Carrier screening before and during pregnancy
UK guidelines recommend considering preconception testing (or premarital testing, if appropriate) for haemoglobinopathies in individuals of childbearing age who are considered high risk due to family origin.[44]Bain BJ, Daniel Y, Henthorn J, et al. Significant haemoglobinopathies: a guideline for screening and diagnosis: a British Society for Haematology guideline. Br J Haematol. 2023 Jun;201(6):1047-65.
https://onlinelibrary.wiley.com/doi/10.1111/bjh.18794
http://www.ncbi.nlm.nih.gov/pubmed/37271570?tool=bestpractice.com
Thalassaemia screening is recommended for all women in the UK during early pregnancy (before 10 weeks’ gestation). Screening for alpha-thalassaemia aims to identify pregnancies in which both parents are alpha(0) thalassaemia carriers and the baby is at risk of alpha-thalassaemia major. If antenatal screening suggests that the mother is an alpha(0) thalassaemia carrier, testing is offered to the biological father if he is considered high risk (based on assessment of family origin). DNA testing is required to confirm alpha-thalassaemia status.[40]GOV.UK. Antenatal screening. Jul 2025 [internet publication].
https://www.gov.uk/government/publications/handbook-for-sickle-cell-and-thalassaemia-screening/antenatal-screening
The American College of Obstetricians and Gynecologists recommends universal haemoglobinopathy testing for those planning pregnancy.[39]American College of Obstetricians and Gynecologists. Hemoglobinopathies in pregnancy: practice advisory. Aug 2022 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/08/hemoglobinopathies-in-pregnancy
[42]American College of Obstetricians and Gynecologists. Committee opinion no. 690: carrier screening in the age of genomic medicine. Mar 2017 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-in-the-age-of-genomic-medicine
Haemoglobin electrophoresis or molecular genetic testing should be performed when planning pregnancy, or at the initial antenatal visit if there are no previous test results available.[39]American College of Obstetricians and Gynecologists. Hemoglobinopathies in pregnancy: practice advisory. Aug 2022 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/08/hemoglobinopathies-in-pregnancy
If a woman is found to be a carrier, her reproductive partner should be offered screening.[42]American College of Obstetricians and Gynecologists. Committee opinion no. 690: carrier screening in the age of genomic medicine. Mar 2017 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-in-the-age-of-genomic-medicine
Information and counselling should be offered alongside screening.[42]American College of Obstetricians and Gynecologists. Committee opinion no. 690: carrier screening in the age of genomic medicine. Mar 2017 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-in-the-age-of-genomic-medicine
[43]American College of Obstetricians and Gynecologists. Committee opinion no. 691: carrier screening for genetic conditions. Mar 2017 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-for-genetic-conditions
Thorough genetic counselling, including a discussion of reproductive options (including pre-implantation genetic testing or prenatal diagnosis) should be offered to all individuals who test positive during screening.[45]GOV.UK. Counselling and referral for prenatal diagnosis (PND). Jul 2025 [internet publication].
https://www.gov.uk/government/publications/handbook-for-sickle-cell-and-thalassaemia-screening/prenatal-diagnosis-guidelines
[39]American College of Obstetricians and Gynecologists. Hemoglobinopathies in pregnancy: practice advisory. Aug 2022 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/08/hemoglobinopathies-in-pregnancy
Antenatal diagnosis
Pre-implantation genetic testing to prevent a pregnancy with alpha-thalassaemia major is an option for prospective parents considering in vitro fertilisation.[37]MacKenzie TC, Amid A, Angastiniotis M, et al. Consensus statement for the perinatal management of patients with alpha thalassemia major. Blood Adv. 2021 Dec 28;5(24):5636-9.
https://ashpublications.org/bloodadvances/article/5/24/5636/477884/Consensus-statement-for-the-perinatal-management
http://www.ncbi.nlm.nih.gov/pubmed/34749399?tool=bestpractice.com
[45]GOV.UK. Counselling and referral for prenatal diagnosis (PND). Jul 2025 [internet publication].
https://www.gov.uk/government/publications/handbook-for-sickle-cell-and-thalassaemia-screening/prenatal-diagnosis-guidelines
Available tests for patients with an at-risk pregnancy 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).[36]ACOG Committee on Obstetrics. ACOG practice bulletin no. 78: hemoglobinopathies in pregnancy. Obstet Gynecol. 2007 Jan;109(1):229-37.
http://www.ncbi.nlm.nih.gov/pubmed/17197616?tool=bestpractice.com
[37]MacKenzie TC, Amid A, Angastiniotis M, et al. Consensus statement for the perinatal management of patients with alpha thalassemia major. Blood Adv. 2021 Dec 28;5(24):5636-9.
https://ashpublications.org/bloodadvances/article/5/24/5636/477884/Consensus-statement-for-the-perinatal-management
http://www.ncbi.nlm.nih.gov/pubmed/34749399?tool=bestpractice.com
[45]GOV.UK. Counselling and referral for prenatal diagnosis (PND). Jul 2025 [internet publication].
https://www.gov.uk/government/publications/handbook-for-sickle-cell-and-thalassaemia-screening/prenatal-diagnosis-guidelines
These are invasive tests and carry a risk of fetal loss.
Ultrasound is an important non-invasive means of detecting alpha-thalassaemia major in at-risk pregnancies and may reduce the need for invasive testing.[60]Li X, Zhou Q, Zhang M, et al. Sonographic markers of fetal alpha-thalassemia major. J Ultrasound Med. 2015 Feb;34(2):197-206.
http://www.ncbi.nlm.nih.gov/pubmed/25614392?tool=bestpractice.com
[61]Norton ME, Chauhan SP, Dashe JS; Society for Maternal-Fetal Medicine. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol. 2015 Feb;212(2):127-39.
https://www.ajog.org/article/S0002-9378(14)02443-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25557883?tool=bestpractice.com
[62]Harn-A-Morn P, Wanapirak C, Sirichotiyakul S, et al. Effectiveness of ultrasound algorithm in prenatal diagnosis of hemoglobin Bart's disease among pregnancies at risk. Int J Gynaecol Obstet. 2022 Nov;159(2):451-6.
http://www.ncbi.nlm.nih.gov/pubmed/35152406?tool=bestpractice.com
It is usually performed relatively late in pregnancy.
Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal circulation is emerging as a antenatal screening test for haemoglobinopathies such as thalassaemia and sickle cell disease.[39]American College of Obstetricians and Gynecologists. Hemoglobinopathies in pregnancy: practice advisory. Aug 2022 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/08/hemoglobinopathies-in-pregnancy
[63]Hudecova I, Chiu RW. Non-invasive prenatal diagnosis of thalassemias using maternal plasma cell free DNA. Best Pract Res Clin Obstet Gynaecol. 2017 Feb;39:63-73.
http://www.ncbi.nlm.nih.gov/pubmed/27887921?tool=bestpractice.com
[64]Yang X, Ye Y, Fan D, et al. Non‑invasive prenatal diagnosis of thalassemia through multiplex PCR, target capture and next‑generation sequencing. Mol Med Rep. 2020 Aug;22(2):1547-57.
https://www.spandidos-publications.com/10.3892/mmr.2020.11234
http://www.ncbi.nlm.nih.gov/pubmed/32627040?tool=bestpractice.com
NIPT may be considered as a screening test to detect alpha-thalassaemia major, used in combination with established methods for fetal diagnosis.[16]Thalassaemia International Federation. Guidelines for the management of alpha-thalassaemia (2023). 2023 [internet publication].
https://thalassaemia.org.cy/publications/tif-publications/guidelines-for-the-management-of-%ce%b1-thalassaemia
Newborn screening
Alpha-thalassaemia is not included in the United States Recommended Uniform Screening Panel for state newborn screening programmes. However, current screening methodologies used to detect sickle cell disease (reported by all states) also detect alpha-thalassaemia.[35]Bender MA, Yusuf C, Davis T, et al. Newborn screening practices and alpha-thalassemia detection - United States, 2016. MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1269-72.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6936a7.htm
http://www.ncbi.nlm.nih.gov/pubmed/32915167?tool=bestpractice.com
Asymptomatic patient with microcytosis
Screening can be performed in an asymptomatic patient with mild anaemia and microcytosis to establish a diagnosis and thus avoid unnecessary and perhaps even harmful iron supplementation.