What's New in Newborn Screening?

Bradford L. Therrell; Colleen Buechner; Michele A. Lloyd-Puryear; Peter C. van Dyck; Marie Y. Mann


Pediatr Health. 2008;2(4):411-429. 

In This Article

General Considerations in US Newborn Screening Systems

A US national NBS policy does not currently exist, but each state has a law that results in required screening. As part of the statutory requirements, the state public health authority has (at a minimum) oversight responsibility designed to ensure a properly run screening program (or programs, since in some states NDBS and NHS are separate programs).[12] Laws and rules/regulations vary, sometimes specifying certain critical responsibilities, such as when a screening is to occur and who must ensure that it happens. In some cases, portions of program infrastructure may be contracted out rather than provided within the public health system. For example, some programs contract laboratory services to other states or private screening laboratories (Figure 1), and some contract part or all of patient tracking and follow-up, usually to academic or specialty centers. For this reason, the NBS system components (education, screening, follow-up, diagnosis, management/treatment and evaluation) must be carefully defined along with the responsibilities of each component, and systems operations must be seamlessly integrated for maximum efficiency and effectiveness.[13,14,15]

Figure 1.

Various newborn screening laboratory models in use in the USA - June 2008. MS/MS: Tandem mass spectrometry.

As part of quality NBS activities, NDBS laboratories comply with certification requirements of the Clinical Laboratory Improvement Act (CLIA).[16] Quality assurance of NBS nonlaboratory activities are generally self-defined and guided by best practices that ensure timely interventions that lead to positive medical outcomes.[17] In addition to professional organizations, such as the American Academy of Pediatrics (AAP) who have provided NBS guidance for their members over time, the Clinical Laboratory Standards Institute (CLSI) - formerly known as the National Committee for Clinical Laboratory Standards (NCCLS) - has played a pivotal role in developing national standards for NBS. For 20 years there has been a CLSI/NCCLS national standard for blood collection on filter paper (LA4),[18] which defines many of the pre-analytic activities appropriate for quality NDBS. More recently, the CLSI has issued a guideline for NBS follow-up (I/L27-A),[19] which addresses follow-up issues applicable to both NDBS and NHS. Since premature and sick newborns present special screening challenges,[20,21] a CLSI guideline (I/L31) defining NBS screening protocols in intensive care situations is currently in development. Committees preparing CLSI standards and guidelines include international representation to encourage global acceptance and procedural harmonization. Where specific NBS performance standards and guidelines do not exist, such as diagnostic procedures and clinical management, the best practices that lead to optimal health outcomes serve as surrogates.

Most NBS programs have external advisory committees that serve as consultants, advisors and advocates.[12,13,15] Since NDBS and NHS advisory committees may be the primary mechanism by which a program obtains outside input, advisory committees are usually multidisciplinary. They include not only medical professionals, but also consumer advocates, ethicists and other NBS stakeholders. NBS program personnel serve to assist with committee activities but usually do not function as committee members. Advisory committees exist to provide a mechanism for stakeholder input and for vetting program decisions, which in turn serves to increase community acceptance of policy decisions. In cases where outside advocacy can assist with program changes, the advisory committee often serves in this role.

In the USA, NDBS specimen collection and NHS usually occur at a birthing facility 24-48 h after birth (before discharge from the facility), or as soon as possible if the infant is born outside of such a facility. In the case of newborns in intensive care units, a heelstick blood specimen is usually drawn before 7 days of age, in compliance with AAP recommendations that originated with newborn hypothyroidism screening.[22] NHS usually occurs during the same time period, in accordance with recommendations of the AAP Joint Committee on Infant Hearing (JCIH).[23,24] In the case of hospital transfers, the transferring hospital is usually responsible for ensuring that a NDBS specimen has been collected or that the receiving hospital is aware of the need for collection of a blood specimen and completion of a hearing screen.

Ideally, out-of-range (abnormal) NBS results trigger rapid patient follow-up that leads to timely confirmatory testing and initiation of appropriate clinical management. While NDBS programs have well-established short-term follow-up systems, usually in the state public health system, NHS short-term follow-up is often hospital based and follow-up data at the state level may not be well organized. In an effort to better utilize existing NDBS infrastructure and improve NHS follow-up, at least a third of state programs now include NHS result reports either as part of NDBS specimen collection card information or as part of the information collected on electronic birth certificates. By centralizing screening data, the opportunity for better follow-up and administrative management/oversight of NHS exists.[25]

It is preferable for prospective parents to receive information about NBS before the birthing event,[26,27,28] but many still receive this information as part of their maternity information materials upon admission to the hospital or postpartum. The responsibility to explain NBS often resides with nurses in the newborn nursery who may also collect the NDBS specimen and/or provide hearing screening. In the hospital setting, NDBS specimens may be collected by a laboratory phlebotomist while a midwife may obtain specimens on newborns born in other settings. The NDBS specimen collection process is defined by the state NDBS program, and is usually based on the current CLSI standard (LA4-A5). In some cases, an additional specimen may be collected at the parents' request for other purposes (e.g., additional screening, baby book, etc.). NHS, on the other hand, may be performed by a trained NHS technician[29,30] and may include either an evoked otoacoustic emission or an auditory brainstem response test (or a combination of the two). In some states, a certification program may exist, which prescribes the NHS protocol, while in others the protocol may be defined by individual hospitals.

Dried blood-spot specimens for biochemical screening are sent either by mail or courier to a state designated screening laboratory, which may be either the state public health laboratory, a contracted laboratory (either private, public or nonprofit) or a combination of the two. Several models of laboratory service exist (Figure 1) and each has been found to provide acceptable screening laboratory services in its own unique setting. While state public health laboratories provide the majority of screening services, some state programs find it effective to utilize the services of private or nonprofit laboratories. Many of the smaller population states utilize the services of 'regional' public health or university laboratories. Regionalization of some NDBS genetics specialty services for follow-up also exists.[31] NDBS laboratory regionalization has been shown to improve testing quality through increased case access and case identification, and cost savings are realized through economies of scale. Proficiency testing for all NDBS laboratories is provided by the NBS Quality Assurance Program (NSQAP) at the US CDC (program details are available at[101]). This program is voluntary, but all state NDBS programs utilize the services to satisfy their licensure requirements for proficiency testing. The NSQAP now serves over 325 NDBS laboratories in 53 countries worldwide.[16]

Newborn screening follow-up is a shared responsibility among the NBS program, parents and appropriate healthcare professionals. Long-term follow-up and case management and follow-up are also essential shared activities aimed at optimizing health outcomes and evaluating program effectiveness.[15] Quality indicators for these and all aspects of the NBS system have been defined in a Performance Evaluation and Assessment Scheme (PEAS), developed by national working groups as part of a Health Resources and Services Administration (HRSA)-funded initiative of the US National NBS and Genetics Resource Center (NNSGRC).[102] This self-evaluation tool provides a basis for NBS quality improvement by helping programs to define missing or deficient system elements.[32]


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