Am J Perinatol 2024; 41(06): 783-789
DOI: 10.1055/a-1788-6281
Original Article

Prediction of Cerebral Palsy or Death among Preterm Infants Who Survive the Neonatal Period

Alan M. Peaceman
1   Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois
,
Lisa Mele
2   Department of Biostatistics and Bioinformatics, The George Washington University, Washington, District of Columbia
,
Dwight J. Rouse
3   Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
,
Kenneth J. Leveno
4   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Brian M. Mercer
5   Department of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio
6   Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee
,
7   Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
,
Uma M. Reddy
8   Pregnancy and Perinatology Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
,
Ronald J. Wapner
9   Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, Pennsylvania
10   Department of Obstetrics and Gynecology, Drexel University, Philadelphia, Pennsylvania
,
Yoram Sorokin
11   Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan
,
John M. Thorp
12   Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
,
Susan M. Ramin
13   Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston-Children's Memorial Hermann Hospital, Houston, Texas
,
Fergal D. Malone
14   Department of Obstetrics and Gynecology, Columbia University, New York, New York
,
Mary J. O'Sullivan
15   Department of Obstetrics and Gynecology, University of Miami, Miami, Florida
,
Donald J. Dudley
16   Department of Obstetrics and Gynecology, University of Texas at San Antonio, San Antonio, Texas
,
Steve N. Caritis
17   Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania
,
for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network › Author Affiliations
Funding The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897], MO1-RR-000080, and by the National Institute of Neurological Disorders and Stroke (NINDS). Comments and views of the authors do not necessarily represent views of the NICHD and NINDS.

Abstract

Objective To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death.

Study Design This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created.

Results Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67–0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1–13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6–104.6), and male gender (OR: 2.5, CI: 1.4–4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78–0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants.

Conclusion IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae.

Key Points

  • Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.

  • A model was created and validated using these findings to counsel parents.

  • The risk of death or CP can be calculated at the time of hospital discharge.

Note

Presented at the 32nd Annual Meeting of the Society for Maternal-Fetal Medicine, Dallas, Texas, February 6–11, 2012. The parent trial for this study was registered on ClinicalTrials.gov Web site with number NCT00014989.




Publication History

Received: 07 October 2021

Accepted: 18 February 2022

Accepted Manuscript online:
04 March 2022

Article published online:
12 May 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Tyson JE, Parikh NA, Langer J, Green C, Higgins RD. National Institute of Child Health and Human Development Neonatal Research Network. Intensive care for extreme prematurity–moving beyond gestational age. N Engl J Med 2008; 358 (16) 1672-1681
  • 2 Wood NS, Costeloe K, Gibson AT, Hennessy EM, Marlow N, Wilkinson AR. EPICure Study Group. The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth. Arch Dis Child Fetal Neonatal Ed 2005; 90 (02) F134-F140
  • 3 Vohr BR, Wright LL, Poole WK, McDonald SA. Neurodevelopmental outcomes of extremely low birth weight infants <32 weeks' gestation between 1993 and 1998. Pediatrics 2005; 116 (03) 635-643
  • 4 Rouse DJ, Hirtz DG, Thom E. et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359 (09) 895-905
  • 5 Yoon BH, Romero R, Park JS. et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000; 182 (03) 675-681
  • 6 Wu YW, Colford Jr JM. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA 2000; 284 (11) 1417-1424
  • 7 Yoon BH, Kim CJ, Romero R. et al. Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits. Am J Obstet Gynecol 1997; 177 (04) 797-802
  • 8 Patrick LA, Gaudet LM, Farley AE, Rossiter JP, Tomalty LL, Smith GN. Development of a guinea pig model of chorioamnionitis and fetal brain injury. Am J Obstet Gynecol 2004; 191 (04) 1205-1211