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Maternal use of selective serotonin reuptake inhibitors (SSRI) during pregnancy—neonatal outcomes in correlation with placental histopathology

Journal of Perinatology volume 40, pages 1017–1024 (2020)Cite this article

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Abstract

Objective

We investigated the association between prenatal selective serotonin reuptake inhibitors (SSRI) exposure and pregnancy-outcomes with correlation to placental-histopathology.

Study design

Included were pregnancies with maternal SSRI use throughout pregnancy (SSRI-group) and the control group was matched with pregnancies unexposed to SSRI. Placental lesions were classified according to the “Amsterdam” criteria. Adverse neonatal outcome was defined as ≥1 early neonatal-complications.

Results

SSRI group had lower birthweights (p < 0.001), higher rates of meconium (p = 0.009), NICU admissions (p < 0.001), and adverse neonatal-outcome (p < 0.001). SSRI placentas had lower birthweight-to-placental-weight ratio (p = 0.02) and higher rates of fetal vascular malperfusion (FVM) lesions (p = 0.03). Using multivariable analyses: GA < 37 weeks (aOR = 2.1, 95%CI 1.7–4.6) and SSRI (aOR = 1.7, 95%CI 1.3–3.9) were independently associated with adverse neonatal outcome while GA < 37 weeks (aOR = 1.6, 95%CI 1.2–3.4), SSRI (aOR = 1.3, 95%CI 1.1–2.6), and smoking (aOR = 1.2, 95%CI 1.1–4.0) were independently associated with FVM lesions.

Conclusion

SSRI use during pregnancy was independently associated with adverse neonatal outcome and placental FVM.

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References

  1. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol. 2005;106:1071–83.

    PubMed  Google Scholar 

  2. Quevedo LA, Silva RA, Godoy R, Jansen K, Matos MB, Tavares Pinheiro KA, et al. The impact of maternal post-partum depression on the language development of children at 12 months. Child Care Health Dev. 2012;38:420–4.

    CAS  PubMed  Google Scholar 

  3. Grigoriadis S, VonderPorten EH, Mamisashvili L, Tomlinson G, Dennis C-L, Koren G, et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74:e321–41.

    PubMed  Google Scholar 

  4. Patten SB. Updated CANMAT guidelines for treatment of major depressive disorder. Can J Psychiatry. 2016;61:504–5.

  5. Lewis AJ, Galbally M, Opie G, Buist A. Neonatal growth outcomes at birth and one month postpartum following in utero exposure to antidepressant medication. Aust N. Z J Psychiatry. 2010;44:482–7.

    PubMed  Google Scholar 

  6. Suri R, Altshuler L, Hellemann G, Burt VK, Aquino A, Mintz J. Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. Am J Psychiatry. 2007;164:1206–13.

    PubMed  Google Scholar 

  7. Maschi S, Clavenna A, Campi R, Schiavetti B, Bernat M, Bonati M. Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study. BJOG. 2008;115:283–9.

    CAS  PubMed  Google Scholar 

  8. Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal antidepressant exposure. Am J Psychiatry. 2002;159:2055–61.

    PubMed  Google Scholar 

  9. Wen SW, Yang Q, Garner P, Fraser W, Olatunbosun O, Nimrod C, et al. Selective serotonin reuptake inhibitors and adverse pregnancy outcomes. Am J Obstet Gynecol. 2006;194:961–6.

    CAS  PubMed  Google Scholar 

  10. Malm H, Klaukka T, Neuvonen PJ. Risks associated with selective serotonin reuptake inhibitors in pregnancy. Obstet Gynecol. 2005;106:1289–96.

    CAS  PubMed  Google Scholar 

  11. Nordeng H, van Gelder MMHJ, Spigset O, Koren G, Einarson A, Eberhard-Gran M. Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study. J Clin Psychopharmacol. 2012;32:186–94.

    CAS  PubMed  Google Scholar 

  12. Tyson RW, Staat BC. The intrauterine growth-restricted fetus and placenta evaluation. Semin Perinatol. 2008;32:166–71.

    PubMed  Google Scholar 

  13. Vedmedovska N, Rezeberga D, Teibe U, Melderis I, Donders GGG. Placental pathology in fetal growth restriction. Eur J Obstet Gynecol Reprod Biol. 2011;155:36–40. https://doi.org/10.1016/j.ejogrb.2010.11.017.

    Article  PubMed  Google Scholar 

  14. Brosens I, Pijnenborg R, Vercruysse L, Romero R. The “great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011;204:193–201. https://doi.org/10.1016/j.ajog.2010.08.009.

    Article  PubMed  Google Scholar 

  15. Kovo M, Schreiber L, Bar J. Placental vascular pathology as a mechanism of disease in pregnancy complications. Thromb Res. 2013;131:S18–21.

    CAS  PubMed  Google Scholar 

  16. Weiner E, Schreiber L, Grinstein E, Feldstein O, Rymer-Haskel N, Bar J, et al. The placental component and obstetric outcome in severe preeclampsia with and without HELLP syndrome. Placenta. 2016;47:99–104.

    PubMed  Google Scholar 

  17. Kadyrov M, Kingdom JCP, Huppertz B. Divergent trophoblast invasion and apoptosis in placental bed spiral arteries from pregnancies complicated by maternal anemia and early-onset preeclampsia/intrauterine growth restriction. Am J Obstet Gynecol. 2006;194:557–63.

    PubMed  Google Scholar 

  18. Garmi G, Zafran N, Okopnik M, Gavish I, Romano S, Salim R. Placental pathological findings following adjusting enoxaparin dosage in thrombophilic women: secondary analysis of a randomized controlled trial. Thromb Haemost. 2019;119:87–91.

    PubMed  Google Scholar 

  19. Ortigosa S, Friguls B, Joya X, Martinez S, Marinoso ML, Alameda F, et al. Feto-placental morphological effects of prenatal exposure to drugs of abuse. Reprod Toxicol. 2012;34:73–9.

    CAS  PubMed  Google Scholar 

  20. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ task force on hypertension in pregnancy. Obstet Gynecol. 2013;122:1122–31.

  21. ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2013;122:706–17.

  22. ACOG Practice Bulletin No. 118: antiphospholipid syndrome. Obstet Gynecol. 2011;117:192–9.

  23. Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 190. Obstet Gynecol. 2018;131:e49–64.

    Google Scholar 

  24. ACOG Practice Bulletin No. 201. Obstet Gynecol. 2018;132:e228–48.

  25. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon E-S. Birth weight standards in the live-born population in Israel. Isr Med Assoc J. 2005;7:311–4.

  26. Hermansen CL, Lorah KN. Respiratory distress in the newborn. Am Fam Phys. 2007;76:987–94.

    Google Scholar 

  27. Andrade SE, Gurwitz JH, Davis RL, Chan KA, Finkelstein JA, Fortman K, et al. Prescription drug use in pregnancy. Am J Obstet Gynecol. 2004;191:398–407. https://doi.org/10.1016/j.ajog.2004.04.025.

    Article  PubMed  Google Scholar 

  28. Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler M-A, et al. Sampling and definitions of placental lesions: amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. 2016;140:698–713.

    PubMed  Google Scholar 

  29. Redline RW. Classification of placental lesions. Am J Obstet Gynecol. 2015;213 Suppl 4:S21–8.

    PubMed  Google Scholar 

  30. Levy M, Mizrachi Y, Leytes S, Weiner E, Bar J, Schreiber L, et al. Can placental histopathology lesions predict recurrence of small for gestational age neonates? Reprod Sci. 2018;25:1485–91.

    PubMed  Google Scholar 

  31. Weiner E, Mizrachi Y, Grinstein E, Feldstein O, Rymer-Haskel N, Juravel E, et al. The role of placental histopathological lesions in predicting recurrence of preeclampsia. Prenat Diagn. 2016;36:953–60.

    CAS  PubMed  Google Scholar 

  32. Pinar H, Sung CJ, Oyer CE, Singer DB. Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med. 1996;16:901–7.

    CAS  PubMed  Google Scholar 

  33. Fox GE, Van Wesep R, Resau JH, Sun CC. The effect of immersion formaldehyde fixation on human placental weight. Arch Pathol Lab Med. 1991;115:726–8.

    CAS  PubMed  Google Scholar 

  34. Viktorin A, Lichtenstein P, Lundholm C, Almqvist C, D’Onofrio BM, Larsson H, et al. Selective serotonin re-uptake inhibitor use during pregnancy: association with offspring birth size and gestational age. Int J Epidemiol. 2016;45:170–7.

    PubMed  Google Scholar 

  35. Huang H, Coleman S, Bridge JA, Yonkers K, Katon W. A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry. 2014;36:13–8.

  36. Ross LE, Grigoriadis S, Mamisashvili L, Vonderporten EH, Roerecke M, Rehm J, et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. 2013;70:436–43.

    PubMed  Google Scholar 

  37. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N. Engl J Med. 2006;354:579–87.

    CAS  PubMed  Google Scholar 

  38. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med. 1996;335(Oct):1010–5.

    CAS  PubMed  Google Scholar 

  39. Millard SJ, Weston-Green K, Newell KA. The effects of maternal antidepressant use on offspring behaviour and brain development: Implications for risk of neurodevelopmental disorders. Neurosci Biobehav Rev. 2017;80:743–65. http://www.sciencedirect.com/science/article/pii/S0149763417302804.

    CAS  PubMed  Google Scholar 

  40. Lugo-Candelas C, Cha J, Hong S, Bastidas V, Weissman M, Fifer WP, et al. Associations between brain structure and connectivity in infants and exposure to selective serotonin reuptake inhibitors during pregnancy. JAMA Pediatr. 2018;172:525–33.

    PubMed  PubMed Central  Google Scholar 

  41. Boukhris T, Sheehy O, Mottron L, Berard A. Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatr. 2016;170:117–24.

    PubMed  Google Scholar 

  42. Szegda K, Markenson G, Bertone-Johnson ER, Chasan-Taber L. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960–7.

    PubMed  Google Scholar 

  43. Pearson RM, Melotti R, Heron J, Joinson C, Stein A, Ramchandani PG, et al. Disruption to the development of maternal responsiveness? The impact of prenatal depression on mother-infant interactions. Infant Behav Dev. 2012;35:613–26.

    CAS  PubMed  Google Scholar 

  44. Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295:499–507.

    CAS  PubMed  Google Scholar 

  45. Suri R, Altshuler L, Hendrick V, Rasgon N, Lee E, Mintz J. The impact of depression and fluoxetine treatment on obstetrical outcome. Arch Women’s Ment Health. 2004;7:193–200.

    CAS  Google Scholar 

  46. Sorensen MJ, Gronborg 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.

    PubMed  PubMed Central  Google Scholar 

  47. Yonkers KA, Wisner KL, Stewart DE, Oberlander TF, Dell DL, Stotland N, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114:703–13.

    PubMed Central  Google Scholar 

  48. Kim YM, Bujold E, Chaiworapongsa T, Gomez R, Yoon BH, Thaler HT, et al. Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2003;189:1063–9.

    PubMed  Google Scholar 

  49. Redline RW, Ravishankar S. Fetal vascular malperfusion, an update. APMIS. 2018;126:561–9.

    PubMed  Google Scholar 

  50. Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011;37:501–14.

    CAS  PubMed  Google Scholar 

  51. Redline RW. Placental pathology and cerebral palsy. Clin Perinatol. 2006;33:503–16.

    PubMed  Google Scholar 

  52. Salafia CM, Pezzullo JC, Ghidini A, Lopez-Zeno JA, Whittington SS. Clinical correlations of patterns of placental pathology in preterm pre-eclampsia. Placenta. 1998;19:67–72.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Obstetrics & Gynecology, The Edith Wolfson Medical Center, Holon, Israel

    Michal Levy, Michal Kovo, Hadas Miremberg, Noa Anchel, Hadas Ganer Herman, Jacob Bar & Eran Weiner

  2. Department of Pathology, The Edith Wolfson Medical Center, Holon, Israel

    Letizia Schreiber

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Letizia Schreiber

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  1. Michal Levy
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Correspondence to Michal Levy.

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This study will be presented in the annual meeting of the American Society for Maternal-Fetal Medicine, Grapevine, Texas, February 2020.

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Levy, M., Kovo, M., Miremberg, H. et al. Maternal use of selective serotonin reuptake inhibitors (SSRI) during pregnancy—neonatal outcomes in correlation with placental histopathology. J Perinatol 40, 1017–1024 (2020). https://doi.org/10.1038/s41372-020-0598-0

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