Supplementary A. Search strategy Electronic search from ... · Supplementary A. Search strategy Electronic search from database In PubMed, we used “MeSH” term and keywords to

Supplementary A. Search strategy

Electronic search from database

In PubMed, we used “MeSH” term and keywords to build search strategy. In Embase, we used

“Emtree” term and keywords to build strategy. In Web of Science, we only used keywords in search.

In PubMed, the search strategy was:

("Heart Defects, Congenital"[Mesh] OR "Congenital Heart Defect"[tw] OR "Congenital Heart

Defects"[tw] OR heart Abnormalit*[tw] OR aortic Coarctation*[tw] OR "Coarctation of the

Aorta"[tw] OR "Coarctation of Aorta"[tw] OR "ARVD-C"[tw] OR "Arrhythmogenic Right

Ventricular Cardiomyopathy"[tw] OR "Arrhythmogenic Right Ventricular Dysplasia-

Cardiomyopathy"[tw] OR "Barth Syndrome"[tw] OR "Cor Triatriatum"[tw] OR "Subdivided Left

Atrium"[tw] OR "Subdivided Left Atriums" OR triatrial Heart*[tw] OR "Cor Triatriatum

Sinistrum"[tw] OR "Coronary Vessel Anomalies"[tw] OR "Coronary Vessel Anomaly"[tw] OR

crisscross Heart*[tw] OR "Criss cross Heart"[tw] OR "Criss cross Hearts"[tw] OR

Dextrocardia*[tw] OR "Patent Ductus Arteriosus"[tw] OR "Patency of the Ductus Arteriosus"[tw]

OR epstein Anomal*[tw] OR ebstein's Malformation*[tw] OR epstein Malformation*[tw] OR

ebstein s Malformation*[tw] OR ebstein's Anomal*[tw] OR ebstein s Anomal*[tw] OR "Ectopia

Cordis"[tw] OR "Eisenmenger's Complex"[tw] OR "Eisenmenger Complex"[tw] OR

eisenmenger's Syndrome*[tw] OR eisenmenger Syndrome*[tw] OR eisenmenger Syndrome*[tw]

OR "Heart Septal Defect"[tw] OR "Heart Septal Defects"[tw] OR atrial Isomerism*[tw] OR

"Hypoplastic Left Heart Syndrome"[tw] OR "Isolated Noncompaction of the Ventricular

Myocardium"[tw] OR leopard Syndrome*[tw] OR "Cardio Cutaneous Syndrome"[tw] OR

lentigines Syndrome*[tw] OR "Levocardia"[tw] OR marfan Syndrome*[tw] OR marfan's

Syndrome*[tw] OR noonan Syndrome*[tw] OR "Tetralogy of Fallot"[tw] OR "Fallot's

Tetralogy"[tw] OR "Fallot Tetralogy"[tw] OR "Fallots Tetralogy"[tw] OR "Transposition of Great

Vessels"[tw] OR "Great Vessels Transposition"[tw] OR "Transposition of Great Arteries"[tw] OR

"Great Arteries Transposition"[tw] OR "Dextro-Looped Transposition of the Great Arteries"[tw]

OR "Dextro Looped Transposition of the Great Arteries"[tw] OR "Double-Outlet Right

Ventricle"[tw] OR "Taussig-Bing Anomaly"[tw] OR tricuspid Atresia*[tw] OR "Tricuspid Valve

Atresia"[tw] OR "Tricuspid Valve Atresias"[tw] OR "Absent Right Atrioventricular

Connection"[tw] OR "Trilogy of Fallot"[tw] OR "Fallot Trilogy"[tw] OR "Fallot's Trilogy"[tw]

OR turner Syndrome*[tw] OR turner's Syndrome*[tw] OR turners Syndrome*[tw] OR "Bonnevie

Ullrich"[tw] OR "Congenital Heart Disease"[tw] OR "Congenital Heart Diseases"[tw] OR

"Congenital Cardiac Defect"[tw] OR "Congenital Cardiac Defects"[tw] OR naxos disease*[tw]

OR "Holt Oram syndrome"[tw] OR "heart hand syndrome"[tw] OR "congenital heart block"[tw])

AND ("Smoking"[Mesh] OR Smok*[tw] OR Tobacco*[tw] OR Nicotiana*[tw] OR cigar*[tw] OR

cannab*[tw]) AND ("Pregnancy"[Mesh] OR Pregnan*[tw] OR Gestat*[tw] OR Gravidit*[tw] OR

"child bearing"[tw] OR "childbearing"[tw])

In Embase, the strategy was:

((“congenital heart disease”/exp OR “congenital heart disease” OR “congenital heart diseases” OR

“congenital cardiac disease” OR “congenital cardiac diseases” OR “congenital cardiac distress”

OR “congenital cardiac distresses” OR “congenital heart distress” OR “congenital heart distresses”

OR “congenital heart failure” OR “congenital heart failures” OR “heart congenital disease” OR

“heart congenital diseases” OR “neonatal cardiopathy” OR “persistent truncus arteriosus” OR

“congenital heart block” OR “congenital cardiac block” OR “congenital cardial block” OR

“congenital heart malformation” OR “congenital heart malformations” OR “congenital heart

anomaly” OR “congenital heart anomalies” OR “congenital heart defect” OR “congenital heart

defects” OR “heart right ventricle dysplasia” OR “arrhythmogenic heart right ventricle dysplasia”

OR “arrhythmogenic right ventricular cardiomyopathy” OR “arrhythmogenic right ventricular

dysplasia” OR “cardiomyopathy, arrhythmogenic right ventricular” OR “Naxos disease” OR

“Naxos diseases” OR “right ventricular cardiomyopathy” OR “right ventricular dysplasia” OR

“Holt Oram syndrome” OR “atriodigital syndrome” OR “heart hand syndrome” OR “LEOPARD

syndrome” OR “cardiocutaneous syndrome” OR “cardiomyopathic lentiginosis” OR “lentiginosis

profuse” OR “lentigines syndrome” OR “cardiomyopathic lentiginosis” OR “McKusick Kaufman

syndrome” OR “congenital heart block” OR “congenital cardiac block” OR “congenital cardial

block”) AND (“smoking”/exp OR smok* OR Tobacco* OR Nicotiana* OR cigar* OR cannab*)

AND (“pregnancy”/exp OR pregnan* OR “child bearing” OR “childbearing” OR gestat* OR

gravidit*))

In Web of Science, the strategy was:

((“Congenital Heart Defect” OR “Congenital Heart Defects” OR “Heart Abnormality” OR “Heart

Abnormalities” OR “Aortic Coarctation” OR “Aortic CoarctationS” OR “Coarctation of the Aorta”

OR “Coarctation of Aorta” OR “ARVD-C” OR “Arrhythmogenic Right Ventricular

Cardiomyopathy” OR “Arrhythmogenic Right Ventricular Dysplasia-Cardiomyopathy” OR

“Barth Syndrome” OR “Cor Triatriatum” OR “Subdivided Left Atrium” OR “Subdivided Left

Atriums” OR “Triatrial Heart” OR “Triatrial Hearts” OR “Cor Triatriatum Sinistrum” OR

“Coronary Vessel Anomalies” OR “Coronary Vessel Anomaly” OR “Crisscross Heart” OR “Criss

cross Heart” OR “Criss cross Hearts” OR “Dextrocardia” OR “Patent Ductus Arteriosus” OR

“Patency of the Ductus Arteriosus" OR “Ebstein Anomaly” OR “Ebstein Anomalies” OR

“Ebstein's Malformation” OR “Ebstein's Malformations” OR “Ebsteins Malformation” OR

“Ebsteins Malformations” OR “Ebstein's Anomaly” OR “Ebstein's Anomalies” OR “Ebsteins

Anomaly” OR “Ebsteins Anomalies” OR “Ectopia Cordis” OR “Eisenmenger's Complex” OR

“Eisenmenger Complex” OR “Eisenmenger's Syndrome” OR “Eisenmengers Syndrome” OR

“Eisenmenger Syndrome” OR “Heart Septal Defect” OR “Heart Septal Defects” OR “Atrial

Isomerism” OR “Atrial Isomerism” OR “Hypoplastic Left Heart Syndrome” OR “Isolated

Noncompaction of the Ventricular Myocardium” OR “LEOPARD Syndrome” OR “Cardio

Cutaneous Syndrome” OR “Lentigines Syndrome” OR “Levocardia” OR “Marfan Syndrome” OR

“Marfan's Syndrome” OR “Noonan Syndrome” OR “Tetralogy of Fallot” OR “Fallot's Tetralogy”

OR “Fallot Tetralogy” OR “Fallots Tetralogy” OR “Transposition of Great Vessels” OR “Great

Vessels Transposition” OR “Transposition of Great Arteries” OR “Great Arteries Transposition”

OR “Dextro-Looped Transposition of the Great Arteries” OR “Dextro Looped Transposition of the

Great Arteries” OR “Double-Outlet Right Ventricle” OR “Taussig-Bing Anomaly” OR “Tricuspid

Atresia” OR “Tricuspid Valve Atresia” OR “Tricuspid Valve Atresias” OR “Absent Right

Atrioventricular Connection” OR “Trilogy of Fallot” OR “Fallot Trilogy” OR “Fallot's Trilogy”

OR “Turner Syndrome” OR “Turner's Syndrome” OR “Turners Syndrome” OR “Bonnevie Ullrich”

OR “Congenital Heart Disease” OR “Congenital Heart Diseases” OR “Congenital Cardiac Defect”

OR “Congenital Cardiac Defects” OR “Naxos disease” OR “Holt Oram syndrome” OR

“atriodigital syndrome” OR “heart hand syndrome” OR “congenital heart block” OR “congenital

cardiac block” OR “congenital cardial block”) AND (Smok* OR Tobacco* OR Nicotiana* OR

cigar* OR cannab*) AND (Pregnan* OR Gestat* OR Gravidit* OR “child bearing” OR

“childbearing”))

Supplementary B. Summary for ORs for ordinal smoking data

Study Subtype Smoking RR and 95%CI

Alverson et al. 2011

[25]

Any CHD

1-10 cig/d 1.11 (0.96-1.28)

11-20 cig/d 1.13 (0.95-1.36)

≥21 cig/d 1.07 (0.80-1.45)

ASD

1-10 cig/d 1.41 (0.95-2.11)

11-20 cig/d 1.59 (0.98-2.58)

≥21 cig/d 1.64 (0.74-3.62)

AVSD

1-10 cig/d 1.44 (0.70-2.97)

11-20 cig/d 1.57 (0.68-3.59)

≥21 cig/d 2.00 (0.60-6.71)

CTD

1-10 cig/d 0.83 (0.60-1.15)

11-20 cig/d 1.15 (0.80-1.64)

≥21 cig/d 0.91 (0.48-1.72)

LVOTO

1-10 cig/d 1.42 (1.01-1.99)

11-20 cig/d 0.60 (0.34-1.06)

≥21 cig/d 1.00 (0.48-2.11)

SPD 1-10 cig/d 1.14 (0.93-1.41)

11-20 cig/d 1.19 (0.92-1.54)

≥21 cig/d 1.07 (0.68-1.67)

TGA

1-10 cig/d 0.82 (0.51-1.30)

11-20 cig/d 0.81 (0.46-1.43)

≥21 cig/d 1.12 (0.51-2.47)

TOF

1-10 cig/d 0.84 (0.52-1.35)

11-20 cig/d 1.17 (0.69-1.98)

≥21 cig/d 0.21 (0.03-1.49)

VSD

1-10 cig/d 1.24 (0.96-1.60)

11-20 cig/d 1.13 (0.81-1.58)

≥21 cig/d 1.15 (0.66-2.00)

Cedergren et al. 2006

[59] Any CHD

1-10 cig/d 0.96 (0.88-1.04)

≥11 cig/d 1.00 (0.90-1.12)

Grewal et al. 2008

[32]

CTD ≤5 cig/d 1.0 (0.5-2.0)

>5 cig/d 0.5 (0.2-1.2)

TGA ≤5 cig/d 0.3 (0.1-1.4)

>5 cig/d 0.4 (0.1-1.7)

TOF ≤5 cig/d 1.6 (0.8-3.2)

>5 cig/d 0.5 (0.2-1.7)

Kuciene et al. 2010

[37] SPD

<10 cig/d 2.06 (1.46-2.90)

10-20 cig/d 3.24 (1.67-6.27)

Lupo et al. 2012 [40] Any CHD

< 15 cig/d 1.12 (0.95-1.31)

15-24 cig/d 0.98 (0.75-1.27)

≥25 cig/d 1.81 (1.13-2.89)

Malik et al. 2008 [41]

ASD

< 15 cig/d 2.02 (1.47-2.77)

15-24 cig/d 1.78 (1.05-3.01)

≥25 cig/d 2.35 (0.92-6.00)

AVSD < 15 cig/d 1.02 (0.53-1.97)

15-24 cig/d 2.18 (1.04-4.55)

≥25 cig/d 2.01 (0.44-9.12)

CTD

< 15 cig/d 1.06 (0.82-1.35)

15-24 cig/d 0.84 (0.56-1.27)

≥25 cig/d 0.97 (0.44-2.12)

LVOTO

< 15 cig/d 0.99 (0.74-1.32)

15-24 cig/d 0.89 (0.57-1.38)

≥25 cig/d 0.93 (0.38-2.26)

RVOTO < 15 cig/d 1.25 (0.95-1.65)

15-24 cig/d 0.93 (0.59-1.49)

≥25 cig/d 2.35 (1.21-4.53)

SPD < 15 cig/d 1.44 (1.18-1.76)

15-24 cig/d 1.50 (1.11-2.03)

≥25 cig/d 2.06 (1.20-3.54)

TGA < 15 cig/d 1.08 (0.73-1.58)

15-24 cig/d 0.79 (0.42-1.48)

≥25 cig/d 1.19 (0.41-3.49)

TOF < 15 cig/d 1.03 (0.71-1.48)

15-24 cig/d 0.62 (0.31-1.26)

≥25 cig/d 1.01 (0.30-3.38)

VSD

< 15 cig/d 1.30 (1.00-1.69)

15-24 cig/d 1.33 (0.89-2.00)

≥25 cig/d 1.68 (0.82-3.47)

Patel et al. 2012 [43] AVSD

< 14 cig/d 1.5 (0.9-2.5)

14-24 cig/d 1.2 (0.5-2.7)

≥25 cig/d 4.4 (1.5-12.8)

Tikkanen et al. 1991

[50] VSD

1-14 cig/d 1.18 (0.77-1.83)

15-29 cig/d 1.59 (0.62-4.04)


[51] Any CHD

1-14 cig/d 0.90 (0.69-1.18)

15-29 cig/d 1.64 (0.93-2.87)


[52] CTD

1-14 cig/d 1.07 (0.62-1.85)

15-29 cig/d 0.85 (0.19-3.70)


[53] ASD

1-14 cig/d 0.7 (.03-1.6)

15-29 cig/d 0.8 (0.1-5.7)

Wasserman et al.

1996 [8]

CTD 1-19 cig/d 1.3 (0.84-2.0)

≥20 cig/d 1.4 (0.65-3.0)

TGA 1-19 cig/d 1.4 (0.74-2.6)

≥20 cig/d 2.1 (0.79-5.6)

TOF 1-19 cig/d 1.3 (0.72-2.4)

≥20 cig/d 0.52 (0.08-2.4)

Williams et al. 2004

[57] VSD

1-14 cig/d 1.37 (0.85-2.21)

15-24 cig/d 1.15 (0.66-1.99)

≥25 cig/d 0.90 (0.23-2.45)

ASD: atrial septal defect AVSD: atrioventricular septal defect CHD: congenital heart defect CTD: conotruncal heart defect LVOTO: left ventricular outflow tract obstruction RVOTO: right ventricular outflow tract obstruction SPD: septal defect TGA: transposition of the great arteries TOF: tetralogy of Fallot VSD: ventricular septal defect

Supplementary C. Summary of risk of bias

Red: high risk of bias

Green: low risk of bias

Yellow: unclear

Supplementary D. Linaer dose-response curve (solid line is the fitted line, and dash line is the 95%CI)

any CHD

0.5

1.0

1.5

2.0

2.5

RR

0 5 10 15 20 25smoking (cig/d)

SPD

1.0

1.2

1.4

1.6

1.8

2.0

RR

0 5 10 15 20smoking (cig/d)

TGA

0.6

0.8

1.0

1.2

1.4

1.6

1.8R

R


TOF

0.0

100.0

200.0

300.0

400.0

500.0

600.0

RR


CTD

0.8

1.0

1.2

1.4

1.6R

R

0 5 10 15 20 25smoking (cig/d)

ASD

1.0

1.5

2.0

2.5

3.0

RR

0 5 10 15 20 25smoking (cig/d)

VSD

0.8

1.0

1.2

1.4

1.6

1.8R

R

0 5 10 15 20 25smoking (cig/d)

Supplementary E. Quadratic dose-response curve (solid line is the fitted line, and dash line is the 95%CI)

any CHD

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

RR

0 5 10 15 20 25smoking (cig/d)

SPD

0.8

1.0

1.2

1.4

1.6

1.8

RR


TGA

0.5

1.0

1.5

2.0

2.5R

R


TOF

0.0

500.0

1000.0

1500.0

2000.0

2500.0

3000.0

RR


CTD

0.8

1.0

1.2

1.4

1.6

1.8

2.0R

R

0 5 10 15 20 25smoking (cig/d)

ASD

0.5

1.0

1.5

2.0

2.5

3.0

RR

0 5 10 15 20 25smoking (cig/d)

VSD

0.6

0.8

1.0

1.2

1.4

1.6R

R

0 5 10 15 20 25smoking (cig/d)

Supplementary file F. Funnel Plots (1) Any CHD

(2) ASD

0.2

.4.6

.8

SE

of lo

gR

R

-2 -1 0 1 2log RR

Funnel plot with pseudo 95% confidence limits0

.2.4

.6.8

SE

of lo

gR

R

-1 0 1 2log RR

Funnel plot with pseudo 95% confidence limits

(3) AVSD

(4) CTD

0.1

.2.3

SE

of lo

gR

R

-.5 0 .5 1log RR


0.1

.2.3

.4

SE

of lo

gR

R

-1 -.5 0 .5 1log RR


(5) LVOTO

(6) RVOTO

0.1

.2.3

.4

SE

of lo

gR

R

-1 -.5 0 .5log RR


.1.2

.3.4

SE

of lo

gR

R

-1 -.5 0 .5 1log RR


(7) TGA

(8) TOF

0.5

1

SE

of lo

gR

R

-2 -1 0 1 2log RR


.05

.1.1

5.2

SE

of lo

gR

R

-.4 -.2 0 .2 .4log RR


(9) SPD

(10) VSD

0.1

.2.3

.4

SE

of lo

gR

R

-.5 0 .5 1log RR


0.1

.2.3

.4

SE

of lo

gR

R

-1 -.5 0 .5 1log RR


Documents

Supplementary A. Search strategy Electronic search from ... · Supplementary A. Search strategy Electronic search from database In PubMed, we used “MeSH” term and keywords to