(221) Sex-specific placental histopathology effects on newborn cytokine-chemokine levels in a cohort with universal placental examination

Objective: To determine the association(s) of placental histopathology types with levels of developmentally important regulatory molecules assayed in newborn dried blood spots (DBS), and whether any associations differ by infant sex.

Study Design: 1809 children with complete placental evaluation by a single pathologist (CMS) had DBS retained as part of the New York State Newborn Screening Program. Assays were performed using the Bio-Rad 40-plex Illumina assay. Histopathology types were considered as binary (present/absent), and Mann Whitney U tests compared their relationships with DBS analyte levels. Results were stratified by sex. Acronyms for placental histopathology types with at least one significant association with a DBS analyte in either sex are as follows:

MAIR	Any versus no maternal inflammatory responses
FAIR-UC, FAIR-CV	Any versus no fetal inflammatory responses in umbilical cord (UC) or chorionic plate vessels (CV)
MVP-RVA	Any versus no maternal malperfusion pathology: reduced villous arborization
MVP-INF	Any versus no maternal malperfusion pathology: infarction
MVP-IVT with INF	Any versus no maternal malperfusion pathology: intervillous thrombus with peripheral infarct
FVP-Macro	Any versus no fetal vascular pathology in chorionic plate or fetal stem vessels
FVP-Micro	Any versus no fetal vascular pathology in villous capillaries
Dysmaturity	Immature and/or edematous appearing villi with decreased vasculosyncytial membranes
CPI-Mat	Any versus no chronic inflammation in maternal tissues
CPI- Fet	Any versus no chronic inflammation in placental villi

Results: Multiple significant associations were observed between placental histopathology types and DBS analytes, and the majority were seen either in males or females, but not both (Table).

Conclusion: The dramatic sex-specific differences in associations linking placental histopathology types and DBS analytes make infant sex a critical variable in any study of placental histopathology and its potential downstream and lifelong effects.