Somatic Growth Faltering Precedes Brain Growth Deceleration in Preterm Infants: A Window for Intervention

To identify the timing and clinical risk factors associated with somatic growth faltering (GF) in very preterm infants (VPI, born < 32 weeks' gestation) and explore the relationship with longitudinal brain growth throughout the extrauterine second and third trimesters.

Observational cohort followed with serial growth anthropometrics and brain magnetic resonance imaging at approximately 4-week intervals through term corrected age. Multivariable logistic regression identified clinical covariates associated with GF. Generalized additive models, extended linear mixed models, and multivariable linear mixed models were applied to create trajectories of nutritional intake and weight and brain growth and compare term corrected brain volumes between VPI with and without GF.

118 VPI (68 GF, 50 no GF) underwent 333 magnetic resonance imaging studies (195 GF, 138 no GF). Those with GF were born younger (mean [SD] 27.4 [2.2] vs 28.3 [2.3] weeks, p=0.02) and experienced more clinical comorbidities. Poor weight gain in GF VPI began after 33 weeks corrected age and was associated with early systemic steroids (odds ratio [95% CI] 3.8 [1.2,14.8], P=0.03) and gastrointestinal surgery (odds ratio [95% CI] 7.8 [1.8,53.9], P=0.01). GF infants demonstrated significantly lower lipid, caloric, and maternal milk intake trajectories than non-GF infants. VPI with GF compared with no GF experienced slower volumetric brain growth after 37 weeks corrected age in nearly all brain regions. Term corrected cerebellar (β= -1.74 [-2.95,-0.52], p=0.01) and brainstem (β= -0.29 [-0.55,-0.04], p=0.02) volumes were lower in GF infants after adjusting for significant covariates.

Brain growth is impaired during critical extrauterine periods in GF VPI, with a 4-week interval between the onset of weight faltering and subsequent brain growth deceleration that may represent an important window for clinical intervention.