314 - Impaired brain growth in neonates exposed to HIV in utero at term-equivalent age

Poster Number: 314
Publication Number: 314.124

Nickie Andescavage, Children's National Health System, Washington, DC, United States; Yuan-Chiao Lu, Children's National Hospital, Washington, DC, United States; Kushal Kapse, Developing Brain Institute, Washington, DC, United States; Rachel K. Scott, MedStar Health Research Institute, Baltimore, MD, United States; Catherine Lopez, Children's National Health System, Washington, D.C., DC, United States; Todd C. Richmann, Children's National Health System, Washington, DC, United States; Haleema Saeed, MedStar Washington Hospital Center, Washington, DC, United States; Natella Y. Rakhmanina, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Catherine Limperopoulos, Children's National Health System, Washington, DC, United States

Background: HIV-exposed uninfected (HEU) children may have impaired neurodevelopment when compared to HIV unexposed and uninfected children (HUU).

Objective: To compare quantitative brain development between HEU infants with HUU controls.

Design/Methods: We enrolled HEU newborns and HUU controls in this prospective, observational study. All infants were scanned without sedation using 3T GE scanner. We derived quantitative MRI (qMRI) measures of brain growth from 3D reconstructions of the neonatal brain. Specifically, we measured global and regional brain volumes (including total brain, cerebellar, brainstem, cortical grey, white and deep grey matter volumes) as well as global and lobar cortical features (including gyrification, sulcal depth and surface areas of the frontal, parietal, temporal and occipital lobes and overall cerebrum).

Results: We compared qMRI measures of brain growth from 48 newborns: 12 HEU and 36 age matched HUU, healthy controls) at a mean GA of 42.7±1.7 weeks.  All volumes trended lower in HEU, with statistically significant reductions of cerebellar volume in HEU (HEU 24114±3020 vs HUU 27875±4183 mm3 p=0.02) (Figure 1).  Similarly, gyrification indices and sulcal depths were increased across all measures, with a significant increase in frontal and occipital lobe gyrification (frontal lobe HEU: 2.4±0.2 vs. HUU: 2.2±0.3, p=0.04, occipital lobe HEU: 2.4±0.3 vs HUU: 2.2±03), as well as occipital sulcal depth (HEU: 4.2±0.4 vs HUU: 3.8±0.6) (Figure 2). Conclusion(s): We show reduced regional brain growth and accelerated cortical maturation in HEU neonates compared to HUU controls. The cerebellum undergoes exponential growth in the latter half of gestation and is especially vulnerable to inflammatory processes and disturbances in nutrient and energy supply to the developing fetus. Similarly, accelerated cortical development, as measured by increased gyrification and sulcation, has been associated with adverse intrauterine stressors.  These preliminary data suggest potential alterations in early structural brain development that may contribute to neurodevelopmental impairments in HEU children. Larger studies and long-term follow-up of HEU are warranted.
Figure 1Reductions in neonatal brain volumes of HEU neonates compared to HUU controls.
Figure 2Increased regional gyrification and sulcation of the cerebrum in HEU neonates compared to HUU controls.