Clinical question
How accurate are first-trimester serum markers for the detection of Down syndrome in the antenatal period?
Bottom line
Tests involving 2 markers in combination with maternal age – specifically PAPP-A (pregnancy-associated plasma protein A), free beta-hCG (beta-human chorionic gonadotropin) and maternal age – were significantly better than those involving single markers, with and without age. They detected 7 out of 10 Down-affected pregnancies (3 in 10 were missed), and a fixed 5% of all tested women got a false-positive result. The addition of further markers (triple tests) was not shown to be statistically superior; the studies included were small, with limited power to detect a difference. The screening blood tests themselves had no adverse effects for the woman, over and above the risks of a routine blood test.
Caveat
Some women who have a “high risk” screening test result, and are given amniocentesis or chorionic villus sampling, have a risk of miscarriage of a baby unaffected by Down syndrome. Parents need to weigh up this risk when deciding whether or not to have amniocentesis or chorionic villus sampling following a “high risk” screening result.
Context
Down syndrome is the most common congenital cause of mental disability, and it also leads to numerous metabolic and structural problems. Non-invasive screening based on biochemical analysis of maternal serum or urine, or foetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected, and provides information to guide decisions about definitive testing.
Cochrane Systematic Review
Review Alldred SK et al. First trimester serum tests for Down’s syndrome screening. Cochrane Reviews, 2015, Issue 11. Art. No.: CD011975.DOI: 10.1002/14651858. CD011975. This review contains 56 studies involving 204,759 participants (including 2113 with Down syndrome).
Cochrane Systematic Reviews for primary care practitioners
Developed by the Cochrane Primary Care Field, New Zealand Branch of the Australasian Cochrane Centre at the Department of General Practice and Primary Health Care, University of Auckland and funded by the Ministry of Health and New Zealand Doctor. PEARLS are meant for educational use and not to guide clinical care. New Zealanders can access the Cochrane Library free via www.cochrane.org.nz
![Barbara Fountain, editor of New Zealand Doctor Rata Aotearoa, and Paul Hutchison, GP and senior medical clinician at Tāmaki Health [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/Barbara%20Fountain%2C%20editor%20of%20New%20Zealand%20Doctor%20Rata%20Aotearoa%2C%20and%20Paul%20Hutchison%2C%20GP%20and%20senior%20medical%20clinician%20at%20T%C4%81maki%20Health%20CR%20Simon%20Maude.jpg?itok=-HbQ1EYA)
![Lori Peters, NP and advanced health improvement practitioner at Mahitahi Hauora, and Jasper Nacilla, NP at The Terrace Medical Centre in Wellington [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/2.%20Lori%20Peters%2C%20NP%20and%20advanced%20HIP%20at%20Mahitahi%20Hauora%2C%20and%20Jasper%20Nacilla%2C%20NP%20at%20The%20Terrace%20Medical%20Centre%20in%20Wellington%20CR%20Simon%20Maude.jpg?itok=sUfbsSF1)
![Ministry of Social Development health and disability coordinator Liz Williams, regional health advisors Mary Mojel and Larah Takarangi, and health and disability coordinators Rebecca Staunton and Myint Than Htut [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/3.%20Ministry%20of%20Social%20Development%27s%20Liz%20Williams%2C%20Mary%20Mojel%2C%20Larah%20Takarangi%2C%20Rebecca%20Staunton%20and%20Myint%20Than%20Htut%20CR%20Simon%20Maude.jpg?itok=9ceOujzC)
![Locum GP Helen Fisher, with Te Kuiti Medical Centre NP Bridget Woodney [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/4.%20Locum%20GP%20Helen%20Fisher%2C%20with%20Te%20Kuiti%20Medical%20Centre%20NP%20Bridget%20Woodney%20CR%20Simon%20Maude.jpg?itok=TJeODetm)
![Ruby Faulkner, GPEP2, with David Small, GPEP3 from The Doctors Greenmeadows in Napier [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/5.%20Ruby%20Faulkner%2C%20GPEP2%2C%20with%20David%20Small%2C%20GPEP3%20from%20The%20Doctors%20Greenmeadows%20in%20Napier%20CR%20Simon%20Maude.jpg?itok=B0u4wsIs)
![Rochelle Langton and Libby Thomas, marketing advisors at the Medical Protection Society [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/6.%20Rochelle%20Langton%20and%20Libby%20Thomas%2C%20marketing%20advisors%20at%20the%20Medical%20Protection%20Society%20CR%20Simon%20Maude.jpg?itok=r52_Cf74)
![Specialist GP Lucy Gibberd, medical advisor at MPS, and Zara Bolam, urgent-care specialist at The Nest Health Centre in Inglewood [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/7.%20Specialist%20GP%20Lucy%20Gibberd%2C%20medical%20advisor%20at%20MPS%2C%20and%20Zara%20Bolam%2C%20urgent-care%20specialist%20at%20The%20Nest%20Health%20Centre%20in%20Inglewood%20CR%20Simon%20Maude.jpg?itok=z8eVoBU3)
![Olivia Blackmore and Trudee Sharp, NPs at Gore Health Centre, and Gaylene Hastie, NP at Queenstown Medical Centre [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/8.%20Olivia%20Blackmore%20and%20Trudee%20Sharp%2C%20NPs%20at%20Gore%20Health%20Centre%2C%20and%20Gaylene%20Hastie%2C%20NP%20at%20Queenstown%20Medical%20Centre%20CR%20Simon%20Maude.jpg?itok=Z6u9d0XH)
![Mary Toloa, specialist GP at Porirua and Union Community Health Service in Wellington, Mara Coler, clinical pharmacist at Tū Ora Compass Health, and Bhavna Mistry, specialist GP at Porirua and Union Community Health Service [Image: Simon Maude]](/sites/default/files/styles/thumbnail_cropped_100/public/2025-03/9.%20Mary%20Toloa%2C%20Porirua%20and%20Union%20Community%20Health%20Service%20in%20Wellington%2C%20Mara%20Coler%2C%20T%C5%AB%20Ora%20Compass%20Health%2C%20and%20Bhavna%20Mistry%2C%20PUCHS%20CR%20Simon%20Maude.jpg?itok=kpChr0cc)