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

Microcephaly / Small head circumference for gestational age

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.
S7921
R23968		 Giardinelli (Controls unexposed, disease free), 2018 Head circumference (<10th percentile at the age of 2 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Monotherapy: no or not specified 6.58 [0.71;61.09] C
excluded (control group) 		5/24   1/26 6 24
ref
S7916
R23959		 Giardinelli (Controls unexposed, sick), 2018 Head circumference (<10th percentile at the age of 2 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.41 [0.11;1.49] C 5/24   9/23 14 24
ref
S10597
R39100		 Kerr, 2018 Isolated microcephaly (ICD-9 - Within 6 months after delivery) 1st trimester case control unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 0.52 [0.01;3.04] 1/398   56/11,718 57 398
ref
S5364
R16335		 Nishigori, 2017 Microcephaly (NOS - Until 1 month of age) 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 16.48 [2.24;121.04] 1/172   34/95,433 35 172
ref
S7570
R22782		 Kivistö, 2016 Head circumference <10th centile (in newborns) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Monotherapy: SSRI only 1.20 [0.80;1.79] 28/-   1,709/- 1,737 -
ref
S10040
R36265		 Davidson, 2009 Birth head circumference <10th percentile for age throughout pregnancy retrospective cohort unexposed, disease free Adjustment: No Matched Monotherapy: no or not specified 10.64 [0.53;212.45] C 4/21   0/20 4 21
ref
S490
R15178		 Chambers - Fluoxetine, 1996 Microcephalic (<3rd percentile) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Monotherapy: no or not specified 2.23 [0.31;16.04] C 2/95   2/209 4 95
ref
Total 6 studies 1.69 [0.62;4.59] 1,851 710
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 Giardinelli (Controls unexposed, sick), 2018Giardinelli, 2018 1 0.41[0.11; 1.49]142422%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kerr, 2018Kerr, 2018 0.52[0.01; 3.04]573989%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Nishigori, 2017Nishigori, 2017 16.48[2.24; 121.04]3517214%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kivistö, 2016Kivistö, 2016 1.20[0.80; 1.79]1,737-32%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Davidson, 2009Davidson, 2009 10.64[0.53; 212.45]4218%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Chambers - Fluoxetine, 1996Chambers - Fluoxetine, 1996 2.23[0.31; 16.04]49515%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 58% 1.69[0.62; 4.59]1,8517100.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.96[0.65; 5.95]1,79431266%NAGiardinelli (Controls unexposed, sick), 2018 Nishigori, 2017 Kivistö, 2016 Davidson, 2009 Chambers - Fluoxetine, 1996 5 case control studiescase control studies 0.52[0.03; 9.07]57398 -NAKerr, 2018 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.57[0.78; 8.44]1,83768655%NAKerr, 2018 Nishigori, 2017 Kivistö, 2016 Davidson, 2009 Chambers - Fluoxetine, 1996 5 unexposed, sickunexposed, sick 0.41[0.11; 1.49]1424 -NAGiardinelli (Controls unexposed, sick), 2018 1 Tags Adjustment   - No  - No 2.20[0.44; 10.93]11471066%NAGiardinelli (Controls unexposed, sick), 2018 Kerr, 2018 Nishigori, 2017 Davidson, 2009 Chambers - Fluoxetine, 1996 5   - Yes  - Yes 1.20[0.80; 1.79]1,737- -NAKivistö, 2016 1 MatchedMatched 10.64[0.53; 212.45]421 -NADavidson, 2009 1 Monotherapy   - no or not specified  - no or not specified 2.20[0.44; 10.93]11471066%NAGiardinelli (Controls unexposed, sick), 2018 Kerr, 2018 Nishigori, 2017 Davidson, 2009 Chambers - Fluoxetine, 1996 5   - SSRI only  - SSRI only 1.20[0.80; 1.79]1,737- -NAKivistö, 2016 1 Unexposed sick   - recent illness/treatment (during o ...  - recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy) 0.41[0.11; 1.49]1424 -NAGiardinelli (Controls unexposed, sick), 2018 1 All studiesAll studies 1.69[0.62; 4.59]1,85171058%NAGiardinelli (Controls unexposed, sick), 2018 Kerr, 2018 Nishigori, 2017 Kivistö, 2016 Davidson, 2009 Chambers - Fluoxetine, 1996 60.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.64.11.8330.000Giardinelli (Controls unexposed, sick), 2018Kerr, 2018Nishigori, 2017Kivistö, 2016Davidson, 2009Chambers - Fluoxetine, 1996

Asymetry test p-value = 0.4962 (by Egger's regression)

slope=-0.0221 (0.4468); intercept=0.7324 (0.9796); t=0.7476; p=0.4962

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 7921

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.91[0.99; 8.56]1,84371053%NAGiardinelli (Controls unexposed, disease free), 2018 Kerr, 2018 Nishigori, 2017 Kivistö, 2016 Davidson, 2009 Chambers - Fluoxetine, 1996 6 unexposed, sick controlsunexposed, sick controls Out of scale0.41[0.11; 1.49]1424 -NAGiardinelli (Controls unexposed, sick), 2018 10.510.01.0