增补叶酸预防神经管缺陷:研究进展与展望

神经管缺陷是一类严重威胁新生儿健康的疾病,育龄妇女通过增补叶酸可有效预防神经管缺陷。目前世界各国采用多种方式为育龄妇女增补叶酸,在取得了一定的效果同时也有缺陷和不足。本文通过评价和比较国内外增补叶酸的研究进展,提出了巩固增补叶酸预防神经管缺陷效果的方向。     

叶酸补充过量与生殖风险相关性的研究进展

目的：叶酸参与DNA、RNA的合成，是细胞组织生长繁殖的必需物质，是胚胎生长发育必不可少的维生素之一。为了防止子代神经管畸形的发生，妇女可以在妊娠前后适当补充叶酸。目前临床叶酸应用往往存在着补充剂量大、时间长的问题，叶酸过量的影响尚且缺乏系统概述。本文介绍了国内外相关临床研究和动物试验结果，并进行了分析和归纳，以评价孕妇叶酸摄入过量对生殖风险的影响。对于母体而言，高剂量的叶酸的补充可能导致孕妇免疫功能异常，增加妊娠期糖尿病的风险、引起同型半胱氨酸异常积累。对于子代而言，高剂量叶酸可能增加子代肥胖症、哮喘、代谢、神经系统疾病发生的风险。围妊娠期孕妇补充叶酸应在检测后进行用药，并控制叶酸补充的时间及剂量，避免盲目增补。     

孕前及孕期增补叶酸与子痫前期发生风险的研究

目的 探讨孕前及孕期增补叶酸与子痫前期（PE）发生风险的关系。方法 选取2012年3月至2016年9月于山西医科大学第一医院妇产科住院分娩的9 048例单胎活产孕妇为研究对象,以882例PE孕妇为病例组,8 166例非PE孕妇为对照组,收集孕妇的一般人口学特征、孕前及孕期增补叶酸情况、妊娠并发症及相关影响因素等信息。采用非条件logistic回归分析增补叶酸与PE发生风险的关系及孕前BMI对增补叶酸与PE关系的影响。结果 调整孕妇年龄、文化程度等因素后,与未增补叶酸者相比,增补叶酸者发生PE的风险降低（OR=0.79,95% CI：0.64 ～ 0.96）。孕前和孕期均增补叶酸可降低PE的发生风险（OR=0.63,95% CI：0.49 ～ 0.81）;单纯增补叶酸片及增补叶酸片和含叶酸的复合维生素是PE的保护因素（OR=0.81,95% CI：0.66 ～ 0.99;OR=0.64,95% CI：0.49 ～ 0.85）,单纯增补含叶酸的复合维生素与PE未显示关联;增补叶酸剂量<400、400及>400 μg/d与PE发生风险降低有关（OR=0.62,95% CI：0.42～0.91;OR=0.81,95% CI：0.66～0.99;OR=0.68,95% CI：0.49～0.94）。按孕前BMI分层后,孕前BMI<24.0 kg/m²的孕妇增补叶酸是PE的保护因素（OR=0.75,95% CI：0.59～0.96）;在孕前BMI≥24.0 kg/m²的孕妇中未发现增补叶酸与PE有关。结论 孕前和孕期均增补叶酸与PE发生风险降低有关,且孕前BMI可能影响增补叶酸与PE的关系,应对不同孕前BMI人群分别提出适宜的增补叶酸建议。     

不可小觑过敏性哮喘

2020年的5月7日是第22个世界哮喘日。据国际权威医学期刊《柳叶刀》发表的我国学者完成的《中国成人哮喘流行状况、风险因素与疾病管理现状》研究结果显示,我国20岁及以上人群哮喘患病率为4.2%,其中男性患病率4.6%,女性患病率3.7%,患者总人数为4570万。《中国过敏性哮喘诊治指南》(2019年第1版)中介绍,过敏性哮喘的发病率高于非过敏性哮喘。通过中西医结合方法治疗,加强全程防控,是控制过敏性哮喘及降低过敏性哮喘疾病负担的有效措施。     

影响育龄妇女叶酸增补的因素

出生缺陷已经成为影响新生儿健康和生命的主要疾病 ,神经管畸形及多种出生缺陷的发生与妇女孕早期叶酸缺乏有关 ,孕期前后增补叶酸可以降低胎儿多种出生缺陷的危险性。叶酸增补形式中最方便、经济而有效的是服用叶酸增补剂 ,但由于多种因素影响 ,育龄妇女叶酸增补剂服用率较低。可能影响育龄妇女叶酸增补的因素包括人口、经济及社会学特征 ,生理、心理事件 ,对叶酸的知识、态度和信念 ,以及行为干预等几个方面。     

影响育龄妇女叶酸增补的因素

出生缺陷已经成为影响新生儿健康和生命的主要疾病，神经管畸形及多种出生缺陷的发生与妇女孕早期叶酸缺乏有关，孕期前后增补叶酸可以降低胎儿多种出生缺陷的危险性。叶酸增补形式中最方便、经济而有效的是服用叶酸增补剂，但由于多种因素影响，育龄妇女叶酸增补剂服用率较低。可能影响育龄妇女叶酸增补的因素包括人口、经济及社会学特征，生理、心理事件，对叶酸的知识、态度和信念，以及行为干预等几个方面。     

孕期营养对儿童期哮喘及遗传性过敏性体质发生的影响

20世纪90年代 Barker DJ提出健康与疾病发育起源的学说,越来越多的流行病学调查及动物实验提示母亲孕期营养对其子代成年以后非感染性疾病(代谢性综合征及心肺疾病等)的发生有着重要的联系。而也有一些调查研究发现母亲孕期营养可能引起子代成年时期非感染性疾病,还可能影响子代儿童时期非感染性疾病的发生,如儿童哮喘,喘息,遗传性过敏体质等。这些疾病带给患儿心理负担,严重影响患儿生长发育、生活质量并伴有生命危险。然而大量的研究提示孕期合理营养,科学膳食可以降低子代这些疾病的发病风险。我国目前生活质量提高,现如今多数孕妇营养摄入不平衡,或处饱和甚至过剩状态,而儿童过敏性疾病的发生逐年增加。本文就孕期营养对子代儿童期哮喘,喘息及遗传性过敏性体质发生的影响做一简要的综述。     

成人过敏性哮喘危险因素的病例对照研究

目的 探讨导致成人过敏性哮喘及其发作的危险因素。方法 采用病例对照流行病学研究方法,收集102例成人过敏性哮喘患者和394例健康对照人群的一般社会人口学特征、疾病健康状况、吸烟史、职业接触史、室内环境状况以及家族史等信息。结果 单因素及多因素统计分析结果均显示:成人过敏性哮喘患者职业粉尘接触率高于对照组且差异有统计学显著性(P<0.05,OR=1.78);住房类型为平房/筒子楼较多层/高层楼导致过敏性哮喘或其发作的可能性大(P<0.05,OR=3.24),哮喘患者家中床褥晾晒频率较对照组低且差异具有统计学显著性(P<0.10,OR=1.53);哮喘患者家中起居室地面使用木板比例高于对照组且差异有统计学显著性(P<0.01,OR=2.33);室内油烟污染程度哮喘患者组高于对照组且差异有统计学显著性(P<0.01,OR=2.52);同时还发现,双亲中有慢性支气管炎(慢支)或哮喘疾病史可增加其子女患过敏性哮喘的危险性(P<0.01,OR=2.32)。结论 室内环境因素中住房状况差、床褥晾晒频率少、起居室地面使用木板、室内油烟污染可能是成人过敏性哮喘的危险因素,同时职业接触粉尘、双亲有慢支或哮喘疾病史也与该疾病具有一定的关系。研究结果提示成人过敏性哮喘是遗传和环境双重因素共同作用导致的一种复杂疾病。     

过敏性鼻炎儿童发生支气管哮喘的影响因素分析

  目的  探讨过敏性鼻炎患儿发生支气管哮喘的危险因素,为鼻炎患儿发生哮喘的早期诊断、治疗和预防提供依据。  方法  纳入2019年11月至2020年10月在首都儿科研究所变态反应科门诊就诊的单纯过敏性鼻炎患儿(117例)和过敏性鼻炎继发哮喘患儿(111例),采集病史,检测过敏原,对其临床特征、过敏原种类及危险因素等进行统计分析。  结果  单因素分析显示,鼻炎病程、鼻炎严重度、鼻炎类型、季节特征、宠物接触史、过敏性疾病家族史、霉菌、豚草、粉尘螨和户尘螨致敏与过敏性鼻炎患儿哮喘的发生相关(χ2值分别为6.15,8.79,3.99,9.44,5.17,4.43,8.48,10.38,6.18,5.31,P值均 < 0.05)。多因素Logistic回归分析显示,鼻炎严重度(OR=7.03)、过敏性疾病家族史(OR=8.24)、霉菌(OR=5.19)、粉尘螨(OR=25.25)与过敏性鼻炎患儿哮喘的发生呈正相关(P值均 < 0.05),粉尘螨致敏患儿的风险最高。  结论  儿童过敏性鼻炎继发哮喘受多种因素影响,其中鼻炎严重度、过敏性疾病家族史、尘螨致敏是最主要的因素。     

中国北方部分地区妇女围孕期叶酸服用状况

国内外研究证实,妇女在怀孕前后增补叶酸可以有效地预防大多数神经管畸形病例的发生。一些研究证据还表明,妇女怀孕前后增补叶酸可以预防先天性心脏病、唇腭裂、肢体短缺、肛门闭锁、脐膨出、先天幽门肥大性狭窄等重大出生缺陷的发生。中国为出生缺陷高发的国家之一,许多种出生     

妊娠前干预的方法及效果评价

妊娠前干预是孕前期保健的重要组成部分。对妊娠前风险的准确评估和有效干预可显著改善妊娠结局。目前证明有效的干预方式包括,生活方式改变、环境改善、叶酸补充、遗传咨询以及慢性和感染性疾病控制等。对于生活方式和环境中的危险因素,开展大量的干预研究,效果显著。为保证围妊娠期妇女的叶酸摄入量,普遍采用补充叶酸制剂和食物叶酸强化两种方法。孕前遗传咨询是妊娠前干预的重要手段之一,其涉及生物医学、伦理道德、社会经济等多方面问题,目前还存在一些不足,但发展迅速。对患有慢性或传染性疾病的妇女采取一系列规范化的干预措施,可明显改善妊娠结局。     

Early Folic Acid Supplement Initiation and Risk of Adverse Early Childhood Respiratory Health: A Population-based Study

Objectives Folate plays a vital role in biologic functions yet women often do not meet the recommended dietary intake in pregnancy. It has been suggested that high folic acid intake during pregnancy may increase the risk of respiratory diseases in offspring. However, findings from observational studies in human populations are inconclusive. Methods In this population-based study, we collected self-reported folic acid and prenatal vitamin supplement use during pregnancy 3–6 months postpartum from mothers in Los Angeles whose children were born in 2003. Supplement initiation was based on whichever supplement, either folic acid or prenatal supplements, the women initiated first. In a 2006 follow-up survey, approximately 50% of women were re-contacted to gather information on the child’s respiratory health, including symptoms and diagnoses, at approximately 3.5 years of age. Results Overall, timing of folic acid supplement initiation was not associated with wheeze or lower respiratory tract infection, even after accounting for preterm births and censoring at follow-up. However, children born to mothers with a history of atopy (hay fever, eczema or asthma) who initiate folic acid supplements in late pregnancy, compared to first trimester initiators, have 1.67 (95% CI 1.12, 2.49) times the risk of wheeze in the first 3 years of life and 1.88 (95% CI 1.05, 3.34) times the risk of wheeze in the past year. No association was found among children of non-atopic mothers. Conclusions These findings suggest that early folic acid or prenatal supplementation among atopic women may be important to prevent wheeze among offspring.     

Public health control of hyperhomocysteinemia and its consequences

The etiological role of hyperhomocysteinemia in the origin of neural-tube defects was proved, therefore a mandatory flour folic acid fortification program was introduced in the USA since January 1, 1998. In Hungary one kind of breads was fortified with folic acid, vitamin B12 and vitamin B6. The Hungarian randomised controlled trials of periconceptional folic acid containing micronutrient-combination supplementation also indicated a reduction in the occurrence of congenital cardiovascular malformations, urinary tract's defects and congenital limb deficiencies and these findings were confirmed by US teams. Recent studies showed a positive association between cardiovascular diseases and hyperhomocysteinemia as well, thus it is considered as an independent etiological factor in the pathogenesis of ischemic heart diseases, stroke, deep vein thrombosis, in addition of vascular diseases in the placenta during pregnancy. Other studies showed that hyperhomocysteinemia is more prevalent in demented patients and in persons with impaired cognitive performance. Some association was also found between hyperhomocysteinemia and cancers (e.g. colon). There is strong evidence that four vitamins B, such as vitamin B11 (folate-folic acid), vitamin B12, B2 and B6 can reduce the level of serum homocysteine and subsequently neural-tube defects. In addition the results of intervention studies indicated a protective effect of folic acid and other vitamins B for some other congenital abnormalities, cardiovascular diseases, senile dementia and cancers. The flour fortification with these water-soluble vitamins B is appropriate for an effective public health program for the primary prevention of these hyperhomocysteinemia-related disorders. There is no real risk for side effects on the basis of available US, Canadian and Hungarian experiences. In conclusion an urgent task is to introduce a mandatory flour fortification program in Hungary.     

Primary Prevention of Pediatric Asthma through Nutritional Interventions

Asthma is the most common chronic non-communicable disease in children, the pathogenesis of which involves several factors. The increasing burden of asthma worldwide has emphasized the need to identify the modifiable factors associated with the development of the disease. Recent research has focused on the relationship between dietary factors during the first 1000 days of life (including pregnancy)—when the immune system is particularly vulnerable to exogenous interferences—and allergic outcomes in children. Specific nutrients have been analyzed as potential targets for the prevention of childhood wheeze and asthma. Recent randomized controlled trials show that vitamin D supplementation during pregnancy, using higher doses than currently recommended, may be protective against early childhood wheezing but not school-age asthma. Omega-3 fatty acid supplementation during pregnancy and infancy may be associated with a reduced risk of childhood wheeze, although the evidence is conflicting. Data from observational studies suggest that some dietary patterns during pregnancy and infancy might also influence the risk of childhood asthma. However, the quality of the available evidence is insufficient to allow recommendations regarding dietary changes for the prevention of pediatric asthma. This review outlines the available high-quality evidence on the role of prenatal and perinatal nutritional interventions for the primary prevention of asthma in children and attempts to address unmet areas for future research in pediatric asthma prevention.     

Nutrition and health--vitamins and vitamin supplements

A balanced diet based on the Guidelines of the Netherlands Nutrition Centre provides a suitable basis for the maintenance of good health. However, there are a number of situations where supplementation with vitamins is clearly indicated. These include infants (vitamin A, D and K), young children, and pregnant and lactating women (vitamin D), future expectant mothers (folic acid) and the elderly (vitamin D). If doubts exist about a sufficient vitamin intake via the regular diet, a daily supplement supplying all vitamins at the level of the recommended daily allowance (RDA) is considered to be a responsible and safe choice. Epidemiological research indicates that the incidence of certain diseases is lower if the intake of vitamins is significantly higher than the RDA. However to date, targeted intervention studies have provided little unequivocal evidence to support this argument. For certain vitamins (A, D, folic acid, B6, nicotinic acid and beta-carotene) excessive intakes are associated with a health risk or clear toxicity. In the case of vitamin B6, nicotinic acid, folic acid and beta-carotene this risk is mainly limited to the use of high-dose supplements.     

Interaction of allergic airway inflammation and innate immunity: hygiene and beyond

The lung is constantly exposed to the environment and its microbial components. Infections of the respiratory tract are amongst the most common diseases. Several concepts describe how this microbial exposure interacts with allergic airway disease as it is found in patients with asthma. Infections are classical triggers of asthma exacerbations. In contrast, the hygiene hypothesis offers an explanation for the increase in allergic diseases by establishing a connection between microbial exposure during childhood and the risk of developing asthma. This premise states that the microbial environment interacts with the innate immune system and that this interrelation is needed for the fine-tuning of the overall immune response. Based on the observed protective effect of farming environments against asthma, animal models have been developed to determine the effect of specific bacterial stimuli on the development of allergic inflammation. A variety of studies have shown a protective effect of bacterial products in allergen-induced lung inflammation. Conversely, recent studies have also shown that allergic inflammation inhibits antimicrobial host defense and renders animals more susceptible to bacterial infections. This paper focuses on examples of animal models of allergic disease that deal with the complex interactions of the innate and adaptive immune system and microbial stressors.     

围孕期叶酸补充情况及其对妊娠结局影响

目的 了解单胎妊娠围孕期叶酸补充情况和补充剂量,探讨围孕期叶酸补充与妊娠结局的关系.方法 以2017年10月-2019年6月期间在广州市花都区妇幼保健院分娩的6 536例单胎活产的孕妇作为研究对象.在分娩前或分娩后回顾性的调查孕妇一般人口学特征、围孕期增补叶酸情况及妊娠结局等信息.结果 孕前半年服用叶酸坚持1个月以上的...     

Improper Supplementation Habits of Folic Acid Intake by Hungarian Pregnant Women: Improper Recommendations

Background: Neural tube defects (NTDs) are some of the most common congenital anomalies. Proper folic acid supplementation is a dominant risk factor, which has been shown to decrease the incidence of NTDs. In Canada, the incidence of neuroblastoma has presented a considerable decrease of 60% as a result of enrichment cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of folic acid intake by pregnant women on the incidence of NTDs and neuroblastoma.

Methods: Regular folic acid intake has been recommended to pregnant women in Hungary since the eighties of the last century by health visitors eventually raking effect as an official protocol which had been released in 1997. During 2001, 2002 and 2003, folic acid intake habits of pregnant women were evaluated by health visitors, proving to be successful in collecting data from 95.06% of the pregnant women. The incidence of NTDs has been registered by the Hungarian National Centre of Epidemiology, Department of Human Genetics and Teratology. The Pediatric Cancer Registry provided the incidence of neuroblastoma in children.

Results: Consistent findings revealed a regular intake of supplementary folic acid products by 68.71% of the pregnant women. Out of these, 93.13% of pregnant women who were taking folic acid, started the supplementation after their 7 weeks of pregnancies, a time designated as the completion period of the development of the neural tube. The dose of folic acid supplementation was evaluated as less than 5 mg/day in 84.75% of the pregnant women. In Hungary, the incidence of NTDs has remained constant, while the incidence of neuroblastoma has shown constant slight increase in spite of the introduction of folic acid supplementation in 1997.

Conclusions: Based on our experience, folic acid supplementation was initiated after the recognition of pregnancy and its application in a dose of lower than 5 mg/day neither decreased the incidence of NTDs nor did it have an effect on the neuroblastoma incidence. It is implicated that proper folic acid supplementation, which is started from the conception, can be achieved only with the enrichment of cereal grain flours.     

B-vitamins and prevention of dementia

Elevated plasma homocysteine (Hcy) concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B12 or folate status is responsible for cognitive decline. Most studies reporting associations between cognitive function and Hcy or B-vitamins have used a cross-sectional or case-control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of dementia has attracted considerable interest, as Hcy can be easily lowered by folic acid and vitamin B12, raising the prospect that B-vitamin supplementation could lower the risk of dementia. While some trials assessing effects on cognitive function have used folic acid alone, vitamin B12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individual-patient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.