Prenatal Diagnosis

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Prenatal diagnosis needs to be differentiated from routine antenatal screening. The National Institute for Health and Clinical Excellence (NICE) and the UK National Screening Committee (UK NSC) have laid down standards for antenatal care, including the screening tests that should be offered to all pregnant women.[1] These screening tests do not give a definitive prenatal diagnosis but give a risk/probability of a problem with the fetus, for example Down's syndrome. Further diagnostic tests are required to confirm and diagnose the fetal abnormality.

Prenatal diagnosis is therefore offered to all pregnant women if they have positive antenatal screening results. However, some women may be offered definitive prenatal diagnosis from the outset without any preceding screening tests; for example:

  • If there is a family history of an inherited condition.
  • If they have had a previous pregnancy with fetal abnormality.
  • If they have been exposed to illness such as toxoplasmosis or rubella during the pregnancy.
  • If they have been exposed to teratogens, such as certain drugs or radiation, during the pregnancy.
  • If the woman has type 1 diabetes mellitus, epilepsy or myotonic dystrophy.

The primary aim of a prenatal diagnosis is to provide an accurate diagnosis that will allow the widest possible range of informed choice to those at increased risk of having children with genetic disorders or with congenital abnormalities.[2]

Informed consent should always be obtained before antenatal screening and prenatal diagnostic testing.

In all cases of antenatal screening, the woman must be fully informed and understand the implications of the test, be promptly advised of their test result and be referred for further management and definitive diagnosis if their screening test is positive or high risk.[1]

A positive prenatal diagnosis poses many ethical issues and challenging decisions for parents and clinicians. In those at increased risk of having a baby with a genetic condition, the risk should be identified and discussed fully before pregnancy and options for prenatal diagnosis discussed. Genetic counselling should be provided.[2]

The following subsections cover the antenatal screening tests that are routinely offered.

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Screening for potential for neonatal infection

Testing for hepatitis B, HIV and syphilis and susceptibility to rubella is offered to all women, in each pregnancy, at antenatal booking. This means that effective antenatal intrapartum and postnatal intervention can be offered to infected women to decrease the risk of mother-to-child-transmission.

Screening for haemolytic disease of the newborn

Maternal blood group and RhD status are checked at antenatal booking. Assessment for atypical red cell alloantibodies is also carried out at booking and again at 28 weeks to screen for the possibility of the development of haemolytic disease of the newborn. All non-sensitised pregnant women who are RhD negative are offered routine antenatal anti-D prophylaxis.

Screening for sickle cell disease and thalassaemia

Maternal blood testing for disease and carrier status is offered and, if necessary, paternal blood testing is undertaken so that the probability of the fetus being affected can be assessed.[3] If both parents are found to be carriers of a haemoglobinopathy then prenatal diagnosis will be offered.

Down's syndrome screening

NICE guidelines state that all pregnant women should be offered this screening. In England and Scotland this is done using the the combined test (nuchal translucency measurement combined with serum markers) in the first trimester of pregnancy. For women who book too late for the combined test a quadruple serum screening test should be offered up until 20 weeks of gestation.

In Wales at present the quadruple test is offered for women choosing Down's syndrome screening. The implementation of combined test is being planned.

Northern Ireland does not have a Down's syndrome screening programme but a second trimester fetal anomaly scan is offered.

See separate article Antenatal Screening for Down's Syndrome.

Fetal anomaly screening

Fetal anomaly scanning by ultrasound is offered to all pregnant women in the UK between 18 weeks and 20 weeks 6 days of gestation. Although this can uncover a large number of structural anomalies, the UK NSC has agreed that only those conditions that have sufficiently high detection rates should be formally assessed as part of the programme's pathway standards and quality assurance system.

The following fulfil that criterion and are part of the current programme: anencephaly, open spina bifida, gastroschisis, Edward's syndrome and Patau's syndrome all have detection rates over 90%; cleft lip, exomphalos and bilateral renal agenesis have detection rates between 70 and 80%; diaphragmatic hernia, serious cardiac abnormalities and lethal skeletal dysplasias have detection rates between 50 and 60%.

Measurement of fundal height

Abdominal palpation and measurement of symphysis-fundal distance screen for babies that are small- or large-for-gestational-age and to help detect polyhydramnios or oligohydramnios which may suggest an underlying problem with the fetus that requires further investigation and definitive prenatal diagnosis.

If an antenatal screening test result suggests the pregnancy is at a high risk of a condition, a definitive diagnostic test will be offered to the woman. Women who have had a previous fetal abnormality or who have a family history of an inherited condition may be offered these diagnostic tests from the outset.

The following types of tests are available depending on the condition being tested for:

  • Biochemical analysis: enzyme levels can be assayed to detect inborn errors of metabolism. Alpha-fetoprotein and acetylcholinesterase levels can be measured to help identify and distinguish between neural tube defects, anencephaly and ventral wall defects, such as gastroschisis and omphalocele, that may have been suspected during anomaly scanning. Hormone levels can be assessed to diagnose adrenogenital syndrome.
  • Cytogenetic analysis: analysis for chromosomal abnormalities such as Down's syndrome can be carried out using cell culture and karyotyping. More recently, rapid aneuploidy techniques using polymerase chain reaction (PCR) have been used to detect Down's syndrome, which provide results much more quickly than karyotype analysis from cultured cells, which usually takes 13-14 days.[4][5]
  • Molecular genetic tests: if a disease-causing mutation has been identified in a family, molecular genetic tests can be performed to detect genetic diseases such as cystic fibrosis.

The following techniques are used:


This is the most common invasive prenatal diagnostic procedure carried out in the UK. This is normally carried out from 15 weeks of gestation. A needle is inserted into the amniotic cavity and amniotic fluid is sampled, allowing culture and assessment of fetal cells in the fluid. Fetal cells in the amniotic fluid can then be analysed. See separate article Amniocentesis.

Chorionic villus sampling

This can be carried out earlier - usually between 10-13 weeks. It involves sampling of the developing placenta and again the same type of analysis of fetal cells to detect chromosomal, genetically inherited and endocrine or metabolic conditions, can be performed. See separate article Chorionic Villus Sampling.


This allows visualisation of the fetus, using endoscopic techniques. It is usually carried out between 18-20 weeks of gestation. It allows fetal inspection for structural abnormalities, fetal blood sampling to detect, and possibly allow intervention in, conditions such as haemophilias, thalassaemia and sickle cell disease, as well as fetal skin and liver biopsy.

Cordocentesis/percutaneous umbilical blood sampling

This technique uses ultrasound guidance to obtain fetal blood cells from the umbilical cord. It enables karyotyping/chromosome analysis as well as being used for the assessment and treatment of rhesus iso-immunisation. Intrauterine blood transfusions may be performed using this technique. Fetal viral infection can be confirmed by immunoglobulin assessment of fetal blood and some haematological and metabolic abnormalities can be detected. The fetal loss rate is 1-3%.[2]

Fetal radiology

In suspected skeletal dysplasia, X-rays can be taken around the same time as the routine anomaly ultrasound scan. Prenatal MRI scanning is also used to assess fetuses with spina bifida, look for associated malformations and, along with ultrasound scanning, to help to predict neurological deficit and ambulatory potential.[6][7]

Fetal echocardiography can also be carried out if cardiac defects are suspected; for example, if there is a family history of congenital heart problems, or in maternal diseases with an increased risk of fetal heart defects, eg diabetes.

Maternal blood tests

Maternal serum alpha-fetoprotein levels can be measured to aid the diagnosis of neural tube defects between 15-22 weeks. They are also raised in abdominal wall defects but amniotic fluid analysis of acetylcholinesterase can help to differentiate between these conditions.

Ultrasound-guided percutaneous skin and organ biopsy

This can also be carried out to allow skin, muscle, liver and other fetal organ analysis.

If a prenatal diagnosis is made, the woman may choose to have a termination of the pregnancy. If a potentially lethal fetal abnormality is detected, most parents do opt for termination, which may include feticide.[8] They may, however, choose to continue with the pregnancy and opt for perinatal palliative care. Any woman seeking a termination, for whatever reason, must have grounds under the Abortion Act 1967. This area becomes very grey when considering relatively 'minor' abnormalities detected by prenatal diagnosis, such as cleft lip and palate, limb abnormalities, etc. See separate article Termination of Pregnancy.

Other women prefer to have confirmation of an abnormality using prenatal diagnosis to allow them to prepare perinatally and postnatally. Prenatal diagnosis may allow potential in utero fetal treatment of the condition in some cases - for example, in rhesus iso-immunisation.

This is a technique that allows the analysis of blastocysts conceived through in vitro fertilisation. Embryos that are affected by a specific genetic disorder are in this way not transferred back to the mother.

At present, in most cases, accurate prenatal diagnosis requires invasive testing. There is current research into noninvasive prenatal diagnosis using PCR and molecular genetic techniques to examine fetal DNA obtained from maternal blood.[9][10][11]

Prenatal diagnostic accuracy is improving but, as one UK study showed, may be lower than many clinicians assume - and the public expects - for some important conditions such as diaphragmatic hernia, bladder outlet obstruction and major skeletal defects in which detection rates prenatally were reported still to be less than 70%.[12]

Further reading & references

  1. Antenatal care: routine care for the healthy pregnant woman; NICE Clinical Guideline (March 2008)
  2. Human Genetics Commission; Advisory Committee on Genetic Testing. Prenatal Genetic Testing. Report for Consultation. February 2000.
  3. Sickle Cell and Thalassaemia Screening Programme; NHS - Public Health England
  4. Mann K, Fox SP, Abbs SJ, et al; Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis. Lancet. 2001 Sep 29;358(9287):1057-61.
  5. Chitty LS, Kagan KO, Molina FS, et al; Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study. BMJ. 2006 Feb 25;332(7539):452-5. Epub 2006 Feb 13.
  6. Mangels KJ, Tulipan N, Tsao LY, et al; Fetal MRI in the evaluation of intrauterine myelomeningocele. Pediatr Neurosurg. 2000 Mar;32(3):124-31.
  7. Cochrane DD, Wilson RD, Steinbok P, et al; Prenatal spinal evaluation and functional outcome of patients born with myelomeningocele: information for improved prenatal counselling and outcome prediction. Fetal Diagn Ther. 1996 May-Jun;11(3):159-68.
  8. Breeze AC, Lees CC, Kumar A, et al; Palliative care for prenatally diagnosed lethal fetal abnormality. Arch Dis Child Fetal Neonatal Ed. 2007 Jan;92(1):F56-8. Epub 2006 May 16.
  9. Saito H, Sekizawa A, Morimoto T, et al; Prenatal DNA diagnosis of a single-gene disorder from maternal plasma. Lancet. 2000 Sep 30;356(9236):1170.
  10. Dhallan R, Guo X, Emche S, et al; A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study. Lancet. 2007 Feb 10;369(9560):474-81.
  11. Chi C, Hyett JA, Finning KM, et al; Non-invasive first trimester determination of fetal gender: a new approach for prenatal diagnosis of haemophilia. BJOG. 2006 Feb;113(2):239-42.
  12. Richmond S, Atkins J; A population-based study of the prenatal diagnosis of congenital malformation over 16 years. BJOG. 2005 Oct;112(10):1349-57.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Michelle Wright
Current Version:
Peer Reviewer:
Dr John Cox
Last Checked:
Document ID:
2656 (v25)