. 2013 Jul 19;68(1):8–19. doi: 10.1111/ijcp.12234

Table 4.

Risk of IPD in children

Citation (country)	Methodology	Clinical manifestation	Age range (years)	N	Time period	Comparator children	Risk (95% CI)
Chronic organ disease
Heart disease
Hjuler 2008 (Denmark) ³²	Surveillance database study (all heart disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 2.4 (1.6–3.4)
	Surveillance database study (chronic heart disease)			14			aRR = 3.6 (1.4–9.6)
	Surveillance database study (congenital heart disease^†)			67			aRR = 2.0 (1.4–3.1)
Pilishvili 2010 (USA) ³³	Surveillance study	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 3.5 (2.1–5.7) ^***
van Hoek 2012 (UK) ²²	National GP database study	IPD	2–15	48	2008–2009	No risk factors for IPD	OR = 4.1 (3.1–5.5)
Liver disease
van Hoek 2012 (UK) ²²	National GP database study	IPD	2–15	9	2008–2009	No risk factors for IPD	OR = 29.6 (15.3–57.2)
Lung disease
Hjuler 2008 (Denmark) ³²	Surveillance database study (all lung disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 1.4 (1.0–1.9)
	Surveillance database study (chronic airway disease)			25			aRR = 4.1 (2.1–7.9)
	Surveillance database study (asthma)			60			aRR = 1.1 (0.7–1.6)
	Surveillance database study (congenital respiratory malformation)			11			aRR = 0.9 (0.4–1.9)
Pilishvili 2010 (USA) ³³	Surveillance study (chronic lung condition)	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 3.5 (1.5–8.0) ^***
Pilishvili 2010 (USA) ³³	Surveillance study (asthma)	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 1.8 (1.5–2.2) ^***
Talbot 2005 (USA) ³⁵	Nested case–control study (asthma)	IPD	2–4	26	1995–2002	Children without IPD	aOR = 2.3 (1.4–4.0)
Talbot 2005 (USA) ³⁵	Nested case–control study (asthma)	IPD	5–17	11	1995–2002	Children without IPD	aOR = 4.0 (1.5–10.7)
van Hoek 2012 (UK) ²²	National GP database study	IPD	2–15	9	2008–2009	No risk factors for IPD	OR = 12.7 (8.1–20.0)
Renal disease
Hjuler 2008 (Denmark) ³²	Surveillance database study (all renal disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 4.1 (1.5–11.1)
	Surveillance database study (chronic renal disease)			6			aRR = 18.9 (2.8–127.1)
	Surveillance database study (congenital renal malformation)			7			aRR = 1.6 (0.4–6.3)
Pilishvili 2010 (USA) ³³	Surveillance study (kidney disease [no dialysis])	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 3.6 (1.1–11.4) ^*
Pilishvili 2010 (USA) ³³	Surveillance study (nephrotic syndrome or renal failure)	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 14.7 (2.9–76) ^**
van Hoek 2012 (UK) ²²	National GP database study	IPD	2–15	33	2008–2009	No risk factors for IPD	OR = 11.7 (8.3–16.6)
Gastrointestinal disease
Hjuler 2008 (Denmark) ³²	Surveillance database study (all gastrointestinal disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 1.5 (0.9–2.4)
Hjuler 2008 (Denmark) ³²	Surveillance database study (oesophageal disease)	IPD	0–17	8	1977–2005	Children with no chronic diseases	aRR = 1.1 (0.4–3.5)
Genetic disease/congenital malformation
Hjuler 2008 (Denmark) ³²	Surveillance database study (all genetic disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 2.1 (1.1–4.1)
	Surveillance database study (chromosomal abnormalities)			22			aRR = 2.5 (1.1–5.6)
	Surveillance database study (inborn error of metabolism)			5			aRR = 1.1 (0.3–4.1)
	Surveillance database study (congenital gut malformation^‡)			35			aRR = 1.7 (1.0–2.9)
	Surveillance database study (congenital CNS malformation^§)			23			aRR = 2.9 (1.4–6.2)
	Surveillance database study (cerebral palsy)			18			aRR = 1.2 (0.5–3.0)
Pilishvili 2010 (USA) ³³	Surveillance study (congenital/developmental disorders)	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 4.9 (3.0–8.0) ^***
Immunosuppression
Asplenia/splenic dysfunction/splenectomy
Hjuler 2008 (Denmark) ³²	Surveillance database study	IPD	0–17	6	1977–2005	Children without invasive surgery	aRR = 14.4 (1.3–154.2)
Pilishvili 2010 (USA) ³³	Surveillance study	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 3.9 (0.6–23.5)
van Hoek 2012 (UK) ²²	National GP database study	IPD	2–15	11	2008–2009	No risk factors for IPD	OR = 4.7 (2.6–8.5)
Coeliac disease
Ludvigsson 2008 (Sweden) ³⁶	Cohort study	Sepsis	0–15	–	1964–2003	General population	HR = 3.4 (1.1–10.6)
HIV infection
van Hoek 2012 (UK) ²²	National GP database study	IPD	2–15	6	2008–2009	No risk factors for IPD	OR = 100.8 (44.7–227.2)
Immunological/metabolic disease
Hjuler 2008 (Denmark) ³²	Surveillance database study (all immunological/metabolic disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 2.0 (0.9–4.2)
	Surveillance database study (haemolytic anaemia)			3			aRR = 2.9 (0.6–13.8)
	Surveillance database study (autoimmune disease)			5			aRR = 2.6 (0.6–10.7)
	Surveillance database study (congenital immune deficiency)			12			aRR = 1.4 (0.4–4.8)
	Surveillance database study (diabetes)			1			aRR = 0.4 (0.0–14.8)
Immunosuppression
Pilishvili 2010 (USA) ³³	Surveillance study (any immunocompromising condition)	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 4.9 (3.4–6.9) ^***
	Surveillance study (HIV or immune system disorder)						OR = 14.5 (5.7–36.8) ^***
	Surveillance study (systemic steroid use)						OR = 2.2 (1.6–3.0) ^***
van Hoek 2012 (UK)²²	National GP database study	IPD	2–15	174	2008–2009	No risk factors for IPD	OR = 41.0 (35.0–48.0)
Sickle-cell disease
Pilishvili 2010 (USA)³³	Surveillance study	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 5.6 (1.6–19.4) ^**
Poehling 2010 (TN, USA)²⁷	State-managed healthcare database study	IPD (Hb S or C trait)	< 5 [–]	66	1996–2005	White, with normal Hb	RR = 1.77 (1.22–2.55)
		IPD (Hb S trait)		52			RR = 1.80 (1.20–2.69)
		IPD (Hb C trait)		14			RR = 1.66 (0.81–3.39)
Transplant recipients
Hjuler 2008 (Denmark)³²	Surveillance database study	IPD	0–17	18	1977–2005	Children without invasive surgery	aRR = 14.3 (3.0–68.2)
Tran 2005 (ON, Canada)²⁸	Retrospective single-centre study	IPD	< 5 [–]	522	1990–2001	All < 2 years	p = 0.13 (no RR or OR specified)
Tran 2005 (ON, Canada)²⁸	Retrospective single-centre study	IPD	< 5 [–]	522	1990–2001	All < 5 years	p < 0.001 (no RR or OR specified)
Neoplastic diseases
Hjuler 2008 (Denmark)³²	Surveillance database study (all cancers)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 19.0 (8.7–41.5)
	Surveillance database study (haematological cancers)			44			aRR = 52.1 (13.7–198.2)
	Surveillance database study (non-haematological cancers)			19			aRR = 8.9 (3.1–26.1)
Meisel 2007 (Germany)³⁴	Surveillance database study (acute lymphoblastic leukaemia)	IPD	0–4	5	1997–2003	General population	SIR = 7.6 (2.8–17.0) ^***
			5–9	4			SIR = 50.6 (16.1–122.1) ^***
			0–14	9			SIR = 11.4 (5.6–20.9) ^***
Pilishvili 2010 (USA)³³	Surveillance study (any cancer)	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 78.0 (10.2–593) ^***
Thomas 2008 (UK)²³	Regional hospitalisation database	IPD	0–15	–	1963–2003	General population	Rate ratio = 1.39 (0.51–3.03)
Neurological disease
Hjuler 2008 (Denmark)³²	Surveillance database study (all neurological disease)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 2.5 (1.7–3.6)
	Surveillance database study (epilepsy^¶)			37			aRR = 2.5 (1.5–4.2)
	Surveillance database study (hydrocephalus)			17			aRR = 1.0 (0.4–2.4)
Prematurity^††
Hjuler 2007 (Denmark)³⁷	Multiple database study^‡‡	IPD	0–< 0.5	22	1980–2005	Gestational age 37–42 weeks	aRR = 2.59 (1.39–4.82)
			0.5–< 2	81			aRR = 1.54 (1.18–2.02)
			2–5	22			aRR = 1.31 (0.79–2.18)
Tobacco exposure
Haddad 2008 (USA intermountain west)³⁸	Telephone survey	IPD	< 1	4	1996–2002	Children without IPD	OR = 0.6 (0.2–2.0)
			1–< 2	6			OR = 1.8 (0.4–7.7)
			2–< 5	5			OR = 2.6 (0.4–15.3)
			5–16	5			OR = 1.2 (0.3–4.6)
Pilishvili 2010 (USA)³³	Surveillance study (household exposure to smoking)	IPD	3 months–< 5 years	–	2001–2004	No tobacco exposure	OR = 1.4 (1.2–1.7) ^***
	Surveillance study (> 20 cigarettes/day)						OR = 1.7 (1.2–2.4) ^***
	Surveillance study (11–20 cigarettes/day)						OR = 0.9 (0.6–1.3)
	Surveillance study (1–10 cigarettes/day)						OR = 1.7 (1.3–2.2) ^***
General high-risk patients
Haddad 2008 (USA intermountain west)³⁸	Telephone survey^§§	IPD	0–16	32	1996–2002	Children without IPD	32 of 120 cases vs. 1 of 156 controls (no RR or OR specified)
Hjuler 2008 (Denmark)³²	Surveillance database study (all chronic diseases^¶¶)	IPD	0–17	744	1977–2005	Children with no chronic diseases	aRR = 2.4 (2.0–2.9)
Hjuler 2008 (Denmark)³²	Surveillance database study (all chronic diseases excluding high-risk groups^†††)	IPD	0–17	–	1977–2005	Children with no chronic diseases	aRR = 2.1 (1.7–2.6)
Hsu 2011 (MA, USA)³⁹	Surveillance database study^‡‡‡	IPD	0–17	14	2001–2002	Children with no known risk conditions	–
			0–17	23	2002–2003		aOR = 1.5 (0.7–3.3)
			0–17	11	2003–2004		aOR = 0.9 (0.4–2.1)
			0–17	20	2004–2005		aOR = 1.6 (0.7–3.5)
			0–17	14	2005–2006		aOR = 0.8 (0.4–1.9)
			0–17	13	2006–2007		aOR = 0.6 (0.3–1.5)
			5–17	39	2001–2007		aOR = 2.8 (1.8–4.5)
Pilishvili 2010 (USA)³³	Surveillance study^§§§	IPD	3 months–< 5 years	–	2001–2004	Children without IPD	OR = 3.3 (2.4–4.5) ^***
van Hoek 2012 (UK)²²	National GP database study^¶¶¶	IPD	2–15	261	08–09	No risk factors for IPD	OR = 11.7 (10.2–13.3)

p < 0.05; **p < 0.01; ***p < 0.001.

^†

Septal heart defects contributed to 40%.

^‡

Major contributors were biliary atresia (26%) and oesophageal atresia (20%).

^§

Major contributors were cerebral cysts (20%), microcephalus (20%) and congenital hydrocephalus (20%).

^¶

Concomitant chronic neurological disease in 43%.

^††

‘Prematurity’ defined as gestational age 19–36 weeks.

^‡‡

Databases include national Streptococcus, civil registration, childcare, birth, patient and labour market databases.

^§§

‘High risk’ defined as any underlying chronic illness (including cancer, asplenia, lupus, renal failure, liver disease, congenital heart disease, immunosuppressive therapy to prevent transplant rejection, and CNS disorders characterised by severe developmental delay, failure to thrive, or craniofacial structural abnormalities).

^¶¶

The total number is lower than the number of specific chronic diseases because patients may have > 1 of the specific chronic diseases.

^†††

Excluding children with cancer, chronic renal disease, splenectomy or transplantation; not adjusted for specific chronic diseases.

^‡‡‡

‘High-risk’ defined as sickle-cell disease, congenital or acquired asplenia or splenic dysfunction, HIV infection, cochlear implants, congenital immune deficiency, diseases associated with immunosuppressive therapy or radiation therapy, chronic cardiac disease, chronic pulmonary disease, chronic renal insufficiency, cerebrospinal leaks from congenital malformation, skull fracture or neurological procedure, diabetes mellitus, premature birth (< 38 weeks) or low birth weight (< 2500 g).

^§§§

‘High risk’ defined as any chronic disease.

^¶¶¶

‘High risk’ defined as asplenia/splenic dysfunction (including sickle-cell disease and coeliac syndrome), chronic renal, hepatic, heart or respiratory disease (including organ transplantation), diabetes mellitus, immunosuppression (including HIV, leukaemia and bone marrow transplantation), cochlear implants and cerebrospinal fluid leaks.

aOR, adjusted odds ratio; aRR, adjusted rate ratio; CI, confidence interval; CNS, central nervous system; GP, general practitioner; Hb, haemoglobin; HIV, human immunodeficiency virus; HR, hazard ratio; IPD, invasive pneumococcal disease; OR, odds ratio; RR, relative risk; SIR, standardised incidence ratio.