Genomic Differences between Spontaneous versus Indicated Extreme Preterm Birth

Objective Extremely preterm infants are at high risk of neonatal mortality and morbidity. Extreme preterm birth (PTB) may result from spontaneous preterm labor or preterm premature rupture of membranes or may be indicated due to preeclampsia, eclampsia, hypertension, or other causes. Our objective was to identify single nucleotide polymorphisms (SNPs) and biological pathways associated with spontaneous versus indicated extreme PTB using the neonatal genome. Study Design We evaluated 523 spontaneous births and 134 indicated births weighing 401 to 1,000 g at birth from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network’s Genomics dataset by genome-wide association study (GWAS) and pathway analysis. The TOLSURF cohort was used to replicate the results. Results In the NRN GWAS, no statistically significant results were found, although the Manhattan plot showed one almost significant peak (rs60854043 on chromosome 14 at p ¼ 1.03E-07) along with many other modest peaks at p ¼ 1–9E-06, for a total of 15 suggestive associations at this locus. In the NRN pathway analysis, multiple pathways were identified, with the most significant being “GO_mf:go_low_density_lipoprotein_particle_receptor_activity” at p ¼ 1.14E-06. However, these results could not be replicated in the TOLSURF cohort. Conclusion Genomic differences are seen between infants born by spontaneous versus indicated extreme PTB. Due to the limited sample size, there is a need for larger studies.