Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Prenatal selective serotonin reuptake inhibitors and therapeutic hypothermia for suspected hypoxic ischemic encephalopathy

Journal of Perinatology volume 40, pages 640–645 (2020)Cite this article

Subjects

Abstract

Objective

To evaluate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and postnatal therapeutic hypothermia for suspected hypoxic ischemic encephalopathy.

Study design

Matched case-control study of singleton deliveries at a tertiary hospital from 2010 to 2016. Cases were infants treated with therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Controls were noncase infants, matched on gestational age, maternal age, obstetric provider group, and hospital shift.

Result

Prenatal SSRI exposure occurred in 18.4% of cases compared with 4.1% of controls (aOR: 5.9, 95% CI: 1.8–19.7). Among all cases, 36.8% had evidence of hypoxic ischemic encephalopathy on postnatal MRI. In addition, 28.6% of SSRI-exposed cases and 38.7% of SSRI-unexposed cases had MRI confirmation of hypoxic ischemic encephalopathy, respectively.

Conclusion

Future research to disentangle signs of SSRI exposure from true hypoxic ischemic encephalopathy may facilitate targeting therapeutic hypothermia stewardship toward infants more likely to benefit.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bennett HA, Einarson A, Taddio A, Koren G, Einarson TR. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol. 2004;103:698–709.

    Article  Google Scholar 

  2. Cooper WO, Willy ME, Pont SJ, Ray WA. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol. 2007;196:1–5.

    Article  Google Scholar 

  3. Alwan S, Friedman JM, Chambers C. Safety of selective serotonin reuptake inhibitors in pregnancy: a review of current evidence. CNS Drugs. 2016;30:499–515.

    Article  CAS  Google Scholar 

  4. Sie SD, Wennink JMB, van Driel JJ, te Winkel AGW, Boer K, Casteelen G, et al. Maternal use of SSRIs, SNRIs and NaSSAs: practical recommendations during pregnancy and lactation. Arch Dis Child Fetal Neonatal Ed. 2012;97:F472–6.

    Article  CAS  Google Scholar 

  5. Rampono J, Simmer K, Ilett KF, Hackett LP, Doherty DA, Elliot R, et al. Placental transfer of SSRI and SNRI antidepressants and effects on the neonate. Pharmacopsychiatry. 2009;42:95–100.

    Article  CAS  Google Scholar 

  6. de Vries NKS, 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.

    Article  Google Scholar 

  7. Zhang TN, Gao SY, Shen ZQ, Li D, Liu CX, Lv HC, et al. Use of selective serotonin-reuptake inhibitors in the first trimester and risk of cardiovascular-related malformations: a meta-analysis of cohort studies. Sci Rep. 2017;7:1–9.

    Article  Google Scholar 

  8. Jensen HM, Grøn R, Lidegaard Ø, Pedersen LH, Andersen PK, Kessing LV. Maternal depression, antidepressantuse in pregnancy and Apgar scores in infants. Br J Psychiatry. 2013;202:347–51.

    Article  Google Scholar 

  9. Domar AD, Moragianni VA, Ryley DA, Urato AC. The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond. Hum Reprod. 2013;28:160–71.

    Article  CAS  Google Scholar 

  10. Bot P, Semmekrot BA, Van Der Stappen J. Neonatal effects of exposure to selective serotonin reuptake inhibitors during pregnancy. Arch Dis Child Fetal Neonatal Ed. 2006;91:2006.

    Article  Google Scholar 

  11. Bakaysa SL, Kelly J, Urato A. Does SSRI antidepressant use influence APGAR scores? [29N]. Obstet Gynecol. 2016;127:122S.

  12. 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;10033:1–9.

    Google Scholar 

  13. Ehrenstein V. Association of Apgar scores with death and neurologic disability. Clin Epidemiol. 2009;1:45–53.

    Article  Google Scholar 

  14. Jacobs SE, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cochrane review: cooling for newborns with hypoxic ischaemic encephalopathy. Evid-Based Child Heal A Cochrane Rev J. 2010;5:474–531.

    Article  Google Scholar 

  15. Shah PS, Ohlsson A, Perlman M. Hypothermia to treat neonatal hypoxic ischemic encephalopathy: systematic review. Arch Pediatr Adolesc Med. 2007;161:951–8.

    Article  Google Scholar 

  16. Zhou WH, Cheng GQ, Shao XM, Liu XZ, Shan RB, Zhuang DY, et al. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr. 2010;157:367–372.e3.

    Article  Google Scholar 

  17. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165:692–700.

    Article  Google Scholar 

  18. Azzopardi D, Brocklehurst P, Edwards D, Halliday H, Levene M, Thoresen M, et al. The TOBY study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr. 2008;8:1–12.

    Article  Google Scholar 

  19. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. Lancet. 2005;365:663–70.

    Article  Google Scholar 

  20. McGuire W. Perinatal asphyxia. BMJ Clin Evid. 2007;2007:0320.

  21. Akisu M, Huseyinov A, Yalaz M, Cetin H, Kultursay N. Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia. Prostaglandins Leukot Ess Fat Acids. 2003;69:45–50.

    Article  CAS  Google Scholar 

  22. Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol. 2005;32:11–7.

    Article  Google Scholar 

  23. Battin MR, Uk M, Dezoete JA, Gunn TR, Gluckman PD, Gunn AJ, et al. Mild hypothermia after perinatal asphyxia. Pediatrics 2001;107:480–4.

  24. Huang H-C, Sung F-C, Chen P-C, Chang CY-Y, Muo C-H, Shiue H-S, et al. Obstetric outcomes in pregnant women with and without depression: population-based comparison. Sci Rep. 2017;7:13937.

    Article  Google Scholar 

  25. Shankaran S, Laptook A, Wright LL, Ehrenkranz RA, Donovan EF, Fanaroff AA, et al. Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics. 2002;110:377–85.

    Article  Google Scholar 

  26. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic ischemic encephalopathy. N. Eng. J. Med. 2009;1574–84. https://doi.org/10.1056/NEJMcps050929.

  27. Simbruner G, Mittal RA, Rohlmann F, Muche R. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010;126:e771–8.

    Article  Google Scholar 

  28. Karnatovskaia LV, Wartenberg KE, Freeman WD. Therapeutic hypothermia for neuroprotection: history, mechanisms, risks, and clinical applications. Neurohospitalist. 2014;4:153–63.

    Article  Google Scholar 

  29. Schulzke SM, Rao S, Patole SK. A systematic review of cooling for neuroprotection in neonates with hypoxic ischemic encephalopathy - are we there yet? BMC Pediatr. 2007;7:30.

    Article  Google Scholar 

  30. Papile LA, Baley JE, Benitz W, Cummings J, Carlo WA, Eichenwald E, et al. Clinical Report: hypothermia and neonatal encephalopathy. Pediatrics. 2014;133:1146–50.

  31. Therapeutic Hypothermia: CritiCool Checklists. Boston, MA; 2016.

  32. Walsh BH, Neil J, Morey J, Yang E, Silvera MV, Inder TE, et al. The frequency and severity of magnetic resonance imaging abnormalities in infants with mild neonatal encephalopathy. J Pediatr. 2017;187:26–33.e1.

    Article  Google Scholar 

Download references

Funding

This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. NIH/NIEHS grant K23ES022242 supported HHB time during the project.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Dayna T. Neo, Michele R. Hacker & Brianne Mahoney

  2. University of Massachusetts Medical School, Worcester, MA, USA

    Emily Nuss

  3. Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA

    Michele R. Hacker

  4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Michele R. Hacker

  5. Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Heather H. Burris

  6. Division of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Heather H. Burris

  7. Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA

    Heather H. Burris

Authors
  1. Dayna T. Neo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emily Nuss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michele R. Hacker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brianne Mahoney
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heather H. Burris
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HHB and MRH conceptualized and designed the study, assisted in data analysis, and critically reviewed and revised the manuscript. DTN designed the data collection instruments, collected data, carried out the data analysis, drafted the initial manuscript, and critically reviewed and revised the manuscript. EN collected data and critically reviewed and revised the manuscript. BM assisted in data interpretation and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Heather H. Burris.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Neo, D.T., Nuss, E., Hacker, M.R. et al. Prenatal selective serotonin reuptake inhibitors and therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. J Perinatol 40, 640–645 (2020). https://doi.org/10.1038/s41372-019-0564-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-019-0564-x

Search

Advanced search

Quick links