Global DNA Methylation in Cord Blood and Neurodevelopmental Outcome at 18 Months of Age among Intrauterine Growth Restricted and Appropriate for Gestational Age Infants

Abstract

Background: Intrauterine growth restriction (IUGR) is associated with faltered growth and development later in life. Alteration in DNA methylation may occur among IUGR babies and it can have bearing on the outcome.

Objectives: To compare the DNA methylation in the cord blood among IUGR and appropriate for gestational age (AGA) babies and find it is association with their neurodevelopmental outcome at 18 months of age.

Methodology: Genomic DNA methylation among 40 IUGR and equal number of AGA neonates was estimated by using 5-mC ELISA kit in the cord blood. Infants were assessed at birth and their anthropometric measurements were taken. They were regularly followed up and assessed for neurodevelopment outcome till 18 months of age using DASII (Developmental Assessment Scale for Indian Infants). DNA methylation was correlated with neurodevelopmental outcome. Numbers and percentages were used for categorical data. Mean and SD were used for continuous variables. The significant mean difference between IUGR and AGA was determined by independent Student t-test. To study the association between the DNA methylation and outcome, Spearman correlation was used. A p < 0.05 was considered as statistically significant.

Results: Significant difference in DNA methylation was observed between IUGR and AGA infants (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p < 0.001). Anthropometry (weight, length and head circumference) at birth was significantly decreased among IUGR infants. Hospital stay was significantly longer for IUGR infants. Motor (IUGR: 89.98 ± 18.77; AGA: 101.75 ± 9.62; p < 0.001), and mental (IUGR: 90.81 ± 11.13; AGA: 105.71 ± 7.20; p < 0.001) scores were significantly decreased among IUGR compared with AGA neonates at 18 months of follow-up. Global DNA methylation had a significant positive correlation with mental score but not with motor developmental score.

Conclusion: IUGR babies had lower motor and mental score compared with AGA babies. Cord blood global DNA methylation significantly correlated with mental development score but not with motor development at 18 months of age.

Keywords: DNA methylation; cord blood; intrauterine growth restriction; mental development; motor development.