Christine Kilgore

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

As many as 1 in 20 youth run away from home each year, and you can play a critical role in identifying adolescents at high risk through confidential social histories and discussions, according to a clinical report from the American Academy of Pediatrics.

bodnarchuk/Getty Images

The academy’s data-rich report, “Runaway Youth: Caring for the Nation’s Largest Segment of Missing Children,” details how unaccompanied youth who run away – either on their own or who are asked to leave home – have high rates of trauma and neglect, mental illness, substance abuse, family dysfunction, and disengagement from school.

Children who identify as lesbian, gay, bisexual, transgender, and questioning or queer (LGBTQ) and youth in protective custody also are at high risk of running away and of becoming homeless – and once away from home, they and other runaways are at high risk for additional trauma, victimization, and violence, including sexual exploitation, according to the report published in Pediatrics.

“There clearly are certain populations at higher risk, and we really need to be aware of and in tune with these risks, and ask about the home and the household in order to try to decrease the risk of these kids getting into dangerous situations,” Thresia B. Gambon, MD, said in an interview. She is coauthor of the report and a pediatrician with the Citrus Health Network in Miami.

Among the AAP’s recommendations for practice is the guidance to conduct a thorough and confidential psychosocial assessment such as the HEEADSSS assessment (home environment, education and employment, eating peer-related activities, drugs, sexuality, suicide/depression, and safety) and to use a validated depression screening tool for adolescents, such as the Patient Health Questionnaire for Adolescents (PHQ-A) and the primary care version of the Beck Depression Inventory (BDI).

Broadly speaking, pediatric practices should “consider assessing for previous runaway episodes and risk factors for running away using a trauma-informed approach, which involves being aware of trauma and adverse childhood experiences that can affect health,” according to the report. The AAP Trauma Toolbox for Primary Care is mentioned as a resource.

Most surprising to Dr. Gambon in the research and report-writing process were data showing that disengagement from school is a significant risk factor. “This stood out to me,” she said. “If there are school problems [of various types], kids might run away to avoid attending school.”

Tasked with updating the AAP’s 2004 clinical report, “The Pediatrician’s Role in the Prevention of Missing Children,” Dr. Gambon and coauthor, Janna R. Gewirtz O’Brien, MD, decided to look more closely at runaway youth after studying the numbers – some studies estimate that between 5% and 8% of adolescents run away every year. They saw that, “in general, the number of kids who just go missing has actually decreased [with the help of] cell phones,” Dr. Gambon said in an interview.

“The numbers of kids who are actually running away are high,” she said, “and probably we’re underidentifying these in our primary care clinics.”

Because a significant number of runaway youth become homeless, data on the homeless offers a valuable window not only into the health risks of homelessness for teens (substance abuse, pregnancy, STDs,) but also into risk factors for leaving home in the first place, she noted. Research shows, for instance, that about 20%-40% of teenagers who are homeless identify as LGBTQ, compared with 4%-10% of their nonhomeless peers.

When an adolescent at high risk for running away is identified, you should use practice- and community-based resources to address key issues, support psychological and behavioral health needs of the child and family, and ensure safety.

For youth who have run away, you can share information on local resources, as well as the national Runaway Safeline (1-800-RUNAWAY), which provides 24-hour referrals to community resources, including shelter, food banks, social services, and counseling. You also can ask adolescents whether they have sources of support and shelter (safe, supportive adults who might help in a crisis), and discuss safety plans for leaving home that include health care to mitigate risk, such as reliable contraception and access to mental health care.

“The goal with talking about a safety plan isn’t, of course, to encourage a child to run away, but if they feel as if they need to find somewhere else to live or stay, to discuss what resources are available to them to try to keep them as safe as possible when they’re out of their home,” Dr. Gambon said.

Dr. Gambon speaks partly from experience. She works routinely with youth who have run away from foster care homes, youth who have been trafficked, and other runaways. “I always try to talk with them about safety. I try not to put them down for their decisions but to work with them to make better decisions,” she said. “I work closely with a psychologist because a big part of this is getting them to have self-worth. They often feel as if no one cares, and some just want to be heard and to be able to talk about their situations.”

The AAP report notes that, of more than 70,000 contacts made to Runaway Safeline in 2017, 31% were about youth who were contemplating running away, 16% were about youth who had run away, 5% were about youth asked to leave home or prevented from returning, and 9% concerned youth experiencing homelessness. About three-quarters of the calls came from the youth themselves.

Dr. Gambon and Dr. Gewirtz O’Brien, of the department of pediatrics at the University of Minnesota in Minneapolis, worked with the AAP Committee on Psychosocial Aspects of Child and Family Health and the AAP Council on Community Pediatrics in producing the report. There was no external funding for this report and the authors said they had no conflicts of interest.
 

SOURCE: Gambon TB et al. Pediatrics. 2020 Jan 21. doi: 10.1542/peds.2019-3752.

As many as 1 in 20 youth run away from home each year, and you can play a critical role in identifying adolescents at high risk through confidential social histories and discussions, according to a clinical report from the American Academy of Pediatrics.

bodnarchuk/Getty Images

The academy’s data-rich report, “Runaway Youth: Caring for the Nation’s Largest Segment of Missing Children,” details how unaccompanied youth who run away – either on their own or who are asked to leave home – have high rates of trauma and neglect, mental illness, substance abuse, family dysfunction, and disengagement from school.

Children who identify as lesbian, gay, bisexual, transgender, and questioning or queer (LGBTQ) and youth in protective custody also are at high risk of running away and of becoming homeless – and once away from home, they and other runaways are at high risk for additional trauma, victimization, and violence, including sexual exploitation, according to the report published in Pediatrics.

“There clearly are certain populations at higher risk, and we really need to be aware of and in tune with these risks, and ask about the home and the household in order to try to decrease the risk of these kids getting into dangerous situations,” Thresia B. Gambon, MD, said in an interview. She is coauthor of the report and a pediatrician with the Citrus Health Network in Miami.

Among the AAP’s recommendations for practice is the guidance to conduct a thorough and confidential psychosocial assessment such as the HEEADSSS assessment (home environment, education and employment, eating peer-related activities, drugs, sexuality, suicide/depression, and safety) and to use a validated depression screening tool for adolescents, such as the Patient Health Questionnaire for Adolescents (PHQ-A) and the primary care version of the Beck Depression Inventory (BDI).

Broadly speaking, pediatric practices should “consider assessing for previous runaway episodes and risk factors for running away using a trauma-informed approach, which involves being aware of trauma and adverse childhood experiences that can affect health,” according to the report. The AAP Trauma Toolbox for Primary Care is mentioned as a resource.

Most surprising to Dr. Gambon in the research and report-writing process were data showing that disengagement from school is a significant risk factor. “This stood out to me,” she said. “If there are school problems [of various types], kids might run away to avoid attending school.”

Tasked with updating the AAP’s 2004 clinical report, “The Pediatrician’s Role in the Prevention of Missing Children,” Dr. Gambon and coauthor, Janna R. Gewirtz O’Brien, MD, decided to look more closely at runaway youth after studying the numbers – some studies estimate that between 5% and 8% of adolescents run away every year. They saw that, “in general, the number of kids who just go missing has actually decreased [with the help of] cell phones,” Dr. Gambon said in an interview.

“The numbers of kids who are actually running away are high,” she said, “and probably we’re underidentifying these in our primary care clinics.”

Because a significant number of runaway youth become homeless, data on the homeless offers a valuable window not only into the health risks of homelessness for teens (substance abuse, pregnancy, STDs,) but also into risk factors for leaving home in the first place, she noted. Research shows, for instance, that about 20%-40% of teenagers who are homeless identify as LGBTQ, compared with 4%-10% of their nonhomeless peers.

When an adolescent at high risk for running away is identified, you should use practice- and community-based resources to address key issues, support psychological and behavioral health needs of the child and family, and ensure safety.

For youth who have run away, you can share information on local resources, as well as the national Runaway Safeline (1-800-RUNAWAY), which provides 24-hour referrals to community resources, including shelter, food banks, social services, and counseling. You also can ask adolescents whether they have sources of support and shelter (safe, supportive adults who might help in a crisis), and discuss safety plans for leaving home that include health care to mitigate risk, such as reliable contraception and access to mental health care.

“The goal with talking about a safety plan isn’t, of course, to encourage a child to run away, but if they feel as if they need to find somewhere else to live or stay, to discuss what resources are available to them to try to keep them as safe as possible when they’re out of their home,” Dr. Gambon said.

Dr. Gambon speaks partly from experience. She works routinely with youth who have run away from foster care homes, youth who have been trafficked, and other runaways. “I always try to talk with them about safety. I try not to put them down for their decisions but to work with them to make better decisions,” she said. “I work closely with a psychologist because a big part of this is getting them to have self-worth. They often feel as if no one cares, and some just want to be heard and to be able to talk about their situations.”

The AAP report notes that, of more than 70,000 contacts made to Runaway Safeline in 2017, 31% were about youth who were contemplating running away, 16% were about youth who had run away, 5% were about youth asked to leave home or prevented from returning, and 9% concerned youth experiencing homelessness. About three-quarters of the calls came from the youth themselves.

Dr. Gambon and Dr. Gewirtz O’Brien, of the department of pediatrics at the University of Minnesota in Minneapolis, worked with the AAP Committee on Psychosocial Aspects of Child and Family Health and the AAP Council on Community Pediatrics in producing the report. There was no external funding for this report and the authors said they had no conflicts of interest.
 

SOURCE: Gambon TB et al. Pediatrics. 2020 Jan 21. doi: 10.1542/peds.2019-3752.

As many as 1 in 20 youth run away from home each year, and you can play a critical role in identifying adolescents at high risk through confidential social histories and discussions, according to a clinical report from the American Academy of Pediatrics.

bodnarchuk/Getty Images

The academy’s data-rich report, “Runaway Youth: Caring for the Nation’s Largest Segment of Missing Children,” details how unaccompanied youth who run away – either on their own or who are asked to leave home – have high rates of trauma and neglect, mental illness, substance abuse, family dysfunction, and disengagement from school.

Children who identify as lesbian, gay, bisexual, transgender, and questioning or queer (LGBTQ) and youth in protective custody also are at high risk of running away and of becoming homeless – and once away from home, they and other runaways are at high risk for additional trauma, victimization, and violence, including sexual exploitation, according to the report published in Pediatrics.

“There clearly are certain populations at higher risk, and we really need to be aware of and in tune with these risks, and ask about the home and the household in order to try to decrease the risk of these kids getting into dangerous situations,” Thresia B. Gambon, MD, said in an interview. She is coauthor of the report and a pediatrician with the Citrus Health Network in Miami.

Among the AAP’s recommendations for practice is the guidance to conduct a thorough and confidential psychosocial assessment such as the HEEADSSS assessment (home environment, education and employment, eating peer-related activities, drugs, sexuality, suicide/depression, and safety) and to use a validated depression screening tool for adolescents, such as the Patient Health Questionnaire for Adolescents (PHQ-A) and the primary care version of the Beck Depression Inventory (BDI).

Broadly speaking, pediatric practices should “consider assessing for previous runaway episodes and risk factors for running away using a trauma-informed approach, which involves being aware of trauma and adverse childhood experiences that can affect health,” according to the report. The AAP Trauma Toolbox for Primary Care is mentioned as a resource.

Most surprising to Dr. Gambon in the research and report-writing process were data showing that disengagement from school is a significant risk factor. “This stood out to me,” she said. “If there are school problems [of various types], kids might run away to avoid attending school.”

Tasked with updating the AAP’s 2004 clinical report, “The Pediatrician’s Role in the Prevention of Missing Children,” Dr. Gambon and coauthor, Janna R. Gewirtz O’Brien, MD, decided to look more closely at runaway youth after studying the numbers – some studies estimate that between 5% and 8% of adolescents run away every year. They saw that, “in general, the number of kids who just go missing has actually decreased [with the help of] cell phones,” Dr. Gambon said in an interview.

“The numbers of kids who are actually running away are high,” she said, “and probably we’re underidentifying these in our primary care clinics.”

Because a significant number of runaway youth become homeless, data on the homeless offers a valuable window not only into the health risks of homelessness for teens (substance abuse, pregnancy, STDs,) but also into risk factors for leaving home in the first place, she noted. Research shows, for instance, that about 20%-40% of teenagers who are homeless identify as LGBTQ, compared with 4%-10% of their nonhomeless peers.

When an adolescent at high risk for running away is identified, you should use practice- and community-based resources to address key issues, support psychological and behavioral health needs of the child and family, and ensure safety.

For youth who have run away, you can share information on local resources, as well as the national Runaway Safeline (1-800-RUNAWAY), which provides 24-hour referrals to community resources, including shelter, food banks, social services, and counseling. You also can ask adolescents whether they have sources of support and shelter (safe, supportive adults who might help in a crisis), and discuss safety plans for leaving home that include health care to mitigate risk, such as reliable contraception and access to mental health care.

“The goal with talking about a safety plan isn’t, of course, to encourage a child to run away, but if they feel as if they need to find somewhere else to live or stay, to discuss what resources are available to them to try to keep them as safe as possible when they’re out of their home,” Dr. Gambon said.

Dr. Gambon speaks partly from experience. She works routinely with youth who have run away from foster care homes, youth who have been trafficked, and other runaways. “I always try to talk with them about safety. I try not to put them down for their decisions but to work with them to make better decisions,” she said. “I work closely with a psychologist because a big part of this is getting them to have self-worth. They often feel as if no one cares, and some just want to be heard and to be able to talk about their situations.”

The AAP report notes that, of more than 70,000 contacts made to Runaway Safeline in 2017, 31% were about youth who were contemplating running away, 16% were about youth who had run away, 5% were about youth asked to leave home or prevented from returning, and 9% concerned youth experiencing homelessness. About three-quarters of the calls came from the youth themselves.

Dr. Gambon and Dr. Gewirtz O’Brien, of the department of pediatrics at the University of Minnesota in Minneapolis, worked with the AAP Committee on Psychosocial Aspects of Child and Family Health and the AAP Council on Community Pediatrics in producing the report. There was no external funding for this report and the authors said they had no conflicts of interest.
 

SOURCE: Gambon TB et al. Pediatrics. 2020 Jan 21. doi: 10.1542/peds.2019-3752.

WASHINGTON – Research on pravastatin for the prevention of preeclampsia is moving along after “reassuring” data from pilot studies, with a large National Institutes of Health–funded trial currently recruiting women with a prior history of the disorder with preterm delivery at less than 34 weeks, Maged Costantine, MD, said at the biennial Diabetes in Pregnancy Study Group of North America meeting.

Creatas Images

More should be learned about low-dose aspirin, in the meantime, once the outcomes of a global study involving first-trimester initiation are published, said another speaker, Cynthia Gyamfi-Bannerman, MD, MS. Low-dose aspirin currently is recommended for preeclampsia prevention starting between 12 and 28 weeks, optimally before 16 weeks.

The biological plausibility of using pravastatin for preeclampsia prevention stems from the overlapping pathophysiology of preeclampsia with atherosclerotic cardiovascular disease – endothelial dysfunction and inflammation are common key mechanisms – as well as common risk factors, including diabetes and obesity, said Dr. Costantine, director of the division of maternal-fetal medicine at Ohio State University, Columbus, who is chairing the study.

In animal models of preeclampsia, pravastatin has been shown to upregulate placental growth factor, reduce antiangiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), and upregulate endothelial nitric oxide synthase. Mice have shown improved vascular reactivity, decreased proteinuria, decreased oxidative stress, and other positive effects, without any detrimental outcomes.

A pilot randomized controlled trial conducted with the Obstetric-Fetal Pharmacology Research Units Network and published in the American Journal of Obstetrics and Gynecology in 2016 assigned 10 women to 10 mg daily pravastatin and 10 women to placebo. The drug reduced maternal cholesterol concentrations but there were no differences in birth weight or umbilical cord cholesterol concentrations between the two groups.

Women in the pravastatin group were less likely to develop preeclampsia (none, compared with four in the placebo group), less likely to have an indicated preterm delivery (one, compared with five in the placebo group), and less likely to have their neonates admitted to the neonatal ICU.

There were no differences in side effects, congenital anomalies, or other adverse events. Dr. Costantine, principal investigator of the pilot study, and his colleagues wrote in the paper that the “favorable risk-benefit analysis justifies continued research with a dose escalation” (Am J Obstet Gynecol. 2016 Jun;214[6]:720.e1-17).

The new multicenter randomized controlled trial is randomizing 1,550 women to either 20 mg pravastatin or placebo starting between 12 weeks 0 days and 16 weeks 6 days. The primary outcome is a composite of preeclampsia, maternal death, or fetal loss. Secondary outcomes include a composite of severe maternal morbidity and various measures representing preeclampsia severity and complications, as well as preterm delivery less than 37 weeks and less than 34 weeks and various fetal/neonatal outcomes.

“In addition, we’ll look at development,” Dr. Costantine said, with offspring assessed at 2 and 5 years of age. The trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute.

In the meantime, he said, the use of pravastatin to ameliorate early-onset preeclampsia is being tested in a small European proof-of-concept trial that has randomized women with early-onset preeclampsia (between 24 and 31 6/7 weeks) to 40 mg pravastatin or placebo. The primary outcome is reduction of antiangiogenic markers. Results are expected in another year or 2, he said.

The aspirin trial referred to by Dr. Gyamfi-Bannerman has been looking at the 81-mg dose of aspirin initiated between 6 0/7 and 13 6/7 weeks in nulliparous women who had no more than two previous pregnancy losses. The key question of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) trial – conducted in the NICHD Global Network for Women’s and Children’s Health – is whether low-dose aspirin can reduce the rate of preterm birth. Preeclampsia is a secondary outcome (https://clinicaltrials.gov/ct2/show/NCT02409680).

“It may eventually be that the use of baby aspirin is further expanded to reduce the risk of preterm birth,” she said.

Overall, “we need more data on first-trimester use [of low-dose aspirin] and long-term outcomes,” Dr. Gyamfi-Bannerman said. And with respect to preeclampsia prevention specifically, more research is needed looking at risk reduction levels within specific groups of patients.

Since 2014, the U.S. Preventive Services Task Force (USPSTF) has called for low-dose aspirin at 81 mg/day in women who have one or more high-risk factors for preeclampsia (including type 1 or type 2 diabetes mellitus), and consideration of such treatment in patients with several moderate-risk factors. The American College of Obstetricians and Gynecologists’ recommendation varies slightly in that it advises treatment in patients with more than one (versus several) moderate-level risk factors (Obstet Gynecol. 2018;132[1]:e44-52).

Moderate-level risk factors include nulliparity, obesity, family history of preeclampsia, a baseline demographic risk (African-American or low socioeconomic status), and prior poor history (intrauterine growth restriction/small-for-gestational-age, previous poor outcome). “This is just about everyone I see,” Dr. Gyamfi-Bannerman said.

Dr. Gyamfi-Bannerman said she’d “love to see more data on higher doses” of low-dose aspirin – data that compares 81 mg/day with 150 mg/day, for instance.

A study published in 2017 in the New England Journal of Medicine randomized 1,776 women at high risk for preeclampsia to 150 mg/day or placebo and found a significant reduction in preterm preeclampsia (4.3% vs. 1.6%) in the aspirin group. Women in this European trial were deemed to be at high risk, however, based on a first-trimester screening algorithm that incorporated serum markers (maternal serum pregnancy-associated plasma protein A and placental growth factor) and uterine artery Doppler measures (N Engl J Med. 2017 Aug 17;377[7]:613-22).

“So it was a very interesting study, very provocative, but it’s hard to know how it would translate to the U.S. population [given that such screening practices] are not the way most of us are practicing here,” said Dr. Gyamfi-Bannerman, codirector of the Preterm Birth Prevention Center at Columbia University, New York, and professor of obstetrics and gynecology at the university.

The USPSTF based its recommendations on a systematic review that pooled data from 15 high-quality randomized controlled trials, including 13 that reported preeclampsia incidence among women at highest risk of disease. They found a 24% reduction in preeclampsia, but the actual risk reduction depends on the baseline population risk and may be closer to 10%, she said.

In a presentation on gaps in knowledge, Leslie Myatt, PhD, of the department of obstetrics and gynecology at Oregon Health and Science University, Portland, emphasized that preeclampsia is a syndrome with a heterogeneity of presentation and pathophysiology. “We don’t completely understand the pathophysiology,” he said.

Research needs to be “directed at the existence of multiple pathways [and subtypes],” he said, such that future therapies can be targeted and personalized.

Dr. Costantine did not report any disclosures. Dr. Gyamfi-Bannerman reported a Society of Maternal Fetal Medicine/AMAG Pharmaceuticals unrestricted grant and Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Heart, Lung and Blood Institute funding. Dr. Myatt reported that he has no financial or other ties that pose a conflict of interest.

WASHINGTON – Research on pravastatin for the prevention of preeclampsia is moving along after “reassuring” data from pilot studies, with a large National Institutes of Health–funded trial currently recruiting women with a prior history of the disorder with preterm delivery at less than 34 weeks, Maged Costantine, MD, said at the biennial Diabetes in Pregnancy Study Group of North America meeting.

Creatas Images

More should be learned about low-dose aspirin, in the meantime, once the outcomes of a global study involving first-trimester initiation are published, said another speaker, Cynthia Gyamfi-Bannerman, MD, MS. Low-dose aspirin currently is recommended for preeclampsia prevention starting between 12 and 28 weeks, optimally before 16 weeks.

The biological plausibility of using pravastatin for preeclampsia prevention stems from the overlapping pathophysiology of preeclampsia with atherosclerotic cardiovascular disease – endothelial dysfunction and inflammation are common key mechanisms – as well as common risk factors, including diabetes and obesity, said Dr. Costantine, director of the division of maternal-fetal medicine at Ohio State University, Columbus, who is chairing the study.

In animal models of preeclampsia, pravastatin has been shown to upregulate placental growth factor, reduce antiangiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), and upregulate endothelial nitric oxide synthase. Mice have shown improved vascular reactivity, decreased proteinuria, decreased oxidative stress, and other positive effects, without any detrimental outcomes.

A pilot randomized controlled trial conducted with the Obstetric-Fetal Pharmacology Research Units Network and published in the American Journal of Obstetrics and Gynecology in 2016 assigned 10 women to 10 mg daily pravastatin and 10 women to placebo. The drug reduced maternal cholesterol concentrations but there were no differences in birth weight or umbilical cord cholesterol concentrations between the two groups.

Women in the pravastatin group were less likely to develop preeclampsia (none, compared with four in the placebo group), less likely to have an indicated preterm delivery (one, compared with five in the placebo group), and less likely to have their neonates admitted to the neonatal ICU.

There were no differences in side effects, congenital anomalies, or other adverse events. Dr. Costantine, principal investigator of the pilot study, and his colleagues wrote in the paper that the “favorable risk-benefit analysis justifies continued research with a dose escalation” (Am J Obstet Gynecol. 2016 Jun;214[6]:720.e1-17).

The new multicenter randomized controlled trial is randomizing 1,550 women to either 20 mg pravastatin or placebo starting between 12 weeks 0 days and 16 weeks 6 days. The primary outcome is a composite of preeclampsia, maternal death, or fetal loss. Secondary outcomes include a composite of severe maternal morbidity and various measures representing preeclampsia severity and complications, as well as preterm delivery less than 37 weeks and less than 34 weeks and various fetal/neonatal outcomes.

“In addition, we’ll look at development,” Dr. Costantine said, with offspring assessed at 2 and 5 years of age. The trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute.

In the meantime, he said, the use of pravastatin to ameliorate early-onset preeclampsia is being tested in a small European proof-of-concept trial that has randomized women with early-onset preeclampsia (between 24 and 31 6/7 weeks) to 40 mg pravastatin or placebo. The primary outcome is reduction of antiangiogenic markers. Results are expected in another year or 2, he said.

The aspirin trial referred to by Dr. Gyamfi-Bannerman has been looking at the 81-mg dose of aspirin initiated between 6 0/7 and 13 6/7 weeks in nulliparous women who had no more than two previous pregnancy losses. The key question of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) trial – conducted in the NICHD Global Network for Women’s and Children’s Health – is whether low-dose aspirin can reduce the rate of preterm birth. Preeclampsia is a secondary outcome (https://clinicaltrials.gov/ct2/show/NCT02409680).

“It may eventually be that the use of baby aspirin is further expanded to reduce the risk of preterm birth,” she said.

Overall, “we need more data on first-trimester use [of low-dose aspirin] and long-term outcomes,” Dr. Gyamfi-Bannerman said. And with respect to preeclampsia prevention specifically, more research is needed looking at risk reduction levels within specific groups of patients.

Since 2014, the U.S. Preventive Services Task Force (USPSTF) has called for low-dose aspirin at 81 mg/day in women who have one or more high-risk factors for preeclampsia (including type 1 or type 2 diabetes mellitus), and consideration of such treatment in patients with several moderate-risk factors. The American College of Obstetricians and Gynecologists’ recommendation varies slightly in that it advises treatment in patients with more than one (versus several) moderate-level risk factors (Obstet Gynecol. 2018;132[1]:e44-52).

Moderate-level risk factors include nulliparity, obesity, family history of preeclampsia, a baseline demographic risk (African-American or low socioeconomic status), and prior poor history (intrauterine growth restriction/small-for-gestational-age, previous poor outcome). “This is just about everyone I see,” Dr. Gyamfi-Bannerman said.

Dr. Gyamfi-Bannerman said she’d “love to see more data on higher doses” of low-dose aspirin – data that compares 81 mg/day with 150 mg/day, for instance.

A study published in 2017 in the New England Journal of Medicine randomized 1,776 women at high risk for preeclampsia to 150 mg/day or placebo and found a significant reduction in preterm preeclampsia (4.3% vs. 1.6%) in the aspirin group. Women in this European trial were deemed to be at high risk, however, based on a first-trimester screening algorithm that incorporated serum markers (maternal serum pregnancy-associated plasma protein A and placental growth factor) and uterine artery Doppler measures (N Engl J Med. 2017 Aug 17;377[7]:613-22).

“So it was a very interesting study, very provocative, but it’s hard to know how it would translate to the U.S. population [given that such screening practices] are not the way most of us are practicing here,” said Dr. Gyamfi-Bannerman, codirector of the Preterm Birth Prevention Center at Columbia University, New York, and professor of obstetrics and gynecology at the university.

The USPSTF based its recommendations on a systematic review that pooled data from 15 high-quality randomized controlled trials, including 13 that reported preeclampsia incidence among women at highest risk of disease. They found a 24% reduction in preeclampsia, but the actual risk reduction depends on the baseline population risk and may be closer to 10%, she said.

In a presentation on gaps in knowledge, Leslie Myatt, PhD, of the department of obstetrics and gynecology at Oregon Health and Science University, Portland, emphasized that preeclampsia is a syndrome with a heterogeneity of presentation and pathophysiology. “We don’t completely understand the pathophysiology,” he said.

Research needs to be “directed at the existence of multiple pathways [and subtypes],” he said, such that future therapies can be targeted and personalized.

Dr. Costantine did not report any disclosures. Dr. Gyamfi-Bannerman reported a Society of Maternal Fetal Medicine/AMAG Pharmaceuticals unrestricted grant and Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Heart, Lung and Blood Institute funding. Dr. Myatt reported that he has no financial or other ties that pose a conflict of interest.

WASHINGTON – Research on pravastatin for the prevention of preeclampsia is moving along after “reassuring” data from pilot studies, with a large National Institutes of Health–funded trial currently recruiting women with a prior history of the disorder with preterm delivery at less than 34 weeks, Maged Costantine, MD, said at the biennial Diabetes in Pregnancy Study Group of North America meeting.

Creatas Images

More should be learned about low-dose aspirin, in the meantime, once the outcomes of a global study involving first-trimester initiation are published, said another speaker, Cynthia Gyamfi-Bannerman, MD, MS. Low-dose aspirin currently is recommended for preeclampsia prevention starting between 12 and 28 weeks, optimally before 16 weeks.

The biological plausibility of using pravastatin for preeclampsia prevention stems from the overlapping pathophysiology of preeclampsia with atherosclerotic cardiovascular disease – endothelial dysfunction and inflammation are common key mechanisms – as well as common risk factors, including diabetes and obesity, said Dr. Costantine, director of the division of maternal-fetal medicine at Ohio State University, Columbus, who is chairing the study.

In animal models of preeclampsia, pravastatin has been shown to upregulate placental growth factor, reduce antiangiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), and upregulate endothelial nitric oxide synthase. Mice have shown improved vascular reactivity, decreased proteinuria, decreased oxidative stress, and other positive effects, without any detrimental outcomes.

A pilot randomized controlled trial conducted with the Obstetric-Fetal Pharmacology Research Units Network and published in the American Journal of Obstetrics and Gynecology in 2016 assigned 10 women to 10 mg daily pravastatin and 10 women to placebo. The drug reduced maternal cholesterol concentrations but there were no differences in birth weight or umbilical cord cholesterol concentrations between the two groups.

Women in the pravastatin group were less likely to develop preeclampsia (none, compared with four in the placebo group), less likely to have an indicated preterm delivery (one, compared with five in the placebo group), and less likely to have their neonates admitted to the neonatal ICU.

There were no differences in side effects, congenital anomalies, or other adverse events. Dr. Costantine, principal investigator of the pilot study, and his colleagues wrote in the paper that the “favorable risk-benefit analysis justifies continued research with a dose escalation” (Am J Obstet Gynecol. 2016 Jun;214[6]:720.e1-17).

The new multicenter randomized controlled trial is randomizing 1,550 women to either 20 mg pravastatin or placebo starting between 12 weeks 0 days and 16 weeks 6 days. The primary outcome is a composite of preeclampsia, maternal death, or fetal loss. Secondary outcomes include a composite of severe maternal morbidity and various measures representing preeclampsia severity and complications, as well as preterm delivery less than 37 weeks and less than 34 weeks and various fetal/neonatal outcomes.

“In addition, we’ll look at development,” Dr. Costantine said, with offspring assessed at 2 and 5 years of age. The trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute.

In the meantime, he said, the use of pravastatin to ameliorate early-onset preeclampsia is being tested in a small European proof-of-concept trial that has randomized women with early-onset preeclampsia (between 24 and 31 6/7 weeks) to 40 mg pravastatin or placebo. The primary outcome is reduction of antiangiogenic markers. Results are expected in another year or 2, he said.

The aspirin trial referred to by Dr. Gyamfi-Bannerman has been looking at the 81-mg dose of aspirin initiated between 6 0/7 and 13 6/7 weeks in nulliparous women who had no more than two previous pregnancy losses. The key question of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) trial – conducted in the NICHD Global Network for Women’s and Children’s Health – is whether low-dose aspirin can reduce the rate of preterm birth. Preeclampsia is a secondary outcome (https://clinicaltrials.gov/ct2/show/NCT02409680).

“It may eventually be that the use of baby aspirin is further expanded to reduce the risk of preterm birth,” she said.

Overall, “we need more data on first-trimester use [of low-dose aspirin] and long-term outcomes,” Dr. Gyamfi-Bannerman said. And with respect to preeclampsia prevention specifically, more research is needed looking at risk reduction levels within specific groups of patients.

Since 2014, the U.S. Preventive Services Task Force (USPSTF) has called for low-dose aspirin at 81 mg/day in women who have one or more high-risk factors for preeclampsia (including type 1 or type 2 diabetes mellitus), and consideration of such treatment in patients with several moderate-risk factors. The American College of Obstetricians and Gynecologists’ recommendation varies slightly in that it advises treatment in patients with more than one (versus several) moderate-level risk factors (Obstet Gynecol. 2018;132[1]:e44-52).

Moderate-level risk factors include nulliparity, obesity, family history of preeclampsia, a baseline demographic risk (African-American or low socioeconomic status), and prior poor history (intrauterine growth restriction/small-for-gestational-age, previous poor outcome). “This is just about everyone I see,” Dr. Gyamfi-Bannerman said.

Dr. Gyamfi-Bannerman said she’d “love to see more data on higher doses” of low-dose aspirin – data that compares 81 mg/day with 150 mg/day, for instance.

A study published in 2017 in the New England Journal of Medicine randomized 1,776 women at high risk for preeclampsia to 150 mg/day or placebo and found a significant reduction in preterm preeclampsia (4.3% vs. 1.6%) in the aspirin group. Women in this European trial were deemed to be at high risk, however, based on a first-trimester screening algorithm that incorporated serum markers (maternal serum pregnancy-associated plasma protein A and placental growth factor) and uterine artery Doppler measures (N Engl J Med. 2017 Aug 17;377[7]:613-22).

“So it was a very interesting study, very provocative, but it’s hard to know how it would translate to the U.S. population [given that such screening practices] are not the way most of us are practicing here,” said Dr. Gyamfi-Bannerman, codirector of the Preterm Birth Prevention Center at Columbia University, New York, and professor of obstetrics and gynecology at the university.

The USPSTF based its recommendations on a systematic review that pooled data from 15 high-quality randomized controlled trials, including 13 that reported preeclampsia incidence among women at highest risk of disease. They found a 24% reduction in preeclampsia, but the actual risk reduction depends on the baseline population risk and may be closer to 10%, she said.

In a presentation on gaps in knowledge, Leslie Myatt, PhD, of the department of obstetrics and gynecology at Oregon Health and Science University, Portland, emphasized that preeclampsia is a syndrome with a heterogeneity of presentation and pathophysiology. “We don’t completely understand the pathophysiology,” he said.

Research needs to be “directed at the existence of multiple pathways [and subtypes],” he said, such that future therapies can be targeted and personalized.

Dr. Costantine did not report any disclosures. Dr. Gyamfi-Bannerman reported a Society of Maternal Fetal Medicine/AMAG Pharmaceuticals unrestricted grant and Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Heart, Lung and Blood Institute funding. Dr. Myatt reported that he has no financial or other ties that pose a conflict of interest.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Insomnia, restless legs syndrome (RLS), and frequent snoring were significantly associated with subsequent ADHD symptoms in a large longitudinal study of adolescents in China.

Investigators twice assessed 7,072 middle and high school students participating in the larger longitudinal Shandong Adolescent Behavior & Health Cohort – in 2015 and 1 year later in 2016 – for sleep, mental health, psychosocial factors (using the self-administered Adolescent Health Questionnaire, or AHQ), and for ADHD symptoms (using the Youth Self-Report, or YSR, of the Achenbach Child Behavior Checklist).

At baseline, ADHD symptoms were reported by 7.6% of adolescents and were significantly correlated, after adjusting for adolescent and family covariates, with all the sleep variables studied: sleep duration of 7 hours or less per night, insomnia symptoms, poor sleep quality, RLS symptoms, frequent snorting, and hypnotic use, reported Xianchen Liu, MD, PhD, of Shandong (China) University, and coinvestigators. They noted a dose-response relationship between sleep duration and the odds of having ADHD symptoms.

At 1-year follow-up, 4.5% of the 6,531 participants who did not have ADHD symptoms at baseline now reported them. After adjustments for covariates, any insomnia (odds ratio, 1.48), difficulty initiating sleep (one of the insomnia symptoms) (OR, 2.09), RLS (OR, 1.47), and frequent snoring (OR, 2.30) at baseline were each significantly associated with development of incident ADHD symptoms and with ADHD severity at 1 year, they reported in Sleep.

“Given the fact that sleep disorders in adolescents are often underdiagnosed and untreated primarily in the primary care setting, our findings highlight that clinicians should assess and manage short sleep duration and sleep problems for effective treatment of ADHD in adolescents,” as well as for prevention, they wrote.

The AHQ includes questions that assess nocturnal sleep duration and sleep problems during the past month. The adolescent and family variables that were selected as covariates and controlled for include cigarette smoking, alcohol drinking, use of mental health services, chronic physical diseases, and parental education and occupation. Depression was also a covariate but was assessed through a different scale.

The YSR measures eight ADHD symptoms during the past 6 months on a 3-point scale (not true, somewhat or sometimes true, and very true or often true). The adolescent participants of this study were in grades 7, 8, and 10 at baseline. Their mean age at baseline was 15 years; half were male. They were part of the larger Shandong Adolescent and Behavioral Cohort, a longitudinal study of almost 12,000 adolescents.

Growing evidence has demonstrated a bidirectional relationship between sleep problems and ADHD symptoms in pediatric populations, the investigators wrote, and further research is needed to examine the “mediators, moderators, and biological mechanisms of the sleep-ADHD link [in adolescents].”

While there are multiple potential pathways for this link, sleep problems may sometimes result in a cluster of behavioral and cognitive symptoms that are not true ADHD but that mimic the disorder, they noted.

The investigators also noted that approximately 67% of adolescents who had clinically relevant ADHD symptoms at baseline no longer had these symptoms at 1-year follow-up – a finding that “supports the [idea]” that ADHD symptoms with onset in adolescence may be transient or episodic rather than persistent.

The study was funded in part by the National Natural Science Foundation of China. The authors reported that they have no conflicts of interest.

SOURCE: Liu X et al. Sleep. 2019 Dec 2. doi: 10.1093/sleep/zsz294.

Insomnia, restless legs syndrome (RLS), and frequent snoring were significantly associated with subsequent ADHD symptoms in a large longitudinal study of adolescents in China.

Investigators twice assessed 7,072 middle and high school students participating in the larger longitudinal Shandong Adolescent Behavior & Health Cohort – in 2015 and 1 year later in 2016 – for sleep, mental health, psychosocial factors (using the self-administered Adolescent Health Questionnaire, or AHQ), and for ADHD symptoms (using the Youth Self-Report, or YSR, of the Achenbach Child Behavior Checklist).

At baseline, ADHD symptoms were reported by 7.6% of adolescents and were significantly correlated, after adjusting for adolescent and family covariates, with all the sleep variables studied: sleep duration of 7 hours or less per night, insomnia symptoms, poor sleep quality, RLS symptoms, frequent snorting, and hypnotic use, reported Xianchen Liu, MD, PhD, of Shandong (China) University, and coinvestigators. They noted a dose-response relationship between sleep duration and the odds of having ADHD symptoms.

At 1-year follow-up, 4.5% of the 6,531 participants who did not have ADHD symptoms at baseline now reported them. After adjustments for covariates, any insomnia (odds ratio, 1.48), difficulty initiating sleep (one of the insomnia symptoms) (OR, 2.09), RLS (OR, 1.47), and frequent snoring (OR, 2.30) at baseline were each significantly associated with development of incident ADHD symptoms and with ADHD severity at 1 year, they reported in Sleep.

“Given the fact that sleep disorders in adolescents are often underdiagnosed and untreated primarily in the primary care setting, our findings highlight that clinicians should assess and manage short sleep duration and sleep problems for effective treatment of ADHD in adolescents,” as well as for prevention, they wrote.

The AHQ includes questions that assess nocturnal sleep duration and sleep problems during the past month. The adolescent and family variables that were selected as covariates and controlled for include cigarette smoking, alcohol drinking, use of mental health services, chronic physical diseases, and parental education and occupation. Depression was also a covariate but was assessed through a different scale.

The YSR measures eight ADHD symptoms during the past 6 months on a 3-point scale (not true, somewhat or sometimes true, and very true or often true). The adolescent participants of this study were in grades 7, 8, and 10 at baseline. Their mean age at baseline was 15 years; half were male. They were part of the larger Shandong Adolescent and Behavioral Cohort, a longitudinal study of almost 12,000 adolescents.

Growing evidence has demonstrated a bidirectional relationship between sleep problems and ADHD symptoms in pediatric populations, the investigators wrote, and further research is needed to examine the “mediators, moderators, and biological mechanisms of the sleep-ADHD link [in adolescents].”

While there are multiple potential pathways for this link, sleep problems may sometimes result in a cluster of behavioral and cognitive symptoms that are not true ADHD but that mimic the disorder, they noted.

The investigators also noted that approximately 67% of adolescents who had clinically relevant ADHD symptoms at baseline no longer had these symptoms at 1-year follow-up – a finding that “supports the [idea]” that ADHD symptoms with onset in adolescence may be transient or episodic rather than persistent.

The study was funded in part by the National Natural Science Foundation of China. The authors reported that they have no conflicts of interest.

SOURCE: Liu X et al. Sleep. 2019 Dec 2. doi: 10.1093/sleep/zsz294.

Insomnia, restless legs syndrome (RLS), and frequent snoring were significantly associated with subsequent ADHD symptoms in a large longitudinal study of adolescents in China.

Investigators twice assessed 7,072 middle and high school students participating in the larger longitudinal Shandong Adolescent Behavior & Health Cohort – in 2015 and 1 year later in 2016 – for sleep, mental health, psychosocial factors (using the self-administered Adolescent Health Questionnaire, or AHQ), and for ADHD symptoms (using the Youth Self-Report, or YSR, of the Achenbach Child Behavior Checklist).

At baseline, ADHD symptoms were reported by 7.6% of adolescents and were significantly correlated, after adjusting for adolescent and family covariates, with all the sleep variables studied: sleep duration of 7 hours or less per night, insomnia symptoms, poor sleep quality, RLS symptoms, frequent snorting, and hypnotic use, reported Xianchen Liu, MD, PhD, of Shandong (China) University, and coinvestigators. They noted a dose-response relationship between sleep duration and the odds of having ADHD symptoms.

At 1-year follow-up, 4.5% of the 6,531 participants who did not have ADHD symptoms at baseline now reported them. After adjustments for covariates, any insomnia (odds ratio, 1.48), difficulty initiating sleep (one of the insomnia symptoms) (OR, 2.09), RLS (OR, 1.47), and frequent snoring (OR, 2.30) at baseline were each significantly associated with development of incident ADHD symptoms and with ADHD severity at 1 year, they reported in Sleep.

“Given the fact that sleep disorders in adolescents are often underdiagnosed and untreated primarily in the primary care setting, our findings highlight that clinicians should assess and manage short sleep duration and sleep problems for effective treatment of ADHD in adolescents,” as well as for prevention, they wrote.

The AHQ includes questions that assess nocturnal sleep duration and sleep problems during the past month. The adolescent and family variables that were selected as covariates and controlled for include cigarette smoking, alcohol drinking, use of mental health services, chronic physical diseases, and parental education and occupation. Depression was also a covariate but was assessed through a different scale.

The YSR measures eight ADHD symptoms during the past 6 months on a 3-point scale (not true, somewhat or sometimes true, and very true or often true). The adolescent participants of this study were in grades 7, 8, and 10 at baseline. Their mean age at baseline was 15 years; half were male. They were part of the larger Shandong Adolescent and Behavioral Cohort, a longitudinal study of almost 12,000 adolescents.

Growing evidence has demonstrated a bidirectional relationship between sleep problems and ADHD symptoms in pediatric populations, the investigators wrote, and further research is needed to examine the “mediators, moderators, and biological mechanisms of the sleep-ADHD link [in adolescents].”

While there are multiple potential pathways for this link, sleep problems may sometimes result in a cluster of behavioral and cognitive symptoms that are not true ADHD but that mimic the disorder, they noted.

The investigators also noted that approximately 67% of adolescents who had clinically relevant ADHD symptoms at baseline no longer had these symptoms at 1-year follow-up – a finding that “supports the [idea]” that ADHD symptoms with onset in adolescence may be transient or episodic rather than persistent.

The study was funded in part by the National Natural Science Foundation of China. The authors reported that they have no conflicts of interest.

SOURCE: Liu X et al. Sleep. 2019 Dec 2. doi: 10.1093/sleep/zsz294.

Quality indicators of breast cancer care were successfully computed for more than 15,000 incident cases of breast cancer using electronic administrative databases in a project led by five regional oncology networks in Italy.

The project has shown that, despite some limitations in the use of administrative data to measure health care performance, “evaluating the quality of breast cancer care at a population level is possible,” investigators reported in the Journal of Oncology Practice.

The data obtained “from multiple administrative databases gathered in a real-world setting across five Italian regions” highlighted regional variations in breast cancer care and ways in which clinical guidelines were being overlooked, they wrote.

In doing so, the project confirmed that administrative data is “suitable” for measuring performance in health care and potentially useful for guiding quality improvement interventions. For instance, the project identified extensive use of blood tumor markers in breast cancer follow-up, wrote Valentina Guarneri, PhD, MD, of the University of Padova (Italy) and the Istituto Oncologico Veneto, also in Padova, and coauthors.

Oncologists and epidemiologists from the Italian regional oncology networks identified 46 clinically relevant indicators (9 structure indicators, 29 dealing with process, and 8 outcome indicators) by comparing pathways of care established by each network and identifying commonalities.

Of the 46 indicators, 22 were considered by the project leaders to be “potentially computable” from information retrieved by regional administrative databases. And of these 22 designed to be extractable, 9 (2 indicators of structure and 7 of process) were found to be actually evaluable for 15,342 cases of newly diagnosed invasive and/or in situ breast cancer diagnosed during 2016.

Blood tumor markers were tested in 44.2%-64.5% of patients in the first year after surgery – higher than the benchmark of 20% or less that was established to account for stage IV patients and other specific conditions in which markers might be indicated. National, international, and regional guidelines “discourage the use of blood tumor markers” in breast cancer follow-up, the investigators wrote.

The extensive use of these markers – observed across all five regions – is “a starting point to understanding how to improve clinical practice,” they added.

Other quality indicators that were evaluable included radiotherapy within 12 weeks after surgery if adjuvant chemotherapy is not administered (42%-83.8% in the project, compared with the benchmark of 90% or greater) and mammography 6-18 months after surgery (administered in 55.1%-72.6%, compared with the benchmark of 90% or greater), as well as the proportion of patients starting adjuvant systemic treatment (chemotherapy or endocrine therapy) within 60 days of surgery (for patients receiving systemic treatment).

To calculate the indicators, each regional cancer network used computerized sources of information including hospital discharge forms, outpatient records of diagnostic and therapeutic procedures, prescriptions of drugs reimbursed by the National Health Service in the hospital and outpatient settings, regional health registries, and the regional mortality registries.

All data used in the project came from regional repositories, which collect data from all National Health Service providers in the region, and not from single institutional repositories, the investigators noted.

More than half of the indicators expected to be assessable – but not found to be – were not computable as a result of data being unavailable (for example, pathology data) or incomplete, and as a result of data not being reliable for various reasons. The fact that examinations paid for directly by patients are not reported by the management systems of the National Health System was another complicating factor, they reported.

The authors disclosed funding and relationships with various pharmaceutical companies. The research was supported by the Periplo Association.

SOURCE: Guarneri V et al. J Oncol Pract. 2019 Dec 19. doi: 10.1200/JOP.19.00466.

Quality indicators of breast cancer care were successfully computed for more than 15,000 incident cases of breast cancer using electronic administrative databases in a project led by five regional oncology networks in Italy.

The project has shown that, despite some limitations in the use of administrative data to measure health care performance, “evaluating the quality of breast cancer care at a population level is possible,” investigators reported in the Journal of Oncology Practice.

The data obtained “from multiple administrative databases gathered in a real-world setting across five Italian regions” highlighted regional variations in breast cancer care and ways in which clinical guidelines were being overlooked, they wrote.

In doing so, the project confirmed that administrative data is “suitable” for measuring performance in health care and potentially useful for guiding quality improvement interventions. For instance, the project identified extensive use of blood tumor markers in breast cancer follow-up, wrote Valentina Guarneri, PhD, MD, of the University of Padova (Italy) and the Istituto Oncologico Veneto, also in Padova, and coauthors.

Oncologists and epidemiologists from the Italian regional oncology networks identified 46 clinically relevant indicators (9 structure indicators, 29 dealing with process, and 8 outcome indicators) by comparing pathways of care established by each network and identifying commonalities.

Of the 46 indicators, 22 were considered by the project leaders to be “potentially computable” from information retrieved by regional administrative databases. And of these 22 designed to be extractable, 9 (2 indicators of structure and 7 of process) were found to be actually evaluable for 15,342 cases of newly diagnosed invasive and/or in situ breast cancer diagnosed during 2016.

Blood tumor markers were tested in 44.2%-64.5% of patients in the first year after surgery – higher than the benchmark of 20% or less that was established to account for stage IV patients and other specific conditions in which markers might be indicated. National, international, and regional guidelines “discourage the use of blood tumor markers” in breast cancer follow-up, the investigators wrote.

The extensive use of these markers – observed across all five regions – is “a starting point to understanding how to improve clinical practice,” they added.

Other quality indicators that were evaluable included radiotherapy within 12 weeks after surgery if adjuvant chemotherapy is not administered (42%-83.8% in the project, compared with the benchmark of 90% or greater) and mammography 6-18 months after surgery (administered in 55.1%-72.6%, compared with the benchmark of 90% or greater), as well as the proportion of patients starting adjuvant systemic treatment (chemotherapy or endocrine therapy) within 60 days of surgery (for patients receiving systemic treatment).

To calculate the indicators, each regional cancer network used computerized sources of information including hospital discharge forms, outpatient records of diagnostic and therapeutic procedures, prescriptions of drugs reimbursed by the National Health Service in the hospital and outpatient settings, regional health registries, and the regional mortality registries.

All data used in the project came from regional repositories, which collect data from all National Health Service providers in the region, and not from single institutional repositories, the investigators noted.

More than half of the indicators expected to be assessable – but not found to be – were not computable as a result of data being unavailable (for example, pathology data) or incomplete, and as a result of data not being reliable for various reasons. The fact that examinations paid for directly by patients are not reported by the management systems of the National Health System was another complicating factor, they reported.

The authors disclosed funding and relationships with various pharmaceutical companies. The research was supported by the Periplo Association.

SOURCE: Guarneri V et al. J Oncol Pract. 2019 Dec 19. doi: 10.1200/JOP.19.00466.

Quality indicators of breast cancer care were successfully computed for more than 15,000 incident cases of breast cancer using electronic administrative databases in a project led by five regional oncology networks in Italy.

The project has shown that, despite some limitations in the use of administrative data to measure health care performance, “evaluating the quality of breast cancer care at a population level is possible,” investigators reported in the Journal of Oncology Practice.

The data obtained “from multiple administrative databases gathered in a real-world setting across five Italian regions” highlighted regional variations in breast cancer care and ways in which clinical guidelines were being overlooked, they wrote.

In doing so, the project confirmed that administrative data is “suitable” for measuring performance in health care and potentially useful for guiding quality improvement interventions. For instance, the project identified extensive use of blood tumor markers in breast cancer follow-up, wrote Valentina Guarneri, PhD, MD, of the University of Padova (Italy) and the Istituto Oncologico Veneto, also in Padova, and coauthors.

Oncologists and epidemiologists from the Italian regional oncology networks identified 46 clinically relevant indicators (9 structure indicators, 29 dealing with process, and 8 outcome indicators) by comparing pathways of care established by each network and identifying commonalities.

Of the 46 indicators, 22 were considered by the project leaders to be “potentially computable” from information retrieved by regional administrative databases. And of these 22 designed to be extractable, 9 (2 indicators of structure and 7 of process) were found to be actually evaluable for 15,342 cases of newly diagnosed invasive and/or in situ breast cancer diagnosed during 2016.

Blood tumor markers were tested in 44.2%-64.5% of patients in the first year after surgery – higher than the benchmark of 20% or less that was established to account for stage IV patients and other specific conditions in which markers might be indicated. National, international, and regional guidelines “discourage the use of blood tumor markers” in breast cancer follow-up, the investigators wrote.

The extensive use of these markers – observed across all five regions – is “a starting point to understanding how to improve clinical practice,” they added.

Other quality indicators that were evaluable included radiotherapy within 12 weeks after surgery if adjuvant chemotherapy is not administered (42%-83.8% in the project, compared with the benchmark of 90% or greater) and mammography 6-18 months after surgery (administered in 55.1%-72.6%, compared with the benchmark of 90% or greater), as well as the proportion of patients starting adjuvant systemic treatment (chemotherapy or endocrine therapy) within 60 days of surgery (for patients receiving systemic treatment).

To calculate the indicators, each regional cancer network used computerized sources of information including hospital discharge forms, outpatient records of diagnostic and therapeutic procedures, prescriptions of drugs reimbursed by the National Health Service in the hospital and outpatient settings, regional health registries, and the regional mortality registries.

All data used in the project came from regional repositories, which collect data from all National Health Service providers in the region, and not from single institutional repositories, the investigators noted.

More than half of the indicators expected to be assessable – but not found to be – were not computable as a result of data being unavailable (for example, pathology data) or incomplete, and as a result of data not being reliable for various reasons. The fact that examinations paid for directly by patients are not reported by the management systems of the National Health System was another complicating factor, they reported.

The authors disclosed funding and relationships with various pharmaceutical companies. The research was supported by the Periplo Association.

SOURCE: Guarneri V et al. J Oncol Pract. 2019 Dec 19. doi: 10.1200/JOP.19.00466.

WASHINGTON – Insulin is the preferred agent for type 2 diabetes in pregnant women, yet about a third of pregnancies still have an adverse outcome, according Kim Boggess, MD, who spoke at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“We are not where we need to be,” said Dr. Boggess, who is leading a trial that brings metformin, the first-line agent for type 2 diabetes outside of pregnancy, back into the picture for pregnant women – as an add-on to insulin.

It is an interesting twist, because pregnant women taking metformin for preexisting type 2 or gestational diabetes have been shown in some studies to require supplemental insulin, more than occasionally, to achieve target glycemic control.

This was the case in a small, randomized, controlled trial at Dr. Boggess’ institution, the University of North Carolina at Chapel Hill, in which 43% of pregnant women with type 2 diabetes who were assigned to metformin required supplemental insulin (Am J Perinatol. 2013;30[6]:483-90). The study also found, however, that women treated with metformin had significantly fewer episodes of hypoglycemia, compared with women using insulin (0% vs. 36%, respectively) and fewer reports of glucose values less than 60 mg/dL (7.1% vs. 50%).

“I don’t consider this [need for supplemental insulin] ‘metformin failure,’ because studies that use metformin as monotherapy and that [show some patients] ultimately requiring insulin support ... also show that these women need less insulin,” she said. “What’s the risk of insulin alone? Hypoglycemia. So using less insulin could be a good thing.”

Other research suggests there may be less maternal weight gain, less neonatal hypoglycemia, fewer neonatal complications, and improved maternal glycemic control in patients treated with metformin, alone or with add-on insulin, than with insulin alone. “We’re starting to get a sense in the literature that, at least in the [pregnant] population with type 2 diabetes, there may be a role for metformin,” said Dr. Boggess, professor and program director for maternal-fetal medicine at the university.

* This article was updated 1/2/2020.

WASHINGTON – Insulin is the preferred agent for type 2 diabetes in pregnant women, yet about a third of pregnancies still have an adverse outcome, according Kim Boggess, MD, who spoke at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“We are not where we need to be,” said Dr. Boggess, who is leading a trial that brings metformin, the first-line agent for type 2 diabetes outside of pregnancy, back into the picture for pregnant women – as an add-on to insulin.

It is an interesting twist, because pregnant women taking metformin for preexisting type 2 or gestational diabetes have been shown in some studies to require supplemental insulin, more than occasionally, to achieve target glycemic control.

This was the case in a small, randomized, controlled trial at Dr. Boggess’ institution, the University of North Carolina at Chapel Hill, in which 43% of pregnant women with type 2 diabetes who were assigned to metformin required supplemental insulin (Am J Perinatol. 2013;30[6]:483-90). The study also found, however, that women treated with metformin had significantly fewer episodes of hypoglycemia, compared with women using insulin (0% vs. 36%, respectively) and fewer reports of glucose values less than 60 mg/dL (7.1% vs. 50%).

“I don’t consider this [need for supplemental insulin] ‘metformin failure,’ because studies that use metformin as monotherapy and that [show some patients] ultimately requiring insulin support ... also show that these women need less insulin,” she said. “What’s the risk of insulin alone? Hypoglycemia. So using less insulin could be a good thing.”

Other research suggests there may be less maternal weight gain, less neonatal hypoglycemia, fewer neonatal complications, and improved maternal glycemic control in patients treated with metformin, alone or with add-on insulin, than with insulin alone. “We’re starting to get a sense in the literature that, at least in the [pregnant] population with type 2 diabetes, there may be a role for metformin,” said Dr. Boggess, professor and program director for maternal-fetal medicine at the university.

* This article was updated 1/2/2020.

WASHINGTON – Insulin is the preferred agent for type 2 diabetes in pregnant women, yet about a third of pregnancies still have an adverse outcome, according Kim Boggess, MD, who spoke at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“We are not where we need to be,” said Dr. Boggess, who is leading a trial that brings metformin, the first-line agent for type 2 diabetes outside of pregnancy, back into the picture for pregnant women – as an add-on to insulin.

It is an interesting twist, because pregnant women taking metformin for preexisting type 2 or gestational diabetes have been shown in some studies to require supplemental insulin, more than occasionally, to achieve target glycemic control.

This was the case in a small, randomized, controlled trial at Dr. Boggess’ institution, the University of North Carolina at Chapel Hill, in which 43% of pregnant women with type 2 diabetes who were assigned to metformin required supplemental insulin (Am J Perinatol. 2013;30[6]:483-90). The study also found, however, that women treated with metformin had significantly fewer episodes of hypoglycemia, compared with women using insulin (0% vs. 36%, respectively) and fewer reports of glucose values less than 60 mg/dL (7.1% vs. 50%).

“I don’t consider this [need for supplemental insulin] ‘metformin failure,’ because studies that use metformin as monotherapy and that [show some patients] ultimately requiring insulin support ... also show that these women need less insulin,” she said. “What’s the risk of insulin alone? Hypoglycemia. So using less insulin could be a good thing.”

Other research suggests there may be less maternal weight gain, less neonatal hypoglycemia, fewer neonatal complications, and improved maternal glycemic control in patients treated with metformin, alone or with add-on insulin, than with insulin alone. “We’re starting to get a sense in the literature that, at least in the [pregnant] population with type 2 diabetes, there may be a role for metformin,” said Dr. Boggess, professor and program director for maternal-fetal medicine at the university.

* This article was updated 1/2/2020.

A study that aimed to validate intratumoral ERCC1 levels as a predictive marker of platinum sensitivity in upper GI tumors failed to do so, but it did reach one firm conclusion: That platinum therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was superior in efficacy to a non–platinum-containing regimen of irinotecan and docetaxel (IT).

Approximately 200 untreated patients with unresectable advanced or metastatic HER2-negative adenocarcinoma of the esophagus, stomach or gastroesophageal junction were evaluated in the phase 2 study for mRNA expression of ERCC1 level and then randomized to either a platinum-containing or non–platinum-containing treatment arm with stratification for ERCC1 level (either low, with levels less than 1.7, or high, meaning 1.7 or more).

In retrospective studies of patients with gastric cancer, levels of gene expression of ERCC1 within the primary tumor have had a significant inverse relationship to response to platinum compounds and overall survival; low ERCC1 expression, in other words, has been associated with higher response rates and better survival. This inverse relationship of expression of the ERCC1 gene and platinum sensitivity has been demonstrated in colon cancer and other tumor types as well.

The problem is, approximately 86% of the patients in this phase 2, randomized study had ERCC1 values lower than 1.7 – many more than the investigators anticipated based on data from prior studies. (They expected a 50-50 distribution, roughly.) The predominance of low ERCC1 mRNA expression meant that evaluation of the ERCC1-high subgroup – and evaluation of interactive effects between ERCC1 expression and treatment type – was limited, said Syma Iqbal, MD, of the University of Southern California, Los Angeles, and coinvestigators.

“Unfortunately, this study did not validate or identify ERCC1 as a predictive marker of platinum sensitivity in upper GI tumors,” they wrote in the Journal of Clinical Oncology. However, “it did support the use of FOLFOX, a platinum-containing regimen, as a standard and superior frontline regimen, compared with the non–platinum-containing IT.”

Across all patients in the FOLFOX arm, the median progression-free survival (PFS) was significantly longer – 5.7 months versus 2.9 months in the IT arm (hazard ratio, 0.71; P = .02). The median overall survival was greater with FOLFOX as well, though this difference – 11.4 months versus 8.7 months – did not reach statistical significance. Similarly, in the ERCC1-low subgroup, the median PFS in patients receiving FOLFOX was statistically superior to IT – 5.9 months versus 2.8 months – and overall survival was better as well, though this latter difference was not statistically significant.

In the ERCC1-high subgroup, the median PFS was similar in the FOLFOX and IT arms (4.7 months vs. 5.3 months), the investigators noted. They plotted PFS within ERCC1 quartiles and found a consistent pattern of improved PFS in the FOLFOX versus IT arm, and “thus, little evidence of differential treatment effects on PFS across ERCC1 levels in this population.”

Regarding safety, the investigators noted, of 91 patients who completed protocol therapy in the FOLFOX arm and were analyzed for adverse events, 3 treatment-related deaths were reported and 9 additional patients experienced grade 4 adverse events. Of 98 patients assessed for adverse events in the IT arm, 3 treatment-related deaths were reported and 14 additional patients experienced grade 4 adverse events.

To be eligible for the study patients had to have a Zubrod performance status of 0-1 and been either treatment naive or have completed adjuvant therapy at least 180 days prior to enrollment.

The study was supported by the National Cancer Institute. Dr. Iqbal reported receiving honoraria from Celgene, Eisai, and F. Hoffmann–La Roche; serving a consulting or advisory role for F. Hoffmann–La Roche; serving on the speakers’ bureau for Celgene and Eisai; and receiving research funding from Bayer and Onyx.

SOURCE: Iqbal S et al. J Clin Oncol. 2019 Dec 9. doi: 10.1200/JCO.19.00925.

A study that aimed to validate intratumoral ERCC1 levels as a predictive marker of platinum sensitivity in upper GI tumors failed to do so, but it did reach one firm conclusion: That platinum therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was superior in efficacy to a non–platinum-containing regimen of irinotecan and docetaxel (IT).

Approximately 200 untreated patients with unresectable advanced or metastatic HER2-negative adenocarcinoma of the esophagus, stomach or gastroesophageal junction were evaluated in the phase 2 study for mRNA expression of ERCC1 level and then randomized to either a platinum-containing or non–platinum-containing treatment arm with stratification for ERCC1 level (either low, with levels less than 1.7, or high, meaning 1.7 or more).

In retrospective studies of patients with gastric cancer, levels of gene expression of ERCC1 within the primary tumor have had a significant inverse relationship to response to platinum compounds and overall survival; low ERCC1 expression, in other words, has been associated with higher response rates and better survival. This inverse relationship of expression of the ERCC1 gene and platinum sensitivity has been demonstrated in colon cancer and other tumor types as well.

The problem is, approximately 86% of the patients in this phase 2, randomized study had ERCC1 values lower than 1.7 – many more than the investigators anticipated based on data from prior studies. (They expected a 50-50 distribution, roughly.) The predominance of low ERCC1 mRNA expression meant that evaluation of the ERCC1-high subgroup – and evaluation of interactive effects between ERCC1 expression and treatment type – was limited, said Syma Iqbal, MD, of the University of Southern California, Los Angeles, and coinvestigators.

“Unfortunately, this study did not validate or identify ERCC1 as a predictive marker of platinum sensitivity in upper GI tumors,” they wrote in the Journal of Clinical Oncology. However, “it did support the use of FOLFOX, a platinum-containing regimen, as a standard and superior frontline regimen, compared with the non–platinum-containing IT.”

Across all patients in the FOLFOX arm, the median progression-free survival (PFS) was significantly longer – 5.7 months versus 2.9 months in the IT arm (hazard ratio, 0.71; P = .02). The median overall survival was greater with FOLFOX as well, though this difference – 11.4 months versus 8.7 months – did not reach statistical significance. Similarly, in the ERCC1-low subgroup, the median PFS in patients receiving FOLFOX was statistically superior to IT – 5.9 months versus 2.8 months – and overall survival was better as well, though this latter difference was not statistically significant.

In the ERCC1-high subgroup, the median PFS was similar in the FOLFOX and IT arms (4.7 months vs. 5.3 months), the investigators noted. They plotted PFS within ERCC1 quartiles and found a consistent pattern of improved PFS in the FOLFOX versus IT arm, and “thus, little evidence of differential treatment effects on PFS across ERCC1 levels in this population.”

Regarding safety, the investigators noted, of 91 patients who completed protocol therapy in the FOLFOX arm and were analyzed for adverse events, 3 treatment-related deaths were reported and 9 additional patients experienced grade 4 adverse events. Of 98 patients assessed for adverse events in the IT arm, 3 treatment-related deaths were reported and 14 additional patients experienced grade 4 adverse events.

To be eligible for the study patients had to have a Zubrod performance status of 0-1 and been either treatment naive or have completed adjuvant therapy at least 180 days prior to enrollment.

The study was supported by the National Cancer Institute. Dr. Iqbal reported receiving honoraria from Celgene, Eisai, and F. Hoffmann–La Roche; serving a consulting or advisory role for F. Hoffmann–La Roche; serving on the speakers’ bureau for Celgene and Eisai; and receiving research funding from Bayer and Onyx.

SOURCE: Iqbal S et al. J Clin Oncol. 2019 Dec 9. doi: 10.1200/JCO.19.00925.

A study that aimed to validate intratumoral ERCC1 levels as a predictive marker of platinum sensitivity in upper GI tumors failed to do so, but it did reach one firm conclusion: That platinum therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was superior in efficacy to a non–platinum-containing regimen of irinotecan and docetaxel (IT).

Approximately 200 untreated patients with unresectable advanced or metastatic HER2-negative adenocarcinoma of the esophagus, stomach or gastroesophageal junction were evaluated in the phase 2 study for mRNA expression of ERCC1 level and then randomized to either a platinum-containing or non–platinum-containing treatment arm with stratification for ERCC1 level (either low, with levels less than 1.7, or high, meaning 1.7 or more).

In retrospective studies of patients with gastric cancer, levels of gene expression of ERCC1 within the primary tumor have had a significant inverse relationship to response to platinum compounds and overall survival; low ERCC1 expression, in other words, has been associated with higher response rates and better survival. This inverse relationship of expression of the ERCC1 gene and platinum sensitivity has been demonstrated in colon cancer and other tumor types as well.

The problem is, approximately 86% of the patients in this phase 2, randomized study had ERCC1 values lower than 1.7 – many more than the investigators anticipated based on data from prior studies. (They expected a 50-50 distribution, roughly.) The predominance of low ERCC1 mRNA expression meant that evaluation of the ERCC1-high subgroup – and evaluation of interactive effects between ERCC1 expression and treatment type – was limited, said Syma Iqbal, MD, of the University of Southern California, Los Angeles, and coinvestigators.

“Unfortunately, this study did not validate or identify ERCC1 as a predictive marker of platinum sensitivity in upper GI tumors,” they wrote in the Journal of Clinical Oncology. However, “it did support the use of FOLFOX, a platinum-containing regimen, as a standard and superior frontline regimen, compared with the non–platinum-containing IT.”

Across all patients in the FOLFOX arm, the median progression-free survival (PFS) was significantly longer – 5.7 months versus 2.9 months in the IT arm (hazard ratio, 0.71; P = .02). The median overall survival was greater with FOLFOX as well, though this difference – 11.4 months versus 8.7 months – did not reach statistical significance. Similarly, in the ERCC1-low subgroup, the median PFS in patients receiving FOLFOX was statistically superior to IT – 5.9 months versus 2.8 months – and overall survival was better as well, though this latter difference was not statistically significant.

In the ERCC1-high subgroup, the median PFS was similar in the FOLFOX and IT arms (4.7 months vs. 5.3 months), the investigators noted. They plotted PFS within ERCC1 quartiles and found a consistent pattern of improved PFS in the FOLFOX versus IT arm, and “thus, little evidence of differential treatment effects on PFS across ERCC1 levels in this population.”

Regarding safety, the investigators noted, of 91 patients who completed protocol therapy in the FOLFOX arm and were analyzed for adverse events, 3 treatment-related deaths were reported and 9 additional patients experienced grade 4 adverse events. Of 98 patients assessed for adverse events in the IT arm, 3 treatment-related deaths were reported and 14 additional patients experienced grade 4 adverse events.

To be eligible for the study patients had to have a Zubrod performance status of 0-1 and been either treatment naive or have completed adjuvant therapy at least 180 days prior to enrollment.

The study was supported by the National Cancer Institute. Dr. Iqbal reported receiving honoraria from Celgene, Eisai, and F. Hoffmann–La Roche; serving a consulting or advisory role for F. Hoffmann–La Roche; serving on the speakers’ bureau for Celgene and Eisai; and receiving research funding from Bayer and Onyx.

SOURCE: Iqbal S et al. J Clin Oncol. 2019 Dec 9. doi: 10.1200/JCO.19.00925.

WASHINGTON – Metformin’s role in preventing or delaying the onset of type 2 diabetes in women with a history of gestational diabetes mellitus has been firmly established by the Diabetes Prevention Program (DPP) trial – most recently, by 15-year follow-up data reported this year – and the drug should be front and center for clinicians who hope to stave off the “remarkable” incidence of type 2 diabetes after GDM, Robert E. Ratner, MD, maintained at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

The DPP included “the single largest population of women with a history of GDM that’s been looked at in a randomized controlled trial,” and considering its multiethnic population, the trial offers a reliable representative sample to ponder today when evaluating long-term use of metformin after GDM, said Dr. Ratner, a principal investigator of the National Institutes of Health–sponsored DPP and the DPP Outcomes Study and a former chief scientific & medical officer for the American Diabetes Association.

The drug stacked up equally to lifestyle interventions among DPP participants who had a history of GDM, but it’s important to appreciate that these interventions were intensive and that metformin is inexpensive, well tolerated, and “has a long safety record,” he said.
 

Results of follow-up out to 15 years

Of the more than 3,000 men and women enrolled in the landmark DPP, conducted during 1996-2001, 350 were women with a documented history of GDM and over 1,400 were women who had deliveries but no history of GDM. All participants had impaired glucose tolerance – defined for the trial as having both a fasting plasma glucose value of 95-125 mg/dL and a 2-hour value of 140-199 mg/dL after a 75-g glucose load – and were randomized to placebo, metformin, or intensive lifestyle intervention.

Metformin therapy reduced the incidence of diabetes by approximately 50% in women with a history of GDM, compared with the placebo group – as did lifestyle – over 3 years. The number needed to treat to prevent one case of diabetes was five. Women without a history of GDM, on the other hand, saw only a 14% reduction with metformin when compared with placebo (and a 49% reduction with lifestyle).

“In women with a history of GDM ... one pill twice a day for $4 a month worked as well as intensive lifestyle [change],” Dr. Ratner said, referring to the initial GDM-specific analysis of DPP data published in 2008 (J Clin Endocrinol Metab. 2008;93[12]:4774-9).

In a 10-year postrandomization follow-up, published in 2015, both metformin and lifestyle continued to be equally effective for the GDM group, reducing the progression to diabetes by 40% and 35%, respectively (J Clin Endocrinol Metab. 2015;100:1646-53). The number needed to treat to prevent one case of diabetes was seven. (Among women without a history of GDM, metformin did not reduce progression to diabetes.)

A recent DPP Outcomes Study analysis of metformin’s impact on diabetes prevention at 15 years, moreover, showed a 41% risk reduction among women with a history of GDM (Diabetes Care. 2019;42[4]:601-8).
 

Advice on prescribing metformin prophylactically

Asked after his presentation whether women with a history of GDM and either an elevated fasting plasma glucose value or an elevated 2-hour oral glucose tolerance test (GTT) value – or neither of the two – would benefit from taking metformin, Dr. Ratner said that “we’re stuck with inclusion criteria of the DPP, in which they had to meet both criteria ... What I’d say, though, is that not everyone with a history of GDM needs to be on metformin prophylactically. But [for women who have] prediabetes as defined by the ADA, the cost-benefit analysis points toward metformin.”

And with respect to early initiation and long-term use of the drug, “I would have absolutely no qualms about medicating a 25-year-old who had developed GDM and who in the postpartum period has prediabetes,” Dr. Ratner said during an open discussion. “She’s actually at the highest risk for developing type 2 very early.”

Kim Boggess, MD, who also presented on long-term use of metformin after GDM, said in the discussion period that she is often quick to recommend metformin therapy to her patients who have an elevated fasting plasma glucose value in the postpartum period, even when a 75-g oral GTT has not yet been performed. (The ADA and the American College of Obstetricians and Gynecologists recommend completion of an oral GTT at 4-12 weeks postpartum after GDM.)

“I start them [on metformin] especially if they’ve had a cesarean section. Even 2, 3, 4 weeks of profound hyperglycemia could have potentially deleterious effects,” said Dr. Boggess, professor and maternal-fetal medicine program director at the University of North Carolina, Chapel Hill. “If someone comes in [shortly after] and looks like they have pristine control, then it might be worth stopping the metformin for 3-5 days (and retesting).”

Dr. Ratner said that, in this clinical scenario, he would first ensure that the fasting glucose value “is a true fasting glucose” and “if it’s substantially elevated – I’m talking 100, 105, 110 mg/dL – I’d start metformin, and I’m not even sure I’d do the GTT.” But, he advised, “if you’re going to do the GTT, I’d stop the metformin the day before.”

In her presentation, Dr. Boggess pointed out that metformin wasn’t shown to be superior to lifestyle interventions in the DPP for preventing progression to type 2 DM, and that some women are more motivated for intensive lifestyle change than others. The ADA recommends, in fact, that either metformin or lifestyle interventions be prescribed to women with a history of GDM who are found to have prediabetes.

What is needed, Dr. Boggess said, are more data on the effects of metformin on cardiovascular disease risk, as well as larger studies of metformin in the postpartum period “to help us determine the best dose.” Some research on metformin use in the postpartum period has reported gastrointestinal side effects and dissatisfaction, she noted.

Dr. Ratner said that metformin’s main drawback is the need for occasional testing of B₁₂ levels. Regarding weight loss and what was observed in the DPP, he said, women with a history of GDM who were randomized to intensive lifestyle interventions did not lose as much weight as women without a history of GDM.

Women who entered the DPP with a GDM history, he noted in his presentation, were essentially a “cohort of survivors.” They had an average age of 43 (compared with 52 years in the parous women without GDM) and a mean interval from the index GDM pregnancy of 11 years, which means that women with the highest risk of diabetes conversion were excluded, Dr. Ratner said.

Age was the only significantly different baseline characteristic between parous women with and without GDM, he noted. Women with a history of GDM who were randomized to placebo had a 71% higher incidence of diabetes than women without such a history – a striking natural history, Dr. Ratner said.

He and Dr. Boggess each reported that they have no financial or other interests that pose a conflict of interest.

WASHINGTON – Metformin’s role in preventing or delaying the onset of type 2 diabetes in women with a history of gestational diabetes mellitus has been firmly established by the Diabetes Prevention Program (DPP) trial – most recently, by 15-year follow-up data reported this year – and the drug should be front and center for clinicians who hope to stave off the “remarkable” incidence of type 2 diabetes after GDM, Robert E. Ratner, MD, maintained at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

The DPP included “the single largest population of women with a history of GDM that’s been looked at in a randomized controlled trial,” and considering its multiethnic population, the trial offers a reliable representative sample to ponder today when evaluating long-term use of metformin after GDM, said Dr. Ratner, a principal investigator of the National Institutes of Health–sponsored DPP and the DPP Outcomes Study and a former chief scientific & medical officer for the American Diabetes Association.

The drug stacked up equally to lifestyle interventions among DPP participants who had a history of GDM, but it’s important to appreciate that these interventions were intensive and that metformin is inexpensive, well tolerated, and “has a long safety record,” he said.
 

Results of follow-up out to 15 years

Of the more than 3,000 men and women enrolled in the landmark DPP, conducted during 1996-2001, 350 were women with a documented history of GDM and over 1,400 were women who had deliveries but no history of GDM. All participants had impaired glucose tolerance – defined for the trial as having both a fasting plasma glucose value of 95-125 mg/dL and a 2-hour value of 140-199 mg/dL after a 75-g glucose load – and were randomized to placebo, metformin, or intensive lifestyle intervention.

Metformin therapy reduced the incidence of diabetes by approximately 50% in women with a history of GDM, compared with the placebo group – as did lifestyle – over 3 years. The number needed to treat to prevent one case of diabetes was five. Women without a history of GDM, on the other hand, saw only a 14% reduction with metformin when compared with placebo (and a 49% reduction with lifestyle).

“In women with a history of GDM ... one pill twice a day for $4 a month worked as well as intensive lifestyle [change],” Dr. Ratner said, referring to the initial GDM-specific analysis of DPP data published in 2008 (J Clin Endocrinol Metab. 2008;93[12]:4774-9).

In a 10-year postrandomization follow-up, published in 2015, both metformin and lifestyle continued to be equally effective for the GDM group, reducing the progression to diabetes by 40% and 35%, respectively (J Clin Endocrinol Metab. 2015;100:1646-53). The number needed to treat to prevent one case of diabetes was seven. (Among women without a history of GDM, metformin did not reduce progression to diabetes.)

A recent DPP Outcomes Study analysis of metformin’s impact on diabetes prevention at 15 years, moreover, showed a 41% risk reduction among women with a history of GDM (Diabetes Care. 2019;42[4]:601-8).
 

Advice on prescribing metformin prophylactically

Asked after his presentation whether women with a history of GDM and either an elevated fasting plasma glucose value or an elevated 2-hour oral glucose tolerance test (GTT) value – or neither of the two – would benefit from taking metformin, Dr. Ratner said that “we’re stuck with inclusion criteria of the DPP, in which they had to meet both criteria ... What I’d say, though, is that not everyone with a history of GDM needs to be on metformin prophylactically. But [for women who have] prediabetes as defined by the ADA, the cost-benefit analysis points toward metformin.”

And with respect to early initiation and long-term use of the drug, “I would have absolutely no qualms about medicating a 25-year-old who had developed GDM and who in the postpartum period has prediabetes,” Dr. Ratner said during an open discussion. “She’s actually at the highest risk for developing type 2 very early.”

Kim Boggess, MD, who also presented on long-term use of metformin after GDM, said in the discussion period that she is often quick to recommend metformin therapy to her patients who have an elevated fasting plasma glucose value in the postpartum period, even when a 75-g oral GTT has not yet been performed. (The ADA and the American College of Obstetricians and Gynecologists recommend completion of an oral GTT at 4-12 weeks postpartum after GDM.)

“I start them [on metformin] especially if they’ve had a cesarean section. Even 2, 3, 4 weeks of profound hyperglycemia could have potentially deleterious effects,” said Dr. Boggess, professor and maternal-fetal medicine program director at the University of North Carolina, Chapel Hill. “If someone comes in [shortly after] and looks like they have pristine control, then it might be worth stopping the metformin for 3-5 days (and retesting).”

Dr. Ratner said that, in this clinical scenario, he would first ensure that the fasting glucose value “is a true fasting glucose” and “if it’s substantially elevated – I’m talking 100, 105, 110 mg/dL – I’d start metformin, and I’m not even sure I’d do the GTT.” But, he advised, “if you’re going to do the GTT, I’d stop the metformin the day before.”

In her presentation, Dr. Boggess pointed out that metformin wasn’t shown to be superior to lifestyle interventions in the DPP for preventing progression to type 2 DM, and that some women are more motivated for intensive lifestyle change than others. The ADA recommends, in fact, that either metformin or lifestyle interventions be prescribed to women with a history of GDM who are found to have prediabetes.

What is needed, Dr. Boggess said, are more data on the effects of metformin on cardiovascular disease risk, as well as larger studies of metformin in the postpartum period “to help us determine the best dose.” Some research on metformin use in the postpartum period has reported gastrointestinal side effects and dissatisfaction, she noted.

Dr. Ratner said that metformin’s main drawback is the need for occasional testing of B₁₂ levels. Regarding weight loss and what was observed in the DPP, he said, women with a history of GDM who were randomized to intensive lifestyle interventions did not lose as much weight as women without a history of GDM.

Women who entered the DPP with a GDM history, he noted in his presentation, were essentially a “cohort of survivors.” They had an average age of 43 (compared with 52 years in the parous women without GDM) and a mean interval from the index GDM pregnancy of 11 years, which means that women with the highest risk of diabetes conversion were excluded, Dr. Ratner said.

Age was the only significantly different baseline characteristic between parous women with and without GDM, he noted. Women with a history of GDM who were randomized to placebo had a 71% higher incidence of diabetes than women without such a history – a striking natural history, Dr. Ratner said.

He and Dr. Boggess each reported that they have no financial or other interests that pose a conflict of interest.

WASHINGTON – Metformin’s role in preventing or delaying the onset of type 2 diabetes in women with a history of gestational diabetes mellitus has been firmly established by the Diabetes Prevention Program (DPP) trial – most recently, by 15-year follow-up data reported this year – and the drug should be front and center for clinicians who hope to stave off the “remarkable” incidence of type 2 diabetes after GDM, Robert E. Ratner, MD, maintained at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

The DPP included “the single largest population of women with a history of GDM that’s been looked at in a randomized controlled trial,” and considering its multiethnic population, the trial offers a reliable representative sample to ponder today when evaluating long-term use of metformin after GDM, said Dr. Ratner, a principal investigator of the National Institutes of Health–sponsored DPP and the DPP Outcomes Study and a former chief scientific & medical officer for the American Diabetes Association.

The drug stacked up equally to lifestyle interventions among DPP participants who had a history of GDM, but it’s important to appreciate that these interventions were intensive and that metformin is inexpensive, well tolerated, and “has a long safety record,” he said.
 

Results of follow-up out to 15 years

Of the more than 3,000 men and women enrolled in the landmark DPP, conducted during 1996-2001, 350 were women with a documented history of GDM and over 1,400 were women who had deliveries but no history of GDM. All participants had impaired glucose tolerance – defined for the trial as having both a fasting plasma glucose value of 95-125 mg/dL and a 2-hour value of 140-199 mg/dL after a 75-g glucose load – and were randomized to placebo, metformin, or intensive lifestyle intervention.

Metformin therapy reduced the incidence of diabetes by approximately 50% in women with a history of GDM, compared with the placebo group – as did lifestyle – over 3 years. The number needed to treat to prevent one case of diabetes was five. Women without a history of GDM, on the other hand, saw only a 14% reduction with metformin when compared with placebo (and a 49% reduction with lifestyle).

“In women with a history of GDM ... one pill twice a day for $4 a month worked as well as intensive lifestyle [change],” Dr. Ratner said, referring to the initial GDM-specific analysis of DPP data published in 2008 (J Clin Endocrinol Metab. 2008;93[12]:4774-9).

In a 10-year postrandomization follow-up, published in 2015, both metformin and lifestyle continued to be equally effective for the GDM group, reducing the progression to diabetes by 40% and 35%, respectively (J Clin Endocrinol Metab. 2015;100:1646-53). The number needed to treat to prevent one case of diabetes was seven. (Among women without a history of GDM, metformin did not reduce progression to diabetes.)

A recent DPP Outcomes Study analysis of metformin’s impact on diabetes prevention at 15 years, moreover, showed a 41% risk reduction among women with a history of GDM (Diabetes Care. 2019;42[4]:601-8).
 

Advice on prescribing metformin prophylactically

Asked after his presentation whether women with a history of GDM and either an elevated fasting plasma glucose value or an elevated 2-hour oral glucose tolerance test (GTT) value – or neither of the two – would benefit from taking metformin, Dr. Ratner said that “we’re stuck with inclusion criteria of the DPP, in which they had to meet both criteria ... What I’d say, though, is that not everyone with a history of GDM needs to be on metformin prophylactically. But [for women who have] prediabetes as defined by the ADA, the cost-benefit analysis points toward metformin.”

And with respect to early initiation and long-term use of the drug, “I would have absolutely no qualms about medicating a 25-year-old who had developed GDM and who in the postpartum period has prediabetes,” Dr. Ratner said during an open discussion. “She’s actually at the highest risk for developing type 2 very early.”

Kim Boggess, MD, who also presented on long-term use of metformin after GDM, said in the discussion period that she is often quick to recommend metformin therapy to her patients who have an elevated fasting plasma glucose value in the postpartum period, even when a 75-g oral GTT has not yet been performed. (The ADA and the American College of Obstetricians and Gynecologists recommend completion of an oral GTT at 4-12 weeks postpartum after GDM.)

“I start them [on metformin] especially if they’ve had a cesarean section. Even 2, 3, 4 weeks of profound hyperglycemia could have potentially deleterious effects,” said Dr. Boggess, professor and maternal-fetal medicine program director at the University of North Carolina, Chapel Hill. “If someone comes in [shortly after] and looks like they have pristine control, then it might be worth stopping the metformin for 3-5 days (and retesting).”

Dr. Ratner said that, in this clinical scenario, he would first ensure that the fasting glucose value “is a true fasting glucose” and “if it’s substantially elevated – I’m talking 100, 105, 110 mg/dL – I’d start metformin, and I’m not even sure I’d do the GTT.” But, he advised, “if you’re going to do the GTT, I’d stop the metformin the day before.”

In her presentation, Dr. Boggess pointed out that metformin wasn’t shown to be superior to lifestyle interventions in the DPP for preventing progression to type 2 DM, and that some women are more motivated for intensive lifestyle change than others. The ADA recommends, in fact, that either metformin or lifestyle interventions be prescribed to women with a history of GDM who are found to have prediabetes.

What is needed, Dr. Boggess said, are more data on the effects of metformin on cardiovascular disease risk, as well as larger studies of metformin in the postpartum period “to help us determine the best dose.” Some research on metformin use in the postpartum period has reported gastrointestinal side effects and dissatisfaction, she noted.

Dr. Ratner said that metformin’s main drawback is the need for occasional testing of B₁₂ levels. Regarding weight loss and what was observed in the DPP, he said, women with a history of GDM who were randomized to intensive lifestyle interventions did not lose as much weight as women without a history of GDM.

Women who entered the DPP with a GDM history, he noted in his presentation, were essentially a “cohort of survivors.” They had an average age of 43 (compared with 52 years in the parous women without GDM) and a mean interval from the index GDM pregnancy of 11 years, which means that women with the highest risk of diabetes conversion were excluded, Dr. Ratner said.

Age was the only significantly different baseline characteristic between parous women with and without GDM, he noted. Women with a history of GDM who were randomized to placebo had a 71% higher incidence of diabetes than women without such a history – a striking natural history, Dr. Ratner said.

He and Dr. Boggess each reported that they have no financial or other interests that pose a conflict of interest.

WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

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Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And adverse pregnancy outcomes can have long-lasting residual effects.”

Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.

An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.

The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).

HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.

Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).

Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.

Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”

The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
 

Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data

The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.

Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.

An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).

The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.

Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.

Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.

“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”

Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
 

Racial/ethnic disparities, postpartum care

Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.

Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).

On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.

At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.

A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).

Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.

A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).

“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”

For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.

Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.

WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

FatCamera/E+/Getty Images

Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And adverse pregnancy outcomes can have long-lasting residual effects.”

Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.

An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.

The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).

HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.

Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).

Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.

Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”

The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
 

Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data

The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.

Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.

An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).

The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.

Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.

Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.

“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”

Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
 

Racial/ethnic disparities, postpartum care

Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.

Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).

On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.

At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.

A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).

Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.

A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).

“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”

For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.

Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.

WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

FatCamera/E+/Getty Images

Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And adverse pregnancy outcomes can have long-lasting residual effects.”

Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.

An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.

The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).

HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.

Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).

Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.

Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”

The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
 

Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data

The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.

Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.

An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).

The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.

Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.

Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.

“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”

Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
 

Racial/ethnic disparities, postpartum care

Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.

Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).

On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.

At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.

A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).

Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.

A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).

“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”

For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.

Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.