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:

Association of chorioamnionitis and patent ductus arteriosus in a national U.S. cohort

Journal of Perinatology volume 41, pages 119–125 (2021)Cite this article

Subjects

Abstract

Objective

To estimate the effect of clinical chorioamnionitis on the risk of patent ductus arteriosus (PDA).

Study design

A secondary analysis of all deliveries >23 gestational weeks from the U.S. Consortium on Safe Labor (CSL) study. The primary exposure was a clinical diagnosis of chorioamnionitis, and the outcome was a diagnosis of PDA. Generalized estimating equations with estimated error variance for women with multiple deliveries were utilized. Models adjusted for age, race, region, delivery year, body mass index, infant sex, multiple gestation, mode of delivery, and antenatal corticosteroid exposure.

Results

Among 228,438 deliveries, a diagnosis of PDA was more frequent with chorioamnionitis exposure versus without (9.2% vs. 3.0%; OR: 3.25; 95% CI: 2.92–3.62). Chorioamnionitis was associated with higher adjusted odds of PDA (AOR: 2.18; 95% CI: 1.93–2.45). In sensitivity analyses, the association between chorioamnionitis and PDA held after adjustment for gestational age at delivery (AOR: 1.28; 95% CI: 1.13–1.44).

Conclusions

Chorioamnionitis was associated with increased odds of PDA. Robust exposure and outcome ascertainment with careful assessment of confounding is needed to further investigate this epidemiologic association.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • 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. ACOG Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection.

  2. Peng CC, Chang JH, Lin HY, Cheng PJ, Su BH. Intrauterine inflammation, infection, or both (Triple I): a new concept for chorioamnionitis. Pediatr Neonatol. 2018;59:231–7.

    Article  Google Scholar 

  3. Venkatesh K, Jackson W, Hughes BL, Laughon MM, Thorp JM, Stamilio DM. Association of chorioamnionitis and its duration with neonatal morbidity and mortality. J Perinatol. 2019;39:673.

    Article  Google Scholar 

  4. Venkatesh K, Glover A, Vladutiu C, Stamilio D. Association of chorioamnionitis and adverse maternal outcomes by mode of delivery. Br J Obstet Gynecol. 2018;126:719.

    Article  Google Scholar 

  5. Tita A, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol. 2010;37:339–54.

    Article  Google Scholar 

  6. Hartling L, Liang Y, Lacaze-Masmonteil T. Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F8–17.

    Article  Google Scholar 

  7. Been JV, Lievense S, Zimmermann LJI, Kramer BW, Wolfs TGAM. Chorioamnionitis as a risk factor for necrotizing enterocolitis: a systematic review and meta-analysis. J Pediatr. 2013;162:236–.e232.

    Article  Google Scholar 

  8. Arayici S, Kadioglu Simsek G, Oncel MY, et al. The effect of histological chorioamnionitis on the short-term outcome of preterm infants ≤32 weeks: a single-center study. J Matern-Fetal Neonatal Med. 2014;27:1129–33.

    Article  Google Scholar 

  9. Liu Z, Tang Z, Li J, Yang Y. Effects of placental inflammation on neonatal outcome in preterm infants. Pediatr Neonatol. 2014;55:35–40.

    Article  Google Scholar 

  10. Behbodi E, Villamor-martínez E, Degraeuwe PLJ, Villamor E. Chorioamnionitis appears not to be a risk factor for patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Sci Rep. 2016;6:37967.

    Article  CAS  Google Scholar 

  11. Dice JE, Bhatia J. Patent ductus arteriosus: an overview. J Pediatr Pharmacol Ther. 2007;12:138–46.

    PubMed  PubMed Central  Google Scholar 

  12. Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics. 2010;125:1020–30.

    Article  Google Scholar 

  13. Reese J, Veldman A, Shah L, Vucovich M, Cotton RB. Inadvertent relaxation of the ductus arteriosus by pharmacologic agents that are commonly used in the neonatal period. Semin Perinatol. 2010;34:222–30.

    Article  Google Scholar 

  14. Shelton E, Waleh N, Plosa EJ, et al. Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data. Pediatr Res. 2018;84:458–65.

    Article  CAS  Google Scholar 

  15. García-Muñoz Rodrigo F, Galán Henríquez G, Figueras Aloy J, García-Alix, Pérez A. Outcomes of very-low-birth-weight infants exposed to maternal clinical chorioamnionitis: a multicentre study. Neonatology. 2014;106:229–34.

    Article  Google Scholar 

  16. Kim ES, Kim Ek Fau - Choi CW, Choi Cw Fau -, Kim H-S, et al. Intrauterine inflammation as a risk factor for persistent ductus arteriosus patency after cyclooxygenase inhibition in extremely low birth weight infants. J Pediatr. 2010;157:745–.e741.

    Article  CAS  Google Scholar 

  17. Ryu YH, Oh S, Sohn J, Lee J. The associations between antenatal corticosteroids and in-hospital outcomes of preterm singleton appropriate for gestational age neonates according to the presence of maternal histologic chorioamnionitis. Neonatology. 2019;116:369–75.

    Article  CAS  Google Scholar 

  18. Ananth C, Schisterman EF. Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics. Am J Obstet Gynecol. 2017;217:167–75.

    Article  Google Scholar 

  19. Park HW, Choi Y-S, Kim KS, Kim S-N. Chorioamnionitis and patent ductus arteriosus: a systematic review and meta-analysis. PloS ONE. 2015;10:e0138114.

    Article  Google Scholar 

  20. Zhang J, Troendle J, Reddy UM, Laughon SK, Branch DW, Burkman R, et al. Contemporary cesarean delivery practice in the United States. Am J Obstet Gynecol. 2010;203:326.

    PubMed  PubMed Central  Google Scholar 

  21. Männistö T, Mendola P, Reddy U, Laughon SK. Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease. Am J Epidemiol. 2013;178:731–40.

    Article  Google Scholar 

  22. Venkatesh K, Glover AV, Vladutiu CJ, Stamilio DM. Association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery: a cohort study. BJOG. 2018;126:719.

    Article  Google Scholar 

  23. World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision. 2007; http://apps.who.int/classifications/apps/icd/icd10online/. Accessed 24 Jun 2009.

  24. Hutcheon J, Moskosky S, Ananth CV, Basso O, Briss PA, Ferré CD, et al. Good practices for the design, analysis, and interpretation of observational studies on birth spacing and perinatal health outcomes. Pediatr Perinat Epidemiol. 2019;33:O15–24.

    Google Scholar 

  25. Escobar G, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, et al. Stratification of risk of early-onset sepsis in newborns ≥34 weeks’ gestation. Pediatrics. 2014;133:30–6.

    Article  Google Scholar 

  26. Soraisham A, Singhal N, McMillan DD, Sauve RS, Lee SK. Canadian Neonatal Network. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol. 2009;200:e1–6.

    Article  Google Scholar 

  27. Pistulli E, Hamiti A, Buba S, Hoxha A, Kelmendi N, Vyshka G. The association between patent ductus arteriosus and perinatal infection in a group of low birth weight preterm infants. Iran J Pediatr. 2014;24:42–8.

    PubMed  Google Scholar 

  28. Kluckow M, Jeffery M, Gill A, Evans N. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed. 2014;99:F99–104.

    Article  Google Scholar 

  29. Marissen J, Erdmann H, Böckenholt K, Hoppenz M, Rausch TK, Härtel C, et al. German Neonatal Network. Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants. Acta Paediatr. 2020; https://doi.org/10.1111/apa.15541. Epub ahead of print.

  30. Elwert F, Winship C. Endogenous selection bias: the problem of conditioning on a collider variable. Annu Rev Sociol. 2014;40:31–53.

    Article  Google Scholar 

  31. Gillam-Krakauer M, Reese J. Diagnosis and management of patent ductus arteriosus. NeoReviews. 2018;19:e394–402.

    Article  Google Scholar 

  32. Halil H, Buyuktiryaki M, Atay FY, Oncel MY, Uras N. Reopening of the ductus arteriosus in preterm infants; clinical aspects and subsequent consequences. J Neonatal-Perinat Med. 2018;11:273–9.

    Article  CAS  Google Scholar 

  33. Gergawy M, Vollrath B, Fau -, Cook D, Cook D. The mechanism by which aminoglycoside antibiotics cause vasodilation of canine cerebral arteries. Br J Pharm. 1998;125:1150–7.

    Article  CAS  Google Scholar 

  34. Vucovich MM, Cotton RB, Shelton EL, et al. Aminoglycoside-mediated relaxation of the ductus arteriosus in sepsis-associated PDA. Am J Physiol Heart Circ Physiol. 2014;307:732–40.

    Article  Google Scholar 

  35. Kishibuchi A, Akaike T, Minamisawa S. Standard-dose gentamicin does not increase risk of patent ductus arteriosus. Pediatr Neonatol. 2020;61:45–50.

    Article  Google Scholar 

  36. Fortescue E, Lock JE, Galvin T, McElhinney DB. To close or not to close: the very small patent ductus arteriosus. Congenit Heart Dis. 2010;5:354–65.

    Article  Google Scholar 

  37. Mirea L, Sankaran K, Seshia M, Ohlsson A, Allen AC, Aziz K, et al. Treatment of patent ductus arteriosus and neonatal mortality/morbidities: adjustment for treatment selection bias. J Pediatr. 2012;161:689–91.

    Article  Google Scholar 

  38. Elimian A, Verma U, Beneck D, Cipriano R, Visintainer P, Tejani N. Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes. Obstet Gynecol. 2000;96:333–6. https://doi.org/10.1016/s0029-7844(00)00928-5.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Institutions involved in the Consortium include, in alphabetical order: Baystate Medical Center, Springfield, MA; Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles, CA; Christiana Care Health System, Newark, DE; Georgetown University Hospital, MedStar Health, Washington, DC; Indiana University Clarian Health, Indianapolis, IN; Intermountain Healthcare and the University of Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, NY; MetroHealth Medical Center, Cleveland, OH.; Summa Health System, Akron City Hospital, Akron, OH; The EMMES Corporation, Rockville MD (Data Coordinating Center); University of Illinois at Chicago, Chicago, IL; University of Miami, Miami, FL; and University of Texas Health Science Center at Houston, Houston, Texas.

Acknowledgement of financial support

Supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The Consortium on Safe Labor was funded by the Intramural Research Program of the NICHD, through Contract No. HHSN267200603425C. The study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Intramural investigators designed the study and data was collected by clinical site investigators. The corresponding author has full access to the data and final responsibility for preparation and submission of the paper for publication. Additional funding support for MML was received from NIH K24 HL143283.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of North Carolina Chapel Hill, Chapel Hill, NC, USA

    Celeste A. Green & Robert A. Strauss

  2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina Chapel Hill, Chapel Hill, NC, USA

    Daniel Westreich

  3. Division of Neonatal Perinatal Medicine, Department of Pediatrics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA

    Matthew M. Laughon

  4. Department of Obstetrics and Gynecology, Wake Forest University, Winston-Salem, NC, USA

    David M. Stamilio

  5. Department of Pediatrics, Vanderbilt University, Nashville, TN, USA

    Jeff Reese & Elaine L. Shelton

  6. Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA

    Kartik K. Venkatesh

Authors
  1. Celeste A. Green
    View author publications

    Search author on:PubMed Google Scholar

  2. Daniel Westreich
    View author publications

    Search author on:PubMed Google Scholar

  3. Matthew M. Laughon
    View author publications

    Search author on:PubMed Google Scholar

  4. David M. Stamilio
    View author publications

    Search author on:PubMed Google Scholar

  5. Robert A. Strauss
    View author publications

    Search author on:PubMed Google Scholar

  6. Jeff Reese
    View author publications

    Search author on:PubMed Google Scholar

  7. Elaine L. Shelton
    View author publications

    Search author on:PubMed Google Scholar

  8. Kartik K. Venkatesh
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Kartik K. Venkatesh.

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.

This manuscript was presented as an oral presentation at the Infectious Diseases for Obstetrics and Gynecology (IDSOG) Annual Meeting, August 15, 2020.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Green, C.A., Westreich, D., Laughon, M.M. et al. Association of chorioamnionitis and patent ductus arteriosus in a national U.S. cohort. J Perinatol 41, 119–125 (2021). https://doi.org/10.1038/s41372-020-00866-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41372-020-00866-x

This article is cited by

Search

Advanced search

Quick links