About HDFN

What is HDFN?

HDFN is a rare pregnancy condition which occurs when a mother’s red blood cells are incompatible with the red blood cells of their growing baby (foetus).
- In such cases, the mother’s immune system sees the baby’s red blood cells as a threat and produces alloantibodies (a type of maternal antibody) to attack them.
- These alloantibodies pass through the placenta and attack the growing baby’s own red blood cells, causing haemolysis (or red blood cell destruction).
Globally, HDFN affects 276 of 100,000 live births and can become more severe with each consecutive pregnancy.
Most mothers find out they have these alloantibodies during their first trimester of pregnancy during routine blood tests.
HDFN can cause the baby to become anaemic, which means they do not have enough red blood cells to carry oxygen to the body’s tissues. If it is not treated properly, severe anaemia can result in complications that pose a risk to the baby’s life.

If you receive a diagnosis of HDFN, there are ways to access support and manage the condition with a specialist healthcare team. Timely diagnosis is the best way to improve outcomes for yourself and your developing baby. With proper care, over 95% of newborns with HDFN recover and continue normal long-term development.⁸

What causes HDFN?

HDFN actually refers to the condition that affects babies carried by a mother who is living with a separate condition called maternal alloimmunisation.
Alloimmunisation happens when a person’s body has been exposed to a blood type that carries different markers (called antigens) from its own. This exposure can occur when blood from the mother and baby are mixed during a previous or current pregnancy, or during a previous blood transfusion or an organ transplant. In some cases, the cause is unknown. In such cases, diagnosis often comes as a surprise as the antibodies may not have been present or detected during someone’s first pregnancy.
This mismatch causes the immune system to create alloantibodies specifically designed to attack the blood type of the baby.
If pregnancy is the cause of maternal alloimmunisation, it is most often because the baby has inherited paternal antigens that are different to those of the mother. When these incompatible antigens interact, it can trigger the mother’s immune system to create alloantibodies.
Typically, in a first pregnancy the baby is born before the maternal alloantibodies are fully developed, which does not lead to HDFN.⁹ However, they stay in the body for life and increase in during pregnancies, raising the risk of HDFN. If you know you have alloantibodies, it is very important that you always inform your specialist healthcare team about them if you become pregnant again.

Managing HDFN

Screening is key:
Early in pregnancy, it is important to get routine blood tests to check for incompatible blood types and determine antibody status, both of which could indicate a risk of HDFN.¹⁰ The ABO and Rhesus (Rh) blood type incompatibilities are the most well-known causes of HDFN, but others exist.¹⁰ These tests help identify any risks to the baby and indicate whether you will need specialist care.¹⁰
Monitoring:
- If blood type incompatibility is suspected, additional tests can be done on both parents’ blood to help determine how serious the incompatibility is.¹⁰ This helps doctors understand the type and severity of the incompatibility, allowing them to plan the best care for both the mother and the baby.¹⁰
- If it is confirmed that the mother is making antibodies against the baby's red blood cells, a regular antibody test will be done to check how many antibodies are in the mother’s blood.¹⁰ This then helps doctors understand the level of risk to the baby.
Early intervention and proper treatment:
If foetal anaemia is detected, a maternal foetal specialist can help decide on which early interventions can be taken to prevent complications from developing.¹¹ Babies that are treated for HDFN and do not develop complications typically have a good prognosis⁹¹⁰ Close monitoring and early intervention significantly improve the chances of a healthy pregnancy and baby.
Education and advice:
Knowledge is power when it comes to HDFN, and patient advocacy groups can provide valuable resources and information about the condition. This paired with receiving informed advice from a specialist care team can make a difference for those impacted by HDFN.

Future pregnancies

Proper diagnosis helps doctors manage future pregnancies more effectively.⁹ If alloantibodies were detected during the first pregnancy, they could be produced immediately the next time that person becomes pregnant, depending on incompatibility with the next baby’s blood, posing a high risk of HDFN.¹⁰

What is the impact of HDFN for parents and their babies?

In mild cases, during the newborn period symptoms may resolve themselves without treatment.¹² Babies showing mild signs of anaemia or jaundice are usually monitored through bloodwork after birth to ensure they stay healthy.¹² 
In severe cases, foetal anaemia caused by alloimmunisation can lead to complications for the developing foetus, like hydrops fetalis.¹³ This is where excessive fluid builds up in the baby’s soft tissues and body, leading to heart complications and potentially loss of the baby during pregnancy or shortly after birth.¹³
Blood tests at birth can also reveal if a baby has a condition called neonatal jaundice – a common condition in newborns caused by the build-up of bilirubin, a yellow substance produced when red blood cells breakdown. While severe jaundice can affect brain development, this is rare with the right treatment and care.
When a pregnancy is affected by HDFN, it can be very mentally and emotionally challenging for the mother and their loved ones, outside of the physical toll.¹⁴ The impact of an HDFN pregnancy can affect future family planning, leaving patients hesitant to deal with the risks again. It is important for families dealing with HDFN to seek emotional support and a medical professional’s advice to help navigate these challenges during and after pregnancy.

Useful Resources and Support

Navigating a pregnancy affected by HDFN can be overwhelming, but there are ways to access help and support. From understanding more about the condition, to finding emotional support from people who have gone through it themselves, these useful resources can guide you through every step of your journey.

Explore the options below to find the support that fits your needs.

EFCNI: HDFN is Rare – Be Aware – Ask for specialist care

The European Foundation for the Care of Newborn Infants (EFCNI) is the first pan-European organisation that works to improve the health of premature and newborn babies, and supports families across Europe. Their website offers helpful resources on pregnancy, including information on HDFN and guidance on ensuring proper care.

The HDFN is Rare – Be Aware campaign details key information about HDFN to raise awareness about the condition. It provides essential information for parents and healthcare professionals, emphasising the importance of seeking specialist care on your treatment journey.

Allo Hope Foundation

The Allo Hope Foundation offers a range of comprehensive resources on HDFN, including detailed medical information, treatment options and support for families.

As a source for understanding and managing alloimmune diseases driven by alloantibodies like HDFN, it can empower patients and caregivers with the knowledge they need.

References

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Lee KY et al. Genet Med. 2015; 17(4):245–252.

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Lam B.L et al. Orphanet J Rare Dis. 2021; 16,514.

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Zanolli M et al. Ophthalmic Genet. 2020; 41(1):36.

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Stephenson K A J et al. Int J Mol Sci. 2022; 23(2):995.

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Haer-Wigman L et al. Eur J Hum Genet. 2017; 25(5):591–599.

[7]

ClinicalTrials.gov. Inherited Retinal Diseases. Available at: https://clinicaltrials.gov/search?cond=Inherited%20Retinal%20Diseases&lat=54.5259614&lng=15.2551187&locStr=Europe&distance=500&page=1. Last accessed: February 2024.