UK Newborn Screening Programme Centre Research Articles

Newborn screening to identify cystic fibrosis.

Background Newborn screening (NBS) identifies pre-symptomatic babies who are at risk of carrying or being affected by genetic or congenital conditions (UK Newborn Screening Programme Centre 2012). Screening for cystic fibrosis (CF) is not diagnostic and, once a positive screening result has been obtained, further testing is required to determine whether the child is affected by CF.

Sickle cell and cystic fibrosis carrier results.

Background Newborn screening (NBS) is used to identify pre-symptomatic babies who carry, or are affected by, genetic or congenital conditions ( UK Newborn Screening Programme Centre 2012 ). In England, parents are required to provide informed consent before their babies are screened.

Inherited genetic conditions.

Background While it is known that early diagnosis leads to better health outcomes for children with inherited genetic conditions (IGCs) ( UK Newborn Screening Programme Centre 2012 , Bush 2008 ), families affected by IGCs face difficulties, including those associated with complex treatment regimens.

Data: ‘Initial Clinical Referral Standards after Newborn Screening for Congenital Hypothyroidism: Final Report of the UK Newborn Screening Programme Centre Expert Working Group and Systematic Evidence Review 2010-2011’.

The multidisciplinary Expert Working Group was tasked with revising the existing standards of the UK NHS National Screening Programme for diagnosis and management of babies in whom congenital hypothyroidism (CHT) is suspected after newborn bloodspot screening. This report includes a systematic evidence review and account of the proceedings of the working group in key areas: screening test performance, referral pathways, diagnostic investigations, treatment and communication with parents. After public consultation, the recommendations were adopted as policy. This final report provides an evidence base for reviewing newborn screening for CHT in other populations and outlines a transparent consensus-based process for agreeing changes to screening standards and policy.

Screening for Congenital Hypothyroidism: Comparison of Borderline Screening Cut-Off Points and the Effect on the Number of Children Treated with Levothyroxine

Background: The newborn screening programme for congenital hypothyroidism (CH) has led to the prevention of severe developmental delay associated with this condition. In the UK, thyroid-stimulating hormone (TSH) screening cut-off points have changed over time, in some instances prompted by changing methodological platforms. The use of borderline cut-off points varies throughout the country. Objective: To use discordance in cut-off points to assess the performance of the UK Newborn Screening Programme Centre (UKNSPC) definitions. Methods: Between January 2006 and December 2007, 223,658 newborn infants were screened by the Great Ormond Street Hospital (GOSH) for CH. All children with positive results and those with blood-spot TSH concentrations >6 mU/l on repeat screening were referred to GOSH. We compared the numbers of children detected and treated for CH using the GOSH cut-off points (>6 mU/l) and those of the national screening programme (>10 mU/l). Children were defined as transient CH if levothyroxine treatment had been discontinued by 3 years. Results: Of the children screened between January 2006 and December 2007, 167 out of 223,658 fulfilled the GOSH screening criteria; 136 of these required levothyroxine treatment, but 29 (21%) of the children treated would not have been detected by the current UKNSPC guidelines. Transient CH was found in 17/47 (36%) of the treated children detected with a cut-off point >6 mU/l. Raising the cut-off point to >10 mU/l reduced the number of children treated for transient CH to 4/18 (22%). Conclusion: A significant number of children with true and transient CH are missed with a screening cut-off point of >10 mU/l. Our data suggests that a cut-off point of 6 mU/l is appropriate.

Hypothyroidism in preterm infants following normal screening

Congenital hypothyroidism is screened for in the UK using blood spot thyroid-stimulating hormone (TSH) screening at 5-8 d of age. Although standards are set by the UK Newborn Screening Programme Centre, there are variations in TSH cut-offs used. The introduction of repeat screening of preterm babies at 36 weeks' gestational age in 2005 was controversial in its utility and timing. Two cases of preterm babies are presented, who had normal blood spot TSH values on the first test and who became screen positive when re-tested at term. The first with Trisomy 21 was born at 29 + 6 weeks with an initial blood spot TSH of 3.3 mU/L rising to 263 mU/L at term-corrected gestational age (plasma TSH 476.5 mU/L). The second was born at 24 + 6 weeks' gestational age and on day 7, the heel prick blood spot TSH was <2 mU/L, rising to 6.4 mU/L at 36 weeks corrected gestational age. After a barium enema, the plasma TSH increased to 66.6 mU/L with a free thyroxine of 7.6 pmol/L at day 101. Both cases were treated with thyroxine until death due to complications of prematurity. These cases illustrate the difficulties in screening for congenital hypothyroidism in preterm infants, due to the immaturity of the hypothalamo-pituitary-thyroid axis, and the effect of intercurrent illness and drugs on thyroid function. Despite a reassuring published review of 2200 preterm infants, these cases suggest that it may be unwise not to re-screen ex-preterm infants for congenital hypothyroidism at term.

Congenital Hypothyroidism—Monitoring Thyroid Function in Infants

Guidelines for monitoring thyroid function in congenital hypothyroidism (CH) are published by the American Academy of Pediatrics, the European Society for Paediatric Endocrinology, and the UK Newborn Screening Programme Centre. The fact that the recommendations are not uniform reflects management uncertainty. In addition, clinical care may not always be informed by these guidelines. Recent studies suggest that more frequent monitoring is indicated in some infants. Monitoring to identify delayed thyroid stimulating hormone (TSH) rise is indicated in pre-term, low birth weight, and sick full-term newborns. Monitoring thyroid function in infants with CH monthly after normalization of TSH until six months of age, and every one to two months between six and 12 months of age, will decrease exposure to suboptimal thyroid hormone levels. Assessment for permanency of hypothyroidism should be done only in children in which there is likelihood of resolution and not earlier than three years of age. In some instances when TSH elevations persist after normalization of the free thyroxine, it may be reasonable to try combined therapy with triiodothyronine.

Elevated phenylalanine on newborn screening: follow-up testing may reveal undiagnosed galactosaemia

Introduction Newborn screening for phenylketonuria (PKU) can reveal other conditions which lead to an increased blood spot phenylalanine (Phe) concentration. We have investigated the proportion of blood spot samples that gave a positive screen due to clinically significant conditions other than PKU, compared the positive predictive value (PPV) of our referral Phe cut-off with that recommended by the UK Newborn Screening Programme Centre (UKNSPC) (>210 and >240 μmol/L, respectively) and evaluated the effectiveness of reflex testing for galactosaemia using a lower blood spot Phe cut-off concentration of 130 μmol/L. All blood spot samples that screened positive, for an increased Phe concentration, between April 2001 and March 2008, were identified from the records of the Sheffield Newborn Screening Laboratory and the diagnoses noted. In addition, all cases of galactosaemia detected in or notified to our screening laboratory within this time were also examined and the screened Phe concentrations compared. Out of 438,674 babies who were screened, 67 had Phe concentration >210 μmol/L (15 per 100,000). Of these, 40 had PKU or persistent hyperphenylalaninaemia with a Phe concentration identified by screening between 270 and 2350 μmol/L. A further 11 were diagnosed with another clinically significant disorder: galactosaemia (n = 8), biopterin defects (n = 2), tyrosinaemia Type 1 (n = 1). In addition, 16 had transient elevations in Phe. In total, nine cases of galactosaemia were identified, of whom, three had Phe concentrations <240 μmol/L with one asymptomatic individual having a concentration <210 μmol/L. Adoption of the UKNSPC recommended cut-off (>240 μmol/L) will not affect the detection rate of classical PKU, but will improve the PPV from 76% to 80%. The use of a lower cut-off (130 μmol/L) for reflex galactosaemia testing enables the timely identification of asymptomatic cases that benefit particularly from early treatment, without prompting any unnecessary clinical referrals or delaying any referrals. This intervention may reduce mortality in this vulnerable group.

Difficulties in selecting an appropriate neonatal thyroid stimulating hormone (TSH) screening threshold

BackgroundThe UK Newborn Screening Programme Centre recommends that a blood spot thyroid stimulating hormone (TSH) cut-off of 10 mU/l is used to detect congenital hypothyroidism (CHT). As the value used...

National training resources for newborn bloodspot screening

Policy decisions to expand newborn screening and support informed choice prompted a review of information for parents and resources to support health professionals. The UK Newborn Screening Programme Centre conducted a needs assessment to identify training needs. We took into account existing reports of training needs as well as conducting our own survey of Midwifery Schools and screening laboratories. Prior evaluations, and our own survey, suggested the need for national resources on newborn bloodspot screening, rather than an additional national training programme. Based on these findings we developed resources that could be used within current training initiatives. These resources are now available to midwifery trainers for use alongside or in place of existing resources, as well as to individual midwives as part of a ‘self-learn’ package.

Mothers’ accounts of screening newborn babies in Wales (UK)

Objective to explore mothers’ accounts of screening newborn babies to increase our understanding of how they define screening and talk about the process of consent. Design a purposive sample of mothers, whose newborn babies had recently been screened, were invited to take part in a semi-structured interview. Setting primary and community-care settings in one region of Wales, UK. Participants mothers ( n=18) who had recently given birth and been offered screening for their newborn babies. Findings information giving about newborn screening was reported to be ad hoc, with most women receiving information in the postnatal period. Mothers talked about newborn screening as a routine procedure that ‘had’ to be done. There was some recognition that consent for screening should have been given, but this was often compromised because the test was being offered by a trusted health professional and a social expectation that responsible mothers should have their babies tested. Conclusions mothers agreed that information about newborn-baby screening should be given during pregnancy. This is in line with recent recommendations from the UK Newborn Screening Programme Centre. This policy urgently needs to be translated effectively into everyday practice. In addition, the nature of consent required for each test needs to be clarified so that midwifery practice is not compromised and mothers are aware that some tests are advisable whereas others, for less treatable diseases, are a matter of individual choice.