Table 1.

Characteristics of studies assessing the effect of antidepressants on motor development

Author [reference]	Study design	Data source	Sample size and exposure status	Control group	Outcome measure	Children’s age	Results	Main findings
Casper et al. 2003 [41]	Partly prospective, partly retrospective, clinic-based	Women’s Wellness Clinic or clinicians’ offices in Stanford, California	Exposed = 31 (any time during pregnancy) Control = 13 Exposure ascertainment: medical records	Children of mothers who had a major depressive disorder in pregnancy but received no medication	BSID-II	6–40 months	(SSRI exposed vs. unexposed) Mean ± SD scores on gross motor movement (4.77 ± 0.44 vs. 4.43 ± 0.68, p = 0.17); fine motor movement (5 ± 0 vs. 4.71 ± 0.46, p = 15) and tremulousness (5 ± 0 vs. 4.87 ± 0.46, p = 0.08)	There were differences in motor quality factors, particularly fine motor development and tremulousness, between the SSRI-exposed and unexposed groups; however, these differences were not statistically significant
Zeskind and Stephens 2004 [46]	Prospective cohort study	Carolinas Medical Center in Charlotte, North Carolina	Exposed = 17 (any time during pregnancy) Control = 17 Exposure ascertainment: medical records	Unexposed healthy mothers	NBAS	14–39 h	(SSRI exposed vs. unexposed) Mean ± SE scores on: Tremulousness (2.32 ± 0.2 vs. 1.8 ± 0.2, p = 0.038) Behavioral state (no. of differences: 2.5 ± 0.32 vs. 3.71 ± 0.32, p = 0.009; no. of changes: 7.15 ± 2.34 vs. 16.56 ± 2.34, p = 0.005) Active sleep (no. of epochs: 94.66 ± 6.64 vs. 83.46 ± 6.64, p = 0.13; no. of bouts: 3.36 ± 0.44 vs. 6.58 ± 0.44, p = 0.001; no. of startles: 14.59 ± 2.70 vs. 9.85 ± 2.59, p = 0.13) Motor activity (152.05 ± 21.25 vs. 106.5 ± 21.96, p = 0.08) No. of HRV rhythms (1.98 ± 0.19 vs. 2.39 ± 0.19, p = 0.07)	Infants exposed to SSRIs had insignificantly more active sleep and tremors than unexposed infants
Casper et al. 2011 [47]	Prospective cohort study, clinic-based	Women’s Clinic at Stanford University	Exposed = 55 1st trimester (N = 14); 2nd and 3rd trimester (N = 18); entire pregnancy (N = 23) Exposure ascertainment: medical records	None	BSID-II	12–40 months	PDI (p = 0.012, R2 = 0.11, r = − 0.34)	Longer prenatal exposure to SSRI increased the risk of lower PDI on the BSID-II in infancy. However, there was an imbalance in the demographic characteristics between the groups and potential confounding by depression severity
Galbally et al. 2011 [42]	Prospective case–control study	Mercy Hospital for Women	Cases = 22 (any time during pregnancy) Control = 19 Exposure ascertainment: medical records	Unexposed healthy mothers	BSID-II	18–35 months	(Exposed vs. unexposed) Mean ± SD scores on motor outcomes (fine: 12.84 ± 2.99 vs. 14.18 ± 2.7, p = 0.07; gross: 12.89 ± 2.75 vs. 14.18 ± 3.13, p = 0.09)	Children of mothers exposed to antidepressants during pregnancy had lower score on motor subscales than non-exposed children; however, the differences were not statistically significant
Hanley et al. 2013 [40]	Prospective cohort study, clinic-based	Community midwife clinics, family physician clinics, and a reproductive mental health clinic in metropolitan Vancouver	Exposed = 31 (any time during pregnancy) Control = 52 Exposure ascertainment: medical records	Unexposed healthy mothers	BSID-III	10 months	(Exposed vs. unexposed) Mean ± SD scores on motor outcomes (fine: 11.3 ± 2.2 vs. 11.2 ± 1.7, p = 0.55; gross: 8.3 ± 3.3 vs. 9.5 ± 2.8, p = 0.03)	Infants prenatally exposed to SSRIs had significantly lower gross motor scores than non-exposed infants in subscales of the BSID-III
Austin et al. 2013 [44]	Prospective, longitudinal case–control study	Perinatal mental health clinic at the Royal Hospital for Women	Exposed = 35 (any time during pregnancy) Controls = 23 Exposure ascertainment: self-reported	Unexposed healthy mothers	BSID-III	17–24 months	(Exposed vs. unexposed) Mean ± SD scores of motor outcomes (fine: 12.1 ± 2.4 vs. 11.8 ± 2.0, p = 0.40; gross: 9.2 ± 2.6 vs. 9.1 ± 2.0, p = 0.71)	Antidepressant exposure (mostly SSRIs) during pregnancy was not associated with worse motor development outcomes in infants
Smith et al. 2013 [39]	Prospective cohort study, clinic-based	Clinicians’ offices or hospital-based clinics in Connecticut and western Massachusetts	Exposed = 6 (third trimester) Control = 61 Exposure ascertainment: self-reported	Unexposed healthy mothers	NBAS	24 h (± 8 h) post-delivery	(SSRI exposed vs. unexposed) Mean ± SE of motor scores (25.200 ± 3.962 vs. 28.9 ± 3.055, p = 0.05)	Differences in motor scores were statistically insignificant in infants exposed to SSRIs compared to those with no in utero exposure after controlling for gestational age
Galbally et al. 2015 [45]	Prospective case–control study	Victorian Psychotropic Registry	Exposed = 20 (entire pregnancy) Control = 21 Exposure ascertainment: self-reported	Unexposed healthy mothers	Movement ABC	4 years	(Exposed vs. unexposed) Motor development, total composite score (80.40 ± 13.11 vs. 83.43 ± 12.12, p = 0.45)	Exposure to antidepressants during pregnancy had no effect on motor development in offspring
Brown et al. 2016 [43]	Population-based, prospective cohort study	Finnish Medical Birth Register	Exposed = 15,596 (mothers received at least one prescriptions for antidepressants during pregnancy) Unmedicated = 9537 Control = 31,207 Exposure ascertainment: medical records	Children of depressed women who were untreated during pregnancy and children of non-depressed, healthy women	Diagnostic codes for speech/language, scholastic, or motor disorders	From birth to 14 years	(SSRI-exposed vs. unmedicated group; SSRI-exposed vs. unexposed group) Motor disorder (adjusted HR 1.18, 95% CI 0.81–1.72; 1.26, 95% CI 0.90–1.77)	There was no significant increase in risk of motor disorders in offspring in the SSRI-exposed group compared to the unexposed group and the unmedicated group
van der Veere et al. 2020 [48]	Prospective cohort study SSRIs in pregnant mothers, outcome of the study on children (SMOK)	Pregnant women living near two level-2 hospitals in the north of the Netherlands were recruited through newspapers, midwives, general practitioners, gynecologists, and psychiatrists	SSRI-exposed = 61 (third trimester) Non-SSRI-exposed = 41 Exposure ascertainment: self-reported	Unexposed healthy mothers	BSID-III	2.5 years	(SSRI-exposed vs. unexposed) Mean ± SD of gross motor scores (7.9 ± 2.2 vs. 9.0 ± 2.5, p = 0.01)	Infants prenatally exposed to SSRIs had significantly lower gross motor scores than non-exposed infants in subscales of the BSID-III. However, these differences were not statistically significant when adjusted for maternal anxiety

BSID-II/II Bayley Scales of Infant Development, 2nd/3rd edition, CI confidence interval, HR hazard ratio, HRV heart rate variability, Movement ABC Movement Assessment Battery for Children, NBAS Neonatal Behavioral Assessment Scale, PDI Psychomotor Development Index, SSRI selective serotonin reuptake inhibitor