Aspirin Responsiveness in a Cohort of Pediatric Patients with Right Ventricle to Pulmonary Artery Conduits and Transcatheter Valve Replacement Systems.

The aim of this study was to determine the rate of aspirin responsiveness in a cohort of pediatric patients with in situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or transcatheter valve replacements (TVR). Aspirin is routinely prescribed to these patients. Optimizing anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group. This was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as > 20% platelet aggregation using light transmission platelet aggregometry (LTA) and < 50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made. Thirty patients participated. Median age was 9 years (2 months to 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit and 24 (80%) had a TVR, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n = 7/30) with median LTA 74.55% (60-76%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. Four patients on repeat testing were responsive to aspirin by laboratory tests. The rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%.

Cardiac Rhabdomyomas Presenting with Critical Cardiac Obstruction in Neonates and Infants: Treatment Strategies and Outcome, A Single-Center Experience.

Cardiac rhabdomyomas are the most common benign pediatric heart tumor in infancy, which are commonly associated with tuberous sclerosis complex (TSC). Most rhabdomyomas are asymptomatic and spontaneously regress over time. However, some cases especially in neonates or small infants can present with hemodynamic instability. Surgical resection of the tumor, which has been the gold standard in alleviating obstruction, is not always possible and may be associated with significant morbidity and mortality. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be safe and effective in the treatment of TSC. We present the outcomes of neonates and an infant who received treatment for symptomatic rhabdomyomas at a tertiary cardiology center. Medical records were reviewed to obtain clinical, demographic, and outcome data. Six patients received interventions for symptomatic rhabdomyomas, median age at presentation was 1 day old (range from 1 to 121 days old), and 67% of the patients had a pathogenic mutation in TSC gene. One patient underwent surgical resection of solitary tumor at right ventricular outflow tract (RVOT) successfully. In the four patients with left ventricular outflow tract (LVOT) obstruction, two patients received combined therapy of surgical debulking of LVOT tumor, Stage I palliation procedure, and mTORi and two patients received mTORi therapy. One patient with RVOT obstruction underwent ductal stenting and received synergistic mTORi. Four of the five patients had good response to mTORi demonstrated by the rapid regression of rhabdomyoma size. 83% of patients are still alive at their latest follow-up, at two to eight years of age. One patient died on day 17 post-LVOT tumor resection and Hybrid stage one due to failure of hemostasis, in the background of familial factor VII deficiency. Treatment of symptomatic rhabdomyoma requires individualized treatment strategy based on the underlying pathophysiology, with involvement of multidisciplinary teams. mTORi is effective and safe in inducing rapid regression of rhabdomyomas. A standardized mTORi prescription and monitoring guide will ensure medication safety in neonates and infants with symptomatic cardiac rhabdomyoma. Although the majority of tumors responded to mTORi, some prove to be resistant. Further studies are warranted, ideally involving multiple international centers with a larger number of patients.

Critical congenital heart disease: contemporary prenatal screening performance and outcomes in a multi-centre perinatology service.

BACKGROUND: Prenatal detection of critical congenital heart disease (CCHD) optimises perinatal decision-making and neonatal outcomes. The objective of this study was to determine the prenatal screening performance, care pathways and perinatal outcomes for prenatally and postnatally diagnosed cases of CCHD over a four-year period. STUDY DESIGN: This retrospective cohort study in a tertiary centre and its two affiliated secondary sites examined all cases of CCHD, including cases of pregnancy termination and in-utero fetal death, neonatal death and liveborn babies that underwent cardiac catheterization or surgery in the first six weeks of life. Prenatal and postnatal data were ascertained from the first trimester assessment for all patients diagnosed prenatally. Cases requiring intervention that were first identified in the postnatal period were included to determine prenatal detection rates. Follow-up for all cases of CCHD continued to one year of age. RESULTS: In a consecutive cohort of 49,950 pregnancies in a 4-year period 01/2019 to 12/2022, a prenatal diagnosis of CCHD was made in 96 cases, yielding a prevalence of 1.9 per 1000 births. The prenatal detection for right duct-dependant heart pathology and congenital heart block was 100%, 85% for left duct-dependant pathology and 93% for transposition of the great arteries (TGA). In the prenatally diagnosed group, 37% of cases were complicated by extracardiac structural abnormalities, a genetic diagnosis or both. All cases of prenatal detection were identified in the context of routine anatomy screening rather than specialist Fetal Cardiac screening services. Almost half of all pregnancies complicated by CCHD did not undergo neonatal cardiac intervention, by virtue of parental choice determined either prenatally or after birth. An additional eight babies were diagnosed with CCHD in the neonatal period, such that the prenatal detection rate for CCHD was 92% (96/104, 95% CI = 84%-96%). Survival at 1-year for infants deemed suitable for CCHD surgery was 85%. CONCLUSION: In a large unselected population, optimal rates of prenatal detection of critical congenital heart disease can be achieved by a protocolised approach to mid-trimester fetal anatomy ultrasound, underpinned by a programme of sonographer education and training. The cardiac abnormalities most likely to evade prenatal detection are left-sided obstructive lesions.

Neonatal sepsis and cardiovascular dysfunction I: mechanisms and pathophysiology.

The highest incidence of sepsis across all age groups occurs in neonates leading to substantial mortality and morbidity. Cardiovascular dysfunction frequently complicates neonatal sepsis including biventricular systolic and/or diastolic dysfunction, vasoregulatory failure, and pulmonary arterial hypertension. The haemodynamic response in neonatal sepsis can be hyperdynamic or hypodynamic and the underlying pathophysiological mechanisms are heterogeneous. The diagnosis and definition of both neonatal sepsis and cardiovascular dysfunction complicating neonatal sepsis are challenging and not consensus-based. Future developments in neonatal sepsis management will be facilitated by common definitions and datasets especially in neonatal cardiovascular optimisation. IMPACT: Cardiovascular dysfunction is common in neonatal sepsis but there is no consensus-based definition, making calculating the incidence and designing clinical trials challenging. Neonatal cardiovascular dysfunction is related to the inflammatory response, which can directly target myocyte function and systemic haemodynamics.

Assessment of Myocardial Function in Infants of Mothers with Gestational Diabetes Mellitus Using Deformation Imaging over the First Year of Age.

OBJECTIVE: To assess serial myocardial performance and pulmonary vascular resistance (PVR) in infants of mothers with gestational diabetes mellitus (GDM) over the first year of life. STUDY DESIGN: This was a prospective, observational study. Echocardiography was performed at birth, 6 months, and 1 year of age. Pulmonary artery acceleration time and left ventricular (LV) eccentricity index provided surrogate measurements of PVR. Biventricular function was assessed by tissue Doppler imaging and deformation analysis. RESULTS: Fifty infants of mothers with GDM were compared with 50 controls with no difference in gestation (38.9 ± 0.8 weeks vs 39.3 ± 0.9 weeks; P = .05) or birthweight (3.55 ± 0.49 kg vs 3.56 ± 0.41 kg; P = .95). At 1 year of age, the pulmonary artery acceleration time was lower (70 ± 11 vs 79 ± 10; P = .01) in the GDM group. LV global longitudinal strain (24.7 ± 1.9 vs 28.8 ± 1.8 %; P < .01), LV systolic strain rate (1.8 ± 0.2 vs 2.1 ± 0.3 1/s; P < .01), and RV free wall strain (31.1 ± 4.8 vs 34.6 ± 3.9 %; P < .01) were lower in the GDM cohort at 1 year of age (all P values adjusted for gestation, mode of delivery, and maternal body mass index). CONCLUSIONS: Our findings demonstrate higher indices of PVR and lower biventricular function in infants of mothers with GDM compared with controls at each time point assessed in this study over the first year of life.

Reproducibility of the EL-Khuffash PDA severity score and PDA diameter measurements in extremely preterm infants.

BACKGROUND & AIM: Almost all randomised controlled trials use a Patent Ductus Arteriosus (PDA) diameter ≥ 1.5 mm as the primary criterion to ascribe haemodynamic significance to the PDA. The aim of this study was to evaluate if calculation of a PDA Severity Score (PDAsc) possessed superior intra- and inter-rater reproducibility when compared with the measurement of PDA diameter alone. METHODS: This cross-sectional study assessed echocardiograms performed on infants <30 weeks gestation at 36 to 72 h of age between July 2020 and December 2022 to calculate the PDAsc. Intra-observer reproducibility of the PDA diameter and PDAsc were assessed by blinded repeated measurements performed by one investigator (AS) 4 weeks apart. One set of those measurements was compared with blinded measurements by another investigator (RM) to assess inter-rater reliability. RESULTS: Echocardiograms from 150 infants with mean ± SD gestation and birthweights of 26.5 ± 1.7 weeks and 903 ± 249 g respectively were examined. The PDAsc demonstrated near perfect agreement both within raters (Cohen's Kappa 0.97, p < 0.01) and between raters (Cohen's Kappa 0.94, p < 0.01) with regards to the threshold for treatment (a cut off ≥5.0). The PDA diameter threshold only demonstrated moderate agreement within raters (Kappa 0.57, p < 0.01) and between raters (Kappa 0.54, p < 0.01). In this cohort, 31 % of infants with a low risk PDAsc (< 5.0) also had a PDA diameter >1.5 mm. CONCLUSION: Future RCTs for PDA treatment should strongly consider abandoning the use of PDA diameter in isolation as a criterion for recruitment into clinical trials.

Assessment of myocardial function in infants conceived by assisted reproductive technologies using deformation imaging over the first year of age: A cohort study.

BACKGROUND AND AIM: There is emerging evidence of cardiovascular remodeling and functional impairment in individuals conceived via Assisted Reproductive Technologies (ART). The aim of this study was to serially assess myocardial function and pulmonary hemodynamic measurements in infants conceived via ART over the first year of age and to compare them to a cohort of spontaneously conceived controls. METHODS: This was a prospective, observational study. Echocardiography was performed at Day 2, 6 months and 1 year of age. Biventricular function was assessed by deformation analysis. Pulmonary artery acceleration time (PAAT) and left ventricular (LV) eccentricity index (LVEI) provided surrogate measures of pulmonary vascular resistance (PVR). RESULTS: Fifty infants conceived via ART were compared to 50 spontaneously conceived controls. There were no differences in baseline infant demographics between the two groups. At 1 year of age right ventricular (RV) basal and RV mid cavity diameters were higher in the ART group. PAATi was lower and LVEI higher in the ART group at 6 months and 1 year. In the ART group, LV global longitudinal strain, LV systolic strain rate, LV early diastolic strain rate and RV free wall strain were lower on Day 2, 6 months, and 1 year of age in comparison to the control group (all p < .05). Within the ART group, on linear regression, maternal age, the type of ART treatment or egg characteristics did not influence PAAT or deformation measurements. CONCLUSION: Our findings suggest that greater cardiovascular surveillance of ART conceived infants may be warranted.

The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1).

OBJECTIVE: To assess the impact of milrinone administration on time spent on nitric oxide (iNO) in infants with acute pulmonary hypertension (aPH). We hypothesized that intravenous milrinone used in conjunction with iNO would reduce the time on iNO therapy and the time spent on invasive ventilation in infants ≥34 weeks gestation with a diagnosis of aPH. We aimed to assess the practicality of instituting the protocol and contributing to a sample size calculation for a definitive multicentre study. STUDY DESIGN: This was a multicentre, randomized, double-blind, two arm pilot study, with a balanced (1:1) allocation. Infants with a gestation ≥34 weeks and a birth weight ≥2000 grams aPH, an oxygenation index of ≥10, and commenced on iNO were eligible. Participants on iNO were assigned to either a milrinone infusion (intervention) or a normal saline infusion (placebo) for up to 35 h. The primary outcome was time on iNO and feasibility of conducting the protocol. RESULTS: The trial was terminated early after 4 years of enrollment due to poor recruitment. Four infants were allocated to the intervention arm and 5 to the placebo arm. The groups were well matched for baseline variables. No differences were seen in any of the primary or secondary outcomes. CONCLUSION: Conducting an interventional trial in the setting of acute pulmonary hypertension in infants is not feasible using our current approach. Future studies in this area require alternative trial design to improve recruitment as this topic remains understudied in the neonatal field. TRIAL REGISTRATION: www.isrctn.com ; ISRCTN:12949496; EudraCT Number:2014-002988-16.

Fontaine progeroid syndrome-A case report.

Fontaine progeroid syndrome (FPS) is an autosomal dominant condition caused by pathogenic variants in the SLC25A24 gene. Eleven cases have been described in the literature, with early lethality in some. We discuss the clinical course of a patient from birth until his death at 7 months.

Multisystem inflammatory syndrome in the context of paediatric COVID-19 infection in the Republic of Ireland April 2020 to April 2021.

AIM: Our aim was to describe the epidemiology of multisystem inflammatory syndrome in children (MIS-C) in the Republic of Ireland, in the context of all cases of COVID-19 in children, during the first year of the SARS-CoV-2 pandemic. METHODS: Cases of MIS-C were identified by prospective surveillance in Irish hospitals from April 2020 to April 2021. Paediatric COVID-19 cases and outbreaks in schools or childcare facilities were notified to and routinely investigated by Public Health. Univariate and bivariate analyses were carried out in Excel, Stata and JMP statistical package. RESULTS: Fifty-four MIS-C cases (median age 7.58 years; males 57%) were identified over the study period. MIS-C incidence was higher in certain ethnicities ('black' 21.3/100,000 [95% CI 4.3-38.4]; and 'Irish Traveller' 14.7/100,000 [95% CI -5.7-35.1]) than those of 'white' ethnicity (3.4 /100,000). MIS-C cases occurred in three temporal clusters, which followed three distinct waves of community COVID-19 infection, irrespective of school closures. Formal contact tracing identified an epidemiological link with a COVID-19-infected family member in the majority of MIS-C cases (77%). In contrast, investigation of COVID-19 school outbreaks demonstrated no epidemiological link with MIS-C cases during the study period. CONCLUSION: Efforts at controlling SARS-CoV-2 transmission in the community may be a more effective means to reduce MIS-C incidence than school closures. Establishing a mandatory reporting structure for MIS-C will help delineate the role of risk factors such as ethnicity and obesity and the effect of vaccination on MIS-C incidence.

Serial Assessment of Cardiac Function and Pulmonary Hemodynamics in Infants With Down Syndrome.

BACKGROUND: There is a dearth of longitudinal data describing the evolution of cardiopulmonary hemodynamics in infants with Down syndrome (DS) beyond infancy. We hypothesized that babies with DS, independent of the presence of congenital heart disease (CHD), demonstrate biventricular systolic and diastolic impairment and sustained elevation of pulmonary pressures compared with controls over the first 2 years of age. METHODS: This was a prospective observational cohort study of 70 infants with DS (48 with CHD and 22 without CHD) and 60 controls carried out in 3 tertiary neonatal intensive care units in Dublin, Ireland. Infants with DS with and without CHD and non-DS controls underwent serial echocardiograms at birth, 6 months, 1 year, and 2 years of age to assess biventricular systolic and diastolic function using deformation analysis. Pulmonary vascular resistance was assessed using pulmonary artery acceleration time and left ventricular (LV) eccentricity index. RESULTS: Infants with DS exhibited smaller LV (birth: 27 ± 4 vs 31 ± 2 mm, P < .01; 2 years: 43 ± 5 vs 48 ± 4 mm, P < .01) and right ventricular (birth: 28 ± 3 vs 31 ± 2 mm, P < .01; 2 years: 40 ± 4 vs 44 ± 3 mm, P < .01) lengths and lower LV (birth: -19% ± 3% vs -22% ± 2%, P < .01; 2 years: -24% ± 2% vs -26% ± 2%, P < .01) and right ventricular (birth: -19% ± 4% vs -22% ± 3%, P < .01; 2 years: -29% ± 6% vs -33% ± 4%, P < .01) systolic strain over the 2-year period. Pulmonary artery acceleration time was lower in the DS group throughout the study period (birth: 44 ± 10 vs 62 ± 14 ms, P < .01; 2 years 71 ± 12 vs 83 ± 11 ms, P < .01). No differences were observed between DS infants with and without CHD (all P > .05). CONCLUSIONS: Infants with DS exhibit impaired maturational changes in myocardial function and pulmonary vascular resistance. Such novel findings provide valuable insights into the pathophysiology affecting cardiorespiratory morbidity in this population.

Severe Restriction of a VSD and Development of Pulmonary Atresia in a Patient with Transposition of the Great Arteries: Fetal Diagnosis.

Pulmonary atresia with an intact ventricular septum typically occurs in patients with concordant atrioventricular and ventriculoarterial connections. When it does occur in patients with discordant connections, it is most frequently seen in association with congenitally corrected transposition. We present a rare case of transposition of the great arteries with a ventricular septal defect (VSD) detected in fetal life which evolved throughout pregnancy resulting in the development of pulmonary atresia and severe restriction of the VSD.

Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses.

BACKGROUND: Infants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively. METHODS: Infants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-ß; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1ß, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO). RESULTS: Ninety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1ß, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05). CONCLUSIONS: Children with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children. IMPACT: This study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively. These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population. Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.

Relationship Between Postnatal Pulmonary Arterial Pressure and Altered Diastolic Function in Neonates with Down Syndrome.

OBJECTIVE: To assess the influence of diastolic dysfunction on the evolution of pulmonary hypertension in neonates with Down Syndrome over the early newborn period. STUDY DESIGN: This was a prospective observational cohort study. Echocardiography was performed three times over the first week of life in both Down syndrome and control cohorts. Measurements of pulmonary arterial pressure in addition to left ventricular (LV) and right ventricular systolic and diastolic function were collected. RESULTS: Seventy babies with Down syndrome and 60 control infants were enrolled. Forty-eight of the infants with Down syndrome (69%) were born with congenital heart disease (CHD). Echocardiography surrogates of pulmonary hypertension and myocardial function remained significantly impaired in the Down syndrome group in comparison with control infants (all P < .01). In the Down syndrome group, LV early diastolic strain rate was independently associated with measures of pulmonary hypertension while controlling for gestational age, cesarean delivery, and the presence of CHD (P < .01). CONCLUSIONS: Intrinsic LV diastolic impairment is directly associated with higher indices of pulmonary hypertension in infants with Down syndrome and may be a contributing factor to its evolution.

Multimodality imaging in delineation of complex sinus venosus defects and treatment outcomes over the last decade.

BACKGROUND: Diagnosis of sinus venosus defects, not infrequently associated with complex anomalous pulmonary venous drainage, may be delayed requiring multimodality imaging. METHODS: Retrospective review of all patients from February 2008 to January 2019. RESULTS: Thirty-seven children were diagnosed at a median age of 4.2 years (range 0.5-15.5 years). In 32 of 37 (86%) patients, diagnosis was achieved on transthoracic echocardiography, but five patients (14%) had complex variants (four had high insertion of anomalous vein into the superior caval vein and three had multiple anomalous veins draining to different sites, two of whom had drainage of one vein into the high superior caval vein). In these five patients, the final diagnosis was achieved by multimodality imaging and intra-operative findings. The median age at surgery was 5.2 years (range 1.6-15.8 years). Thirty-one patients underwent double patch repair, four patients a Warden repair, and two patients a single-patch repair. Of the four Warden repairs, two patients had a high insertion of right-sided anomalous pulmonary vein into the superior caval vein, one patient had bilateral superior caval veins, and one patient had right lower pulmonary vein insertion into the right atrium/superior caval vein junction. There was no post-operative mortality, reoperation, residual shunt or pulmonary venous obstruction. One patient developed superior caval vein obstruction and one patient developed atrial flutter. CONCLUSION: Complementary cardiac imaging modalities improve diagnosis of complex sinus venosus defects associated with a wide variation in the pattern of anomalous pulmonary venous connection. Nonetheless, surgical treatment is associated with excellent outcomes.

Peri-operative myocardial performance in infants with Down syndrome undergoing CHD repair.

BACKGROUND: We aimed to characterise the impact of Down syndrome on myocardial performance and loading conditions in infants with Down syndrome and CHD over the peri-operative period by comparing them with infants matched for cardiac lesion with a normal microarray. METHODS: Left ventricular global longitudinal strain, right ventricular free wall longitudinal strain, left ventricular end-systolic wall stress, and right ventricular systolic pressure were measured in the two groups over the peri-operative period. RESULTS: Fifty-five infants had a diagnosis of Down syndrome and these were compared with 29 control infants. Left ventricular global longitudinal strain decreased in both groups post-operatively with the Down syndrome group demonstrating some recovery pre-discharge (18 ± 3 versus 16 ± 3 %, p = 0.01). Right ventricular longitudinal strain significantly decreased in both groups post-operatively with the control group demonstrating better recovery by hospital discharge (14 ± 4 versus 18 ± 6 %, p < 0.01). End-systolic wall stress was lower and right ventricular systolic pressure was higher in the Down syndrome group throughout the study period (all p < 0.05). Down syndrome was an independent predictor of the duration of ventilation, post-operative use of inotropes, and intensive care stay. Right ventricular longitudinal strain was an independent predictor of duration of intensive care stay. CONCLUSION: This study demonstrates the difference between the two groups in relation to left and right ventricular function, particularly prior to discharge, and outlines the additional impact a diagnosis of Down syndrome has on myocardial performance during the peri-operative period.

Multi-Organ Dysfunction in Cerebral Palsy.

Cerebral Palsy (CP) describes a heterogenous group of non-progressive disorders of posture or movement, causing activity limitation, due to a lesion in the developing brain. CP is an umbrella term for a heterogenous condition and is, therefore, descriptive rather than a diagnosis. Each case requires detailed consideration of etiology. Our understanding of the underlying cause of CP has developed significantly, with areas such as inflammation, epigenetics and genetic susceptibility to subsequent insults providing new insights. Alongside this, there has been increasing recognition of the multi-organ dysfunction (MOD) associated with CP, in particular in children with higher levels of motor impairment. Therefore, CP should not be seen as an unchanging disorder caused by a solitary insult but rather, as a condition which evolves over time. Assessment of multi-organ function may help to prevent complications in later childhood or adulthood. It may also contribute to an improved understanding of the etiology and thus may have an implication in prevention, interventional methods and therapies. MOD in CP has not yet been quantified and a scoring system may prove useful in allowing advanced clinical planning and follow-up of children with CP. Additionally, several biomarkers hold promise in assisting with long-term monitoring. Clinicians should be aware of the multi-system complications that are associated with CP and which may present significant diagnostic challenges given that many children with CP communicate non-verbally. A step-wise, logical, multi-system approach is required to ensure that the best care is provided to these children. This review summarizes multi-organ dysfunction in children with CP whilst highlighting emerging research and gaps in our knowledge. We identify some potential organ-specific biomarkers which may prove useful in developing guidelines for follow-up and management of these children throughout their lifespan.