Pediatric Cardiology

, Volume 34, Issue 1, pp 149–154 | Cite as

Association Between Blood Spot Transforming Growth Factor-β and Patent Ductus Arteriosus in Extremely Low-Birth Weight Infants

  • Girija NatarajanEmail author
  • Seetha Shankaran
  • Scott A. McDonald
  • Abhik Das
  • Richard A. Ehrenkranz
  • Ronald N. Goldberg
  • Barbara J. Stoll
  • Jon E. Tyson
  • Rosemary D. Higgins
  • Diana Schendel
  • David M Hougaard
  • Kristin Skogstrand
  • Poul Thorsen
  • Waldemar A. Carlo
Original Article


Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-β appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-β on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-β measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-β on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642–1,896]; median 1,386 pg/ml [range 868–1,913]) compared with others without PDA (median 1,334 pg/ml [range 760–2,064]; median 1,712 pg/ml [range 1,014–2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-β levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-β was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83–1.17; day 7 OR 0.88, 95 % CI 0.74–1.04) on adjusted analyses. Our results suggest that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.


Transforming growth factor Patent ductus arteriosus Preterm Neonate 



Patent ductus arteriosus


Extremely low birth weight


Transforming growth factor



Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Department of Health and Human Services (Grants No. U10 HD21385, U10 HD40689, U10 HD 27871, U10 HD21373, U10 HD36790, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851, and R03 HD054420) and from the National Institutes of Health (Grants No. GCRC M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01 RR 00039, and 5 M01 RR00044). The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Centers for Disease Control and Prevention provided grant support for recruitment for 1999 through 2001 and data analysis for the Neonatal Research Network’s Cytokines Study. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. Data collected at participating NRN sites were transmitted to RTI International, the data-coordinating center (DCC) for the NRN, which stored, managed, and analyzed the data for this study. On behalf of the network, Abhik Das (DCC PI) and Scott A. McDonald (DCC statistician) had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. We are indebted to our medical and nursing colleagues as well as the infants and their parents who agreed to take part in this study.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Girija Natarajan
    • 1
    Email author
  • Seetha Shankaran
    • 1
  • Scott A. McDonald
    • 2
  • Abhik Das
    • 3
  • Richard A. Ehrenkranz
    • 4
  • Ronald N. Goldberg
    • 5
  • Barbara J. Stoll
    • 6
  • Jon E. Tyson
    • 7
  • Rosemary D. Higgins
    • 8
  • Diana Schendel
    • 9
  • David M Hougaard
    • 10
  • Kristin Skogstrand
    • 10
  • Poul Thorsen
    • 11
    • 12
  • Waldemar A. Carlo
    • 13
  1. 1.Department of PediatricsWayne State University School of MedicineDetroitUSA
  2. 2.Department of Statistics and EpidemiologyRTI International, Research Triangle ParkDurhamUSA
  3. 3.Department of Statistics and EpidemiologyRTI InternationalRockvilleUSA
  4. 4.Department of PediatricsYale University School of MedicineNew HavenUSA
  5. 5.Department of PediatricsDuke UniversityDurhamUSA
  6. 6.Department of PediatricsEmory UniversityAtlantaUSA
  7. 7.Department of PediatricsUniversity of Texas Medical School at HoustonHoustonUSA
  8. 8.Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBethesdaUSA
  9. 9.National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionAtlantaUSA
  10. 10.Section of Neonatal Screening and Hormones, Department of Clinical Biochemistry and ImmunologyStatens Serum InstitutCopenhagenDenmark
  11. 11.Department of Obstetrics and GynecologyLillebaelt HospitalKoldingDenmark
  12. 12.Rollins School of Public HealthEmory UniversityAtlantaUSA
  13. 13.Department of PediatricsUniversity of Alabama at BirminghamBirminghamUSA

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