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

Neonatal medical care

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
R78239
Lee (Controls exposed to TCAs), 2025 Admission to neonatal intensive care unit (NICU) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 1.24 [0.36;4.28] C
excluded (control group)
3/71   21/613 24 71
ref
S18441
R78260
Lee (Controls unexposed, general pop), 2025 Admission to neonatal intensive care unit (NICU) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.15 [0.36;3.67] 3/71   8,566/463,440 8,569 71
ref
S13145
R50173
Marks - Duloxetine (Controls exposed to Bupropion), 2021 Neonatal intensive care unit admission during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Monotherapy: SNRI only 2.04 [1.29;3.23] 55/139   91/406 146 139
ref
S14993
R61354
Robinson-Wolrath - SNRI, 2016 Need for any resuscitation during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.80 [1.16;2.79] -/-   -/- - -
ref
S11693
R43003
Reis - SNRI (Controls exposed to TCA), 2010 Respiratory diagnoses 2nd and/or 3rd trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: SNRI only 0.64 [0.43;0.96] C
excluded (control group)
38/538   83/784 121 538
ref
S11694
R43015
Reis - SNRI (Controls unexposed, NOS), 2010 Respiratory diagnoses 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SNRI only 1.52 [1.08;2.14] 38/538   57,487/1,062,190 57,525 538
ref
S13352
R51471
Calderon-Margalit - Venlafaxine, 2009 Neonatal Intensiv Care Unit (NICU) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 3.68 [0.76;17.80] -/9   -/2,493 - 9
ref
Total 5 studies 1.72 [1.37;2.15] 66,240 757
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 1.15[0.36; 3.67]8,569714%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Marks - Duloxetine (Controls exposed to Bupropion), 2021Marks - Duloxetine, 2021 2 2.04[1.29; 3.23]14613924%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Robinson-Wolrath - SNRI, 2016Robinson-Wolrath - SNRI, 2016 1.80[1.16; 2.79]--26%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: unclear Reis - SNRI (Controls unexposed, NOS), 2010Reis - SNRI, 2010 3 1.52[1.08; 2.14]57,52553844%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Calderon-Margalit - Venlafaxine, 2009Calderon-Margalit - Venlafaxine, 2009 3.68[0.76; 17.80]-92%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.72[1.37; 2.15]66,2407570.510.01.0ROB: 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; 3: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.72[1.37; 2.15]66,2407570%NALee (Controls unexposed, general pop), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Robinson-Wolrath - SNRI, 2016 Reis - SNRI (Controls unexposed, NOS), 2010 Calderon-Margalit - Venlafaxine, 2009 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.63[1.26; 2.11]66,0946180%NALee (Controls unexposed, general pop), 2025 Robinson-Wolrath - SNRI, 2016 Reis - SNRI (Controls unexposed, NOS), 2010 Calderon-Margalit - Venlafaxine, 2009 4 exposed to other treatment, sickexposed to other treatment, sick 2.04[1.29; 3.23]146139 -NAMarks - Duloxetine (Controls exposed to Bupropion), 2021 1 Tags Adjustment   - Yes  - Yes 1.72[1.37; 2.15]66,2407570%NALee (Controls unexposed, general pop), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Robinson-Wolrath - SNRI, 2016 Reis - SNRI (Controls unexposed, NOS), 2010 Calderon-Margalit - Venlafaxine, 2009 5 Monotherapy   - no or not specified  - no or not specified 3.68[0.76; 17.81]-9 -NACalderon-Margalit - Venlafaxine, 2009 1   - SNRI only  - SNRI only 1.69[1.35; 2.13]66,2407480%NALee (Controls unexposed, general pop), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Robinson-Wolrath - SNRI, 2016 Reis - SNRI (Controls unexposed, NOS), 2010 4 All studiesAll studies 1.72[1.37; 2.15]66,2407570%NALee (Controls unexposed, general pop), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Robinson-Wolrath - SNRI, 2016 Reis - SNRI (Controls unexposed, NOS), 2010 Calderon-Margalit - Venlafaxine, 2009 50.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.92.40.9650.000Lee (Controls unexposed, general pop), 2025Marks - Duloxetine (Controls exposed to Bupropion), 2021Robinson-Wolrath - SNRI, 2016Reis - SNRI (Controls unexposed, NOS), 2010Calderon-Margalit - Venlafaxine, 2009

Asymetry test p-value = 0.6020 (by Egger's regression)

slope=0.4270 (0.2212); intercept=0.4991 (0.8591); t=0.5810; p=0.6020

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 11693, 18440

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.63[1.26; 2.11]66,0946180%NALee (Controls unexposed, general pop), 2025 Robinson-Wolrath - SNRI, 2016 Reis - SNRI (Controls unexposed, NOS), 2010 Calderon-Margalit - Venlafaxine, 2009 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.16[0.48; 2.83]29174886%NALee (Controls exposed to TCAs), 2025 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Reis - SNRI (Controls exposed to TCA), 2010 30.510.01.0