Introduction
Materials and methods
Search engine | Papers | New selected papers |
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PubMed | 546 | 17 |
The Cochrane Library | 35 | 0 |
Scopus | 485 | 1 |
Embase | 513 | 0 |
OvidSP | 375 | 0 |
PsychInfo | 160 | 0 |
ISI Web of Knowledge | 218 | 0 |
Added from references | 4 | 4 |
Results
Author, kind of study, scale used to assess depression, and severity | Number of participants | Number of babies assessed | Age of the baby at assessment | Timing of mother exposure | Treatment used | NBAS results | Finding |
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Ferreira et al. 2007, Canada Retrospective cohort study Scale used and severity not specified. | 76 exposed on SSRI or venlafaxine; 90 control | 79 exposed to SSRI or venlafaxine; 91 control | At birth | Third trimester | SSRI (paroxetine, fluoxetine, sertraline, citalopram, fluvoxamine) venlafaxine. | All neonatal behavioral signs (tremors, shaking, agitation, spasms, hypertonia or hypotonia, apnea, tachypnea, bradycardia, indrawing, irritability, and sleep disturbances): group 1 = 59 (77.6) group 2 = 37 (41.1) (p < 0.001) | Significant differences between newborns exposed and control for NBAS, prematurity, and birth weight. Neonatal behavioral signs were frequent in exposed newborns, but symptoms were transient and self-limited. Premature infants could be more susceptible to the effects of SSRI and venlafaxine. |
Zeskind and Stephens 2004, USA Prospective cohort study Review of medical records Severity not specified. | 17 exposed to SSRI; 17 control | 17 exposed to SSRI; 17 control | At birth | All pregnancy | SSRI (paroxetine, fluoxetine, sertraline, citalopram) and bupropion | Significant differences between groups in a wide range of neurobehavioral outcomes (tremulousness, behavioral states, active sleep) | Significant differences between newborns exposed and control for NBAS and prematurity. Results provide the first systematic evidence that women who use SSRIs during pregnancy have healthy, full-birth-weight newborn infants who show disruptions in a wide range of neurobehavioral outcomes. |
Rampono et al., 2009 USA Prospective observational study Edinburgh Postnatal Depression Scale (EPDS) >11 | 38 exposed to antidepressant (27 SSRI, 11 SNRI), 18 control | 38 exposed to antidepressant (27 SSRI, 11 SNRI), 18 control | Between 1 and 6 days | Any time throughout pregnancy, trimester is not specified | SSRI (escitalopram, paroxetine, fluoxetine, sertraline, citalopram, fluvoxamine) venlafaxine. | Significant differences in mean NBAS scores between cases and controls for the habituation, social-interactive, motor, and autonomic clusters were found (p < 0.05). | Significant differences between newborns exposed and control in same NBAS scores in the early perinatal period but these were self-limiting and similar for both SSRIs and the SNRI venlafaxine. |
Suri et al., 2011 USA Prospective, naturalistic, blinded study SCID-I for DSM-IV, Hamilton Depression Rating Scale (HDRS) Maximum HDRS score across pregnancy: 18.5/16.4/10.7 | 33 exposed to antidepressant, 16 with a history of MDD not treated during pregnancy, 15 control | 31 exposed to antidepressant, 14 whose mothers had a history of MDD not treated during pregnancy, 14 control | First visit: within 1 week; 2nd visit between 6 and 8 weeks | All women took AD for the 2nd and 3rd trimester, majority for all trimester. | Antidepressant (not specified) | Summary scores for the 7 clusters were not significantly different among groups at either visit 1 or visit 2. Some significant differences were noted on rapidity of buildup item at visit 1, inanimate auditory and defense items at visit 2 but after Bonferroni correction none significant differences. | No significant differences in summary scores of the NBAS among the three study groups. Use of antidepressants in pregnancy was not associated with significant neurobehavioral effects in infants. |
Field et al., 2009, USA Randomized clinical trial SCID-I for DSM-IV, Center for Epidemiological Studies-Depression (CES-D): 23.7/20.3 | 88 massage group, 61 untreated depressed (standard treatment) | 88 massage group, 61 untreated depressed (standard treatment) | At birth | Second and third trimester (20–32 weeks) | 12 weeks massage therapy (twice per week) | The massage group neonates received significant higher scores on habituation, orientation, motor, and depression scores. In addition, they had lower cortisol levels. | Significant differences between newborns of depressed mothers treated with massage therapy and untreated for NBAS, prematurity, low birth weight, and they had lower cortisol levels. The group of treated women reduced depression scores by the end of the therapy period and cortisol levels during the postpartum period. |
Field et al., 2004, USA Randomized clinical trial Profile of Mood States Scale (POMS), CES-D: 24.9/26.2/28.3/6.5 | 84 depressed women divided in three groups: 28, massage therapy; 28, muscle relaxation; 28, standard prenatal care; 28 control | 84 depressed women divided in three groups: 28, massage therapy; 28, muscle relaxation; 28, standard prenatal care; 28 control | Within a few days after birth | Second and third trimester | 16 weeks massage therapy (twice per week) | Significant difference in habituation, range of state, state, autonomic stability, withdrawal, depressed, motor maturity. | Significant better NBAS score for the mother’s baby treated with massage therapy. |
Smith et al. 2013 USA Prospective study Composite International Diagnostic Interview v2.1 (CIDI), EPDS: 7.67/5.18 | 6 exposed to SSRI, 61 control | 5 exposed to SSRI, 41 control | 24 h age (±8 h) | At least more than 1 month during the third trimester | SSRI (fluoxetine, citalopram, sertraline) | Significant difference in motor cluster scores: 25.2/28.9 (S). No other significant differences. | Significant differences between newborns exposed to SSRI and control mothers, the former had poorer motor development at NBAS, lower 5-min APGAR scores, and shorter mean gestational age as compared to unexposed infants. No significant differences in infant sleep state and number of startless and tremulousness. |
Salisbury et al. 2011 USA Prospective, naturalistic cohort study SCID-I for DSM-IV, RSD: 3.8/13.5/12 | 76 control, 7 depressed untreated, 46 depressed treated | 56 control, 20 depressed untreated, 36 depressed treated | Between 1 and 21 days | At least four consecutive weeks during the second and/or third trimesters of this pregnancy. | SSRI | NICU Network Neurobehavioral Scale (NNNS); MDD group infants had lower attention scores compared to CON group infants and MDD + SRI group infants (S). MDD + SRI group infants had lower quality of movement scores and more CNS stress signs than infants in the CON groups (S). Hypertonicity and arousal were significant in the overall model. | Newborns exposed to maternal depression and SSRI treatment during pregnancy had higher risks of different neurobehavioral profiles than control group in the first month of life. |
Author, kind of study, scale used to assess depression and severity | Number of participants | Number of babies assessed | Age of the baby at assessment | Timing of mother exposure | Treatment used | Test used and results | Finding |
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Oberlander et al. 2004, Canada Prospective cohort study VScale used and severity not specified. | 28 exposed to SSRI; 28 exposed to SSRI + BDZ 23 control | 28 exposed to SSRI; 18 exposed to SSRI + BDZ 23 control | At birth, at 2 and 8 months | The majority of women exposed from the first trimester and continued throughout their pregnancy | SSRI (paroxetine, fluoxetine, sertraline)/clonazepam | Bayley: At 2 months: Mental Developmental Index (MDI) = 97/94/96.7 (NS); Psychomotor Developmental Index (PDI) = 104.8/102.9/102.6 (NS). At 8 months: MDI = 100.7/97.2/99.4 (NS); PDI = 91.5/93.1/97.0 at 8 months (NS). | No significant differences in Bayley scores. Transient neonatal symptoms were found at birth in infants after single-agent prenatal exposure to SSRIs and when paroxetine was combined with clonazepam. |
Morison et al. 2001, Canada Prospective cohort study Scale used and severity not specified. | 18 exposed to SSRI; 20 control | Not reported | Between 2 and 8 months | Not reported | SSRI (paroxetine, fluoxetine, sertraline) | Bayley (no results showed, only abstract) | No difference on BSID total score between exposed and control group. |
Reebye et al. 2002, Canada Prospective cohort study Hamilton Depression Rating Scale (HDRS) Scores not reported | 24 exposed to SSRI; 14 exposed to SSRI + clonazepam; 23 control | 24 exposed to SSRI; 14 exposed to SSRI + clonazepam; 3 control | 2 months | Not reported | SSRI (paroxetine, fluoxetine, sertraline)/clonazepam | Bayley: I = 98/93/96 (NS), PDI = 106/102/101 (NS). | No significant difference in Bayley scores, birth weight and gestational age. |
Mortensen et al. 2003, Denmark Follow-up study Scale used and severity not specified. | 435 women on psychotropic drugs (50 on antidepressant), 1,304 control | 340 exposed to drugs, 755 control | Between 7 and 10 months | During all pregnancy, trimester isn’t specified | BDZ, AD, anti-epileptic drugs, neuroleptic drugs | 16 % of baby exposed on antidepressant had abnormal Boel test, 4 % of abnormal test in the control group. Adjusted OR 5.9 (1.1–31.0) | Higher percent of abnormal Boel test among those who were exposed to antidepressants compared to the non-exposed group. |
Hanley et al. 2013, Canada Prospective study Edinburgh Postnatal Depression Scale (EPDS): 6.2/5.0 HRDS: 10.6/7.2 | 31 SSRI, 52 control | 31 SSRI, 52 control | 10 months | All pregnancy | SSRI (paroxetine, fluoxetine, sertraline, citalopram) and venlafaxine | Bayley: Cognitive 10.9/11.5 (NS); Communication: Receptive 10.2/10.2 (NS) Expressive 9.8/9.9 (NS) Motor: Fine 11.2/11.3 (NS) ross 9.5/8.3 (S) Social–emotional 9.6/8.5 (S) Adaptive behavior 73.3/68.4 (S) | Infants prenatally exposed to SRIs score significantly lower on the gross motor, social–emotional |
Makrides et al. 2010, Australia Randomized clinical trial EPDS > 12 | 2,399 depressed women: 1,197 treated with DHA supplement; 1,202 treated with control supplement | 351exposed to DHA supplement; 375exposed to control supplement | 18 months | Second trimester | Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/day of DHA) | Bayley: cognitive standardized score = 101.8/101.75 (NS), language standardized score = 96.47/97.94 (NS), motor standardized score = 102.63/102.57 (NS), social-emotional standardized score = 106.32/107.27 (NS), adaptive behavior standardized score = 99.17/100.75 (NS). | No significant differences in cognitive, motor, social-emotional, adaptive behavior, and language scores between groups in Bayley scores between newborns exposed to DHA-rich fish oil capsules and vegetable oil capsules during pregnancy. The use of DHA-rich fish oil capsules did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood. |
Casper et al. 2011, USA Prospective cohort study SCID-I for DSM IV BDI: 25.3/25.6/19.6 | 55 exposed to SSRI: 14 on 1st trimester, 18 2nd and 3rd, 23 all pregnancy) | 55 exposed to SSRI: 14 on 1st trimester, 18 2nd and 3rd, 23 all pregnancy) | Between 12 and 40 months | 1st, 2nd, and 3rd trimester | SSRI (paroxetine, fluoxetine, sertraline, citalopram) | Bayley: MDI = no association with duration of SSRI exposure. PDI = significant negative correlations with length of exposure. Behavior Rating Scale (BRS) = significant negative correlation with the duration of exposure. | Significant negative correlation between the length of exposure and psychomotor development and Behavior rating scale. No significant correlation with mental development. Timing of exposure to SSRIs during susceptible periods of fetal development and variations in the severity of maternal depression may have contributed to the associations. |
Nulman and Koren 1996, Canada Prospective cohort study Scale used and severity not specified. | 55 exposed on fluoxetine, NControl group not specified | 55 exposed to fluoxetine (37 on 1st trimester, 18 throughout pregnancy) | Between 18 and 30 months | 37 exposed during 1st trimester, 18 during all pregnancy | SSRI (fluoxetine) | Bayley: MDI = 117/115 (NS), McCarthy: General Cognitive Index (GCI) = 114/114 (NS) | No significant differences in Bayley mental development index and in McCarthy scores between newborns exposed to fluoxetine and control. A significant correlation was found between maternal and child’s IQ. |
Nulman et al. 1997, Canada Prospective cohort study Global assessment scale: 62/60/-Center for Epidemiological Studies-Depression (CES-D): 33/35/– | 80 exposed to TCA; 55 exposed to fluoxetine; 4 control | 80 exposed to TCA; 55 exposed to fluoxetine; 84 control | 16–86 months | TCA: 40 exposed during the 1st trimester, 36 all pregnancy, 2 1st and 2nd trimesters, 2 1stand 3rd trimesters. SSRI: 37 exposed during 1st trimester, 18 during all pregnancy | TCA, fluoxetine | Bayley: MDI = 118/117/115 (NS) McCarthy: GCI = 117/114/114 (NS) Reynell Developmental Language Scales: Verbal Comprehension Scale = 1.3/1.2/1.1 (NS) Expressive Language Scale = 0.3/–0.2/0.1 (NS) | No significant differences in cognitive, language, and behavioral development among the children who were exposed to antidepressant drugs in utero and those who were not. In utero exposure to either TCA or fluoxetine does not adversely affect the neurodevelopment of pre-school children. |
Nulman et al. 2002, Canada Prospective study CES-D: 39.9/28.0/10.7 | 40 exposed to fluoxetine; 46 exposed to TCA; 36 control | 40 exposed to fluoxetine; 46 exposed to TCA; 36 control | At birth, between 15 and 71 months | All pregnancy | TCA, fluoxetine | Bayley: MDI = 104.4/110.9/104.1 (NS), PDI = 97.7/100.1/98.3 (NS). McCarthy: GCI = (NS) Reynell Developmental Language Scales: Verbal comprehension Scale = 0.2/1.1/0.4 group 2 > 1,3 (S) Expressive Language Scale = −0.3/0.2/–0.1 (NS) | No significant differences in Bayley mental and psychomotor development index and in global cognitive index in McCarthy test between groups. Newborns exposed to TCA had a significant higher score at verbal comprehension scale but within the normal range. Mothers’ depression is associated with less cognitive and language achievement by their children. |
Mattson et al. 1999
Prospective cohort study Scale used and severity not specified. | 66 exposed to Fluoxetine; 30 control | Not reported | Between 48 and 72 months | Not reported | Fluoxetine | Weschsler Preschool and Primary Scale of intelligence (no results showed, only abstract) | No significant differences in WPPSI-R. |
Galbally et al. 2011, Australia Prospective case–control study BDI-II: 16.71/7.85 | 19 exposed to antidepressant; 22 control | 19 exposed to antidepressant; 22 control | Between 18 and 35 months | At any point across the three trimesters of pregnancy | Sertraline, venlafaxine, fluoxetine, fluvoxamine, citalopram, escitalopram, mianserin, mirtazapine, paroxetine | Bayley: Cognitive = 13.5/13.16 (NS), Communication: Receptive = 12/11.42 (NS); Expressive = 11.24/10.53 (NS); Motor: fine motor = 14.18/12.84 (NS); gross motor = 14.18/12.89 (NS); Socio-emotional scaled score = 11.06/10.61 (NS). | No significant differences between groups. They found only a differences on the motor subscale with a moderate Cohen’s effect size d = 0.47 for fine motor and d = 0.43 for gross motor (p = 0.07 and I = 0.09, respectively). |
Casper et al. 2003, USA Follow-up study Structured Clinical Interview for DSM-IV (SCID-I) Depression rating (Likert scale 1–10):4.8/6.1 Beck Depression Inventory (BDI): 21.3/24.0 | 31 exposed to SSRI; 13 depressed untreated | 31 exposed to SSRI; 13 exposed to untreated depression | At birth, between 6 and 40 months | 1st, 2nd, 3rd trimester | SSRI (paroxetine, fluoxetine, sertraline, fluvoxamine) and unspecified psychotherapy for both groups. | Bayley: MDI = 91/94 (NS), PDI = 90/98.2 (S), BRS = 76/89.5 (NS after correction for APGAR score). Motor quality and fine motor movement = (S) | No significant differences in Bayley mental development scores between groups. Significant lower scores for psychomotor development index and motor quality in the exposed group. The behavioral rating scale is not significant only after correction for Apgar score that is lower in exposed newborns. |
Nulman et al. 2012, Canada Prospective cohort study Visual analogue scale (0–10): 2.46/3.54/4.55/0 | 62 exposed to SNRI; 62 exposed to SSRI; 54 depressed untreated; 62 control | 62 exposed to SNRI; 62 exposed to SSRI; 54 exposed to untreated depression; 62 control | Between 3 years and 6 years, 11 months | 81 exposed throughout pregnancy, 21 1st trimester only, 4 1st and 2nd, 2 2nd only, 11 2nd and 3rd, 5 in the 3rd only | Venlafaxine/sertraline paroxetine, citalopram, fluoxetine, fluvoxamine. | Wechsler Preschool and Primary Scale of Intelligence 3rd Ed.: Full scale IQ = 105/105/108/112. SNRI and SSRI group < control (S), Verbal IQ = 106/107/109/113. SNRI and SSRI group < control (S), Performance IQ = 103/102/105/108. SSRI < control (S) | Babies exposed to SNRI or SSRI had significant lower IQ than control, but there was no significant difference for the baby of untreated depressed mothers. Significant predictors for the child’s IQ were maternal IQ and child’s sex. None result was predicted by dose or duration of antidepressant treatment in pregnancy. |