Prevalence of pulmonary hypertension among children with Down syndrome: A systematic review and meta-analysis

Table 1 Characteristics of studies included in the meta-analysis

Ref.	Year	Timing of data collection	Study design	Country	Population size	Cases with PH	Prevalence of PH
De Rubens et al[48]	2003	Retrospective	Observational	Mexico	275	41	14.90909
Shah et al[33]	2004	Retrospective	Observational	Canada	175	24	13.71429
Cua et al[35]	2007	Retrospective	Observational	USA	58	7	12.06897
Weijerman et al[40]	2010	Prospective	Cohort	Netherlands	820	25	3.04878
Banjar et al[41]	2012	Retrospective	Observational	Saudi Arabia	59	44	74.57
Mourato et al[42]	2013	Retrospective	Cross-sectional	Brazil	138	42	30.43478
Sharma et al[43]	2013	Prospective	Observational	India	35	18	51.42857
Shrestha et al[36]	2013	Prospective	Observational	Nepal	50	21	42
Espinola-Zavaleta et al[44]	2015	Prospective	Observational	Mexico city	127	102	80.31496
Bermudez et al[34]	2015	Retrospective	Observational	Brazil	1207	57	4.722452
Zonouzi et al[45]	2015	Prospective	Cross-sectional	Iran	110	23	20.90909
Joffre et al[6]	2016	Retrospective	Observational	France	66	19	28.78788
Okeniyi et al[37]	2017	Prospective	Observational	Nigeria	70	14	20
Bush et al[38]	2018	Retrospective	Cohort	USA	1252	346	27.63578
Martin et al[39]	2018	Retrospective	Cohort	Ireland	121	41	33.8843
Zahari et al[46]	2019	Retrospective	Cohort	Malaysia	754	160	21.22016
Alsuwayfee et al[47]	2020	Prospective	Cross-sectional	Iraq	76	23	30.26

PH: Pulmonary hypertension.

Table 2 Screening methodology of the included studies

Ref.	Diagnosis established by	Age group, (mean ± SD, yr)	Sex (M:F)	Diagnostic criteria for PH
De Rubens et al[48]	Echocardiography	Less than 16 yr	1:1	NM
Shah et al[33]	Echocardiography	Newborn	10:7	Right to left shunting at ductal or atrial level in the absence of severe pulmonary parenchymal disease
Cua et al[35]	Echocardiography	Neonate	25:33	Right-to-left shunt at the ductal level or flattening of the IVS in the absence of a PDA
Weijerman et al[40]	Echocardiography	Neonate	NM	Right-to-left shunt at the ductal level
Banjar et al[41]	Echocardiography	3.3 ± 3.9	34:25	> 50% of systolic systemic pressure
Mourato et al[42]	Echocardiography	Infant	61:77	mPAP > 25 mmHg
Sharma et al[43]	Echocardiography	Less than 12 yr	4:3	mPAP >25 mmHg
Shrestha et al[36]	Echocardiography	4 mo to 12 yr	1:1.4	NM
Espinola-Zavaleta et al[44]	Echocardiography	Up to 18 yr	64:63	mPAP > 30 mm Hg
Bermudez et al[34]	Echocardiography	Up to 11 mo	NM	mPAP > 25 mmHg
Zonouzi et al[45]	Echocardiography	1 mo-20 yr	53:57	NM
Joffre et al[6]	Echocardiography	1mo-16 yr	2:1	NM
Okeniyi et al[37]	Echocardiography	3 mo-9 yr	3:4	NM
Bush et al[38]	Echo or catheterization	Birth to 21 yr	688:564	mPAP > 25 mmHg; IVS flattening, RV dilation, or presence of RV hypertrophy
Martin et al[39]	Echocardiography	Neonate	62:59	Right to-left shunt across the PDA, IVS bowing into the left ventricle, or the presence of a TR jet
Zahari et al[46]	Echocardiography	Newborn	189:225	IVS flattening, a dilated main pulmonary artery, and dilated right cardiac chambers
Alsuwayfee et al[47]	Echocardiography	< 15 yr	0.85:1	mPAP > 25 mmHg

PH: Pulmonary hypertension; IVS: Interventricular septum; PDA: Patent ductus arteriosus; TR: Tricuspid regurgitation; PAP: Pulmonary artery pressure; NM: Not mentioned.

Table 3 Quality assessment of the included studies

STROBE quality of reporting
Ref.	The title and abstract (Item 1)	Introduction (Item 2-3)	Methods (Item 4-12)	Results (Item 13-17)	Discussion and other information (Item 18-22)	Quality score (0-22)
De Rubens et al[48]	1	2	6	4	2	15
Shah et al[33]	0	2	5	2	3	12
Cua et al[35]	1	2	5	3	4	15
Weijerman et al[40]	1	2	4	4	4	15
Banjar et al[41]	1	2	4	4	4	15
Mourato et al[42]	1	2	5	2	4	14
Sharma et al[43]	1	2	5	3	4	15
Shrestha et al[36]	1	2	4	4	4	15
Espinola-Zavaleta et al[44]	1	2	5	3	3	14
Bermudez et al[34]	1	2	4	2	4	13
Zonouzi et al[45]	1	2	4	3	5	15
Joffre et al[6]	1	2	5	2	4	14
Okeniyi et al[37]	1	2	5	3	3	14
Bush et al[38]	1	2	5	3	5	16
Martin et al[39]	1	2	5	4	4	16
Zahari et al[46]	1	2	5	3	4	15
Alsuwayfee et al[47]	1	2	5	4	4	16

Table 4 Risk of bias assessment of included studies using the Hoy et al[26] 2012 tool

Ref.	Representation	Sampling	Random selection	Non response bias	Data collection	Case definition	Reliability and validity of study tool	Method of data collection	Prevalence period	Numerator and denominator	Summary assessment
De Rubens et al[48]	HR	HR	HR	HR	HR	HR	LR	LR	HR	LR	HR
Shah et al[33]	HR	HR	HR	HR	HR	HR	LR	LR	HR	LR	HR
Cua et al[35]	LR	LR	LR	LR	LR	LR	LR	LR	HR	LR	LR
Weijerman et al[40]	HR	HR	HR	HR	HR	LR	LR	LR	HR	LR	MR
Banjar et al[41]	HR	HR	LR	HR	LR	HR	LR	LR	LR	LR	MR
Mourato et al[42]	HR	HR	HR	HR	LR	LR	LR	LR	HR	LR	MR
Sharma et al[43]	HR	LR	LR	HR	LR	LR	LR	LR	LR	LR	LR
Shrestha et al[36]	LR	LR	LR	HR	LR	LR	LR	LR	HR	LR	LR
Espinola-Zavaleta et al[44]	LR	LR	LR	HR	HR	HR	LR	LR	HR	LR	MR
Bermudez et al[34]	LR	LR	HR	HR	LR	HR	LR	LR	HR	LR	MR
Zonouzi et al[45]	HR	HR	HR	HR	LR	HR	LR	LR	HR	LR	MR
Joffre et al[6]	HR	HR	HR	HR	HR	HR	HR	HR	LR	LR	HR
Okeniyi et al[37]	LR	LR	LR	HR	HR	LR	LR	LR	HR	LR	LR
Bush et al[38]	LR	LR	LR	HR	HR	LR	LR	LR	HR	LR	LR
Martin et al[39]	LR	LR	LR	HR	HR	LR	LR	LR	HR	LR	LR
Zahari et al[46]	HR	LR	HR	HR	LR	HR	LR	LR	HR	LR	MR
Alsuwayee et al[47]	HR	HR	HR	HR	LR	LR	LR	LR	LR	LR	MR

HR: High risk; LR: Low risk; MR: Moderate risk (LR: 0-3; MR: 4-6; HR: 7-9).

Table 5 Prevalence in different subgroups

Stratification group	Number of studies	Total number of subjects	Total number of events	I2	P value	Prevalence	95%CI
Sex
Male	4	801	210	28.22	0.243	24.3	18.8-30.6
Female	4	695	189	56.44	0.076	26.2	18.8-35.3
Age
Infant (< 1 yr)	7	3273	356	95.35	0.000	13.4	6.6-25.4
Children (> 1 yr)	9	2061	607	94.68	0.000	33.7	22.6-47.0
Region
Asia	6	1084	289	93.68	0.000	38.4	23.7-55.7
Not Asia	11	4309	718	97.92	0.000	19.8	10.9-33.2
Studies published
Before 2011	4	1328	97	93.79	0.000	9.4	4.1-20.2
2011 - 2020	13	4065	910	97.13	0.000	33.0	22.5-45.4
Risk of bias
High risk	3	516	84	76.20	0.015	17.8	11.6-26.5
Moderate risk	8	2119	437	97.91	0.000	34.0	16.6-57.1
Low risk	6	2758	486	97.63	0.000	20.0	9.3-37.7
Etiology
Cardiac	7	724	372	97.06	0.000	14.4	7.4-26.1
Non-cardiac	7	724	352	96.63	0.000	8.9	4.4-17.5