Prenatal antidepressant exposure and the risk of attention-deficit hyperactivity disorder in children: a systematic review and meta-analysis.
Open accessAbstract
This systematic review assesses the association between prenatal antidepressant exposure and risk of ADHD in children. Electronic databases were searched up to 25 July 2017. Observational studies examining this association were included in the review and meta-analysis was conducted where appropriate. Eight relevant studies were identified. The seven studies included in the meta-analysis comprised a total of 2,886,502 children. The pooled estimates comparing prenatal exposure to non-exposure showed an adjusted rate ratio (aRR) of 1.39 (95%CI 1.21-1.61). Similarly, an increased risk was found comparing previous antidepressant users and non-users: aRR = 1.56 (95%CI 1.25-1.95). The relationship between maternal psychiatric conditions and ADHD in children yielded an aRR of 1.90 (95%CI 1.47-2.45). Three studies conducted sibling-matched analyses with aRR of 0.94 (95%CI 0.75-1.16). These data suggest that the observed association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication because the results from sibling-matched analyses do not support an increased risk of ADHD in discordant exposed siblings.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a sensitivity analysis of class I or II evidence, the random-effects risk ratio for ADHD in children with SSRI/non-SSRI use was 1.67 (95% CI, 1.53-1.82), based on 22 studies, with class II/Moderate evidence.
“RR: 1.67 | (1.53 to 1.82)”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as Man et al, 48 2018
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552 · see citing works
Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis
Thomas, R., Sanders, S., Doust, J., Beller, E., & Glasziou, P. (2015) · Pediatrics · doi:10.1542/peds.2014-3482 · Cited by 1,976 · cited 1× · see citing works
“T (Polanczyk et al., 2014; Thomas et al., 2015).”
Polanczyk, G. V., Willcutt, E. G., Salum, G. A., Kieling, C., & Rohde, L. A. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt261 · Cited by 1,822 · see citing works
Depression and cortisol responses to psychological stress: A meta-analysis
Burke, H. M., Davis, M. C., Otte, C., & Mohr, D. C. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.02.010 · Cited by 1,194 · see citing works
Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice
Ansorge, M. S., Zhou, M., Lira, A., Hen, R., & Gingrich, J. A. (2004) · Science · doi:10.1126/science.1101678 · Cited by 817 · see citing works
Perinatal Risks of Untreated Depression during Pregnancy
Bonari, L., Pinto, N., Ahn, E., Einarson, A., Steiner, M. S., & Koren, G. (2004) · The Canadian Journal of Psychiatry · doi:10.1177/070674370404901103 · Cited by 524 · see citing works
First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects
Louik, C., Lin, A. E., Werler, M. M., Hernández–Dı́az, S., & Mitchell, A. A. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa067407 · Cited by 500 · see citing works
Yonkers, K. A., Wisner, K. L., Stewart, D. E., Oberlander, T. F., Dell, D. L., Stotland, N., Ramin, S., Chaudron, L., & Lockwood, C. (2009) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2009.04.003 · Cited by 469 · see citing works
Ronald, A., Simonoff, E., Kuntsi, J., Asherson, P., & Plomin, R. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2007.01857.x · Cited by 466 · see citing works
Self-citationImplications of Antenatal Depression and Anxiety for Obstetric Outcome
Andersson, L., Sundström-Poromaa, I., Wulff, M., Åström, M., & Bixo, M. (2004) · Obstetrics & Gynecology · doi:10.1097/01.aog.0000135277.04565.e9 · Cited by 362 · see citing works
D’Onofrio, B. M., Lahey, B. B., Turkheimer, E., & Lichtenstein, P. (2013) · American Journal of Public Health · doi:10.2105/ajph.2013.301252 · Cited by 343 · see citing works
Depression during Pregnancy: Overview of Clinical Factors
Bennett, H. A., Einarson, A., Taddio, A., Koren, G., & Einarson, T. R. (2004) · Clinical Drug Investigation · doi:10.2165/00044011-200424030-00004 · Cited by 317 · see citing works
Schneeweiß, S., Patrick, A. R., Stürmer, T., Brookhart, M. A., Avorn, J., Maclure, M., Rothman, K. J., & Glynn, R. J. (2007) · Medical Care · doi:10.1097/mlr.0b013e318070c08e · Cited by 255 · see citing works
Placental Transfer of SSRI and SNRI Antidepressants and Effects on the Neonate
Rampono, J., Simmer, K. N., Ilett, K. F., Hackett, L. P., Doherty, D. A., Elliot, R. H., Kok, C. H., Coenen, A., & Forman, T. (2009) · Pharmacopsychiatry · doi:10.1055/s-0028-1103296 · Cited by 254 · see citing works
Sujan, A. C., Rickert, M. E., Öberg, A. S., Quinn, P. D., Hernández-Díaz, S., Almqvist, C., Lichtenstein, P., Larsson, H., & D’Onofrio, B. M. (2017) · JAMA · doi:10.1001/jama.2017.3413 · Cited by 226 · see citing works
Lahey, B. B., & D’Onofrio, B. M. (2010) · Current Directions in Psychological Science · doi:10.1177/0963721410383977 · Cited by 207 · see citing works
Malm, H., Brown, A. S., Gissler, M., Gyllenberg, D., Hinkka-Yli-Salomäki, S., McKeague, I. W., Weissman, M., Wickramaratne, P., Artama, M., Gingrich, J. A., et al. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.02.013 · Cited by 206 · see citing works
British National Formulary (BNF) 50
Mehta, D. K. (2005) · Cited by 205 · see citing works
Smalley, S. L. (1997) · The American Journal of Human Genetics · doi:10.1086/515485 · Cited by 199 · see citing works
Clements, C. C., Castro, V. M., Blumenthal, S. R., Rosenfield, H. R., Murphy, S. N., Fava, M., Erb, J. L., Churchill, S. E., Kaimal, A. J., Doyle, A. E., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.90 · Cited by 197 · see citing works
Grigoriadis, S., VonderPorten, E. H., Mamisashvili, L., TOMLINSON, G. A., Dennis, C., Koren, G., Steiner, M. S., Mousmanis, P., Cheung, A. M., & Ross, L. E. (2014) · BMJ · doi:10.1136/bmj.f6932 · Cited by 197 · see citing works
Under Diagnosis of Adult ADHD: Cultural Influences and Societal Burden
Asherson, P., Akehurst, R., Kooij, J. J. S., Huss, M., Beusterien, K., Sasané, R., Gholizadeh, S., & Hodgkins, P. (2012) · Journal of Attention Disorders · doi:10.1177/1087054711435360 · Cited by 189 · see citing works
Huang, H., Coleman, S., Bridge, J. A., Yonkers, K., & Katon, W. (2014) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2013.08.002 · Cited by 180 · see citing works
Man, K. K. C., Chan, E. W., Ip, P., Coghill, D., Simonoff, E., Chan, P. K. L., Lau, W. C. Y., Schuemie, M. J., Sturkenboom, M. C. J. M., & Wong, I. C. K. (2017) · BMJ · doi:10.1136/bmj.j2350 · Cited by 135 · see citing works
Self-citationMyles, N., Newall, H. D., Ward, H. R. G., & Large, M. M. B. (2013) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867413492219 · Cited by 126 · see citing works
Man, K. K. C., Tong, H. H. Y., Wong, L. Y. L., Chan, E. W., Simonoff, E., & Wong, I. C. K. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.020 · Cited by 126 · see citing works
Self-citationFigueroa, R. (2010) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e3181e5ac93 · Cited by 116 · see citing works
Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up study
Karam, R. G., Breda, V., Picon, F. A., Rovaris, D. L., Victor, M. M., Salgado, C. A. I., Vitola, E. S., Silva, K. L., Guimarães-da-Silva, P. O., Mota, N. R., et al. (2015) · Psychological Medicine · doi:10.1017/s0033291714003183 · Cited by 113 · see citing works
British National Formulary (BNF)
Thompson, D. (2005) · Cited by 112 · see citing works
Castro, V. M., Kong, S. W., Clements, C. C., Brady, R., Kaimal, A. J., Doyle, A. E., Robinson, E. B., Churchill, S. E., Kohane, I. S., & Perlis, R. H. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.190 · Cited by 82 · see citing works
Confounders, Mediators, or Colliders
Sjölander, A., & Zetterqvist, J. (2017) · Epidemiology · doi:10.1097/ede.0000000000000649 · Cited by 67 · see citing works
Laugesen, K., Olsen, M. S., Telén Andersen, A. B., Frøslev, T., & Toft Sørensen, H. (2013) · BMJ Open · doi:10.1136/bmjopen-2013-003507 · Cited by 58 · see citing works
Review: The Use of Antidepressants in Pregnant and Breastfeeding Women: A Review of Recent Studies
Kendall-Tackett, K. A., & Hale, T. W. (2009) · Journal of Human Lactation · doi:10.1177/0890334409342071 · Cited by 44 · see citing works
Boukhris, T., Sheehy, O., & Bérard, A. (2017) · Paediatric and Perinatal Epidemiology · doi:10.1111/ppe.12378 · Cited by 34 · see citing works
Fleck, K., Jacob, C., Philipsen, A., Matthies, S., Graf, E., Hennighausen, K., Haack‐Dees, B., Weyers, P., Warnke, A., Rösler, M., et al. (2015) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-014-0164-8 · Cited by 28 · see citing works
The safety of antidepressants in pregnancy
Pedersen, L. H. (2017) · BMJ · doi:10.1136/bmj.j2544 · Cited by 3 · see citing works
Flagged first, then by citations
1 of the 39 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review
Dragioti, E., Solmi, M., Favaro, A., Fusar-Poli, P., Dazzan, P., Thompson, T., Stubbs, B., Firth, J., Fornaro, M., Tsartsalis, D., et al. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.2859 · Cited by 215 · see citing works
Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture
Sing, C., Wong, A. Y. S., Kiel, D. P., Cheung, E. Y. N., Lam, J. K. Y., Cheung, T. T., Chan, E. W., Kung, A. W. C., Wong, I. C. K., & Cheung, C. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3448 · Cited by 94 · see citing works
Self-citationA systematic meta-review of systematic reviews on attention deficit hyperactivity disorder
Chaulagain, A., Lyhmann, I., Halmøy, A., Widding‐Havneraas, T., Nyttingnes, O., Bjelland, I., & Mykletun, A. (2023) · European Psychiatry · doi:10.1192/j.eurpsy.2023.2451 · Cited by 93 · see citing works
Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link
Hanswijk, S. I., Spoelder, M., Shan, L., Verheij, M. M. M., Muilwijk, O. G., Li, W., Liu, C., Kolk, S. M., & Homberg, J. R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165850 · Cited by 86 · see citing works
Benefits and Risks of Antidepressant Drugs During Pregnancy: A Systematic Review of Meta-analyses
Desaunay, P., Eude, L.-G., Dreyfus, M., Alexandre, C., Fédrizzi, S., Alexandre, J., Uğuz, F., & Guenolé, F. (2023) · Pediatric Drugs · doi:10.1007/s40272-023-00561-2 · Cited by 65 · see citing works
Lupattelli, A., Chambers, C., Bandoli, G., Handal, M., Skurtveit, S. O., & Nordeng, H. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.1435 · Cited by 54 · see citing works
Sujan, A. C., Öberg, A. S., Quinn, P. D., & D'Onofrio, B. M. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13004 · Cited by 52 · see citing works
Wang, J., & Cosci, F. (2021) · Psychotherapy and Psychosomatics · doi:10.1159/000516031 · Cited by 46 · see citing works
Araújo, J. N. D. M., Delgado, I. F., & Paumgartten, F. J. R. (2020) · Cadernos de Saúde Pública · doi:10.1590/0102-311x00026619 · Cited by 28 · see citing works
Should Antidepressants be Avoided in Pregnancy?
Besag, F., & Vasey, M. J. (2022) · Drug Safety · doi:10.1007/s40264-022-01257-1 · Cited by 25 · see citing works
Uğuz, F. (2020) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1724 · Cited by 22 · see citing works
Lupattelli, A., Mahic, M., Handal, M., Ystrøm, E., Reichborn‐Kjennerud, T., & Nordeng, H. (2021) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.16743 · Cited by 22 · see citing works
van der Veere, C. N., de Vries, N. K. S., Braeckel, K. N. J. A. V., & Bos, A. F. (2020) · Early Human Development · doi:10.1016/j.earlhumdev.2020.105075 · Cited by 21 · see citing works
Wang, Z., Ho, P. W. H., Choy, M. T. H., Wong, I. C. K., Brauer, R., & Man, K. K. C. (2018) · Drug Safety · doi:10.1007/s40264-018-0755-y · Cited by 18 · see citing works
Self-citationHo, F. K. W., Allan, M., Shao, H., Man, K. K. C., Jani, B., Lyall, D. M., Hastie, C. E., Fleming, M., Mackay, D., Cleland, J. G. F., et al. (2024) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2024.101075 · Cited by 13 · see citing works
Self-citationOlstad, E. W., Nordeng, H., Sandve, G. K., Lyle, R., & Gervin, K. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02441-2 · Cited by 12 · see citing works
Corcoran, J., Marinescu, I., Vogelsang, C. J., & Kim, J. C. (2022) · Journal of Public Health · doi:10.1007/s10389-021-01662-3 · Cited by 10 · see citing works
Interaksi Faktor Genetik dan Lingkungan pada Attention Deficit/Hyperactivity Disorder (ADHD)
Setiawati, Y. (2017) · Jurnal Psikiatri Surabaya · doi:10.20473/jps.v6i2.19434 · Cited by 12 · see citing works
Leung, M. T. Y., Wong, K. H. T. W., Ho, P. W. H., Ip, P., Wei, L., Wong, I. C. K., & Man, K. K. C. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.040 · Cited by 6 · see citing works
Self-citationSylte, O. C., Johansen, J. S., Heinla, I., Houwing, D. J., Olivier, J. D. A., Heijkoop, R., & Snoeren, E. M. S. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05984-8 · Cited by 5 · see citing works
Self-orthogonalizing attractor neural networks emerging from the free energy principle
Spisák, T., & Friston, K. J. (2026) · Neurocomputing · doi:10.1016/j.neucom.2026.133472 · Cited by 5 · see citing works
Antidepressant Prescription in Pregnancy
Andrade, C. (2020) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.20f13347 · Cited by 6 · see citing works
Chan, J. K. N., Zhong, A. H. F., Lam, J. Y. H., Wong, C. S. M., Solmi, M., Correll, C. U., & Chang, W. C. (2026) · The Lancet Psychiatry · doi:10.1016/s2215-0366(26)00089-1 · Cited by 5 · see citing works
Ali, A. M. (2019) · Scientific Journal of Research & Reviews · doi:10.33552/sjrr.2019.01.000509 · Cited by 4 · see citing works
Magnesium as a potential complementary treatment for ADHD - a review of recent literature
Smykiewicz, K., Michalczewska, A., Wierzejska, N., Pach, M., Nowak, A., Fugas, A., Chmielowiec, Z., Partyka, A., Dziedzic, M., & Dobrzańska, J. (2024) · Journal of Education Health and Sport · doi:10.12775/jehs.2024.68.50663 · Cited by 3 · see citing works
Psychotropic drugs in pregnancy and lactation
Marazziti, D., Crowther, L. F., Arone, A., Russomanno, G., Gurrieri, R., Weiss, F., & Perugi, G. (2025) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2025.2593995 · Cited by 2 · see citing works
Brikell, I. (2018) · Figshare · Cited by 2 · see citing works
Grigoriadis, S., & Peer, M. (2019) · Springer eBooks · doi:10.1007/978-3-319-92919-4_5 · Cited by 1 · see citing works
Psiquiatría y embarazo: la madre y el hijo
Sutter‐Dallay, A., Scotta, G., Lemoigne, S., & Gressier, F. (2020) · EMC - Ginecología-Obstetricia · doi:10.1016/s1283-081x(20)44317-6 · Cited by 1 · see citing works
Are There Prenatal Risk Factors for ADHD?
Eme, R. F. (2020) · The ADHD Report · doi:10.1521/adhd.2020.28.2.6
Lupattelli, A., Mahic, M., Handal, M., Ystrøm, E., Reichborn‐Kjennerud, T., & Nordeng, H. (2020) · doi:10.22541/au.160133485.51800404
Administer antidepressants during pregnancy on a case-by-case basis
Lamb, Y. N., & Fung, S. S.-P. (2024) · Drugs & Therapy Perspectives · doi:10.1007/s40267-024-01053-0
- Authors
- Man, K. K. C., Chan, E. W., Ip, P., Coghill, D., Simonoff, E., Chan, P. K. L., Lau, W. C. Y., Schuemie, M. J., Sturkenboom, M. C. J. M., & Wong, I. C. K.
- Affiliations
- Erasmus MC (NL)
- University of Hong Kong (HK)
- The University of Melbourne (AU)
- King's College London (GB)
- Queen Mary Hospital (CN)
- Janssen Research & Development (United States) (US)
- UCL School of Pharmacy (GB)
- Corresponding author
- Wong, Ian C.K.
- ORCID
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 86
- Pages
- 1-11
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2775655637
- Cited by
- 32
- References
- 39
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 4 · 2017: 1
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- prenatal antidepressant exposure, attention deficit hyperactivity disorder, children, confounding by indication, sibling discordance, maternal medication use
- MeSH terms
- Antidepressive Agents, Attention Deficit Disorder with Hyperactivity, Female, Humans, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
