Sertraline updated on 07-01-2025

ASD (Autism spectrum disorder): Diagnosis

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.
S18383
R77480		 Heuvelman, 2023 Autism spectrum disorder - Validated Read code list among primary care clinical and referral records - Mean age at end of follow-up 10.04 years, range 4–22 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy) 1.37 [0.88;2.14] -/2,088   -/16,330 - 2,088
ref
S18249
R76576		 Suarez (Controls unexposed, discontinuers), 2022 Autism Spectrum Disorder - ≥ 2 dates with ICD-9 Dx 299.xx (except 299.1x) - At ≥ 1 year of age 2nd and/or 3rd trimester retrospective cohort (claims database) 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) 1.11 [0.82;1.49] 324/55,722   66/11,529 390 55,722
ref
S18250
R76584		 Suarez (Controls unexposed, general pop), 2022 Autism Spectrum Disorder - ≥ 2 dates with ICD-9 Dx 299.xx (except 299.1x) - At ≥ 1 year of age 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 0.99 [0.88;1.13]
excluded (control group) 		324/55,788   11,437/2,996,295 11,761 55,788
ref
S10011
R35971		 Ames, 2021 Autism spectrum disorder (ASD): diagnostic criteria on the Autism Diagnostic Observation Schedule and the full ASD diagnostic criteria on the ADI-R or one of three alternative criteria on the ADI-R (age NOS). 3 months (or more) before pregnancy or during pregnancy excluded case control unexposed, disease free Adjustment: No Monotherapy: no or not specified 1.52 [0.99;2.32] C
excluded (exposition period) 		49/89   1,318/2,949 1,367 89
ref
S6549
R18030		 Brown, 2017 Autism spectrum disorder (ASD) Diagnostic (ICD-9/OHIP: 299; ICD-10: F84) - Age: 4-10 years (mean: 4.95 years) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: no or not specified 2.39 [0.56;9.82] -/-   -/- - -
ref
S11339
R41748		 Rai (Controls exposed to TCA), 2017 Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) - At 4-17 years during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Monotherapy: no or not specified 0.48 [0.26;0.90] C
excluded (control group) 		31/912   16/235 47 912
ref
S7484
R22402		 Rai (Controls unexposed, disease free), 2017 Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) at 4-17 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Monotherapy: no or not specified 1.68 [1.18;2.41] C
excluded (control group) 		31/912   4,889/238,943 4,920 912
ref
S7828
R23241		 Rai (Controls unexposed, sick), 2017 Autism spectrum disorder (ICD-9 (299), ICD-10 (F84), or DSM-IV (299) codes) at 4-17 years during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.45 [0.98;2.16] 31/912   353/12,325 384 912
ref
S7636
R22599		 Viktorin (Controls unexposed, NOS), 2017 Autism spectrum disorder (ICD10- F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, or F84.9) at 7-8 years during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Monotherapy: no or not specified 1.35 [0.87;2.08]
excluded (control group) 		22/1,016   1,524/172,646 1,546 1,016
ref
S7819
R23227		 Viktorin (Controls unexposed, sick), 2017 Autism spectrum disorder (ICD10- F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, or F84.9) at 7-8 years during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified 1.17 [0.71;1.95] 16/672   -/- - 672
ref
S7864
R23799		 Bérard, 2016 Autism spectrum disorder (ICD-9 codes 299.0, 299.8, 299.9; ICD-10 codes F84.0, F84.1, F84.5, F84.8, F84.9) - Age : 0-11 years (mean: 4.0) 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) 0.45 [0.05;4.26] 1/292   1,004/142,716 1,005 292
ref
Total 6 studies 1.25 [1.03;1.51] 1,779 59,686
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 Heuvelman, 2023Heuvelman, 2023 1.37[0.88; 2.14]-2,08819%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: criticalROB mesure: criticalROB reporting: low Suarez (Controls unexposed, discontinuers), 2022Suarez, 2022 1 1.11[0.82; 1.49]39055,72241%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Brown, 2017Brown, 2017 2.39[0.56; 9.82]--2%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Rai (Controls unexposed, sick), 2017Rai, 2017 2 1.45[0.98; 2.16]38491223%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Viktorin (Controls unexposed, sick), 2017Viktorin, 2017 3 1.17[0.71; 1.95]-67214%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard, 2016Bérard, 2016 0.45[0.05; 4.26]1,0052921%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 0% 1.25[1.03; 1.51]1,77959,6860.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, discontinuers; 2: Controls unexposed, sick; 3: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.25[1.03; 1.51]1,77959,6860%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 Bérard, 2016 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.30[0.27; 6.28]1,00529235%NABrown, 2017 Bérard, 2016 2 unexposed, sickunexposed, sick 1.24[1.02; 1.51]77459,3940%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 4 Tags Adjustment   - Yes  - Yes 1.25[1.03; 1.51]1,77959,6860%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 Bérard, 2016 6 Monotherapy   - no or not specified  - no or not specified 1.26[1.04; 1.52]77459,3940%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 5   - substance alone among all Antidep ( ...  - substance alone among all Antidep (SSRI, SNRI, ...) 0.45[0.05; 4.15]1,005292 -NABérard, 2016 1 Unexposed sick   - intermediate history of illness/tre ...  - intermediate history of illness/treatment (3-12 months before pregnancy) 1.37[0.88; 2.14]-2,088 -NAHeuvelman, 2023 1   - old history of illness/treatment (> ...  - old history of illness/treatment (> 12 months before pregnancy) or not specified 1.34[0.98; 1.82]3841,5840%NARai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 2   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 1.11[0.82; 1.50]39055,722 -NASuarez (Controls unexposed, discontinuers), 2022 1 All studiesAll studies 1.25[1.03; 1.51]1,77959,6860%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 Bérard, 2016 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.72.91.3610.000Heuvelman, 2023Suarez (Controls unexposed, discontinuers), 2022Brown, 2017Rai (Controls unexposed, sick), 2017Viktorin (Controls unexposed, sick), 2017Bérard, 2016

Asymetry test p-value = 0.8922 (by Egger's regression)

slope=0.1982 (0.1768); intercept=0.1067 (0.7389); t=0.1444; p=0.8922

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 11339, 7484, 7636, 18250

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.28[0.91; 1.79]19,23258,00862%NASuarez (Controls unexposed, general pop), 2022 Brown, 2017 Rai (Controls unexposed, disease free), 2017 Viktorin (Controls unexposed, NOS), 2017 Bérard, 2016 5 unexposed, sick controlsunexposed, sick controls 1.24[1.02; 1.51]78159,3940%NAHeuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls Out of scale0.48[0.26; 0.90]47912 -NARai (Controls exposed to TCA), 2017 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Halvorsen (Autism spectrum disorder _ Cohort ...Halvorsen (Autism spectrum disorder _ Cohort studies) 1.42[0.93; 2.16]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT2 metaPregmetaPreg 1.25[1.03; 1.51]0%59,686----Heuvelman, 2023 Suarez (Controls unexposed, discontinuers), 2022 Brown, 2017 Rai (Controls unexposed, sick), 2017 Viktorin (Controls unexposed, sick), 2017 Bérard, 2016 60.510.01.0