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Hidden cardiovascular morbidity in children and young adults born with congenital diaphragmatic hernia: A population-based study

  • Katarina Övermo Tydén
    Correspondence
    Corresponding author at: Pediatric Cardiology Unit, Karolinska University Hospital, Eugeniavägen 23 C8:34, Stockholm 171 76, Sweden.
    Affiliations
    Department of Women's and Children's Health, Karolinska Institutet, Sweden

    Pediatric Cardiology Unit, Karolinska University Hospital, Eugeniavägen 23 C8:34, Stockholm 171 76, Sweden
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  • Felicia Nordenstam
    Affiliations
    Department of Women's and Children's Health, Karolinska Institutet, Sweden

    Pediatric Cardiology Unit, Karolinska University Hospital, Eugeniavägen 23 C8:34, Stockholm 171 76, Sweden
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  • Björn Frenckner
    Affiliations
    Department of Women's and Children's Health, Karolinska Institutet, Sweden

    Department of Pediatric Surgery, Karolinska University Hospital, Sweden

    ECMO Centre, Karolinska University Hospital, Stockholm, Sweden
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  • Carmen Mesas Burgos
    Affiliations
    Department of Women's and Children's Health, Karolinska Institutet, Sweden

    Department of Pediatric Surgery, Karolinska University Hospital, Sweden

    ECMO Centre, Karolinska University Hospital, Stockholm, Sweden
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Open AccessPublished:April 06, 2022DOI:https://doi.org/10.1016/j.jpedsurg.2022.03.028

      Highlights

      • To our knowledge, there has been no previous published data concerning born with CDH and cardiovascular morbidity in childhood and young adulthood.
      • The study shows that there is an overrepresentation of cardiovascular diagnoses in a cohort born with CDH after one year of age.

      Abstract

      Introduction

      Congenital diaphragmatic (CDH) hernia is a rare congenital malformation with considerable mortality and morbidity in the neonatal period. The majority of the children today survive but little is known about long term cardiovascular morbidity.

      Material and methods

      This was a nationwide population-based prospective case-control study within a cohort of Swedish children with CDH, born 1982–2015. Five controls for each patient were randomly sampled from the population. The outcomes were the corresponding International Statistical Classification of Disease (ICD) codes for cardiovascular diagnoses according to ICD 9 and 10.

      Results

      There was an overrepresentation of cardiovascular diagnoses in the CDH group after one year of age compared to the control group, 8.0vs 0.5% (n = 53 versus n = 16). The risk of having a cardiovascular diagnosis in this CDH group was 15 times higher compared to the control group (HR 15.8, 95% CI: 9–27.6, p < 0.005). The diagnoses of cardiac arrhythmias and systemic hypertension were less common in the CDH group before the age of one year compared to the CDH group beyond the age of one year. Arrhythmia 3.7 vs 15.1%, systemic hypertension 3.7 vs 7.5%.

      Conclusion

      CDH survivors have increased cardiovascular morbidity during childhood and young adulthood. This implies that structured follow up programs, covering cardiovascular morbidity, needs to be developed and should be offered in pediatric and adult care. Being born with CDH seems to be a risk factor for future cardiovascular diagnoses.

      Level of evidence

      Level 3: Case-Control Study

      Keywords

      Abbreviations:

      CDH (congenital diaphragmatic hernia), CI (confidence interval), CV (cardiovascular), CVE (cerebral vascular event), ECMO (extra corporal membrane oxygenation>), HR (hazard ratio), ICD (International Classification of Disease), MBR (Medical Birth Register), N (number), WHO (World Health Organization?), NPR (National Patient Register), OR (odds ratio)

      1. Introduction

      Congenital diaphragmatic hernia (CDH) is a severe malformation that affects approximately 2.5/10,000 live births [
      • Kirby E.
      • Keijzer R.
      Congenital diaphragmatic hernia: current management strategies from antenatal diagnosis to long-term follow-up.
      ]. It consists of a defect in the diaphragm that allows the abdominal contents to migrate into the thoracic cavity during fetal development. It has been suggested that the lack of space in the thoracic cavity affects the development of the lungs and the heart, partly because of the mechanical pressure [
      • Chandrasekharan P.K.
      • Rawat M.
      • Madappa R.
      • Rothstein D.H.
      • Lakshminrusimha S.
      Congenital diaphragmatic hernia - a review.
      ]. This results in pulmonary hypoplasia with abnormal vascularity and also a risk of cardiac hypoplasia [
      • Chandrasekharan P.K.
      • Rawat M.
      • Madappa R.
      • Rothstein D.H.
      • Lakshminrusimha S.
      Congenital diaphragmatic hernia - a review.
      ,
      • Patel N.
      • Kipfmueller F.
      Cardiac dysfunction in congenital diaphragmatic hernia: pathophysiology, clinical assessment, and management.
      . The consequences in the postnatal period involve different degrees of pulmonary hypertension combined with different degrees of right and left heart dysfunction [
      • Patel N.
      • Lally P.A.
      • Kipfmueller F.
      • Massolo A.C.
      • Luco M.
      • Van Meurs K.P.
      • et al.
      Ventricular dysfunction is a critical determinant of mortality in congenital diaphragmatic hernia.
      ]. The newborn child can be severely ill and often needs intensive care and sometimes extra corporal membrane oxygenation (ECMO) support [
      • McHoney M.
      • Hammond P.
      Role of ECMO in congenital diaphragmatic hernia.
      ]. The care of these children has improved over time and the mortality has decreased [
      • Chiu P.P.
      • Ijsselstijn H.
      Morbidity and long-term follow-up in CDH patients.
      ,
      • Burgos C.M.
      • Ost E.
      • Wannberg M.
      • Frenckner B.
      [High survival rate among newborns with congenital diaphragmatic hernia. 20-year follow up of patients treated in Stockholm].
      . Unfortunately, there is still a high morbidity in the overall group of CDH in newborns and high mortality among the most severe cases [
      • Chiu P.P.
      • Ijsselstijn H.
      Morbidity and long-term follow-up in CDH patients.
      ,
      • Wittekindt B.
      • Doberschuetz N.
      • Schmedding A.
      • Theilen T.M.
      • Schloesser R.
      • Gfroerer S.
      • et al.
      Epidemiology and one-year follow-up of neonates with CDH-data from health insurance claims in Germany.
      .
      As the mortality has decreased there is a new group of survivors, those who have been severely ill during the neonatal period [
      • Harting M.T.
      Congenital diaphragmatic hernia-associated pulmonary hypertension.
      ]. Historically, the main cardiac focus has been to screen for pulmonary hypertension and severe cardiac dysfunction [
      • IJ H.
      • Breatnach C.
      • Hoskote A.
      • Greenough A.
      • Patel N.
      • Capolupo I.
      • et al.
      Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.
      ]. Without other cardiac diagnoses, sign of pulmonary hypertension or cardiac dysfunction, the cardiac check-ups are most often not extended beyond early childhood [
      • IJ H.
      • Breatnach C.
      • Hoskote A.
      • Greenough A.
      • Patel N.
      • Capolupo I.
      • et al.
      Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.
      ] and are only offered on demand. Previous studies have shown that children born with CDH have more gastrointestinal disease compared to children without CDH [
      • Safavi A.
      • Synnes A.R.
      • O'Brien K.
      • Chiang M.
      • Skarsgard E.D.
      • Chiu P.P.
      Multi-institutional follow-up of patients with congenital diaphragmatic hernia reveals severe disability and variations in practice.
      ]. They are also more prone to pulmonary problems such as asthma and pulmonary infections [
      • Lally K.P.
      • Engle W.
      American Academy of Pediatrics Section on SAmerican Academy of Pediatrics Committee on F, Newborn
      Postdischarge follow-up of infants with congenital diaphragmatic hernia.
      ]. Earlier studies have shown that cardiovascular morbidity is overrepresented in the newborn baby with CDH [
      • Chandrasekharan P.K.
      • Rawat M.
      • Madappa R.
      • Rothstein D.H.
      • Lakshminrusimha S.
      Congenital diaphragmatic hernia - a review.
      ] but until now there is little known about cardiovascular morbidity in older children and young adults born with CDH [
      • Safavi A.
      • Synnes A.R.
      • O'Brien K.
      • Chiang M.
      • Skarsgard E.D.
      • Chiu P.P.
      Multi-institutional follow-up of patients with congenital diaphragmatic hernia reveals severe disability and variations in practice.
      ,
      • Morini F.
      • Valfre L.
      • Bagolan P.
      Long-term morbidity of congenital diaphragmatic hernia: a plea for standardization.
      .
      We hypothesized that being born with CDH has a long lasting impact on cardiovascular function in adult life. Further we hypothesized that children born with CDH were at risk of suffering from cardiovascular disorders during childhood and adulthood.
      The aim of this study was to evaluate the risk of cardiovascular morbidity among children and young adults born with CDH compared with healthy controls.

      2. Methods

      2.1 Study design

      The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children with CDH in Sweden who survived the neonatal period during the observational period from 1st January 1982 until 31st December 2015. The study exposure was CDH and the study outcomes were cardiovascular diagnoses according to International Classification of Disease, ICD 9 and ICD 10. Data were assessed through linkages between registries administrated by the Swedish National Board of Health and Welfare.

      2.2 Registries

      The Swedish National Board of Health and Welfare administers full-covered population health related registries. All Swedish residents are assigned a unique 10-digit personal identification number at the time of birth or following immigration. This enables linkage among the different national registries and a complete follow-up. The National Patient Register (NPR) contains prospectively collected information on all hospital admissions in Sweden, including diagnoses according to the WHO ICD system and surgical procedures. The Medical Birth Register (MBR) contains prospective data on pregnancies and deliveries in Sweden.

      2.3 Assessment of exposures and definition of cases and controls

      Eligible participants were children born with CDH during the observational period and that survived the neonatal period. The following codes of the International Classification of Diseases (ICD) were used to identify the diagnosis of CDH: ICD-9 756.6 ICD-10 Q79.0 and Q79.1 Five control participants for each case were randomly sampled from the population register and matched for birth year and gender. A sub-group analysis was performed, including only CDH survivors beyond one year of age.

      2.4 Outcome assessment and variables

      The Cardiovascular diagnosis, categorized according to the ICD 9 and ICD 10 codes as shown in Table 1 were included.
      Table 1Describing five different sub-groups of cardiovascular diagnoses, according to international statistical classification of diseases and related health problems (ICD 10, 9-SE).
      Diagnoses
      Pulmonary hypertension
      I27

      Other pulmonary heart disease
      I28

      Disease of pulmonary vessels unspecified
      415

      Acute pulmonary heart disease

      416

      Chronic pulmonary heart disease

      417

      Other diseases of pulmonary circulation
      Heart failure
      I50.9

      Heart failure, unspecified

      I50.0

      Right ventricular heart failure
      I50.1

      Left ventricular heart failure

      428

      Heart failure

      Arrhythmias
      I45

      Conduction disorders
      I47

      Paroxysmal tachycardia
      I48

      Atrial fibrillation and flutter
      I49

      Other cardiac arrythmias
      426

      Conduction disorder

      427

      Cardiac dysrhythmias
      Systemic hypertension
      I11

      Hypertensive heart disease
      I10

      Essential (primary) hypertension
      I13

      Hypertensive heart and kidney disease
      I15

      Secondary hypertension
      401

      Essential hypertension
      402

      Hypertensive heart disease
      404

      Hypertensive heart and chronic kidney disease
      405

      Secondary hypertension
      Cerbral vascular event (CVE)
      I60

      Non traumatic subarachnoid hemorrhage
      I61

      Non traumatic intracerebral hemorrhage

      I62

      Other and unspecified nontraumatic intracranial hemorrhage
      I63

      Cerebral infarction
      I64

      Stroke, non specified as hemorrhage or infarction
      430

      Subarachnoid hemorrhage
      431

      Intracerebral hemorrhage
      432

      Other and unspecified intracranial hemorrhage
      433

      Occlusion and stenosis of precerebral arteries
      434–438

      Other defined and ill defined cerebral vascular disease

      2.5 Statistical analysis

      Categorical data were expressed as frequencies or proportions. Continuous data were expressed as mean ± SD or median (interquartile range). For numerical data, Students T-test or Mann-Whitney U test were performed to investigate difference between groups. For categorical data, Fishers test was performed to investigate differences between groups. Cox regression was used to explore an association between CDH and the different cardiovascular disorders, results were expressed as odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals. P values <0.05 were considered significant. Kaplan -Meier curves were constructed for time to event analyzes. All statistics were performed in R software version 2.38 (http://CRAN.R-project.org/package=survival).

      2.6 Ethics

      The study was approved by the regional ethical committee in Stockholm. Dnr 2013/1550–31/3.

      3. Results

      A total of 972 children with CDH were born during the study. 56.5% were males in the CDH group compared to 56.9% in the control group. The one-year mortality rate in the CDH group during the first year of life was 31.3%, compared to 0.7% in the control group. In the control group 0.7% (n = 34) had a cardiovascular diagnosis during the follow up period compared to 12.4% (n = 118) in the CDH group. Among these, 8.4% (n = 82) of the cardiovascular diagnoses were found in the first year of life, but as many as in 30% of the cases (n = 36) the first cardiovascular diagnosis was found after the first year of life. Of the 118 cases with cardiovascular diagnoses 79.7 (n = 94) had only one cardiovascular diagnosis, 19.5%(had two cardiovascular diagnoses and 0.8 (n = 1) had four cardiovascular diagnoses.
      The most common diagnosis during the first year of life was pulmonary hypertension (76.8%), followed by cerebral vascular event (CVE) (9.8%) heart failure (6.1%), arrhythmia (3.7%) and systemic hypertension (3.7%). The number of cardiovascular diagnoses in the control group was 5. The odds ratio to obtain a cardiovascular diagnosis, if born with CDH during the first year of life was 97.9 (OR 97.9, CI 35.8–267, p < 0.001).
      In the sub-group analysis, 659 CDH survivors beyond one year of age were included. 57.5% were males. Among those, 8.0% (n = 53) had a cardiovascular diagnosis compared to 0.5% (n = 16) among the controls beyond one year of age.
      A higher mortality rate remained in the CDH survivors beyond one year of age compared to the control group beyond one year of age (2.4 vs 0.4%). The average age of death was higher in the control group than in this CDH group (mean 13. 4 years of age vs. mean 17.7 years of age) (Table 2).
      Table 2Background information; the sub-group CDH (congenital diaphragmatic hernia)group after one year of age. Standard deviation (SD). Cardiovascular (CV).
      CDH groupControl groupTotal
      N survived > 1 year65931693828
      Gender (%)Male379 (57.5)1837 (58.0)2216 (57.9)
      Female280 (42.5)1332 (42.0)1612 (42.1)
      Born year 2000 (%)Born 2000 or earlier336 (51%)1609 (50.8%)1945 (50.8)
      Born after 2000323 (49%)1560 (49.2%)1883 (49.2)
      Age last follow (mean (SD))15.45 (8.46)15.61 (8.50)15.58 (8.49)
      Age group (%)<15329 (49.9)1562 (49.3)1891 (49.4)
      15–2089 (13.5)428 (13.5)517 (13.5)
      21–25135 (20.5)653 (20.6)788 (20.6)
      26–3095 (14.4)460 (14.5)555(14.5)
      31–4011 (1.7)66 (2.1)77 (2.0)
      Deceased>1 year (%)16 (2.4)13 (0.4)29 (0.8)
      Deceased age > 1 year(mean(SD))13.35 (8.37)17.74(9.17)15.32 (8.86)
      Age first CV-diagnosis, (mean (SD))5.16 (7.06)14.23 (8.94)
      Age group first CV diagnosis (n (%))1–440(75.5)3(18.8)
      5–94(7.5)2(12.5)
      10–174(7.5)5(31.2)
      18+5(9.4)6(37.5)
      The most common cardiovascular diagnosis after 1 year of age (n = 53) was pulmonary hypertension (60.4%) followed by arrhythmia (15.1%), heart failure (9.4%), systemic hypertension (7.5%), CVE (7.5%). In the control group beyond 1 year of age the most common cardiovascular diagnoses (n = 16) was arrhythmia (50%) followed by systemic hypertension (18.8%), pulmonary hypertension (12.5%), CVE (12.5%) and heart failure (6.2%). Over all, there was a higher risk to obtain a cardiovascular diagnosis beyond the age of one year if born with CDH; HR 15.8 (95% CI, 9–27.6; p < 0.001).
      Kaplan - Meier curve analysis, regarding time at risk to event, showed shorter time to cardiovascular diagnosis in the CDH group (n = 53). The difference in number of cardiovascular diagnoses between the CDH group and the control group increased over time (Fig. 1).
      Fig. 1
      Fig. 1Time at risk to first cardiovascular diagnosis after one year of age. The Kaplan Meier curve describes the probability of an event at a given time interval. In this study it illustrates time to cardiovascular diagnosis in the CDH group and the control group after the age of one year. Case refers to cardiovascular diagnoses in the CDH group after one year of age (n = 53) The time to event is estimated with 95% confidence interval (dotted line). CDH: Congenital Diaphragmatic Hernia.
      The specific HR for each subgroup is presented in Table 3.
      Table 3Describing hazard ratio (HR) for four different sub- groups of cardiovascular diagnoses. Number (N), CI (confidance interval).
      Event NHR95% CIpAssumption of proportional hazard
      Pulmonary Hypertension
      Control2
      Case3584.620.3–352<0.001p = 0.978
      Arrhythmia
      Control8
      Case106.022.38–15.3<0.001p = 0.222
      Systemic Hypertension
      Control3
      Case57.891.88–33.10.005p = 0.199
      Cerebral Vascular Event
      Control3
      Case58.331.99–34.90.004p = 0.293
      The Kaplan -Meier analysis showed shorter time to event for pulmonary hypertension, arrhythmia and systemic hypertension diagnoses for CDH survivors compared to controls. The difference in number of events increased over time (Fig. 2).
      Fig. 2
      Fig. 2Time at risk to diagnosis in four sub-groups. Kaplan-Meier time at risk to event curves illustrates time at risk to first cardiovascular diagnoses in four different sub-groups. Upper left; time to first diagnosis pulmonary hypertension. Upper right; time to first diagnosis arrhythmia. Lower left; time to first diagnosis systemic hypertension. Lower right; time to first diagnosis cerebral vascular event. Case refers to cardiovascular diagnoses in the CDH group after one year of age (n = 53). The time to event is estimated with 95% confidence interval (dotted line). CDH: Congenital Diaphragmatic Hernia.

      4. Discussion

      This study showed that there was a significant overrepresentation of cardiovascular diagnoses after the age of one year in a group of children and young adults born with CDH between 1982 and 2015 compared to a matched control group. Not surprising, the diagnosis pulmonary hypertension was increased in the CDH group also beyond the age of one year. The diagnoses heart failure does not increase in absolute numbers beyond the first years of life. CDH survivors obtained the diagnoses cardiac arrhythmia and systemic hypertension at an earlier age and in a larger extent compared to the control group. This difference increased over time. There was, after one year of age, a higher mortality in the CDH group compared to the control group. The cause of death was not penetrated in this study, but earlier studies have shown that cause of death varies among CDH survivors, it is not only caused by cardiovascular disease [
      • Burgos C.M.
      • Frenckner B.
      Addressing the hidden mortality in CDH: a population-based study.
      ].
      These findings highlight the severity of the diagnose CDH among children and young adolescents. Furthermore, it identifies the need of a structured cardiovascular follow-up beyond childhood. It is well known that a newborn child with CDH can be severely ill [
      • Patel N.
      • Lally P.A.
      • Kipfmueller F.
      • Massolo A.C.
      • Luco M.
      • Van Meurs K.P.
      • et al.
      Ventricular dysfunction is a critical determinant of mortality in congenital diaphragmatic hernia.
      ]. Owing to pulmonary hypoplasia and abnormal pulmonary vascularity the child develops different degrees of pulmonary hypertension with right and left heart failure [
      • Patel N.
      • Kipfmueller F.
      Cardiac dysfunction in congenital diaphragmatic hernia: pathophysiology, clinical assessment, and management.
      ]. There is still a considerably high mortality among the most severely affected children with CDH [
      • Chandrasekharan P.K.
      • Rawat M.
      • Madappa R.
      • Rothstein D.H.
      • Lakshminrusimha S.
      Congenital diaphragmatic hernia - a review.
      ]. Despite this, the majority of children born with CDH are discharged from hospital alive, and most of the children's heart function seems to completely recover [
      • Safavi A.
      • Synnes A.R.
      • O'Brien K.
      • Chiang M.
      • Skarsgard E.D.
      • Chiu P.P.
      Multi-institutional follow-up of patients with congenital diaphragmatic hernia reveals severe disability and variations in practice.
      ]. Exercise testing during childhood have showed divergent results, both that there is no difference in work capacity [
      • Peetsold M.G.
      • Heij H.A.
      • Nagelkerke A.F.
      • Ijsselstijn H.
      • Tibboel D.
      • Quanjer P.H.
      • et al.
      Pulmonary function and exercise capacity in survivors of congenital diaphragmatic hernia.
      ] and that there is a decrease in work capacity among children born with CDH [
      • Toussaint-Duyster L.C.C.
      • van der Cammen-van Zijp M.H.M.
      • de Jongste J.C.
      • Tibboel D.
      • Wijnen R.M.H.
      • Gischler S.J.
      • et al.
      Congenital diaphragmatic hernia and exercise capacity, a longitudinal evaluation.
      ].
      In Sweden, most of the children with CDH born today participate in a structured follow-up program. This program covers gastrointestinal, pulmonary diseases, neurodevelopmental and cardiac check-ups. The main focus at the cardiac follow-up has been to look primarily for signs of pulmonary hypertension [
      • IJ H.
      • Breatnach C.
      • Hoskote A.
      • Greenough A.
      • Patel N.
      • Capolupo I.
      • et al.
      Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.
      ]; with less focus on subtle ventricular dysfunction. If routine control of the cardiac function is considered normal, the cardiac control becomes more sporadic during childhood and is often discontinued at older age [
      • IJ H.
      • Breatnach C.
      • Hoskote A.
      • Greenough A.
      • Patel N.
      • Capolupo I.
      • et al.
      Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.
      ]. The result of this study showed that there was an overrepresentation of cardiovascular morbidity among a group of children and young adults born with CDH. This study concerns a new group of survivors [
      • Kardon G.
      • Ackerman K.G.
      • McCulley D.J.
      • Shen Y.
      • Wynn J.
      • Shang L.
      • et al.
      Congenital diaphragmatic hernias: from genes to mechanisms to therapies.
      ]. The increased cardiovascular morbidity might be the result of the increased survival rate owing to improved intensive care and surgery [
      • Chandrasekharan P.K.
      • Rawat M.
      • Madappa R.
      • Rothstein D.H.
      • Lakshminrusimha S.
      Congenital diaphragmatic hernia - a review.
      ]. The study showed that there was a significant overrepresentation of cardiovascular diagnosis in the group of CDH also after their first year of life, and that the pattern of cardiovascular diagnosis changed with age. The results of this study strengthen the indication for a prolonged follow-up of children and young adults born with CDH, and that structured transition of care programs, that include cardiovascular functions, should be developed.

      4.1 Limitations and strengths

      A limitation of the study was that the population presented corresponds to a relatively young cohort born between 1982 and 2015. Because of this, there are few CDH cases in the older age groups. A possible limitation is that the CDH group, owing to other morbidity such as pulmonary and gastrointestinal disease, might have more care visits then their controls. Blood pressure will therefore be measured more often in the CDH group than in the control group, leading to a diagnosis's bias.
      Another limitation of the present study was that information of known risk factors for severity, such as defect size and liver position were not available in these nationwide registries. It was not possible to correlate the results of this study with the severity of the condition. This must be taken into consideration when investigating the results. Further studies on older children and adults born with CDH are needed to confirm that there is an overrepresentation of cardiac diagnosis including cardiac arrhythmias and hypertension among this group. However, this study provides several strengths, where the robustness and completeness of the data is one. In addition, the data covered the entire population at a national level and with high validity. Finally, there was a negligible risk of missing a patient using a combination of the two registers [

      Centre for Epidemiology the Swedish National Board of Health and Welfare. The Swedish medical birth register–a summary of content and quality.

      ].

      5. Conclusion

      The results of this study indicate that there is an overrepresentation of cardiovascular morbidity among the group of children and young adults born with CDH, even beyond their first year of age. Our findings indicate that cardiac arrhythmia and systemic hypertension were more common among children and young adults with CDH compared to controls. This hidden cardiovascular morbidity emphasizes the need for continued and meticulous cardiac controls of children and young adults born with CDH; including looking for systemic hypertension and cardiac arrhythmia.

      Previous communication

      None

      Financial support statement

      This work was supported by Karolinska University Hospital, the Foundation Samaritan and the Foundation Sällskapet Barnavård

      Appendix A. Supplementary materials

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