Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) updated on 07-01-2025

Low Apgar score (< 7) (at 5 min)

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S18440
R78237		 Lee (Controls exposed to TCAs), 2025 5-minute Apgar score<7 during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 1.74 [0.20;15.08] C
excluded (control group) 		1/71   5/613 6 71
ref
S18441
R78258		 Lee (Controls unexposed, general pop), 2025 5-minute Apgar score<7 during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.87 [0.26;1.36] 1/71   1,721/463,440 1,722 71
ref
S18310
R77109		 Martin - Venlafaxine, 2024 Low Apgar score at 5 min (<7) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 2.04 [1.76;2.37] 209/5,769   30,996/2,078,011 31,205 5,769
ref
S13145
R50180		 Marks - Duloxetine (Controls exposed to Bupropion), 2021 5 Min APGAR <7 during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Monotherapy: SNRI only 1.34 [0.78;2.30] C 22/139   50/406 72 139
ref
S13352
R51470		 Calderon-Margalit - Venlafaxine, 2009 APGAR Score at 5 minute <7 during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 11.60 [1.85;72.60] -/9   -/2,493 - 9
ref
Total 4 studies 1.93 [1.30;2.88] 32,999 5,988
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Lee (Controls unexposed, general pop), 2025Lee, 2025 1 1.87[0.26; 1.36]1,7227116%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Martin - Venlafaxine, 2024Martin - Venlafaxine, 2024 2.04[1.76; 2.37]31,2055,76952%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Marks - Duloxetine (Controls exposed to Bupropion), 2021Marks - Duloxetine, 2021 2 1.34[0.78; 2.30]7213927%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Calderon-Margalit - Venlafaxine, 2009Calderon-Margalit - Venlafaxine, 2009 11.60[1.85; 72.60]-94%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 48% 1.93[1.30; 2.88]32,9995,9880.550.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, general pop; 2: Controls exposed to Bupropion;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.93[1.30; 2.88]32,9995,98848%NALee (Controls unexposed, general pop), 2025 Martin - Venlafaxine, 2024 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Calderon-Margalit - Venlafaxine, 2009 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.28[1.32; 3.95]32,9275,84942%NALee (Controls unexposed, general pop), 2025 Martin - Venlafaxine, 2024 Calderon-Margalit - Venlafaxine, 2009 3 exposed to other treatment, sickexposed to other treatment, sick 1.34[0.78; 2.30]72139 -NAMarks - Duloxetine (Controls exposed to Bupropion), 2021 1 Tags Adjustment   - No  - No 1.34[0.78; 2.30]72139 -NAMarks - Duloxetine (Controls exposed to Bupropion), 2021 1   - Yes  - Yes 2.28[1.32; 3.95]32,9275,84942%NALee (Controls unexposed, general pop), 2025 Martin - Venlafaxine, 2024 Calderon-Margalit - Venlafaxine, 2009 3 Monotherapy   - no or not specified  - no or not specified 11.60[1.85; 72.67]-9 -NACalderon-Margalit - Venlafaxine, 2009 1   - SNRI only  - SNRI only 1.48[0.94; 2.33]1,7942100%NALee (Controls unexposed, general pop), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 2   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 2.04[1.76; 2.37]31,2055,769 -NAMartin - Venlafaxine, 2024 1 All studiesAll studies 1.93[1.30; 2.88]32,9995,98848%NALee (Controls unexposed, general pop), 2025 Martin - Venlafaxine, 2024 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Calderon-Margalit - Venlafaxine, 2009 40.550.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.92.91.1230.000Lee (Controls unexposed, general pop), 2025Martin - Venlafaxine, 2024Marks - Duloxetine (Controls exposed to Bupropion), 2021Calderon-Margalit - Venlafaxine, 2009

Asymetry test p-value = NaN (by Egger's regression)

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18440

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.28[1.32; 3.95]32,9275,84942%NALee (Controls unexposed, general pop), 2025 Martin - Venlafaxine, 2024 Calderon-Margalit - Venlafaxine, 2009 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.36[0.80; 2.30]782100%NALee (Controls exposed to TCAs), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 20.510.01.0