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Association between use of systematic reviews and national policy recommendations on screening newborn babies for rare diseases: systematic review and meta-analysis

BMJ 2018; 361 doi: (Published 09 May 2018) Cite this as: BMJ 2018;361:k1612
  1. Sian Taylor-Phillips, associate professor1,
  2. Chris Stinton, senior research fellow1,
  3. Lavinia Ferrante di Ruffano, research fellow2,
  4. Farah Seedat, research associate1,
  5. Aileen Clarke, professor of public health and health services research1,
  6. Jonathan J Deeks, professor of biostatistics2 3
  1. 1Warwick Medical School, The University of Warwick, Coventry CV4 7AL, UK
  2. 2Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK
  3. 3National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK
  1. Correspondence to: S Taylor-Phillips S.taylor-phillips{at}
  • Accepted 16 March 2018


Objective To understand whether international differences in recommendations of whether to screen for rare diseases using the newborn blood spot test might in part be explained by use of systematic review methods.

Design Systematic review and meta-analysis.

Data sources Website searches of 26 national screening organisations.

Eligibility criteria for study selection Journal articles, papers, legal documents, presentations, conference abstracts, or reports relating to a national recommendation on whether to screen for any condition using the newborn blood spot test, with no restrictions on date or language.

Data extraction Two reviewers independently assessed whether the recommendation for or against screening included systematic reviews, and data on test accuracy, benefits of early detection, and potential harms of overdiagnosis.

Analysis The odds of recommending screening according to the use of systematic review methods was estimated across conditions using meta-analysis.

Results 93 reports were included that assessed 104 conditions across 14 countries, totalling 276 recommendations (units of analysis). Screening was favoured in 159 (58%) recommendations, not favoured in 98 (36%), and not recommended either way in 19 (7%). Only 60 (22%) of the recommendations included a systematic review. Use of a systematic review was associated with a reduced probability of screening being recommended (23/60 (38%) v 136/216 (63%), odds ratio 0.17, 95% confidence interval 0.07 to 0.43). Of the recommendations, evidence for test accuracy, benefits of early detection, and overdiagnosis was not considered in 115 (42%), 83 (30%), and 211 (76%), respectively.

Conclusions Using systematic review methods is associated with a reduced probability of screening being recommended. Many national policy reviews of screening for rare conditions using the newborn blood spot test do not assess the evidence on the key benefits and harms of screening.


  • Contributors: ST-P designed the study, was first reviewer, undertook the analysis, drafted the manuscript, and is the guarantor. CS and LFdR were second reviewers. FS ran the searches. AC assisted with study design and write up. JD contributed to study design and planned the statistical analysis. All authors contributed to the write up and approved the final version.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: support from the National Institute for Health Research (NIHR) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Funding: This study presents independent research that was in part funded by the NIHR through a career development fellowship for ST-P. ST-P, AC, and CS are supported by the NIHR CLAHRC West Midlands initiative. JD is supported in part by the NIHR Birmingham Biomedical Research Centre and an NIHR senior investigator award. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health.

  • Ethical approval: Not required.

  • Data sharing: The authors are willing to share data by personal communication to ST-P.

  • Transparency: The lead author (ST-P) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant) have been explained.

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