Introduction
Methods
Study Objective
Literature Search
Definition of CHD
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Uncorrected or palliated cyanotic or acyanotic CHD with pulmonary hypertension
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Systolic pulmonary arterial pressure ≥40 mmHg or mean pulmonary arterial pressure ≥25 mmHg, and/or
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Need for medication to manage congestive heart failure.
Outcomes of Interest
Evaluation of Data
Statement of Ethics Compliance
Results
Articles Selected
Incidence of RSVH in Infants and Children with CHD
Study | Country | Study design | Study definition of CHD/HS-CHD | RSVH rate/1000 children | Risk ratio (95% CI) | |
---|---|---|---|---|---|---|
CHD | Non-CHD | |||||
RSVH rates for studies of infants and children with CHD
| ||||||
Resch 2016 [27] | Austria | 3-year retrospective study (2004–2008) of 602 children <3 years with HS-CHD or non-hsCHD; RSV immunoprophylaxis recommendation documented in 27.2% with HS-CHD and 2.2% with non-hsCHD | CHD classified as being HS-CHD or non-hsCHD according to definition of authors (pediatric cardiologists) | CHD: 96.0 HS-CHD: 73.0 Non-hsCHD: 104.0 | NR | NR |
Resch 2011 [28] | Austria | 6-year retrospective study (2004–2009) of 433 infants <12 months hospitalized for RSV (388 [89.6%]) or influenza at tertiary care center; 50 children with CHD | Not defined | 129.0 | NR | NR |
Wang 1997 [36] | Canada | 2-year prospective study (1993–1995) of 427 children <3 years (253 complex CHD and 14 heart/lung disease); eight tertiary centers; no data on RSV immunoprophylaxis | Complex CHD defined as congenital heart abnormality needing cardiac surgery or dependence on cardiac medication. Patients who were digoxin-dependent or had not received corrective cardiac surgery were included | Overall: 30.0 0–3 months: 360.0 3–6 months: 60.0 6–12 months: 0.0 12–24 months: 10.0 24–36 months: 10.0 | NR | NR |
Kristensen 2012 [37] | Denmark | 6-year retrospective study (1997–2003) of 452,205 children <2 years; 2720 with CHD; 118 received ≥1 dose RSV immunoprophylaxis | CHD not defined. Cardiac diagnoses included only if established at 1 of the 3 centres for pediatric cardiology | 107.0 | NR | 1.70 (1.45–1.99) |
Kristensen 2009 [38] | Denmark | 7-year retrospective, multicenter study (1996–2003) of 3239 children <2 years with heart disease; no child received RSV immunoprophylaxis | Categorized as HS-CHD in all patients who were cyanotic, decompensated or required anti-congestive therapy. In other patients hemodynamic significance categorized as determined by the attending pediatric cardiologist | CHD/HS-CHD: 102.0 0–5 months: 71.3a,b
6–11 months: 73.2a,b
12–17 months: 43.4a,b
18–23 months: 29.6a,b
0–23 months: 56.5a,b
| NA | HS-CHD: 1.53 (1.04–2.26)c
Cardiomyopathy: 5.84 (1.26–27.16)c
|
Medrano López 2010 [5] | Spain | 4-year prospective, multicenter study (2004–2008) of 2613 children <2 years with HS-CHD hospitalized for ARI (3.8% diagnosed RSV); 90.5% received RSV prophylaxis | Definition of HS-CHD stipulated by the Spanish Society of Pediatric Cardiology | HS-CHD: 38.0 | NR | NR |
Erikkson 2002 [40] | Sweden | 12-year retrospective study (1987–1998) of 1503 episodes of RSVH in children <2 years; infants with cardiac malformation (2.9% catchment area; 13% from other areas); no data on RSV immunoprophylaxis | Cardiac malformation/lesion—not defined | CHD: 28.0–64.0d
| NR | NR |
Simoes 1998 [44] | US | 3-year prospective, multicenter, randomized, controlled study of 416 children <4 years with CHD or cardiomyopathy (214 control group—no RSV immunoprophylaxis) | Not defined | CHD: 150.0 (control group) <6 months: 240.0 (control group) >6 months: 90.0 (control group) | NR | NR |
RSVH rates for studies with mixed populations of infants and children
| ||||||
Lanari 2004 [45] | Italy | 6-month retrospective study (1999–2000) of 1214 children <2 years hospitalized for LRTI or developed RSV LRTI whilst hospitalized in 32 tertiary centers (3.5% non-surgically corrected CHD) | Not defined | CHD: 357.0 Nosocomially acquired RSV: 98.0 | NR | NR |
Pezzotti 2009 [43] | Italy | 6-year retrospective cohort study (2000–2006) of 2407 preterm infants (<36 wGA) followed to 3 years but analyzed at <18 months (34 [1.4%] CHD); 13.5% received ≥1 dose RSV immunoprophylaxis | ICD-9 codes used to classify children. SIO also used to identify infants with diagnosis of CHD | Overall: 47.0 CHD data not presented <18 months: 75.8b
| <18 months: 46.6b
| CHD: 1.64 (0.52–5.19) |
Meberg 2006 [8] | Norway | 18-year retrospective, population-based study (1987–2004) of 43,470 live births (527 [1.2%] CHD; all RSVH ≤2 years); no data on RSV immunoprophylaxis | CHDs defined based on previously published criterion [51] HS-CHD defined as those in need of surgery or catheter intervention | All CHD: 48.0e
HS-CHD: 92.0f
HNS-CHD: 33.0 | NR | NR |
Tatachenko 2010 [46] | Russian Federation | 6-month prospective, multicenter, observational study (2008–2009) of 519 children ≤2 years admitted with LRTI (18 [3.5%] high-risk RSV + children, including CHD); No RSV immunoprophylaxis | Not defined | Overall: 380.0 CHD data not presented | NR | NR |
Hervás 2012 [47] | Spain | 2-year retrospective, single center study (2005–2006) of 2384 children ≤2 years hospitalized for acute bronchiolitis (62.7% RSV) | Not defined | CHD: 23.0 | Overall: 55 | NR |
Bonillo-Perales 2000 [35] | Spain | 3-year retrospective study (1997–2000) of 12,895 newborn infants hospitalized for bronchiolitis in region | Presence of CHD with pulmonary obstruction, demonstrated by Doppler echocardiography | CHD: 58.8 | NR | NR |
Duppenthaler 2004 [30] | Switzerland | 6-year prospective, population-based study (1997–2003) of 729 children <2 years hospitalized for RSV (10 [1.4%] with CHD). No RSV immunoprophylaxis. | CHD defined as hemodynamically significant cardiac malformation | CHD: 14.0 <12 months: 20.0b
12–24 months: 5.0b
| <12 months: 12.0b
12–24 months: 2.0b
| NR |
Baysal 2013 [42] | Turkey | Prospective study of 419 children <2 years with LRTI (241 [57%] HS-CHD); no data on RSV immunoprophylaxis | Not defined | CHD: 14.0 | NR | NR |
Boyce 2000 [29] | US | 3-year retrospective study (1989–1993) of all children <3 years (enrolled in Medicaid program; included children with CHD) | ICD-9 codes used to classify children | CHD: 50.0 0–6 months: 120.8 6–<12 months: 63.5 12–24 months: 18.2 24–36 months: 4.8 | 0–6 months: 44.1g
6 to <12 months: 15.0g
12–24 months: 3.7g
24–36 months: 1.0g
| ≤12 months: 2.8 (2.3–3.3) |
Summary | |||
---|---|---|---|
Number of studies | Number of countries | Population age range and timeframe of studies | RSVH per 1000 (all CHD) |
15 | 11 | <4 years; 1979–2009 | 14–357 |
Morbidity and Healthcare Resource Utilization
Study | Country | Study participants | Hospital LOS (days) | Admitted intensive care (%) | ICU LOS (days) | Mechanical ventilation or respiratory support (%) | Oxygen therapy (%) | Case fatality rate (%) |
---|---|---|---|---|---|---|---|---|
Rates for studies of infants and children with CHD
| ||||||||
Resch 2016 [27] | Austria | 602 children <3 years with HS-CHD and non-hsCHD | HS-CHD: 14 (median, SD 2–39) Non-hsCHD: 7 (median, SD 1–70) | HS-CHD: 46 Non-hsCHD: 17 | HS-CHD: 10 (median, SD 0–27) Non-hsCHD: 9.5 (SD, 0–70) | NR | HS-CHD: 64 Non-hsCHD:47 | 0 |
Butt 2014 [6] | Canada | 30 children <6 years with CHD (40% HS-CHD) | 10 (median, 1–65) | 53.3 | 11 (median, 1–43) | 50 (30 mechanical ventilation; 20 CPAP or non-invasive positive pressure | 33.3 | 3.3 |
Kristensen 2009 [38] | Denmark | 3239 infants < 2 years with heart disease | 6 (mean 0–74) | NR | NR | Mechanically ventilated: 3.9 CPAP: 25.8 | 27.5 | 0 |
Medrano López 2010 [5] | Spain | 2613 infants aged <2 years with HS-CHD | 7 (median) (IQR 5–7) | 30.4a
| 10 (median) (IQR 5–18)a
| NR | NR | 1.98b
|
Medrano 2007 [39] | Spain | 760 infants <2 years with HS-CHD | 9.7 (mean, 1–56) | NR | NR | NR | NR | 0.8b
|
Friedman 2016 [48] | US | 4468 infants 12–23 months with various CHD diagnoses | 4.4 (mean) | NR | NR | Mechanically ventilated: 11.4 | NR | 1.6 |
Altman 2000 [10] | US | 63 children with CHD ≤28 months (52% >12 months) | 7.4 (mean) | 25 | 9.7 (mean) | Mechanically ventilated: 11 | NR | 3.12 |
Simoes 1998 [44] | US | 416 children <4 years with CHD or cardiomyopathy | 107 days/100 childrenc
| 5c
| 68 days/100 childrenc
| Mechanically ventilated: 3c
| NR | 1.4 |
Rates for studies with mixed populations of infants and children
| ||||||||
Lanari 2004 [45] | Italy | 1214 infants <2 years hospitalized for LRTI or developed RSV LRTI whilst hospitalized in 32 tertiary centers (3.5% non-surgically corrected CHD) | 9.2 (mean) | NR | NR | NR | NR | NR |
Meberg 2006 [8] | Norway | 43 470 live births [527 (1.2%) CHD] | 7.6 (mean) | 2 | NR | 0 | NR | 0.2 |
Fjaerli 2004 [52] | Norway | 764 infants < 2 years hospitalized for RSV bronchiolitis [20 (2.6%) CHD: 12 CHD; 4 CHD and prematurity; 4 CHD and Down syndrome] | 6 (median, 2–14)d
| NR | NR | NR | NR | 0.3 |
Tatachenko 2010 [46] | Russian Federation | 519 infants ≤2 years admitted with LRTI [18 (3.5%) high-risk RSV + children, including CHD] | 4–13 (range)e
| NR | NR | 0e
| 28e
| 0 |
Hervás 2012 [47] | Spain | 2384 infants ≤2 years hospitalized for acute bronchiolitis (62.7% RSV of which 2.3% had CHD) | 6 (median, IQR 3–8) | NR | NR | NR | NR | 0.13f
|
Erikkson 2002 [40] | Sweden | 1503 episodes of RSVH in infants <2 years; infants with cardiac malformation (2.9% catchment area; 13% from other areas) | 17.1 (mean, IQR 3–11) | 22 | NR | 12 | NR | 0.3 |
Duppenthaler 2004 [30] | Switzerland | 729 infants <2 years hospitalized for RSV (10 [1.4%] with CHD) | 6.5 (median, 2–41) | 50 | 1.5 (median, 0–25) | 20 | 100 | 10g
|
Baysal 2013 [42] | Turkey | 419 infants <2 years with LRTI [241 (57%) HS-CHD] | 9.9 (5–17) | 30h
| NR | 18h
| NR | 2 |
Willson 2003 [33] | US | 684 infants ≤1 year hospitalized for bronchiolitis or RSV pneumonia | 6.0 (median) | NR | 4.1 (median) | 31.7 | NR | 0.15 |
Summary for studies infants and children with CHD | ||||
---|---|---|---|---|
Outcome | Number of studies | Number of countries | Population age range and timeframe of studies | Value |
Hospital LOS | 7 | 5 | <6 years; 1994–2012 | 4.4–14j
|
ICU admission | 5 | 4 | <6 years; 1992–2009 | 5–53.3 k
|
ICU LOS | 4 | 4 | <6 years; 1994–2009 | 9.5–11i
|
Oxygen therapy | 3 | 3 | <6 years; 1996–2009 | 27.5–64k
|
Invasive mechanical ventilation | 5 | 3 | <6 years; 1992–2012 | 3–30k
|
CPAP or non-invasive positive pressure ventilation | 2 | 2 | <6 years; 1996–2003 | 20–25.8k
|
Case fatality rate | 8 | 5 | <6 years; 1992–2009 | 0–3.3k
|
Parameter | CHD (n = 10) | BPD (n = 15) | Prematurity ≤35 wGA (n = 60) | Age <1 month (n = 90) | No risk factor (n = 554) |
---|---|---|---|---|---|
Hospital LOSa
| 6.5 (2–41) | 11 (4–23) | 6 (2–23) | 8 (1–27) | 5 (1–30) |
Supplemental oxygenb
| 100 | 80 | 73 | 86 | 66 |
ICU admissionb,c
| 50 | 6.7 | 20 | 32 | 7.0 |
ICU LOSa
| 1.5 (0–25) | 0 (0–5) | 0 (0–16) | 0 (0–17) | 0 (0–18) |
Mechanical ventilationb
| 20 | 0 | 1.7 | 5.6 | 1.3 |
Impact of RSV Infection on Cardiac Surgery for CHD
Case Fatality Rates
Limitations
Summary Box
Key statements/findings | Level of evidencea
|
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CHD, in particular HS-CHD, is a significant risk factor for severe RSV infection with RSVH rates ranging from 14–357 per 1000 | Level 1 (Level 1 studies: n = 9; Risk of biasb: very low) |
Children with CHD spend an average of 4.4–14 days in hospital for RSV infection, with up to 53% requiring admission to the ICU | Level 1 (Level 1 studies: n = 8; Risk of biasb: very low) |
Children with CHD have a more severe disease course (increased ICU admission and ventilation) than children without CHD | Level 1 (Level 1 studies: n = 2; Risk of biasb: very low) |
RSV infection can delay and impact surgery for CHD, increasing post-operative complications, such that the timing of surgery is an important consideration | Level 2 (Level 1 studies: n = 1; Level 2 studies: n = 1; Level 3 studies: n = 2 Risk of biasb: very low) |
Case fatality rates associated with RSVH in children with CHD are reported to range from 0–3.3% | Level 1 (Level 1 studies: n = 6; Risk of biasb: very low) |
Key areas for research | |
Further research and specific studies are needed to determine the longer-term effects of severe RSV infection in infants and young children with HS-CHD as well as those with CHD that is not hemodynamically significant. Additional data are also required to assess outcomes of HS-CHD and non-hsCHD in children, independent of chromosomal/non-chromosomal anomalies and other serious pre-existing medical disorders |