Selective Serotonin Reuptake Inhibitor (SSRI) updated on 07-01-2025

Large for gestational age (weight)

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.
S18442
R78277		 Lee (Controls exposed to TCAs), 2025 Large for gestational age (birth weight >2 standard deviations above the mean for gestational age) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 1.09 [0.52;2.27] C
excluded (control group) 		26/1,465   10/613 36 1,465
ref
S18408
R77699		 Lee (Controls unexposed, general pop), 2025 Large for gestational age (birth weight >2 standard deviations above the mean for gestational age) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.80 [0.53;1.21] 26/1,465   9,744/463,440 9,770 1,465
ref
S18131
R76224		 Raviv, 2025 Large for gestational age (birthweight z-scores > 1.28) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.66 [0.54;0.80] C 103/2,321   6,827/103,607 6,930 2,321
ref
S14988
R61340		 Gover, 2023 Large for gestational age throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: no or not specified 1.00 [0.13;7.85] C 2/21   2/21 4 21
ref
S15009
R61493		 Scannell, 2020 Large for gestational age during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.51 [0.27;0.97] 25/149   -/- - 149
ref
S7570
R22775		 Kivistö, 2016 Large for gestational age (birthweight >10th centile) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 0.99 [0.69;1.46] 35/358   2,191/24,402 2,226 358
ref
S5430
R21319		 Norby, 2016 Large for gestational age (NOS) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 1.10 [1.00;1.20] -/17,736   -/718,533 - 17,736
ref
S13017
R49398		 Hannerfors (Controls unexposed, NOS), 2015 Large for gestational age (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) excluded Adjustment: No Monotherapy: no or not specified 0.85 [0.36;2.01] C
excluded (control group) 		7/207   24/609 31 207
ref
S13016
R49390		 Hannerfors (Controls unexposed, sick), 2015 Large for gestational age (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Monotherapy: no or not specified 4.17 [0.23;74.20] C 7/207   0/56 7 207
ref
S6999
R19855		 Reis (Controls exposed to TCA), 2010 Large for gestational age (>2 S.D. from expected weight) 2nd and/or 3rd trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Monotherapy: SSRI only 0.81 [0.60;1.08] C
excluded (control group) 		292/4,809   58/784 350 4,809
ref
S5410
R17515		 Reis (Controls unexposed, NOS), 2010 Large for gestational age (>2 S.D. from expected weight) 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.06 [0.93;1.19] 292/4,809   68,814/1,062,190 69,106 4,809
ref
S10179
R37277		 Zeskind, 2004 Large for gestational age (NOS) throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched Monotherapy: SSRI only 2.31 [0.36;14.72] C 4/17   2/17 6 17
ref
Total 9 studies 0.90 [0.74;1.09] 88,049 27,083
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 0.80[0.53; 1.21]9,7701,46512%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Raviv, 2025Raviv, 2025 0.66[0.54; 0.80]6,9302,32120%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Gover, 2023Gover, 2023 1.00[0.13; 7.85]4211%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Scannell, 2020Scannell, 2020 0.51[0.27; 0.97]-1497%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Kivistö, 2016Kivistö, 2016 0.99[0.69; 1.46]2,22635813%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Norby, 2016Norby, 2016 1.10[1.00; 1.20]-17,73624%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Hannerfors (Controls unexposed, sick), 2015Hannerfors, 2015 2 4.17[0.23; 74.20]72070%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Reis (Controls unexposed, NOS), 2010Reis, 2010 3 1.06[0.93; 1.19]69,1064,80923%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Zeskind, 2004Zeskind, 2004 2.31[0.36; 14.72]6171%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (9 studies) I2 = 72% 0.90[0.74; 1.09]88,04927,0830.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, general pop; 2: Controls unexposed, sick; 3: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.90[0.74; 1.09]88,04927,08372%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Scannell, 2020 Kivistö, 2016 Norby, 2016 Hannerfors (Controls unexposed, sick), 2015 Reis (Controls unexposed, NOS), 2010 Zeskind, 2004 9 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.93[0.77; 1.13]88,04226,72775%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Kivistö, 2016 Norby, 2016 Reis (Controls unexposed, NOS), 2010 Zeskind, 2004 7 unexposed, sickunexposed, sick 0.90[0.14; 5.56]735649%NAScannell, 2020 Hannerfors (Controls unexposed, sick), 2015 2 Tags Adjustment   - No  - No 0.94[0.60; 1.48]6,94720,30282%NARaviv, 2025 Gover, 2023 Norby, 2016 Hannerfors (Controls unexposed, sick), 2015 Zeskind, 2004 5   - Yes  - Yes 0.91[0.71; 1.16]81,1026,78152%NALee (Controls unexposed, general pop), 2025 Scannell, 2020 Kivistö, 2016 Reis (Controls unexposed, NOS), 2010 4 MatchedMatched 1.59[0.40; 6.30]10380%NAGover, 2023 Zeskind, 2004 2 Monotherapy   - no or not specified  - no or not specified 0.80[0.52; 1.23]6,94120,43485%NARaviv, 2025 Gover, 2023 Scannell, 2020 Norby, 2016 Hannerfors (Controls unexposed, sick), 2015 5   - SSRI only  - SSRI only 1.03[0.92; 1.16]81,1086,6490%NALee (Controls unexposed, general pop), 2025 Kivistö, 2016 Reis (Controls unexposed, NOS), 2010 Zeskind, 2004 4 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.51[0.27; 0.97]-149 -NAScannell, 2020 1 All studiesAll studies 0.90[0.74; 1.09]88,04927,08372%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Scannell, 2020 Kivistö, 2016 Norby, 2016 Hannerfors (Controls unexposed, sick), 2015 Reis (Controls unexposed, NOS), 2010 Zeskind, 2004 90.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.31.7620.000Lee (Controls unexposed, general pop), 2025Raviv, 2025Gover, 2023Scannell, 2020Kivistö, 2016Norby, 2016Hannerfors (Controls unexposed, sick), 2015Reis (Controls unexposed, NOS), 2010Zeskind, 2004

Asymetry test p-value = 0.4853 (by Egger's regression)

slope=0.0587 (0.0943); intercept=-0.6843 (0.9290); t=0.7366; p=0.4853

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6999, 13017, 18442

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.93[0.78; 1.12]88,07326,93471%NALee (Controls unexposed, general pop), 2025 Raviv, 2025 Gover, 2023 Kivistö, 2016 Norby, 2016 Hannerfors (Controls unexposed, NOS), 2015 Reis (Controls unexposed, NOS), 2010 Zeskind, 2004 8 unexposed, sick controlsunexposed, sick controls 0.90[0.14; 5.56]2335649%NAScannell, 2020 Hannerfors (Controls unexposed, sick), 2015 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.84[0.64; 1.11]3866,2740%NALee (Controls exposed to TCAs), 2025 Reis (Controls exposed to TCA), 2010 20.510.01.0