603 - Placental histopathologic lesions and infant neurodevelopment following a term or late preterm birth

Publication Number: 3584.603

Madeline Meirhaeghe, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Mary Akel, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Samantha P.. Gottlieb, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Ivy Gleason, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Jiafeng Li, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Kennedi Williams, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Estefania Espinosa, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Elizabeth S.. Norton, Northwestern University, Evanston, IL, United States; Lauren S.. Wakschlag, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Jeffery Goldstein, Northwestern University, Chicago, IL, United States; Stephanie A.. Fisher, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Tonia Branche, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Leena B. Mithal, Ann and Robert H. Lurie Children's Hospital of Chicago / Northwestern University The Feinberg School of Medicine, Chicago, IL, United States

Background: Placental histopathologic lesions are associated with abnormal neurodevelopment in infants born extremely preterm. Knowledge of the impact of placental abnormalities on neurodevelopment among term or late preterm infants is limited.

Objective: To examine associations between placental histopathologic lesions and infant neurodevelopment in a low-risk cohort of term and late preterm infants.

Design/Methods: The Chicago Perinatal Origins of Disease cohort follows mother-infant dyads from pregnancy through two years of life. A perinatal pathologist examined placentas from deliveries ≥34w0d gestation to identify the following individual lesions: maternal and fetal inflammatory response (MIR, FIR), chronic inflammation, and maternal and fetal vascular malperfusion (MVM, FVM). At 4-6 months, parents completed the Ages and Stages Questionnaire-3rd Ed. (ASQ). At 12-16 months, the ASQ or the Bayley Scales of Infant and Toddler Development-4th Ed. (Bayley, in-person) was administered. The primary outcome was abnormal neurodevelopment assessment, defined as abnormal composite ASQ ("below cut off", or ≥2 standard deviations below the mean in at least one subdomain at either 4-6 or 12-16 months) or abnormal composite Bayley score (≤16th percentile); individual subdomains were secondarily assessed. Logistic regression was used to estimate odds ratios and 95% confidence intervals (CI), adjusted for maternal education, parity, and fetal sex (aOR).

Results: Among 90 dyads, the median gestational age at birth was 39.1 weeks, and 52% of birthing parents were non-White (Table 1). Placental lesions were not associated with greater odds of abnormal neurodevelopment (Figure 1). FVM was associated with greater odds of an abnormal ASQ personal-social score (aOR 7.1, 95%CI 1.6, 36.8). FIR presence (vs. FIR absence) was associated with greater odds of an abnormal Bayley cognitive score (median [IQR] 50 [5,75] vs. 16 [n=1]; OR 129, 95%CI 3.3-46194) or motor score (55 [50-73] vs. 14 [n=2]; OR 37, 95%CI 1.4, 6595); neither association remained significant in adjusted models (Table 2).

Conclusion(s): In this low-risk cohort placental histopathologic lesions were not associated with abnormal infant neurodevelopment assessment. Placental abnormalities in infants born at term or late preterm do not appear to portend risk of abnormal neurodevelopment assessment as in those born extremely preterm. While specific weak associations were observed with FIR and FVM, investigation in larger cohorts is needed to clarify the role of fetal vascular pathology and inflammation in shaping early neurodevelopment of term/late preterm infants.

Table 1. Cohort characteristics


Figure 1. Composite neurodevelopmental assessment outcomes by placental lesion
Abbreviations: Chronic inflammation (CI), maternal inflammatory response (MIR), fetal inflammatory response (FIR), maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM)
Figure 1 legend: a) Composite ASQ-3 score ("Below cut off" in at least 1 category was considered abnormal) at 4-6 or 12-16 months in presence or absence of specific placental lesions b) Composite Bayley-4 score (≤16th percentile in at least one subcategory categorized as abnormal) at 12-16 months in presence or absence of specific placental lesions. In some cases, chorion or amnion were not available to examine, thus total "n" may differ for certain placental lesions. *All comparisons between the presence or absence of placental lesion and infant composite developmental outcome were not statistically significant (p < 0.05).

Table 2. Association of specific placental histopathologic subtypes with abnormal infant neurodevelopmental assessments
Abbreviations: Odds ratio (OR), adjusted odds ratio (aOR), CI-confidence interval
a^An abnormal ASQ-3 score was defined as having a "below cutoff" score at either 4-6 or 12-18 months.
b^Firth's penalized logistic regression was used to examine the association of placental lesions with abnormal neurodevelopmental assessment.
c^Multivariate models were adjusted for maternal education, parity, and fetal sex.
d^In some cases, tissue to assess fetal inflammatory response (amnion) was not available.