16 - Materno-Placental Proximal and Distal Risk Factors and Their Association with Outcomes in Neonatal Encephalopathy Due to Presumed Hypoxic-Ischemic Insult

Publication Number: 1014.16

Hannah Bills, The Hospital for Sick Children, Toronto, ON, Canada; Ashley Danguecan, The Hospital for Sick Children, Toronto, ON, Canada; Meredith Kinoshita, The Hospital for Sick Children, Toronto, ON, Canada; Astha Amrit, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada; Emily Lo, The Hospital for Sick Children, Toronto, ON, Canada; Amr El Shahed, The Hospital for Sick Children, Toronto, ON, Canada; Diane Wilson, The Hospital for Sick Children, Toronto, ON, Canada; Emily WY. Tam, The Hospital for Sick Children, Toronto, ON, Canada; Vann Chau, The Hospital for Sick Children, Toronto, ON, Canada; Helen Branson, The Hospital for Sick Children, Toronto, ON, Canada; Linh G. Ly, The Hospital for Sick Children, Toronto, ON, Canada; Rhandi Christensen, The Hospital for Sick Children, Toronto, ON, Canada; Mehmet Cizmeci, The Hospital for Sick Children, Toronto, ON, Canada

Background: Determining timing of injury in neonatal encephalopathy (NE) due to hypoxic-ischemic encephalopathy has prognostic value. The American College of Obstetricians and Gynaecologists define proximal risk factors as acute events occurring immediately prior to injury (e.g., placental abruption) and distal as chronic or remote conditions (e.g., chronic placental inflammation and maternal diabetes).

Objective: To determine whether proximal versus distal risk factors were associated with mortality and neurodevelopmental outcomes, and to determine their prognostic value.

Design/Methods: The study cohort included infants admitted to the Hospital for Sick Children, Toronto from October 2020 to May 2023 for therapeutic hypothermia. Placental histopathology, maternal risk factors, and neonatal clinical, biochemical, electrographic, and neuroimaging data were used to classify infants into 3 risk factor groups: proximal, distal, and proximal-on-distal. For outcome analyses, infants were further categorized as proximal-predominant or distal-predominant. The composite adverse outcome was defined as the presence of mortality, global developmental delay, any grade of cerebral palsy, or severe neurosensory impairment. Outcomes were assessed at 18 months' corrected age using standardized tests.

Results: The final analysis included 98 infants with available placental histopathology. Of these, 34 infants were categorised in the distal risk factor group, 43 in the proximal group and 21 in the proximal-on-distal group. The severity of NE, initial clinical and biochemical presentation, and clinical course during hospitalization were similar across the groups. Total brain injury scores on brain MRI were comparable across groups (distal: median 5, interquartile range (IQR) 4-19; proximal: 4, IQR 3-7; proximal-on-distal: 5, IQR 3-12; p=0.4). Mortality was 21% (9/43) in the distal-predominant group and 16% (6/38) in the proximal-predominant group (p=0.5), while composite adverse outcomes occurred in 28% (12/43) and 26% (10/38), respectively (p=0.9). The timing of materno-placental risk factors did not predict adverse outcomes after adjusting for the severity of NE (adjusted odds ratio 1.17, 95% CI 0.38-3.58; p=0.8).

Conclusion(s): Materno-placental proximal and distal risk factors were not associated with mortality or adverse neurodevelopmental outcomes at 18 months of age in our cohort and did not demonstrate prognostic significance after accounting for NE severity.

Table 1. Clinical, demographic and imaging results by risk factor grouping
Data are presented as n (%) unless specified otherwise
aKruskal-Wallis test, bChi-Squared test
*Data available in 97/98 infants
†Data available in 95/98 infants

Table 2. Outcomes by risk factor grouping
Data are presented as n (%) unless specified otherwise
aChi-Squared test
bStudent's t-test
*Data available in 34/43 and 32/38 infants
†The Bayley Scales of Infant and Toddler Development, 3rd edition, was used for assessments completed prior to July 2022, and the 4th edition was used thereafter

Figure 1. Bayley composite subscores
The Bayley Scales of Infant and Toddler Development, 3rd edition, was used for assessments completed prior to July 2022, and the 4th edition was used thereafter