Background: Mental disorders are the leading cause of global non-fatal disease burden, with rising prevalence among children, adolescents, and youth. This study analyzed location-, age-, and sex-specific estimates for nine mental disorders from 1990 to 2021 using GBD 2021 data, projecting burden to 2050.Methods: Methods included calculating average annual percentage change (AAPC) and annual percentage change (APC) for age-standardized prevalence rate (ASPR) and disability-adjusted life years rate (ASDR), alongside decomposition, inequality, frontier, comparative risk, and Bayesian age-period-cohort analyses.Results: Compared to 1990, the 2021 global burden significantly increased among youth [the AAPC of ASPR = 0.15, 95% confidence interval (CI): 0.14 to 0.16; the AAPC of ASDR = 0.40, 95% CI: 0.29 to 0.51], accelerating sharply after 2019 (the APC of ASPR = 4.74, 95% CI 4.55 to 4.93; the APC of ASDR = 6.64, 95% CI 4.88 to 8.42). Males experienced a higher burden than females, with variations in sex-specific patterns across age groups. Burden varied substantially by socio-demographic index (SDI), being highest in high-SDI regions [ASPR = 12913.13, 95% uncertainty interval (UI): 11135.82 to 14874.98; ASDR = 1750.41, 95% UI: 1253.46 to 2328.87]. We found that the burden changes of nine mental disorders vary at the global, regional, and national levels. Decomposition analysis highlighted that the changes in prevalence and the disability-adjusted life years (DALYs) were predominantly driven by population growth (84.86% and 57.92%), with the most significant improvements observed in higher SDI regions. Frontier analysis revealed the potential for burden reduction in higher income countries and territories. Globally, key risk factors included childhood sexual abuse, bullying, intimate partner violence, and lead exposure were identified for anxiety disorders, depressive disorders, and idiopathic developmental intellectual disability, respectively. Projections indicated that the burden of mental disorders is likely to continue its decline in 2050 (ASPR = 6120.71 per 100,000, 95% CI: 3973.57 to 8267.85; ASDR = 844.71 per 100,000, 95% CI: 529.48 to 1159.94).Conclusion: Despite projected rate declines by 2050, the global burden of mental disorders is increasing, with significant disparities across populations and a recent surge demanding intensified prevention and equitable healthcare expansion worldwide.

Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF? In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose. Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking. We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre. Women <43 years of age with AFC <10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1–6 started with 300 IU/day, while women with AFC 7–9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks’ gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective. We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99–1.38), risk difference 0.07 (95% CI, −0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83–1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91–1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44–1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer. As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results. In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs. This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work. Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944. 17 March 2019 20 March 2019

Background: The purpose of this study was to investigate the relationship between folic acid and iron nutrition during pregnancy and congenital heart disease (CHD) in the offspring. Methods: Conditional logistic regression models and nonlinear mixed-effects models were used to analyze the effects of folic acid and iron nutrition during pregnancy on CHD in offspring. Results: After adjusting for confounders, folic acid or iron supplementation during pregnancy reduced the risk for fetal CHD (OR = 0.60 (0.45, 0.82) or 0.36 (0.27, 0.48)). Similarly, dietary iron intake during pregnancy (≥29 mg/d) was associated with a reduced risk of fetal CHD (OR = 0.64 (0.46, 0.88)). Additionally, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or iron (OR = 0.32 (0.16, 0.60)), women who supplemented both folic acid and iron had lower risk for newborns with CHD (OR = 0.22 (0.15, 0.34)). Similarly, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or higher dietary iron intake (≥29 mg/d) (OR = 0.60 (0.33, 1.09)), women who supplemented both folic acid and higher dietary iron intake (≥29 mg/d) had lower risk for the newborn with CHD (OR = 0.41 (0.28, 0.62)). The combined effects were significant in the multiplication model (OR = 0.35 (0.26, 0.48) or 0.66 (0.50, 0.85)) but not in the additive model. Conclusions: Our study found that folic acid and iron nutrition during pregnancy were associated with a reduced risk of CHD in the offspring and confirmed a statistically significant multiplicative interaction between folic acid and iron nutrition on the reduced risk of CHD in offspring.

The association between folic acid supplementation and birth defects other than neural tube defects remains unclear. We utilized data from a large population-based survey to examine the association between folic acid supplementation and birth defects in Northwestern China. A total of 29,204 women with infants born between 2010 and 2013 were surveyed in Shaanxi province, Northwestern China, using a stratified multistage sampling method. Propensity scores were used to match 9,293 women with optimal folic acid supplementation with 9,293 women with nonoptimal folic acid supplementation, and the effects of optimal folic acid supplementation on birth defects were assessed by a conditional logistic regression model. After propensity score matching, the overall birth defect rate, cardiovascular system defect rate and nervous system defect rate for the women with optimal folic acid supplementation were lower than those for the women with nonoptimal folic acid supplementation (overall birth defects: OR = 0.71, 95% CI = 0.57–0.89, P = 0.003; cardiovascular system defects: OR = 0.65, 95% CI = 0.44–0.96, P = 0.032; nervous system defects: OR = 0.13, 95% CI = 0.02–0.99, P = 0.049). Optimal folic acid supplementation was associated with a decreased prevalence of birth defects, especially in the cardiovascular system and nervous system. Our findings have important implications for birth defect intervention with folic acid supplementation for countries with a high prevalence of birth defects, such as China.

Few studies have investigated the association between maternal dietary patterns (DP) during pregnancy, derived from reduced-rank regression (RRR), and fetal growth. This study aims to identify DP during pregnancy associated with macro- and micronutrient intakes, using the RRR method, and to examine their relationship with birth weight (BW). We used data of 7194 women from a large-scale cross-sectional survey in Northwest China. Dietary protein, carbohydrate, haem Fe density and the ratio of PUFA and MUFA:SFA were used as the intermediate variables in the RRR model to extract DP. Generalised estimating equation models were applied to evaluate the associations between DP and BW and related outcomes (including BW z-score, low birth weight (LBW) and small for gestational age (SGA)). Four DP during pregnancy were identified. Socio-demographically disadvantaged pregnant women were more likely to have lower BW and lower adherence to DP1 (high legumes, soyabean products, vegetables and animal-source foods, with relative low wheat and oils). Women with medium and high adherence to DP1 had significantly increased BW (medium 28·6 (95 % CI 7·1, 50·1); high 25·2 (95 % CI 2·7, 47·6)) and BW z-score and had significantly reduced risks of LBW and SGA. The associations were stronger among women with babies <3100 g. There is no association between other DP and outcomes. Higher adherence to the DP that was high in legumes, soyabean products, vegetables and animal-source foods was associated with improved BW in the Chinese pregnant women, particularly among those with disadvantageous socio-demographic conditions.