Increased risk of orofacial clefts associated with maternal obesity: case–control study and Monte Carlo‐based bias analysis

Stott‐Miller M, Heike CL, Kratz M, Starr JR. Increased risk of orofacial clefts associated with maternal obesity: case–control study and Monte Carlo‐based bias analysis. Paediatric and Perinatal Epidemiology 2010. Our objective was to evaluate whether infants born to obese or diabetic women are at higher risk of non‐syndromic orofacial clefting. We conducted a population‐based case–control study using Washington State birth certificate and hospitalisation data for the years 1987–2005. Cases were infants born with orofacial clefts (n = 2153) and controls infants without orofacial clefts (n = 18 070). The primary exposures were maternal obesity (body mass index ≥30) and diabetes (either pre‐existing or gestational). We estimated adjusted odds ratios (ORs) to compare, for mothers of cases and controls, the proportions of obese vs. normal‐weight women and diabetic vs. non‐diabetic women. We additionally performed Monte Carlo‐based simulation analysis to explore possible influences of biases. Obese women had a small increased risk of isolated orofacial clefts in their offspring compared with normal‐body mass index women [adjusted OR 1.26; 95% confidence interval 1.03, 1.55]. Results were similar regardless of type of cleft. Bias analyses suggest that estimates may represent underlying ORs of stronger magnitude. Results for diabetic women were highly imprecise and inconsistent. We and others have observed weak associations of similar magnitude between maternal obesity and risk of non‐syndromic orofacial clefts. These results could be due to bias or residual confounding. However, it is also possible that these results represent a stronger underlying association. More precise exposure measurement could help distinguish between these two possibilities.     

Risk factors for oral clefts: a population-based case-control study in Shenyang, China

Shenyang in Northern China has one of the highest reported prevalence rates of oral clefts in the world. To explore the risk factors for oral clefts in Shenyang, we carried out a population-based case-control study. A total of 360 990 births in 2000 to 2007 were screened for oral clefts; the overall prevalence was 1.76 per 1000. The ratio of cleft lip with or without cleft palate (CL ± P) : cleft palate only (CP) was 5.60:1. The overall male : female ratio was 2.02:1. CLP and CL were more common in males than in females with a sex ratio (SR) of 2.88:1 and 1.86:1 respectively, whereas CP was more common in females with an SR of 0.71:1.
Using a multivariable conditional logistic regression model, 586 oral clefts cases were compared with 1172 control mothers. Maternal factors significantly associated with increased risk for oral clefts were history of a fever or cold (adjusted OR 2.34, 95% CI 1.06, 5.60); use of analgesic and antipyretic drugs (adjusted OR 3.10, 95% CI 1.41, 6.86); poor ventilation during heating (adjusted OR 2.25, 95% CI 1.10, 4.60); and consumption of pickled vegetables >6 per week (adjusted OR 3.86, 95% CI 1.11, 13.47) during pregnancy. Factors which appeared to be protective were meat consumption ≥4 times per week (adjusted OR 0.43, 95% CI 0.28, 0.67); and legume consumption >6 times per week (adjusted OR 0.60, 95% CI 0.41, 0.89). Differences in risk were found between the two most common phenotypes, CL ± P and CP only. Most of the environmental factors had stronger associations with risk for CL ± P rather than CP, whereas history of oral clefts, as well as legume consumption, were more strongly associated with the risk for CP than for CL ± P. The findings suggest that aetiological heterogeneity may exist between CL ± P and CP.     

MTHFR基因多态性与非综合征性唇腭裂的遗传易感性

目的　探讨 MTHFR基因热敏感性多态性在非综合征性唇腭裂 (NSCL / P)发病以及遗传易感性中的作用。方法　应用聚合酶链反应 -限制性片段长度多态性 (PCR- RFL P)方法检测 MTH-FR热敏感性基因型 ;对 2 9个 NSCL / P核心家庭进行以父母为对照的病例对照研究 ,计算 TDT和HHRR;另外对该 2 9例 NSCL / P患儿及其父母和 5 8例正常儿童及其父母进行了成组病例对照研究 ,分别计算 MTHFR热敏感性纯合突变对 NSCL / P的比值比。结果　核心家庭分析显示 TDT(χ2 ) =3.5 6 ,P >0 .0 5 ,HHRR(成组χ2 ) =1.6 9,P >0 .0 5 ;患儿及其母亲、父亲 MTHFR热敏感性纯合突变对 NSCL / P的相对危险度 OR值分别为 0 .72、1.11和 0 .75 ,P >0 .0 5。结论　 MTHFR基因热敏感性多态性可能不是 NSCL / P的遗传易感性因素     

The contribution of maternal epilepsy and its treatment to the etiology of oral clefts: A population based case-control study

The associations between maternal epilepsy and anticonvulsant drug therapy with the risk of oral clefts in the offspring were investigated using data from a population-based case-control study. Cases included 238 infants with cleft lip ± cleft palate (CLP) and 107 infants with cleft palate (CP) ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1968 and 1980. Controls included 3029 population-based normal infants. Histories of maternal epilepsy and drug therapy during pregnancy were compared between cases and controls using maternal interviews and reviews of hospital medical records. Maternal epilepsy was associated with increased risk of nonsyndromic CLP (OR = 3.78, 95% C.I. 1.65–7.88), and less with CP (OR = 1.75, 95% C.I. 0.20–6.99). Therapy during pregnancy was associated with the greatest excess risk (CLP OR = 7.77, C.I. 2.02–26.0; CP OR = 3.61, C.I. 0.08–26.5). The use of polytherapy was associated with the highest risk (CLP OR = 10.5, C.I. 1.52–59.9). Adjustment for potential confounding variables in the study did not change these findings. In this well-defined population, maternal epilepsy and its treatment account for a small proportion of nonsyndromic oral clefts (attributable fraction CLP = 3.3%, CP = 0.9%). © 1994 Wiley-Liss, Inc.     

叶酸代谢相关基因多态性在母胎医学领域的应用及相关性研究

目的 探讨叶酸代谢相关基因多态性在母胎医学领域的应用及相关性研究.方法 该研究应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法,研究叶酸代谢与唐氏综合征(DS)、非综合征性唇腭裂(NSCL/P)之间的关系.结果 DS与叶酸代谢之间,经Logistic回归分析,携带MTHFR TT基因型母亲孕育DS患儿的风险是CC基因型的2.41倍(OR=2.41,95％CI:1.32～9.48,P＜0.05),MTRR基因GG基因型母亲生育DS患儿的风险增加2.74倍(OR=2.74,95％ CI:1.23 ～8.38,P＜0.05).NSCL/P与叶酸代谢之间,经Logistic回归分析,携带CBS基因的rs397589 TT基因型使NSCL/P的患病风险提高2.51倍(OR=2.51,95％ CI:1.23～ 14.38,P＜0.05).结论 采用分子医学检测,在一定程度上能够解释叶酸利用能力障碍所导致的胚胎发育异常,但是也有一定的局限性.     

Poor adherence to folic acid and iodine supplement recommendations in preconception and pregnancy: a cross‐sectional analysis

Objective: To determine pregnant women's knowledge of and adherence to the recommendations for periconceptional folic acid supplementation (PFS) and iodine supplementation (IS). Secondary objectives include determining predictors of adherence, and identifying influential nutrition information sources. Methods: A cross‐sectional online survey was completed by 857 pregnant women, including a national cohort (n=455) recruited using an online panel provider and a South Australian cohort (n=402) recruited from a public maternity hospital. Results: Adherence to PFS and IS recommendations was 27% and 23%, respectively. Planning pregnancy and awareness of the correct timing of recommendations were predictors of adherence for both recommendations. Not consuming any alcohol during pregnancy and living in metropolitan areas also predicted adherence to the IS recommendation. Awareness of the recommendation was greater for folic acid (more than 90%) than iodine (56–69%). Knowledge of the importance of folic acid and iodine was greater than knowledge regarding the recommended dose and timing of supplementation. Main healthcare providers were considered the most influential nutrition information sources. Conclusions and implications: Knowledge of and adherence to supplement recommendations for preconception and pregnancy needs improvement. While main healthcare providers may play an important role, further research is needed to explore strategies for increasing adoption of recommendations.     

MTHFR C667T基因多态性与食管癌易感性关系Meta分析

  目的  探讨山西省长治市移民与非移民人群血浆叶酸含量、亚甲基叶酸还原酶MTHFR C677T和甲硫氨酸合成酶MS A2756G位点多态性分布特点,为进一步研究其与疾病的相关性提供依据。  方法  于2014年5月 — 2015年6月采用酶联免疫吸附试验（ELISA）对80名长治林州移民和108名长治本地健康人群测定血浆中叶酸含量。同时采用聚合酶链反应-限制性片段长度多态性技术（PCR-RFLP）分析长治市人群MTHFR677位点和MS 2756位点基因多态性。  结果  移民组与非移民组人群叶酸含量差异有统计学意义（P = 0.006）。移民组内不同性别、年龄和是否饮酒的人群之间叶酸水平差异有统计学意义（P < 0.05）;非移民组组内不同血型的人群间差异有统计学意义（P < 0.05）。2组组间比较结果表明：女性、 > 60岁、体质指数（BMI） < 18.5 kg/m²、不吸烟和不饮酒的人群叶酸水平差异有统计学意义,MTHFR、MS的基因型和等位基因频率比较差异有统计学意义（P < 0.05）。  结论  在不同特征的长治移民与非移民人群中血浆叶酸含量不同,2组人群MTHFR和MS基因多态性分布存在明显差异。     

Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA). Methods: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation. Results. The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares. Conclusions: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications.     

Folic Acid Is Related to Muscle Strength and Vitamin A Is Related to Health-Related Quality of Life: Results of the Korea National Health and Nutrition Examination Survey (KNHANES VII 2016–2018)

This study investigated how folic acid affects muscle strength and the effects of vitamin A on quality of life in adults. Baseline data from the Korea National Health and Nutrition Examination Survey (KNHANES VII 2016–2018) was used to find 6112 adults (ages 19–80) meeting study criteria. The participants were divided into three groups: young adults (ages 19–39), middle-aged (ages 40–64), and elderly (≥65 years). Muscle strength was measured using a digital grip strength dynamometer. The EuroQol five-dimension questionnaire measured quality of life. Associations were assessed using multivariate regression and logistic regression. Vitamins and handgrip strength were divided into low and high groups based on the mean. Although vitamin A and folate levels were related to handgrip strength in all subjects, regression demonstrated a significant association between folate and handgrip strength in the elderly. The odds ratios (OR) of higher handgrip strength were statistically significant for elderly participants with high levels of folate compared to those with low levels (OR: 1.55). Vitamin A was associated with quality of life, especially in the self-care dimension for the elderly. Further longitudinal research is needed to examine the relationship between vitamins and muscle strength, as well as vitamins and quality of life.     

Folate status and socio‐demographic predictors of folate status,among a national cohort of women aged 26–36 in Australia, 2004–2006

Objective : To describe serum folate status and the socio‐demographic correlates of serum folate status in a national sample of women aged 26–36 years in Australia, 2004–2006. Methods: Stored serum samples from 1,046 women, collected as part of the Childhood Determinants of Adult Health study, were analysed for serum folate. Results: Median (IQR) serum folate was 27.1 nmol/L (18.8–35.0 nmol/L) with only 7.0% of samples below 11 nmol/L. Serum folate was positively associated with supplement use, educational level, occupational status and urban dwelling. Conclusions: In this population‐based sample, most women had folate levels in the normal range with few having low serum folate. Those of lower socioeconomic position or with poorer health behaviours had lower folate levels, though most were still within the normal range. Implications: In the absence of comprehensive national survey data on the folate status of women of child‐bearing age, these data provide a valuable baseline for evaluating the impact of mandatory folic acid fortification in Australia, which commenced in 2009. It is likely that mandatory fortification of the food supply with folic acid will reduce the disparities in folate status between socioeconomic groups and in people with poorer health behaviours.     

Prevalence of vitamin B12 deficiency in healthy Indian school‐going adolescents from rural and urban localities and its relationship with various anthropometric indices: a cross‐sectional study

Background

Micronutrient deficiency is a global health burden, especially among developing countries. The present cross‐sectional study aimed to determine the prevalence of vitamin B₁₂ deficiency in healthy Indian school‐going adolescents, based on area of residence, sex and body mass index (BMI) . Furthermore, the relationship of serum B₁₂ concentration with dietary vitamin B₁₂ intake and anthropometric indices was assessed among adolescents from rural and urban India.

Methods

A total of 2403 school‐going adolescents (11–17 years) from National Capital Region and rural areas of Haryana, India were selected. Serum B₁₂ concentrations were estimated using an electrochemiluminescence immunoassay. Dietary assessments were conducted on 65% of total participants (n  = 1556) by two 24‐h diet recalls.

Results

The prevalence of vitamin B₁₂ deficiency in the total study population was 32.4% (rural: 43.9% versus urban: 30.1%, P  < 0.001; male: 34.4% versus female: 31.0%, P  < 0.05; normal weight: 28.1%, versus overweight: 39.8%, versus obese: 51.2%, P  < 0.001). More than half (51.2%) of obese adolescents were vitamin B₁₂ deficient. On multiple linear regression analysis, serum B₁₂ in rural adolescents was associated with age (β = ?0.12, P  < 0.05). Among urban adolescents, serum B₁₂ was associated with BMI (β = ?0.08, P  < 0.05) and adjusted dietary vitamin B₁₂ intake (β = 0.14, P  < 0.001). Serum vitamin B₁₂ levels were found to be lower in rural females (β = ?0.12, P  = 0.030) and urban males (β: 0.11, P  < 0.001) compared to their respective contemporaries.

Conclusions

Vitamin B₁₂ deficiency was higher among rural school‐going adolescents. Boys had a higher B₁₂ deficiency than girls. Inverse associations of serum B₁₂ with adiposity indices were observed. Serum B₁₂ levels were positively associated with dietary vitamin B₁₂ intake.