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Hypoxemia in infants with trisomy 21 in the neonatal intensive care unit

Abstract

Objective

Newborns with trisomy 21 (T21) often require NICU hospitalization. Oxygen desaturations are frequently observed in these infants, even in the absence of congenital heart defects (CHD). We hypothesized that NICU patients with T21 have more hypoxemia than those without T21.

Design

All infants with T21 without significant CHD discharged home from the NICU between 2009 and 2018 were included (n = 23). Controls were matched 20:1 for gestational age and length of stay. We compared daily severe hypoxemia events (SpO2 < 80% for ≥10 s) for the whole NICU stay and the pre-discharge week.

Results

Infants with T21 showed significantly more daily hypoxemia events during their entire NICU stay (median 10 versus 7, p = 0.0064), and more so in their final week (13 versus 7, p = 0.0008).

Conclusion

NICU patients with T21 without CHD experience more severe hypoxemia events than controls, particularly in the week before discharge. Whether this hypoxemia predicts or contributes to adverse outcomes is unknown.

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Fig. 1: SpO2 trend in a representative infant with T21 and without T21.
Fig. 2: Distribution of all SpO2 values 60–80%.
Fig. 3: Number of events of desaturation <80% per day for infants with and without T21.

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References

  1. Boghossian NS, Hansen NI, Bell EF, Stoll BJ, Murray JC, Laptook AR, et al. Survival and morbidity outcomes for very low birth weight infants with down syndrome. Pediatrics. 2010;126:1132–40.

    Article  Google Scholar 

  2. Martin T, Smith A, Breatnach CR, Kent E, Shanahan I, Boyle M, et al. Infants born with down syndrome: burden of disease in the early neonatal period. J Pediatr. 2018;193:21–26.

    Article  Google Scholar 

  3. Mann JP, Statnikov E, Modi N, Johnson N, Springett A, Morris JK. Management and outcomes of neonates with down syndrome admitted to neonatal units. Birth Defects Res Part A Clin Mol Teratol. 2016;106:468–74.

    Article  CAS  Google Scholar 

  4. Ergaz-Shaltiel Z, Engel O, Erlichman I, Naveh Y, Schimmel MS, Tenenbaum A. Neonatal characteristics and perinatal complications in neonates with down syndrome. Am J Med Genet A. 2017;173:1279–86.

    Article  CAS  Google Scholar 

  5. McAndrew S, Acharya K, Nghiem-Rao TH, Leuthner S, Clark R, Lagatta J. NICU management and outcomes of infants with trisomy 21 without major anomalies. J Perinatol. 2018;38:1068–73.

    Article  Google Scholar 

  6. Waters KA, Castro C, Chawla J. The spectrum of obstructive sleep apnea in infants and children with down syndrome. Int J Pediatr Otorhinolaryngol. 2020;129:109763.

    Article  Google Scholar 

  7. Wong W, Rosen D. Isolated mild sleep-associated hypoventilation in children with down syndrome. Arch Dis Child. 2017;102:821–4.

    Article  Google Scholar 

  8. Colvin KL, Yeager ME. What people with down syndrome can teach us about cardiopulmonary disease. Eur Respir Rev. 2017;26:1–16.

  9. Stanley MA, Shepherd N, Duvall N, Jenkinson SB, Jalou HE, Givan DC, et al. Clinical identification of feeding and swallowing disorders in 0–6 month old infants with down syndrome. Am J Med Genet A. 2019;179:177–82.

    Article  Google Scholar 

  10. Nagraj VP, Sinkin RA, Lake DE, Moorman JR, Fairchild KD. Recovery from bradycardia and desaturation events at 32 weeks corrected age and NICU length of stay: an indicator of physiologic resilience? Pediatr Res. 2019;86:622–7.

    Article  Google Scholar 

  11. Fairchild KD, Nagraj VP, Sullivan BA, Moorman JR, Lake DE. Oxygen desaturations in the early neonatal period predict development of bronchopulmonary dysplasia. Pediatr Res. 2019;85:987–93.

    Article  Google Scholar 

  12. Poets CF. Intermittent hypoxia and long-term neurological outcome: How are they related? Semin Fetal Neonatal Med. 2020;25:101072.

    Article  Google Scholar 

  13. Bush D, Galambos C, Ivy DD, Abman SH, Wolter-Warmerdam K, Hickey F. Clinical characteristics and risk factors for developing pulmonary hypertension in children with down syndrome. J Pediatr. 2018;202:212–19. e2

    Article  Google Scholar 

  14. Shah PS, Hellmann J, Adatia I. Clinical characteristics and follow up of down syndrome infants without congenital heart disease who presented with persistent pulmonary hypertension of newborn. J Perinat Med. 2004;32:168–70.

    Article  Google Scholar 

  15. Galambos C, Minic AD, Bush D, Nguyen D, Dodson B, Seedorf G, et al. Increased lung expression of anti-angiogenic factors in down syndrome: potential role in abnormal lung vascular growth and the risk for pulmonary hypertension. PLoS ONE. 2016;11:e0159005.

    Article  Google Scholar 

  16. Weijerman ME, van Furth AM, van der Mooren MD, van Weissenbruch MM, Rammeloo L, Broers CJ, et al. Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with down syndrome. Eur J Pediatr. 2010;169:1195–9.

    Article  Google Scholar 

  17. Cua CL, Blankenship A, North AL, Hayes J, Nelin LD. Increased incidence of idiopathic persistent pulmonary hypertension in down syndrome neonates. Pediatr Cardiol. 2007;28:250–4.

    Article  CAS  Google Scholar 

  18. Ramani M, Bradley WE, Dell’Italia LJ, Ambalavanan N. Early exposure to hyperoxia or hypoxia adversely impacts cardiopulmonary development. Am J Respir Cell Mol Biol 2015;52:594–602.

    Article  CAS  Google Scholar 

  19. Horne RSC, Sakthiakumaran A, Bassam A, Thacker J, Walter LM, Davey MJ, et al. Children with down syndrome and sleep disordered breathing have altered cardiovascular control. Pediatr Res. 2020.

  20. Martin RJ, Di Fiore JM, Macfarlane PM, Wilson CG. Physiologic basis for intermittent hypoxic episodes in preterm infants. Adv Exp Med Biol. 2012;758:351–8.

    Article  CAS  Google Scholar 

  21. Das D, Medina B, Baktir MA, Mojabi FS, Fahimi A, Ponnusamy R, et al. Increased incidence of intermittent hypoxemia in the Ts65Dn mouse model of down syndrome. Neurosci Lett. 2015;604:91–96.

    Article  CAS  Google Scholar 

  22. Cooney TP, Thurlbeck WM. Pulmonary hypoplasia in down’s syndrome. N Engl J Med. 1982;307:1170–3.

    Article  CAS  Google Scholar 

  23. Bush D, Abman SH, Galambos C. Prominent intrapulmonary bronchopulmonary anastomoses and abnormal lung development in infants and children with down syndrome. J Pediatr. 2017;180:156–62. e1

    Article  Google Scholar 

  24. Simpson R, Oyekan AA, Ehsan Z, Ingram DG. Obstructive sleep apnea in patients with down syndrome: current perspectives. Nat Sci Sleep. 2018;10:287–93.

    Article  Google Scholar 

  25. Lee C-F, Lee C-H, Hsueh W-Y, Lin M-T, Kang K-T. Prevalence of obstructive sleep apnea in children with down syndrome: a meta-analysis. J Clin Sleep Med. 2018;14:867–75.

    Article  Google Scholar 

  26. Southall DP, Stebbens VA, Mirza R, Lang MH, Croft CB, Shinebourne EA. Upper airway obstruction with hypoxaemia and sleep disruption in down syndrome. Dev Med Child Neurol. 1987;29:734–42.

    Article  CAS  Google Scholar 

  27. Goffinski A, Stanley MA, Shepherd N, Duvall N, Jenkinson SB, Davis C, et al. Obstructive sleep apnea in young infants with down syndrome evaluated in a down syndrome specialty clinic. Am J Med Genet A. 2015;167A:324–30.

    Article  Google Scholar 

  28. Coverstone AM, Bird M, Sicard M, Tao Y, Grange DK, Cleveland C, et al. Overnight pulse oximetry for evaluation of sleep apnea among children with trisomy 21. J Clin Sleep Med. 2014;10:1309–15.

    Article  Google Scholar 

  29. Siriwardhana LS, Nixon GM, Davey MJ, Mann DL, Landry SA, Edwards BA, et al. Children with down syndrome and sleep disordered breathing display impairments in ventilatory control. Sleep Med. 2020;77:161–9.

    Article  Google Scholar 

  30. O’Driscoll DM, Horne RSC, Davey MJ, Hope SA, Anderson V, Trinder J, et al. Cardiac and sympathetic activation are reduced in children with down syndrome and sleep disordered breathing. Sleep. 2012;35:1269–75.

    PubMed  PubMed Central  Google Scholar 

  31. Breslin J, Spanò G, Bootzin R, Anand P, Nadel L, Edgin J. Obstructive sleep apnea syndrome and cognition in down syndrome. Dev Med Child Neurol. 2014;56:657–64.

    Article  Google Scholar 

  32. Lott IT. Antioxidants in down syndrome. Biochim Biophys Acta. 2012;1822:657–63.

    Article  CAS  Google Scholar 

  33. Huggard D, Kelly L, Ryan E, McGrane F, Lagan N, Roche E, et al. Increased systemic inflammation in children with down syndrome. Cytokine. 2020;127:154938.

    Article  CAS  Google Scholar 

  34. Pecze L, Randi EB, Szabo C. Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in down syndrome. Mol Med. 2020;26:102.

    Article  Google Scholar 

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Funding

NICHD R01HD072071.

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Correspondence to Karen D. Fairchild.

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Krahn, K.N., Nagraj, V.P., McCulloch, M.A. et al. Hypoxemia in infants with trisomy 21 in the neonatal intensive care unit. J Perinatol 41, 1448–1453 (2021). https://doi.org/10.1038/s41372-021-01105-7

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