Review Article | Published:

Fetal programming of neuropsychiatric disorders by maternal pregnancy depression: a systematic mini review

Pediatric Researchvolume 85pages134145 (2019) | Download Citation




Maternal depression complicates a large proportion of pregnancies. Current evidence shows numerous harmful effects on the offspring. Reviews, which include depression, concluded that stress has harmful effects on the offspring’s outcomes neuro-cognitive development, temperament traits, and mental disorders.


This mini review of recent studies, sought to narrow the scope of exposure and identify studies specifically assessing prenatal depression and offspring neuropsychiatric outcomes.

Study eligibility criteria

The review included longitudinal, cohort, cross-sectional, clinical, quasi-experimental, epidemiological, or intervention study designs published in English from 2014 to 2018.


Study populations included mother-child dyads, mother-father-child triads, mother-alternative caregiver-child triads, and family studies utilizing sibling comparisons.


We searched PubMED and Web of Science. Study inclusion and data extraction were based on standardized templates. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS).


Thirteen studies examining neuropsychiatric outcomes were included. We judged the evidence to be moderate to high quality.


Our review supports that maternal prenatal depression is associated with neuropsychiatric adversities in children.


Future investigations should unravel the biological underpinnings and target timely interventions as early in pregnancy as possible to prevent offspring neuropsychiatric harms.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    O’Donnell, K. J. & Meaney, M. J. Fetal origins of mental health: the developmental origins of health and disease hypothesis. Am. J. Psychiatry 174, 319–328 (2017).

  2. 2.

    Van den Bergh, B. R. H. et al. Prenatal developmental origins of behavior and mental health: the influence of maternal stress in pregnancy. Neurosci. Biobehav. Rev. 2017 Jul 28. pii: S0149-7634(16)30734-5. [Epub ahead of print].

  3. 3.

    Gluckman, P. D. & Hanson, M. A. The developmental origins of health and disease: an overview. Dev. Orig. Health Dis. New York, USA:Cambridge University Press, 2006:1–5.

  4. 4.

    Barker, D. J. P. The origins of the developmental origins theory. J. Intern. Med. 261, 412–417 (2007).

  5. 5.

    Goodman, J. H. Women’s attitudes, preferences, and perceived barriers to treatment for perinatal depression. Birth 36, 60–69 (2009).

  6. 6.

    Bauer, A., Parsonage, M., Knapp, M., Iemmi, V. & Adelaja, B. Costs of perinatal mental health problems.London, England:Centre For Mental Health, 2014 [Internet]. [cited 2018 May 7].

  7. 7.

    Russell, S., Lang, B., Clinton, J., Adams, C. J. L. Perinatal Mental Health: Mental Health Experiences of Women and Health, 2013. (

  8. 8.

    Kumpulainen, S. M. et al. Maternal early pregnancy obesity and depressive symptoms during and after pregnancy. Psychol. Med. 48(14):2353-2363.(2018) e-pub ahead of print, 17 January 2018.

  9. 9.

    Girchenko, P. et al. Cohort profile: prediction and prevention of preeclampsia and intrauterine growth restriction (PREDO) study. Int. J. Epidemiol. 46, 1380–1381g (2017).

  10. 10.

    Jarde, A. et al. Neonatal outcomes in women with untreated antenatal depression compared with women without depression: A systematic review and meta-analysis. JAMA Psychiatry 73, 826–837 (2016).

  11. 11.

    Gentile, S. Untreated depression during pregnancy: short- and long-term effects in offspring. A systematic review. Neuroscience 342, 154–166 (2017).

  12. 12.

    Andalib, S. et al. Maternal SSRI exposure increases the risk of autistic offspring: a meta-analysis and systematic review. Eur. Psychiatry 45, 161–166 (2017).

  13. 13.

    Gentile, S. & Fusco, M. L. Placental and fetal effects of antenatal exposure to antidepressants or untreated maternal depression. J. Matern. Fetal Neonatal Med. 30, 1189–1199 (2017).

  14. 14.

    Ornoy, A., Weinstein-Fudim, L. & Ergaz, Z. Antidepressants, antipsychotics, and mood stabilizers in pregnancy: what do we know and how should we treat pregnant women with depression. Birth Defects Res. 109, 933–956 (2017).

  15. 15.

    Mezzacappa, A. et al. Risk for autism spectrum disorders according to period of prenatal antidepressant exposure: a systematic review and meta-analysis. JAMA Pediatr. 171, 555–563 (2017).

  16. 16.

    Moher, D., Liberati, A. & Tetzlaff, J. A. D. PRISMA 2009 Flow Diagram. Prism. Statement 6, 1000097 (2009).

  17. 17.

    Wells, G. A. et al. Ottawa Hosp. Res. Inst. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses, 2013. (

  18. 18.

    Higgins J., Green S., editors. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. Version 5. The Cochrane Collaboration; 2011.

  19. 19.

    Eichler, A. et al. Children of prenatally depressed mothers: externalizing and internalizing symptoms are accompanied by reductions in specific social-emotional competencies. J. Child Fam. Stud. 26, 3135–3144 (2017).

  20. 20.

    Korhonen, M., Luoma, I., Salmelin, R. & Tamminen, T. Maternal depressive symptoms: associations with adolescents’ internalizing and externalizing problems and social competence. Nord. J. Psychiatry 68, 323–332 (2014).

  21. 21.

    Lahti, M. et al. Maternal depressive symptoms during and after pregnancy and psychiatric problems in children. J. Am. Acad. Child Adolesc. Psychiatry 56, 30–39 (2017). e7.

  22. 22.

    El Marroun, H. et al. Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children. Br. J. Psychiatry 205, 95–102 (2014).

  23. 23.

    Hermansen, T. K., Røysamb, E., Augusti, E.-M. & Melinder, A. Behavior and inhibitory control in children with prenatal exposure to antidepressants and medically untreated depression. Psychopharmacology (Berl), 233, 1523–35 (2016).

  24. 24.

    O’Donnell, K. J., Glover, V., Barker, E. D. & O’Connor, T. G. The persisting effect of maternal mood in pregnancy on childhood psychopathology. Dev. Psychopathol. 26, 393–403 (2014).

  25. 25.

    Plant, D. T., Pariante, C. M., Sharp, D. & Pawlby, S. Prenatal depression and offspring depression in adulthood: role of child maltreatment. Br. J. Psychiatry 207, 213–220 (2015).

  26. 26.

    Leis, J. A., Heron, J., Stuart, E. A. & Mendelson, T. Associations between maternal mental health and child emotional and behavioral problems: does prenatal mental health matter? J Abnorm Child Psychol. 42, 161–71 (2014).

  27. 27.

    Johnson, K. C., Smith, A. K., Stowe, Z. N., Newport, D. J. & Brennan, P. A. Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function. J. Clin. Psychiatry 77, E176–E182 (2016).

  28. 28.

    Edwards, R. C. & Hans, S. L. Prenatal depressive symptoms and toddler behavior problems: the role of maternal sensitivity and child sex. Child Psychiatry Hum. Dev. 47, 696–707 (2016).

  29. 29.

    Capron, L. E. et al. Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years. J. Affect Disord. 187, 20–26 (2015).

  30. 30.

    Wolford, E. et al. Maternal depressive symptoms during and after pregnancy are associated with attention-deficit/hyperactivity disorder symptoms in their 3-to 6-year-old children. PLoS ONE 12, 1–13 (2017).

  31. 31.

    Gjerde, L. C. et al. Maternal perinatal and concurrent depressive symptoms and child behavior problems: a sibling comparison study. J. Child Psychol. Psychiatry 58, 779–786 (2017).

  32. 32.

    Wieckowski, B. M., Mukhtar, Y., Lee, J. J., Xing, G. & Walker, C. K. Higher autism in children of women with psychiatric diagnoses. Res. Autism Spectr. Disord. 33, 10–20 (2017).

  33. 33.

    Su, K.-P. et al. Different cutoff points for different trimesters? The use of Edinburgh Postnatal Depression Scale and Beck Depression Inventory to screen for depression in pregnant Taiwanese women. Gen. Hosp. Psychiatry 29, 436–441 (2007).

  34. 34.

    Harris, B., Huckle, P., Thomas, R., Johns, S. & Fung, H. The use of rating scales to identify post-natal depression. Br. J. Psychiatry 154, 813–817 (1989).

  35. 35.

    Tambs, K. & Røysamb, E. Selection of questions to short-form versions of original psychometric instruments in MoBa. Nor. Epidemiol. 24, 195–201 (2014).

  36. 36.

    Gjerde, L. C. et al. Strong genetic correlation between interview-assessed internalizing disorders and a brief self-report symptom scale. Twin Res. Hum. Genet. 14, 64–72 (2011).

  37. 37.

    McBride, O., Bebbington, P. & Cooper, C. Could the lower prevalence of affective disorder in older people be due to measurement error? Reliability of the Revised Clinical Interview Schedule in younger and older adults. J. Affect. Disord. 148, 310–315 (2013).

  38. 38.

    Briggs-Gowan, M. J., Carter, A. S., Irwin, J. R., Wachtel, K. & Cicchetti, D. V. The Brief Infant-Toddler Social and Emotional Assessment: screening for social-emotional problems and delays in competence. Journal of Pediatric Psychology 29, 143–155 (2004).

  39. 39.

    Molyneaux, E., Poston, L., Ashurst-williams, S. & Howard, L. M. Obesity and mental disorders during pregnancy and postpartum: a systematic review and meta-analysis. Obstet. Gynecol. 123, 857–867 (2014).

  40. 40.

    Steinig, J., Nagl, M., Linde, K., Zietlow, G. & Kersting, A. Antenatal and postnatal depression in women with obesity: a systematic review. Arch. Womens Ment. Health 20, 569–585 (2017).

  41. 41.

    Räisänen, S. et al. Risk factors for and perinatal outcomes of major depression during pregnancy: population-based analysis during 2002-2010 in Finland. BMJ Open 4 (2014).

  42. 42.

    Sanchez, C. E. et al. Maternal pre-pregnancy obesity and child neurodevelopmental outcomes: a meta-analysis. Obes. Rev. 19, 464–484 (2018).

  43. 43.

    Mina, T. H. et al. Prenatal exposure to very severe maternal obesity is associated with adverse neuropsychiatric outcomes in children. Psychol. Med. 47, 353–362 (2017).

  44. 44.

    Nahum Sacks, K. et al. Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring. Am. J. Obstet. Gynecol. 215, 380 (2016). e1-380.e7.

  45. 45.

    Wan, H., Zhang, C., Li, H., Luan, S. & Liu, C. Association of maternal diabetes with autism spectrum disorders in offspring: a systemic review and meta-analysis. Medicine (Baltimore) 97, e9438 (2018).

  46. 46.

    Van Lieshout, R. J. & Voruganti, L. P. Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms. J. Psychiatry Neurosci. 33, 395–404 (2008).

  47. 47.

    Xiang, A. H. et al. Association of maternal diabetes with autism in offspring. JAMA 313, 1425–1434 (2015).

  48. 48.

    Girchenko, P. et al. Maternal early pregnancy obesity and related pregnancy and pre-pregnancy disorders: associations with child developmental milestones in the prospective PREDO Study. Int. J. Obes. (2018).

  49. 49.

    Pesonen, A. K. et al. Maternal prenatal positive affect, depressive and anxiety symptoms and birth outcomes: the PREDO study. PLoS ONE 11, 1–13 (2016).

  50. 50.

    Pyhälä, R. et al. Self-reported mental health problems among adults born preterm: a meta-analysis. Pediatrics 139, e20162690 (2017).

  51. 51.

    D’Onofrio, B. M. et al. Preterm birth and mortality and morbidity: a population-based quasi-experimental study. JAMA Psychiatry 70, 1231–1240 (2013).

  52. 52.

    Class, Q. A., Rickert, M. E., Larsson, H., Lichtenstein, P. & D’Onofrio, B. M. Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison. Br. J. Psychiatry 205, 355–361 (2014).

  53. 53.

    Räikkönen, K. et al. Depression in young adults with very low birth weight: the Helsinki study of very low-birth-weight adults. Arch. Gen. Psychiatry 65, 290–296 (2008).

  54. 54.

    Heinonen, K. et al. Common mental disorders in young adults born late-preterm. Psychol. Med. 46, 2227–2238 (2016).

  55. 55.

    Riaz, M., Lewis, S., Naughton, F. & Ussher, M. Predictors of smoking cessation during pregnancy: a systematic review and meta-analysis. Addiction 113, 610–622 (2018). (e-pub ahead of print 30 Jan 2018).

  56. 56.

    Ekblad, M., Lehtonen, L., Korkeila, J. & Gissler, M. Maternal smoking during pregnancy and the risk of psychiatric morbidity in singleton sibling pairs. Nicotine Tob. Res. 1, 597–604 (2017).

  57. 57.

    Quinn, P. D. et al. Association between maternal smoking during pregnancy and severe mental illness in offspring. JAMA Psychiatry 74, 589 (2017).

  58. 58.

    Stetler, C. & Miller, G. E. Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom. Med. 73, 114–126 (2011).

  59. 59.

    Zorn, J. V. et al. Cortisol stress reactivity across psychiatric disorders: a systematic review and meta-analysis. Psychoneuroendocrinology 77, 25–36 (2017).

  60. 60.

    Bleker, L. S., Roseboom, T. J., Vrijkotte, T. G., Reynolds, R. M. & de Rooij, S. R. Determinants of cortisol during pregnancy—the ABCD cohort. Psychoneuroendocrinology 83, 172–181 (2017).

  61. 61.

    Thomas, J. C., Letourneau, N., Bryce, C. I., Campbell, T. S. & Giesbrecht, G. F. Biological embedding of perinatal social relationships in infant stress reactivity. Dev. Psychobiol. 59, 425–435 (2017).

  62. 62.

    Räikkönen, K. et al. Maternal licorice consumption during pregnancy and pubertal, cognitive, and psychiatric outcomes in children. Am. J. Epidemiol. 185, 317–328 (2017).

  63. 63.

    van der Knaap, N. J. F. et al. Maternal depressive symptoms during pregnancy are associated with amygdala hyperresponsivity in children. Eur. Child Adolesc. Psychiatry 27, 57–64 (2018).

  64. 64.

    Soe, N. N. et al. Perinatal maternal depressive symptoms alter amygdala functional connectivity in girls. Hum. Brain Mapp. 39, 680–690 (2018). e-pub 2 November 2017.

  65. 65.

    Wen, D. J. et al. Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children. Transl. Psychiatry 7, e1103 (2017).

  66. 66.

    Buss, C. et al. Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc. Natl Acad. Sci. USA 109, E1312–E1319 (2012).

  67. 67.

    Rogers, C. E. et al. Neonatal amygdala functional connectivity at rest in healthy and preterm infants and early internalizing symptoms. J. Am. Acad. Child Adolesc. Psychiatry 56, 157–166 (2017).

  68. 68.

    Zaretsky, M. V., Alexander, J. M., Byrd, W. & Bawdon, R. E. Transfer of inflammatory cytokines across the placenta. Obstet. Gynecol. 103, 546–550 (2004).

  69. 69.

    Shelton, M. M., Schminkey, D. L. & Groer, M. W. Relationships among prenatal depression, plasma cortisol, and inflammatory cytokines. Biol. Res. Nurs. 17, 295–302 (2015).

  70. 70.

    Karlsson, L. et al. Cytokine profile and maternal depression and anxiety symptoms in mid-pregnancy-the FinnBrain Birth Cohort Study. Arch. Womens Ment. Health 20, 39–48 (2017).

  71. 71.

    Köhler, O. et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects. JAMA Psychiatry 71, 1381 (2014).

  72. 72.

    Huang, R., Wang, K. & Hu, J. Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients 8, 483 (2016). [cited 2018 Apr 26].

  73. 73.

    Canetta, S. et al. Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort. Am. J. Psychiatry 171, 960–968 (2014).

  74. 74.

    Brown, A. S. et al. Elevated maternal C-reactive protein and autism in a national birth cohort. Mol. Psychiatry 19, 259–264 (2014).

  75. 75.

    Zerbo, O. et al. Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study. Transl. Psychiatry 6, e783 (2016).

  76. 76.

    Gilman, S. E. et al. Prenatal immune programming of the sex-dependent risk for major depression. Transl. Psychiatry 6, e822–e822 (2016).

  77. 77.

    Plant, D. T., Pawlby, S., Sharp, D., Zunszain, P. A. & Pariante, C. M. Prenatal maternal depression is associated with offspring inflammation at 25 years: a prospective longitudinal cohort study. Transl. Psychiatry 6, e936 (2016).

  78. 78.

    Kang, L. J. et al. Maternal depressive symptoms linked to reduced fecal Immunoglobulin A concentrations in infants. Brain Behav. Immun. 68, 123–131 (2018).

  79. 79.

    Krause, L., Einsle, F., Petzoldt, J., Wittchen, H. U. & Martini, J. The role of maternal anxiety and depressive disorders prior to and during pregnancy and perinatal psychopathological symptoms for early infant diseases and drug administration. Early Hum. Dev. 109, 7–14 (2017).

  80. 80.

    Ryan, J., Mansell, T., Fransquet, P. & Saffery, R. Does maternal mental well-being in pregnancy impact the early human epigenome? Epigenomics 9, 313–332 (e-pub ahead of print 3 January 2017).

  81. 81.

    Palma-Gudiel, H., Córdova-Palomera, A., Eixarch, E., Deuschle, M. & Fañanás, L. Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis. Epigenetics 10, 893–902 (2015).

  82. 82.

    Räikkönen, K. et al. Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors. Psychol. Med. 45, 3217–3226 (2015).

  83. 83.

    Reynolds, R. M. et al. Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity. Psychol. Med. 45, 2023–30 (2015). (e-pub ahead of print 28 January 2015).

  84. 84.

    Mina, T. H., Räikkönen, K., Riley, S. C., Norman, J. E. & Reynolds, R. M. Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: role of obesity and sex. Psychoneuroendocrinology 59, 112–122 (e-pub 2015).

  85. 85.

    Suarez, A. et al. The epigenetic clock at birth: associations with maternal antenatal depression and child psychiatric problems. J. Am. Acad. Child Adolesc. Psychiatry 2018; 57(5),321–328.

  86. 86.

    Lahti-Pulkkinen, M. et al. Placental morphology is associated with maternal depressive symptoms during pregnancy and toddler psychiatric problems. Sci. Rep. 8, 1–12 (2018) (Article 791).

  87. 87.

    Shankar, R., Badker, R., Brain, U., Oberlander, T. F. & Misri, S. Predictors of recovery from depression and anxiety in women: a longitudinal study from childbirth to 6 years. Can. J. Psychiatry 62, 318–326 (2017).

  88. 88.

    Kong, L. L., Zhou, T. T., Wang, B. L., Gao, Z. B. & Wang, C. X. The risks associated with the use of lamotrigine during pregnancy. Int J. Psychiatry Clin. Pract. 22, 2–5 (2018).

  89. 89.

    Paulzen, M. et al. Pregnancy exposure to citalopram—therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood. Prog. Neuropsychopharmacol. Biol. Psychiatry 79, 213–219 (2017).

  90. 90.

    Siu, A. L. et al. Screening for depression in adults. JAMA 315, 380 (2016).

  91. 91.

    van Ravesteyn, L. M., Lambregtse-van den Berg, M. P., Hoogendijk, W. J. G. & Kamperman, A. M. Interventions to treat mental disorders during pregnancy: a systematic review and multiple treatment meta-analysis. PLoS ONE 12, e0173397 (2017) (e collection 2017).

  92. 92.

    Knight, M., Nair, M., Derek Tuffnell, J. S. & Sara Kenyon, J. J. K. (eds). National Perinatal Epidemiology Unit. Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2013–15, 2014. (

  93. 93.

    Ashford, M. T., Ayers, S. & Olander, E. K. Supporting women with postpartum anxiety: exploring views and experiences of specialist community public health nurses in the UK. Health Soc. Care Community 25, 1257–1264 (2017).

  94. 94.

    Lee, E. W., Denison, F. C., Hor, K. & Reynolds, R. M. Web-based interventions for prevention and treatment of perinatal mood disorders: a systematic review. BMC Pregnancy Childbirth 16, 38 (2016).

  95. 95.

    Nwebube, C., Glover, V. & Stewart, L. Prenatal listening to songs composed for pregnancy and symptoms of anxiety and depression: a pilot study. BMC Complement. Altern. Med. 17, 256 (2017).

  96. 96.

    Farshbaf-Khalili, A., Mohammad-Alizadeh, S., Farshbaf-Khalili, A., Mohammadi, F. & Ostadrahimi, A. Fish-oil supplementation and maternal mental health: a triple-blind, randomized controlled trial. Iran Red Crescent Med. J. 19, e36237 (2017) (e-pub a head of print 4 October 2016).

  97. 97.

    Sparling, T. M., Henschke, N., Nesbitt, R. C. & Gabrysch, S. The role of diet and nutritional supplementation in perinatal depression: a systematic review. Matern. Child Nutr. 13, (2017) (e-pub ahead of print 3 February 2016).

Download references


Funding for this review comes from an Academy of Finland Program Grant, European Commission Horizon 2020 Award SC1-2016-RTD-733280 for RECAP, European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL) No. 724363 for PremLife, and the Signe and Ane Gyllenberg Foundation.

Author information


  1. Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland

    • Rachel Robinson
    • , Marius Lahti-Pulkkinen
    • , Kati Heinonen
    •  & Katri Räikkönen
  2. University/British Heart Foundation Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

    • Rebecca M. Reynolds


  1. Search for Rachel Robinson in:

  2. Search for Marius Lahti-Pulkkinen in:

  3. Search for Kati Heinonen in:

  4. Search for Rebecca M. Reynolds in:

  5. Search for Katri Räikkönen in:

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Rachel Robinson.

Electronic supplementary material

About this article

Publication history