Guthrie test

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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.


Dr Robert Guthrie
Dr Robert Guthrie
Gutherie card
A neonatal blood screening test developed by Dr Robert Guthrie (1916-95) at University of Buffalo.
The "Heel Prick" test.

The "Heel Prick" test is now routinely carried out on neonatal (newborn) blood for a variety of known genetic disorders. Different countries have different policies on the archiving of this material and deidentified availability for genetic research purposes. The clinical term "phlebotomy" describes the act of drawing or removing blood from the circulatory system through an incision or puncture to obtain a sample for analysis and diagnosis.

An ultrasound study[1] has identified the shortest depth of perichondrium was in the centre of the heel and ranged from 3 to 8 mm. In 78 of the 80 infants in the study (GA24 to 42 weeks), the distance was 4 mm or more. Showing that the standard automated lancets for preterm use (puncture to a depth of 2.4 mm) may be safely used anywhere over the plantar surface of the heel avoiding the posterior aspect of the heel. A more recent study[2] identified the whole heel plantar surface is safe for obtaining blood in term and preterm infants of more than GA 33 weeks. A small amount of sucrose (0.012–0.12 g) can be given as an analgesic for newborns undergoing venepuncture or capillary heel-pricks.[3]

Blood is collected using a heelprick and spotted onto a test sheet to dry for later testing. Different countries and medical services have different policies on not only what will be tested for but also how long the test card will be kept following analysis. Check your local service for specific information.

Diagnosis Links: Prenatal Diagnosis | Pregnancy Test | Amniocentesis | Chorionic villus sampling | Ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

Some Recent Findings

UK Neonatal blood spot test (August 2013)
  • Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes[4] "Many inborn errors of metabolism (IEMs) may present as sudden infant death (SID). Nowadays, increasing numbers of patients with IEMs are identified pre-symptomatically by population neonatal bloodspot screening (NBS) programmes. However, some patients escape early detection because their symptoms and signs start before NBS test results become available, they even die even before the sample for NBS has been drawn or because there are IEMs which are not included in the NBS programmes. This was a comprehensive systematic literature review to identify all IEMs associated with SID, including their treatability and detectability by NBS technologies. Reye syndrome (RS) was included in the search strategy because this condition can be considered a possible pre-stage of SID in a continuum of aggravating symptoms. RESULTS: 43 IEMs were identified that were associated with SID and/or RS. Of these, (1) 26 can already present during the neonatal period, (2) treatment is available for at least 32, and (3) 26 can currently be identified by the analysis of acylcarnitines and amino acids in dried bloodspots (DBS). We advocate an extensive analysis of amino acids and acylcarnitines in blood/plasma/DBS and urine for all children who died suddenly and/or unexpectedly, including neonates in whom blood had not yet been drawn for the routine NBS test. The application of combined metabolite screening and DNA-sequencing techniques would facilitate fast identification and maximal diagnostic yield."
  • UK National Screening Committee - Newborn babies will be tested for four more disorders[5] "The test is already used to screen for phenylketonuria, hypothyroidism, sickle cell disease, cystic fibrosis, and medium chain acyl-CoA dehydrogenase deficiency. To these five conditions four more will now be added: homocystinuria, maple syrup urine disease, glutaric aciduria type 1, and isovaleric acidaemia."
  • The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States[6] "We aimed to measure separately the contributions of heat and humidity to changes in levels of 34 markers of inborn disorders in dried-blood-spot (DBS) samples. We stored paired sets of DBSs at 37°C for predetermined intervals in low-humidity and high-humidity environments. Marker levels of all samples in each complete sample set were measured in a single analytic run. During the 30 ± 5 day studies, galactose-1-phosphate uridyltransferase and biotinidase lost almost 65% of initial activities in low-humidity storage; most of the degradation in 27 other markers was attributable to adverse effects of high-humidity storage; seven markers in DBSs stored at high humidity lost more than 90% of initial levels by the end of the study and 4 of the 7 lost more than 50% of initial levels within the first week of storage."
  • Newborn hearing screening and genetic testing in 8974 Brazilian neonates.[7]"We have found 17 individuals who failed in transient otoacoustic emissions (TOAE). Among them, we detected 4 homozygous newborns for 35delG mutation and 3 individuals with A827G mutation in the MTRNR1 mitochondrial gene."
  • Whole genome microarray analysis, from neonatal blood cards. [8]] "Neonatal blood, obtained from a heel stick and stored dry on paper cards, has been the standard for birth defects screening for 50 years. Such dried blood samples are used, primarily, for analysis of small-molecule analytes. More recently, the DNA complement of such dried blood cards has been used for targeted genetic testing, such as for single nucleotide polymorphism in cystic fibrosis. Expansion of such testing to include polygenic traits, and perhaps whole genome scanning, has been discussed as a formal possibility. However, until now the amount of DNA that might be obtained from such dried blood cards has been limiting, due to inefficient DNA recovery technology. ...Together, these data suggest that DNA obtained from less than 10% of a standard neonatal blood specimen, stored dry for several years on a Guthrie card, can support a program of genome-wide neonatal genetic testing."
More recent papers  
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Search term: neonatal blood test

Y N Paudel, M R Ali, S Bawa, S Shah, M Adil, A Siddiqui, A S Basheer, M Q Hassan, M Sharma Evaluation of 4-methyl-2-[(2-methylbenzyl) amino]-1,3-thiazole-5-carboxylic acid against hyperglycemia, insulin sensitivity, and oxidative stress-induced inflammatory responses and β-cell damage in the pancreas of streptozotocin-induced diabetic rats. Hum Exp Toxicol: 2017;960327117692133 PubMed 29233026

Alex Grier, Xing Qiu, Sanjukta Bandyopadhyay, Jeanne Holden-Wiltse, Haeja A Kessler, Ann L Gill, Brooke Hamilton, Heidie Huyck, Sara Misra, Thomas J Mariani, Rita M Ryan, Lori Scholer, Kristin M Scheible, Yi-Horng Lee, Mary T Caserta, Gloria S Pryhuber, Steven R Gill Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth. Microbiome: 2017, 5(1);158 PubMed 29228972

Michelle Desforges, Alexandra Rogue Rogue, Nick Pearson, Carlo Rossi, Elena Olearo, Roy Forster, Mark Lees, Neil Sebire, Susan Greenwood, Colin Sibley, Anna L David, Paul Brownbill In vitro human placental studies to support an adenovirus-mediated VEGF-DΔNΔC maternal gene therapy for the treatment of severe early-onset fetal growth restriction. Hum Gene Ther Clin Dev: 2017; PubMed 29228803

Zainab Al-Ibraheemi, Lois Brustman, Brianne E Bimson, Natalie Porat, Barak Rosenn Misoprostol With Foley Bulb Compared With Misoprostol Alone for Cervical Ripening: A Randomized Controlled Trial. Obstet Gynecol: 2017; PubMed 29215514

Anna Catherine Tottman, Jane Marie Alsweiler, Frank Harry Bloomfield, Greg Gamble, Yannan Jiang, Myra Leung, Tanya Poppe, Benjamin Thompson, Trecia Ann Wouldes, Jane Elizabeth Harding, PIANO Study Group Long-Term Outcomes of Hyperglycemic Preterm Infants Randomized to Tight Glycemic Control. J. Pediatr.: 2017; PubMed 29198539

Search term: Guthrie test

Caroline M Mitchell, Sujatha Srinivasan, Anna Plantinga, Michael C Wu, Susan D Reed, Katherine A Guthrie, Andrea Z LaCroix, Tina Fiedler, Matthew Munch, Congzhou Liu, Noah G Hoffman, Ian A Blair, Katherine Newton, Ellen W Freeman, Hadine Joffe, Lee Cohen, David N Fredricks Associations between improvement in genitourinary symptoms of menopause and changes in the vaginal ecosystem. Menopause: 2017; PubMed 29206774

Jonathan Stokes, Mei-See Man, Bruce Guthrie, Stewart W Mercer, Chris Salisbury, Peter Bower The Foundations Framework for Developing and Reporting New Models of Care for Multimorbidity. Ann Fam Med: 2017, 15(6);570-577 PubMed 29133498

Alessandro Borghesi, Maria Antonietta Mencarelli, Luigi Memo, Giovanni Battista Ferrero, Andrea Bartuli, Maurizio Genuardi, Mauro Stronati, Alberto Villani, Alessandra Renieri, Giovanni Corsello, their respective Scientific Societies Intersociety policy statement on the use of whole-exome sequencing in the critically ill newborn infant. Ital J Pediatr: 2017, 43(1);100 PubMed 29100554

Dipesh Uprety, Amir Bista, Adithya Chennamadhavuni, Abesh Niroula, Syed Imran Mustafa Jafri, Angela Smith, Lubina Arjyal Survival trends among patients with metastatic melanoma in the pretargeted and the post-targeted era: a US population-based study. Melanoma Res.: 2017; PubMed 29023264

Deborah J Baldie, Bruce Guthrie, Vikki Entwistle, Thilo Kroll Exploring the impact and use of patients' feedback about their care experiences in general practice settings-a realist synthesis. Fam Pract: 2017; PubMed 28985368

Routine Screened Disorders

This list may differ between countries.

  • Phenylketonuria (PKU)
  • Biotinidase Deficiency (OMIM)
  • Congenital Adrenal Hyperplasia (CAH) (OMIM)
  • Congenital Hypothyroidism (CH)
  • Congenital Toxoplasmosis
  • Cystic Fibrosis (CF) (OMIM)
  • Galactosemia (GAL) (OMIM)
  • Homocystinuria (OMIM)
  • Maple Syrup Urine Disease (MSUD) (OMIM)
  • Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) (OMIM)
  • Toxoplasma gondii IgM antibodies[9]


NSW Newborn Screening Programme

NSW Newborn Screening Programme

Each year test more than 90,000 babies and detects about 90 who need urgent assessment and treatment. In NSW and Victoria, the bloodspot cards are currently stored indefinitely.

  • Phenylketonuria (PKU) - 1 in 10,000 live births (about 10 babies per year). PKU causes high blood levels of phenylalanine and severe intellectual disability. A diet low in phenylalanine, started in the first two to three weeks results in normal development.
  • Primary congenital hypothyroidism - 1 in 3,500 live births (about 26 babies per year). It is caused by the absence or abnormal formation or function of the thyroid gland. This causes growth and intellectual disability if not treated. Medication with thyroid hormone started early, results in normal growth and development.
  • Cystic Fibrosis (CF) - 1 in 2,500 live births (about 34 babies per year). Without treatment babies develop chest infections and often have very serious failure to thrive. Early institution of treatment greatly improves the health of babies with CF. Newborn bloodspot screening detects about 95% of babies with CF but also detects a few babies who may only be healthy carriers. For these babies a sweat test at about six weeks of age determines whether the baby has CF or is a healthy carrier.
  • Galactosaemia - 1 in 40,000 births (about 1-3 cases per year). Babies cannot process galactose, a component of lactose. Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first week is life saving.
  • Rarer metabolic disorders - Some fatty acid, organic acid and other amino acid defects can now be detected using Tandem Mass Spectrometry. These much rarer metabolic disorders affect about 15 – 18 babies per year. Early detection is important as diet and medications can treat most of these disorders. Without appropriate management they can cause severe disability or death.

Potential uses and access of stored bloodspots

  • Identified cards may be used for family benefit or research and only with separate consent obtained before testing.
  • Non-identifiable cards (identifiers permanently removed) may be used for research approved by a Health Research Ethics Committee – consent is not required.
  • Parents have a right to access their child’s information. Other access requires parental consent except where there is a court order, to date this has not occurred.

Genetics services in NSW - coordinated by the NSW Genetics Service Advisory Committee, which is supported by the Statewide Services Development Branch of the Strategic Development Division, NSW Department of Health. (Information from NSW Health - Newborn Bloodspot Screening Policy 13-Nov-2006)

Links: NSW Genetics Health


State laws mandate that blood be drawn from all newborn infants to screen for health-threatening conditions.


  1. A Jain, N Rutter Ultrasound study of heel to calcaneum depth in neonates. Arch. Dis. Child. Fetal Neonatal Ed.: 1999, 80(3);F243-5 PubMed 10212093
  2. J Arena, J I Emparanza, A Nogués, A Burls Skin to calcaneus distance in the neonate. Arch. Dis. Child. Fetal Neonatal Ed.: 2005, 90(4);F328-f331 PubMed 15871987
  3. B Stevens, J Yamada, A Ohlsson Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev: 2004, (3);CD001069 PubMed 15266438
  4. Willemijn J van Rijt, Geneviève D Koolhaas, Jolita Bekhof, M Rebecca Heiner Fokkema, Tom J de Koning, Gepke Visser, Peter C J I Schielen, Francjan J van Spronsen, Terry G J Derks Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes. Neonatology: 2016, 109(4);297-302 PubMed 26907928
  5. Newborn babies will be tested for four more disorders, committee decides BMJ 2014; 348 doi: (Published 13 May 2014) BMJ 2014;348:g3267 UK National Screening Committee
  6. B W Adam, E M Hall, M Sternberg, T H Lim, S R Flores, S O'Brien, D Simms, L X Li, V R De Jesus, W H Hannon The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States. Clin. Biochem.: 2011, 44(17-18);1445-50 PubMed 21963384
  7. Karin de A B Nivoloni, Sueli M da Silva-Costa, Mariza C A Pomílio, Tânia Pereira, Karen de C Lopes, Vanessa C S de Moraes, Fabiana Alexandrino, Camila A de Oliveira, Edi L Sartorato Newborn hearing screening and genetic testing in 8974 Brazilian neonates. Int. J. Pediatr. Otorhinolaryngol.: 2010, 74(8);926-9 PubMed 20538352
  8. Jill Hardin, Richard H Finnell, David Wong, Michael E Hogan, Joy Horovitz, Jenny Shu, Gary M Shaw Whole genome microarray analysis, from neonatal blood cards. BMC Genet.: 2009, 10;38 PubMed 19624846 | BMC
  9. The national neonatal screening programme for congenital toxoplasmosis in Denmark: results from the initial four years, 1999-2002. Schmidt DR, Hogh B, Andersen O, Fuchs J, Fledelius H, Petersen E. Arch Dis Child. 2006 Aug;91(8):661-5. PMID: 16861484]


Jet van der Spek, Rolf H H Groenwold, Mirjam van der Burg, Joris M van Montfrans TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review. J. Clin. Immunol.: 2015; PubMed 25893636


B W Adam, E M Hall, M Sternberg, T H Lim, S R Flores, S O'Brien, D Simms, L X Li, V R De Jesus, W H Hannon The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States. Clin. Biochem.: 2011, 44(17-18);1445-50 PubMed 21963384

A Streetly, R Latinovic, K Hall, J Henthorn Implementation of universal newborn bloodspot screening for sickle cell disease and other clinically significant haemoglobinopathies in England: screening results for 2005-7. J. Clin. Pathol.: 2009, 62(1);26-30 PubMed 19103854

P D Whiteman, B E Clayton, R S Ersser, P Lilly, J W Seakins Changing incidence of neonatal hypermethioninaemia: implications for the detection of homocystinuria. Arch. Dis. Child.: 1979, 54(8);593-8 PubMed 507913

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Cite this page: Hill, M.A. 2017 Embryology Guthrie test. Retrieved December 18, 2017, from

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