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Reduced Occipital Regional Volumes at Term Predict Impaired Visual Function in Early Childhood in Very Low Birth Weight Infants

¹From the Department of Neonatal Neurology, Royal Children’s Hospital, Murdoch Children’s Research Institute, Melbourne, Australia; the ²Department of Pediatrics, St. Louis Children’s Hospital, Washington University, St. Louis, Missouri; the ³Department of Ophthalmology, Christchurch Hospital, Christchurch, New Zealand; the ⁴Department of Ophthalmology, Royal Children’s Hospital, Melbourne, Australia; the ⁵Neonatal Service, Christchurch Women’s Hospital, Christchurch, New Zealand; the ⁶Canterbury Child Development Research Group, University of Canterbury, Christchurch, New Zealand; the ⁷Howard Florey Institute, Melbourne, Australia; and the ⁸Departments of Radiology, Children’s Hospital, Brigham and Women’s Hospital, Boston, Massachusetts.

PURPOSE. Premature infants are at increased risk of impaired visual performance related to both cortical and subcortical pathways for oculomotor control. The hypothesis for the current study was that preterm infants with impaired saccades, smooth pursuit, and binocular eye alignment at age 2 years would have smaller occipital brain volumes at term equivalent, as measured by volumetric magnetic resonance (MR) techniques, than would preterm infants without such abnormalities.

METHODS. Study participants consisted of 68 infants from a representative regional cohort of 100 preterm infants born between 23 and 33 weeks’ gestation. At term equivalent, all infants underwent MR imaging, and the images were coregistered, tissue segmented into five cerebral tissue subtypes, and further subdivided into eight regions for each hemisphere. At 2 years corrected, all infants completed a comprehensive orthoptic evaluation performed by a single examiner.

RESULTS. Twenty-four (35%) of the 68 infants had abnormal oculomotor control at 2 years, including abnormalities in saccadic movements (n = 7), smooth pursuit (n = 14), or strabismus (n = 9, four with esotropia and five with exotropia). When compared with preterm infants without visuomotor impairment, these infants had significantly smaller inferior occipital region brain tissue volumes bilaterally (n = 24 vs. n = 44; total tissue, mean ± SD, left, 37.9 ± 7.4 cm³ vs. 43.7 ± 7.4 cm³; mean difference [95% CI] –5.7 [–9.4 to –2.0] cm³, P = 0.003; right, 36.8 ± 7.1 cm³ vs. 41.4 ± 6.2 cm³, mean difference –4.6 [–7.9 to –1.3] cm³, P = 0.007). This difference remained significant after adjusting for intracranial volume (ICV; left, mean difference –3.5 [–6.7 to –0.2] cm³, P = 0.04; right, mean difference –2.4 [–5.2 to –0.4] cm³, P = 0.09). Within this region, the cortical gray matter volume was the most significantly reduced (left, 20.4 ± 6.2 cm³ vs. 25.4 ± 5.6 cm³, mean difference –3.1 [–5.7 to –0.5] cm³, P = 0.02; right 21.0 ± 5.4 cm³ vs. 24.9 ± 5.0 cm³, mean difference –2.2 [–4.4 to 0.0] cm³, P = 0.05, ICV adjusted). Abnormalities in saccadic eye movements accounted for the largest effect on inferior occipital regional brain volumes (left side, P = 0.02).

CONCLUSIONS. Volumetric MR imaging techniques demonstrated an overall reduction in the inferior occipital regional brain volumes in preterm infants at term corrected who later exhibit impaired oculomotor function control. These findings assist in understanding the neuroanatomic correlates of later visual difficulties experienced by infants born prematurely.

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