dr. Laughlin-Tommaso looked at more recent trends in the management of fibroids using data from the multicenter COMPARE-UF study, which enrolled women between 2015 and 2020 undergoing fibroid treatment into a longitudinal registry to track their outcomes. She found that Black women underwent hysterectomies at a lower rate than did White women and were instead more likely to undergo myomectomy or UAE. 

Some of the change may reflect lack of approved minimally invasive procedures before 2000. “But now that we have expanded options, I think most women are opting not to have a hysterectomy,” Dr. Laughlin-Tommaso said.

Dr. Katon has research funding from the VA to look more closely at racial disparities in the treatment of fibroids. In a study published in April 2023, she reported some surprising trends. 

During the period from 2010 to 2018, she found that Black veterans diagnosed with fibroids were less likely than White veterans were to receive treatment, regardless of their age or the severity of their symptoms. This finding held even among women with anemia, which should have been a clear indication for treatment.

But, as in the COMPARE-UF study, the subset of Black veterans who received an interventional treatment were less likely than their White peers were to undergo hysterectomy in favor of a fertility-sparing treatment as their initial procedure. Dr. Katon called it a “welcome but unexpected finding.” 

But another significant barrier remains: The two newest types of procedures, RFA and guided focused ultrasound, are not commonly performed outside of tertiary care facilities. However, studies have found that all these procedures are cost effective (studies for myomectomy, UAE, MRgFUS, and TFA). The implementation of a category 1 billing code for laparoscopic RFA in 2017 has led more insurance companies to cover the service, and a category 1 code will be available for TFA effective January 2024. 

Although RFA does require investment in specialized equipment, which limits facilities from offering the procedure, any gynecologist who routinely performs hysteroscopy can easily learn to do TFA. And the VA, which is committed to eliminating disparities in women’s health, established a 2-year advanced fellowship in minimally invasive gynecologic surgery in 2022 to help expand their capacity to offer these procedures. 

The VA has been rapidly expanding their gynecology services, and Katon said that she is confident that ultrasound-guided procedures and RFA will become more available within the system. “I would say we’re keeping pace. And in some ways, you know, as a national system we may be positioned to actually outpace the rest of the U.S.”

Dr. Segars reported prior research funding for clinical trials from BioSpecifics Technologies, Bayer, Allergan, AbbVie, and ObsEva and currently receives funding from Myovant Sciences. Dr. Hansen-Lindner reported personal fees from Gynesonics. Dr. Singh, Dr. Laughlin-Tommaso, and Dr. Katon reported no financial conflicts of interest. 

A version of this article first appeared on Medscape.com.

In 2022, two colleagues from Johns Hopkins University, Baltimore, Bhuchitra Singh, MD, MPH, MS, MBA, and James Segars Jr., MD, reviewed the available literature to evaluate the effectiveness of newer minimally invasive therapies in reducing bleeding and improving the quality of life and control of symptoms linked to uterine fibroids. 

Their goal, according to Dr. Segars, a professor of obstetrics and gynecology and director of the division of women’s health research at Johns Hopkins, was to help guide clinicians and patients in making decisions about the use of the newer therapies, including radiofrequency ablation and ultrasound-guided removal of lesions. 

But he and Dr. Singh, the director of clinical research at the Howard W. and Georgeanna Seegar Jones Laboratory of Reproductive Sciences and Women’s Health Research, were surprised by their findings. “The outcomes were relatively the same,” Dr. Segars said. “All of the modalities lead to significant reduction in bleeding and other fibroid-related symptoms.” 

The data on long-term complications and risk for recurrence are sparse for some of the newer approaches, and not enough high-quality long-term studies have been conducted for the Food and Drug Administration to approve them as fertility-sparing treatments.

But perhaps, the biggest challenge now is to ensure that women can take advantage of these newer therapies, with large gaps in both the diagnosis of fibroids and geographic access to minimally invasive treatments.
 

A widespread condition widely underdiagnosed 

Uterine fibroids occur in most women (the incidence rises with age) and can be found in up to 70% of women by the time they reach menopause. Risk factors include family history, increasing interval since last birth, hypertension, and obesity. Increasing parity and use of oral contraceptives are protective.

But as many as 50% of cases go undiagnosed, and one reason for this is the failure of clinicians to dig deeply enough into women’s menstrual histories to diagnose fibroids. 

“The most common cause of anemia is heavy menstrual bleeding,” said Shannon Laughlin-Tommaso, MD, MPH, a professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minn. She frequently sees patients who have already undergone colonoscopy to work-up the source of their anemia before anyone suspects that fibroids are the culprit. 

“When women tell us about their periods, what they’ve been told is normal [bleeding] – or what they’ve always had and considered normal – is actually kind of on the heavier spectrum,” she said. 

Ideally, treatment for uterine fibroids would fix abnormally prolonged or heavy menstrual bleeding, relieve pain, and ameliorate symptoms associated with an enlarged uterus, such as pelvic pressure, urinary frequency, and constipation. And the fibroids would never recur.

By those measures, hysterectomy fits the bill: Success rates in relieving symptoms are high, and the risk for recurrence is zero. But the procedure carries significant drawbacks: short-term complications of surgery, including infection, bleeding, and injury to the bowels and bladder along with potential long-term risks for cardiovascular disease, cancer, ovarian failure and premature menopause, depression, and decline in cognitive function. Those factors loom even larger for women who still hope to have children. 

For that reason, the American College of Obstetricians and Gynecologists recommends myomectomy, or surgical removal of individual fibroids, for women who desire uterine preservation or future pregnancy. And the literature here is solid, according to Dr. Singh, who found that 95% of myomectomy patients achieved control of their bleeding symptoms, whether it was via laparoscopy, hysteroscopy, or laparotomy. Up to 40% of women may develop new fibroids, or leiomyomas, within 3 years, although only 12.2% required a second surgery up to after 5 years. 

But myomectomy is invasive, requiring general anesthesia, incisions in the uterus, and stitches to close the organ. 

Newer techniques have emerged that can effectively treat symptoms of fibroids without requiring surgery. Uterine artery embolization (UAE), which involves passing a catheter into the femoral artery, or laparoscopic uterine artery occlusion can be used to cut off the blood supply of the fibroid. Other techniques, including focused ultrasound surgery and radiofrequency ablation (RFA), use various forms of energy to heat and ablate fibroids. The latter two can be performed in outpatient settings and often without general anesthesia.

Approved for use in 1994, UAE has the most data available, with reduction in the volume of fibroids and uterine tissue lasting up to 5 years, and rates of reintervention of 19%-38% between 2 and 5 years after the procedure. Dr. Singh’s review found that 79%-98.5% of recipients of the procedure reported declines in bleeding that persisted for several years, which is comparable to myomectomy. Quality of life and pain scores also showed good improvement, with follow-up in the different studies ranging from 12 months to over 5 years, the analysis showed.

UAE does have its drawbacks. In rare cases, embolization can deprive the entire uterus and ovaries of blood, which can cause ovarian dysfunction and potentially result in premature menopause, although this outcome is most common in women who are older than 45 years. The procedure can often also be painful enough that overnight hospitalization is required.

Focused ultrasound surgeries, which include magnetic resonance–guided focused ultrasound surgery (MRgFUS) and high-intensity focused ultrasound (HIFU), were approved by the FDA in 2004. Focused ultrasound waves pass through the abdominal wall and produce significant heating, causing a burn that destroys the targeted tissue without damaging surrounding tissue. As with UAE, improvements in fibroid-associated bleeding and measures of quality of life were similar to those after myomectomy up to 3 years later.

But Dr. Singh noted that both focused ultrasound and RFA can damage the skin or internal organs. “[As] always with the thermal interventions, there is the probability of skin as well as internal organs that might get the thermal energy if it’s not focused correctly on to the fibroid itself,” he said. In addition, MRgFUS is not an option for women who are not good candidates to undergo an MRI, such as those with claustrophobia or pacemakers.

Also, with focus ultrasound and RFA, “we do worry about that fibroid getting blood flow back,” which can lead to recurrence of heavy menstrual bleeding, Dr. Laughlin-Tommaso noted. 

Although data on RFA are limited to 12 months of follow-up, most women reported meaningful reductions in bleeding symptoms. Longer follow-up has been reported for bleeding symptoms after MRgFUS, with similar results up to 3 years later. 

For Leslie Hansen-Lindner, MD, chief of obstetrics and gynecology at Atrium Health in Charlotte, N.C., choosing the right procedure starts with a patient-centered conversation weighing the pros and cons of the options and the woman’s goals. 

“Is their goal to reduce the size and impact of their fibroid, bleed less, and have a better quality of life on their period?” Dr. Hansen-Lindner said. “Or is their goal to have the entire fibroid removed?” 

If the former, an RFA is appealing to many women. If the latter, laparoscopic or mini-laparotomy myomectomy might be a better choice. Although fewer than 10% of patients require surgical reintervention at 3 years of follow-up for RFA, myomectomy has more consistent long-term evidence showing that fewer women require re-intervention and preserve their fertility, she added. 

Age also plays a role in the decision: The closer a woman is to menopause, the less likely she is to experience a recurrence, so a less-invasive procedure is preferable. But for younger women hoping to become pregnant, the lower risk for recurrence and good prognosis for future fertility might sway the choice toward myomectomy.

The first laparoscopic RFA procedures were approved for uterine fibroids in 2012. Dr. Hansen-Lindner is a proponent of transcervical fibroid ablation (TFA), a newer RFA procedure that the FDA approved in 2018. Performed through the cervix, TFA requires no incisions and can generally be done without general anesthesia. Eligible candidates would be any woman with symptomatic fibroids, such as heavy menstrual bleeding, pain, or bulk symptoms. The contraindications are few.

“It’s going to come down to size and location of fibroids, and whether or not they would be accessible by the TFA,” Dr. Hansen-Lindner said. “I have to make sure that there isn’t a fibroid blocking their cervix and that the fibroids are accessible with this device.” 

TFA also is not suitable for removing most submucosal lesions, which typically must be removed by hysteroscopic myomectomy. Dr. Hansen-Lindner said that she often uses TFA in conjunction with hysteroscopic myomectomy for this scenario. Although data on pregnancy after RFA (including TFA), MRgFUS, and HIFU are lacking, Gynesonics, the manufacturer of the Sonata System (the device that delivers radiofrequency energy to shrink the fibroid) has documented 79 pregnancies among the 2,200 women who have undergone TFA in the United States since 2018.
 

Disparities hampering care

Uterine fibroids are a particular problem for Black women, whose symptoms are more likely to be ignored by clinicians, according to Jodie Katon, PhD, a core investigator at the Veterans Affairs Greater Los Angeles Center for the Study of Healthcare Innovation, Implementation and Policy. Dr. Katon cited studies in which Black women interviewed about their experiences reported a consistent theme: Clinicians dismissed their symptoms, told them these were nothing to worry about, and advised them to lose weight. Those interactions not only delayed diagnosis among Black women but also led many of them to mistrust clinicians and avoid the health care system altogether.

The failure of clinicians to take their complaints seriously is just one of the disparities affecting Black women. In reviewing the literature, Dr. Laughlin-Tommaso, who also serves as the associate dean for Education Diversity, Equity, and Inclusion at the Mayo Clinic, found that African American women experience two to three times the risk for fibroids, compared with White women, as well as earlier onset and more severe disease, as measured by number and size of the lesions. 

According to Dr. Katon, the etiology of fibroids is still poorly understood. “What we do know is that Black women are disproportionately exposed to a variety of factors that we have shown through observational studies are associated with increased risk of development of uterine fibroids.” 

The list includes factors like stress; interpersonal racism; early age at menarche; various indicators of poor diets, such as vitamin D deficiency; the use of certain beauty products, specifically hair straighteners; as well as exposure to air pollution and other environmental toxins.

Laughlin-Tommaso also pointed to historical disparities in management, citing a doubled risk for hysterectomy for Black women in a study published in 2007 despite survey data suggesting that Black women report being more interested in uterine-preserving therapies rather than a hysterectomy.
 

Breaking down barriers of access to new treatments

Dr. Laughlin-Tommaso looked at more recent trends in the management of fibroids using data from the multicenter COMPARE-UF study, which enrolled women between 2015 and 2020 undergoing fibroid treatment into a longitudinal registry to track their outcomes. She found that Black women underwent hysterectomies at a lower rate than did White women and were instead more likely to undergo myomectomy or UAE. 

Some of the change may reflect lack of approved minimally invasive procedures before 2000. “But now that we have expanded options, I think most women are opting not to have a hysterectomy,” Dr. Laughlin-Tommaso said.

Dr. Katon has research funding from the VA to look more closely at racial disparities in the treatment of fibroids. In a study published in April 2023, she reported some surprising trends. 

During the period from 2010 to 2018, she found that Black veterans diagnosed with fibroids were less likely than White veterans were to receive treatment, regardless of their age or the severity of their symptoms. This finding held even among women with anemia, which should have been a clear indication for treatment.

But, as in the COMPARE-UF study, the subset of Black veterans who received an interventional treatment were less likely than their White peers were to undergo hysterectomy in favor of a fertility-sparing treatment as their initial procedure. Dr. Katon called it a “welcome but unexpected finding.” 

But another significant barrier remains: The two newest types of procedures, RFA and guided focused ultrasound, are not commonly performed outside of tertiary care facilities. However, studies have found that all these procedures are cost effective (studies for myomectomy, UAE, MRgFUS, and TFA). The implementation of a category 1 billing code for laparoscopic RFA in 2017 has led more insurance companies to cover the service, and a category 1 code will be available for TFA effective January 2024. 

Although RFA does require investment in specialized equipment, which limits facilities from offering the procedure, any gynecologist who routinely performs hysteroscopy can easily learn to do TFA. And the VA, which is committed to eliminating disparities in women’s health, established a 2-year advanced fellowship in minimally invasive gynecologic surgery in 2022 to help expand their capacity to offer these procedures. 

The VA has been rapidly expanding their gynecology services, and Katon said that she is confident that ultrasound-guided procedures and RFA will become more available within the system. “I would say we’re keeping pace. And in some ways, you know, as a national system we may be positioned to actually outpace the rest of the U.S.”

Dr. Segars reported prior research funding for clinical trials from BioSpecifics Technologies, Bayer, Allergan, AbbVie, and ObsEva and currently receives funding from Myovant Sciences. Dr. Hansen-Lindner reported personal fees from Gynesonics. Dr. Singh, Dr. Laughlin-Tommaso, and Dr. Katon reported no financial conflicts of interest. 

A version of this article first appeared on Medscape.com.

In 2022, two colleagues from Johns Hopkins University, Baltimore, Bhuchitra Singh, MD, MPH, MS, MBA, and James Segars Jr., MD, reviewed the available literature to evaluate the effectiveness of newer minimally invasive therapies in reducing bleeding and improving the quality of life and control of symptoms linked to uterine fibroids. 

Their goal, according to Dr. Segars, a professor of obstetrics and gynecology and director of the division of women’s health research at Johns Hopkins, was to help guide clinicians and patients in making decisions about the use of the newer therapies, including radiofrequency ablation and ultrasound-guided removal of lesions. 

But he and Dr. Singh, the director of clinical research at the Howard W. and Georgeanna Seegar Jones Laboratory of Reproductive Sciences and Women’s Health Research, were surprised by their findings. “The outcomes were relatively the same,” Dr. Segars said. “All of the modalities lead to significant reduction in bleeding and other fibroid-related symptoms.” 

The data on long-term complications and risk for recurrence are sparse for some of the newer approaches, and not enough high-quality long-term studies have been conducted for the Food and Drug Administration to approve them as fertility-sparing treatments.

But perhaps, the biggest challenge now is to ensure that women can take advantage of these newer therapies, with large gaps in both the diagnosis of fibroids and geographic access to minimally invasive treatments.
 

A widespread condition widely underdiagnosed 

Uterine fibroids occur in most women (the incidence rises with age) and can be found in up to 70% of women by the time they reach menopause. Risk factors include family history, increasing interval since last birth, hypertension, and obesity. Increasing parity and use of oral contraceptives are protective.

But as many as 50% of cases go undiagnosed, and one reason for this is the failure of clinicians to dig deeply enough into women’s menstrual histories to diagnose fibroids. 

“The most common cause of anemia is heavy menstrual bleeding,” said Shannon Laughlin-Tommaso, MD, MPH, a professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minn. She frequently sees patients who have already undergone colonoscopy to work-up the source of their anemia before anyone suspects that fibroids are the culprit. 

“When women tell us about their periods, what they’ve been told is normal [bleeding] – or what they’ve always had and considered normal – is actually kind of on the heavier spectrum,” she said. 

Ideally, treatment for uterine fibroids would fix abnormally prolonged or heavy menstrual bleeding, relieve pain, and ameliorate symptoms associated with an enlarged uterus, such as pelvic pressure, urinary frequency, and constipation. And the fibroids would never recur.

By those measures, hysterectomy fits the bill: Success rates in relieving symptoms are high, and the risk for recurrence is zero. But the procedure carries significant drawbacks: short-term complications of surgery, including infection, bleeding, and injury to the bowels and bladder along with potential long-term risks for cardiovascular disease, cancer, ovarian failure and premature menopause, depression, and decline in cognitive function. Those factors loom even larger for women who still hope to have children. 

For that reason, the American College of Obstetricians and Gynecologists recommends myomectomy, or surgical removal of individual fibroids, for women who desire uterine preservation or future pregnancy. And the literature here is solid, according to Dr. Singh, who found that 95% of myomectomy patients achieved control of their bleeding symptoms, whether it was via laparoscopy, hysteroscopy, or laparotomy. Up to 40% of women may develop new fibroids, or leiomyomas, within 3 years, although only 12.2% required a second surgery up to after 5 years. 

But myomectomy is invasive, requiring general anesthesia, incisions in the uterus, and stitches to close the organ. 

Newer techniques have emerged that can effectively treat symptoms of fibroids without requiring surgery. Uterine artery embolization (UAE), which involves passing a catheter into the femoral artery, or laparoscopic uterine artery occlusion can be used to cut off the blood supply of the fibroid. Other techniques, including focused ultrasound surgery and radiofrequency ablation (RFA), use various forms of energy to heat and ablate fibroids. The latter two can be performed in outpatient settings and often without general anesthesia.

Approved for use in 1994, UAE has the most data available, with reduction in the volume of fibroids and uterine tissue lasting up to 5 years, and rates of reintervention of 19%-38% between 2 and 5 years after the procedure. Dr. Singh’s review found that 79%-98.5% of recipients of the procedure reported declines in bleeding that persisted for several years, which is comparable to myomectomy. Quality of life and pain scores also showed good improvement, with follow-up in the different studies ranging from 12 months to over 5 years, the analysis showed.

UAE does have its drawbacks. In rare cases, embolization can deprive the entire uterus and ovaries of blood, which can cause ovarian dysfunction and potentially result in premature menopause, although this outcome is most common in women who are older than 45 years. The procedure can often also be painful enough that overnight hospitalization is required.

Focused ultrasound surgeries, which include magnetic resonance–guided focused ultrasound surgery (MRgFUS) and high-intensity focused ultrasound (HIFU), were approved by the FDA in 2004. Focused ultrasound waves pass through the abdominal wall and produce significant heating, causing a burn that destroys the targeted tissue without damaging surrounding tissue. As with UAE, improvements in fibroid-associated bleeding and measures of quality of life were similar to those after myomectomy up to 3 years later.

But Dr. Singh noted that both focused ultrasound and RFA can damage the skin or internal organs. “[As] always with the thermal interventions, there is the probability of skin as well as internal organs that might get the thermal energy if it’s not focused correctly on to the fibroid itself,” he said. In addition, MRgFUS is not an option for women who are not good candidates to undergo an MRI, such as those with claustrophobia or pacemakers.

Also, with focus ultrasound and RFA, “we do worry about that fibroid getting blood flow back,” which can lead to recurrence of heavy menstrual bleeding, Dr. Laughlin-Tommaso noted. 

Although data on RFA are limited to 12 months of follow-up, most women reported meaningful reductions in bleeding symptoms. Longer follow-up has been reported for bleeding symptoms after MRgFUS, with similar results up to 3 years later. 

For Leslie Hansen-Lindner, MD, chief of obstetrics and gynecology at Atrium Health in Charlotte, N.C., choosing the right procedure starts with a patient-centered conversation weighing the pros and cons of the options and the woman’s goals. 

“Is their goal to reduce the size and impact of their fibroid, bleed less, and have a better quality of life on their period?” Dr. Hansen-Lindner said. “Or is their goal to have the entire fibroid removed?” 

If the former, an RFA is appealing to many women. If the latter, laparoscopic or mini-laparotomy myomectomy might be a better choice. Although fewer than 10% of patients require surgical reintervention at 3 years of follow-up for RFA, myomectomy has more consistent long-term evidence showing that fewer women require re-intervention and preserve their fertility, she added. 

Age also plays a role in the decision: The closer a woman is to menopause, the less likely she is to experience a recurrence, so a less-invasive procedure is preferable. But for younger women hoping to become pregnant, the lower risk for recurrence and good prognosis for future fertility might sway the choice toward myomectomy.

The first laparoscopic RFA procedures were approved for uterine fibroids in 2012. Dr. Hansen-Lindner is a proponent of transcervical fibroid ablation (TFA), a newer RFA procedure that the FDA approved in 2018. Performed through the cervix, TFA requires no incisions and can generally be done without general anesthesia. Eligible candidates would be any woman with symptomatic fibroids, such as heavy menstrual bleeding, pain, or bulk symptoms. The contraindications are few.

“It’s going to come down to size and location of fibroids, and whether or not they would be accessible by the TFA,” Dr. Hansen-Lindner said. “I have to make sure that there isn’t a fibroid blocking their cervix and that the fibroids are accessible with this device.” 

TFA also is not suitable for removing most submucosal lesions, which typically must be removed by hysteroscopic myomectomy. Dr. Hansen-Lindner said that she often uses TFA in conjunction with hysteroscopic myomectomy for this scenario. Although data on pregnancy after RFA (including TFA), MRgFUS, and HIFU are lacking, Gynesonics, the manufacturer of the Sonata System (the device that delivers radiofrequency energy to shrink the fibroid) has documented 79 pregnancies among the 2,200 women who have undergone TFA in the United States since 2018.
 

Disparities hampering care

Uterine fibroids are a particular problem for Black women, whose symptoms are more likely to be ignored by clinicians, according to Jodie Katon, PhD, a core investigator at the Veterans Affairs Greater Los Angeles Center for the Study of Healthcare Innovation, Implementation and Policy. Dr. Katon cited studies in which Black women interviewed about their experiences reported a consistent theme: Clinicians dismissed their symptoms, told them these were nothing to worry about, and advised them to lose weight. Those interactions not only delayed diagnosis among Black women but also led many of them to mistrust clinicians and avoid the health care system altogether.

The failure of clinicians to take their complaints seriously is just one of the disparities affecting Black women. In reviewing the literature, Dr. Laughlin-Tommaso, who also serves as the associate dean for Education Diversity, Equity, and Inclusion at the Mayo Clinic, found that African American women experience two to three times the risk for fibroids, compared with White women, as well as earlier onset and more severe disease, as measured by number and size of the lesions. 

According to Dr. Katon, the etiology of fibroids is still poorly understood. “What we do know is that Black women are disproportionately exposed to a variety of factors that we have shown through observational studies are associated with increased risk of development of uterine fibroids.” 

The list includes factors like stress; interpersonal racism; early age at menarche; various indicators of poor diets, such as vitamin D deficiency; the use of certain beauty products, specifically hair straighteners; as well as exposure to air pollution and other environmental toxins.

Laughlin-Tommaso also pointed to historical disparities in management, citing a doubled risk for hysterectomy for Black women in a study published in 2007 despite survey data suggesting that Black women report being more interested in uterine-preserving therapies rather than a hysterectomy.
 

Breaking down barriers of access to new treatments

Dr. Laughlin-Tommaso looked at more recent trends in the management of fibroids using data from the multicenter COMPARE-UF study, which enrolled women between 2015 and 2020 undergoing fibroid treatment into a longitudinal registry to track their outcomes. She found that Black women underwent hysterectomies at a lower rate than did White women and were instead more likely to undergo myomectomy or UAE. 

Some of the change may reflect lack of approved minimally invasive procedures before 2000. “But now that we have expanded options, I think most women are opting not to have a hysterectomy,” Dr. Laughlin-Tommaso said.

Dr. Katon has research funding from the VA to look more closely at racial disparities in the treatment of fibroids. In a study published in April 2023, she reported some surprising trends. 

During the period from 2010 to 2018, she found that Black veterans diagnosed with fibroids were less likely than White veterans were to receive treatment, regardless of their age or the severity of their symptoms. This finding held even among women with anemia, which should have been a clear indication for treatment.

But, as in the COMPARE-UF study, the subset of Black veterans who received an interventional treatment were less likely than their White peers were to undergo hysterectomy in favor of a fertility-sparing treatment as their initial procedure. Dr. Katon called it a “welcome but unexpected finding.” 

But another significant barrier remains: The two newest types of procedures, RFA and guided focused ultrasound, are not commonly performed outside of tertiary care facilities. However, studies have found that all these procedures are cost effective (studies for myomectomy, UAE, MRgFUS, and TFA). The implementation of a category 1 billing code for laparoscopic RFA in 2017 has led more insurance companies to cover the service, and a category 1 code will be available for TFA effective January 2024. 

Although RFA does require investment in specialized equipment, which limits facilities from offering the procedure, any gynecologist who routinely performs hysteroscopy can easily learn to do TFA. And the VA, which is committed to eliminating disparities in women’s health, established a 2-year advanced fellowship in minimally invasive gynecologic surgery in 2022 to help expand their capacity to offer these procedures. 

The VA has been rapidly expanding their gynecology services, and Katon said that she is confident that ultrasound-guided procedures and RFA will become more available within the system. “I would say we’re keeping pace. And in some ways, you know, as a national system we may be positioned to actually outpace the rest of the U.S.”

Dr. Segars reported prior research funding for clinical trials from BioSpecifics Technologies, Bayer, Allergan, AbbVie, and ObsEva and currently receives funding from Myovant Sciences. Dr. Hansen-Lindner reported personal fees from Gynesonics. Dr. Singh, Dr. Laughlin-Tommaso, and Dr. Katon reported no financial conflicts of interest. 

A version of this article first appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

A version of this article first appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

A version of this article first appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

A version of this article first appeared on Medscape.com.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

Screening with a “smart,” artificial-intelligence (AI)–enhanced investigational digital stethoscope (Eko Duo) that provides phonocardiogram and electrocardiogram (ECG) readings doubled the detection of peripartum cardiomyopathy in a large study of obstetric patients in Nigeria.

Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.

“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”

If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.

Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.

“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.

Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.

“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.

This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.

Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.

A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
 

Findings ‘absolutely startling’

The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”

Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.

“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.

“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”

“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.

The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.

With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.

“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?

“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”

However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.

Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.

“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
 

AI-guided screening study

Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.

In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.

The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).

In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.

In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.

The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.

The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).

For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.

Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.

A version of this article appeared on Medscape.com.

Screening with a “smart,” artificial-intelligence (AI)–enhanced investigational digital stethoscope (Eko Duo) that provides phonocardiogram and electrocardiogram (ECG) readings doubled the detection of peripartum cardiomyopathy in a large study of obstetric patients in Nigeria.

Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.

“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”

If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.

Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.

“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.

Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.

“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.

This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.

Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.

A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
 

Findings ‘absolutely startling’

The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”

Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.

“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.

“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”

“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.

The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.

With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.

“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?

“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”

However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.

Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.

“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
 

AI-guided screening study

Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.

In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.

The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).

In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.

In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.

The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.

The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).

For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.

Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.

A version of this article appeared on Medscape.com.

Screening with a “smart,” artificial-intelligence (AI)–enhanced investigational digital stethoscope (Eko Duo) that provides phonocardiogram and electrocardiogram (ECG) readings doubled the detection of peripartum cardiomyopathy in a large study of obstetric patients in Nigeria.

Demilade A. Adedinsewo, MD, MPH, from Mayo Clinic, Jacksonville, Fla., reported these findings from the Screening for Pregnancy Related Heart Failure in Nigeria (SPEC-AI Nigeria) trial in a press briefing and in a late-breaking trial session at the annual scientific sessions of the American Heart Association.

“The key takeaway,” Dr. Adedinsewo said in an interview, “is recognizing that a simple, low-impact tool like a digital stethoscope can dramatically improve the diagnosis of a life-threatening condition, and we can treat it. A large proportion of the women will recover; if we identify them early and treat them appropriately, we can reduce the risk of dying.”

If the device predicted low ejection fraction, the patient went on to have an echocardiogram to confirm cardiomyopathy, defined as a left ventricular ejection fraction (LVEF) <50%.

Peripartum cardiomyopathy was detected in 4% of the women who were screened with this tool, compared with 1.8% of those who received usual care, which included a traditional ECG.

“I believe that the control arm also has about 4% of cardiomyopathy cases, but because they didn’t have the same screening and echo, we’re missing them,” Dr. Adedinsewo said.

Diagnosis of peripartum cardiomyopathy is challenging, she noted, owing to overlap of common symptoms in pregnancy, such as lower-extremity swelling, fatigue, and shortness of breath with mild activity, which are also cardinal symptoms of heart failure.

“We were really impressed by the effectiveness of the tool, looking at how accurate it was when it comes to the sensitivity,” she added. She noted that the digital stethoscope correctly identified 92% of women with LVEF < 50% and 100% of those with LVEF < 40%.

This was the first large, clinical trial to evaluate an AI intervention in pregnancy. The investigators used a portable, battery-operated device that yielded AI results in real time.

Nigeria has the highest rate of pericardium cardiomyopathy of any country. However, one study showed a 16-fold higher rate of cardiomyopathy among African American women, compared with White women in the United States, Dr. Adedinsewo noted. “It will be important to identify who we should be screening to identify more cases,” she said.

A digital stethoscope that provides an ECG is currently available, but the algorithm that powers detection of cardiomyopathy is not yet commercially available.
 

Findings ‘absolutely startling’

The study discussant in the press briefing, Alexander Tarlochan Singh Sandhu, MD, from Stanford (Calif.) University congratulated the authors on this “valuable study that uses AI tools to solve a real health problem.”

Finding that 4% of the women in the intervention arm had reduced ejection fraction is “absolutely startling,” he said, “and speaks to how important improving our diagnosis in this space is.

“Where the burden of disease is high, a tool like this can be so incredibly valuable,” he said. He noted that the investigators identified 2% more patients with peripartum cardiomyopathy.

“This is an example of the potential of AI tools that can actually improve access to care and improve quality of care in resource-limited settings,” he said. “We need to move to understanding how to implement this into subsequent care [and] figure out what the next steps are to improve their outcomes.”

“The main takeaway is that, in areas where there is a very high prevalence of a morbid condition, a prescreening tool like this may be helpful” for diagnosis, the assigned discussant in the session, Marco Perez, MD, also from Stanford University, told this news organization.

The number of women needed to screen to detect peripartum cardiomyopathy by echocardiography alone is 1 in 23 in Nigeria and 1 in 970 in the United States, he said.

With an AI tool such as this one (sensitivity, 92%; specificity, 80%), the number needed to screen would be 1 in 5.7 in Nigeria and 1 in 194 in the United States, he estimates on the basis of incidence data.

“Because it is so common in Nigeria, a screening method makes a lot of sense,” Dr. Perez said. “The big question that remains is, what is the best screening modality?

“Certainly, this tool helped in bringing down the number of echoes needed to find a case, from the mid 20s down to about 5 or 6, so it certainly does seem to be helpful.”

However, the investigators did not say whether this tool is better than a clinical review of ECG or an AI analysis of ECG alone. It’s not clear whether the phonocardiogram component is significant in conjunction with the ECG component.

Nevertheless, “In a place where there’s a very high prevalence of peripartum cardiomyopathy, like Haiti, like Nigeria, doing something like this makes a lot of sense.

“For the U.S. and the rest of the world, where the prevalence is much lower, even with a tool like this you still would need to do a lot of echoes to find one case, and that may end up not being cost-effective. You would need to screen 200 women with echo to find one case.”
 

AI-guided screening study

Nigeria has the highest reported incidence of peripartum cardiomyopathy mortality (1 in 100 live births) and the highest number of maternal deaths.

In the United States, where rates of peripartum cardiomyopathy are much lower, maternal deaths are nevertheless higher than in other developed countries and have trended up over the past 3 decades; cardiomyopathy is a key contributor.

The investigators enrolled 1,195 women who were pregnant or had given birth in the past 12 months. The patients were from six teaching hospitals in Nigeria (two in the north and four in the south). They were randomly assigned in a 1:1 ratio to the intervention group (587) or the control group (608).

In the intervention group, clinicians used a smart stethoscope to record a phonocardiogram and a single-lead ECG reading in the V2 position and in an angled position on the patient’s chest wall and to record an ECG from the patient’s fingers. The recordings were sent to a Bluetooth-enabled mobile device (tablet or smartphone), which displayed the phonocardiogram and ECG images and that indicated whether the ejection fraction was normal or low. All patients in the intervention group received an echocardiogram.

In the control group, patients received usual care plus a traditional ECG. They were not required to have an echocardiogram because undergoing an echocardiogram is not part of usual care; however, they could receive an echocardiogram if the ECG suggested that they might need further testing.

The mean age of all the patients was 31 years, and all were Black. At study entry, 73% were pregnant, and 26% were post partum. They had similar comorbidities.

The primary outcome, cardiomyopathy (LVEF <50%) was detected in 24 of 587 patients (4.1%) in the intervention group and in 11 of 608 patients (1.8%) in the control group (odds ratio, 2.3; 95% confidence interval, 1.1-4.8; P = .02).

For the detection of LVEF <50%, the sensitivity was 92% and the specificity was 80%. For the detection of LVEF <40% (a secondary outcome), the sensitivity was 100% and the specificity was 79%.

Dr. Adedinsewo is supported by the Mayo Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program, which is funded by the National Institutes of Health. The trial was funded by Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research) and in part by the Mayo Clinic BIRCWH Program. Portable ECG, phonocardiogram recordings, and AI predictions using the digital stethoscope were extracted by the Eko Health team and were sent to the coordinating center for analysis. Eko Health had no role in study design, data collection, data analysis, or data interpretation.

A version of this article appeared on Medscape.com.

Maternal depressive symptoms probably start at or before pregnancy, with trajectories that remain stable across the perinatal into the postnatal period, new research suggests.

The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.

The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore. 

“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”

This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
 

Start screening sooner 

The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian. 

The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).

The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.

“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”

The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”

Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception. 

“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.” 
 

Depression is likely worse in the United States

Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”

John Abbott/Columbia University

Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”

“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded. 

This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.

A version of this article appeared on Medscape.com.

Maternal depressive symptoms probably start at or before pregnancy, with trajectories that remain stable across the perinatal into the postnatal period, new research suggests.

The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.

The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore. 

“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”

This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
 

Start screening sooner 

The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian. 

The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).

The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.

“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”

The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”

Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception. 

“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.” 
 

Depression is likely worse in the United States

Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”

John Abbott/Columbia University

Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”

“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded. 

This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.

A version of this article appeared on Medscape.com.

Maternal depressive symptoms probably start at or before pregnancy, with trajectories that remain stable across the perinatal into the postnatal period, new research suggests.

The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.

The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore. 

“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”

This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
 

Start screening sooner 

The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian. 

The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).

The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.

“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”

The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”

Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception. 

“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.” 
 

Depression is likely worse in the United States

Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”

John Abbott/Columbia University

Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”

“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded. 

This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.

A version of this article appeared on Medscape.com.

Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.

The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.

Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.

“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.

In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
 

High-sensitivity genomic panel

“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”

As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”

According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.

“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. Therefore, using this panel for early detection of this type of tumor during lactation should contribute to addressing a medical need that, until today, has gone unmet,” noted Dr. Vivancos.

As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
 

More direct contact with tumor cells

In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.

As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”

Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”

The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
 

Goal: Standardize the test as a screening method

“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.

When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”

When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”

“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.

Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”

Dr. Saura and Dr. Vivancos reported no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.

The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.

Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.

“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.

In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
 

High-sensitivity genomic panel

“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”

As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”

According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.

“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. Therefore, using this panel for early detection of this type of tumor during lactation should contribute to addressing a medical need that, until today, has gone unmet,” noted Dr. Vivancos.

As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
 

More direct contact with tumor cells

In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.

As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”

Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”

The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
 

Goal: Standardize the test as a screening method

“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.

When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”

When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”

“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.

Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”

Dr. Saura and Dr. Vivancos reported no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.

The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.

Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.

“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.

In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
 

High-sensitivity genomic panel

“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”

As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”

According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.

“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. Therefore, using this panel for early detection of this type of tumor during lactation should contribute to addressing a medical need that, until today, has gone unmet,” noted Dr. Vivancos.

As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
 

More direct contact with tumor cells

In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.

As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”

Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”

The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
 

Goal: Standardize the test as a screening method

“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.

When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”

When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”

“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.

Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”

Dr. Saura and Dr. Vivancos reported no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.