Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies.

BACKGROUND: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. OBJECTIVE: To quantify the association between periconception maternal RBC folate and offspring CHD risk. DESIGN: Prospective, nested, case-control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644). SETTING: 29 maternity institutions in 12 districts of Greater Shanghai, China. PARTICIPANTS: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). MEASUREMENTS: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. RESULTS: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). LIMITATION: Potential confounding due to unmeasured covariates in the nested case-control study. CONCLUSION: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

Comparison of Efficacy of Acupuncture-Related Therapy in the Treatment of Rheumatoid Arthritis: A Network Meta-Analysis of Randomized Controlled Trials.

Background: The refractory, repetitive, and disabling characteristic of rheumatoid arthritis (RA) has seriously influenced the patients' quality of life, and makes it a major public health problem. As a classic complementary and alternative therapy, acupuncture is usually applied for RA combined with disease-modifying anti-rheumatic drugs (DMARDs). However, there are various types of acupuncture, and the curative effects are different in different acupuncture therapies. In this study, we evaluated the clinical efficacy of different acupuncture therapies combined with DMARDs in the treatment of RA. Methods: The randomized controlled trials (RCTs) of acupuncture combined with DMARDs in the treatment of RA were searched in both English and Chinese database of PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, VIP database, Wanfang, and SinoMED, up to October 2021. Literature screening, data extraction, and evaluation of the risk of bias were carried out independently by two researchers, and the data were analyzed by Stata14.2 and GeMTC 0.14.3 software. Results: A total of 32 RCTs were included, including 2,115 RA patients. The results of network meta-analysis were as follows: in terms of improving DAS28 score, Electro-acupuncture + DMARDs has the best efficacy. In terms of improving VAS score, Fire Needle + DMARDs showed the best efficacy. In terms of improving morning stiffness time, acupuncture-related therapies combined with DMARDs were not better than DMARDs alone in improving morning stiffness time in RA patients. In terms of reducing CRP and ESR, Fire Needle + DMARDs showed the best efficacy. In terms of reducing RF, Moxibustion + DMARDs has the best efficacy. Conclusions: The comprehensive comparison of the outcome indicators in 8 different treatments indicates that electro-acupuncture combined with DMARDs is the best combined therapy in improving DAS28 score, while in terms of improving pain and serological markers, fire needle combined with DMARDs and moxibustion combined with DMARDs were the best combined therapies. However, it is impossible to find out which is better between fire needle and moxibustion due to the limited studies. Clinically, appropriate treatment should be selected according to the actual situation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, CRD42021278233.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Maternal folate levels during pregnancy and children's neuropsychological development at 2 years of age.

OBJECTIVE: To explore the relationship between maternal folate levels during pregnancy and children's neuropsychological development at 2 years of age. METHODS: In the birth cohort MKFOAD, maternal serum folate concentrations at 12-14, 22-26, and 34-36 weeks of gestation were measured, as well as red blood cell (RBC) folate at 12-14 weeks. Neurodevelopment of 2-year-old children was assessed by Gesell Development Scale (GDS), which contained subscales of gross motor, fine motor, language, adaptive behavior, and social behavior. Linear regression models were applied to investigate the association of maternal folate levels with children's developmental quotients (DQs). RESULTS: One hundred and eighty singleton children participated the GDS assessment, of whom 97 (53.9%) were boys. Median RBC folate concentration was 1002.8 (IQR = 577.6) nmol L-1 in early pregnancy and median serum folate concentrations were, respectively, 33.9 (IQR = 9.2) nmol L-1, 26.3 (IQR = 14.3) nmol L-1, and 26.7 (IQR = 18.9) nmol L-1. Maternal serum folate concentration in late pregnancy was significantly associated with children's language development, where language DQ increases by 3.1 (95% CI 0.6, 5.5) for every 10 nmol L-1 increment of serum folate concentration. And maternal serum folate in early pregnancy was significantly associated with children's fine motor development, with 2.0 (95% CI 0.1, 4.0) DQ decrease for 10 nmol L-1 increase of serum folate. CONCLUSIONS: Maternal serum folate in late pregnancy was significantly associated with children's language development at age 2, which supports the importance of remaining folic acid supplementation across the entire gestation. However, maternal serum folate in early pregnancy was also inversely associated with children's fine motor development.