MORPHOLOGICAL SPECTRUM OF NEURAL TUBE DEFECTS IN ABORTED HUMAN FETUSES AND ITS POSSIBLE ASSOCIATION WITH MTHFR C677T POLYMORPHISM IN MOTHERS

Abstract

Background: Neural tube defects (NTDs) represent a heterogeneous group of congenital malformations resulting from failure of neural tube closure during early embryogenesis. The MTHFR C677T polymorphism is a known genetic risk factor for NTDs in some populations, but data from Central Asia, particularly Uzbekistan, remain limited.

Objective: To characterize the morphological spectrum of NTDs in aborted human fetuses and investigate its possible association with the MTHFR C677T polymorphism in mothers.

Materials and Methods: A cross-sectional study was conducted at the clinics of Tashkent State Medical University (January 2021 – December 2024). A total of 145 aborted fetuses (12–28 weeks gestation) with confirmed NTDs were examined morphologically. Maternal blood samples (n=145) were genotyped for MTHFR C677T using PCR-RFLP. A control group of 150 mothers of healthy fetuses aborted for non-genetic indications was included.

Results: The morphological spectrum included anencephaly (34.5%), myelomeningocele (28.3%), encephalocele (15.9%), craniorachischisis (11.0%), and iniencephaly (6.2%). Associated anomalies (e.g., hydrocephalus, clubfoot, renal agenesis) were present in 53.8% of cases. The MTHFR 677T allele frequency was significantly higher in case mothers (0.386) vs. controls (0.213) (p<0.001). The CT genotype conferred an OR of 2.4 (95% CI: 1.4–4.1), and TT genotype an OR of 4.7 (95% CI: 2.3–9.6) for NTD-affected pregnancy. Stratified analysis showed that myelomeningocele and anencephaly were most strongly associated with TT genotype (OR 6.1 and 5.3 respectively).

Conclusion: The MTHFR C677T polymorphism is significantly associated with NTDs in the Uzbek population, particularly with open NTD phenotypes. Prenatal screening for this variant may be beneficial in high-risk families.