TABLE 1

Psychomotor Development Studies That Satisfied the Criteria for Inclusion in the Systematic Review

StudyStudy Design and NGroups ComparedAge at TestingMedicationMotor MeasureQuality Rating (of 9)
Reebye et al48Prospective cohortExposure to SSRI alone (n = 24)2 moSSRI only: paroxetine fluoxetine sertralineBSID-II5
N = 61Exposure to SSRI and benzodiazepine (n = 14)
No depression and no psychotropic medication (n = 23)SSRI and clonazepam
Nulman et al19ProspectiveTricyclics (n = 46)Between 15 mo and 71 moAmitriptyline (39%)BSID-II (PDI) up to 30 mo of age8
N = 122Fluoxetine (n = 40)Imipramine (26%)
Clomipramine (15%)MSCA after 30 mo of age
No psychiatric or MDD history and no exposure to medications (n = 36)Desipramine (6.5%)
Nortriptyline (6.5%)
Doxepin (4%)
Maprotiline (2%)
Fluoxetine (20–80 mg per d): n = 40; 100% of group
Simon et al49Retrospective case controlExposure to SSRIs during pregnancy (n = 185)Birth to 2 yFluoxetine (33%)Pediatrician health monitoring with diagnosis by physician and formal motor development evaluation5
N = 788No exposure to SSRIs during pregnancy (n = 185)Amitriptyline (17%)
Imipramine (12%)
Exposure to TCA during pregnancy (n = 209)Doxepin (9%)
Nortriptyline (8%)
Sertraline (8%)
Paroxetine (7%)
Desipramine (6%; some multiple exposures)
No exposure to TCA during pregnancy (n = 209)
Casper et al20Controlled, cohort comparisonMDD diagnosis during pregnancy and treated with SSRIs (n = 31)Between 6 mo and 40 moSertraline (48%)BSID-II7
MDD diagnosis during pregnancy but no SSRI treatment (n = 13)Paroxetine (26%)PDI and BRS
Fluoxetine (23%)
Fluvoxamine (3%)
N = 44
Mortensen et al21Retrospective cohortNo medication (n = 755)7–10 moADs not specifiedBOEL test6
ADs (n = 50)
N = 1095Benzodiazepines (n = 82)
Antiepileptics (n = 145)
Neuroleptics (n = 63)
Oberlander et al50Prospective cohort Exposure to SSRI alone (n = 28)2 mo and 8 moSSRI aloneBSID-II PDI score5
N = 69Exposure to SSRI and benzodiazepine (n = 18) Paroxetine (61%)
 Fluoxetine (25%)
 Sertraline (14%)
Nonexposed control group (n = 23)SSRI and clonazepam
 Paroxetine (89%)
 Fluoxetine (11%)
Oberlander et al51Prospective cohortPrenatal exposure to SSRIs only (n = 11)2 mo and 8 moParoxetine (71%)BSID-II (PDI)5
N = 63Prenatal and postnatal exposure (via breastfeeding) to SSRIs (n = 30)Fluoxetine (19.5%)
No psychotropic agents and no history of maternal mental illness (n = 22)Sertraline (19.5%)
Pedersen et al52Large-scale, population-based pregnancy cohort No severe depressive symptoms and no SSRI exposure during pregnancy (n = 81 042)6 mo and 19 moFluoxetine (25.5%)Computer-assisted telephone interviews with mothers reporting on motor development milestones7
Depressive symptoms during pregnancy but no SSRI exposure (n = 489)Citalopram (26%)
N = 81 946Depressive symptoms during pregnancy and SSRI exposure (n = 415)Paroxetine (23%)
Sertraline (25.5%)
Klinger et al53Prospective cohortSSRI exposure with NAS at birth (n = 30)2–6 y (no additional details provided)FluoxetineDDST-II gross motor and fine motor scores7
N = 82SSRI without NAS at birth (n = 52)Paroxetine
Citalopram
Sertraline
Fluvoxamine
Venlafaxine
Casper et al25Cohort comparisonSSRI exposure during first trimester (n = 14)Average : 14 moSertraline (36%)BSID-II PDI6
SSRI exposure during second and/or third trimester (n = 18)Fluoxetine (33%)
N = 55SSRI exposure during first, second, and third trimester (n = 23)Paroxetine (27%)
Citalopram (4%)
Galbally et al54Prospective case controlMDD and exposure to ADs at any time during pregnancy (n = 22)18–35 mo postpartumAt first trimesterBSID-III7
N = 41No exposure to ADs during pregnancy (n = 19) No medications (50%)
 Sertraline (19%)
 Venlafaxine (9.5%)
 Citalopram (7.1%)
 Fluoxetine (2.4%)
 Escitalopram (2.4%)
 Mianserin (2.4%)
 Mirtazapine (2.4%)
 Paroxetine (2.4%)
Suri et al55Prospective, naturalistic, blinded cohortMDD history and AD (unspecified type) use during pregnancy (n = 33)Within first wk (n = 59) and at 6–8 wk (n = 57)Sertraline 90.5±50.3 mg (36%)BNBAS9
MDD history without AD (unspecified type) use in pregnancy or discontinued (n = 16)Fluoxetine 22.5±7.5 mg (38%)
N = 64No exposure to AD (unspecified type) and no psychiatric history (n = 15)Other ADs (unspecified type; 26%)
Johnson et al56Prospective controlledPregnancy exposure to antipsychotics (n = 22)6 moUnspecified AD medicationINFANIB6
N = 309Pregnancy exposure to ADs (n = 202)
No exposure to psychotropic agents in pregnancy (n = 85)
Batton et al57Retrospective case controlPreterm infants (<36 and sixth-sevenths wk)24 mo and/or 36 moParoxetine (9.5%)BINS4
Exposed to SSRIs (n = 19)Fluoxetine (28.5%)BSID (pre-2006)
N = 38Preterm infants not exposed to SSRIs (n = 19)Sertraline (43%)
Citalopram (9.5%)BSID-III (post- 2006)
Escitalopram (9.5%)
de Vries et al58Prospective observationalSSRI-exposed infants (n = 63)Assessed during first wk after birth and again at 3–4 moParoxetine (43%)GMs and an MOS7
N = 107Nonexposed infants (n = 44; included 9 with depression and/or anxiety)Citalopram (22%)
Venlafaxine (16%)
Fluoxetine (13%)
Sertraline (3%)
Changed medications (3%)
Hanley et al59Prospective cohortMood disorder and SRI use during pregnancy (n = 31)10 moParoxetine (13%)BSID-III8
N = 83No exposure to SRIs during pregnancy (n = 52)
Fluoxetine (10%)
Sertraline (16%)
Venlafaxine (38%)
Citalopram (23%)
Austin et al24Controlled, prospective longitudinal cohortAD (unspecified type) exposure of mother during pregnancy (n = 35)18 moSertraline (31%)BSID-III6
No history of mood disorder and no AD (unspecified type) exposure during pregnancy (n = 23)Fluoxetine (17%)
N = 58Citalopram (14%)
Dothiepin (14%)
Venlafaxine (11%)
Escitalopram (6%)
Paroxetine (3%)
Fluvoxamine (3%)
Santucci et al60Longitudinal, observational cohortNo MDD and no SRI exposure (n = 98)12 wk, 26 wk, 52 wk, and 78 wk, corrected for prematuritySertraline (33%)BSID-II PDI and MQI8
MDD during pregnancy but no SRI exposure (n = 27)
N = 166MDD and SRI exposure during pregnancy (n = 41)Fluoxetine (24%)
Escitalopram (16%)
Citalopram (11%)
Venlafaxine (11%)
Fluvoxamine (2%)
Paroxetine (2%)
Galbally et al26Prospective case-controlledAD (unspecified type) use during mother’s pregnancy (n = 20)4 yBefore attritionMovement ABC7
No depression and no AD (unspecified type) use during pregnancy (n = 21) SSRI (84%)
N = 41 SNRI (9%)
 TCA (3%)
 NaSSA (3%)
Handal et al61Large-scale, population-based, prospective cohortNo SSRI exposure (n = 50 544)3 ySSRI medications not specifiedMaternal reports of gross and fine motor skills using selected items from the ASQ7
Prepregnancy SSRI use only (n = 479)
N = 51 404SSRI use during 1 pregnancy phase (n = 222)
Prolonged SSRI use (n = 159)
Hurault-Delarue et al62Observational Exposed to psychotropic medications in utero (n = 493)9 mo and again at 24 moMost common ADs (unspecified type) were as follows:General practitioner or pediatrician ratings on 14 items of psychomotor development5
N = 32 796No exposure to psychotropic medications in utero (n = 32 303) Amitriptyline
 Paroxetine
 Fluoxetine
 Venlafaxine
 Imipramine
Brown et al63Prospective birth cohortExposed to SSRIs during pregnancy (n = 15 596)Mean: 7.73 yFluoxetineMedical examination by physician recorded in the Finnish Hospital Discharge Register8
N= 56 340MDD history without AD (unspecified type) use during pregnancy (n = 9537)Citalopram
No MDD and no AD (unspecified type) exposure during pregnancy (n = 31 207)Paroxetine
Sertraline
Fluvoxamine
Escitalopram
Partridge et al64Cross-sectional cohortPregnancy exposure to SRI (n = 15)4–5 ySertraline (64%)Kinematic analysis of reach-and-drop task6
Untreated MDD during pregnancy (n = 10)Citalopram (24%)
N = 40Unexposed control group (n = 15)Escitalopram (4%)
Galbally et al65Population specific longitudinal cohortAD (unspecified type) use during pregnancy (n = 31)6 moBefore attrition or exclusionASQ6
Ceased AD (unspecified type) use during pregnancy (n = 11) SSRI (78%)
N = 42 SNRI (22%)
  • Movement ABC, Movement Assessment Battery for Children; AD, antidepressant; ASQ, Ages and Stages Questionnaire; BINS, Bayley Infant Neurodevelopmental Screener; BNBAS, Brazelton Neonate Behavior Assessment Scale; BOEL, blicken orienterar efter ljudet; BRS, Behavioral Rating Scale; BSID, Bayley Scales of Infant Development; DDST-II, Denver Developmental Screening Test II; GM, general movement; INFANIB, Infant Neurologic International Battery; MDD, major depressive disorder; MOS, motor optimality score; MQI, Motor Quality Index; MSCA, McCarthy Scales of Children’s Abilities; NaSSA, noradrenergic and specific serotonergic antidepressant; PDI, Psychomotor Development Index; SNRI, serotonin and norepinephrine reuptake inhibitor; SRI, serotonin reuptake inhibitor; TCA, tricyclic antidepressant.