Reduced hippocampal subfield volumes and memory function in school-aged children born preterm with very low birthweight (VLBW)

Abstract

Background: The hippocampus, an essential structure for learning and memory, has a reduced volume in preterm born (gestational age < 37 weeks) individuals with very low birth weight (VLBW: birth weight < 1500 g), which may affect memory function. However, the hippocampus is a complex structure with distinct subfields related to specific memory functions. These subfields are differentially affected by a variety of neuropathological conditions, but it remains unclear how these subfields may be affected by medical complications following preterm birth which may cause aberrant brain development, and the consequences of this on learning and memory function in children with VLBW. Methods: Children born preterm with VLBW (n = 34) and term-born controls from the Norwegian Mother and Child Cohort Study (MoBa) (n = 104) underwent structural MRI and a neuropsychological assessment of memory function at primary school age. FreeSurfer 6.0 was used to analyze the volumes of hippocampal subfields which were compared between groups, as was memory performance. Correlations between abnormal hippocampal subfields and memory performance were explored in the VLBW group. Results: All absolute hippocampal subfield volumes were lower in the children with VLBW compared to MoBa term-born controls, and the volumes of the left and right dentate gyrus and the right subiculum remained significantly lower after correcting for total intracranial volume. The VLBW group had inferior working memory performance and the score on the subtest Spatial Span backwards was positively correlated to the volume of the right dentate gyrus. Conclusions: Hippocampal subfield volumes seem to be differently affected by early brain development related to preterm birth. The dentate gyrus appears particularly susceptible to adverse effects of preterm birth. Reduced working memory function among children with VLBW was associated with smaller volume of right dentate gyrus. This finding demonstrates alterations in hippocampal structure-function relationships associated with early brain development related to preterm birth. Keywords: Preterm birth, Very low birth weight, Hippocampus, Memory function, Structural MRI, Hippocampal subfields, Norwegian Mother and Child Cohort Study (MoBa)