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.

  • Original Article
  • Published:

Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia

Journal of Perinatology volume 33, pages 553–557 (2013)Cite this article

Subjects

Abstract

Objective:

To identify the association between birth weight (BW)-for-gestational age (GA) and pulmonary hypertension (PHTN) at 36 weeks in infants with moderate–severe bronchopulmonary dysplasia (BPD).

Study Design:

In this retrospective cohort study, we followed 138 premature infants (⩽28 weeks) with moderate and severe BPD (National Institutes of Health consensus definition) born at Prentice Women’s Hospital between 2005 and 2009. BW percentiles were calculated using the Fenton growth curve for premature infants. PHTN was determined using a standardized algorithm of echocardiogram review at 36 weeks. Logistic regression was used to evaluate the associations between BW percentile subgroups and PHTN, taking into account antenatal and neonatal factors that were related to PHTN.

Result:

PHTN was associated with small BW-for-GA, ranging from thresholds of <10th to <25th percentile (P<0.001). These associations remained significant when comparing BW <25th percentile to the reference group (50 to 89th percentile); after adjustment for GA, gender, multiple gestation, race/ethnicity (odds ratio (OR)=4.2; 95% confidence interval (CI)=1.5, 12.1); and after further adjustment for maternal vascular disease, intrauterine infection, oligohydramnios and relevant postnatal factors (OR=5.7; 95% CI=1.5, 21.2). Longitudinal follow-up of this cohort showed a trend toward higher morbidity and death among PHTN infants with BW <25th percentile.

Conclusion:

BW-for-GA is an important predictor of PHTN in premature infants with moderate–severe BPD. Our findings contribute to the growing evidence supporting fetal mechanisms of later onset pulmonary vascular disease.

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

Figure 1

Similar content being viewed by others

References

  1. An HS, Bae EJ, Kim GB, Kwon BS, Beak JS, Kim EK et al. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Korean Circ J 2010; 40 (3): 131–136.

    Article  Google Scholar 

  2. Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 2007; 120 (6): 1260–1269.

    Article  Google Scholar 

  3. Slaughter JL, Pakrashi T, Jones DE, South AP, Shah TA . Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation. J Perinatol 2011; 31 (10): 635–640.

    Article  CAS  Google Scholar 

  4. Mourani PM, Mullen M, Abman SH . Pulmonary hypertension in bronchopulmonary dysplasia. Prog Pediatr Cardiol 2009; 27 (1-2): 43–48.

    Article  Google Scholar 

  5. Bose C, Van Marter LJ, Laughon M, O’Shea TM, Allred EN, Karna P et al. Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation. Pediatrics 2009; 124 (3): e450–e458.

    Article  Google Scholar 

  6. Lal MK, Manktelow BN, Draper ES, Field DJ . Chronic lung disease of prematurity and intrauterine growth retardation: a population-based study. Pediatrics 2003; 111 (3): 483–487.

    Article  Google Scholar 

  7. Rozance PJ, Seedorf GJ, Brown A, Roe G, O’Meara MC, Gien J et al. Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep. Am J Physiol Lung Cell Mol Physiol 2011; 301 (6): L860–L871.

    Article  CAS  Google Scholar 

  8. Rueda-Clausen CF, Morton JS, Davidge ST . Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood. Cardiovasc Res 2009; 81 (4): 713–722.

    Article  CAS  Google Scholar 

  9. Bhat R, Salas AA, Foster C, Carlo WA, Ambalavanan N . Prospective analysis of pulmonary hypertension in extremely low birth weight infants. Pediatrics 2012; 129 (3): e682–e689.

    Article  Google Scholar 

  10. Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA et al. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics 2005; 116 (6): 1353–1360.

    Article  Google Scholar 

  11. Denton CP, Cailes JB, Phillips GD, Wells AU, Black CM, Bois RM . Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Br J Rheumatol 1997; 36 (2): 239–243.

    Article  CAS  Google Scholar 

  12. Galie N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The task force on diagnosis and treatment of pulmonary arterial hypertension of the European Society of Cardiology. Eur Heart J 2004; 25 (24): 2243–2278.

    Article  Google Scholar 

  13. Porta N, Wax DF, Lestrud SO, Beier JM, Gotteiner NL . Echocardiographic assessment of ventricular dimensions predict degree of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Pediat Res 2010 E-PAS2010 3708.

  14. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 101: ultrasonography in pregnancy. Obstet Gynecol 2009; 113 (2 Pt 1): 451–461.

    Google Scholar 

  15. Fenton TR . A new growth chart for preterm babies: Babson and Benda’s chart updated with recent data and a new format. BMC Pediatr 2003; 3: 13.

    Article  Google Scholar 

  16. ACOG Committee on Obstetric Practice ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002; 77 (1): 67–75.

    Article  Google Scholar 

  17. Papile LA, Burstein J, Burstein R, Koffler H . Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 gm. J Pediatr 1978; 92 (4): 529–534.

    Article  CAS  Google Scholar 

  18. Walsh MC, Kliegman RM . Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33 (1): 179–201.

    Article  CAS  Google Scholar 

  19. Barker DJ . The fetal and infant origins of disease. Eur J Clin Invest 1995; 25 (7): 457–463.

    Article  CAS  Google Scholar 

  20. Jayet PY, Rimoldi SF, Stuber T, Salmon CS, Hutter D, Rexhaj E et al. Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia. Circulation 2010; 122 (5): 488–494.

    Article  Google Scholar 

  21. Kim DH, Kim HS, Choi CW, Kim EK, Kim BI, Choi JH . Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology 2012; 101 (1): 40–46.

    Article  Google Scholar 

  22. Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B . Annual summary of vital statistics: 2004. Pediatrics 2006; 117 (1): 168–183.

    Article  Google Scholar 

  23. Zeitlin J, Ancel PY, Saurel-Cubizolles MJ, Papiernik E . The relationship between intrauterine growth restriction and preterm delivery: an empirical approach using data from a European case-control study. Br J Obstet Gynaecol 2000; 107 (6): 750–758.

    Article  CAS  Google Scholar 

  24. Zeitlin J, El Ayoubi M, Jarreau PH, Draper ES, Blondel B, Kunzel W et al. Impact of fetal growth restriction on mortality and morbidity in a very preterm birth cohort. J Pediatr 2010; 157 (5): 733–9 e1.

    Article  Google Scholar 

  25. Mourani PM, Sontag MK, Younoszai A, Ivy DD, Abman SH . Clinical utility of echocardiography for the diagnosis and management of pulmonary vascular disease in young children with chronic lung disease. Pediatrics 2008; 121 (2): 317–325.

    Article  Google Scholar 

Download references

Acknowledgements

This project was supported by NHLBI Grant K23 HL093302 (PI: Mestan).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    J Check, N Porta, R Steinhorn & K K Mestan

  2. Department of Pediatrics, Division of Cardiology, Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    N Gotteiner

  3. Department of Pediatrics, Mary Ann and J Milburn Smith Child Health Research Program, Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    X Liu

  4. Department of Obstetrics and Gynecology, Divisions of Maternal Fetal Medicine and Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    E Su

Authors
  1. J Check
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Gotteiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. X Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Porta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Steinhorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K K Mestan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K K Mestan.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Check, J., Gotteiner, N., Liu, X. et al. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia. J Perinatol 33, 553–557 (2013). https://doi.org/10.1038/jp.2012.164

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2012.164

Keywords

This article is cited by

Search

Advanced search

Quick links