Neurobehavioral Patterns in the NICU Tied to Adverse Outcomes in ToddlersJuly 18, 2022
Among very preterm infants, neonatal neurobehavioral patterns may go beyond medical findings to inform predictions of motor, cognitive, and behavioral outcomes at 2 years of age.
Infants born at less than 30 weeks of gestation and exhibiting risky behavioral and medical features were four times more likely to have motor scores below 85 on the Bayley Scales of Infant and Toddler Development (Bayley-III) at age 2, compared with similarly preterm but lower-risk infants (adjusted relative risk [aRR] 4.1, 95% 2.9-5.1).
Cognitive scores on the Bayley-III also more often fell below 85 at toddlerhood among babies at both high behavioral risk and high medical risk (aRR 2.7, 95% CI 1.8-3.4), reported Elisabeth McGowan, MD, of Brown Alpert Medical School and Women and Infants Hospital in Providence, Rhode Island, and colleagues.
Yet it was the cohort of preterm infants that was at high behavioral, but low medical risk that tended to be more prone to later behavior problems per Child Behavior Checklist (CBCL) internalizing (aRR 2.3, 95% CI 1.1-4.5) and total problem (aRR 2.5, 95% CI 1.2-4.4) scores, the NOVI study showed in JAMA Network Open.
“Neurobehavior belongs at the table when it comes to evaluating preterm infants in the [neonatal intensive care unit] NICU,” McGowan told MedPage Today.
“It adds information above and beyond that provided by medical factors and in the case of behavior problems, for our cohort, only neurobehavior predicted that outcome. Also, we can identify which infants are most at risk before hospital discharge, so we can focus on developing treatment in the NICU and help with the transition to home and the connection with providers,” she said.
In the NOVI cohort, medical factors that conferred high risk included bronchopulmonary dysplasia, severe retinopathy of prematurity, necrotizing enterocolitis, and culture-positive sepsis. Infants with at least two of these factors were considered to be at high medical risk.
Meanwhile, McGowan’s group considered infants to be at high behavioral risk if they matched NICU Network Neurobehavioral Scale (NNNS) behavior profiles five and six, reflecting the poorest functioning in multiple domains such as attention, lethargy, and reflexes.
“It’s never too early to assess neurobehavior in infants. Their movements and responses to the environment may be subtle, but if we look closely, they are there. Once we identify the responses, then we can help enhance or support them, and that is exciting,” according to McGowan.
Her group noted that early dysregulated behavior in infants may increase the likelihood of long-term issues in social, home, and academic functioning.
NOVI was a cohort study that enrolled 679 infants born at less than 30 weeks of gestation at nine U.S. university-affiliated NICUs. Enrollment was between April 2014 and June 2016 with a 2-year follow-up assessment. Criteria for exclusion included maternal age of under 18, maternal or infant death, maternal cognitive impairment, and infants with major congenital anomalies.
Data were adjusted for site, maternal socioeconomic and demographic factors, maternal psychopathology, and infant sex.
Study authors acknowledged that the subgroup with high behavioral and high medical risk infants was relatively small. The follow-up rate was only 82% as well. Finally, the dichotomization of risk factors could have prevented a more granular understanding of the study results, according to McGowan and colleagues.
“The work by McGowan, et al. represents an important step toward accurate prediction of childhood developmental and behavioral problems in preterm infants. Nevertheless, even with the added information provided by the NNNS, precise estimates of later risk remain relatively elusive,” according to Sara DeMauro, MD, from the University of Pennsylvania Perelman School of Medicine in Philadelphia, and Stephanie Merhar, MD, from Cincinnati Children’s Hospital Medical Center.
“For example, among infants with the high behavioral risk and high medical risk profile, 53% had a Bayley-III cognitive composite score below 85 and 53% had a motor composite score below 85. In other words, almost half of infants with high behavioral and high medical risk did not have developmental delays on the Bayley-III,” DeMauro and Merhar cautioned in an editorial.
“In addition, the investigators have not yet reported associations between NNNS profiles and more significant delays or behavioral diagnoses,” the duo wrote.
McGowan and colleagues also noted that 2-year outcomes may be limited in predicting school-age outcomes, but they intend to continue following the cohort in order to examine longer-term outcomes.
“Child development is a continuum, and different problems arise during different stages of development,” McGowan stated. “Assessment of long-term trajectories is critical, for this cohort as well as other large cohorts. It’s been encouraging to see other investigators recognizing the importance of early infant behavior. Now we need to keep exploring prenatal and antenatal mechanisms that are driving these behaviors.”
The study received funding from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development.
McGowan reported no conflicts of interest.
DeMauro reported receiving grants from the NIH, Thrasher Research Fund, and Agency for Healthcare Research and Quality. Merhar disclosed NIH grants as well.