Relationship Between Neonatal Brain Injury and Objective Measures of Head Trauma: A Case-Control Study

Abstract

Background and objectives: Neonatal brain injury is a common and devastating diagnosis conferring lifelong challenges for children and families. The role of mechanical forces applied to the head, often referred to as "birth trauma," are often considered although evidence for this association is lacking. The objective of this study was to investigate the association between common types of neonatal brain injury and scalp swelling using a novel method to quantify scalp swelling as an unbiased proxy for mechanical forces applied to the head.

Methods: Case-control study using population-based, prospectively collected tertiary care center databases and healthy controls from the Human Connectome Development Project. Included were infants born 32-42 weeks gestational age and MRI in the first 9 days. Outcomes categories included healthy neonates, hypoxic ischemic encephalopathy (HIE) with or without brain injury, or stroke (ischemic or hemorrhagic). Volume of scalp swelling was objectively quantified by a novel imaging method blinded to brain injury. Variables included mode of delivery and use of instrumentation. Statistical tests included Kruskal-Wallis test, chi square, and multivariable and multinomial logistic regression.

Results: There were 309 infants included (55% male): 72 healthy controls, 77 HIE without brain injury on MRI, 78 HIE with brain injury, and 82 with stroke (60 ischemic, 22 hemorrhagic). Scalp swelling was present in 126 (40.8%, 95% confidence interval [CI] 35.2%-46.5%) with no difference in proportions between outcome groups. Compared to healthy controls, median volume was higher in those with HIE without brain injury (17.5 mL, 95% CI 6.8-28.2), HIE with brain injury (12.1 mL, 95% CI 5.5-18.6), but not ischemic stroke (4.7 mL, 95% CI -1.2-10.6) nor hemorrhagic stroke (8.3 mL, 95% CI -2.2-18.8). Scalp swelling was associated with instrumented delivery (OR 2.1, 95% CI 1.0-4.1), but not associated with increased odds of brain injury in those with HIE (OR 1.5, 95% CI 0.76-3.30). Scalp swelling measures were highly reliable (ICC = 0.97).

Discussion: "Birth trauma" quantified by scalp swelling volume was more common in infants with difficult deliveries, but not associated with greater odds of brain injury due to hypoxia or stroke. These results may help parents and practitioners to dissociate the appearance of trauma with the risk of brain injury.

Figure 1. MRI Method of Scalp Trauma Quantification

(A) A sagittal MRI image showing a patient with no scalp trauma. (B) A coronal T2-weighted image with extracranial trauma on the right side of the scalp and a neonatal arterial ischemic stroke (NAIS) on the left side of the brain (yellow dashed line). (C) A parasagittal T1 MRI image showing an area of scalp swelling denoted by the yellow arrow. The image intensity of the swelling is distinct from the surrounding tissues, facilitating the automated segmentation. (D) Areas of swelling were selected by thresholding signal intensity, assigning positive values to swelling (red), and assigning negative values to surrounding areas. Nontrauma areas may also be included in the selection at this stage. (E) To further refine the selection precision, seeds were placed within the areas of swelling to initialize the semiautomated 3D contour segmentation process (pink circles). The 3D region of interest (ROI) was expanded outward from the seeds until over 90% of the area was selected (pink). (F) Additional remaining trauma areas denoted by yellow arrows were manually added to the ROI on individual slices using the adaptive brush tool based on image intensity. Measurement of the final trauma ROI volume was then extracted. Images are presented in radiologic convention (right side of image is left side of patient).

Figure 2. Birth-Related Scalp Swelling and Brain Injury

(A) Proportion of patients with scalp swelling, error bars show 95% CI. (B) Violin plot demonstrating the distribution of scalp swelling volumes for patients with scalp swelling quantification (excluding those without scalp swelling). p values determined by generalized linear model (Gamma family) of scalp swelling volume, controlling for age at MRI, birth weight, gestational age, and male sex (Table 3).

Figure 3. Scalp Swelling Volume Is Not Related to Brain Injury Outcome

A multinomial model depicting probability of each outcome by volume of scalp swelling controlling for age at MRI, birth weight, gestational age, and male sex (eTable 3, links.lww.com/WNL/D219).