Integrating NRG1 and OXT Polymorphisms, Maternal Psychological Vulnerability, and Obstetric-Neonatal Outcomes: A Genotype-Phenotype Pilot Study.

Background and

Objectives

Maternal psychological vulnerability during pregnancy is associated with adverse obstetric and neonatal outcomes, but the contribution of candidate genetic markers remains insufficiently defined. This exploratory pilot case-control study examined NRG1 rs35753505, NRG1 rs3924999, and OXT rs2740210 together with validated psychological screening and obstetric-neonatal phenotyping in Romanian primiparous women.

Methods

Eighty-two primiparous women were enrolled between February 2024 and February 2025 at a tertiary maternity centre in Timișoara. After genotyping quality control, 79 women with complete data for all three SNPs (50 cases and 29 controls) formed the analytic sample. Fifty women with at least one obstetric complication were compared with 29 women with uncomplicated pregnancies. Participants completed the EPDS, GAD-7, PSS-10, and CD-RISC-25 at 20-28 gestational weeks. Genotyping was performed using TaqMan® allelic discrimination assays, with Hardy-Weinberg equilibrium assessment and exploratory carrier, allele-dosage, correlation, ANOVA, and logistic-regression analyses.

Results

The study lot had higher EPDS, GAD-7, and PSS-10 scores and lower CD-RISC-25 scores than controls (all p < 0.001). The three SNPs were in Hardy-Weinberg equilibrium and did not show statistically significant single-locus case-control differences. NRG1 rs3924999 A-carriers showed the strongest exploratory association pattern, including lower neonatal birth weight and higher psychological vulnerability scores. Across exploratory genetic risk score (GRS) tertiles, birth weight, Apgar-5, perceived stress, and resilience differed significantly; however, the formal multiplicative GRS × PSS-10 model for low birth weight was not significant. Stratified correlations suggested that the PSS-10-birth weight relationship was stronger in the high-GRS tertile.

Conclusions

NRG1 rs3924999 and the composite NRG1/OXT score may help define future replication hypotheses, but larger genotype-stratified cohorts are required before clinical risk stratification can be proposed. The composite score is an investigator-weighted, internally derived exploratory index rather than a validated genetic risk model, and the formal gene-environment interaction test was null, so the stratified correlations are descriptive only. The findings should be interpreted as hypothesis-generating.