Achievements and hidden concerns in neural tube defect prevention and control in China: temporal trends in disease burden (1990 to 2023) and a 10-year forecasting based on GBD 2023

Neural tube defects (NTDs) pose a serious threat to perinatal survival and long-term quality of life. Although folic acid intervention has been effective, the dynamic evolution of disease burden and residual risks remain incompletely elucidated. By analyzing the temporal trends of NTDs burden in China from 1990 to 2023, age-period-cohort effects, and projections for 2024-2033, this study aims to identify priority directions for intervention.

Data on prevalence, mortality, and disability-adjusted life years (DALYs) of NTDs in China were extracted from the Global Burden of Disease (GBD) 2023 database. Age-standardized rates (ASRs) were calculated using the GBD global reference population. Joinpoint regression was employed to identify turning points in temporal trends, and annual percent change (APC), and average annual percent change (AAPC), with their 95% confidence intervals (CI). An age-period-cohort model was applied to data from 1994-2023, stratified into 5-year intervals (age groups: <5 years to 80−84 years; birth cohorts: 1914-1918 to 2019-2023), to assess the contributions of age, period, and cohort effects to changes in NTDs prevalence. An autoregressive integrated moving average (ARIMA) model was employed to predict age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of NTDs in China from 2024 to 2033.

From 1990 to 2023, the AAPC of ASPR, ASMR, and ASDR for NTDs in China was−0.90% (95%CI:−1.01% to−0.78%), −8.51% (95%CI:−8.84% to −8.18%), and−7.89% (95%CI:−8.04% to−7.57%), respectively, indicating significant overall downward trends. Joinpoint regression analysis revealed a 3-phase fluctuation in ASPR: a continuous decline from 1990 to 2000 (1990-1995: APC=−7.98%, P<0.05; 1995-2000: APC=−4.80%, P<0.05); an overall rebound from 2000 to 2019 (2000-2005: APC=0.56%, P<0.05; 2005-2010: APC=5.18%, P<0.05; 2010-2015: APC= 0.01%, P>0.05; 2015-2019: APC=2.33%, P<0.05); and another decline from 2019 to 2023 (APC=−0.23%, P<0.05). Both ASMR and ASDR exhibited a 3-stage pattern: a slight increase from 1990 to 1997 (ASMR: APC=1.57%, P<0.05; ASDR: APC=1.44%, P<0.05), a sustained decline from 1997 to 2021 (all P<0.05), and a modest rebound from 2021 to 2023 (ASMR: APC=1.43%, P<0.05; ASDR: APC=0.91%, P>0.05). Sex-stratified analysis showed that ASPR was consistently higher in males than in females; however, ASMR and ASDR were higher in males before 2004 but reversed to consistently higher in females after 2004. In terms of age distribution, the peak number of prevalent cases occurred in the 5-9 year age group, while deaths and DALYs were highly concentrated in the neonatal period (<1 year). The age-period-cohort model demonstrated that age effects were heaviest during infancy (0-5 years), declining rapidly with increasing age; period effects showed an overall downward trend from 1994-2023, but weakened after 2015 (relative risk increased from 0.91 in 1999-2003 to 1.30 in 2019-2023); cohort effects, with 1964 as the reference, showed that risk was at a relatively low level in early cohorts, gradually rising to a peak in 1969-1973, followed by an overall fluctuating decline, dropping to a recent low in 2004-2008 before rebounding again, with a slight decline in 2019-2023. The ARIMA model projected a slight upward trend in ASPR, ASMR, and ASDR from 2024 to 2033, reaching 6.78/100000 (95%CI: 5.11 to 8.45), 0.12/100000 (95%CI:−0.60 to 0.83), and 12.37/100000 (95%CI:−51.15 to 75.89), respectively, by 2033.

The overall burden of NTDs in China decreased substantially from 1990 to 2023, but the mid-term rebound in prevalence and the projected upward trend indicate that the gains in prevention and control remain fragile, necessitating targeted interventions addressing residual risks.

Precision stratified interventions should be implemented on the foundation of consolidated universal folic acid supplementation; novel combined interventions such as inositol should be explored for folic acid non-responders; periconceptional folic acid monitoring and follow-up for advanced maternal age and high-risk populations should be strengthened, and the coverage of prenatal NTDs screening services expanded; integrated demonstration zones for “prevention-screening-intervention” should be established in high-prevalence provinces such as Shanxi; risk prediction models should be constructed using cohort data to promote the transition from universal supplementation to stratified precision prevention, and cross-departmental information sharing mechanisms for surveillance should be improved.