NOVI Study Reveals New Insight Into Neurodevelopmental Profiles of VPT Infants
“Child-Centered” Assessments May Provide Clinically Useful Information
Assessing Neurodevelopmental Outcomes in VPT Infants
In recent years there have been marked improvements in survival and outcomes for infants born at less than 30 weeks of gestational age.1 Despite this positive trend, children born very preterm (VPT) remain at high risk for long-term physical and mental health problems, as well as developmental delays. In longitudinal follow-up studies, VPT children have shown deficits or delays in cognitive, motor and language development and are at increased risk for disorders such as cerebral palsy and autism spectrum disorder.2-6
However, most studies examining neurodevelopmental outcomes in VPT children report rates of impairment for individual outcomes separately, when in fact it is more likely some outcomes co-occur. An alternative to this approach is to integrate across multiple measures to identify subgroups of children with similar neuroatypical patterns of behavior.
NOVI Studies VPT Infants
The Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) multicenter study enrolled infants born at less than 30 weeks of postmenstrual age (PMA) from nine NICUs affiliated with six universities located throughout the country from April 2014 to June 2016. The regional diversity and volume of patients enrolled are strengths of the NOVI study. Often research into VPT patient outcomes has been limited to single-center studies.
Another unique aspect of the NOVI study is that it not only concerns neonatal-perinatal risk, but the environment of raising the child, exposure to environmental modulators and the frequency and severity of any illness or developmental impairments, as well as therapeutic services utilized.
The Level IV Neonatal Intensive Care Unit at Children’s Mercy Kansas City is one of the sites that originally enrolled VPT infants in this project and continues to follow them to 7 years of age. Brian Carter, MD, Children’s Mercy Neonatologist and Bioethicist, serves as the site’s principal investigator.
Neurodevelopmental Profiles of VPT Infants at 2 Years of Age
The researchers involved in the NOVI study have begun analyzing data gathered from 587 infants born at less than 30 weeks of PMA from the participating sites. To date, they have authored several notable papers, including one recently published online in Pediatric Research that addresses the neurodevelopmental profiles of infants born at less than 30 weeks of gestation at 2 years of age.7
Their objective was to describe neurodevelopmental profiles of these children using cognitive, language, motor and behavioral characteristics. Age 2 outcomes included Bayley-III subscale scores, Child Behavior Checklist syndrome scores, diagnosis of cerebral palsy, and positive screen for autism spectrum disorder risk. They used latent profile analysis to group children into mutually exclusive profiles.
What the researchers found were four discrete neurodevelopmental profiles indicating distinct combinations of developmental and behavioral outcomes.
- Two of the profiles included 72.7% of the sample, with most having Bayley scores within the normal range.
- The other two profiles included the remaining 27.3% of the sample, with most having Bayley scores outside the normal range. Only one profile (11% of sample) comprised children with elevated behavioral problems. These children are most at risk for adverse outcomes.
While there are additional findings within each profile, this study illustrates the need to move beyond individual variable analysis and toward novel approaches to study different risk profiles in this patient population.
How “Child-Centered" Assessments Could Help VPT Infants
The researchers concluded that “child-centered” analysis techniques may provide clinically useful information and could facilitate the development of targeted intervention strategies for VPT children.
For example, relatively few NICUs across the nation routinely conduct the NICU Network Neurobehavioral Scale (NNNS) assessment before a VPT infant is discharged. This assessment is a valid biomarker for detecting at-risk infants and predicting their outcomes. Results could help identify infants in greatest need for enhanced surveillance in NICU follow-up clinics and determine which infants may benefit most from rapid enrollment in early intervention services, giving them the opportunity for the best possible outcome.
This type of universal screening is consistent with the American Academy of Pediatrics8,9 promotion of universal screening for a wide range of neurodevelopmental and behavioral conditions that impact children’s long-term developmental and achievement potential and the provision of early intervention referral for high-risk children, even in the absence of a specific diagnosis.
The researchers anticipate additional publications and insights into this important issue as the data collected from this project is further analyzed and published.
Learn more about the Division of Neonatology at Children's Mercy
Brian Carter, MD, Neonatologist; Bioethicist and Co-Director, Pediatric Bioethics Certificate Course, Children’s Mercy Kansas City
For consults, admissions or transport call: 1 (800) GO MERCY / 1 (800) 466-3729.
1. Glass HC, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ. Outcomes for extremely premature infants. Anesth Analg. 2015;120(6):1337–1351. doi:10.1213/ANE.0000000000000705
2. Aarnoudse-Moens CSH, Weisglas-Kuperus N, van Goudoever JB, Oosterlaan J. Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics. 2009;124(2):717–728. doi:10.1542/peds.2008-2816
3. Stephens BE, Vohr BR. Neurodevelopmental outcome of the premature infant. Pediatr Clin North Am. 2009;56(3):631–646. doi:10.1016/j.pcl.2009.03.005
4. Allen MC. Neurodevelopmental outcomes of preterm infants. Curr Opin Neurol. 2008;21(2):123–128. doi:10.1097/WCO.0b013e3282f88bb4
5. 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(3):635–643. doi:10.1542/peds.2004-2247
6. Agrawal S, Rao SC, Bulsara MK, Patole SK. Prevalence of autism spectrum disorder in preterm infants: a meta-analysis. Pediatrics. 2018;142(3):e20180134. doi:10.1542/peds.2018-0134
7. Camerota M, McGowan EC, Hofheimer JA, et al. Neurodevelopmental profiles of infants born <30 weeks gestation at 2 years of age. Pediatric Res. Published online December 9, 2021. doi:10.1038/s41390-021-01871-2
8. Lipkin PH, Macias MM; Council on Children with Disabilities, Section on Developmental and Behavioral Pediatrics. Promoting optimal development: identifying infants and young children with developmental disorders through developmental surveillance and screening. Pediatrics. 2020;145(1):e20193449. doi:10.1542/peds.2019-3449
9. Council on Children with Disabilities; Section on Developmental Behavioral Pediatrics; Bright Futures Steering Committee; Medical Home Initiatives for Children with Special Needs Project Advisory Committee. Identifying infants and young children with developmental disorders in the medical home: an algorithm for developmental surveillance and screening. Pediatrics. 2006;118(1):405–420. doi:10.1542/peds.2006-1231
1. Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI
2. Department of Pediatrics, Women & Infants Hospital, Providence, RI
3. Department of Pediatrics, Warren Alpert Medical School of Brown University, Providence, RI
4. Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
5. Department of Pediatrics-Neonatology, Children’s Mercy Kansas City
6. Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC
7. Department of Pediatrics, University of Hawaii John A. Burns School of Medicine, Honolulu, HI
8. Department of Pediatrics, Spectrum Health-Helen DeVos Hospital, Grand Rapids, MI
9. Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA
Children’s Mercy Kansas City is an independent, non-profit, 390-bed pediatric health system, providing over half a million patient encounters each year for children from across the country. Children’s Mercy is ranked by U.S. News & World Report in all ten specialties. We have received Magnet® recognition five times for excellence in nursing services. In affiliation with the University of Missouri-Kansas City, our faculty of nearly 800 pediatric specialists and researchers is actively involved in clinical care, pediatric research and educating the next generation of pediatricians and pediatric subspecialists. The Children’s Mercy Research Institute (CMRI) integrates research and clinical care with nationally recognized expertise in genomic medicine, precision therapeutics, population health, health care innovation and emerging infections. In 2021 the CMRI moved into a nine-story, 375,000-square-foot space emphasizing a translational approach to research in which clinicians and researchers work together to accelerate the pace of discovery that enhances care.