Maternal genetic risk factors for spontaneous preterm birth: a
systematic review and meta-analysis
Abstract
Background: Despite various genomic approaches used in prior studies
investigating association of maternal genetic variability with
spontaneous preterm birth (sPTB), results show inconsistency and
contradictions. Objectives: To: conduct a systematic review of studies
analysing the association between maternal genetic variants and sPTB;
evaluate retrieved studies based on selection criteria; classify studies
into hypothesis-based and hypothesis-free; perform a meta-analysis to
identify the strongest associations. Search Strategy: PubMed, Scopus and
reference lists were searched until October 2023. Selection Criteria:
English-language case-control, cross-sectional and prospective cohort
studies examining the association between maternal genetic variations
and sPTB were included. Data collection and Analysis: Data on authors,
publication year, ethnicity, genes/variants, P-values, study type,
sample size, inclusion criteria and methods were collected. The
association strength was estimated using odds ratios with 95%
confidence intervals. Main Results: 81 studies met eligibility criteria:
72 utilized a hypothesis-based and 9 a hypothesis-free approach. 34
studies qualified for a meta-analysis revealing a significant
association in TNF-α (rs1800629) gene for alleles, additive and
recessive genetic models (P<0.05). From the hypothesis-free
approach, 7 variants in 5 genes (EBF1, EESEC, HSPA1L, ASTN1, MAST1)
reached global significance (P < 5 x10 -8).
Conclusions: No specific genes or variants were clearly associated with
the risk of sPTB. Among hypothesis-based studies, limited gene overlap
indicates inconsistent SNP associations. TNF-α (rs1800629) emerges as
the only with a modest signal for future analyses. Additional 5 genes
from the hypothesis-free approach showed a globally significant
association. Funding: / Keywords: Preterm Birth, Genetic Association
Study, Genome-Wide Association Study, Exome Sequencing