(977) Impact of maternal aspirin therapy on neonatal epigenetic patterns

Aspirin 81mg (bASA) between 10-12 weeks gestation is recommended for the prevention of preeclampsia. Maternal preeclampsia is associated with cord-blood epigenetic changes and childhood cardiovascular disease. However, little is known about the effects of bASA on the neonate. We examined epigenetic differences in neonatal cord blood with maternal exposure to bASA compared to control group (non-exposed).

Study Design:

Prospective study examining differential DNA methylation in cord blood cells of term singleton infants born to mothers with or without bASA use.  Deliveries complicated by chorioamnionitis or gestational hypertension spectrum were excluded. The umbilical cord blood was collected and genomic DNA was isolated using QIAamp Blood Mini kit. The Illumina Methylation EPIC Array technology was utilized to interrogate the methylation level at each CpG-site across the genomic DNA. The Illumina iScan Reader was used to analyze the image and data from Methylation EPIC Bead Chip. Data processing was performed with Illumina GenomeStudio software. Partek Genomics Suite software was used to determine if there was statistical significance and validity for each methylation site.

Results:

Patients in each group did not differ in maternal diabetes or hypertension (p=0.52). The two groups exhibited statistically significant differences in DNA methylation across the genome (Figure 1). Notably, the top canonical pathway involved was TGF signaling (p=7.73E-04, overlap 3.1%, 3/96) and top disease processes included hematologic (p=4.06E-02 – 4.23E-05, N=23 molecules) and cardiovascular (p= 4.41E-02 – 2.64E-04, N=10 molecules) (Table 1).

Conclusion:

We identified significant differences in the epigenetic methylation patterns of genomic clusters between bASA exposed and non-exposed neonates. TGF signaling was significantly altered between groups and is implicated in fetal vascular, lung, and cardiac development and maternal/fetal immune tolerance. Whether bASA can mitigate the infant epigenetic impact of maternal preeclampsia remains to be seen.