Bronchopulmonary dysplasia and neurobehavioural outcomes at birth and 2 years in infants born before 30 weeks.

OBJECTIVE: To identify neurobehavioural risks in preterm infants with bronchopulmonary dysplasia (BPD) prior to hospital discharge. DESIGN AND PATIENTS: Longitudinal study of 676 newborns born before 30 weeks of gestation. SETTING: Nine university NICUs affiliated with six universities. All were Vermont Oxford Network (VON) participants. PATIENTS AND INTERVENTIONS: Infants were enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study from April 2014 to June 2016. Prospective medical record reviews, VON definitions and criteria, and maternal interviews were used to collect maternal and neonatal medical variables and socioenvironmental data. MAIN OUTCOME MEASURES: NICU Network Neurobehavioral Scale (NNNS) at the time of hospital discharge; Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and Gross Motor Function Classification System at 2 years' corrected age. RESULTS: Infants with moderate/severe BPD were less attentive (Wald χ2 9.68, p=0.008), more lethargic (Wald χ2 9.91, p=0.007), with increased non-optimal reflexes (Wald χ2 7.37, p=0.025). Infants with moderate/severe BPD were more likely to have Bayley-III language and motor scores <85 (adjusted OR (aOR) 1.74, 95% CI 1.06 to 2.85, and aOR 2.06, 95% CI 1.10 to 3.85). Infants with both moderate/severe and mild BPD were more likely to have a cerebral palsy diagnosis (aOR 2.96, 95% CI 1.34 to 6.54, and aOR 2.81, 95% CI 1.32 to 5.99). CONCLUSIONS: BPD severity presents risks for poor neurodevelopment at NICU discharge and at age 2 years. Early identification of poorly regulated behaviour can provide critical information for early preventive and targeted interventions with potential to improve long-term outcomes.

Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants.

Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed. Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes. Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to January 2022. Exposures: Adverse medical and psychosocial conditions; neurobehavior. Main Outcomes and Measures: Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive, language, and motor scores of less than 85 and Child Behavior Checklist (CBCL) T scores greater than 63. NNNS examinations were completed the week of NICU discharge, and 6 profiles of neurobehavior were identified by latent profile analysis. Generalized estimating equations tested associations among NNNS profiles, neonatal medical risk, and 2-year outcomes while adjusting for site, maternal socioeconomic and demographic factors, maternal psychopathology, and infant sex. Results: A total of 679 enrolled infants had medical and NNNS data; 2-year follow-up data were available for 479 mothers and 556 infants (mean [SD] postmenstrual age at birth, 27.0 [1.9] weeks; 255 [45.9%] female). Overall, 268 mothers (55.9%) were of minority race and ethnicity, and 127 (26.6%) lived in single-parent households. The most common neonatal medical morbidity was BPD (287 [51.7%]). Two NNNS behavior profiles, including 157 infants, were considered high behavioral risk. Infants with at least 2 medical morbidities (n = 123) were considered high medical risk. Infants with high behavioral and high medical risk were 4 times more likely to have Bayley-III motor scores less than 85 compared with those with low behavioral and low medical risk (adjusted relative risk [aRR], 4.1; 95% CI, 2.9-5.1). Infants with high behavioral and high medical risk also had increased risk for cognitive scores less than 85 (aRR, 2.7; 95% CI, 1.8-3.4). Only infants with high behavioral and low medical risk were in the clinical range for CBCL internalizing and total problem scores (internalizing: aRR, 2.3; 95% CI, 1.1-4.5; total: aRR, 2.5; 95% CI, 1.2-4.4). Conclusions and Relevance: In this study, high-risk neonatal neurobehavioral patterns at NICU discharge were associated with adverse cognitive, motor, and behavioral outcomes at 2 years. Used in conjunction with medical risk, neonatal neurobehavioral assessments could enhance identification of infants at highest risk for delay and offer opportunities to provide early, targeted therapies.

Associations between maternal pre-pregnancy body mass index and neonatal neurobehavior in infants born before 30 weeks gestation.

OBJECTIVE: To examine the relationship between maternal pre-pregnancy body mass index (BMI) and neonatal neurobehavior in very premature infants. STUDY DESIGN: Multi-center prospective observational study of 664 very preterm infants with 227 born to obese mothers. The NICU Network Neurobehavioral Scale (NNNS) assessed neurobehavior at NICU discharge. RESULTS: Elevated BMI combined with infection increased the odds of having the most poorly regulated NNNS profile by 1.9 times per BMI SD. Infants born to mothers with elevated BMI in combination with: infection had poorer self-regulation, chorioamnionitis had increased asymmetrical reflexes, diabetes had poorer attention, and low SES required more handling. CONCLUSION: Maternal pre-pregnancy BMI alone did not affect short-term neonatal neurobehavior in infants born before 30 weeks gestation. Infants born to mothers with elevated pre-pregnancy weight in addition to infections, diabetes, or socioeconomic adversity demonstrated increased risk of having the most poorly regulated NNNS profile and deficits in multiple domains.

Sociodemographic and medical influences on neurobehavioral patterns in preterm infants: A multi-center study.

BACKGROUND: Among preterm infants, neurodevelopmental outcomes are influenced by both medical and sociodemographic factors. Less is known about the impact on these factors on neonatal neurobehavioral patterns. OBJECTIVE: To determine associations between demographic, psychosocial and medical risk factors and neonatal neurobehavior. METHODS: Multi-center observational study of infants born <30 weeks enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study between April 2014-May 2016. Maternal medical, demographic, and psychological variables and infant medical variables were prospectively collected. Demographic, substance, psychological and medical risk indices were developed. Neurobehavioral assessment was performed using the NICU Network Neurobehavioral Scale (NNNS) at NICU discharge. RESULTS: 709 infants were enrolled in the NOVI study, and for 679 infants with neurobehavioral assessments, 6 NNNS behavioral profiles were calculated using latent profile analysis. Profile 6 infants (n = 47/679, 7%) were atypical, having poor attention, self-regulation and movement quality, hypertonia and increased stress signs. After adjustment for site, profile 6 infants had significantly smaller head circumferences at birth (ß -0.87; -1.59, -0.14), and higher rates of late sepsis (OR 3.38; CI 1.66, 6.92) compared to Profiles 1-5 infants. There were no significant differences in other neonatal morbidities between the two groups. Profile 6 infants had a higher prenatal demographic risk score (1.46 vs 1.07;ß 0.34; CI 0.06, 0.61) compared to Profiles 1-5 infants. CONCLUSION: NNNS behavioral profiles identify an atypical behavioral pattern that is associated with early influences of demographic and medical variables. Such behavioral patterns may be seen as early as NICU discharge.