Brain development of very preterm and very low-birthweight children in childhood and adolescence: a meta-analysis.

Aim: The aim of this article was to clarify the impact and consequences of very preterm birth (born <32wks of gestation) and/or very low birthweight ([VLBW], weighing <1500g) on brain volume development throughout childhood and adolescence.

Method: The computerized databases PubMed, Web of Knowledge, and EMBASE were searched for studies that reported volumetric outcomes during childhood or adolescence using magnetic resonance imaging and included a term-born comparison group. Fifteen studies were identified, encompassing 818 very preterm/VLBW children and 450 term-born peers. Average reductions in the total brain volume, white matter volume, grey matter volume, and in the size of the cerebellum, hippocampus, and corpus callosum were investigated using meta-analytic methods.

Results: Very preterm/VLBW children were found to have a significantly smaller total brain volume than the comparison group (d=-0.58; 95% confidence interval [CI] -0.43 to -0.73; p<0.001), smaller white matter volume (d=-0.53; CI -0.40 to -0.67; p<0.001), smaller grey matter volume (d=-0.62; CI -0.48 to -0.76; p<0.001), smaller cerebellum (d=-0.74; CI -0.56 to -0.92; p<0.001), smaller hippocampus (d=-0.47; CI -0.26 to -0.69; p<0.001), and smaller corpus callosum (d=-0.71; CI -0.34 to -1.07; p<0.001). Reductions have been associated with decreased general cognitive functioning, and no relations with age at assessment were found.

Interpretation:   Very preterm/VLBW birth is associated with an overall reduction in brain volume, which becomes evident in equally sized reductions in white and grey matter volumes, as well as in volumes of diverse brain structures throughout childhood and adolescence.