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Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study

Journal of Perinatology volume 42, pages 1183–1188 (2022)Cite this article

Subjects

Abstract

Background

Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA).

Methods

We used the multicenter Diaphragmatic Hernia Research & Exploration Advancing Molecular Science (DHREAMS) study to include neonates enrolled from 2005 to 2019. Chi-squared or Fisher’s exact tests were used to compare categorical variables and t tests or Wilcoxon rank sum for continuous variables. Cox model analyzed time to event outcomes and logistic regression analyzed binary outcomes.

Results

589 neonates were examined. Ninety were SGA (15.3%). SGA patients were more likely to be female (p = 0.003), have a left sided CDH (p = 0.05), have additional congenital anomalies and be diagnosed with a genetic syndrome (p < 0.001). On initial single-variable analysis, SGA correlated with higher frequency of death prior to discharge (p < 0.001) and supplemental oxygen requirement at 28 days (p = 0.005). Twice as many SGA patients died before repair (12.2% vs 6.4%, p = 0.04). Using unadjusted Cox model, the risk of death prior to discharge among SGA patients was 1.57 times the risk for AGA patients (p = 0.029). There was no correlation between SGA and need for ECMO, pulmonary hypertensive medication at discharge or oxygen at discharge. After adjusting for confounding variables, SGA no longer correlated with mortality prior to discharge or incidence of unrepaired defects but remained significant for oxygen requirement at 28 days (p = 0.03).

Conclusion

Infants with CDH who are SGA have worse survival and poorer lung function than AGA infants. However, the outcome of SGA neonates is impacted by other factors including gestational age, genetic syndromes, and particularly congenital anomalies that contribute heavily to their poorer prognosis.

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Acknowledgements

Institutions contributing data to the study included: Columbia University Irving Medical Center, St Louis Children’s Hospital, Children’s Hospital of Pittsburgh, Cincinnati Children’s Hospital and Medical Center, Omaha Children’s Hospital, University of Michigan Mott’s Children’s Hospital, Vanderbilt Children’s Hospital, Wisconsin Children’s Hospital, Cohen Children’s Medical Center- Northwell Health, Oregon Health and Science University, Meriter-Unity Point Health in Madison, UT Southwestern Medical Center. We would like to thank the patients and their families for their generous contribution. We are grateful for the technical assistance provided by Patricia Lanzano, Jiangyuan Hu, Jiancheng Guo, and Liyong Deng, from Columbia University. We thank our clinical coordinators across the DHREAMS centers: Jessica Conway at Washington University School of Medicine, Melissa Reed, Elizabeth Erickson, and Madeline Peters at Cincinnati Children’s Hospital, Sheila Horak at Children’s Hospital & Medical Center of Omaha, Jeannie Kreutzman and Irene St. Charles at CS Mott Children’s Hospital, Tracy Perry at Monroe Carell Jr. Children’s Hospital, Dr. Michelle Kallis at Northwell Health, Andrew Mason and Alicia McIntire at Oregon Health and Science University, Gentry Wools and Lorrie Burkhalter at Children’s Medical Center Dallas, Elizabeth Jehle at Hassenfeld Children’s Hospital, Michelle Knezevich and Cheryl Kornberg at Medical College of Wisconsin, Min Shi at Children’s Hospital of Pittsburgh. Funding support was provided by grants from CHERUBS, CDHUK, and the National Greek Orthodox Ladies Philoptochos Society, Inc. and generous donations from the Williams Family, Wheeler Foundation, Vanech Family Foundation, Larsen Family, Wilke Family and many other families. The authors declare that there was no funding provided for this study. Meeting Presentation: American College of Surgeons, San Francisco, CA. October 2019.

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Authors and Affiliations

  1. Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA

    A. Zenilman, A. Abramov, G. Aspelund & V. P. Duron

  2. Department of Biostatistics, Columbia University Irving Medical Center, New York, NY, USA

    W. Fan

  3. Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA

    R. Hernan, J. Wynn & W. K. Chung

  4. Department of Neonatology, Columbia University Irving Medical Center, New York, NY, USA

    C. Farkouh-Karoleski

  5. Department of Pediatric Cardiology, Columbia University Irving Medical Center, New York, NY, USA

    U. S. Krishnan

  6. Department of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University Irving Medical Center, New York, NY, USA

    J. Khlevner

  7. Pediatric Surgery Division, Department of Surgery, Oregon Health & Science University, Portland, OR, USA

    K. Azarow

  8. Division of Pediatric General, Thoracic, and Fetal Surgery, Center for Molecular Fetal Therapy, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    T. Crombleholme

  9. Division of Pediatric Surgery, University of Nebraska Medical Center College of Medicine, Omaha, NE, USA

    R. Cusick

  10. Department of Pediatric Surgery, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN, USA

    D. Chung & M. E. Danko

  11. Division of Pediatric Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    D. Potoka

  12. Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Fetal Care Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    F. Y. Lim

  13. Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA

    D. J. McCulley

  14. Section of Pediatric Surgery, Fetal Diagnosis and Treatment Center, University of Michigan Health System, Ann Arbor, MI, USA

    G. B. Mychaliska

  15. Division of Pediatric Surgery, UT Southwestern Medical Center, Dallas, TX, USA

    D. Schindel

  16. Department of Pediatric Surgery, Northwell Health, New York, NY, USA

    S. Soffer

  17. Division of Pediatric Surgery, Children’s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA

    A. J. Wagner

  18. Division of Pediatric Surgery, Washington University School of Medicine, St. Louis, MO, USA

    B. W. Warner

  19. Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    W. K. Chung

  20. Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA

    W. K. Chung

Authors
  1. A. Zenilman
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  4. J. Wynn
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  24. V. P. Duron
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Contributions

AZ: primary author, database organization, interpretation of results, compilation of tables, manuscript writing. WF: statistician, interpretation of results, manuscript editing. RH: collection of data, coordination across the sites active in DHREAMS database in organization of data, manuscript editing. JW: collection of data, coordination across the sites active in DHREAMS database in organization of data, manuscript editing. AA: interpretation of data, table organization, manuscript writing and editing. CFK: data contribution, organization of data, manuscript editing. GA: data contribution, organization of data, manuscript editing. USK: data contribution, organization of data, manuscript editing. GA: data contribution, organization of data, manuscript editing. JK: data contribution, organization of data, manuscript editing. KA: data contribution, organization of data, manuscript editing. TC: data contribution, organization of data, manuscript editing. RC: data contribution, organization of data, manuscript editing. DC: data contribution, organization of data, manuscript editing. MED: data contribution, organization of data, manuscript editing. DP: data contribution, organization of data, manuscript editing. FYL: data contribution, organization of data, manuscript editing. DJM: data contribution, organization of data, manuscript editing. GBM: data contribution, organization of data, manuscript editing. DS: data contribution, organization of data, manuscript editing. SS: data contribution, organization of data, manuscript editing. AJW: data contribution, organization of data, manuscript editing. WKC: data contribution, organization of data, manuscript editing. VPD: collection of data, coordination across the sites active in DHREAMS database in organization of data, outline of manuscript, manuscript editing.

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Correspondence to A. Zenilman.

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Zenilman, A., Fan, W., Hernan, R. et al. Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study. J Perinatol 42, 1183–1188 (2022). https://doi.org/10.1038/s41372-022-01326-4

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