Skip to main content
SpringerLink
Log in

Thyroid autoimmunity and risk of post-partum depression: a systematic review and meta-analysis of longitudinal studies

  • Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to systematically investigate whether, and to what extent, the detection of thyroid autoimmunity during pregnancy and in the weeks after childbirth is associated with an increased risk of developing post-partum depression (PPD), a condition associated with possible adverse outcomes for both mother and offspring. We performed a systematic review and meta-analysis of longitudinal studies, assessing the incidence of PPD in women with and without anti-thyroperoxidase antibody (TPOAb) positivity.

Methods

We searched MEDLINE, EMBASE, Web of Science, Cochrane Library, and CINAHL. Methodological quality of the studies was assessed by the Newcastle–Ottawa Scale. In the presence of even modest between-studies heterogeneity, assessed by Cochrane Q and I2 tests, risk ratios (RRs) for PPD were combined using a random effects model. Funnel plot and trim-and-fill analysis were used to assess publication bias.

Results

Five included studies provided information on 449 women with TPOAb-positive and 2483 TPOAb-negative women. Pooled RR indicated a significantly increased risk to develop PPD in TPOAb-positive group (RR 1.49, 95% CI 1.11–2.00; P = 0.008; I2 = 47%, Pfor heterogeneity = 0.11). Consistent with a possible publication bias, the trim-and-fill test detected two putative missing studies in the funnel plot. Nevertheless, the adjustment for publication bias produced a negligible effect on the pooled estimate (adjusted RR 1.41, 95% CI 1.18–1.68, P = 0.0002).

Conclusions

Thyroid autoimmunity during pregnancy and in the weeks after childbirth is associated with an increased risk of developing PPD. Further well-designed studies are warranted to confirm this association and elucidate underlying pathophysiological mechanisms.

PROSPERO registration

CRD42019129643.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Shorey S, Chee CYI, Ng ED, Chan YH, Tam WWS, Chong YS (2018) Prevalence and incidence of postpartum depression among healthy mothers: a systematic review and meta-analysis. J Psychiatr Res 104:235–248

    Article  Google Scholar 

  2. Beck C, Gable R (2001) Comparative analysis of the performance of the postpartum depression screening scale with two other depression instruments. Nurs Res 50:242–250

    Article  CAS  Google Scholar 

  3. Putnam KT, Wilcox M, Robertson-Blackmore E, Sharkey K, Bergink V, Munk-Olsen T, Deligiannidis KM, Payne J, Altemus M, Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium et al (2017) Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an International Consortium. Lancet Psychiatry 4:477–485

    Article  Google Scholar 

  4. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T (2005) Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol 106:1071–1083

    Article  Google Scholar 

  5. Owora A, Carabin H, Reese J, Garwe T (2016) Diagnostic performance of major depression disorder case-finding instruments used among mothers of young children in the United States: a systematic review. J Affect Disord 201:185–193

    Article  Google Scholar 

  6. Lindahl V, Pearson JL, Colpe L (2005) Prevalence of suicidality during pregnancy and the postpartum. Arch Women’s Mental Health 8:77–87

    Article  CAS  Google Scholar 

  7. Farías-Antúnez S, Xavier MO, Santos IS (2018) Effect of maternal postpartum depression on offspring’s growth. J Affect Disord 228:143–152

    Article  Google Scholar 

  8. Flynn HA, Davis M, Marcus SM, Cunningham R, Blow FC (2004) Rates of maternal depression in pediatric emergency department and relationship to child service utilization. Gen Hosp Psychiatry 26:316–322

    Article  Google Scholar 

  9. Guintivano J, Manuck T, Meltzer-Brody S (2018) Predictors of postpartum depression: a comprehensive review of the last decade of evidence. Clin Obstet Gynecol 61:591–603

    Article  Google Scholar 

  10. Muller AF, Drexhage HA, Berghout A (2001) Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr Rev 22:605–630

    Article  CAS  Google Scholar 

  11. Weetman AP (2010) Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol 6:311–318

    Article  CAS  Google Scholar 

  12. Harris B, Othman S, Davies JA, Weppner GJ, Richards CJ, Newcombe RG, Lazarus JH, Parkes AB, Hall R, Phillips DI (1992) Association between postpartum thyroid dysfunction and thyroid antibodies and depression. BMJ 305:152–156

    Article  CAS  Google Scholar 

  13. Pop VJ, deRooy HA, Vader HL, van der Heide D, van Son MM, Komproe IH (1993) Microsomal antibodies during gestation in relation to postpartum thyroid dysfunction and depression. Acta Endocrinol 129:26–30

    Article  CAS  Google Scholar 

  14. Lazarus JH, Hall R, Othman S, Parkes AB, Richards CJ, McCulloch B, Harris B (1996) The clinical spectrum of postpartum thyroid disease. Q J Med 89:429–435

    Article  CAS  Google Scholar 

  15. Oomen HAPC, Schipperijn AJM, Drexhage HA (1996) The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests. Clin Endocrinol 45:215–223

    Article  CAS  Google Scholar 

  16. Kuijpens JL, Vader HL, Drexhage HA, Wiersinga WM, van Son MJ, Pop VJ (2001) Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum. Eur J Endocrinol 145:579–584

    Article  CAS  Google Scholar 

  17. Wesseloo R, Kamperman AM, Bergink V, Pop VJM (2018) Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: a prospective cohort study. J Affect Disord 225:399–403

    Article  CAS  Google Scholar 

  18. Kent GN, Stuckey BGA, Allen JR, Lambert T, Gee V (1999) Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity. Clin Endocrinol 51:429–438

    Article  CAS  Google Scholar 

  19. Albacar G, Sans T, Martín-Santos R, García-Esteve L, Guillamat R, Sanjuan J, Cañellas F, Carot JM, Gratacòs M, Bosch J, Gaviria A et al (2010) Thyroid function 48 h after delivery as a marker for subsequent postpartum depression. Psychoneuroendocrinology 35:738–742

    Article  CAS  Google Scholar 

  20. Bunevicius R, Kusminskas L, Bunevicius A, Nadisauskiene RJ, Jureniene K, Pop VJM (2009) Psychosocial risk factors for depression during pregnancy. Acta Obstet Gynecol Scand 88:599–605

    Article  Google Scholar 

  21. Moher D, Liberati A, Tezlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analysis: the PRISMA Statement. PLOS Med 6:e1000097

    Article  Google Scholar 

  22. Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F et al (2003) Evaluating non randomized intervention studies. Health Technol Assess 7:1–173

    Article  Google Scholar 

  23. Sterne JA, Egger M (2001) Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 54:1046–1055

    Article  CAS  Google Scholar 

  24. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463

    Article  CAS  Google Scholar 

  25. Dama M, Steiner M, Lieshout RV (2016) Thyroid peroxidase autoantibodies and perinatal depression risk: a systematic review. J Affect Disord 1:108–121

    Article  Google Scholar 

  26. Stagnaro-Green A, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Negro R (2011) High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy. J Clin Endocrinol Metab 96:652–657

    Article  CAS  Google Scholar 

  27. Smallridge RC (2000) Postpartum thyroid disease: a model of immunologic dysfunction. Clin Appl Immunol Rev 1:89–103

    Article  CAS  Google Scholar 

  28. Stagnaro-Green A (2012) Approach to the patient with postpartum thyroiditis. J Clin Endocrinol Metab 97:334–342

    Article  CAS  Google Scholar 

  29. Zhou Y, Wang X, Zhao Y, Liu A, Zhao T, Zhang Y, Shan Z, Teng W (2017) Elevated thyroid peroxidase antibody increases risk of post-partum depression by decreasing prefrontal cortex BDNF and 5-HT levels in mice. Front Cell Neurosci 9:10–307

    Google Scholar 

  30. Jia N, Li Q, Sun H, Song Q, Tang G, Sun Q, Wang W, Chen R, Li H, Zhu Z (2015) Alterations of group I mGluRs and BDNF associated with behavioral abnormity in prenatally stressed offspring rats. Neurochem Res 40:1074–1082

    Article  CAS  Google Scholar 

  31. Daftary SS, Calderon G, Rios M (2012) Essential role of brain-derived neurotrophic factor in the regulation of serotonin transmission in the basolateral amygdala. Neuroscience 8:125–134

    Article  Google Scholar 

  32. Wells TT, Beevers CG, McGeary JE (2010) Serotonin transporter and BDNF genetic variants interact to predict cognitive reactivity in healthy adults. J Affect Disord 126:223–229

    Article  CAS  Google Scholar 

  33. Gibney SM, McGuinness B, Prendergast C, Harkin A, Connor TJ, Poly I (2013) C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression. Brain Behav Immun 28:170–181

    Article  CAS  Google Scholar 

  34. Yu D, Zhou H, Yang Y, Jiang Y, Wang T, Lv L, Zhou Q, Yang Y, Dong X, He J et al (2015) The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety and depression-like behaviors in rats. Horm Behav 69:106–115

    Article  CAS  Google Scholar 

  35. Wichers M, Maes M (2002) The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol 5:375–388

    Article  CAS  Google Scholar 

  36. Dantzer R (2009) Cytokine, sickness behavior, and depression. Immunol Allergy Clin N Am 29:247–264

    Article  Google Scholar 

  37. Lichtblau N, Schmidt FM, Schumann R, Kirkby KC, Himmerich H (2013) Cytokines as biomarkers in depressive disorder: current standing and prospects. Int Rev Psychiatry 25:592–603

    Article  Google Scholar 

  38. Postal M, Appenzeller S (2015) The importance of cytokines and autoantibodies indepression. Autoimmun Rev 14:30–35

    Article  CAS  Google Scholar 

  39. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ et al (2016) Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 27:315–389

    Article  Google Scholar 

Download references

Funding

This work was supported by Ministero dell’Università e della Ricerca Scientifica, Italy.

Author information

Authors and Affiliations

  1. Department of Life, Health and Environment Sciences, University of L’Aquila, Via Vetoio, 67100, L’Aquila, Italy

    E. Minaldi, S. D’Andrea, C. Castellini, A. Martorella, F. Francavilla, S. Francavilla & A. Barbonetti

Authors
  1. E. Minaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. D’Andrea
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Castellini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Martorella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. Francavilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Francavilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Barbonetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EM: acquisition of data, analysis and interpretation of data, and drafting the article; SD: analysis and interpretation of data, and drafting the article; CC: acquisition of data; AM: acquisition of data; FF: critical revision for important intellectual content; SF: statistical analysis and interpretation of data; AB: conception and design, analysis and interpretation of data, critical revision for important intellectual content, drafting the article, and final approval of the version to be published. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to A. Barbonetti.

Ethics declarations

Conflict of interest

The authors have no potential conflicts of interest to disclosure.

Ethical approval

Ethics approval is not required as this study is a meta-analysis based on published studies.

Informed consent

Patient consent is not required as this study is a meta-analysis based on published studies.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Minaldi, E., D’Andrea, S., Castellini, C. et al. Thyroid autoimmunity and risk of post-partum depression: a systematic review and meta-analysis of longitudinal studies. J Endocrinol Invest 43, 271–277 (2020). https://doi.org/10.1007/s40618-019-01120-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-019-01120-8

Keywords

Search

Navigation