新生儿疾病筛查工作中的伦理学思考

新生儿疾病筛查是出生缺陷的三级预防策略,对提高人口素质有非常重要的作用。其作为一项医疗活动,也存在着必要性、可行性、知情同意、隐私保护、消极与积极优生、严重病例处理等伦理问题。应在有利、尊重和公正等医学伦理原则上依法开展,并提高筛查质量,确保患儿的诊疗和随访,减少残疾儿童的发生,促进社会的和谐。     

基因测试与筛查

正为基因诊断提出相关预防和治疗措施对个体可能存在的某些遗传特性和遗传疾病有关的基因进行测试。测试与筛查是同步的,筛查以测试为前提,测试的过程同时实现筛查的目的。基因测试与筛查包括生殖遗传检查、新生儿遗传检测、人口检测及公共卫生方面的预测性遗传检查等。概述自开展基因检测以来,全球已有近2 000种疾病可以通过基因检测来提示患病风险,基因检测指导下的个性化用药等工作也有了很大进展,以基因检测为先导的一种新的医学形态正在形成。美国早在1996年     

新生儿基因筛查的价值位点——新生儿父母的视角

新生儿父母之间对于基因筛查的价值理解和价值选择存在很大很多差异,在此称其为类似于基因位点的价值位点。面对新生儿出生缺陷的现实,新生儿父母有着参加和接受新生儿基因筛查的行动自觉;对基因筛查结果,新生儿父母的期待充满矛盾;面对筛查结果,有的新生儿父母可能会怀疑、否定;知晓筛查结果后,有的新生儿父母会知情恐惧、拒绝,甚至会分裂式的追责;新生儿父母希望医院、政府、社会以及家庭都能在政策和舆论等方面给予他们更多的实际支持。     

有关乳腺癌群体筛查若干问题的思考

乳腺癌是全球女性恶性肿瘤发病率最高的疾病,对适龄妇女进行群体性的乳腺癌筛查旨在早发现、早诊断、早治疗,从而有效降低乳腺癌的死亡率。欧美国家于数十余年前开始全国范围的乳腺癌的群体筛查,早期的观察性研究认为筛查能独立降低乳腺癌的死亡率,而近期的许多群体研究结果却不断对钼靶筛查的获益提出质疑。中国对肿瘤的筛查早已有之,包括乳腺癌在各地区的群体性筛查也开展多年,但尚无一个权威性的研究结论供我们参考。笔者借鉴国内外的相关研究结果和自己在临床工作中的机会性筛查体会,对中国乳腺癌筛查的相关问题进行了思考,提出群体性的钼靶筛查并不适合中国国情,不应予以提倡和推广。应当建立符合中国乳腺癌发病特征的风险评估模型,根据风险评估结果,有针对性地对高危女性进行重点筛查,结合机会性筛查,采取临床触诊、彩超和钼靶相互结合为主的筛查方法,才是适合中国国情的乳腺癌筛查之道。     

产前筛查的几点思考

产前筛查是指通过经济、便捷、无创伤的方法,查找出某些严重病症的高危个体,从而提高出生人口素质。是阻止新生儿出生缺陷的有效手段之一。本文从哲学和医学伦理学角度对产前筛查的认识、意义和运用进行综合分析。     

新生儿对语音的感知、辨别和学习

新生儿自娩出起便开始利用臻于成熟的听觉系统对语音的各要素进行大脑表征和学习记忆。考察新生儿语音加工特点,不仅能揭示语言功能在人类发展最初阶段的认知神经机制,还能对自闭症等神经发育性疾病的早期预警和临床诊断提供有价值的线索。我们回顾并总结了新生儿对语音的感知、辨别和学习以及语言发展对自闭症的预测作用,发现新生儿对特定语音存在感知偏好;新生儿具备独特的音素辨别能力;婴儿期语言加工的脑功能或结构指标对自闭症具有一定的预测价值。我们建议未来研究从三个方面开展工作。在基础研究方面：第一,严格控制语音材料的韵律因素,重新审查新生儿语言加工特征及大脑偏侧化问题;第二,揭示新生儿语音学习的认知神经机制以及睡眠的记忆巩固作用。在临床转化研究方面,以高风险自闭症新生儿为追踪对象,基于纵向多模态脑观测数据,建立疾病风险评估系统,揭示出生早期语言发展脑指标对自闭症的预测价值。     

应用PSA筛查前列腺癌的争论焦点

前列腺癌是最常见的导致欧美国家男性死亡的疾病之一,我国男性前列腺癌发病率呈明显上升趋势.血PSA检测作为筛查前列腺癌的手段被广泛应用于临床.然而PSA筛查的价值还是成为当今泌尿和肿瘤学界争论最多的问题之一.本文着重介绍了男性接受PSA筛查前列腺癌的重要性以及前列腺癌筛查的潜在危害.     

应用PSA筛查前列腺癌的争论焦点

前列腺癌是最常见的导致欧美国家男性死亡的疾病之一,我国男性前列腺癌发病率呈明显上升趋势。血PSA检测作为筛查前列腺癌的手段被广泛应用于临床。然而PSA筛查的价值还是成为当今泌尿和肿瘤学界争论最多的问题之一。本文着重介绍了男性接受PSA筛查前列腺癌的重要性以及前列腺癌筛查的潜在危害。     

浅谈肿瘤患者医患共同决策的临床实践

正随着社会经济的不断发展,人民物质生活水平的提高,肿瘤疾病的发病率也在持续升高。无论城市还是农村,肿瘤都是我国居民死亡的主要原因之一,而肺癌则是目前肿瘤中的头号杀手。因此,有针对性地开展对肺癌的早期筛查成为了当前工作的重中之重。恶性肿瘤是特殊的疾病,其临床决策过程具有更高的复杂性和特殊性,在临床工作中也需要多次与患者及其家属进行沟通。笔者将结合自身在江苏省肿瘤医院与临床肿瘤患者的沟通经历,对医患共同决策的相关问题做一浅释及     

自闭症谱系障碍的早期筛查工具

基于35项实证研究, 遵循诊断准确性研究的质量评估(QUADAS-2)的循证程序对自闭症谱系早期预警特征筛查工具开展质量评估, 包括婴儿阶段(10个筛查工具, 159388人)、幼儿阶段(14项筛查工具, 11712人), 旨在为自闭症谱系风险的早期识别提供全面的理解。结果表明：幼儿阶段的筛查工具的分类准确性要高于婴儿阶段, 在婴儿阶段达到良好水平的筛查工具有M-CHAT-R/F、PDQ-1; 在幼儿阶段达到优秀水平的筛查工具有OERA、TIDOS。其中, “改良的幼儿自闭症检查表-有修订的后续随访” (M-CHAT-R/F)是目前最具潜力的自闭症谱系风险筛查工具之一。最后, 我们探讨了应用QUADAS-2评估研究质量的局限性, 强调需要规范工具的质量评估标准与进一步验证研究的必要性。     

Macropremies: underprivileged newborns

The focus of neonatal intensive care has been on very low birthweight infants, who comprise only 1.4% of neonates. Too little attention is paid to moderately preterm infants that we call macropremies or moderately low birthweight infants (MLBW, with birthweights 1500-2500 grams). Admitting over half MLBW infants to normal nurseries presumes that they have few needs and an excellent prognosis similar to fullterm newborns. It does not take into account the macropremie's vulnerability to complications of prematurity due to immature organ systems. Obstetricians are increasingly willing to deliver these infants prematurely for signs of fetal distress. As many as 25% of children with cerebral palsy referred to a disability clinic in Paris were MLBW, with hypoxic-ischemic-inflammatory associated disorders in one-third. The majority of MLBW infants who required neonatal intensive care at a tertiary care center in Baltimore had complications of prematurity: 47% had respiratory problems, 20% had feeding intolerance and 9% had hypoglycemia. MLBW infants comprise 5-7% of the neonatal population but account for 14% of neonatal deaths, 18-37% of children with cerebral palsy and 7-12% of children with mental retardation. Increasing the level of neonatal care for the macropremie's transition to extrauterine life would be economically feasible if it prevented as few as 30% of cases of major disability. A change in attitude towards this low risk (but not risk free) group of MLBW infants will both reduce morbidity and improve their health and neurodevelopmental outcome. It includes: 1) Providing an intermediate level of neonatal care for a short duration, with close monitoring and prompt intervention as needed, and 2) Neonatal neurodevelopmental screening to allow focused neurodevelopmental followup of MLBW infants with abnormalities.     

Genetic Screening Services Provided in Turkey

In Turkey, the rate of consanguineous marriage is quite high (22–24 %) and as a result, the incidence of autosomal recessive diseases and congenital anomalies is also very high and gives rise to a serious public health problem. In the last three decades, great effort has been made to avoid increases in the prevalence of these hereditary diseases. For this purpose, population-based premarital, prenatal, neonatal and adult genetic screening programs are performed in various centers such as Community Health Centers, Early Diagnosis of Cancer and Education Centers (KETEM), Prenatal and Neonatal Departments of Universities and State Hospitals and Thalessemia Screening Centers. Such centers are staffed by health professionals including physicians, family physicians, nurses, midwives, biologists and medical geneticists. Genetic counseling is also provided to patients attending these centers after screening tests are performed. Since there are no specialized training programs for genetic counselors, genetic counseling is generally provided by doctors or medical geneticists. The aim of this paper is to give an overview of the genetic screening services provided in Turkey, the prevalence of genetic diseases and the design of intensive educational programs for health professionals.     

A pediatric screening instrument to detect problematic infant–parent interactions: Initial reliability and validity in a sample of high‐ and low‐risk infants

The purpose of this study was to determine the initial reliability and validity of a screening instrument developed to detect problematic interactions between infants and parents as part of a pediatric well‐baby exam. Participants included 117 infant–mother dyads (57 preterms and 60 full terms) assessed when infants were 6 to 9 months old. Mothers and infants were observed playing an interactional game such as peek‐a‐boo during the course of the pediatric exam. The game was scored for degree of interactional reciprocity using the Pediatric Infant Parent Exam (PIPE). Acceptable levels of interrater reliability were achieved. As predicted, higher risk infants and their mothers exhibited more problematic interactions than lower risk infants and their mothers. Results indicated that the PIPE was a reliable means of screening for interactional difficulties, that was sensitive to, but not synonymous with, neonatal health indices. ©2001 Michigan Association for Infant Mental Health.     

Congenital Hypothyroidism: An Analysis of Persisting Deficits and Associated Factors

Congenital hypothyroidism (CH) is a neonatal disorder that is caused by a prolonged loss of thyroid hormone, which is essential for early brain development. While CH was once the leading cause of mental retardation, newborn screening for CH now allows for early identification and treatment. As a result, affected children now show normal physical and psychological development. Nevertheless, because they still undergo a brief but circumscribed period of thyroid hormone insufficiency, they are at risk for subtle selective impairments. This paper examines several of the persisting deficits observed in children with CH that was identified early in life by newborn screening as well as the relevant disease- and treatment-related factors contributing to such deficits. Highlighted will be (a) a weakness in visuospatial processing, which is associated with prenatal thyroid hormone insufficiency, (b) selective memory deficits associated with postnatal thyroid hormone insufficiencies, (c) a weakness in sensorimotor abilities also reflecting postnatal thyroid hormone insufficiencies, and (d) attention deficits, which are due to abnormal thyroid hormone levels at time of testing. Because these four disabilities implicate different neural substrates, the findings described presently will provide insights as to the specific time windows when different brain structures in the human critically need thyroid hormone.     

Congenital hypothyroidism: an analysis of persisting deficits and associated factors.

Congenital hypothyroidism (CH) is a neonatal disorder that is caused by a prolonged loss of thyroid hormone, which is essential for early brain development. While CH was once the leading cause of mental retardation, newborn screening for CH now allows for early identification and treatment. As a result, affected children now show normal physical and psychological development. Nevertheless, because they still undergo a brief but circumscribed period of thyroid hormone insufficiency, they are at risk for subtle selective impairments. This paper examines several of the persisting deficits observed in children with CH that was identified early in life by newborn screening as well as the relevant disease- and treatment-related factors contributing to such deficits. Highlighted will be (a) a weakness in visuospatial processing, which is associated with prenatal thyroid hormone insufficiency, (b) selective memory deficits associated with postnatal thyroid hormone insufficiencies, (c) a weakness in sensorimotor abilities also reflecting postnatal thyroid hormone insufficiencies, and (d) attention deficits, which are due to abnormal thyroid hormone levels at time of testing. Because these four disabilities implicate different neural substrates, the findings described presently will provide insights as to the specific time windows when different brain structures in the human critically need thyroid hormone.     

A Brief,Hospital-Initiated Motivational Interviewing and Acceptance and Commitment Therapy Intervention to Link Postpartum Mothers Who Use Illicit Drugs With Treatment and Reproductive Care: A Case Report

Maternal substance use during the prenatal period often results in infants with compromised health outcomes. The American College of Obstetrics and Gynecology recommends screening, brief motivational interviewing, and referral to existing treatment for women who use illicit substances prenatally. However, many of these women do not present for prenatal care and are not identified as using substances until delivery of their infants, many of whom are admitted to the neonatal intensive care unit (ICU). We describe a case from a novel, hospital-initiated intervention study, Moms in ACTion (MIACT) that combines motivational interviewing (MI) and acceptance and commitment therapy (ACT) to target new mothers with an infant in the neonatal ICU who screen positive for illicit substance use prenatally or at delivery. The MIACT program consists of an adaptive intervention that includes up to three sessions. Initiation of substance use treatment and reproductive care via a gynecological visit are the primary targets of the intervention. Urine samples were collected at 2- and 6-month follow-up visits. The participant successfully completed the program, achieved both treatment outcomes, and had negative urine drug screens at follow-up visits. Improvements in readiness to change and psychological flexibility were also observed. The present case report of a new mother who used substances demonstrated feasibility for combining MI and ACT treatments and the potential for MIACT to increase treatment and contraception initiation, ultimately preventing future substance-exposed pregnancies.     

A Case of Partial Biotinidase Deficiency Associated With Autism

We report the case of a child with partial biotinidase deficiency and autistic developmental disorder. We arrived at the diagnosis of biotinidase deficiency when the child was almost 4 years of age. Consequently, he began cofactor biotin treatment (10 mg daily) which did not resolve his autistic behavior. His younger brother was affected by partial biotinidase deficiency diagnosed at birth through our neonatal screening program. He was precociously treated with cofactor biotin therapy (10 mg daily) and did not show any behavioral abnormality or developmental delay. Since the brain is quite vulnerable to biotin deficiency, delayed biotin therapy could result in neurological damage. Our patient is the first case of partial biotinidase deficiency associated with autism. We hypothesize that the low biotinidase activity could have caused biotin deficiency in his brain and cerebrospinal fluids and consequently serious neurological problems, such as stereotyped and autistic behaviors, which were irreversible in spite of biotin supplementation.     

A case of partial biotinidase deficiency associated with autism.

We report the case of a child with partial biotinidase deficiency and autistic developmental disorder. We arrived at the diagnosis of biotinidase deficiency when the child was almost 4 years of age. Consequently, he began cofactor biotin treatment (10 mg daily) which did not resolve his autistic behavior. His younger brother was affected by partial biotinidase deficiency diagnosed at birth through our neonatal screening program. He was precociously treated with cofactor biotin therapy (10 mg daily) and did not show any behavioral abnormality or developmental delay. Since the brain is quite vulnerable to biotin deficiency, delayed biotin therapy could result in neurological damage. Our patient is the first case of partial biotinidase deficiency associated with autism. We hypothesize that the low biotinidase activity could have caused biotin deficiency in his brain and cerebrospinal fluids and consequently serious neurological problems, such as stereotyped and autistic behaviors, which were irreversible in spite of biotin supplementation.     

PRENATAL COCAINE EXPOSURE AND NEONATAL CONDITION

Infants who are prenatally exposed to cocaine have an increased risk of suffering neonatal medical complications. We hypothesized that this effect is mediated by the relation between cocaine use and prenatal medical risk of the mother, birth weight, and intrapartum risk, that would lead to increased neonatal complications. This study used structural equation modeling to assess the direct and indirect effects of prenatal cocaine exposure on neonatal medical risk in a sample of 337 neonates. Prenatal cocaine exposure had a significant indirect, but not direct effect on neonatal medical risk. Several paths contributed to this indirect effect. The strongest was via cocaine's impact on birth weight, and birth weight's effect on neonatal medical risk. The paths through prenatal risk and intrapartum risk also contributed to the total indirect effect. These results suggest that the observed relation between prenatal cocaine exposure and neonatal medical complications is mediated by prenatal and intrapartum risk factors.     

Delivering Genetic Education and Genetic Counseling for Rare Diseases in Rural Brazil

Brazil is the largest country in Latin America, with an ethnically diverse, Portuguese-speaking and predominantly Roman Catholic population of some 194 million. Universal health care is provided under the Federal Unified Health System (Sistema Único de Saúde) but, as in many other middle and low income countries, access to medical genetics services is limited in rural and remote regions of the country. Since there is no formally recognized Genetic Counseling profession, genetic counseling is provided by physicians, trained either in medical genetics or a related clinical discipline. A comprehensive medical genetics program has been established in Monte Santo, an inland rural community located in the state of Bahia in Northeast Brazil, with high prevalences of a number of autosomal recessive genetic disorders, including non-syndromic deafness, phenyketonuria, congenital hypothyroidism and mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Genetic education, counseling and treatment are locally provided, with a neonatal screening program for MPSVI currently under trial.