Pathways of neuronal and cognitive development in children born small-for-gestational age or late preterm

To assess the effects of late small-for-gestational-age (SGA) birth and late prematurity on cognitive outcomes and structural changes in the central nervous system at primary school age, using a novel approach to examine changes in neuronal integrity of the retina.

We conducted a cross-sectional study of 347 children aged 6-13 years, including in the analysis only infants born after 34 weeks' gestation. We recorded all perinatal outcomes through a survey of parents. Neuronal damage was evaluated using optical coherence tomography of the retina. In a subgroup of 112 children aged 6-8 years, visuospatial perception was evaluated with the Children's Bender Visual Motor Gestalt Test.

The proportions of SGA and late preterm children were 11.8 and 6.3%, respectively. Prematurity and SGA were simultaneously present in five children. When compared with controls, SGA children showed significantly lower than average retinal nerve fiber layer (RNFL) thickness (94.1 vs 98.8 μm; P = 0.007) and an increased percentage of abnormal Bender scores (27.3 vs 6.2%; P = 0.017) (odds ratio 5.6 (95% CI, 1.2-26.8)). These differences increased when late SGA infants with a birth weight below the 3(rd) percentile were compared with SGA infants with a birth weight between the 3(rd) and 10(th) percentiles and with controls, for RNFL thickness (92.5 vs 94.6 and 98.8 μm, respectively; P = 0.021) and abnormal Bender tests (33.3 vs 25.0 and 6.2%, respectively; P = 0.036). However, no differences were found in retinal structure and visuomotor performance between late preterm and term infants.

These data suggest that late SGA and late prematurity induce a distinct neuronal pattern of structural changes that persist at school age. Late-onset SGA infants are at increased risk for axonal loss in the retina and present specific visuomotor difficulties.