Introduction
Background
Mechanical circulatory support has revolutionised the care of paediatric patients with CHD. Devices such as the ventricular assist device, and extracorporeal membrane oxygenation are frequently used as bridging therapy to recovery, decision-making, and heart transplantation, providing critical support to the failing heart. In the United States, extra-corporeal membrane oxygenation is used in over 1,500 paediatric cases annually. Reference Barbaro, Paden and Guner1 Other forms of mechanical circulatory support include the total artificial heart and the intra-aortic balloon pump.
Despite the life-saving potential of extra-corporeal membrane oxygenation, these interventions come with significant risks including affecting neurodevelopmental outcomes in a developing child. Studies suggest large variability in the incidence and outcomes of neurodevelopment problems for paediatric patients who undergo mechanical circulatory support such as cognitive delay, motor dysfunction, and behavioural problems. These adverse outcomes are influenced by extra-corporeal membrane oxygenation factors including the duration of support, type of support, underlying cardiac lesion, and complications including stroke or seizure during or post. Reference Pastuszko, Katz and Ravvin2
Many reports have focused on neurological complications from organic causes such as stroke post-extra-corporeal membrane oxygenation. However, we found limited studies examining the neurodevelopmental outcomes post-extra-corporeal membrane oxygenation or even defining it clearly. Studies often used phrases including neurodevelopmental, neuropsychiatric, neuropsychological, and motor functions interchangeably. However, we defined neurodevelopment as the developmental progress of a child’s brain and nervous system, encompassing a range of functions including cognitive abilities, motor skills, language development, and social–emotional behaviour. These outcomes are typically measured through assessments that evaluate intellectual functions such as memory, attention, and problem-solving, as well as physical abilities like gross and fine motor coordination. Language development, both in terms of understanding and expression, and a child’s capacity to form relationships and regulate emotions, are also critical components. Although neurological outcomes post-extra-corporeal membrane oxygenation have previously been studied, we found limited data on neurodevelopmental outcomes. This is important especially as they reflect a broader and more nuanced functional impairments that affect quality of life.
Whilst routine auditing of mortality outcomes is well established in the UK, supported by the National Congenital Heart Disease Audit, 3 complications and other outcomes other than mortality are not regularly studied. There is currently no consensus agreement on which morbidities should be monitored post-cardiac surgery or how they should be precisely defined. Understanding the impact of extra-corporeal membrane oxygenation on neurodevelopment is crucial in evaluating its influence on long-term quality of life and functional abilities. In the UK, over 5,000 paediatric cardiac surgeries are performed each year, Reference Brown, Pagel and Ridout4 with significant improvements in peri-operative mortality rates due to advances in clinical care and data-sharing practices. To support the consistent monitoring of neurodevelopmental outcomes post-paediatric cardiac surgery, we aim to examine the different objectives by which institutions qualify neurodevelopmental outcomes. While methods for reporting risk-adjusted mortality outcomes are well established in adult cardiac surgery for quality improvement in the UK, similar approaches for monitoring morbidities are less developed in paediatric cardiac surgery.
The priorities of the James Lind Alliance align closely with the objectives of this review. 5 For instance, their focus on improving mental health outcomes for individuals with CHD resonates with our study putting emphasis on evaluating long-term complications and psychological impacts. These shared priorities highlight the importance of addressing these critical areas to enhance patient care and outcomes. To identify the clinical research priorities in CHD, it is essential to engage patients, clinicians, and other key stakeholders following the James Lind Alliance CHD methodology. While patient-reported outcome measures capture patient perspectives, Reference Francis, Prothasis, George and Stoica6 incorporating insights from diverse groups as advocated by the James Lind Alliance methodology can help mitigate potential biases and ensure a more comprehensive understanding of the issues at hand.
Given the increasing reliance on these technologies, it is imperative to evaluate the current evidence to guide clinical practice and improve patient outcomes. This systematic review aimed to investigate the impact of extra-corporeal membrane oxygenation on neurodevelopment in paediatric heart patients, both post-cardiotomy and non-cardiotomy patients.
Methodology
Literature search strategy
A systematic review was conducted in accordance with the Cochrane Collaboration published guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for all relevant literature was performed using the PubMed, SCOPUS, and PsychInfo database.
Search terms included (“paediatric cardiac patients” OR “paediatric heart surgery” OR “congenital heart disease” OR “CHD” OR “congenital heart defect” OR “pediatric cardiac patient” OR “pediatric heart surgery” OR “heart defect”) AND (“mechanical circulatory support” OR “ECMO” OR “ECLS” OR “extracorporeal membrane oxygenation”) AND (“growth” OR “physical development” OR “neurodevelopment” OR “cognitive development” OR “height” OR “weight” OR “body mass index” OR “BMI” OR “cognitive outcomes” OR “neurodevelopmental outcome” OR “memory” OR “executive function” OR “psychosocial development” OR “quality of life” OR “QOF” OR “developmental delays”)
Study inclusion and exclusion criteria
Search criteria included articles being available in the English language, full-text articles, and primary research papers. The population was inclusive of both post-cardiotomy and non-cardiotomy patients. Studies which focused only on neurological outcomes were excluded from this review. References of identified papers were also reviewed to ascertain if any further papers could be included for screening.
Study selection
Duplicates were removed prior to screening. All articles yielded by the search were screened using title and abstract in Rayyan by two independent reviewers (JF and AC) before a decision was made. A third independent reviewer (AG) resolved any disagreements between the two reviewers. Subsequently, screened articles were analysed through a full-text review. Review articles and secondary articles were excluded from our study. Studies which focused only on neurological outcomes were also excluded from this review. Other forms of mechanical circulatory support, including studies focused primarily on ventricular assist device data, were excluded due to differing risk profiles, anticoagulation strategies, and subsequent stroke and neurodevelopmental risks. The inclusion criteria included articles which focused on the effect of extra-corporeal membrane oxygenation on growth and neurodevelopment. Figure 1 outlines the preferred reporting items for systematic reviews and meta-analysis flow diagram.
PRISMA flow chart.
Data extraction and appraisal of evidence
All full text of included articles were read and reviewed by two authors (JF and AC) and a unanimous decision was made regarding the inclusion or exclusion of studies. When there was a disagreement, the final decision was made by a third reviewer (AG). Using a pre-established protocol, the following data were extracted: first author, study design, date, aim of study, population number, and main objectives, main outcomes, type of mechanical circulatory support used, and outcome measure tool utilised. A data extraction sheet for this review was developed and pilot-tested using three randomly selected included studies and subsequently was refined accordingly. Data extraction was performed by two review authors (JF and AC). The correctness of the tabulated data was validated by a third author (AG).
Risk of bias
The risk of bias in the selected articles was evaluated using an adopted Cochrane collaboration risk of bias tool (Figure 2). The methodological quality of studies was assessed based on domains: Reference Barbaro, Paden and Guner1 study participation, Reference Pastuszko, Katz and Ravvin2 study response, 3 outcome measurement, Reference Brown, Pagel and Ridout4 statistical analysis and reporting, 5 and study confounding. An overall grading of low, medium, or high risk was then allocated.
Cochrane collaboration risk of bias tool.
Results
Study selection
A total of 5488 articles were identified in the literature search, of which 5230 articles were screened following deduplication and were read in full and assessed in accordance with the inclusion and exclusion criteria. A total of eight studies were included in this review following critical appraisal, featuring 302 patients. A summary of the studies collected, location of study, year of study, population size, type of mechanical circulatory support, measure of neurodevelopment, main objectives, and main outcomes are found in Table 1.
Resultant studies investigating the neurodevelopment outcome following mechanical circulatory support in paediatric cardiac patients
Measures of Neurodevelopment Outcome.
BSID –Bayley Scale of Infant Development.
SBI - Stanford-Binet Intelligence test.
WPPSI - Wechsler Preschool and Primary Scale of Intelligence.
WISC - Wechsler Intelligence Scale for Children-Revised.
POPC - Paediatric Overall Performance Category (POPC) scale.
PCPC - Paediatric Cerebral Performance Category (PCPC).
ASQ-3 Questionnaire - Ages & Stages Questionnaires.
MCSA - McCarthy Scales of Children’s Abilities.
PedsQL 4.0 – Paediatric Quality of Life.
Discussion
The systematic review provides insight into the variability and spectrum of neurodevelopmental outcomes, highlighting both the potential for recovery and the persistence of impairments.
Outcomes
Across the eight studies, neurodevelopmental impairments in mechanical circulatory support survivors are reported with significant variability, often contingent on the type of support and patient-specific factors. For example, Quadir et al. (2022) found that one in four infants who underwent extra-corporeal membrane oxygenation had moderate to severe neurodevelopmental impairment, with gross motor and language functions most impacted. Reference Quadir, Popat, Crowle, Galea, Chong and Goh7 Comparably, another study found that half of the surviving infants had abnormal cognitive outcomes. Reference Hamrick, Gremmels and Keet14 Ibrahim et al. (2000) highlighted that 59% of extra-corporeal membrane oxygenation patients showed moderate to severe neurological impairment, significantly higher than those supported by VADs, where only 20% experienced similar impairments (p = 0.03). In contrast, another study which focused on neurodevelopmental delays after congenital cardiac surgery showed that extra-corporeal membrane oxygenation patients had significantly worse outcomes in gross motor and problem-solving skills compared to non-extra-corporeal membrane oxygenation patients (P = 0.03). Reference Basgoze, Temur and Ozcan11 These studies highlight the broad variability of outcomes depending on the support modality and the type of developmental assessment used. With advancements in medical and surgical treatments, there has been a significant shift from focusing solely on survival to addressing long-term morbidity including neurodevelopmental outcomes in CHD patients. Many school-aged survivors of infant cardiac surgery require support services, such as tutoring, special education, and various therapies. Reference Ijsselstijn, Schiller Raisa and Holder15
However, it is imperative to note that these impairments are not uniform across the studies. One study found that the long-term survivors exhibit a lower prevalence of cognitive deficits, with many children showing a complete recovery by follow-up. Reference Di Leo, Biban and Mercolini9 This discrepancy could be attributed to the duration and timing of the follow-up, as longer-term follow-ups often reveal more encouraging neurodevelopmental trajectories. This is further emphasised by highlighting how 81% of extra-corporeal membrane oxygenation patients had normal to mild neurodevelopmental disability by the 2-year follow-up, Reference Chrysostomou, Maul and Callahan10 showing significant recovery from earlier impairments.
Cognitive impairments were frequently reported, with significant variability across studies. For instance, Quadir et al. (2022) identified that while 10% of extra-corporeal membrane oxygenation patients had severe cognitive impairments, 34.5% showed no impairment. This aligned with a similar study where 50% of surviving infants had normal cognitive outcomes. Reference Hamrick, Gremmels and Keet14 Critically, when comparing extra-corporeal membrane oxygenation and ventricular assist device, extra-corporeal membrane oxygenation patients exhibited a significantly higher rate of moderate to severe cognitive impairment than ventricular assist device patients (59% vs. 20%). Reference Ibrahim, Duncan, Blume and Jonas12 This suggests that the type of mechanical support plays a pivotal role in determining cognitive outcomes, with ventricular assist device patients generally improving better than those on extra-corporeal membrane oxygenation.
Interestingly, Lequier et al. (2008) found that 50% of extra-corporeal membrane oxygenation survivors had mental delay, but these impairments were not associated with the duration of cardiopulmonary resuscitation, pointing to other perioperative factors influencing cognitive outcomes such as lactate levels as a predictor of poor cognitive outcomes (HR = 1.13, 95% CI: 1.08–1.27). Quadir et al. (2022) also found lactate to be a significant association. This highlights the importance of acknowledging pre-extra-corporeal membrane oxygenation clinical status as a determinant of long-term neurodevelopment when devising outcome measures for neurodevelopment. Studies also suggest that while early cognitive impairments are common, their severity might diminish over time with proper follow-up and intervention. Therefore, standardising early neurodevelopmental assessments and providing timely interventions could mitigate these cognitive delays in the long term.
Motor impairments, particularly gross motor function deficits, were found to be the most significantly affected neurodevelopmental domain in many studies. Quadir et al. (2022) found that 62.1% of patients had gross motor impairment, with 38.9% having severe deficits. This finding is corroborated by Hamrick et al. (2003), where 72% of survivors had normal neuromotor outcomes, but the remaining 28% had abnormal or suspect outcomes. These results suggest that motor impairments, though common, may vary in severity depending on the clinical and perioperative factors influencing each patient. Sadhwani et al. (2019) further add to this, noting that extra-corporeal membrane oxygenation patients demonstrated persistent gross motor delays in 61% of cases. The association between motor impairments and perioperative hypoxic injury was also well-established across studies. An important consideration is whether gross motor impairments are the most frequently reported neurodevelopmental deficit due to their higher visibility, rather than a higher incidence of injury. Gross motor deficits are easily observable, making them more readily detected during clinical assessments. In contrast, cognitive impairments, which may be subtler and harder to identify in the early stages, could be underreported. It is possible that neurodevelopmental injuries affecting cognitive functions occur just as frequently but are less apparent in the immediate post-operative period or may require more specialist assessment for accurate detection.
Language impairments, though less frequently highlighted than motor and cognitive outcomes, were still a notable concern in several studies. One study observed that 27.6% of patients had receptive language impairments, while 20.1% had expressive language impairments. Reference Quadir, Popat, Crowle, Galea, Chong and Goh7 However, language impairments were generally less severe and pervasive than motor deficits. Reference Hamrick, Gremmels and Keet14 One study found that long-term survivors of extra-corporeal membrane oxygenation did not report significant language impairments, Reference Di Leo, Biban and Mercolini9 reflecting recovery over time in these functions—a pattern that contrasts with shorter-term studies such as Quadir et al. (2022). The variability in language outcomes could be due to differences in assessment methods and follow-up durations across the studies. For instance, shorter-term follow-ups might have captured earlier, more pronounced language delays, while longer-term follow-ups may reveal improvements in language skills over time. As language development is closely tied to cognitive and motor functions, early interventions targeting these areas might also benefit language outcomes, further supporting the need for comprehensive and longitudinal assessments. The Extracorporeal Life Support Organization guidelines currently advocate for post-extra-corporeal membrane oxygenation MRI brain, especially for high-risk groups with neurological events, to identify unrecognised brain injuries and stratify patients for closer follow-up. Reference Thiagarajan, Barbaro and Rycus16
The studies also highlight the role of perioperative factors in motor outcomes. Ibrahim et al. (2000) found that smaller patient size and circulatory arrest during surgery were significant predictors of motor impairments, which were more common in extra-corporeal membrane oxygenation than ventricular assist device patients. A similar study found that longer aortic cross-clamp times and perioperative complications were associated with worse motor outcomes. Reference Hamrick, Gremmels and Keet14 This reinforces the notion that surgical complexity and perioperative management are crucial factors in determining the extent of motor impairment post-mechanical circulatory support, and they suggest that ventricular assist device patients, who may avoid some of these high-risk factors, tend to survive better in terms of motor function.
Extra-corporeal membrane oxygenation versus ventricular assist device
Only one study compared outcomes between extra-corporeal membrane oxygenation and ventricular assist device. Reference Ibrahim, Duncan, Blume and Jonas12 The study found that extra-corporeal membrane oxygenation patients exhibited much higher rates of moderate to severe neurological impairment than ventricular assist device patients (59% vs. 20%). This was largely attributed to the fact that extra-corporeal membrane oxygenation patients tend to be younger and have more complex CHDs. Ventricular assist device-supported patients generally demonstrated more favourable long-term cognitive and motor outcomes, which could be linked to the different pathophysiological impacts of these devices Reference Sadhwani, Cheng and Stopp8 including differing anticoagulation and thromboembolic risk profiles.
The differences in outcomes between extra-corporeal membrane oxygenation and ventricular assist device may stem from the less invasive nature of ventricular assist device and its ability to support the heart for longer durations without the same degree of risk for ischaemic or hypoxic brain injury. Reference Hervey-Jumper, Annich, Yancon, Garton, Muraszko and Maher17 Extra-corporeal membrane oxygenation, particularly when used in an emergency setting such as extracorporeal cardiopulmonary resuscitation, can exacerbate the risks of neurological damage due to the rapid and often critical nature of its initiation. The relatively higher incidence of neurological injury in paediatric extra-corporeal membrane oxygenation, compared to ventricular assist device, raises questions about the trade-off between immediate survival and severe long-term neurodevelopmental quality of life, a consideration that is often overlooked in acute decision-making. Reference Twilhaar, Wade, de Kieviet, van Goudoever, van Elburg and Oosterlaan18 Ultimately, extra-corporeal membrane oxygenation is a short-term mechanical circulatory support option, whilst ventricular assist device can support patients for weeks to years in some cases. As such, the prolonged duration of ventricular assist device support allows for better neurodevelopmental recovery, closer monitoring, and rehabilitation, whereas extra-corporeal membrane oxygenation patients face higher risks of acute neurological injury due to its emergent nature and shorter support duration. Therefore, direct comparisons between extra-corporeal membrane oxygenation and ventricular assist device neurodevelopmental outcomes may not be appropriate, as their distinct mechanisms, durations of support, and patient selection criteria influence outcomes in fundamentally different ways.
Outcome measures
Multiple instruments were used to measure neurodevelopment ranging from independent assessments by a paediatrician to established tools such as the Bayley Scales of Infant Development. The Bayley Scales of Infant Development is a well-established tool in paediatric research as it provides a comprehensive assessment across key neurodevelopmental domains. One of the main advantages of the Bayley Scales of Infant Development is its ability to break down neurodevelopment into specific categories, such as gross motor, fine motor, and cognitive abilities etc. However, the tool was validated for younger children, typically under 3 years of age. As a result, it may not be as useful for tracking long-term developmental outcomes, particularly those that emerge later in childhood, such as behavioural or attention-related issues. Critically, a child who performs well on the Bayley Scales of Infant Development may still struggle with more complex tasks measured by the Wechsler Intelligence Scale for Children, leading to apparent inconsistencies in results. Cognitive outcomes in pre-term children are also highly variable, and early assessment tools such as the Bayley Scales of Infant Development can often fail to capture long-term cognitive and behavioural issues that emerge in adolescence. Reference Fernando, Scott and Talarico19 Future studies should aim for consistency in tools used across time points or develop cross-compatible methodologies to allow for holistic longitudinal tracking.
The Stanford-Binet Intelligence test and the Wechsler Preschool and Primary Scale of Intelligence were also employed in some studies. These tools assess a wider range of cognitive functions and are suitable for older children, which helps address some of the limitations seen with the Bayley Scales of Infant Development. However, they still present challenges in terms of cultural adaptability and the long-term follow-up of behavioural or attention-related issues.
Another outcome measure used was a modified Ages & Stages Questionnaires (ASQ-3). The ASQ-3 provides an age-appropriate screening for developmental delays and is usually administered by the guardian. While the Bayley Scales of Infant Development offers more precise and clinician-driven insights, the ASQ-3 is more accessible and practical for ongoing developmental monitoring in everyday environments. The variability in the depth and method of assessment between these tools highlights the importance of selecting the appropriate tool based on the clinical need and setting, with the Bayley Scales of Infant Development being more suited for formal diagnosis and the ASQ-3 for early and broad screening.
One study adopted a broader approach to assessing neurodevelopmental outcomes by utilising a combination of parent-reported questionnaires and medical assessments (Ibrahim et al., 2000). This method allowed for the inclusion of long-term survivors who may not have had access to structured developmental testing. The advantage of this approach is that it captures a wider range of developmental indicators over a longer follow-up period, potentially identifying issues that might not emerge in early childhood. However, the lack of standardised testing could lead to underreporting or overreporting of developmental issues e.g., parents might be unaware of subtler impairments, or doctors may have inconsistent evaluation criteria. Educating families on the potential for long-term neurodevelopmental post-mechanical circulatory support is essential. Reference Thiagarajan, Barbaro and Rycus16 Families need to be informed that some deficits may only become apparent as the child grows, requiring vigilant monitoring for issues such as academic difficulties or issues surrounding social interactions. Additionally, families of extra-corporeal membrane oxygenation survivors also experience significant stress and support should form a key component comprehensive post-mechanical circulatory support care.
One study utilised the use of neurological examinations at specific intervals (1.5, 2.5, and 4.5 years), providing a more clinically accurate perspective on determining motor and cognitive outcomes. Reference Hamrick, Gremmels and Keet14 This combination of formal developmental testing and clinical neurological assessments allows for the identification of motor abnormalities, such as language processing or tremors, that might not be captured through developmental scales alone. However, the major disadvantage of clinical examinations is that they are often less sensitive to subtle cognitive delays or behavioural issues that may only become apparent through structured and standardised testing. The Paediatric Overall Performance Category scale and Paediatric Cerebral Performance Category are also often used to assess global functioning, but their broader scope can miss specific cognitive impairments. This gap could be filled by incorporating more standardised neuropsychological assessments, particularly for older children. A recent study found that survivors of extra-corporeal membrane oxygenation life support had a 24% higher rate of new mental health diagnoses after discharge compared to other ICU survivors. Reference Jiang, Yan and Wang20
A significant limitation across all studies is the inconsistent definition of what constitutes a “normal” or “impaired” neurodevelopmental outcome. While some studies used standard deviation cut-offs to categorise levels of impairment (mild, moderate, severe) Reference Quadir, Popat, Crowle, Galea, Chong and Goh7,Reference Ibrahim, Duncan, Blume and Jonas12 , others relied more on qualitative descriptions provided by clinical observations. Reference Di Leo, Biban and Mercolini9 The lack of standardisation in defining and categorising impairments complicates the interpretation of neurodevelopmental trajectories and the comparison of outcomes across studies. Moving forward, a universally accepted framework for defining and measuring neurodevelopmental impairments would provide much-needed consistency.
The main benefit of using tools such as the Bayley Scale of Infant Development, McCarthy Scales of Children’s Abilities, and PedsQL 4.0 is their reliability and established validity in paediatric neurodevelopmental assessments. These tools are sensitive to a wide range of cognitive and motor impairments, particularly in young children. However, their primary disadvantage is the limited scope of follow-up. Cognitive and behavioural issues that arise later in childhood, such as executive functioning or attention deficits, are often missed by early childhood assessments. The McCarthy Scales of Children’s Abilities and the Paediatric Quality of Life (PedsQL 4.0) also offer robust frameworks for capturing a wide range of cognitive, motor, and emotional outcomes, particularly in children with chronic conditions. The Extracorporeal Life Support Organization has provided a set of recommendations for assessing and evaluating neurologic outcomes after extra-corporeal membrane oxygenation decannulation and following hospital discharge. Reference Thiagarajan, Barbaro and Rycus16
Finally, standardised tests may not always translate effectively across different cultural or linguistic contexts and may lead to inaccurate assessments or misinterpretation of results. In some settings, locally developed tools may be necessary to better reflect the developmental milestones and cognitive challenges relevant to specific populations. A single assessment tool may not fully capture the diversity of neurodevelopmental outcomes in paediatric patients, particularly given the prevalence of learning disabilities in this population. The NHS England Congenital Heart Disease Standards and Specifications emphasise the importance of having learning disabilities teams available 21 , as approximately 10% of CHD patients present with learning disabilities by the time they reach adult services. Reference Jiang, Yan and Wang20 Given the complexity of CHD, care plans should integrate neurodevelopmental assessments into routine follow-up visits, allowing tracking of neurodevelopment over time.
Recovery
Early neurological assessments might not always predict long-term outcomes accurately as initial impairments identified shortly after extra-corporeal membrane oxygenation support may not persist into later childhood or adulthood. This variability suggests that neurodevelopmental recovery is possible, with many patients demonstrating significant improvement over time. The capacity for recovery further highlights the importance of comprehensive and longitudinal follow-up to understand the full impact of mechanical circulatory support on neurodevelopment.
One study found that cerebral infarctions were a key factor associated with long-term neurological deterioration. Reference Chrysostomou, Maul and Callahan10 While most patients improved, those who experienced significant cerebral injuries had worse outcomes, highlighting the importance of neuroprotection during extra-corporeal membrane oxygenation. 75% of patients had significant impairments at discharge, and only 19% had moderate to severe disabilities by the 2-year follow-up, indicating significant potential for recovery. Reference Chrysostomou, Maul and Callahan10 Similarly, a study by Jiang et al. (2024) showed that with appropriate rehabilitation and early interventions, many extra-corporeal membrane oxygenation survivors can experience meaningful improvements in cognitive and motor functions within 3–5 years post-surgery. This potential for recovery highlights the importance of long-term follow-up and early therapeutic interventions. Children with early cognitive delays often show marked improvements by school age, provided they receive timely support (23). However, despite initial recovery, children supported by extra-corporeal membrane oxygenation often experience subtle but significant impairments in cognitive flexibility and social interaction that do not manifest until later in childhood, challenging assumptions about the completeness of early recovery.
Neurodevelopmental outcomes following extra-corporeal membrane oxygenation vary with age, as infants are more vulnerable to hypoxic–ischaemic injury and early disruptions in brain development, leading to motor, cognitive, and language delays. While some catch up over time, others face persistent deficits. In contrast, teenagers, with more developed neural networks, may recover better but are prone to executive function deficits and psychosocial challenges. Younger children require ongoing developmental monitoring, while older patients often need academic and social support post-recovery.
Previous research has proposed management frameworks for the surveillance, screening, evaluation, and management of developmental disorders in children with CHD, stratifying patients into risk categories. Reference Ijsselstijn, Schiller Raisa and Holder15 Periodic evaluations throughout childhood are recommended to identify and address deficits early, allowing for appropriate therapeutic interventions
Overall, the neurodevelopmental outcomes for survivors of mechanical circulatory support devices are diverse, with evidence indicating both significant impairments and positive developmental trajectories. The variability in outcomes across studies highlights the need for further research to standardise assessment methods and improve our understanding of long-term neurodevelopmental recovery.
Duration of follow-up
Short-term follow-ups typically capture the immediate post-extra-corporeal membrane oxygenation neurodevelopmental status but may not fully reflect the long-term outcomes of these patients. For example, Quadir et al. (2022), at 12 months follow-up from discharge, found that 62.1% of patients had gross motor impairments and 10.3% had severe cognitive impairments—these early findings indicate significant deficits in neurodevelopment. However, studies with longer follow-up durations which extended over 4–6 years, observed much more encouraging recovery trajectories. Di Leo et al. (2019) highlighted that 90% of long-term extra-corporeal membrane oxygenation survivors showed no cognitive impairment, and 95% had no significant language or motor deficits. Similarly, Chrysostomou et al. (2013), with a follow-up of 2 years, reported that 81% of extra-corporeal membrane oxygenation patients had improved to mild or no neurodevelopmental disability. These findings suggest that many neurodevelopmental impairments identified early may improve with age, particularly with adequate rehabilitative support and interventions.
However, recovery is not guaranteed for all patients. For instance, Sadhwani et al. (2019) found that despite a follow-up of 2 years, gross motor and cognitive delays persisted in a substantial portion of extra-corporeal membrane oxygenation patients, suggesting that certain impairments may be more resistant to recovery. This variability in results across studies underscores that neurodevelopmental recovery depends not only on the length of follow-up but also on the type and timing of interventions, as well as patient-specific factors such as the severity of the underlying cardiac condition, other comorbidities, and the duration of mechanical circulatory support support.
Limitations
This systematic review is subject to several limitations. First, the studies included used a variety of neurodevelopmental assessment tools, leading to inconsistencies in the measurement and reporting of outcomes. This lack of standardisation makes direct comparisons across studies challenging including performing a meta-analysis and may have introduced bias in the interpretation of results. In addition, there was variability in the indications for extra-corporeal membrane oxygenation, the type of mechanical circulatory support used, and the patient’s condition at the time of extra-corporeal membrane oxygenation initiation, including whether extracorporeal cardiopulmonary resuscitation was required. These differences complicate the analysis, as each of these factors could independently influence neurodevelopmental outcomes.
Moreover, some studies relied on subjective assessments, such as parental or clinician reporting, which may not be as accurate or comprehensive as objective, standardised neuropsychological testing. Future research should aim to address these limitations by employing standardised assessment tools, larger multi-centre cohorts, and longer-term follow-ups to better understand the full impact of extra-corporeal membrane oxygenation on neurodevelopmental outcomes. The Extracorporeal Life Support Organization guidelines provide a framework for structured follow-up programmes post-extra-corporeal membrane oxygenation including timing and assessments. Follow-up should begin within the first 3 months of discharge, with subsequent evaluations at 6 months and 1 year to assess for early detection of neurodevelopmental delays or complications.
A key limitation of the studies reviewed is the absence of an appropriate control group. The comparison of extra-corporeal membrane oxygenation patients to those managed without such interventions is crucial to understanding the true benefits of mechanical circulatory support beyond survival. Evidence suggests that survivors of cardiac arrest or low cardiac output states without mechanical circulatory support experience significant end-organ damage, particularly brain injury with subsequent neurodevelopmental dysfunction. However, ethical and logistical challenges in withholding life-saving interventions limit the feasibility of randomised controlled trials. Comparative studies that retrospectively examine outcomes in patients managed with and without extra-corporeal membrane oxygenation could address this gap in the literature. Ultimately, the decision-making process for a patient requiring mechanical circulatory support often involves balancing survival against potential neurodevelopmental impairments. This is a deeply personal decision for families. Emerging evidence suggests that many parents value the opportunity for their child to survive, even with the possibility of developmental delays, as these impairments may improve over time with appropriate interventions. Future qualitative studies exploring parental perspectives could further inform clinical practices and enhance shared decision-making frameworks.
When assessing neurodevelopmental outcomes, there is ongoing debate regarding the most appropriate methods, especially in resource-limited settings. While higher neurodevelopmental burdens may cause concern for families in high-income countries, their significance in resource-constrained environments can be quite different. In these settings, the focus often shifts toward more severe outcomes, such as a child’s capacity for independent living. As a result, pre- or intra-operative interventions aimed at reducing neurodevelopmental impairments may not always be feasible, with the priority instead shifting from achieving marginal cognitive gains to preventing severe disability.
Conclusion
This systematic review highlights the variability in neurodevelopmental outcomes for paediatric cardiac patients undergoing extra-corporeal membrane oxygenation. While these interventions are lifesaving, they come with considerable risks of neurodevelopmental impairments, especially in cognitive, motor, and language domains. Neurodevelopmental impairments are common but vary depending on the type of support, patient-specific factors, and follow-up duration. For example, ventricular assist device patients generally demonstrate better cognitive and motor outcomes than extra-corporeal membrane oxygenation patients, likely due to differences in device invasiveness and clinical context. Encouragingly, many patients exhibit substantial recovery over time, especially with appropriate rehabilitative support and interventions. However, there remains a substantial gap in our understanding of these outcomes due to inconsistent definitions and measurement protocols. The lack of standardised outcome measures and inconsistent definitions of neurodevelopmental impairments poses a challenge to interpreting and comparing results across studies. Future research should focus on establishing universal assessment protocols and addressing gaps in the literature, such as the role of perioperative factors and family perspectives in decision-making.
Acknowledgements
None.
Funding statement
No funding was received for this research article.
Competing interests
None.
Ethical standard
None required.
