Slower postnatal growth related to prematurity correlated with significant delay in development of cortical gray matter during infants’ first weeks after birth, paired brain imaging studies showed.
Lower gestational age, birth weight, and weight gain at 40 weeks postmenstrual age had independent associations with higher fractional anisotropy (FA), an imaging-based measure of cortical development. The association was limited to cortical gray matter (P<0.001), as no association was observed between postnatal growth and cortical white matter, according to an article published online in Science Translational Medicine.
The studies have potentially major clinically implications, said Steven Miller, MD, from the University of British Columbia in Vancouver and the University of Toronto, and colleagues.
“Neonatal growth over and above birth weight, brain injury, and systemic illness correlated with cortical gray matter maturation in the neonatal intensive care unit (NICU),” Miller’s group wrote. “Therefore, by diagnosing, treating, and preventing poor postnatal growth, clinicians may have the opportunity to optimize conditions for cortical development to proceed normally in infants born very preterm.”
Survival of preterm infants has improved substantially but comorbidity associated with prematurity has not decreased. Consequently, neonatal comorbidities continue to pose a threat to white matter development.
Intrauterine growth restriction (IUGR <10th percentile for age) is associated with reduced cortical volumes and other developmental abnormalities of the brain. Premature IUGR infants have an increased likelihood of poorer neurodevelopmental outcomes. However, most preterm infants are not born IUGR, which means IUGR cannot account entirely for brain injuries and neurodevelopmental abnormalities in preterm infants, the authors noted.
Premature infants often develop postnatal growth deficits that persist to discharge from the NICU, such that a majority of the infants are growth restricted. Postnatal growth delay or failure increases the risk of cerebral palsy and impaired neurodevelopment. Additionally, the rate of change in cortical surface area between 24 and 44 weeks postmenstrual age is associated with cognitive performance at 2 and 6 years, they said.
Diffusion tensor imaging (DTI), an MRI technique, permits assessment of FA, which reflects changes in water diffusion directionality. FA typically decreases in the cerebral cortex between 25 and 40 weeks postmenstrual age but increases with maturation in white matter.
The authors used DTI to test the hypothesis that poorer growth in the NICU is associated with delayed cortical maturation, irrespective of prenatal growth, illness, or brain injury. Investigators performed two DTI studies in 95 infants born at 24 to 32 weeks of gestation between 2006 and 2009. The first scan was done at a median postmenstrual age of 32 weeks and the second at 40 weeks.
Data analysis included associations between changes in the infants’ weight, length, and head circumference and development of cortical microstructure.
Adjusted longitudinal models revealed several factors that had independent associations with increased FA in cortical gray matter:
- Lower gestational age (P<0.001)
- Birth weight (P=0.016)
- Slower weight gain between DTI scans (P<0.001)
The results also showed that “neonatal growth was associated with cortical gray matter maturation in the NICU, independent of birth weight, brain injury, and systemic illness.”
In contrast, weight change did not significantly affect FA values in white matter. Instead, postnatal infection was the only independent predictor of lower white matter FA values (P=0.005).
With respect to length change, DTI results revealed three factors that had independent associations with increased FA in cortical gray matter in patients who did not receive corticosteroids postnatally:
- Lower gestational age (P=0.002)
- Confirmed necrotizing enterocolitis (P=0.012)
- Slower linear growth between DTI scans (P<0.001)
Analysis of FA values in relation to change in head circumference showed that lower gestational age (P=0.004) and slower head growth (P<0.001) between the two scans were independent predictors of increased FA in cortical gray matter.
“The consistency in findings across measures of weight, length, and head circumference supports the hypothesis that the alterations in cortical development reflect growth rather than fluid management,” the authors wrote. “Our study was able to account for several medical confounders, which were likely to affect both growth and brain development, although residual confounding remains possible.”
The authors said they are following these infants through childhood “to determine whether neonatal growth-related delays in cortical maturation are associated with abnormal neurodevelopmental outcomes.”
The study was supported by the Canadian Institutes of Health Research.
The authors reported no conflicts of interest.