Congenital heart disease (CHD) refers to a range of heart abnormalities that are present from birth and affect the structure or function of the heart. These conditions can affect blood flow through the heart and body, with some defects causing minimal issues and others requiring prompt medical attention.
Early diagnosis and appropriate specialist care can improve outcomes for children with congenital heart disease. Many children can lead active and fulfilling lives, although the outlook and follow-up needed depend on the type and severity of the heart defect.
Understanding the symptoms, diagnostic process, and treatment options can help you feel more confident when navigating your child’s care. With timely intervention and appropriate follow-up, many heart defects can be managed successfully, improving both short-term outcomes and long-term quality of life.
What Is Congenital Heart Disease?
Congenital heart disease describes a group of conditions that develop before birth and affect the structure or function of your child’s heart. These abnormalities can involve the heart walls, valves, or major blood vessels, which may change the way blood flows through the heart and around the body.
The effects of congenital heart disease can vary considerably from one child to another. Some heart defects are mild and may cause few or no symptoms, while others are more complex and require specialist treatment soon after birth or during childhood.
If your child is diagnosed with congenital heart disease, understanding the specific type and severity of the condition is an important first step. This information helps your healthcare team determine the most appropriate monitoring, treatment, and long-term care plan for your child.
How Common Is CHD in Children?
Congenital heart disease is one of the most common conditions present at birth, affecting about 8 in every 1,000 babies. Because CHD includes a wide range of heart defects, the impact on each child can vary significantly, from mild abnormalities to complex conditions requiring specialist care.
Many children with congenital heart disease have mild defects that cause few problems and may not need major treatment. Some small septal defects may close without treatment, while other mild defects remain stable and only require regular monitoring. Whether treatment is needed depends on the exact defect and its effect on blood flow and heart function.
Even when symptoms appear mild, early diagnosis remains important. Identifying congenital heart disease as soon as possible allows your child’s medical team to monitor their heart health closely and provide treatment promptly if it becomes necessary.
Evidence Note
Echocardiography is a central test for confirming and defining congenital heart defects. Additional imaging or cardiac catheterisation may be needed in more complex cases. The need for treatment and the long-term outlook depend on the specific diagnosis, although advances in specialist care have improved survival and quality of life for many children with CHD.
Common Types of Heart Defects
Congenital heart disease includes a wide range of heart defects that can affect how blood flows through your child’s heart and body. One of the most common types is a septal defect, which involves a hole in the wall separating the heart chambers, such as a ventricular septal defect (VSD) or atrial septal defect (ASD).
Your child may also be diagnosed with a valvular defect, where one or more heart valves do not open or close properly, affecting blood flow through the heart. Obstructive defects are another common group of conditions and occur when a blood vessel or part of the heart is narrowed, making it harder for blood to circulate efficiently.
Some children have cyanotic defects, which allow oxygen-poor blood to enter the body’s circulation and can lead to lower oxygen levels in the blood. Because each type of heart defect affects the heart differently, the symptoms, treatment needs, and long-term outlook can vary considerably from one child to another.
How Heart Defects Affect the Body
If your child has a congenital heart defect, the condition can affect how efficiently blood circulates around the body. When blood flow is disrupted, the heart may need to work harder, and some organs and tissues may not receive the oxygen and nutrients they need to function properly.
As a result, your child may experience symptoms such as tiredness, difficulty feeding, poor weight gain, breathlessness, or slower growth and development. The severity of these symptoms often depends on the type and complexity of the heart defect.
Complex congenital heart defects may be associated with complications such as heart failure, abnormal heart rhythms or pulmonary hypertension. Some complications can develop even after treatment, which is why ongoing specialist follow-up may remain important.
Signs and Symptoms in Infants
If your baby has congenital heart disease, the symptoms may be obvious from birth or develop gradually over time. One of the most common signs is rapid or laboured breathing, particularly during feeding, sleeping, or periods of activity.
You may also notice that your baby becomes tired while feeding, struggles to finish feeds, or is not gaining weight as expected. Some babies with heart defects have a bluish tint to their lips, tongue, skin, or fingernails, known as cyanosis, which can indicate lower oxygen levels in the blood.
As these symptoms may be subtle, it is essential to seek prompt medical advice if you are concerned about your baby’s breathing, feeding, or growth. Early assessment can help identify any underlying heart condition and ensure your child receives appropriate care as soon as possible.
Symptoms in Older Children
As your child gets older, the symptoms of congenital heart disease may become more noticeable during physical activity or everyday routines. You might find that your child becomes tired more quickly than their peers, struggles to keep up during sports, or needs frequent rest breaks after exercise.
Older children may experience shortness of breath, reduced exercise tolerance, palpitations, chest discomfort, dizziness or fainting. These symptoms are not specific to congenital heart disease, but recurring symptoms or symptoms that develop during exercise should be assessed by a healthcare professional.
If these symptoms recur, particularly during exercise, discuss them with your child’s doctor. Further assessment may be needed to determine whether a heart condition or another cause is responsible.
When to Seek Medical Advice
Ask for an urgent GP appointment or contact NHS 111 if you think your child may have symptoms of congenital heart disease, such as persistent breathlessness, poor feeding, poor growth, unusual tiredness, swelling or recurring palpitations.
Call 999 if your child’s lips, tongue, face or skin suddenly turn blue or grey, or if they have severe difficulty breathing, collapse, become limp or are not responding normally. Do not drive your child to A&E if their condition appears life-threatening; follow the instructions given by the 999 call handler.
A heart murmur does not always mean that a child has congenital heart disease, as many childhood murmurs are harmless. However, your child’s doctor may arrange further assessment if the murmur has concerning features or occurs with other symptoms.
How Doctors Diagnose CHD
If your doctor suspects that your child may have congenital heart disease, they will begin with a detailed medical history and physical examination. During the assessment, they will listen to your child’s heart for murmurs, check their breathing, measure oxygen levels, and evaluate their growth and overall development.
Your doctor will also look for signs that suggest the heart is not pumping blood efficiently, such as poor weight gain, cyanosis, or unusual fatigue. These findings can provide important clues about whether a heart defect may be present.
To confirm the diagnosis, your child may need specialised tests that allow doctors to examine the structure and function of the heart in more detail. These investigations help identify the type of heart defect, assess its severity, and guide decisions about treatment and ongoing care.
Echocardiography and Imaging
If your child is being assessed for congenital heart disease, an echocardiogram is usually one of the most important diagnostic tests. This ultrasound uses sound waves to produce detailed images of the heart, enabling specialists to assess the chambers, valves, vessels, and blood flow.
An echocardiogram is painless, non-invasive, and provides valuable information about the type and severity of a heart defect. In many cases, it provides enough information to confirm the diagnosis and guide treatment planning, although additional tests may be needed for more complex defects.
For more complex heart conditions, your child may also need additional imaging tests such as an MRI scan or CT scan. These investigations can provide a more detailed view of the heart and surrounding blood vessels, helping specialists plan surgery or other treatments with greater precision.
Electrocardiogram (ECG) and Other Tests
If your child is being evaluated for congenital heart disease, an electrocardiogram (ECG) may be used to assess how the heart’s electrical system is working. This simple, painless test can help detect abnormal heart rhythms and electrical patterns that may suggest enlargement or strain affecting particular heart chambers.
Your doctor may also recommend additional tests to build a more complete picture of your child’s heart health. A chest X-ray can show the size and shape of the heart and identify signs of fluid in the lungs, while pulse oximetry estimates the percentage of oxygen carried in the blood.
These tests are often used alongside an echocardiogram and physical examination to help confirm a diagnosis. By combining information from multiple investigations, your child’s healthcare team can better understand the nature of the heart defect and determine the most appropriate treatment plan.
Fetal Diagnosis of CHD
Some congenital heart defects can be identified before your baby is born through routine pregnancy scans and specialised fetal echocardiography. These tests allow doctors to examine your baby’s heart structure and function while they are still developing in the womb.
The 20-week pregnancy scan can identify some congenital heart defects, but it cannot detect every condition. A normal pregnancy scan therefore does not completely exclude CHD, and some defects are first diagnosed after birth or later in childhood.
If a heart defect is detected during pregnancy, you and your healthcare team can prepare for your baby’s delivery and immediate care after birth. Early diagnosis can help ensure that the right specialists and treatments are available when your baby needs them.
Having a prenatal diagnosis can also give you time to understand your baby’s condition and discuss the possible treatment options with your medical team. This preparation can help you feel more informed and supported throughout your child’s care journey.
Treatment Approaches Overview
The treatment your child needs for congenital heart disease will depend on the type of heart defect, its severity, and how it affects their health. Some children may only need regular check-ups and monitoring, while others may require medications, catheter-based procedures, or heart surgery.
Your child’s healthcare team will create a treatment plan based on their individual needs and how the condition changes over time. The main aim is to improve blood flow, support oxygen delivery, reduce symptoms and help your child’s growth and development.
Thanks to advances in paediatric cardiology, many children with CHD can now achieve positive long-term outcomes. Regular follow-up appointments allow doctors to monitor your child’s progress and address any complications as early as possible.
Medications for CHD
If your child has congenital heart disease, medications may be used to manage symptoms, support heart function, or reduce the risk of complications. The type of medicine prescribed will depend on your child’s specific heart defect and how it affects their circulation and overall health.
Your child may be prescribed diuretics to reduce excess fluid. ACE inhibitors can reduce the heart’s workload in selected children with heart failure, while beta-blockers may be used for certain rhythm problems, blood pressure conditions or other specific indications. These medicines are usually carefully adjusted based on your child’s needs and response to treatment.
Medication is often only one part of your child’s overall care plan. Your healthcare team may combine medicines with regular monitoring, procedures, or surgery to help maintain healthy heart function and support your child’s growth and development.
Catheter-Based Procedures
Selected congenital heart defects can be treated using catheter-based procedures, sometimes avoiding or delaying open-heart surgery. Other children may still require surgery or more than one procedure as they grow. During these procedures, your child’s doctor guides a thin tube called a catheter through a blood vessel to reach the heart and repair or improve the affected area.
Catheter techniques may be used to close certain holes between heart chambers, such as some septal defects, or to widen narrowed heart valves and blood vessels. The most suitable approach will depend on your child’s specific heart condition and overall health.
For some children, these procedures can reduce the need for major surgery and may involve a shorter recovery time. Your child’s specialist will discuss whether a catheter-based treatment is an appropriate option based on the type and severity of the heart defect.
Surgical Options
If your child has a complex or severe congenital heart defect, open-heart surgery may be recommended to repair the problem and improve how the heart functions. Depending on the defect, surgery may fully repair the abnormality or improve circulation without completely correcting the underlying heart structure. The aim may be to improve blood flow and oxygen delivery to the body.
The type of surgery your child needs will depend on the specific heart defect, its severity, and your child’s age and overall health. Some children may need a single operation, while others may require multiple procedures as they grow.
Advances in paediatric cardiac surgery have greatly improved outcomes for children with congenital heart disease. With specialist care, careful monitoring, and ongoing follow-up, many children can go on to lead active and healthy lives.
Postoperative Care
After heart surgery, your child will be monitored carefully in hospital. The medical team will assess their heart function, circulation, oxygen levels, breathing, pain and surgical wounds while watching for possible complications. The length of the hospital stay and overall recovery time will depend on the operation, your child’s health and how they respond to treatment.
Long-term follow-up is an important part of your child’s care after surgery. Regular appointments allow your healthcare team to monitor growth, development, and any ongoing heart concerns so that any issues can be identified and managed early.
Long-Term Outlook
With the right treatment and ongoing care, many children with congenital heart disease can grow up to lead healthy and active lives. Your child’s long-term outlook will depend on the type of heart defect, the treatment they receive, and how well their condition is managed over time.
Some children may need only occasional monitoring, while others may require continued specialist care throughout their lives. Advances in diagnosis, surgery, and medical treatment have significantly improved outcomes for many children with CHD.
Even after a successful repair, congenital heart disease is not always considered cured. Some children need lifelong congenital cardiology follow-up to monitor heart function, heart rhythm, valves, blood vessels and previous repairs.
Regular follow-up appointments with a paediatric cardiologist are important for monitoring your child’s heart health as they grow. These checks help identify any late complications early and ensure your child receives the support they need at each stage of development.
Lifestyle Considerations
If your child has congenital heart disease, their activity levels may need to be adjusted depending on the type of heart defect and how well their heart is functioning. Your child’s cardiologist can advise which activities are safe and whether any restrictions are needed.
Encouraging participation in appropriate physical activities can support your child’s overall health and development. Most children should be encouraged to be physically active within the limits agreed with their paediatric cardiologist. Any restrictions or progression plan should be individualised according to the child’s diagnosis, treatment, heart function and symptoms.
A balanced diet, good nutrition, and regular health check-ups are also important parts of your child’s long-term care. Working closely with your healthcare team can help support healthy growth, development, and overall wellbeing.
Supporting Emotional Health
Living with congenital heart disease can affect your child’s emotional wellbeing as they grow and become more aware of their condition. Encouraging your child to talk openly about their feelings and answering their questions in an age-appropriate way can help them feel supported and confident.
Children may worry about medical appointments, treatments, or feeling different from peers. Providing reassurance and seeking support from healthcare professionals, counsellors, or support groups when needed can help your child manage these emotions.
Caring for a child with CHD can also be challenging for you as a parent or caregiver. Accessing guidance, support networks, and reliable information can help you feel more prepared while providing the best possible support for your child’s physical and emotional health.
Education and School Considerations
If your child has congenital heart disease, they may need some additional support at school depending on their condition and how it affects their daily activities. Some children may have reduced stamina, need regular breaks, or require medication during school hours.
Working together with your child’s teachers, school nurse, and support staff can help create a safe and supportive learning environment. Sharing information about your child’s condition, activity limits, and any warning signs to look out for can help staff respond appropriately if concerns arise.
With the right adjustments and understanding, many children with CHD can take part in school life, friendships, and activities. Regular communication between you, your child’s healthcare team, and the school can help ensure your child receives the support they need to thrive.
Monitoring and Follow-Up
Regular monitoring with a paediatric cardiologist is an important part of managing your child’s congenital heart disease. These follow-up appointments allow your healthcare team to check heart function, track growth and development, and assess how well your child is coping with everyday activities.
During these reviews, your child’s doctor can look for any changes in their condition and identify potential complications at an early stage. The frequency of appointments will depend on the type of heart defect, the treatment your child has received, and their individual needs.
Keeping up with regular check-ups helps ensure your child receives the right support as they grow. Ongoing monitoring allows their care plan to be adjusted when needed, helping to protect their long-term heart health and wellbeing.
Advances in CHD Care
Advances in fetal diagnosis, imaging, catheter procedures, surgery and intensive care have improved outcomes for many children with congenital heart disease. Care increasingly focuses not only on survival but also on development, emotional wellbeing, education, exercise and transition into adult congenital heart services.
Genetic and Environmental Factors
Congenital heart disease usually develops through a complex combination of genetic and other factors. Some cases are associated with chromosomal conditions, altered genes, maternal health conditions, certain infections or particular medicines and exposures during pregnancy. However, in many children no single cause is identified. Parents should be reassured that congenital heart disease is not usually caused by something they did or did not do during pregnancy.
Understanding possible risk factors can help your healthcare team provide appropriate advice, monitoring, and support for your child. If a genetic cause is suspected, your doctor may recommend additional assessments or genetic counselling to help you better understand your child’s condition.
Having information about potential causes can help you and your medical team plan the right approach to care. Regardless of the cause, early diagnosis, specialist support, and ongoing monitoring are important for helping your child achieve the best possible health outcomes.
When to Seek Emergency Care
Call 999 if your child’s lips, tongue, face or skin suddenly turn blue or grey, they have severe difficulty breathing, collapse, become unresponsive, or are unusually limp or floppy. These signs may indicate a life-threatening problem and require immediate assessment.
Contact your child’s specialist team, request an urgent GP appointment or call NHS 111 if your child develops new or worsening rapid breathing, poor feeding, swelling, unusual tiredness, palpitations or a noticeable deterioration in their usual symptoms but does not appear immediately life-threatening.
If your child already has an emergency plan from their congenital cardiac team, follow that plan. When you are uncertain and your child appears seriously unwell, call 999.
Myth vs Fact
| Myth | Fact |
| All congenital heart defects are severe and require surgery. | Some small heart defects may close without intervention, while other mild defects remain present but only require monitoring. Treatment depends on the exact diagnosis. |
| CHD always prevents a child from leading an active and fulfilling life. | Many children with CHD can lead active and fulfilling lives, although some need ongoing treatment, follow-up or individual adjustments. |
| Only infants show symptoms of CHD. | Older children may develop noticeable symptoms during activity or everyday routines. |
| Exercise is unsafe for children with CHD. | Physical activity can be beneficial when tailored to the child’s condition and advised by a cardiologist. |
| Genetic factors are the only cause of CHD. | Genetics can play a role, while certain maternal health conditions, infections, medicines or other exposures during pregnancy may also be associated with risk. In many cases, no single cause is identified. |
| Blue or grey colouring can always be watched at home if a child has known CHD. | New or worsening blue or grey lips, tongue, face or skin needs urgent assessment. Call 999 if the change is sudden, severe or occurs with breathing difficulty, collapse or reduced responsiveness. |
| CHD is always detected immediately at birth. | Some defects are subtle and may only be identified during routine exams or later in childhood. |
Key Takeaways
- CHD includes many different heart defects, ranging from mild conditions to complex abnormalities requiring early treatment.
- Symptoms may include breathing or feeding difficulties, poor growth, unusual tiredness, reduced exercise tolerance, palpitations or cyanosis.
- Echocardiography is a central diagnostic test, with ECG, MRI, CT or other investigations used when appropriate.
- Treatment may include monitoring, medicines, catheter procedures or surgery.
- Some children require lifelong congenital cardiology follow-up, including after successful repair.
- Call 999 for sudden blue or grey lips or tongue, severe breathing difficulty, collapse or reduced responsiveness.
Frequently Asked Questions
1. What is congenital heart disease in children?
Congenital heart disease (CHD) refers to structural abnormalities of the heart that are present at birth. These defects can affect the heart walls, valves or blood vessels and may change how blood flows through the body. Some heart defects are mild and require little or no treatment, while others are more complex and need ongoing medical care. The impact on a child’s health depends on the type and severity of the condition.
2. What causes congenital heart disease?
In many cases, the exact cause of CHD is unknown. Some heart defects are associated with genetic conditions, chromosomal differences or a family history of congenital heart disease. Certain factors during pregnancy, such as infections, uncontrolled diabetes or exposure to specific medications, may also increase the risk. However, many children with CHD are born to parents with no known risk factors. In many cases, no single cause can be identified, and parents should not assume that they caused the condition.
3. What are the most common symptoms of congenital heart disease?
Symptoms can vary depending on the type of heart defect and the child’s age. Common signs include rapid breathing, difficulty feeding, poor weight gain, fatigue and a bluish colour to the lips or skin. Older children may experience shortness of breath, reduced exercise tolerance, palpitations, chest discomfort, dizziness or fainting. Some mild heart defects may not cause noticeable symptoms and are discovered during routine examinations.
4. Can congenital heart disease be detected before birth?
Yes, some forms of CHD can be identified during pregnancy through routine ultrasound scans. If a heart problem is suspected, a fetal echocardiogram may be performed to provide more detailed images of the baby’s heart. Early diagnosis allows healthcare teams to plan treatment and support before and immediately after birth. This can be particularly important for more complex heart defects. However, pregnancy scans cannot detect every congenital heart defect, and some conditions are first diagnosed after birth or later in childhood.
5. How is congenital heart disease diagnosed in children?
Diagnosis usually begins with a medical history and physical examination. Doctors may detect a heart murmur, abnormal oxygen levels or other signs that suggest a heart condition. Echocardiography provides detailed information about the heart’s structure and blood flow. ECGs, pulse oximetry, chest X-rays, MRI, CT or cardiac catheterisation may provide additional information when needed. These investigations help specialists identify the type and severity of the defect and plan appropriate care.
6. Does every child with congenital heart disease need surgery?
No, not every child with CHD requires surgery. Some small defects may close without treatment or only require monitoring, while others may be managed with medicines or catheter-based procedures. Surgery may be recommended when a defect cannot be managed safely through observation or other treatments, or when repairing it could prevent symptoms, heart strain or future complications. The decision depends on the specific defect and your child’s individual health.
7. Can children with congenital heart disease lead active lives?
Many children with CHD go on to lead healthy and active lives, particularly when their condition is diagnosed and treated early. Advances in medical care, surgery and long-term monitoring have greatly improved outcomes. Some children may need ongoing follow-up appointments or activity modifications, depending on their condition. Regular specialist care helps support long-term health and wellbeing.
8. Can children with congenital heart disease take part in sports and physical activities?
Many children with CHD can participate in physical activity, although recommendations vary depending on the type and severity of the heart defect. Exercise is often encouraged because it supports physical and emotional wellbeing. A paediatric cardiologist can advise on suitable activities and any restrictions that may be necessary. Individual assessment is important to ensure participation is safe.
9. Will congenital heart disease affect a child’s growth and development?
Some children with more severe heart defects may experience slower growth, feeding difficulties or developmental delays, particularly during infancy. Feeding and growth may improve after treatment, but some children continue to need nutritional, developmental, educational or psychological support. Regular assessment helps identify and address these needs early.
10. When should emergency medical attention be sought for a child with congenital heart disease?
Call 999 if your child develops sudden blue or grey lips, tongue, face or skin, severe breathing difficulty, collapses, becomes unresponsive, or is unusually limp or floppy. Contact the specialist team, an urgent GP service or NHS 111 for other new or worsening symptoms that are concerning but do not appear immediately life-threatening.
Final Thoughts: Supporting Children with Congenital Heart Disease
A diagnosis of congenital heart disease can feel overwhelming, but advances in paediatric cardiology, imaging, surgical techniques and long-term care have transformed outcomes for many children. While every heart defect is different, early diagnosis, appropriate treatment and regular specialist follow-up can help children achieve the best possible quality of life and support healthy growth and development.
Many children with congenital heart disease go on to attend school, participate in activities and enjoy active, fulfilling lives. The key is ongoing monitoring, personalised care and prompt attention to any new symptoms or concerns. If you are concerned about your child’s breathing, feeding, growth, exercise tolerance, heart rhythm or development, seek medical advice. An assessment can help determine whether your child needs further tests, specialist monitoring or treatment. If you are concerned about symptoms that could be related to congenital heart disease, contact London Paediatric Clinic for an initial assessment and advice on whether referral for specialist paediatric cardiology care is appropriate.
References:
- NHS (2025) Congenital heart disease. Last reviewed 11 December 2025. Available at: https://www.nhs.uk/conditions/congenital-heart-disease/
- NHS England (2026) Congenital heart disease (CHD): information for parents. Updated 6 March 2026. Available at: https://www.gov.uk/government/publications/congenital-heart-disease-description-in-brief/congenital-heart-disease-information-for-parents-html
- NHS England (2026) Fetal anomaly screening programme handbook: 20-week screening scan. Updated 15 July 2026. Available at: https://www.gov.uk/government/publications/fetal-anomaly-screening-programme-handbook/20-week-screening-scan
- British Heart Foundation (BHF) (no date) Congenital heart conditions: congenital heart disease. Available at: https://www.bhf.org.uk/informationsupport/conditions/congenital-heart-disease
- Liu, Y., Chen, S., Zühlke, L., Black, G.C., Choy, M.K., Li, N. and Keavney, B.D. (2019) ‘Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies’, International Journal of Epidemiology, 48(2), pp. 455–463. Available at: https://pubmed.ncbi.nlm.nih.gov/30783674/
- Lopez, L., Saurers, D.L., Barker, P.C.A. et al. (2024) ‘Guidelines for performing a comprehensive pediatric transthoracic echocardiogram: recommendations from the American Society of Echocardiography’, Journal of the American Society of Echocardiography, 37(2), pp. 119–170. Available at: https://pubmed.ncbi.nlm.nih.gov/38309834/
- Sood, E., Newburger, J.W., Anixt, J.S. et al. (2024) ‘Neurodevelopmental outcomes for individuals with congenital heart disease: updates in neuroprotection, risk-stratification, evaluation, and management’, Circulation, 149(13), pp. e997–e1022. Available at: https://pubmed.ncbi.nlm.nih.gov/38385268/
- Pierpont, M.E., Brueckner, M., Chung, W.K. et al. (2018) ‘Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association’, Circulation, 138(21), pp. e653–e711. Available at: https://pubmed.ncbi.nlm.nih.gov/30571578/
- Takken, T., Giardini, A., Reybrouck, T. et al. (2012) ‘Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease’, European Journal of Preventive Cardiology, 19(5), pp. 1034–1065. Available at: https://pubmed.ncbi.nlm.nih.gov/23126001/