Exposição intrauterina a antidepressivos e risco de transtornos de neurodesenvolvimento e psiquiátricos: uma revisão sistemática

Araujo, Jessica Salvador Areias de; Delgado, Isabella Fernandes; Paumgartten, Francisco José Roma

Jessica Salvador Areias de Araujo

Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.

Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.

http://orcid.org/0000-0003-0944-1067

Isabella Fernandes Delgado

Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.

http://orcid.org/0000-0003-0610-5324

Francisco José Roma Paumgartten

Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.

http://orcid.org/0000-0002-6207-0149

Correspondence
F. J. R. Paumgartten Laboratório de Toxicologia Ambiental, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz. Av. Brasil 4036, sala 101-104, Rio de Janeiro, RJ 21040-361, Brasil. paum@ensp.fiocruz.br

Contributors

J. S. A. Araujo contributed to the conception and study design, data collection and analysis, and drafting of the manuscript. I. F. Delgado contributed to the study design, data analysis, and review of manuscript. F. J. R. Paumgartten conceived and designed the study, contributed for data collection and interpretation and wrote a first draft of the manuscript. The final version of the article submitted for publication was approved by all authors.

Additional informations

ORCID: Jessica Salvador Areias de Araujo (0000-0003-0944-1067); Isabella Fernandes Delgado (0000-0003-0610-5324); Francisco José Roma Paumgartten (0000-0002-6207-0149).

Study (year, country)	Drug exposure	Design/Sample characteristics (N)	Main results [OR, HR or RR (95%CI)]	Strengths/Limitations	NOS	Conclusion/Remarks
Croen et al. ⁴⁴44. Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011; 68:1104-12. (2011, USA)	ADs (before pregnant 1^st, 2^nd & 3^rd trimesters)	Population-based case-control study. Kaiser Permanent Medical Care Program in Northern California (KPNC) between January 1995 and June 1999. Cases (n = 298 and their mothers): children with ASD. Controls (n = 1,507 and their mothers): children without ASD randomly selected KPNC in January 1995-November 2002. Exposure: ADs dispensed at a KPNC pharmacy	ASD and maternal use of ADs during the year prior to delivery: 2.2 (1.2-4.3%). ASD and 1^st trimester AD: 3.8 (1.8-7.8). No association with history of mental illnesses in the absence of antenatal exposure to ADs	Data on pharmacy dispensing may not reflect actual use. No control of confounders (maternal data/lifestyle)	6	A 2-fold increase in risk of ASD associated with antenatal exposure to ADs. Risk of ASD was even higher for exposures to ADs in the 1^st trimester of pregnancy
Hviid et al. ³⁶36. Hviid A, Melbye M, Pasternak B. Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. N Engl J Med 2013; 369:2406-15. (2013, Denmark)	SSRI (before and during pregnancy)	Population-based cohort (all 626,875 singleton live births in Denmark) January 1996-December 2005, with follow-up until January 1^st, 2010, or until the child reached 10 years of age, died or was lost to follow-up, or received a diagnosis of ASD (Danish Psychiatric Central Register)	3,892 ASD cases. No use of SSRIs (before and pregnancy) vs. prenatal SSRI: fully adjusted RR = 1.20 (0.90-1.61). No SSRI vs. use of SSRI before but not during pregnancy: fully adjusted RR = 1.46 (1.17-1.81)	Large cohort. Reduced potential for selection and recall biases. Low prevalence of pregnancy-related use of SSRI. No control of potential confounders (mother data/lifestyle)	8	No significant association between antenatal exposure to SSRIs and increased risk of ASD in children
Sørensen et al. ⁴⁰40. Sørensen MJ, Grønborg TK, Christensen J, Parner ET, Vestergaard M, Schendel D, et al. Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clin Epidemiol 2013; 5:449-59. (2013, Denmark)	ADs (during pregnancy)	Population-based cohort of all children born alive in Denmark (n = 668,468) January 1996-December 2006. ASD diagnosis by December 2010, from Danish Psychiatric Central Register; ICD-10 code F84.0, F84.1, F84.5, F84.8, F84.9). Exposure: women filling a prescription for ADs 30 days before conception to day of birth. From Danish National Prescription Registry (January 1996-December 2006)	Prevalence of ASD = 1.5% (5,437 children), average age of diagnosis 6.7 years. ASD: prenatally AD vs. unexposed: adjusted HR: 1.5 (1.2-1.9). Children born to mothers with affective disorders: AD vs. unexposed; adjusted HR: 1.2 (0.7-2.1). AD vs. unexposed siblings in families with at least one child with ASD: adjusted HR: 0.9 (0.4-2.0)	Large cohort. Low potential for selection, recall and misclassification biases. Prescription filling data may not reflect actual use. No control of confounding (mother data/lifestyle)	8	Association of antenatal AD with ASD was not significant when confounding (maternal illness, and family-related factors) was controlled
Rai et al. ⁴⁸48. Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013; 346:f2059. (2013, Sweden)	SSRI & non-SSRI (pregnancy)	Population-based nested case-control study (Stockholm cohort, 589,114 people 0-17 years, 2001-2007). 4,429 ASD cases (2,601 without intellectual disability); 43,277 controls (age and sex-matched). ASD cases: ICD-9 (299.0), ICD-10 (F84.0) and DSM-IV (299). AD use: drug use data from first antenatal interview - Swedish Medical Birth Register	Mother’s (but not father’s) depression associated with ASD: OR: 1.49 (1.08-2.08). Depression plus prenatal AD (SSRI or non-SSRI) and ASD (adjusted disorders other than depression): 3.34 (1.5-7.47). AD and ASD: 1.90 (1.15-3.14), AD and ASD without intellectual disability: 2.54 (1.37-4.68)	Mother’s depression possibly under ascertained. Confounding: AD use may reflect severe depression and thus severe depression (not AD) would be in fact associated with ASD	8	Prenatal AD (SSRI & non-SSRI) associated with ASD without intellectual disability. Association may be non-causal: additional. Further research needed to clarify whether AD use would reflect severe maternal depression
Rai et al. ⁴⁹49. Rai D, Lee BK, Dalman C, Newschaffer C, Lewis G, Magnusson C. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ 2017; 358:j2811. (2017, Sweden)	SSRI & non-SSRI (pregnancy)	Prospective cohort study (Stockholm county, 2001-2011, 254,610 individuals aged 4-17 years, including 5,378 with ASD). ASD: ICD-9 (299.0), ICD-10 (F84.0) and DSM-IV (299). AD use: drug use data from first antenatal interview - Swedish Medical Birth Register. AD use: drug use data from first antenatal interview - Swedish Medical Birth Register	3,342 children prenatally exposed to AD. 4.1% had ASD compared to a prevalence of 2.9% among those not exposed to AD whose mothers had mental illnesses. Adjusted OR: 1.45 (1.13-1.85). Risk increase concerned children with ASD with no intellectual disability	Large sample size (total population of Stockholm county) and multisource ascertainment of cases. Absence of detailed measurements of severity of depression in pregnancy. No trimester assessment	8	Weak (OR = 1.45) association of ASD in pregnancy (particularly ASD without intellectual disability) with AD (SSRI & non-SSRI)
El Marroun et al. ⁵⁰50. El Marroun H, White TJ, van der Knaap NJ, Homberg JR, Fernández G, Schoemaker NK, et al. Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children. Br J Psychiatry 2014; 205:95-102. (2014, Netherlands)	SSRI (pregnancy)	5,976 children (study embedded in the ongoing population-based cohort: Generation R Study). Births from April 2002 to January 2006. SSRI exposure: maternal self-report assessed by questionnaires, prescription records from pharmacies. Parent reported autistic symptoms (traits) using Child Behavior Checklists and Social Responsiveness Scale.	Adjuested (including adjustment for postnatal maternal depression) OR, pervasive develop. problems, prenatal SSRI vs. unexposed: 1.91 (1.13-3.47). Autistic traits (social responsiveness scale) β = 0.15, 95%CI: 0.08-0.22	Prospective study using 2 measures of autistic symptoms. SSRI-treated women may have overestimated problems with their child. No clinical assessments of ASD. Small number of SSRI-exposed children. Residual confounding remained	6	Results suggested association between prenatal SSRI and autistic traits in children
Harrington et al. ⁴⁷47. Harrington RA, Lee LC, Crum RM, Zimmerman AW, Hertz-Picciotto I. Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics 2014; 133:e1241-8. (2014, USA)	SSRI (1^st, 2^nd & 3^rd trimester)	Population-based case-control study. CHARGE (Childhood Autism Risks from Genetics and Environment). Mother-child pairs. Children 2-5 years old from California with ASD (n = 492) or DD other than ASD (n = 154) and typical development, TD (n = 320). Interview (SSRI use, mental health history, sociodemographic information)	OR: among boys (♂) prenatally exposed to SSRI: ASD vs. TD: 2.91 (1.07-7.93). 1^st trimester: 3.22 (1.17-8.84)	Relatively large sample of cases. Potential recall bias. Residual confounding by indication of SSRI, no assessment of depression severity. No data on SSRI dosage	8	In boys, prenatal exposure to SSRI increases risk of ASD
Gidaya et al. ⁴⁵45. Gidaya NB, Lee BK, Burstyn I, Yudell M, Mortensen EL, Newschaffer CJ. In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder. J Autism Dev Disord 2014; 44:2558-67. (2014, Denmark)	SSRI (pre-conception, 1^st, 2^nd & 3^rd trimesters)	Population-based (Danish Civil Registration System) case-control study. All children (singleton or one selected at random from multiple births) born alive in Denmark (n = 628,408) Januarty 1997-December 2006. Cases: ASD diagnosis (Danish National Hospital Register, January 1999-March 2011). Controls without ASD. 10 per case. Exposure: dispensed. From: Danish Drug Prescription Registry	1.5% of cases and 0.7% of controls exposed to SSRI during pregnancy. Adjusted OR, ASD vs. maternal SSRI use (> 45 days); preconception; 2.1 (1.6-2.8); 1^st trimester; 2.4 (1.7-3.3); 2^nd trimester; 2.4 (1.6-3.5); 3^rd trimester; 2.9 (1.9-4.4). Adjusted for: age, child sex, mother depression; other SSRI indications	Large population-based case-control study. Residual confounding by indication of SSRI and severity of maternal depression	8	Study results suggest that antenatal exposure to SSRI increases child’s risk associated with ASD
Clements et al. ⁴¹41. Clements CC, Castro VM, Blumenthal SR, Rosenfield HR, Murphy SN, Fava M, et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry 2015; 20:727-34. (2015, USA)	SSRI/non-SSRI (pre-conception, 1^st, 2^nd & 3^rd trimesters)	Case-control study. Cases: children from The Partners HealthCare EHR (New England, Boston, Massachusetts) with 2-19 years, if they had at least one ICD-9 code of 299, 1997-2000. Cases: 1,377 children with ASD; Controls: no prior history of ASD, ADHD or intellectual disability; matched (1:3) for birth year, birth hospital, sex, insurance type (proxy for socioeconomic status), ethnicity, preterm vs. full term. AD prescription (outpatient EHR) and dispensing (inpatient pharmacy)	Adjusted OR; pre-pregnancy (adjusted mother’s depression) 1.62 (1.17-2.23). Pregnancy (pre-pregnancy-delivery), non-adjusted 1.49 (1.01-2.18), adjuested 1.10 (0.70-1.70), 1^st trimester 1.47 (0.81-2.61), 2^nd trimester (1.34 (0.77-2.27), 3^rd trimester 1.08 (0.61-1.88)	Relatively large sample of cases. Confounding by indication, misclassification bias	7	ASD risk associated with prenatal ADs was no longer significant after controlling for maternal depression
Boukhris et al. ⁴⁶46. Boukhris T, Sheehy O, Mottron L, Bérard A. Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatr 2016; 170:117-24. (2016, Canada)	ADs (1^st, 2^nd & 3^rd trimesters)	Population-based cohort, January 1998-December 2009. 145,456 full-term singleton infants born alive. ASD: children with at least 1 ASD diagnosis between date of birth and last follow-up	1,054 (0.7%, 4♂:1♀) with ASD. Age of children at the end of follow-up was 6.24 (3.19) years. 2^nd/3^rd trimester adjuested HR; ADs = 1.87 (1.15-3.04), SSRIs = 2.17 (1.20-3.93). Adjuested for maternal depression: ADs = 1.75 (1.03-2.97)	Large cohort, 11-year follow-up. Prescription filling data (may not reflect actual use), lack of control of potential confounders (mother data/lifestyle)	8	Antenatal ADs, (predominantly SSRIs), in the 2^nd/3^rd trimester increases ASD risk
Castro et al. ³⁷37. Castro VM, Kong SW, Clements CC, Brady R, Kaimal AJ, Doyle AE, et al. Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study. Transl Psychiatry 2016; 6:e708. (2016, USA)	SSRI/non-SSRI (pre-pregnancy, 1^st, 2^nd & 3^rd trimester)	Case-control study. Cases: children from The Partners HealthCare EHR with 2-19 years, at least one ICD-9 code of 299. 1997-2010. Cases: 1,245. ASD; Controls: no prior history of ASD, ADHD or intellectual disability; matched (1:3) for birth year, birth hospital, sex, insurance type (proxy for socioeconomic status), ethnicity, preterm vs full term. Mother-child pairs included in the previous report by Clements et al. ⁴¹ were excluded. AD prescription (outpatient EHR) and dispensing (inpatient pharmacy)	Adjusted OR; pre-pregnancy (adjusted for maternal depression) 1.54 (1.02-2.30). Pregnancy (pre-pregnancy-delivery), non-adjusted 0.99 (0.63-1.51), adjusted 0.90 (0.50-1.54), 1^st trimester 0.89 (0.40-1.78), 2^nd trimester (1.11 (0.50-2.26), 3^rd trimester 0.85 (0.38-1.74)	Relatively large sample of cases. Some risk of confounding by indication, misclassification bias	7	Pre-pregnancy only use of ADs associated with ASD. No association between mother use of AD in pregnancy and ASD
Sujan et al. ⁴²42. Sujan AC, Rickert ME, Öberg AS, Quinn PD, Hernández-Díaz S, Almqvist C, et al. Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. JAMA 2017; 317:1553-62. (2017, Sweden)	ADs (1^st trimmester)	Retrospective cohort study: Swedish offspring born 1996-2012 followed through 2013, death or emigration. Maternal self-reported 1^st trimester use and dispensation of ADs; data from Medical Birth Register, and Prescribed Drug Register. ASD inpatient and outpatient diagnoses made by a specialist according to ICD-9 and ICD-10 criteria (Swedish registers)	Analytical cohort (1,580,629 children, 48.6% females), 1.4% were exposed (mother self-report) to ADs during 1^st trimester and of these, 82% were exposed to SSRIs. ASD exposed vs. unexposed; HR: 2.0 (1.8-2.3). Siblings analysis adjusted pregnancy, maternal, paternal traits; ASD; 0.8 (0.6-1.1)	Large population based sample (cohort study), Sibling analysis. Exposure conferred both to self-report and dispensation. Recall bias. No assessment of maternal depression severity. 1^st trimester exposure only. Mostly SSRIs	8	After taking into account confounding; no association of 1^st trimester exposure to ADs with ASD
Malm et al. ³⁵35. Malm H, Brown AS, Gissler M, Gyllenberg D, Hinkka-Yli-Salomäki S, McKeague IW, et al. Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: a national register-based study. J Am Acad Child Adolesc Psychiatry 2016; 55:359-66. (2016, Finland)	SSRI (pregnancy)	Population-based cohort study. Data from Finnish National Registers. 845,345 singleton live births in Finland between January 1996-December 2010. Age range from birth to age 14, mother child pairs - National Medical Birth Register. Drug Reimbursement Register (prescription drug purchases). Outcome: ASD	ASD, adjusted HR; SSRI gestation vs. Mother psychiatric disease and no medication, 0.88 (0.65-1.20), SSRI pregnancy vs. SSRI pre-pregnancy only, 1.30 (0.88-1.92), SSRI pregnancy vs. no maternal disease, no medication, 1.40 (1.02-1.92)	Large population based prospective cohort. No pregnancy trimester. analysis. No confirmation of adherence to purchased drugs. No information on postnatal environment	7	Taking into account maternal illness, prenatal SSRI was not associated with increased risk of ASD.
Brown et al. ³⁸38. Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association between serotonergic antidepressant use during pregnancy and autism spectrum disorder in children. JAMA 2017; 317:1544-52. (2017, Canada)	SSRI/SNRI (during pregnancy)	Retrospective cohort study using health administrative data from Ontario, Canada, children (35,906 singleton births) born to mothers receiving public prescription drug (4.2% births) from 2002-2010. Outcome followed through 2014. ASD diagnosed after the age of 2 years	ASD adjusted HR; SSRI vs. unexposed 1.59 (1.17-2.17), sibling analysis, 1.60 (0.69-3.74)	No remarkable strength limited to women in Ontario’s publicly funded drug plan (lower social class). Potential misclassification bias (filled-out prescriptions not used)	8	Prenatal exposure to SSRI or SNRI was not associated to ASD in children
Viktorin et al. ³⁹39. Viktorin A, Uher R, Reichenberg A, Levine SZ, Sandin S. Autism risk following antidepressant medication during pregnancy. Psychol Med 2017; 47:2787-96. (2017, Sweden)	ADs (pregnancy)	Population based cohort of 179,007 Swedish children born in 2006-2007 followed through 2014 when they were aged 7 and 8. Mother and children identified in the Swedish Medical Birth Register. Exposure: data on prescription drug dispensed - Swedish Drug Register, ASD; ICD-10 codes F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, F84.9 - Swedish Patient Register	ASD adjusted RR (95%CI), full sample, ADs vs. unexposed: 1.23 (0.96-1.57). Subsample of mothers with at least one diagnosis of depression or anxiety in their lifetime; ADs (2 dispensations overlapping pregnancy) vs. unexposed: 1.07 (0.80-1.43). citalopram/escitalopram: 1.47 (0.92-2.35), clomipramine: 2.86 (1.04-7.82)	Nationwide population-based cohort. Severity of maternal mental illness not known	8	Prenatal exposure to ADs was not causally associated with ASD in children
Hagberg et al. ⁴³43. Hagberg KW, Robijn AL, Jick S. Maternal depression and antidepressant use during pregnancy and the risk of autism spectrum disorder in offspring. Clin Epidemiol 2018; 10:1599-612. (2018, UK)	ADs (pre-pregnancy, 1^st, 2^nd & 3^rd trimester)	Cohort study (with nested sibling case-control analysis) using a population-based electronic medical database (UK Medical Practice Research Datalink, CPRD). Mothers (aged 13 to 44 years) and their live born singleton infants, born between 1989 and 2011. Cohort entry was baby delivery date minus 365 days. Children: at least 3 years of follow-up after birth. 3 cohorts of exposed women (depressed treated with AD); depressed untreated with AD in pregnancy; non-depressed treated with AD in pregnancy). 194,494 mother-baby pairs; 2,154 with ASD	RR; unexposed vs. treated depression: 1.72 (1.54-1.93); unexposed vs. untreated depression: 1.50 (1.28-1.75); unexposed vs. AD for disorders other than depression: 0.73 (0.41-1.29). Sibling analysis yield results similar to those of main study. Additional analysis indicated that risk of ASD increased with increasing severity of depression (duration of last episode of untreated depression; < 12 months vs. 12-35.9 months)	Large population-based cohorts. Assessment of effects of untreated depression and severity of untreated depression. No remarkable weakness	9	Pregnant women with depression have increased risk of having a child with ASD, whether or not she used ADs during pregnancy

Study (year, country)	Drug exposure	Design/Sample characteristics (N)	Main results [OR or HR (95%CI)]	Strengths/Limitations	NOS	Conclusion/Remarks
Figueroa ⁵²52. Figueroa R. Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31:641-8. (2010, USA)	ADs (1^st, 2^nd & 3^rd trimesters)	Retrospective cohort study. Claims data (self-insured employers) on 38,074 children born 1997-2002 and their families until they were 4 years old (1997-2006). Data on in/outpatient prescription claims; diagnoses and others. Outcome: ADHD at the age of 5 or earlier	431 children diagnosed or treated for ADHD ≤ 5 years. SSRI in pregnancy OR = 0.91 (0.51-1.60); BUP in pregnancy 3.63 (1.20-11.04); 1^st trimester 2.06 (0.35-12.16), 2^nd trimester 14.66 (3.27-65.73); other ADs in pregnancy: 0.65 (0.09-4.79)	ADHD typically diagnosed in children > 5 years. Prescription data may not reflect actual use. Failure to control confounding (mother’s disease and lifestyle)	7	Prenatal SSRIs and ADs other than BUP not associated with ADHD in children at the age of 5 or younger. Bupropion, especially in the 2^nd trimester, increased risks of ADHD
Laugesen et al. ⁵¹51. Laugesen K, Olsen MS, Telén Andersen AB, Frøslev T, Sørensen HT. In utero exposure to antidepressant drugs and risk of attention deficit hyperactivity disorder: a nationwide Danish cohort study. BMJ Open 2013; 3:e003507. (2013, Denmark)	ADs (1^st, 2^nd & 3^rd trimesters)	Cohort of all singletons born alive (N = 877,778) in Denmark (Danish Medical Birth Registry) from 1996 until the end of 2009. Exposure: maternal redemption of an AD prescription through the Danish National Prescription Registry. Outcome: diagnosis of ADHD or prescription for ADHD medication (Danish Psychiatric Registry, Danish National Registry of Patients. Overall median follow up time = 8 years	15,008 (1.7%) were exposed to AD. 12,841 (1.5%) developed ADHD. SSRI the most used (78% of AD users). Adjusted HR any AD pregnancy 1.2 (1.1-1.4), 1^st trimester 1.2 (1.0-1.4), 2^nd trimester 1.5 (0.9-2.4), 3^rd trimester 0.8 (0.3-2.0), pregnancy use: SSRI, 1.2 (1.0-1.5), SNRI 1.0 (0.4-2.5), TCA 1.1 (0.6-20), others 1.6 (0.8-3.0). Sibling analysis: 0.7 (0.4-1.4). Former users vs. never users: 1.6 (1.5-1.8)	Large population-based cohort. No data on actual AD intake by the mother (prescription is a proxy)	8	Long-term follow-up: no evidence of association of prenatal AD with ADHD
Clements et al. ⁴¹41. Clements CC, Castro VM, Blumenthal SR, Rosenfield HR, Murphy SN, Fava M, et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry 2015; 20:727-34. (2015, USA)	SSRI/non-SSRI (pre-pregnancy, 1^st, 2^nd & 3^rd trimesters)	Case-control study. Children from The Partners HealthCare EHR (Boston, Massachusetts) with 2-19 years. Cases: 2,243 children with ADHD (but no ASD); Controls (5,631): no prior history of ADHD, ASD or intellectual disability; matched (1:3) for birth year, birth hospital, sex, insurance type (proxy for socioeconomic status), ethnicity, pre-term vs. full term. AD prescription (outpatient EHR) and dispensing (inpatient pharmacy)	Adjusted OR; pre-pregnancy (adjusted history of maternal depression) 1.18 (0.86-1.61). Pregnancy (pre-pregnancy-delivery), non-adjusted 2.30 (1.62-3.24), adjusted 1.81 (1.22-2.70), 1^st trimester 2.03 (1.19-3.44), 2^nd trimester 0.98 (0.56-1.68), 3^rd trimester 1.29 (0.76-2.15)	Relatively large sample of cases. Confounding by indication, misclassification bias	7	Prenatal ADs was associated with a modest increase in risk of ADHD even after adjustment to maternal depression
Castro et al. ³⁷37. Castro VM, Kong SW, Clements CC, Brady R, Kaimal AJ, Doyle AE, et al. Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study. Transl Psychiatry 2016; 6:e708. (2016, USA)	AD (SSRI/non-SSRI) (pre-pregnancy, 1^st, 2^nd & 3^rd trimesters)	Case-control study. Children from The Partners HealthCare EHR with 2-19 years. Cases: 1,701 ADHD; Controls: no prior history of ADHD, ASD, or intellectual disability; matched (1:3) for birth year, birth hospital, sex, insurance type (proxy for socioeconomic status), ethnicity, pre-term vs. full term. AD prescription (outpatient EHR) and dispensing (inpatient pharmacy)	Adjusted OR pre-pregnancy (adjusted history of maternal depression) 1.50 (1.00-2.20). Pregnancy (pre-pregnancy-delivery), non-adjusted 0.91 (0.56-1.42), adjusted 0.97 (0.53-1.69), 1^st trimester 0.69 (0.29-1.49), 2^nd trimester 1.11 (0.50-2.26), 3^rd trimester 0.73 (0.29-1.62)	Relatively large sample of cases. Risk of confounding by indication, misclassification bias	7	Pre-pregnancy use of ADs modestly associated with ADHD in children. No association between maternal use of AD in pregnancy and ADHD in the offspring
Malm et al. ³⁵35. Malm H, Brown AS, Gissler M, Gyllenberg D, Hinkka-Yli-Salomäki S, McKeague IW, et al. Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: a national register-based study. J Am Acad Child Adolesc Psychiatry 2016; 55:359-66. (2016, Finland)	SSRI (during pregnancy)	Population-based cohort study. Data from Finnish National Registers. 845,345 singleton live births between January 1996-December 2010. Age range: birth to age 14, mother child pairs - National Medical Birth Register. ICD-8, ICD-9 and ICD-10 (since 1996) Drug Reimbursement Register (prescription drug purchases). Outcome: ADHD	ADHD, adjusted HR (95%CI); SSRI gestation vs. Mother psychiatric disease and no medication, 0.98 (0.77-1.24), SSRI pregnancy vs. SSRI pre-pregnancy only, 0.98 (0.75-1.27), SSRI pregnancy vs. no maternal disease, no medication, 1.66 (1.27-2.16)	Large population based prospective cohort. No pregnancy trimester analysis. No confirmation of drug adherence. No data on postnatal environment	8	Taking into account maternal disorder, prenatal SSRI was not associated with ADHD in children
Sujan et al. ⁴²42. Sujan AC, Rickert ME, Öberg AS, Quinn PD, Hernández-Díaz S, Almqvist C, et al. Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. JAMA 2017; 317:1553-62. (2017, Sweden)	ADs (pregnancy 1^st trimester)	Retrospective cohort study Swedish offspring born 1996-2012 followed through 2013, death or emigration. Maternal self-reported 1^st trimester use and dispensation of ADs; data from Medical Birth Register, and prescribed Drug Register. ADHD, inpatient and outpatient diagnoses made by specialist according to ICD-9 and ICD-10 criteria (Swedish registers)	Analytical cohort (1,580,629 children, 48.6% females), 1.4% were exposed (maternal self-report) to ADs during 1^st trimester and of these, 82% were exposed to SSRIs. ADHD exposed vs unexposed; HR (95%CI): 2.2 (2.0-2.4). Comparison of siblings, adjusted pregnancy, maternal, paternal traits; ADHD; 1.0 (0.8-1.3)	Large population based sample (cohort study), Sibling comparison. Exposure conferred both to self-report and dispensation. Recall bias. Register-based approach did not assess maternal depression and its severity. 1^st trimester exposure only. Mostly SSRIs	8	After accounting for confounding factors; no association of 1^st trimester exposure to ADs with ADHD in children
Man et al. ⁵⁸58. Man KKC, Chan EW, Ip P, Coghill D, Simonoff E, Chan PKL, et al. Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study. BMJ 2017; 357:j2350. (2017, China)	ADs (1^st, 2^nd & 3^rd trimesters)	Population-based cohort study (Hong Kong territory wide) nested in Clinical Data Analysis and Reporting System (CDARS). All live born children in Hong Kong from January 2001 to December 2009 (n = 190,618). Exposure: maternal ADs prescribing and dispensing records at CDARS Outcome ADHD after at least 6 years follow-up (ICD-9-CM code 314) until December 2015	5,659 children (3%) had a diagnosis of ADHD. Adjusted HR, ADHD, any AD users in pregnancy vs. non-users: 1.39 (1.07-1.82); 1^st trimester 1.43 (1.05-1.95), 2^nd trimester 1.50 (1.08-2.09), 3^rd trimester 1.43 (1.03-1.98). Prenatal SSRI 1.11 (0.77 to 1.60), prenatal non-SSRI 0.59 (1.19-2.14). 1st trimester 1.64 (1.13-2.38), 2^nd trimester 1.72 (1.16-2.53), 3^rd trimester 1.65 (1.13-2.40). Sibling analysis: prenatal AD 0.54 (0.17-1.74); AD non-users: maternal mental disease vs. no disease: 1.84 (1.54-2.18)	Relatively large population based cohort. Prescription/dispensing data may not reflect actual use. Possible misclassification bias. Residual confounding by indication	8	Increased risk of ADHD in children prenatally exposed to ADs and non-SSRIs but not to SSRI. Associations could be at least in part explained by maternal depression or confounding by indication of AD
Boukhris et al. ⁵⁷57. Boukhris T, Sheehy O, Bérard A. Antidepressant use in pregnancy and the risk of attention deficit with or without hyperactivity disorder in children. Paediatr Perinat Epidemiol 2017; 31:363-73. (2017, Canada)	SSRI, SNRI, MAOI, TCA (1^st & 2^nd/3^rd trimesters)	Population-based cohort study with data from ongoing Quebec Pregnancy Children Cohort. All full-term singletons born alive (n = 144,406) in Quebec-Canada in January 1998-December 2009. Exposure: mothers with at least one AD prescription during pregnancy recorded in the Prescription Drug database. Outcome: ADHD diagnosis. Follow-up: birth up to first diagnosis, death or December 31, 2009, whichever occurred first	4,564 infants (3.2%) with a diagnosis of ADHD. Mean age at first diagnosis 6.3 years. Adjusted HR: AD 1^st trimester 1.0 (0.9-1.2); 2^nd/3^rd trimesters 1.3 (1.0-1.6). 2^nd/3^rd trimesters: SSRI 1.2 (0.9-1.6), SNRI 1.4 (0.8-2.5), TCA 1.8 (1.0-3.1), other ADs 0.5 (0.1-2.2)	Large population based cohort study. Prescription filling data may not reflect actual use. Lack of information on several potential confounders (maternal lifestyle, smoking). Residual confounding by indication remained	8	After taking into account maternal history of depression/anxiety, prenatal exposure to AD, especially in the 2^nd/3^rd trimesters, was associated with increased risk of ADHD

Study (year, country)	Drug	Pregnancy exposure	Age at evaluation	Results and conclusions/remarks
Nulman et al. ⁶¹61. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, et al. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997; 336:258-62. (1997, Canada)	TCA, FLX	1^st, 2^nd & 3^rd trimesters	16 to 86 months	TCA and FLX in pregnancy did not affect global IQ, language development or behavioral development in preschool children
Nulman et al. ⁶²62. Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002; 159:1889-95. (2002, Canada)	TCA, FLX	1^st, 2^nd & 3^rd trimesters	15 to 71 months	TCA and FLX in pregnancy did not affect child’s global IQ, language development, or behavior development. IQ was negatively associated with duration of maternal depression and language with number of depressive episodes after delivery
Reebye et al. ⁷¹71. Reebye PN, Morison SJ, Panikkar H, Misri S, Grunau RE. Affect expression in prenatally psychotropic exposed and nonexposed mother-infant dyads. Infant Ment Health J 2002; 23:403-16. (2002, Canada)	SSRI/SSRI+CZP	Pregnancy	3 months	Exposure to SSRI and SSRI+CZP in pregnancy did not alter scores for infant development at the age of 2 months as evaluated by the BSID
Casper et al. ⁶⁴64. Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, et al. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003; 142:402-8. (2003, USA)	SSRI	Pregnancy	At birth and 6 to 40 months	SSRI exposed newborns showed lower 1 and 5 min Apgar scores. SSRI infants had slightly delayed psychomotor development (adjusted for Apgar). No difference in mental development. SSRI in breast milk not ruled out
Misri et al. ⁸⁰80. Misri S, Reebye P, Kendrick K, Carter D, Ryan D, Grunau RE, et al. Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications. Am J Psychiatry 2006; 163:1026-32. (2006, Canada)	SSRI/SSRI+CZP	Pregnancy	48 to 60 months	Levels of internalizing behaviors (fearfulness, social withdrawal and somatic complaints) did not differ between SSRI and SSRI+CZP and non-exposed at age of 4 years. Increased maternal anxiety/depression associated with increased internalizing behaviors in their children
Oberlander et al. ⁷⁹79. Oberlander TF, Reebye P, Misri S, Papsdorf M, Kim J, Grunau RE. Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy. Arch Pediatr Adolesc Med 2007; 161:22-9. (2007, Canada)	SSRI	Pregnancy	48 months	Externalizing (physical/verbal aggressiveness, disruptive behavior) and attentional behaviors did not differ between prenatal SSRI exposed and non-exposed 4-year-old children. Current maternal mood/stress predicts child externalizing behavior regardless prenatal SSRI and depression
Casper et al. ⁷²72. Casper RC, Gilles AA, Fleisher BE, Baran J, Enns G, Lazzeroni LC. Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development. Psychopharmacology (Berl) 2011; 217:211-9. (2011, USA)	SSRI	1^st, 2^nd & 3^rd trimesters	At birth and 14 months	SSRI associated with lower Apgar. SSRI increased risks for lower psychomotor test scores. Mental development and motor function by neurological examination within the normal range
Salisbury et al. ⁹⁸98. Salisbury AL, Wisner KL, Pearlstein T, Battle CL, Stroud L, Lester BM. Newborn neurobehavioral patterns are differentially related to prenatal maternal major depressive disorder and serotonin reuptake inhibitor treatment. Depress Anxiety 2011; 28:1008-19. (2011, USA)	SSRI	Pregnancy	At birth and 3 weeks	SSRI associated with lower GA at birth. Controlling for GA, SSRI exposed had lower quality of movements and more CNS stress signs
Nulman et al. ⁶³63. Nulman I, Koren G, Rovet J, Barrera M, Pulver A, Streiner D, et al. Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. Am J Psychiatry 2012; 169:1165-74. (2012, Canada)	SNRI (VLX), SSRI	1^st, 2^nd & 3^rd trimesters	36 to 83 months	Offspring from VLX, SSRI and untreated maternal depression groups had similar full-scale IQs. VLX and SSRI had lower IQs than children born to non-depressed women
Weikum et al. ⁹⁹99. Weikum WM, Oberlander TF, Hensch TK, Werker JF. Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception. Proc Natl Acad Sci U S A 2012; 109 Suppl 2:17221-7. (2012, Canada)	SNRI (VLX), SSRI	Pregnancy	Still in utero, 6 and 10 months	As expected, children from non-depressed non-treated mothers succeed the non-native speech and visual language discrimination test at 6 and failed it at 10 months whereas SSRI exposed succeeded it at both ages. As expected, control fetuses responded to vowel but not to consonant discrimination, whereas SSRI-exposed responded for both vowel and consonant
Austin et al. ⁶⁵65. Austin MP, Karatas JC, Mishra P, Christl B, Kennedy D, Oei J. Infant neurodevelopment following in utero exposure to antidepressant medication. Acta Paediatr 2013; 102:1054-9. (2013, Australia)	ADs/mostly SSRI	1^st, 2^nd & 3^rd trimesters	17-24 months	ADs (mostly SSRI) not associated (BSID-III) with poorer cognitive, language or motor development outcomes in 18-month-old infants
Batton et al. ⁷³73. Batton B, Batton E, Weigler K, Aylward G, Batton D. In utero antidepressant exposure and neurodevelopment in preterm infants. Am J Perinatol 2013; 30:297-301. (2013, Canada)	SSRI	Pregnancy	24-36 months	Cohort of preterm born infants: antenatal SSRI did not increase risk of adverse neurodevelopment (BSID) above the baseline risk for this degree of prematurity
Hanley et al. ¹⁰⁰100. Hanley GE, Brain U, Oberlander TF. Infant developmental outcomes following prenatal exposure to antidepressants, and maternal depressed mood and positive affect. Early Hum Dev 2013; 89:519-24. (2013, Canada)	SRI	Pregnancy	10 months	SRI-exposed 10-month-old infants scored lower than non-exposed on gross-motor, social-emotional and adaptive behaviors (BSID). Controlled for pre/postnatal maternal depression
Pedersen et al. ⁷⁶76. Pedersen LH, Henriksen TB, Bech BH, Licht RW, Kjaer D, Olsen J. Prenatal antidepressant exposure and behavioral problems in early childhood: a cohort study. Acta Psychiatr Scand 2013; 127:126-35. (2013, Denmark)	ADs	1^st, 2^nd & 3^rd trimesters	48 to 60 months	Children behavior assessed by parent reported SDQ. AD not associated with abnormal SDQ scores. Prenatal untreated depression associated abnormal SDQ
de Vries et al. ¹⁰¹101. de Vries NK, van der Veere CN, Reijneveld SA, Bos AF. Early neurological outcome of young infants exposed to selective serotonin reuptake inhibitors during pregnancy: results from the observational SMOK study. PLoS One 2013; 8:e64654. (2013, Netherlands)	SSRI	Pregnancy	2 and 7 days, 3 to 4 months	Prenatal SSRI impaired quality of infant movements (assessed by Prechtl and motor optimality scales) irrespective of maternal depression/anxiety. Severity of maternal depression remained as residual confounding
Santucci et al. ⁷⁴74. Santucci AK, Singer LT, Wisniewski SR, Luther JF, Eng HF, Dills JL, et al. Impact of prenatal exposure to serotonin reuptake inhibitors or maternal major depressive disorder on infant developmental outcomes. J Clin Psychiatry 2014; 75:1088-95. (2014, USA)	SRI	Pregnancy	12, 26, 52 and 78 weeks	No impact of prenatal SRI or maternal depression on mental (cognitive) development index scores. Effect of SRI on (first year) psychomotor development scores, a possibly transitory effect
Skurtveit et al. ⁷⁵75. Skurtveit S, Selmer R, Roth C, Hernandez-Diaz S, Handal M. Prenatal exposure to antidepressants and language competence at age three: results from a large population-based pregnancy cohort in Norway. BJOG 2014; 121:1621-31. (2014, Norway)	SSRI	Pregnancy up to 6 month old	36 months	SSRI in pregnancy associated with lower language competence (measured by mother’s report on language-grammar scale) at 3 years independently of anxiety/depression before/during pregnancy. Anxiety/depression in pregnancy also associated with language competence delay
Eriksen et al. ¹⁰²102. Eriksen HL, Kesmodel US, Pedersen LH, Mortensen EL. No association between prenatal exposure to psychotropics and intelligence at age five. Acta Obstet Gynecol Scand 2015; 94:501-7. (2015, Denmark)	ADs/anxiolytics	Pregnancy	60-64 months	No association between children’s IQ (Wechsler Preschool and Primary Scale of Intelligence) and prenatal exposure to ADs and anxiolytics. Low statistical power study
Hanley, et al. ⁷⁸78. Hanley GE, Brain U, Oberlander TF. Prenatal exposure to serotonin reuptake inhibitor antidepressants and childhood behavior. Pediatr Res 2015; 78:174-80. (2015, Canada)	SRI	Pregnancy	36-72 months	SRI in pregnancy was associated with increased internalizing and anxious behavior (after controlling for maternal depression) but not with externalizing behavior in early childhood
Brown et al. ¹⁰³103. Brown AS, Gyllenberg D, Malm H, McKeague IW, Hinkka-Yli-Salomäki S, Artama M, et al. Association of selective serotonin reuptake inhibitor exposure during pregnancy with speech, scholastic, and motor disorders in offspring. JAMA Psychiatry 2016; 73:1163-70. (2016, Finland)	SSRI	30 days before, 1^st, 2^nd & 3^rd trimesters	< 14 year old, most < 9 years	Children born to mothers who used SSRI during pregnancy had an increased risk of speech/language disorders compared with the offspring of mothers diagnosed as having depression or other psychiatric disorders not treated with ADs
Grzeskowiak et al. ⁷⁷77. Grzeskowiak LE, Morrison JL, Henriksen TB, Bech BH, Obel C, Olsen J, et al. Prenatal antidepressant exposure and child behavioural outcomes at 7 years of age: a study within the Danish National Birth Cohort. BJOG 2016; 123:1919-28. (2016, Denmark)	SSRI, SNRI, TCA	1^st, 2^nd & 3^rd trimesters	48, 60, 84 months	SSRI in pregnancy did not increase risks of behavioral problems (SDQ) in 7-year-old children after adjustment for maternal illness. Untreated prenatal depression increased risks of behavioral problems compared with unexposed children
Handal et al. ¹⁰⁴104. Handal M, Skurtveit S, Furu K, Hernandez-Diaz S, Skovlund E, Nystad W, et al. Motor development in children prenatally exposed to selective serotonin reuptake inhibitors: a large population-based pregnancy cohort study. BJOG 2016; 123:1908-17. (2016, Norway)	SSRI	180 days before and pregnancy	36 months	SSRIs during pregnancy was weakly associated with a delayed motor development (Ages & Stages Questionnaire) at age of 3 years, but the delay was very short and of no clinical importance
Handal et al. ⁷⁰70. Handal M, Skurtveit S, Roth C, Hernandez-Diaz S, Selmer R. Prenatal exposure to folic acid and antidepressants and language development: a population-based cohort study. J Clin Psychopharmacol 2016; 36:333-9. (2016, Norway)	SSRI	Pregnancy	36 months	SSRIs plus folic acid supplementation in pregnancy increased risks of delayed language competence in the offspring. SSRI without folic acid did not alter risks of delayed language competence. Unexpected interaction
Johnson et al. ⁶⁶66. Johnson KC, Smith AK, Stowe ZN, Newport DJ, Brennan PA. Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function. J Clin Psychiatry 2016; 77:e176-82. (2016, USA)	SRI	Pregnancy	30-66 months	Prenatal SRI weakly associated with some preschool outcomes (expressive language and behavior problems) but not with cognitive function
Hermansen et al. ⁶⁷67. Hermansen TK, Røysamb E, Augusti EM, Melinder A. Behavior and inhibitory control in children with prenatal exposure to antidepressants and medically untreated depression. Psychopharmacology (Berl) 2016; 233:1523-35. (2016, Norway)	SSRI	Pregnancy	60-72 months	No effects of prenatal depression or SSRIs upon general cognition or inhibition. Both SSRI and maternal depression associated with higher levels of externalizing behaviors compared to non-exposed controls. SSRI exposed children showed higher levels of internalizing behaviors
Salisbury et al. ¹⁰⁵105. Salisbury AL, O'Grady KE, Battle CL, Wisner KL, Anderson GM, Stroud LR, et al. The roles of maternal depression, serotonin reuptake inhibitor treatment, and concomitant benzodiazepine use on infant neurobehavioral functioning over the first postnatal month. Am J Psychiatry 2016; 173:147-57. (2016, USA)	SSRI/SSRI+BZP	Pregnancy	1^st postnatal month	Infants of pregnant mothers treated with SSRI and SSRI+BZP had lower motor scores and more CNS stress signs. Infants of depressed mothers had low arousal throughout the 30-day period. Infants of SSRI+BZP group had the least favorable scores on the Neonatal Intensive Care Unit Network Neurobehavioral Scale
Hermansen, et al. ¹⁰⁶106. Hermansen TK, Yrttiaho S, Røysamb E, Melinder A. Perceptual interference processing in preschool children, with and without prenatal exposure to selective serotonin reuptake inhibitors. Psychopharmacology (Berl) 2017; 234:339-51. (2017, Norway)	SSRI	Pregnancy	Circa 68 months	Prenatal exposure to SSRIs and depression was not directly associated with abilities of interference suppression (behavioral flanker task while recording event-related potential ERPs)
El Marroun et al. ⁶⁸68. El Marroun H, White TJ, Fernandez G, Jaddoe VW, Verhulst FC, Stricker BH, et al. Prenatal exposure to selective serotonin reuptake inhibitors and non-verbal cognitive functioning in childhood. J Psychopharmacol 2017; 31:346-55. (2017, Netherlands)	SSRI	Pregnancy	48, 60 and 84 months	SSRI in pregnancy was not related to maternal reported executive function at 4 years, nor was it related with observed non-verbal intelligence at age 5 or neuropsychological function at 7 years. SSRI and untreated maternal depression in pregnancy had no major impact on child non-verbal cognition
Viktorin et al. ⁶⁹69. Viktorin A, Uher R, Kolevzon A, Reichenberg A, Levine SZ, Sandin S. Association of antidepressant medication use during pregnancy with intellectual disability in offspring. JAMA Psychiatry 2017; 74:1031-8. (2017, Sweden)	ADs/SSRI	Pregnancy	Circa 96 months	No evidence of association between maternal AD use in pregnancy and child intellectual disability after adjustment for confounding factors
Lupatelli et al. ⁸¹81. Lupattelli A, Wood M, Ystrom E, Skurtveit S, Handal M, Nordeng H. Effect of time-dependent selective serotonin reuptake inhibitor antidepressants during pregnancy on behavioral, emotional, and social development in preschool-aged children. J Am Acad Child Adolesc Psychiatry 2018; 57:200-8. (2018, Norway)	ADs/SSRI	Pregnancy	18 to 60 months	SSRI in pregnancy did not increase risks for externalizing, emotional, or social problems in preschool-aged children

[1] Correspondence
F. J. R. Paumgartten Laboratório de Toxicologia Ambiental, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz. Av. Brasil 4036, sala 101-104, Rio de Janeiro, RJ 21040-361, Brasil. paum@ensp.fiocruz.br

Brasil

Brasil

Exposição intrauterina a antidepressivos e risco de transtornos de neurodesenvolvimento e psiquiátricos: uma revisão sistemática

Resumo: