Guidance

Newborn screening

Updated 6 July 2018

Screening for sickle cell disease (SCD) is offered as part of the newborn blood spot (NBS) screening programme. It also detects babies who are genetic carriers of some haemoglobin variants. The main reason for offering newborn screening is that babies with sickle cell disease are vulnerable to life-threatening infections. By identifying them promptly after birth, they can be offered potentially life-saving prophylactic antibiotics, and be referred for specialist care.

There is no routine screen for babies at risk of inheriting thalassaemia major. However, most cases of beta thalassaemia major should be detected during newborn screening, but beta thalassaemia carriers are not.

All babies under one year of age (up to but not including their first birthday) are eligible for NBS screening. If a baby under one year of age does not have documented result or decline, screening should be offered if the blood spot sample can be taken before they reach one year of age.

The sickle cell and thalassaemia (SCT) and NBS screening programmes have published standards for newborn screening, against which screening services will be assessed and monitored. In addition, the NBS programme handbook provides information on all aspects of this screening programme.

1. Linked antenatal and newborn screening programme

Linking the results of parents and babies is particularly important for the SCT screening programme, as it helps accurate diagnosis of babies. All maternal carrier results, and at-risk couple results, should be linked to the appropriate newborn screening results.

The at risk pregnancy alert form should be used to inform NBS screening laboratories of any carrier women and at-risk couples identified antenatally.

2. Offer of the newborn blood spot screen

Parents must be offered information about the NBS test before the offer of screening. The parent information leaflet, Screening tests for you and your baby is available to support information from a healthcare professional. The leaflet is also available in a number of languages and easy read versions.

Guidance on offering NBS screening, taking the sample and recording consent or decline is available in the guidelines for newborn blood spot sampling.

If the screen for SCD is accepted, this should be recorded in the maternity record and personal child health record (PCHR). If the screen is accepted and the baby is in hospital, then consent should also be recorded in the baby’s hospital records.

If the screen for SCD is declined:

• this should be recorded on the blood spot card and sent to the laboratory
• this must be recorded in the maternity records and the PCHR
• the baby’s GP, health visitor and child health records department (CHRD) must be informed
• the parents should be given a letter that confirms their decision and details of who to contact if they change their mind or would like further information

3. Babies born to at-risk couples

Couples at risk of having a baby with a major haemoglobin disorder, where the results of both parents are known, may want to know their baby’s result earlier than normal.

Local policies should be in place to have an early newborn blood spot test (in addition to the day 5 test), at the parents’ request. Some trusts offer a liquid capillary blood specimen (not cord blood), which can be taken for analysis soon after birth. This is not part of the screening programme and does not replace NBS screening.

The blood sample must be analysed in a laboratory which has expertise in haemoglobinopathy analysis in the newborn period. Please refer to the sickle cell and thalassaemia handbook for newborn laboratories for more details.

4. Preterm babies

Preterm babies or those in neonatal units:

• should have the NBS sample taken on day 5
• benefit from the coordination of the NBS with other blood tests to minimise discomfort

Be aware that preterm babies do not always show their adult haemoglobin clearly, depending on their gestational age.

5. Transfused babies

On admission to neonatal units, babies less than 5 days of age must routinely have a single circle blood spot sample taken to screen for SCD, in case the baby needs a blood transfusion. This should be on a separate blood spot card marked ‘pre-transfusion’. More information can be found in the blood spot sampling guidelines.

If, for any reason, the admission sample was not taken, babies that need a blood transfusion before day 5 must have a NBS for SCD taken before the transfusion. The remaining conditions are to be screened for on day 5 as routine, on a separate blood spot card.

If the baby has received a blood transfusion before a NBS screening sample for SCD has been taken, it is possible to perform DNA testing on post-transfusion samples. The DNA test will detect the presence of the sickle haemoglobin gene.

The test is able to differentiate between babies with:

• only the sickle gene present
• those with the sickle gene and another globin gene (the test does not identify the non-sickle haemoglobin)
• no sickle gene present

6. Follow-up of newborn DNA screening results

6.1 No sickle cell gene (mutation) detected

A negative result means the baby does not carry the sickle cell gene mutation on any chromosome. The baby does not have sickle cell disease but this does not exclude other haemoglobin variants or conditions

1. Review parental haemoglobinopathy results

2. If parents are carriers and the baby at risk of inheriting a significant condition, for example beta thalassaemia major, then a liquid blood sample must be taken at least 4 months after the last blood transfusion was given and sent to the specialist haematology laboratory linked to the clinical network.

6.2 Sickle cell gene detected

If one sickle cell gene is detected this individual is most likely to be a sickle cell carrier but a compound heterozygous condition with another haemoglobin variant or a beta thalassaemia mutation cannot be excluded.

If 2 sickle cell genes are detected it is likely the baby has inherited sickle cell disease.

1. Review parental haemoglobinopathy results.

2. Follow up via the appropriate clinical pathway for possible sickle cell disease patients for confirmation of diagnosis and counselling.

3. Babies with 2 sickle cell genes should start prophylactic antibiotics routinely while diagnosis is being confirmed.

7. Newborn screening results

7.1 Screen negative

Approximately 97% of babies will be screen negative. This means the baby does not have SCD, and none of the specified haemoglobin variants have been detected.

Parents must receive ‘not suspected’ screening results by 6 weeks. The current agreed method for communicating these results is to send a letter to parents. This letter should be saved in the baby’s personal child health record (PCHR).

7.2 Haemoglobin variant carrier

Approximately 9,000 babies every year in England are found to be a healthy carrier of one of the specified haemoglobin variants. This is a prevalence of 1 in 70 births.

The haemoglobin gene variants that NBS screening must identify are:

• Hb S
• Hb C
• Hb DPunjab (further investigations may be required to confirm this result)
• Hb E
• Hb OArab (additional investigations may be required to confirm this result)

The results will show the presence of fetal haemoglobin, Hb A and the haemoglobin variant.

Parents of babies found to be a carrier of a haemoglobin variant should receive these results by 6 weeks of age and must be given the opportunity for a face-to-face discussion with a suitably trained professional to enable the significance of the carrier status to be explained. It is important for the parents to understand that their child could pass on the gene for unusual haemoglobin to future generations when they have their own baby. Appendix 1: Haemoglobinopathy carriers has more information on haemoglobin variant carriers.

There are 2 parent information leaflets to support the information given by a healthcare professional:

Information for mums and dads: your baby carries a gene for sickle cell

Information for mums and dads: your baby carries a gene for unusual haemoglobin

Both leaflets are available in English, French, Bengali and Urdu.

It is important to remember it is not possible to identify those babies that are beta thalassaemia carriers using routine newborn screening methods.

7.3 Inconclusive results

For babies found to have a haemoglobin variant other than those stated above, the NBS result will be issued as ‘condition not suspected’. The wording will state that haemoglobin S, C, DPunjab, E, and OArab have not been detected. Further investigations may be required if a significant condition is suspected and the initial result is unclear.

8. Benign haemoglobin conditions

A number of haemoglobin conditions that are usually clinically benign may be detected by NBS screening. In such cases, the parents must be informed before the baby’s health check at 6 to 8 weeks. The baby must be referred to a named clinician for follow-up and counselling. There may be an indication to re-screen these babies. See Appendix 2: Benign haemoglobin conditions for further details of the haemoglobin conditions below:

• Hb CC and C/βthalassaemia
• Hb DD and D/βthalassaemia
• Hb CD
• Hb CE
• Hb DE
• Hb EE

9. Baby has sickle cell disease

Results from babies with SCD (sickle cell anaemia, Hb SS) show the presence of HbF and HbS, in the absence of HbA. Other sickle cell conditions show HbF and HbS with another haemoglobin variant, although this depends on the specific genotype.

Between 260 and 350 babies a year in England have a SCD result. This is a prevalence of approximately 1 per 2,500 births.

The table below shows the newborn screening result for babies with a possible SCD. Appendix 3: Sickle cell disease has details of the clinical impact of the most common of these sickle cell conditions.

Newborn screening result	Possible disease/condition
FS	Hb SS (sickle cell anaemia)
FS	Hb S/β thalassaemia (includes Hb S/β0, Hb S/δβ, Hb S/γδβ, Hb S/εγδβ and Hb S/Lepore)
FS	Hb S/HPFH
FSA or FS	Hb S/β⁺ thalassaemia
FSC	Hb SC
FSD	Hb S/DPunjab
FSE	Hb S/E
FSO	Hb S/OArab
Hb S/V	Hb S plus a variant not identified above

The early identification of affected babies allows:

• the opportunity to inform and educate the parents of the condition
• prophylactic oral antibiotics to be started
• early medical intervention to reduce morbidity and mortality
• timely entry into specialist haemoglobinopathy care

The parents of babies who have a SCD result from the NBS screening test must be informed of the result before the baby is 28 days of age. This is an auditable standard in the SCT screening programme.

The parents must be informed by an appropriately trained professional, with sensitivity to the parents’ concerns, and an understanding of the condition. Best practice is for the parents to be informed by a healthcare professional, preferably a haemoglobinopathy specialist nurse they have met in the antenatal period, along with the family’s health visitor. The family must be given the name and contact numbers of all relevant healthcare professionals who will be involved in the care of their baby. The GP should also be informed of the result.

An example of a form that can be used to support the counselling session, and as a template for a referral letter, is in Appendix 9.

The standard is for affected babies to attend a haemoglobinopathy centre (medical) by 90 days of age.

An online parent information book has detailed guidance on how to care for an affected child.

10. Beta thalassaemia

The NBS programme does not specifically screen for beta thalassaemia major, but babies with severe thalassaemia major will generally be detected. Results from a baby with beta thalassaemia major will usually have only HbF present and no HbA. It is important to remember that not all thalassaemia conditions will be detected by NBS screening.

Babies with a beta thalassaemia condition must be referred for follow-up and care to a haemoglobinopathy centre (medical) by 90 days of age.

It is important to remember it is not possible to identify babies who are beta thalassaemia carriers. Parents should be informed of this in the antenatal period if relevant.

11. Non-paternity

Healthcare professionals involved in newborn screening must be aware there is the potential for the results to identify possible non-paternity of the baby. Such cases must be handled sensitively.