【作者】 陈英耀；

【导师】 陈洁； 钱序； 薛迪；

【作者基本信息】 复旦大学 ， 社会医学与卫生事业管理， 2006， 博士

【摘要】 研究背景据世界卫生组织(WHO)报道，出生缺陷是导致婴儿死亡率和儿童发病率升高的主要原因，不但引起死亡，而且大部分存活下来的出生缺陷儿伴有各种残疾，给病人本人、父母和家庭造成极大的心理压力和精神痛苦，社会各方经济负担沉重。随着我国社会经济的快速发展和人民健康水平的提高，出生缺陷已凸现成为我国一个严重的公共卫生问题。我国每年约新发先天残疾儿童80万～120万，约占每年出生人口数的4％～6％。出生缺陷将逐渐成为导致儿童死亡、患病、伤残及影响生命质量的重要原因之一，将对我国医疗保健服务体系提出重大挑战。我国政府相继颁布了一系列法律、法规、政策性文件，为预防控制出生缺陷营造了良好的政策环境。目前国内在预防控制出生缺陷方面，存在研究滞后、缺乏立足国情的疾病基础数据和干预的科学评价结果等问题，不利于我国出生缺陷干预工程的系统化和科学化建设。本次研究正是着眼于填补这一空白，为我国预防出生缺陷系统工程服务，为提高我国出生人口素质服务。研究目的本研究从社会的角度，测算我国几种主要出生缺陷的疾病负担，对相应的出生缺陷预防干预措施进行经济学评价，为有效控制出生缺陷和减少残疾，为提高出生人口素质，提供科学的决策依据和政策建议。研究内容1．测量我国唐氏综合征和先天性心脏病的疾病负担，包括疾病经济负担和无形负担；定量分析我国神经管畸形的发生率。2．评价神经管畸形、唐氏综合征和先天性心脏病三种出生缺陷的预防干预措施的效果、成本效果或成本效益。妇女妊娠前后服用叶酸预防神经管畸形是一级预防策略；唐氏综合征产前诊断技术是二级预防策略；先天性心脏病手术治疗是三级预防策略。3．提出适合我国国情，推进出生缺陷预防干预有效实施的政策建议。研究方法1．疾病经济负担研究方法。课题组在河北省、陕西省和上海市开展现场调查，通过妇幼保健机构、残联、教育机构等途径从社区中查找唐氏综合征病人；通过开展先天性心脏病手术服务量较大的医疗机构查找先天性心脏病病人。三地共调查唐氏综合征病人222例和先天性心脏病病人303例。结合卫生服务调查和文献评阅，主要采用发病率法测算每新发1例病人生命周期的疾病经济负担，疾病经济负担测算的范畴包括直接卫生保健费用、间接卫生保健费用、发展性服务和特殊教育费用(为改善出生缺陷症状、提高病人生活适应性而发生的相关费用)和间接经济负担。本研究的疾病经济负担包括基于现实的医疗、康复等服务的实际利用率水平测算的“实际”疾病经济负担，也包括根据需要测算的疾病经济负担。2．定性研究方法。和所有调查唐氏综合征和先天性心脏病病人的直接照料者进行半结构化访谈，了解疾病对家庭的影响和家庭的期望。3．生命质量评价方法。利用EQ-5D生命质量量表测量唐氏综合征和先天性心脏病病人直接照料者的生命质量，并分析生命质量的影响因素。4．经济学评价方法。在现场调查和文献评阅基础上，利用决策树模型，模拟10000名目标对象的不同健康结局，对妇女妊娠前后增补叶酸预防神经管畸形、产前诊断预防唐氏综合征(和其他染色体异常)和手术治疗先天性心脏病的干预进行成本效果或成本效益分析，利用敏感性分析发现主要参数变化对模型结果的影响。主要研究结果1．唐氏综合征和先天性心脏病的疾病经济负担本研究采用发病率法和患病率法测算了唐氏综合征的疾病经济负担。以发病率法计算，2003年全国约有18000名新发病人(95％可信区间16000人～20000人)，从社会角度，一位新发唐氏综合征病人生命周期的经济负担为45万元，全国新发病例生命周期的总经济负担为81亿元(95％可信区间73亿元～90亿元)。以患病率估计，截至2003年存活病人近64万人(95％可信区间57万～71万)，从社会角度，2003年我国所有存活唐氏综合征病人1年累计的疾病经济负担达50亿元(95％可信区间45亿元～55亿元)。以发病率法计算，2003年全国约有11万～16万名新发病先天性心脏病病人，从社会角度，每位新发先天性心脏病病人生命周期的经济负担为9.7万元，全国新发病例生命周期的总经济负担为109亿元～156亿元。根据需要测算的疾病经济负担高于根据需求测算的水平，说明服务中的公平性和可及性问题。2．唐氏综合征和先天性心脏病的无形负担出生缺陷病人及家庭所承载的无形负担，包括巨大的心理压力和精神负担，对正常生活和工作的严重影响和沉重的经济压力。通过EQ-5D生命质量量表的测量，唐氏综合征和先天性心脏病病人直接照料者的健康指数分别为0.75和0.69，健康分值分别为0.49和0.55，明显低于北京普通人群的健康分值。这说明出生缺陷病人的疾病可能给病人家庭成员施加了无形压力。3．不同出生缺陷预防干预的经济学评价妇女妊娠前后服用叶酸预防神经管畸形，全国普遍实施增补叶酸干预的方案(FA2)和北方普遍干预且南方农村干预的方案(FA4)效果较好，成本效果分析发现效果相对较差的仅北方干预的方案(FA3)每预防1例神经管畸形胎儿发生的成本最低，为39770元，FA4每预防1例神经管畸形发生的成本为55036元，而FA2的成本效果比最高，为65436元。产前诊断预防唐氏综合征的三种不同策略，以孕早期筛查策略(PD4)的效果和安全性最好，孕中期筛查策略(PD3)次之，而年龄筛查策略(PD2)的效果和安全性均较前两者逊色。PD4、PD3和PD2分别能预防唐氏综合征1.73人、1.41人和0.53人，而从成本效果比分析，PD2、PD3和PD4的平均成本效果比分别为11万元、46万元和38万元。考虑预防唐氏综合征为效益，PD2和PD4是具有成本效益的方案；若既考虑预防唐氏综合征的效益又考虑引发流产的损失，则三方案效益均不抵成本。若考虑发现其他的染色体异常为有益的效果，则PD2、PD3和PD4的平均成本效果比大幅下降，分别为3万元、17万元和15万元，三方案效益均超过成本。先天性心脏病手术治疗每治愈1位存活病人的成本为37619元，相对于保守治疗的增量成本效果比为34253元。这是一个成本效果较好的干预策略。主要结论1．唐氏综合征和先天性心脏病等出生缺陷的疾病负担相当沉重，政策决策者应当给予相当的重视出生缺陷疾病负担研究是卫生政策需要评价的重要内容。出生缺陷的疾病负担表现在对病人、家庭和社会三个层面，无论是经济负担还是无形负担均相当沉重。出生缺陷这一凸现的公共卫生问题，对我国提高出生人口素质和促进经济可持续全面协调发展带来极大的挑战。决策者必须明确认识到出生缺陷预防干预的必要性和紧迫性。2．出生缺陷预防干预的经济学评价，有利于提高卫生资源的配置和利用效率妇女妊娠前后增补叶酸预防神经管畸形干预项目，以北方普遍干预而南方农村干预方案的效果和成本效果较佳。产前诊断预防唐氏综合征干预项目，尽管按年龄筛查的策略每预防1例唐氏综合征的成本最低，但其预防效果和安全性最差，孕早期和孕中期产前筛查-诊断策略属于成本高而效果和安全性好的方案。如果考虑因孕母血筛查而发现其他染色体异常的病例，孕早期和孕中期产前筛查-诊断策略的成本效果和成本效益均有明显改善。因此，孕早期和孕中期筛查策略更值得推广，孕早期筛查策略的效果、安全性和成本效果较佳。手术治疗先天性心脏病项目，较姑息保守治疗效果、成本效果更好。各干预措施的经济学评价受许多因素的影响，包括：疾病的发病率和患病率因素、卫生技术的技术能力问题(如治疗功效、诊断准确性)、服务提供者的依从性问题、服务对象的接受性问题、卫生技术的推广和管理因素、卫生服务项目的价格和项目间的比价关系等。政策建议1．健全出生缺陷监测体系，开展科学研究，摸清出生缺陷发生规律；2．动员全社会的力量，整合社会资源，减轻出生缺陷病人和家庭的过重负荷；3．积极投入，开展三级预防干预，有效控制出生缺陷；4．兼顾需要和可能，提出切实可行的出生缺陷预防干预策略；5．采取系统管理的手段，精心组织实施，提高预防干预的绩效；6．形成出生缺陷预防控制策略框架，促进相关知识向政策、服务和行动的转化。更多还原

【Abstract】 BackgroundBirth defects are becoming an important factor that increases infant mortality and children morbidity based on the WHO report. Birth defects not only lead to the patient’s premature death, morbidity and disability, but also bring about the psychological stress and depression to their parents and families, and create heavy economic burdens to the society.With rapid socioeconomic development and health improvement in China, birth defects are becoming an outstanding public health issue in China. It is estimated that 800-1,200 thousand new babies are born with any birth defect every year, sharing 4%-6% of total births annually in China. Birth defects are becoming an important factor leading to children death, premature death, morbidity, disability and low quality of life, and are challenging the Chinese health care delivery system. The central government has enacted some laws, regulations, and policies consecutively, which are targeting prevention and control of birth defects, and has developed a good context to conduct preventive interventions for birth defects.There are several barriers for systematic and scientific development of birth defects prevention programs in China, including studies lag behind, lack of basic information of birth defects of our country, and absence of evidence based evaluation of interventions. This study is intended to narrow those gaps to some extent, and is served for facilitating birth defects prevention programs and the health improvement in China.Study goalThis study is to measure disease burdens of some main birth defects, to conduct economic evaluation of interventions on birth defects, and to provide evidence-based policy suggestions in order to control birth defects and disabilities effectively and improve the population’s health in China.Study contents1. To measure disease burdens due to Down’s syndrome (DS) and congenital heart diseases (CHD), including disease economic burdens and intangible burdens, and to describe the incidence of neural tube defects (NTD).2. To assess effectiveness, cost-effectiveness or cost-benefit of different prevention strategies for NTD, DS and CHD. The periconceptional folic acid supplementation for NTD is a strategy of the primary prevention, the prenatal diagnosis for DS is a strategy of the secondary prevention, and the surgery for CHD is a strategy of the tertiary prevention.3. To propose policy suggestions based on evidences, and to facilitate effective implementation of preventions for birth defects in China.Study methodologies1. Method of disease economic burden. The study conducted the field survey in Hebei, Shaanxi and Shanghai, approaching DS’s families in communities by helps of local maternal and child health institutions, disabled person unions, and special education institutions, and looking for CHD’s patients in hospitals that provide the heart operation services. There were 222 cases of DS and 303 cases of CHD surveyed. Based on the survey of health services and literature reviews, the study measured the lifespan economic burden of a new case mainly by the incidence-based method. The economic burden of birth defects is calculated from direct healthcare costs, direct non-healthcare costs, developmental and special education costs, and indirect costs such as productivity loss. Estimation of the economic burden in the study includes both of those based on the effective demand and those based on the health care need.2. Method of qualitative study. All DS and CHD patients’ caregivers were interviewed by the semi-structured interview; it was intended to have a good understanding of impacts of diseases on families and their expectations.3. Method of measuring quality of life. The study employed the EQ-5D instrument to measure quality of life for caregivers of DS and CHD patients, and analyzed factors that influence the EQ-5D health index and score.4. Method of economic evaluation. Based on the field survey and literature reviews, the study developed three decision tree models for three interventions, simulated different health outcomes in a cohort of 10 thousand target population, and evaluated their cost-effectiveness or cost-benefit. These interventions are periconceptional folic acid supplementation for NTD, prenatal diagnosis for DS (and other chromosome diseases), and surgery for CHD. Sensitivity analysis was used to test the robustness of models, and identify main factors that influence the results of models.Main results1. Disease economic burden due to DS and CHDThe study measured the economic burden of DS by the incidence and prevalence method. By incidence-based approach, there were 18 (95% CI 16-20) thousand new DS cases in 2003 in China; the average lifetime economic burden of a new DS amounted to 450 thousand Yuan from the societal perspective, and the total economic burden of all new DS cases accumulated to 8.1 (95% CI 7.3-9.0) billion Yuan in 2003 in China. By prevalence-based approach, there were 640 thousand (95% CI 570-710 thousand) alive DS cases in China by 2003; and the total economic burden of all alive DS was summed up to 5 (95%CI 4.5-5.5) billion Yuan in 2003 in China from the societal perspective.By incidence-based approach, there were 110-160 thousand new CHD cases in 2003 in China; the average lifetime economic burden of a new CHD amounted to 97 thousand Yuan from the societal perspective, and the total economic burden of all new CHD cases accumulated to 10.9-15.6 billion Yuan in 2003 in China.Economic burdens based on health care needs are higher than those based on health care demands, and it reveals issues of equity and access to care.2. Disease intangible burden due to DS and CHDIntangible burdens of birth defects on affected patients and families were composed of the great psychological stress and mental depression, the serious negative impacts on daily life and work, and tremendous economic burdens. By the EQ-5D quality of lifeinstrument, EQ-5D health index for DS and CHD caregivers were 0.75 and 0.69, respectively, and EQ-5D visual analogue scale score for DS and CHD caregivers were 0.49 and 0.55, respectively. Those figures were much lower than those of Beijing general population. It may reflect that birth defects have intangible pressures to patients’ family members.3. Economic evaluation of preventive interventions for different birth defectsThe study found that the periconceptual folic acid supplementation strategy covering the whole nation (FA2) and the strategy covering both urban and rural areas in the north and rural areas in the south (FA4) can avert more NTDs than the strategy covering the north areas only (FA3). Average cost-effectiveness ratios of FA2, FA3 and FA4 were 65 thousand Yuan, 40 thousand Yuan, and 55 thousand Yuan, respectively.The study revealed that maternal serum and ultrasound screening in the first trimester (PD4) had the most effective and the safest outcome; maternal serum screening in the second trimester (PD3) was inferior to PD4 slightly, and maternal age screening (PD2) was worst. PD4, PD3 and PD2 could avert 1.73,1.41 and 0.53 DS cases, respectively. From cost-effectiveness analysis, the average cost-effectiveness ratio for PD2, PD3 and PD4 was 110 thousand, 460 thousand, and 380 thousand Yuan, respectively. Considering averted DS as benefits, PD2 and PD4 were paid off; and considering averted DS as benefits and miscarriage due to diagnosis as loss, costs for three strategies were over their benefits. If considering detection of other chromosome diseases as outcomes, average cost-effectiveness ratios for PD2, PD3 and PD4 declined dramatically, 30 thousand, 170 thousand, and 150 thousand Yuan respectively, and benefit-cost ratio were all over 1.The study estimated that costs for curing 1 alive CHD patient by operation was 38 thousand Yuan, incremental cost-effectiveness ratio was 35 thousand Yuan compared to the palliative treatment. The surgery for CHD is a cost-effective strategy.Main conclusions1. Disease burdens due to birth defects (such as DS and CHD) are dramaticallyheavy, so policy makers should pay more attentions to reduce or avoid burdens.Studies of disease burdens due to birth defects are an essential part of needs assessment for health policy. Disease burdens due to birth defects could be measured from the patient, the patient’s family, and the society perspectives. Both economic burdens and intangible burdens due to birth defects are tremendously heavy. Birth defects, outstanding public health issues, are big threats to population’s health improvement and socioeconomic development in a sustainable, holistic, and consistent way. Policy makers should realize the necessity, relevance and urgency of preventions of birth defects.2. Economic evaluation of preventive interventions for birth defects is to facilitate the efficiency of health resource allocation and utilization.Periconceptional folic acid supplementation for reducing NTDs, the strategy covering both the north areas and rural areas in the south would be better than other strategies in terms of effectiveness and cost-effectiveness.Prenatal diagnosis for preventing DS, the maternal age screening strategy was cheapest of the average cost-effectiveness ratio, but it is the worst in terms of effectiveness and safety. Screenings in the first trimester and the second trimester are strategies with higher costs and higher effectiveness and safety. If other chromosome diseases are included into consideration, screenings in the first trimester and the second trimester will be improved significantly in terms of cost-effectiveness and cost-benefits. In conclusion, screening strategies in the first trimester and the second trimester are worth implementing, and the screening strategy in the first trimester would be better than other strategies in terms of effectiveness, safety and cost-effectiveness.Surgery for CHD is a more cost-effective strategy, compared to the palliative treatment.Several factors influence cost-effectiveness of different interventions, including the incidence and prevalence of different birth defects, technical capacity of healthtechnology (such as efficacy of treatment, accuracy of diagnosis), providers’ motivation and compliance, acceptance of the target population, dissemination and administration of health technology, price of health services and price ratio among services, etc.Policy recommendation1. To strengthen development of birth defects surveillance system, to conduct scientific researches, and to have a better understanding of birth defects.2. To mobilize the society and integrate societal resources, and to alleviate heavy burdens from patients with birth defects and their families.3. To input resources positively, to implement three tier preventive interventions, and to control birth defects effectively.4. To take health care needs and feasibilities into accounts, and to design practical preventive intervention programs for birth defects.5. To take comprehensive measures, to implement preventions in a deliberated way, and to improve quality and cost-effectiveness of different preventive interventions for birth defects.6. To formulate a framework of birth defects preventive interventions, and to promote knowledge transfer to policy, services and practices.更多还原