NEWBORN SCREENING PILOT STUDIES

新生儿筛查试点研究

• 批准号: 10710760
• 负责人: MICHELE CAGGANA
• 金额: $ 136.19万
• 依托单位: NYSDOH/HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-28 至 2024-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710760
• 关键词: 5 year old; Address; Advisory Committees; Affect; American; Antiviral Agents; Anxiety; Biological Assay; Birth; Blood; Centers for Disease Control and Prevention (U.S.); Cessation of life; Child; Child Health; Clinical; Cochlear Implants; Contractor; Cytomegalovirus; DNA; DNA-Directed DNA Polymerase; Data; Detection; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Disease; Early Diagnosis; Early treatment; Ethics; Evaluation; Future; Ganciclovir; Goals; Hearing; Hepatosplenomegaly; Hereditary Disease; Icterus; Infant; Infection; Intellectual functioning disability; Language; Language Delays; Left; Life; Medical Genetics; Methods; Microcephaly; Minnesota; Monitor; Neonatal Screening; Nervous System Trauma; Neurologic; Neutropenia; Newborn Infant; Oral; Petechiae; Pilot Projects; Polymerase Chain Reaction; Population; Population Heterogeneity; Pregnancy; Prevalence; Public Health; Randomized; Rare Diseases; Recommendation; Reporting; Risk; Saliva; Sampling; Seizures; Sensorineural Hearing Loss; Severities; Source; Specificity; Speech; Spottings; Symptoms; Syndrome; Testing; Time; Tissues; Treatment Side Effects; United States; Universities; Urine; Valganciclovir; Viral Load result; Visual impairment; base; congenital cytomegalovirus; congenital infection; follow-up; hearing impairment; hearing loss risk; hearing screening; high risk population; improved; improved outcome; infant death; infant infection; language outcome; long-term sequelae; medical schools; neonatal infection; neonate; overtreatment; physically handicapped; population based; prevent; programs; salivary assay; screening; screening guidelines; screening panel; screening program; symptom treatment

The goal of newborn screening (NBS) is to detect potentially fatal or disabling conditions in newborns, thereby providing a window of opportunity for early treatment, often while the child is still asymptomatic. Such early detection and treatment can have a profound impact on the clinical severity of the condition in the affected child. If left undiagnosed and untreated, the consequences of the targeted disorders can be dire, many causing irreversible neurological damage; intellectual, developmental, and physical disabilities; and even death. In 2006, the American College of Medical Genetics (ACMG) developed newborn screening guidelines that recommend that all newborn infants be screened for 35 "core conditions" and that 26 secondary conditions identified during the core evaluations be reported. These recommendations were accepted by the HHS Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) (authorized by the Children's Health Act of 2000) and by the Secretary of HHS, and formed the basis of the Recommended Uniform Screening Panel (RUSP). Most states now use the RUSP or very similar panels for newborn screening. Currently, there are thousands of rare disorders that have been identified and hundreds that could potentially benefit from newborn screening. Congenital cytomegalovirus (cCMV) is the most common congenital infection and is estimated to occur in 0.6% of all pregnancies, impacting ~23,000 births in the United States each year.1 This makes cCMV more common than most conditions currently on the RUSP. The manifestations of cCMV are highly variable and include sensorineural hearing loss (SNHL), developmental delays, and visual impairment. The extreme presentation at birth is one of microcephaly, hepatosplenomegaly, petechiae, seizures, and jaundice, occurring in ~10-15% of infected newborns and resulting in infant death in 5-10% of those with symptoms.2,3 In addition, of those newborns who are symptomatic, 50-90% will have long-term neurologic and developmental complications.4 However, the remaining ~90% of newborns with cCMV will be clinically asymptomatic at birth. For asymptomatic newborns, the risk of long-term sequelae is ~10% to 15%, which often presents as isolated SNHL, and may not be detected through newborn hearing screening as it may be late onset or progressive, presenting through age 5 years.5, 6 If an infant diagnosed with cCMV develops symptoms, treatment with antiviral medications (IV ganciclovir, oral valganciclovir) has been shown to improve outcomes with regard to hearing and development, 7,8 although some of these gains have not been sustained in more recent reviews.9 However, transient neutropenia is a known side effect of the treatment, which has led some experts to not routinely recommend antiviral treatment of asymptomatic infected infants.10 Nonetheless, identification of asymptomatic infants with cCMV allows for neurodevelopmental evaluation, follow-up, and monitoring for hearing loss, with prompt treatment to prevent language delays or language loss in this high-risk population. Frequent audiologic monitoring at 6-month intervals has been recommended in this population until age 5 years, with more frequent monitoring every 3 months when hearing levels are changing or until the child is talking.11 Cochlear implants are recommended for children with acquired severe hearing loss to improve speech and language outcomes.12 NBS screening for cCMV, whether population-wide or targeted only to infants who fail their newborn hearing screening, raises important ethical and public health considerations, including concerns about both under- and over-diagnosis, overtreatment of asymptomatic screen-positive infants, parental anxiety and vulnerable child syndrome, and the added burden on state public health programs.

新生儿筛查(NBS)的目标是发现新生儿可能致命或致残的情况，从而为早期治疗提供机会之窗，通常是在儿童仍无症状的情况下。这种早期发现和治疗可能对受影响儿童的病情临床严重程度产生深远影响。如果不加以诊断和治疗，针对性疾病的后果可能是可怕的，许多疾病会导致不可逆转的神经损伤；智力、发育和身体残疾；甚至死亡。2006年，美国医学遗传学学会(ACMG)制定了新生儿筛查指南，建议对所有新生儿进行35种“核心疾病”的筛查，并报告在核心评估中发现的26种次要疾病。HHS新生儿和儿童遗传性疾病问题秘书咨询委员会(ACHDNC)(由2000年《儿童健康法》授权)和HHS秘书接受了这些建议，并构成了建议的统一筛查小组(RUSP)的基础。大多数州现在使用RUSP或非常类似的小组进行新生儿筛查。目前，已发现数千种罕见疾病，数百种可能从新生儿筛查中受益。 先天性巨细胞病毒(CCMV)是最常见的先天性感染，估计发生在所有妊娠的0.6%，每年影响到美国约23,000名新生儿。1这使得CCMV比RUSP目前的大多数疾病更常见。CCMV的表现具有很高的变异性，包括感觉神经性听力损失(SNHL)、发育迟缓和视力障碍。出生时的极端表现是小头畸形、肝脾肿大、瘀点、癫痫和黄疸，发生在约10%-15%的感染新生儿中，并在有症状的新生儿中导致5%-10%的婴儿死亡。2、3此外，在那些有症状的新生儿中，50%-90%会有长期的神经和发育并发症。4然而，其余~90%的CCMV新生儿出生时将没有临床症状。对于无症状的新生儿，长期后遗症的风险约为10%至15%，通常表现为孤立性SNHL，可能无法通过新生儿听力筛查发现，因为它可能是晚发或进行性的，表现为5岁。 如果被诊断为CCMV的婴儿出现症状，使用抗病毒药物治疗(IV 更昔洛韦，口服伐更昔洛韦)已被证明可以改善听力和 9然而，短暂性中性粒细胞减少症是治疗的一个已知副作用，这导致一些专家不常规地建议对无症状感染婴儿进行抗病毒治疗。10尽管如此，确认患有CCMV的无症状婴儿可以进行神经发育评估、跟踪和监测听力损失，并及时进行治疗，以防止在这一高危人群中出现语言延迟或语言丧失。建议该人群在5岁之前每隔6个月进行一次听力监测，在听力水平发生变化或儿童说话之前每3个月进行一次更频繁的监测。11建议后天严重听力损失的儿童植入人工耳蜗术以改善言语和语言结果。12国家统计局对CCMV进行筛查，无论是在整个人口范围内还是仅针对未通过新生儿听力筛查的婴儿，引起了重要的伦理和公共卫生考虑，包括对诊断不足和过度诊断、对无症状筛查阳性婴儿的过度治疗、父母焦虑和易受伤害的儿童综合征，以及对国家公共卫生计划的额外负担。