Tag Archive for: congenital heart disease

flow chart of pulse ox study

Newborn screening for critical congenital heart disease serves as vital safety net

One of the nation’s longest-running newborn screening programs for critical congenital heart disease (CCHD) finds that screening continues to serve as a necessary tool to help identify every child with CCHD — even in states where the majority of babies are diagnosed before birth.

The screening program study findings were published in Pediatrics. The data is some of the first to provide long-term evidence for using pulse oximetry to screen newborns for critical congenital heart disease 24 hours after birth. This screening test was added to the Department of Health and Human Services Recommended Uniform Screening Panel in 2011 and is now required in all 50 states.

“This study reinforces why pulse oximetry screening for CCHD is an important tool in our arsenal to identify and treat critical congenital heart disease, and other conditions that affect the flow of oxygen throughout the body, as soon as possible,” says Bryanna Schwarz, M.D., a cardiology fellow at Children’s National Hospital and lead author. “We know that prompt, early detection and swift intervention is crucial to positive long-term outcomes for these kids.”

The team looked at the data and outcomes for all babies born throughout eight years at Holy Cross Hospital in suburban Maryland, one of the first community birthing hospitals in the country to routinely perform the screening. Over the eight-year period, 64,780 newborns were screened at the site. Of those:

  • Thirty-one failed the screening, and every baby who failed was found to have congenital heart disease or another important medical condition.
  • Twelve of the failures (38.7%) were babies with critical congenital heart disease who were not previously identified by prenatal detection.
  • Nine others (29%) had a non-critical congenital heart condition.
  • Ten additional babies (32%) had a non-cardiac condition.

The authors note that the 12 newborns with CCHD identified through pulse oximetry screening are noteworthy because they represent critical congenital heart disease cases that are not found before birth in the state of Maryland, where rates of prenatal diagnosis are relatively high. The finding indicates that screening after birth continues to play a critical role in ensuring every baby with critical congenital heart disease is identified and treated as quickly as possible.

“Holy Cross Health and Children’s National have had a decades-long relationship, as we mutually care for women and infants throughout the region. With Children’s National having the U.S. News & World Report #1 ranking Neonatology service in the nation and Holy Cross Hospital being among the top 10 hospitals for the number of babies delivered each year, we are honored to be leading together the great work that is being done to serve our health care community,” says Ann Burke, M.D., vice president of Medical Affairs at Holy Cross Hospital. “We are committed to continuing to do our part to care for women and infants, as well as contribute to the national landscape for neonatal care. We are delighted in the outcomes we have seen and look forward to continued advancement.”

In this study, infants who did not have critical congenital heart disease were considered “false positives” for CCHD. Still, every one of them was found to have another underlying condition, including non-critical congenital heart disease or non-cardiac conditions (such as sepsis and pneumonia) that would also require monitoring and treatment.

The researchers also ran a projection of recently recommended updates to the screening protocol, which include removing a second re-screen after a newborn fails the initial test, to look at whether removing the second rescreen to verify results would decrease accuracy. While the false positive rate did increase slightly from .03% to .04%, eliminating a second re-screen allowed the newborns who were identified to receive crucial care sooner without having to wait an additional hour for one more test to verify their condition.

“It’s time to stop asking if pulse oximetry is a necessary tool to detect critical heart disease in babies,” says Gerard Martin, M.D., M.A.C.C., senior author of the study and C.R. Beyda Professor of Cardiology at Children’s National Hospital. “Our focus now should be on making evidence-based refinements to the screening protocol based on collected data to ensure the process is simple, can be performed consistently and provides as accurate results as possible.”

Crowded makeshift buildings of a shantytown

Calling greater attention to sub-Saharan Africa’s pressing challenges in pediatric cardiac care

Crowded makeshift buildings of a shantytown

Sub-Saharan Africa has only 0.19 pediatric cardiac surgeons per million children — nowhere near enough surgeons to care for all the pediatric congenital heart disease and acquired heart disease present in the people who live there.

A literature review in the journal Current Opinion in Cardiology draws further attention to the pressing needs for better pediatric cardiac care in regions of the world where the population continues to grow, but the development of specialty care for children continues to lag. The article focuses specifically on sub-Saharan Africa.

“If 40% of live births occur in Africa by 2050 as the projections suggest, congenital heart disease may well become the most important contributor to infant mortality rate in sub-Saharan Africa in the next three decades,” stated the authors, including Annette Ansong, M.D., who recently joined Children’s National Hospital as medical director of outpatient cardiology.

As highlighted previously by other authors within the Global Health Initiative at Children’s National and through the work of the American Heart Association, the region’s needs are already significant in  tackling the impacts of existing congenital heart disease and rheumatic heart disease. Rheumatic heart disease is a devastating long-term outcome of rheumatic fever caused by untreated streptococcus infections.

Annette Ansong

“If 40% of live births occur in Africa by 2050 as the projections suggest, congenital heart disease may well become the most important contributor to infant mortality rate in sub-Saharan Africa in the next three decades,” stated the authors, including Annette Ansong, M.D., who recently joined Children’s National Hospital as medical director of outpatient cardiology.

Dr. Ansong and colleagues reiterate the point that today, “whereas one cardiac center caters to approximately 120,000 people in North America, 33 million people in sub-Saharan Africa must depend on one center for care.” They also note that this region of Africa has only 0.19 pediatric cardiac surgeons per million children compared with more than 58 times as many in North America.

Changing the trajectory of pediatric cardiac care in sub-Saharan Africa will take motivation on several fronts, the authors write. Dedication to early detection and intervention (medical or surgical), an emphasis on building an in-country pipeline of human resources and skills’ sets are needed to tackle the increasing numbers of children requiring this specialty care. Political will and better financial resources can also support the training and development of centers that specialize in these capabilities.

pregnant hispanic woman

Significant health disparities in detection of critical congenital heart disease

pregnant hispanic woman

Mothers who are Hispanic or who come from rural or low socioeconomic status neighborhoods are less likely to have their child’s critical heart condition diagnosed before birth, according to a new study in the journal Circulation.

Mothers who are Hispanic or who come from rural or low socioeconomic status neighborhoods are less likely to have their child’s critical heart condition diagnosed before birth, according to a new study in the journal Circulation.

This is the largest and most geographically diverse study of these challenges to date. The study compared patient data of more than 1,800 children from the United State and Canada diagnosed with two of the most common, and the most serious, critical congenital heart defects: hypoplastic left heart syndrome (HLHS), when the left side of the heart is not developed completely, and transposition of the great arteries (TGA), when the two main arteries that carry blood away from the heart are reversed.

“The earlier we diagnose a heart defect, especially a serious one such as HLHS or TGA, the sooner we can make a plan for how to safely deliver the infant and reduce the impacts of that heart defect on the rest of the body,” says Anita Krishnan, M.D., first author and cardiologist at Children’s National Hospital. “Early detection and diagnosis of these conditions is crucial to ensuring the best possible outcome for the child, especially in protecting the brain.”

Even when infants’ heart defects were detected before birth, babies from neighborhoods with lower socioeconomic status were detected later in gestation than others.

“The COVID-19 pandemic has brought the idea of significant disparities in health care to the forefront of our national attention,” says Dr. Krishnan. “Even though many health care providers have seen these inequities firsthand in their own clinical experience, it was still surprising to see the strength of the association between socioeconomic position and the care available to mothers.”

In both the United States and Canada, expectant mothers are first screened as part of routine prenatal care in the first trimester for early signs of congenital heart defects and other genetic disorders via blood screen and ultrasound. In the second trimester, a comprehensive ultrasound evaluation for structural anomalies is routine. If any issues are detected, the mother is referred for a fetal echocardiogram and counseling.

The authors suggest that decreased linkages between neighborhoods and people identified in the study and subspecialists could contribute to the disparities found in the study.

“Prenatal detection rates may improve if we are able to leverage outreach and telehealth to strengthen the relationships between these specialties and the groups we identified in the study,” Dr. Krishnan says.

The study included a total of 1,862 patients, including 1,171 patients with HLHS (91.8% prenatally diagnosed) and 691 with TGA (58% prenatally diagnosed). The study group included prenatally diagnosed fetuses with HLHS or TGA and postnatally diagnosed infants less than two months old with HLHS or TGA. Data was collected from institutions participating in the Fetal Heart Society, a non-profit 501(c) multicenter research collaborative with a mission to advance the field of fetal cardiovascular care and science. Mary Donofrio, M.D., director of Prenatal Cardiology at Children’s National, is society president and served as a senior author on this study.

Read the AHA’s press release: Prenatal detection of heart defects lower in rural, poor areas and among Hispanic women.

little girl at the dentist

Limit antibiotic use before dental procedures to high-risk heart patients, says AHA

little girl at the dentist

A new scientific statement from the American Heart Association (AHA) says that good oral hygiene and regular dental care are the most important ways to reduce the risk of a heart infection called infective endocarditis (IE) caused by bacteria in the mouth.

A new scientific statement from the American Heart Association (AHA) says that good oral hygiene and regular dental care are the most important ways to reduce the risk of a heart infection called infective endocarditis (IE) caused by bacteria in the mouth. The statement was published in Circulation, the AHA’s flagship journal.

This statement addresses the impact of the major changes made in the 2007 AHA infective endocarditis (IE) guidelines that limited antibiotic prophylaxis (AP) prior to dental procedures to cardiac conditions at highest risk of complications from endocarditis by focusing on the following:

  • What was the acceptance of and compliance with the 2007 recommendations?
  • Was there an increased incidence of viridians group streptococci (VGS) infective endocarditis (IE)?
  • Were the recommendations from the guideline valid and should they be revised?

While the statement speaks to all types of heart disease, one area of particular interest in congenital heart disease was highlighted by statement co-author Craig Sable, M.D., F.A.H.A., associate division chief of Cardiology at Children’s National Hospital.

He noted that the statement specifies that children and adult congenital heart patients undergoing pulmonary valve replacement can be at higher risk for IE. The most significant risk factor for IE is the material the valve is made from, regardless of whether it is placed by surgery or catheterization.

Read more about this statement from the AHA

Watch AHA’s video explaining the statement, which features Dr. Sable.

chest x-ray showing pacemaker

Medical device pitch competition focuses on pediatric electrophysiology devices for CHD

chest x-ray showing pacemaker

While the last decade brought great advances in technologies that improve the care of adult arrhythmias, pediatric patients have been left behind, with only five devices approved for use in children in the same period.

Congenital heart disease (CHD) affects six out of 1,000 babies born in the U.S. each year and is often complicated by arrhythmias, a condition where the heart beats too rapidly, too slowly or irregularly due to a misfiring of the body’s electrical impulses. While the last decade brought great advances in technologies that improve the care of adult arrhythmias, pediatric patients have been left behind, with only five devices approved for use in children in the same period. As a result, pediatric specialists are often using off-label or improvised devices to treat pediatric arrhythmias, including the smallest newborns.

Recognizing this unmet need, the National Capital Consortium for Pediatric Device Innovation (NCC-PDI), in collaboration with MedTech Innovator, is accepting applications through April 12, 2021, for its annual “Make Your Medical Device Pitch for Kids!” competition. This year’s competition focuses on innovations in pediatric devices that treat CHD, with an emphasis on electrophysiology devices such as pacemaker systems, ablation catheters, wearable monitoring devices and related technologies that address arrhythmias in children.

“NCC-PDI was created, with the support of the Food and Drug Administration (FDA), to seek out and address significant unmet needs in pediatric medical devices,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “We have learned from the experts that pediatric-specific technologies for treating arrhythmias would be a game changer in the care of their patients, so we are focusing our competition and grant awards on this opportunity.”

Kolaleh-Eskandanian

“We have learned from the experts that pediatric-specific technologies for treating arrhythmias would be a game changer in the care of their patients, so we are focusing our competition and grant awards on this opportunity,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI.

Using a virtual format, semi-finalists chosen from all submissions will make their first pitch on May 12, 2021. Up to 10 finalists selected from this event earn participation in a special pediatric-focused track of the MedTech Innovator accelerator program, the largest medtech accelerator in the world, beginning in June 2021. These innovators then participate in the pediatric competition finals in September 2021 where judges will award up to $150,000 in FDA-sponsored grants to the devices selected as most impactful and commercially viable.

How significant is the need for pediatric devices to address arrhythmias? In a recent survey of members conducted by the Pediatric and Congenital Electrophysiology Society (PACES), the vast majority (96%) said they believe there is a deficiency in devices available to serve the needs of pediatric patients. Conducted with the U.S.FDA, the survey also asked respondents to identify the biggest unmet need, which physicians identified as cardiovascular implantable electronic devices that are smaller, have better battery life and have pediatric-specific algorithms. Specifically, a leadless pacemaker designed for pediatric care was consistently on the most-wanted list.

NCC-PDI is one of five members in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children, which lags significantly behind the advancement of adult medical devices. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital and the A. James Clark School of Engineering at the University of Maryland with support from partners MedTech Innovator, BioHealth Innovation and design firm Archimedic.

Eskandanian says that enhancing access to resources for pediatric innovators is also one of the aims of the Children’s National Research & Innovation Campus, a first-of-its-kind focused on pediatric health care innovation, with the first phase currently open on the former Walter Reed Army Medical Center campus in Washington, D.C. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on-site incubator Johnson and Johnson Innovation – JLABS, the campus provides a rich ecosystem of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.

 

Dr. Martin interacts with a patient

Gerard Martin, M.D., F.A.C.C, recognized with American College of Cardiology top honor

Dr. Martin interacts with a patient

Gerard Martin, M.D., F.A.C.C., has been awarded the 2021 Master of the ACC Award by the American College of Cardiology in honor of contributions to the cardiovascular profession.

Gerard Martin, M.D., F.A.C.C., has been awarded the 2021 Master of the ACC Award by the American College of Cardiology in honor of contributions to the cardiovascular profession. Dr. Martin will be recognized for these achievements along with all 2021 Distinguished Award winners during Convocation at the hybrid 70th Annual Scientific Session & Expo taking place May 15-17, 2021 in Atlanta and virtually.

“Dr. Martin has made lasting contributions to the field of cardiovascular medicine through his dedication to improving cardiovascular health and enhancing patient care,” said ACC President Athena Poppas, MD, F.A.C.C. “It is an honor to be able to recognize Dr. Martin with the Master of the ACC Award and celebrate his tremendous achievements in the cardiovascular field.”

The Master of the ACC (MACC) Award recognizes and honors fellows of the American College of Cardiology who have consistently contributed to the goals and programs of the college and who have provided leadership in important college activities. MACC designees have been members of the college for at least 15 years and have served with distinction and provided leadership on various college programs and committees. Only four distinguished members of the American College of Cardiology are selected for this honor each year.

Dr. Martin is a cardiologist at Children’s National Hospital, where he has been in practice since 1986. He founded the Children’s National Heart Institute in 2004 and was named the C. Richard Beyda Professor of Cardiology in 2007. He has published over 150 peer-reviewed manuscripts, book chapters and invited publications and has presented abstracts at over 125 meetings. Dr. Martin is an invited lecturer who has traveled to over 200 meetings, hospitals and universities within the U.S. and around the world.

Dr. Martin is an advocate for congenital heart disease (CHD) efforts nationally and internationally. He played integral roles in the development and dissemination of critical congenital heart disease screening in using pulse oximetry — a practice that is now standard for all newborns across the United States. He also has volunteered on countless medical missions to developing countries.

Dr. Martin is board-certified in pediatric cardiology, a fellow of the American Academy of Pediatrics and the American College of Cardiology and is also a member of the Society for Pediatric Research and the American Board of Pediatrics.

Nineteen Distinguished Awards will be presented at ACC.21 this year, each recognizing an individual who has made outstanding contributions to the field of cardiovascular medicine. Recipients are nominated by their peers and then selected by the American College of Cardiology Awards Committee.

The American College of Cardiology envisions a world where innovation and knowledge optimize cardiovascular care and outcomes. As the professional home for the entire cardiovascular care team, the mission of the College and its 54,000 members is to transform cardiovascular care and to improve heart health. The ACC bestows credentials upon cardiovascular professionals who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. The College also provides professional medical education, disseminates cardiovascular research through its world-renowned JACC Journals, operates national registries to measure and improve care, and offers cardiovascular accreditation to hospitals and institutions. For more, visit acc.org.

illustration of brain with stem cells

Innovative phase 1 trial to protect brains of infants with CHD during and after surgery

A novel phase 1 trial looking at how best to optimize brain development of babies with congenital heart disease (CHD) is currently underway at Children’s National Hospital.

Children with CHD sometimes demonstrate delay in the development of cognitive and motor skills. This can be a result of multiple factors including altered prenatal oxygen delivery, brain blood flow and genetic factors associated with surgery including exposure to cardiopulmonary bypass, also known as the heart lung machine.

This phase 1 trial is the first to deliver mesenchymal stromal cells from bone marrow manufactured in a lab (BM-MSC) into infants already undergoing cardiac surgery via cardiopulmonary bypass. The hypothesis is that by directly infusing the MSCs into the blood flow to the brain, more MSCs quickly and efficiently reach the subventricular zone and other areas of the brain that are prone to inflammation. The trial is open to eligible patients ages newborn to six months of age.


Learn more in this overview video.

The trial is part of a $2.5 million, three-year grant from the National Institutes of Health (NIH) led by Richard Jonas, M.D.Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D.. The project involves collaboration between the Prenatal Cardiology program of Children’s National Heart Institute, the Center for Cancer and Immunology Research, the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

“NIH supported studies in our laboratory have shown that MSC therapy may be extremely helpful in improving brain development in animal models after cardiac surgery,” says Dr. Ishibashi. “MSC infusion can help reduce inflammation including prolonged microglia activation that can occur during surgery that involves the heart lung machine.”

Staff from the Cellular Therapy Laboratory, led by director Patrick Hanley, Ph.D., manufactured the BM-MSC at the Center for Cancer and Immunology Research, led by Dr. Bollard.

The phase 1 safety study will set the stage for a phase 2 effectiveness trial of this highly innovative MSC treatment aimed at reducing brain damage, minimizing neurodevelopmental disabilities and improving the postoperative course in children with CHD. The resulting improvement in developmental outcome and lessened behavioral impairment will be of enormous benefit to individuals with CHD.

For more information about this new treatment, contact the clinical research team: Gil Wernovsky, M.D., Shriprasad Deshpande, M.D., Maria Fortiz.

Mended Little Hearts’ Volunteer of the Year, Maryann Mayhood, and her son Joseph delivered the Hospital of the Year award to Dr. Donofrio in November 2020.

Mended Little Hearts names Children’s National Hospital as ‘Hospital of the Year’

Mended Little Hearts’ Volunteer of the Year, Maryann Mayhood, and her son Joseph delivered the Hospital of the Year award to Dr. Donofrio in November 2020.

Mended Little Hearts’ Volunteer of the Year, Maryann Mayhood, and her son Joseph delivered the Hospital of the Year award to Dr. Donofrio in November 2020.

Children’s National Hospital was named Hospital of the Year by Mended Little Hearts, one of the top organizations in the U.S. for patients with congenital heart disease and their families. Children’s National was selected as the Hospital of the Year across all divisions of the Mended Little Hearts national network and the Washington, D.C. region. The hospital is recognized with the award for its efforts to empower Mended Little Hearts volunteers and make it possible for the group to provide peer support and education to children and adults with congenital heart disease, their families and the surrounding communities.

“It’s an honor to be recognized as a champion by a group like Mended Little Hearts that truly represents the voices and needs of patients and their families. We embrace and encourage their work because we know that providing the best care for children and their families goes beyond simply outstanding clinical service,” says Charles Berul, M.D., chief of Cardiology and co-director of the Children’s National Heart Institute. “We are privileged to have a group of dedicated volunteers from Mended Little Hearts who are willing to work side-by-side with our team to share peer support, education and guidance for our families at Children’s National.”

Though many in-person activities are currently on hold or held virtually for the health and safety of everyone during the COVID-19 public health emergency, Children’s National and Mended Little Hearts continue to coordinate closely together to support families as much as possible by making virtual connections and via the Mended Little Hearts “Bravery Bags,” which are given to every family and include personal essentials for a hospital stay as well as important guidance such as questions to ask care providers and how to seek more information about the care plan.

For the last few years, the hospital has also provided space within the hospital for the group to host family breakfasts and other events, making sure families have access to the information and support items they need during a hospital stay. They are also welcomed to many of the hospital’s annual events for adults and children with congenital heart disease and their families, to connect and share experiences.

“We are honored to recognize Children’s National Hospital for the outstanding work they have done to support heart patients and their families,” said Mended Hearts Inc. President Ron Manriquez. “That they have won this award is proof of the deep commitment they have to their members, families and the community at large. We are grateful for the work they do to support the Mended Little Hearts mission.”

Mended Little Hearts and its parent group, Mended Hearts, are organizations that inspire hope and seek to improve the quality of life for heart patients and their families through ongoing peer-to-peer support.

a telehealth video visit with a patient family

Steady rates of patient satisfaction, reimbursement for cardiac telehealth during COVID-19

a telehealth video visit with a patient family

In the first two weeks of COVID-19’s major impact on the U.S., Children’s National Hospital moved most of its subspecialty in-person day-to-day clinics to virtual care. Children’s National Heart Institute was one of the first divisions to offer telehealth visits — in part because the team was an early adopter of telehealth in cardiology for both physician-to-physician consultations and direct-to-patient care, and stood poised to widely implement it.

A poster presentation at the American Heart Association Scientific Sessions 2020 quantified how the rapid transition to direct-to-consumer telehealth services impacted families with children who have congenital heart disease. The findings were presented by first author Kristine Mehrtens, M.S., B.S.N., R.N., C.P.N., clinical manager for the Heart Institute’s Ambulatory Services.

The team found that though in-person cardiology visits decreased during the COVID-19 pandemic, direct-to-patient telehealth visits were able to partially compensate for the sudden drop.

Additionally, payer reimbursement rates for these direct-to-consumer telehealth visits were similar to in-person clinic visits.

”This is exciting as prior to COVID-19  we have seen a lower reimbursement rates for these cardiology direct-to-consumer telehealth visits compared to in-person cardiology clinic visits,” said Ashraf S. Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who has utilized direct-to-consumer telehealth visits since 2016 and is a senior author on the new study.

Patient satisfaction scores for care providers, including the likelihood of recommending a care provider from Children’s National Hospital, was the same for telehealth follow-up visits as it was for in-person clinic visits before the pandemic.

“As a multidisciplinary team, we agreed that diagnostic studies such as echocardiograms were important to include with follow-up visits,” says Mehrtens. “Together we developed a strategy to ensure we could meet the needs of the patients and also safely conduct in-person visits when necessary.”

Why is this important?

The pandemic and the resulting temporary halt to in-person, non-urgent/emergent visits earlier this year put the most vulnerable people with congenital heart disease at high risk for complications or worsening of their existing heart disease because they are unable to follow the recommended schedule for follow-ups.

The readiness of the Children’s Heart Institute team to quickly move to a telehealth platform successfully bridged the gap between in-person visits for some patients, allowing cardiology surveillance to continue safely.

“I am proud of our team of physicians and advanced care providers,” Harahsheh concludes. “We went from three providers (8%) pre-COVID 19 to 31 (79%) providers offering direct-to-consumer telehealth visits during the pandemic.”

What’s next?

Building on previous, smaller studies of telehealth before the pandemic began, the team will continue to conduct research to assess the safety and efficacy of these telehealth visits over time. The increase in patients who are continuing to see their providers for routine follow-ups via telehealth will allow a larger sample for effective study of this care model.

American Heart Association Scientific Sessions 2020
Impact of Telemedicine on Pediatric Cardiac Center’s Ambulatory Response to the 2019 Novel Coronavirus Disease (covid-19) Pandemic
P1692
9:00am – 10:00am
Fri, Nov 13  (CST)

Read additional news stories about cardiology telehealth:

newborn in ICU

Cardiac technology advances show promise for kids but only if right-sized

newborn in ICU

“Smaller patients, and those with congenital heart disease, can benefit from minimally-invasive methods of delivering pacemakers and defibrillators without the need for open-chest surgery,” says Charles Berul, M.D.

How to address the growing need for child-sized pacemakers and defibrillators, and finding better surgical techniques to place them, is the topic of an invited session called The Future is Now (or Coming Soon): Updates on New Technologies in Congenital Heart Care at the 2020 American Heart Association Scientific Sessions.

“Smaller patients, and those with congenital heart disease, can benefit from minimally-invasive methods of delivering pacemakers and defibrillators without the need for open-chest surgery,” says Charles Berul, M.D., co-director of the Children’s National Heart Institute and chief of Cardiology at Children’s National Hospital, who presented at the session.

“This unmet need can only be met by innovative pediatric research, geared towards miniaturization technologies for use in the smallest of children,” he says.

His presentation focused on the devices and approaches that have caught the attention of pediatric cardiology, such as pacemakers and subcutaneous defibrillators designed without lead wires, as well as less-invasive surgical approaches that may reduce recovery time for children with congenital heart disease who require these assist devices.

Using them in kids comes with added challenges, however. Often pediatric cardiologists have to be creative in how to make them work for smaller patients, Dr. Berul notes. This reiterates the important point that simply applying an adult technology to a child isn’t the right approach. The subcutaneous defibrillator, for example, is still pretty large for a child’s body. Some studies also show these devices may not be as accurate in children as in adults.

Investigators in the Sheikh Zayed Institute working together with the cardiologists at Children’s National Hospital are focused on product development and commercialization of tools and techniques to allow percutaneous minimally-invasive placement of devices, taking advantage of the newest devices and surgical techniques as they develop.

In his presentation, Dr. Berul stressed that as the technology for adults advances, it creates an opportunity for pediatric cardiology, but only if the devices, and the techniques to place them, are specifically redesigned for pediatric application.

American Heart Association Scientific Sessions 2020
The Future is Now (or Coming Soon): Updates on New Technologies in Congenital Heart Care – On Demand Session
CH.CVS.715
9:00am – 10:00am
Fri, Nov 13  (CST)

Yves d'Udekem

Yves d’Udekem, M.D., Ph.D., joins Children’s National as Cardiac Surgery Chief

Yves d’Udekem, M.D., Ph.D., a pediatric cardiac surgeon recognized for expertise in the most challenging procedures for newborns and children with complex congenital heart disease, has joined Children’s National Hospital as chief of Cardiac Surgery and co-director of the Children’s National Heart Institute.

“Children’s National has the cases and expertise I was looking for,” he says. “Even better, when you visit it’s clear that the entire Heart Institute team is energetic about working together. They’re constantly seeking better ways to do this work and improve how we care for children and their families.”

Dr. d’Udekem comes to Children’s National from The Royal Children’s Hospital in Melbourne, Australia, an institution that has led the advancement of congenital heart disease care and research, performing more than 500 surgical procedures with cardiopulmonary bypass each year.

He has a broad spectrum of pediatric cardiac surgery expertise, with special emphasis in single ventricle congenital heart defects, when one lower chamber of the heart does not develop. One area of his research portfolio includes clinical research into long-term quality of life for people who had Fontan procedures — a critical surgical approach to adapt blood flow for people born with single ventricle heart disease. He has additional expertise in valve repair, artificial hearts and other cardiac assist devices.

“Sometimes it seems like I’ve been born and put on this earth for that single purpose — I have to bring life to patients with single ventricle hearts or assist devices,” he says. He describes his path to pediatric cardiac surgery as serendipity, “It’s more like pediatric cardiac surgery chose me.”

“It is an honor to welcome Yves d’Udekem to the Children’s National Heart Institute,” says David Wessel, M.D., executive vice president and chief medical officer of Hospital and Specialty Services at Children’s National. “He is a surgeon, physician and leader of the highest caliber. I can say without hesitation that Yves’ leadership of our cardiac surgery team will change the lives of hundreds, if not thousands, of children and adults with congenital heart disease.”

In preparation for Dr. d’Udekem’s arrival, the Children’s National Heart Institute and hospital leadership created a framework plan for success that will build on the legacy of excellence established by Richard Jonas, M.D. Dr. Jonas, a world leader in congenital heart surgery who has made significant clinical and academic advances in the field, will continue his award-winning laboratory-based research at Children’s National on neurodevelopmental outcomes for children with congenital heart disease.

Dr. d’Udekem is Belgian-born with Canadian and Australian citizenship. He received his early training in Belgium and Toronto. As an attending cardiac surgeon in Belgium, he operated on both adults and children with congenital heart disease. Dr. d’Udekem then worked with internationally recognized heart surgeon Marc de Leval, M.D., FRCS, and others in London to train in congenital heart surgery at the Great Ormond Street Hospital for Children. From there, he was recruited to The Royal Children’s Hospital in Melbourne, Australia, where he has been ever since.

Dr. d’Udekem has more than 350 research publications and has obtained more than $7 million in grant funding in the past five years for work to create the first research network of Australian children and adults who have undergone the Fontan procedure.

He started seeing patients at Children’s National in mid-September.

doctors operating

U.S. DoD awards $2M for study to protect neurological function after cardiac surgery

doctors operating

A collaboration between clinical and basic science researchers including Drs. Ishibashi, Hashimoto-Torii, Jonas, and Deutsch, seeks to to understand how caspase enzyme activation plays a role in the development of fine and gross motor skills in children who underwent cardiac surgery for CHD repair.

The U.S. Department of Defense has awarded $2 million to Children’s National Hospital to study how a family of protease enzymes known as caspases may contribute to brain cell degeneration when activated by prolonged anesthesia and cardiopulmonary bypass during cardiac surgery for congenital heart disease.

This U.S. Army Medical Research Acquisition Activity Award, Anesthesia Neurotoxicity in Congenital Heart Disease, is led by principal investigator Nobuyuki Ishibashi, M.D., with both clinical and basic science co-investigators including Kazue Hashimoto-Torii, Ph.D., (Neuroscience), Richard Jonas, M.D., (Cardiovascular Surgery) and Nina Deutsch, M.D., (Anesthesiology).

While the specific cellular and molecular mechanisms of how anesthesia and cardiac surgery impact cortical development are poorly understood, both seem to impact brain growth and development in young children. The most common neurologic deficit seen in children after CHD surgical repair is the impairment of fine and gross motor skills.

Both anesthetic agents and inflammation like that seen as a result of cardiopulmonary bypass have also been shown to contribute to the activation of a specific group of enzymes that play an essential role in the routine (programmed) death of cells: caspases. However, recent pre-clinical research shows that these enzymes may also contribute to other alterations to cells beyond cell death, including making changes to other cell structures. In pre-clinical models, these changes cause impairments to fine and gross motor skills – the same neurological deficits seen in children with CHD who have undergone procedures requiring prolonged anesthesia and cardiopulmonary bypass.

The research team hypothesizes that caspases are extensively activated as a result of cardiac surgery and while that activation is rarely causing reduced numbers of neurons, the changes that caspase enzymes trigger in neurons are contributing to neurological deficits seen in children with CHD after surgery.

While the study focuses specifically on the impacts of cardiac surgery for correction of a heart defect, the findings could have major implications for any pediatric surgical procedure requiring prolonged anesthesia and/or cardiopulmonary bypass.

Nobuyuki Ishibashi

R01 grant funds white matter protection study for congenital heart disease

Nobuyuki Ishibashi

Nobuyuki Ishibashi, M.D., is the principal investigator on a $3.2 million NIH R01 to study white matter growth and repair in utero for fetal brains affected by congenital heart disease.

Many of the neurological deficits seen in children with congenital heart disease (CHD) are related to abnormal white matter development early in life caused by reduced oxygen supply to the brain while in utero. Children with immature white matter at birth also commonly sustain additional white matter injuries following cardiac surgery.

The NIH recently awarded a prestigious R01 grant totaling more than $3.2 million to a collaborative project led by the Center for Neuroscience Research, the Sheikh Zayed Institute for Pediatric Surgical Innovation and the Children’s National Heart Institute at Children’s National Hospital as well as MedStar Washington Hospital Center.

The research, titled “White matter protection in the fetus with congenital heart disease,” looks specifically at whether providing a supplemental amount of the naturally occurring tetrahydrobiopterin (BH4) for pregnant women could rescue white matter development of fetuses with congenital heart disease whose brains aren’t receiving enough oxygen – or suffering from hypoxic-ischemic events.

Previous preclinical studies have shown that this lack of oxygen depletes the brain’s natural BH4 level, and the researchers hypothesize that BH4 levels play a critical role in the growth and development of white matter in the fetal brain by triggering key cellular/molecular processes. Specifically, the study will focus on three aims:

  1. Establish in a preclinical model the optimal protective regiment for women pregnant with a fetus who has CHD to receive BH4.
  2. Determine the appropriate approach to deliver BH4 to this population
  3. Leverage genetic tools and biochemical techniques in the laboratory to better understand where and how BH4 levels play a role in the growth (or lack thereof) of oligodendrocytes—the primary cells of white matter.

This laboratory-based work is the first step to determining if the neurodevelopment of babies born with CHD can be preserved or recovered by addressing key brain development that occurs before the baby is even born. Findings related to congenital heart disease may also translate to other populations where white matter development is affected by hypoxia-ischemia, including premature infants.

The project is led by principal investigator Nobuyuki Ishibashi, M.D., with co-investigators Vittorio Gallo, Ph.D., Joseph Scafidi, D.O., and Mary Donofrio, M.D. as well as colleagues at MedStar Washington Hospital Center.

telemedicine control room

Telehealth connects pediatric heart experts about critical COVID-19 details

telemedicine control room

Telehealth is more than a doctor-to-patient tool during COVID-19. Experts in congenital heart disease meet weekly to share details about how it affects their vulnerable patients.

During the COVID-19 pandemic, telehealth has been crucial in allowing doctors to maintain safe contact with patients who require ongoing medical care without an office visit. Just as important is the role that telehealth is playing to connect care providers with each other to ensure that everyone around the world has the information they need to provide the best care possible for this swift-moving disease.

One good example of this specialist-to-specialist thought leadership connection is the ongoing weekly meeting hosted by the Children’s National Hospital cardiac critical care specialists. Since early in the spread of COVID-19, the Cardiac-ICU team, led by cardiovascular specialists including Ricardo Munoz, M.D., chief of cardiac critical care medicine and executive director of telehealth at Children’s National, have connected pediatric clinicians around the world to discuss how best to care for particularly vulnerable patients with pre-existing heart diseases, and to discuss breaking news in epidemiology of the disease and the effectiveness of various treatment approaches.

The video conference attracts hundreds of physicians and nurses who specialize in pediatric cardiac care from countries all over the world. In the last week of April, the meeting featured a late-breaking session to discuss new pediatric intensive care observations of inflammatory symptoms similar to Kawasaki disease, which were being detected in the United Kingdom, Paris and the United States. While more information is needed about this discovery, the ability of these experts to gather and compare disease phenotypes from country to country facilitates both the additional classification of pediatric-related symptoms and improves how all centers, no matter their location, can prepare to treat children who present locally with these symptoms.

In recent weeks, cardiac physicians and nurses from some of the world’s hardest hit regions, including Italy and Spain, have shared detailed information about their on-the-ground experiences to help colleagues in the U.S. and elsewhere better prepare for new developments.

“This new disease is a moving target, especially when it comes to understanding how it might impact children and adults with existing cardiac disease, particularly those with congenital heart disease,” says Dr. Munoz. “It is extremely important that we learn from each other, especially when we are able to connect with our colleagues in the epicenters of the most serious outbreaks of COVID-19. We are happy to host this important weekly meeting with the goal of helping every specialist keep as many patients with cardiac diseases as safe as possible throughout the global health emergency.”

If you would like to join these weekly telehealth meetings, please send your request to COVIDMultiCICUResponse@childrensnational.org.

CHD global outcomes set

New CHD global outcomes set released

The International Consortium for Health Outcomes Measurement (ICHOM) announced the release of a Congenital Heart Disease Standard Set (CHDSS) in late April 2020.

Gerard Martin, M.D., FAAP, FACC, FAHA, cardiologist at Children’s National Hospital, chaired the working group and contributed to the standards’ writing. In ICHOM‘s press release, he noted that, “Having a global set of outcomes that matters most to adult patients and parents of children with congenital heart disease will provide a road map for healthcare professionals and organizations engaged in setting care strategies for this population around the world. I would like to acknowledge the efforts of the Working Group and ICHOM staff for their incredible effort on this project.”

The CHDSS is a minimum core set of standards, comprised of Patient, Parent, and Clinician – Reported Outcome Measures already being collected by most practices in routine clinical care. The CHDSS measures 14 outcomes under the ICHOM framework for comprehensive outcomes measurement. These overarching domains are Overall Health, Social Health, Mental Health, and Physical Health.

Learn more about the CDHSS, the contributors and read the ICHOM press release.

CHD global outcomes set

The CHDSS measures 14 outcomes under the ICHOM overarching domains of Overall Health, Social Health, Mental Health, and Physical Health.

Patients and staff at the Uganda Heart Institute

Lifesaving heart surgeries for RHD complications in Uganda go on despite COVID-19

Patients and staff at the Uganda Heart Institute

Patients and staff at the Uganda Heart Institute for RHD-related heart surgeries in Uganda, March 2020. These patients were originally scheduled as part of the cancelled medical mission, but UHI cardiovascular surgeon successfully managed these cases without the support of the mission doctors from the U.S.

In early March as countries around the globe began to wrestle with how best to tackle the spread of COVID-19, a group of doctors, nurses, researchers and other medical staff from Children’s National Hospital were wrestling with a distinct set of challenges: What to do about the 10 Ugandan children and adults who were currently scheduled for lifesaving heart surgery (and the countless others who would benefit from the continued training of the local heart surgery team) to correct complications of rheumatic heart disease (RHD) during an impending medical mission in the country.

Rheumatic heart disease impacts over 39 million people globally and causes nearly 300,000 deaths per year. RHD is the result of frequent, untreated streptococcal throat infections in childhood that ultimately cause the body’s immune system to repeatedly damage heart valves. It is completely preventable, yet the majority of the world’s children still live in impoverished and overcrowded conditions that predispose them to RHD. Most patients present with advanced valvular heart disease. For example, in Uganda, an RHD registry includes over 600 children with clinical RHD, of which nearly 40% die within four years and the median survival time from enrollment in the registry is only nine months. For these patients, heart surgery is the only viable solution for long-term survival and normal quality of life.

Patricia: 9-year-old from Gulu

Patricia: 9-year-old from Gulu (northern Uganda), had mitral valve replacement and was doing well on a recent follow-up visit at her home.

The scheduled trip from Washington was part of a nearly 20-year partnership** between doctors, nurses, researchers and other medical staff in the United States, including Craig Sable, M.D., associate chief of cardiology, and and Pranava Sinha, M.D.,pediatric cardiovascular surgeon, at Children’s National Hospital in Washington, D.C., and the Uganda Heart Institute in Kampala, Uganda. The partnership aims to tackle RHD head-on. It provides surgical skill transfer, allows for treatment of more complex patients, and increases sustainable surgical capacity for Uganda’s RHD patients over time. As a result, over the last 15 years more than 1,000 children have received lifesaving heart surgery in Uganda, with the Uganda Heart Institute (UHI) performing one to two heart valve surgeries every two weeks over the last few years.

Jackline: 12-year-old from Gulu

Jackline: 12-year-old from Gulu, had mitral valve repair and aortic valve replacement. Jackline and Patricia were diagnosed through one of our research programs and benefit from our novel telehealth program, which helps connect patients from remote parts of Uganda to specialists at UHI.

COVID-19 was changing the current plan, however. Travel between countries was limited, and the team from the U.S. wouldn’t have been permitted to leave the U.S. and return according to schedule. The trip, and the support teams who were scheduled to arrive to help with the surgeries, were cancelled. The U.S. team members who had already arrived in Uganda were sent home after helping their UHI colleagues set up and prepare for the surgeries as much as possible. Knowing that patients and families were counting on the surgery mission to go forward after waiting for months or years to have surgery for heart valve disease, UHI decided not to cancel the majority of the surgeries. Instead, for the first time, they planned and successfully completed five valve-related cases in a single week – several of them quite complex. The cardiologists and cardiac surgeons from Children’s National who were supposed to be in-country for these procedures were forced to limit their in person assistance to the set-up activities the week prior to surgery and telehealth consult during the procedures.

“It was hard not to be able to stay  and work with the UHI team to help these families,” says Dr. Sable. “But we are so proud of the UHI team for meeting this challenge on their own. We knew they had the skills to perform at this volume and complexity. It’s a proud moment to see the team accomplish this major milestone, and to see the patients they cared for thrive.”

The patients are the most important outcome: The five who had successful open-heart surgery are all doing well, either on their way to recovery or already discharged to their communities, where they will, for the first time in memory, be able to play, exercise and go to school or work.

Longer term, this success demonstrates the UHI medical team’s ability to manage greater surgical capacity even when surgical missions from the U.S. resume. The partnership’s goal is to complete at least 1,000 annual operations (both pediatric and adult), with the majority being performed by the local team. Having this capacity available will mean the difference between life and death for many children and adults who have RHD in Uganda and the surrounding countries.

**This work is supported by the Edwards Life Sciences/Thoracic Surgery Foundation, the Emirates Airline Foundation, Samaritan’s Purse Children’s Heart Project and Gift of Life International.

Yves d'Udekem

Yves d’Udekem, M.D., Ph.D., named Chief of Cardiac Surgery and Co-Director of the Children’s National Heart Institute

Yves d'Udekem

Children’s National Hospital announced that world-class surgeon Yves d’Udekem, M.D., Ph.D., will become the next Chief of Cardiac Surgery and Co-Director of the Children’s National Heart Institute this summer.

Dr. d’Udekem is Belgian-born with Canadian and Australian citizenship and received his early training in Belgium and Toronto. As an attending cardiac surgeon in Belgium, he operated on both adults and children with congenital heart disease. Dr. d’Udekem then worked with internationally recognized heart surgeon Marc de Laval, M.D., FRCS, and others in London to train in congenital heart surgery at the Great Ormond Street Hospital for Children.

From there, he was recruited to The Royal Children’s Hospital in Melbourne, Australia, an institution that has been a leader in advancing the field of congenital heart disease. In Melbourne, Dr. d’Udekem built an outstanding reputation for clinical excellence and an exceptional academic career. He has over 300 publications and is highly cited and respected. Dr. d’Udekem obtained more than $7 million in grant funding over the past five years as the creator and leader of the highly touted Fontan Registry.

The Children’s National Cardiology team and hospital leadership have built a framework for Dr. d’Udekem to succeed and advance the legacy that has been so successfully created in cardiac surgery by Richard Jonas, M.D. Dr. Jonas is a world leader in congenital heart surgery who made significant clinical and academic advances in the field and will continue his award-winning research career at Children’s National in the laboratory focusing on neurodevelopmental outcomes for children with heart disease.

Children’s National offers a comprehensive surgical program that includes a team of experienced surgeons performing the full range of procedures available for treatment of pediatric cardiac disease and congenital heart defects. The high volume program serves neonates through adults with congenital heart disease with particular attention to neurodevelopmental outcomes.

tiny stent illustration

Thinking small for newborns with critical congenital heart disease

tiny stent illustration

Illustration of a hybrid stage I palliation with bilateral bands on the lung vessels and a stent in the ductus arteriosus for patients with small left heart structures.

A new LinkedIn post from Kurt Newman, M.D., president and CEO of Children’s National Hospital, tells a story about the hospital’s cardiac surgeons and interventional cardiologists working with the U.S. Food and Drug Administration (FDA) to bring a better-sized, less-invasive vascular stent to the U.S. for the first time. The stent holds open a newborn’s ductus arteriosus, a key blood vessel that keeps blood flowing to the body, until the baby is big and strong enough to undergo a serious open-heart procedure for repair of hypoplastic left heart syndrome.

He writes, “Why is this important? At less than 6 lbs., these patients have arteries that are thinner than a toothpick – less than 2mm in diameter. Currently, the stent used in these children is an FDA approved device for adult vascular procedures, adapted and used off-label in children. It is not always well suited for the smallest babies as it is too large for insertion through the artery and often too long as well. The extra length can create immediate and long-term complications including obstructing the vessel it is supposed to keep open.

“While I am proud of the talent and dedication of our Children’s National cardiac surgery and interventional cardiology teams, I tell this story to illustrate a larger point – innovation in children’s medical devices matters. What’s unfortunate is that development and commercialization of pediatric medical devices in the U.S. continues to lag significantly behind adults…We can and must do better.”

Read Dr. Newman’s full post on LinkedIn.

Pediatric angiography

Congenital heart disease more deadly in low-income countries

Pediatric angiography

Even though mortality from congenital heart disease (CHD) has declined over the last three decades as diagnosis and treatments have advanced, the chances for a child to survive a CHD diagnosis significantly differs based on the country where he or she is born.

This eye-opening finding is drawn from the first comprehensive study of congenital heart disease across 195 countries, prepared using data from the Global Burden of Diseases, Injuries and Risk Factors Study 2017 (GBD), and recently published in The Lancet.

“Previous congenital heart estimates came from few data sources, were geographically narrow and did not evaluate CHD throughout the life course,” write the authors, known collectively as the 2017 GBD Congenital Heart Disease Collaborators. Co-lead author Meghan D. Zimmerman, M.D., worked on the study while completing her pediatric cardiology and American Heart Association Global Health Fellowships at Children’s National Hospital, and two pediatric cardiologists from Children’s National, Cardiology Associate Chief Craig Sable, M.D., and Gerard Martin, M.D., medical director of Global Services, provided leadership and oversight of this paper. The remaining collaborators are from more than 45 institutions around the world, spanning cardiology, public health and schools of medicine on every continent.

This is the first time the GBD study data was used along with all available data sources and previous publications – making it the most comprehensive study on congenital heart disease burden to date. Key differences between this study and prior estimates include:

  • Anatomic groupings of CHD by type, rather than simply categorized as moderate, severe or critical.
  • Inclusion of new data sources, including data from screening programs, congenital registries, administrative data and data sources in mortality and survival.
  • A control mechanism to account for cases of CHD that remit on their own to reduce the risk of overestimating prevalence.
  • Inclusion of all cases of congenital heart disease, including those with chromosomal or genetic anomalies such as Trisomy 21 that often co-occur.

This more comprehensive data set led to findings that showed lower predicted long-term survival, higher remission, and lower prevalence than previous studies that extrapolated evidence from studies of high-income countries. However, it also means these new estimates are a more accurate representation of the current global state of affairs. Overall, the study found:

  • A 34.5% decline in deaths from congenital disease between 1990 to 2017.
  • Nearly 70% of deaths caused by CHD in 2017 (180,624) were in infants less than one year old.
  • Most CHD deaths occurred in countries within the low and low-middle socio-demographic index (SDI) quintiles.
  • Mortality rates get lower as a country’s SDI rises.
  • Birth prevalence of CHD was not related to a country’s socio-demographic status, but overall prevalence was much lower in the poorest countries of the world. This is because children in these countries do not have access to life saving surgical services.
  • Nearly 12 million people are currently living with CHD globally, 18.7% more than in 1990.
  • The burden of CHD is not fully realized by just looking at prevalence and mortality. The measure “Years of Life Lost” provides deeper insight into the staggering burden of CHD, taking into account both absolute mortality and age at death.

“In high income countries like the United States, we diagnose some heart conditions prenatally during the 20-week ultrasound,” says Gerard Martin, M.D., a pediatric cardiologist at Children’s National Hospital who contributed to the study. “We catch others right after birth with a pulse oximetry screening for critical congenital heart disease. We can operate to correct a critical issue within the first week of life. And now our CHD kids are growing and thriving through adulthood and having families of their own.”

“For children born in middle- and low-income countries, these data draw stark attention to what we as cardiologists already knew from our own work in these countries – the lack of diagnostic and treatment tools leads to lower survival rates for children born with CHD,” adds Craig Sable, M.D., associate chief of cardiology at Children’s National, another primary contributor. “This is one of the most significant publications I have been a part of as it highlights the substantial loss of life to CHD in infancy around the globe.”

The authors write, “The UN has prioritized reduction of premature deaths from heart disease, but to meet the target of ‘ending preventable deaths of newborns and children under 5 years of age,’ health policy makers will need to develop specific accountability measures that address barriers and improve access to care and treatment.”

The study also includes a 400-page appendix breaking down each area by type of congenital anomaly, world region and country.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation

Maternal mental health alters structure and biochemistry of developing fetal brain

Even when pregnant women have uncomplicated pregnancies and high socioeconomic status, when they experience elevated anxiety, stress or depression these prenatal stressors can alter the structure of the developing fetal brain and disrupt its biochemistry, according to Children’s National Hospital research published online Jan. 29, 2020, in JAMA Network Open.

The Children’s National research findings “have enormous scientific, clinical and public health implications,” Charles A. Nelson III, Ph.D.,  Boston Children’s Hospital, writes in a companion editorial.

“Previously we found that 65% of pregnant women who received a diagnosis of fetal congenital heart disease had elevated levels of stress. It’s concerning but not surprising that pregnant women who wonder if their baby will need open heart surgery would feel stress,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s senior author. “In this latest study, we ran the same panel of questionnaires and were surprised to find a high proportion of otherwise healthy pregnant women whose unborn babies are doing well also report high levels of stress.”

Anxiety and depression are the most common mental health problems during pregnancy. To learn more about the implications for the developing fetal brain, the Children’s National research team recruited 119 healthy volunteers with low-risk pregnancies from obstetric clinics in Washington, D.C., from Jan. 1, 2016, to April 17, 2019. The women’s mean age was 34.4 years old. All were high school graduates, 83% were college graduates, and 84% reported professional employment.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation. Segmentation results of total brain (orange), cortical gray matter (green), white matter (blue), deep gray matter (brown), brainstem (yellow), cerebellum (light blue), left hippocampus (purple) and right hippocampus (red) on a 3-Dimensional reconstructed T2-weighted MR image of a fetus at 26.4 gestational weeks. The hippocampus plays a central role in memory and behavioral inhibition and contains high concentrations of corticosteroid receptors and, thus, this brain region is sensitive to stress. Credit: JAMA Network Open.

The team performed 193 fetal brain magnetic resonance imaging (MRI) sessions between 24-40 weeks gestation and measured the volume of the total fetal brain as well as the cortical gray matter, white matter, deep gray matter, cerebellum, brainstem and hippocampus volumes. On the same day as their MRI visit, the pregnant women completed validated questionnaires to measure maternal stress, anxiety and depression, answering questions such as “how do you feel right now,” “how do you generally feel” as well as the degree of stressful feelings they experienced the month prior.

Of the pregnant women in the study:

  • 27% tested positive for stress
  • 26% tested positive for anxiety
  • 11% tested positive for depression
  • Maternal anxiety and stress were associated with increased fetal cortical gyrification
  • Elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain
  • Maternal stress scores decreased with increasing gestational age, while anxiety and depression did not

“We report for the first time that maternal psychological distress may be associated with increased fetal local gyrification index in the frontal and temporal lobes,” says Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author. “We also found an association with left fetal hippocampal volume, with maternal psychological distress selectively stunting the left hippocampal volumetric growth more than the right. And elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain,” Wu adds.

Late in pregnancy – at the time these women were recruited into the cohort study – the fetal brain grows exponentially and key metabolite levels also rise. Creatine facilitates recycling of adenosine triphosphate, the cell’s energy currency. Typically, levels of this metabolite rise, denoting rapid changes and higher cellular maturation; creatine also is known to support cognitive function. Choline levels also typically rise, marking cell membrane turnover as new cells are generated and support memory, mental focus and concentration.

“These women were healthy, and of high socioeconomic status and educational level, leading us to conclude that the prevalence of prenatal maternal psychological distress may be underestimated,” Limperopoulos adds. “While stress is an everyday reality for most of us, this is different because elevated stress during pregnancy can alter fetal brain programming. Our findings underscore the critical need to universally screen all pregnant women for prenatal psychological distress, even young mothers whose pregnancies wouldn’t otherwise raise red flags.”

In addition to Limperopoulos and Wu, Children’s National study co-authors include Yuan-Chiao Lu, Ph.D., research associate; Marni Jacobs, Ph.D., biostatistician; Subechhya Pradhan, Ph.D., research faculty; Kushal Kapse, MS, staff engineer; Li Zhao, Ph.D., research faculty; Nickie Niforatos-Andescavage, M.D., neonatologist; Gilbert Vezina, M.D., director of the neuroradiology program; and Adré  J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Research coordinators Catherine Lopez, MS, Kathryn Lee Bannantine, BSN, and Jessica Lynn Quistorff, MPH, assisted with subject recruitment.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. RO1 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

Journal Reference:
Yao Wu, Yuan-Chiao Lu, Marni Jacobs, Subechhya Pradhan, Kushal Kapse, Li Zhao, Nickie Niforatos-Andescavage, Gilbert Vezina, Adré J. du Plessis, Catherine Limperopoulos. “Association of prenatal maternal psychological distress with fetal brain growth, metabolism and cortical maturation,” JAMA Network Open, 3(1): e1919940, 2020