Assistant Professor Division Neonatology University of Washington School of Medicine Burien, Washington, United States
Background: Poor growth during neonatal intensive care unit hospitalization is common in extremely premature infants (EP, < 28 weeks gestation). Deficiencies in infant linear and weight growth velocities have been associated with adverse neurodevelopment (ND), but less is known about the role of occipitofrontal circumference (OFC). As OFC is a proxy for brain volume, it may serve as an early indicator of ND. Furthermore, most studies examining growth parameter associations with ND do not take overall growth trajectories into account by adjusting for all anthropometric measurements. Objective: This study investigates whether OFC growth in EP from birth to two years is associated with two-year ND when accounting for important covariates as well as weight and length measures. Design/Methods: This is a secondary analysis of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT) . Weight, length, and OFC z-scores were calculated at birth, discharge, and two-years using growth charts for sex and gestational age (Fenton and CDC). Two-year ND was assessed by Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). Linear mixed models with random effects by infant were employed to determine OFC z-score growth trajectories from birth to two years of age adjusting for fixed effects of covariates associated with growth and ND (Table 1). As a sensitivity analysis, OFC z-scores were further adjusted by respective weight and length z-scores at each time point. Results: 629 infants were included from PENUT. Cohort characteristics are shown in Table 2. In the main analysis, after adjustment for covariates, OFC growth (per model SD increase) was significantly associated with BSID-III Cognition (2.05 [0.86 - 3.25], p = 0.001), BSID-III Language (2.24 [0.87 - 3.6], p = 0.001), and BSID-III Motor (1.79 [0.56 - 3.02], p = 0.004) scores. Sensitivity analysis revealed attenuated, yet consistent, findings: BSID-III Cognition (1.45 [0.29 - 2.61], p = 0.015), BSID-III Language (1.92 [0.59 - 3.26], p = 0.005), and BSID-III Motor (1.37 [0.16 - 2.59], p = 0.027) (Figure 1). There were no significant differences observed by sex.
Conclusion(s): Positive associations between OFC growth trajectory and BSID-III scores emphasize the importance of tracking OFC longitudinally as a prognostic indicator for ND in EP. Further research is needed to determine if OFC trajectory can identify infants at risk for delays in ND and guide interventions to promote OFC growth.