Screening

Carrier screening before and during pregnancy

In the UK, screening early in pregnancy (before 10 weeks' gestation) is recommended for women at high risk of being sickle cell carriers (either living in a high prevalence area or based on family origin). If a woman is found to be a carrier, screening is offered to the father.[15]​​[36]​​ UK guidelines recommend considering preconception testing (or premarital testing, if appropriate) for sickle cell disease in women from high-risk ethnic groups, although this is not included in the National Screening Programme. If the woman is found to be a carrier, her partner should be offered screening.​[15]

The American College of Obstetricians and Gynecologists recommends universal haemoglobinopathy testing for those planning pregnancy.[16][17]​​ Haemoglobin electrophoresis or molecular genetic testing (e.g., expanded carrier screening that includes sickle cell disease) should be performed when planning pregnancy, or at the initial antenatal visit if there are no previous test results available.[16] If a woman is found to be a carrier, her reproductive partner should be offered screening.[17] Information and counselling should be offered alongside screening.[17][18]

Offering antenatal screening for sickle cell disease at the time of pregnancy confirmation in primary care may modestly increase the proportion of women screened before 10 weeks' gestation.[19]

Antenatal diagnosis

Counselling and antenatal diagnosis may be considered if both parents are either carriers or affected by sickle cell disease (or the woman is a carrier or affected and the status of the father is unknown). Available tests for patients who are pregnant include chorionic villus sampling (typically performed at 10-12 weeks' gestation in the US; 11-14 weeks' gestation in the UK) and amniocentesis (typically performed after 15 weeks' gestation).[20][21] ​These are invasive tests and carry a risk of fetal loss.

Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal circulation is emerging as a potential antenatal screening test for haemoglobinopathies such as sickle cell disease and thalassaemia.[16]

Preimplantation genetic testing to prevent a pregnancy with sickle cell disease is an option for prospective parents considering in vitro fertilisation.[20][21]​​

Newborn screening

In the US, all states practise universal neonatal screening to ensure that all infants with sickle cell disease are identified.[22] Blood for screening is usually taken by heel-stick sample (within 48 hours of birth) and haemoglobin evaluation carried out (ideally within 24 hours of collection).[23][24]

Newborn screening is typically performed using haemoglobin isoelectric focusing (Hb IEF) or high-performance liquid chromatography (HPLC) fractionation. Confirmatory testing should be performed by an alternative method (IEF, HPLC, electrophoresis, or DNA sequencing); timely confirmation is important (no later than aged 3 months) to ensure prompt initiation of antibiotic prophylaxis.[15][25]​​​ 

When an abnormal result is confirmed, the laboratory must have a system in place for rapid communication of results to the patient's healthcare provider.​​ Appropriate referral to a specialty sickle cell clinic for education, genetic counselling, and routine follow-up care is essential and should occur as soon as the diagnosis is made.

UK newborn blood spot (NBS) screening

Worldwide approaches to neonatal screening vary. In the UK, all newborns are offered screening for sickle cell disease as part of the NHS newborn blood spot screening programme. A heel-stick sample is taken on day 5 after birth (or earlier if there is a family history of sickle cell disease).[15][29]​​

For babies newly arriving in the UK (or those who missed newborn screening) screening is offered to up to age 1 year.​[29]

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