Non-Isolated Neural Tube Defects with Comorbid Malformations Are Responsive to Population-Level Folic Acid Supplementation in Northern China.

Che, Xiaoyu; Liu, Jufen; Galea, Gabriel L; Zhang, Yali; Greene, Nicholas D. E.; Zhang, Le; Jin, Lei; Wang, Linlin; Ren, Aiguo; Li, Zhiwen

Simple Summary: Neural tube defects are severe congenital malformations of the central nervous system. Some cases also have comorbid malformations in other organ systems, which cause morbidity and mortality in affected individuals. Although folic acid is effective in preventing neural tube defects, whether folic acid prevents those cases which have comorbid malformations, or only isolated neural tube defects is unknown. In this study, we described the epidemiology of neural tube defects with comorbid malformations and assessed the impact of folic acid supplementation. We found the prevalence of neural tube defects with comorbid malformations decreased after population-level folic acid supplementation in northern China. Malformations of various organ systems are more common in people with neural tube defects, suggesting common etiology. For fetuses with NTDs, clinicians are also suggested to consider screening for possible comorbid congenital malformations. Objective: Comorbid congenital malformation of multiple organs may indicate a shared genetic/teratogenic causality. Folic acid supplementation reduces the population-level prevalence of isolated neural tube defects (NTDs), but whether complex cases involving independent malformations are also responsive is unknown. We aimed to describe the epidemiology of NTDs with comorbid malformations in a Chinese population and assess the impact of folic acid supplementation. Study Design: Data from five counties in Northern China were obtained between 2002 and 2021 through a population-based birth defects surveillance system. All live births, stillbirths, and terminations because of NTDs at any gestational age were recorded. NTDs were classified as spina bifida, anencephaly, or encephalocele. Isolated NTDs included spina bifida cases with presumed secondary malformations (hydrocephalus, hip dislocation, talipes). Non-isolated NTDs were those with independent concomitant malformations. Results: A total of 296,306 births and 2031 cases of NTDs were recorded from 2002–2021. A total of 4.8% of NTDs (97/2031) had comorbid defects, which primarily affected the abdominal wall (25/97), musculoskeletal system (24/97), central nervous system (22/97), and face (15/97). The relative risk of cleft lip and/or palate, limb reduction defects, hip dislocation, gastroschisis, omphalocele, hydrocephalus, and urogenital system defects was significantly greater in infants with NTDs than in the general population. Population-level folic acid supplementation significantly reduced the prevalence of both isolated and non-isolated NTDs. Conclusion: Epidemiologically, non-isolated NTDs follow similar trends as isolated cases and are responsive to primary prevention by folic acid supplementation. Various clinically-important congenital malformations are over-represented in individuals with NTDs, suggesting a common etiology.

CHINA; FOLIC acid; NEURAL tube defects; HUMAN abnormalities; DIETARY supplements; SPINA bifida; COMORBIDITY

Biology (2079-7737), 2022, Vol 11, Issue 9, p1371

2079-7737

Academic Journal

10.3390/biology11091371