Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age Magnetic Resonance Imaging in Infants Born Very Preterm

Nehal A Parikh, Puneet Sharma, Lili He, Hailong Li, Mekibib Altaye, Venkata Sita Priyanka Illapani, Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators, Anita Arnsperger, Traci Beiersdorfer, Kaley Bridgewater, Tanya Cahill, Kim Cecil, Kent Dietrich, Christen Distler, Juanita Dudley, Brianne Georg, Cathy Grisby, Lacey Haas, Karen Harpster, Scott K Holland, Kristin Kirker, Julia E Kline, Beth M Kline-Fath, Matt Lanier, Stephanie L Merhar, Greg Muthig, Brenda B Poindexter, David Russell, Kari Tepe, Leanne Tamm, Julia Thompson, Jean A Tkach, Sara Stacey, Jinghua Wang, Brynne Williams, Kelsey Wineland, Sandra Wuertz, Donna Wuest, Weihong Yuan, Nehal A Parikh, Puneet Sharma, Lili He, Hailong Li, Mekibib Altaye, Venkata Sita Priyanka Illapani, Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators, Anita Arnsperger, Traci Beiersdorfer, Kaley Bridgewater, Tanya Cahill, Kim Cecil, Kent Dietrich, Christen Distler, Juanita Dudley, Brianne Georg, Cathy Grisby, Lacey Haas, Karen Harpster, Scott K Holland, Kristin Kirker, Julia E Kline, Beth M Kline-Fath, Matt Lanier, Stephanie L Merhar, Greg Muthig, Brenda B Poindexter, David Russell, Kari Tepe, Leanne Tamm, Julia Thompson, Jean A Tkach, Sara Stacey, Jinghua Wang, Brynne Williams, Kelsey Wineland, Sandra Wuertz, Donna Wuest, Weihong Yuan

Abstract

Objective: To identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm.

Study design: A prospective cohort of 392 infants born very preterm (≤32 weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45 weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA.

Results: Of the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (P = .027), severe bronchopulmonary dysplasia (BPD) (P = .009), severe retinopathy of prematurity (P < .001), and male sex (P = .041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P = .004), duration of caffeine therapy for severe BPD (P = .009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P = .049).

Conclusions: Severe retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.

Keywords: epidemiology; etiology; infant; magnetic resonance imaging; preterm.

Conflict of interest statement

Conflict of Interest: None of the authors have any conflicts of interest to disclose. The funders played no role in the design, analysis, or presentation of the findings. The first author, NAP, wrote the first draft of the manuscript.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1.. Semiautomated segmentation of diffuse white…
Figure 1.. Semiautomated segmentation of diffuse white matter abnormality (DWMA) in the periventricular and central white matter.
A. Top three panels display raw axial T2-weighed magnetic resonance images through the central part of the brain from a 28 week very preterm boy. Higher signal intensity can be appreciated in the white matter from the surrounding gray matter. Bottom three panels display the segmented (yellow) moderate degree of DWMA white matter regions. B. Top three panels display raw axial T2-weighed MR images from a 30 week very preterm boy. Higher signal intensity can be appreciated in the periventricular and central white matter from the surrounding gray matter. Bottom three panels display the segmented (yellow) severe DWMA.

References

    1. Jeon TY, Kim JH, Yoo SY, Eo H, Kwon JY, Lee J, et al. Neurodevelopmental outcomes in preterm infants: comparison of infants with and without diffuse excessive high signal intensity on MR images at near-term-equivalent age. Radiology. 2012;263(2):518–26.
    1. Torchin H, Morgan AS, Ancel P-Y. International comparisons of neurodevelopmental outcomes in infants born very preterm. Seminars in Fetal and Neonatal Medicine. 2020;25(3):101109.
    1. Pascal A, Govaert P, Oostra A, Naulaers G, Ortibus E, Van den Broeck C. Neurodevelopmental outcome in very preterm and very-low-birthweight infants born over the past decade: a meta-analytic review. Dev Med Child Neurol. 2018;60(4):342–55.
    1. Engelhardt E, Inder TE, Alexopoulos D, Dierker DL, Hill J, Van Essen D, et al. Regional impairments of cortical folding in premature infants. Ann Neurol. 2015;77(1):154–62.
    1. Kline JE, Illapani VSP, He L, Altaye M, Logan JW, Parikh NA. Early cortical maturation predicts neurodevelopment in very preterm infants. Arch Dis Child Fetal Neonatal Ed. 2019.
    1. Parikh NA, He L, Bonfante-Mejia E, Hochhauser L, Wilder PE, Burson K, et al. Automatically quantified diffuse excessive high signal intensity on MRI predicts cognitive development in preterm infants. Pediatr Neurol. 2013;49(6):424–30.
    1. Cayam-Rand D, Guo T, Grunau RE, Benavente-Fernandez I, Synnes A, Chau V, et al. Predicting developmental outcomes in preterm infants: A simple white matter injury imaging rule. Neurology. 2019;93(13):e1231–e40.
    1. Parikh NA, He L, Priyanka Illapani VS, Altaye M, Folger AT, Yeates KO. Objectively Diagnosed Diffuse White Matter Abnormality at Term Is an Independent Predictor of Cognitive and Language Outcomes in Infants Born Very Preterm. J Pediatr. 2020;220:56–63.
    1. Brostrom L, Bolk J, Padilla N, Skiold B, Eklof E, Martensson G, et al. Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm. PLoS One. 2016;11(2):e0149578.
    1. Skiold B, Horsch S, Hallberg B, Engstrom M, Nagy Z, Mosskin M, et al. White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study. Acta Paediatr. 2010;99(6):842–9.
    1. Counsell SJ, Shen Y, Boardman JP, Larkman DJ, Kapellou O, Ward P, et al. Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age. Pediatrics. 2006;117(2):376–86.
    1. Parikh NA, Pierson CR, Rusin JA. Neuropathology Associated With Diffuse Excessive High Signal Intensity Abnormalities on Magnetic Resonance Imaging in Very Preterm Infants. Pediatr Neurol. 2016;65:78–85.
    1. Back SA. White matter injury in the preterm infant: pathology and mechanisms. Acta Neuropathol. 2017;134(3):331–49.
    1. Volpe JJ. Dysmaturation of Premature Brain: Importance, Cellular Mechanisms, and Potential Interventions. Pediatr Neurol. 2019;95:42–66.
    1. Murner-Lavanchy IM, Kidokoro H, Thompson DK, Doyle LW, Cheong JLY, Hunt RW, et al. Thirteen-Year Outcomes in Very Preterm Children Associated with Diffuse Excessive High Signal Intensity on Neonatal Magnetic Resonance Imaging. J Pediatr. 2019;206:66–71 e1.
    1. Parikh NA, He L, Li H, Priyanka Illapani VS, Klebanoff MA. Antecedents of Objectively Diagnosed Diffuse White Matter Abnormality in Very Preterm Infants. Pediatr Neurol. 2020;106:56–62.
    1. Hart AR, Smith MF, Rigby AS, Wallis LI, Whitby EH. Appearances of diffuse excessive high signal intensity (DEHSI) on MR imaging following preterm birth. Pediatr Radiol. 2010;40(8):1390–6.
    1. Calloni SF, Cinnante CM, Bassi L, Avignone S, Fumagalli M, Bonello L, et al. Neurodevelopmental outcome at 36 months in very low birth weight premature infants with MR diffuse excessive high signal intensity (DEHSI) of cerebral white matter. Radiol Med. 2015;120(11):1056–63.
    1. Morel B, Antoni G, Teglas JP, Bloch I, Adamsbaum C. Neonatal brain MRI: how reliable is the radiologist’s eye? Neuroradiology. 2016;58(2):189–93.
    1. Rath CP, Desai S, Rao SC, Patole S. Diffuse excessive high signal intensity on term equivalent MRI does not predict disability: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2020.
    1. He L, Parikh NA. Automated detection of white matter signal abnormality using T2 relaxometry: application to brain segmentation on term MRI in very preterm infants. Neuroimage. 2013;64:328–40.
    1. He L, Parikh NA. Atlas-guided quantification of white matter signal abnormalities on term-equivalent age MRI in very preterm infants: findings predict language and cognitive development at two years of age. PLoS One. 2013;8(12):e85475.
    1. Parikh NA, Lasky RE, Kennedy KA, McDavid G, Tyson JE. Perinatal factors and regional brain volume abnormalities at term in a cohort of extremely low birth weight infants. PLoS One. 2013;8(5):e62804.
    1. Tamm L, Patel M, Peugh J, Kline-Fath BM, Parikh NA, Cincinnati Infant Neurodevelopment Early Prediction Study G. Early brain abnormalities in infants born very preterm predict under-reactive temperament. Early Hum Dev. 2020;144:104985.
    1. Friston KJ, Holmes AP, Worsley KJ, Poline J-P, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: A general linear approach. Human Brain Mapping. 1994;2(4):189–210.
    1. Kidokoro H, Neil JJ, Inder TE. New MR imaging assessment tool to define brain abnormalities in very preterm infants at term. AJNR Am J Neuroradiol. 2013;34(11):2208–14.
    1. Nelson KB, Ellenberg JH. Antecedents of cerebral palsy. Multivariate analysis of risk. N Engl J Med. 1986;315(2):81–6.
    1. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, Investigators DS. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics. 2006;117(1):75–83.
    1. Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF, et al. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003;289(9):1124–9.
    1. Schmidt B, Davis PG, Asztalos EV, Solimano A, Roberts RS. Association between severe retinopathy of prematurity and nonvisual disabilities at age 5 years. JAMA. 2014;311(5):523–5.
    1. Msall ME, Phelps DL, DiGaudio KM, Dobson V, Tung B, McClead RE, et al. Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group. Pediatrics. 2000;106(5):998–1005.
    1. Beligere N, Perumalswamy V, Tandon M, Mittal A, Floora J, Vijayakumar B, et al. Retinopathy of prematurity and neurodevelopmental disabilities in premature infants. Semin Fetal Neonatal Med. 2015;20(5):346–53.
    1. Kline JE, Illapani VSP, He L, Altaye M, Parikh NA. Retinopathy of Prematurity and Bronchopulmonary Dysplasia are Independent Antecedents of Cortical Maturational Abnormalities in Very Preterm Infants. Sci Rep. 2019;9(1):19679.
    1. Smith LEH. Pathogenesis of retinopathy of prematurity. Growth Hormone & IGF Research. 2004;14:140–4.
    1. Tremblay S, Miloudi K, Chaychi S, Favret S, Binet F, Polosa A, et al. Systemic inflammation perturbs developmental retinal angiogenesis and neuroretinal function. Invest Ophthalmol Vis Sci. 2013;54(13):8125–39.
    1. Sood BG, Madan A, Saha S, Schendel D, Thorsen P, Skogstrand K, et al. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity. Pediatr Res. 2010;67(4):394–400.
    1. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015;314(10):1039–51.
    1. Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia. J Pediatr. 2014;165(6):1258–60.
    1. Schmidt B, Roberts RS, Anderson PJ, Asztalos EV, Costantini L, Davis PG, et al. Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of Prematurity: An 11-Year Follow-up of the CAP Randomized Clinical Trial. JAMA Pediatr. 2017;171(6):564–72.
    1. Rhein LM, Dobson NR, Darnall RA, Corwin MJ, Heeren TC, Poets CF, et al. Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial. JAMA Pediatr. 2014;168(3):250–7.
    1. Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, et al. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med. 2017;23(2):174–84.
    1. Iris M, Tsou PS, Sawalha AH. Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity. Clin Immunol. 2018;192:68–77.
    1. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112–21.
    1. Parikh NA, Harpster K, He L, Illapani VSP, Khalid FC, Klebanoff MA, et al. Novel diffuse white matter abnormality biomarker at term-equivalent age enhances prediction of long-term motor development in very preterm children. Sci Rep. 2020;10(1):15920.
    1. Anderson JW, Johnstone BM, Remley DT. Breast-feeding and cognitive development: a meta-analysis. Am J Clin Nutr. 1999;70(4):525–35.
    1. Horwood LJ, Darlow BA, Mogridge N. Breast milk feeding and cognitive ability at 7-8 years. Arch Dis Child Fetal Neonatal Ed. 2001;84(1):F23–7.
    1. Belfort MB, Anderson PJ, Nowak VA, Lee KJ, Molesworth C, Thompson DK, et al. Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks’ Gestation. J Pediatr. 2016;177:133–9 e1.
    1. Isaacs EB, Fischl BR, Quinn BT, Chong WK, Gadian DG, Lucas A. Impact of breast milk on intelligence quotient, brain size, and white matter development. Pediatr Res. 2010;67(4):357–62.
    1. Pogribna U, Burson K, Lasky RE, Narayana PA, Evans PW, Parikh NA. Role of diffusion tensor imaging as an independent predictor of cognitive and language development in extremely low-birth-weight infants. AJNR Am J Neuroradiol. 2014;35(4):790–6.
    1. Blesa M, Sullivan G, Anblagan D, Telford EJ, Quigley AJ, Sparrow SA, et al. Early breast milk exposure modifies brain connectivity in preterm infants. Neuroimage. 2019;184:431–9.
    1. de Bruine FT, van den Berg-Huysmans AA, Leijser LM, Rijken M, Steggerda SJ, van der Grond J, et al. Clinical implications of MR imaging findings in the white matter in very preterm infants: a 2-year follow-up study. Radiology. 2011;261(3):899–906.
    1. Hong HK, Lee HJ, Ko JH, Park JH, Park JY, Choi CW, et al. Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity. J Neuroinflammation. 2014;11:87.
    1. Klinger G, Levy I, Sirota L, Boyko V, Lerner-Geva L, Reichman B, et al. Outcome of early-onset sepsis in a national cohort of very low birth weight infants. Pediatrics. 2010;125(4):e736–40.
    1. Chen ML, Allred EN, Hecht JL, Onderdonk A, VanderVeen D, Wallace DK, et al. Placenta microbiology and histology and the risk for severe retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2011;52(10):7052–8.
    1. Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016;387(10030):1827–36.
    1. Zeng L, Tian J, Song F, Li W, Jiang L, Gui G, et al. Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2018;103(6):F506–F11.
    1. Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2017;10:CD001146.
    1. Suresh GK, Davis JM, Soll RF. Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants. Cochrane Database Syst Rev. 2001(1):CD001968.
    1. Askie LM, Darlow BA, Davis PG, Finer N, Stenson B, Vento M, et al. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Cochrane Database Syst Rev. 2017;4:CD011190.
    1. Hanson LA, Hahn-Zoric M, Berndes M, Ashraf R, Herias V, Jalil F, et al. Breast feeding: overview and breast milk immunology. Acta Paediatr Jpn. 1994;36(5):557–61.
    1. Walker A. Breast milk as the gold standard for protective nutrients. J Pediatr. 2010;156(2 Suppl):S3–7.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere