Prenatal Decision Tree

Are you a patient or a provider?*
- Patient
- MFM
- OB
- Midwife
- Other health care provider
What country are you located in?*
Country
What is your age?*
- Under 20 years old
- 20-29 years old
- 30-39 years old
- 40-49 years old
- 50-59 years old
- 60-69 years old
- ≥70 years old
Email
Has the female patient been diagnosed with red blood cell antibodies or maternal alloimmunization?*
- Yes
- No
That’s great!
Please see our section on preventing alloimmunization for more information on ways to prevent alloimmunization.
Which antibody or antibodies does the patient have?
According to the medical literature, anti-D, K, c and E are the antibodies most frequently associated with fetal disease requiring therapy prior to birth¹. However, all IgG alloantibodies are capable of crossing the placenta and causing fetal anemia. If there are multiple antibodies present these can combine to make fetal anemia worse as compared to the presence of a single antibody.
Is the patient currently pregnant or has she given birth within the past 3 months?*
- Currently pregnant
- Recently postpartum
- Neither
Not currently pregnant, and not recently postpartum
Thank you for interest in our pregnancy tree. To see an outline of the entire pregnancy tree, please click here. If you are looking for information about alternatives to natural conception or ways to grow your family, please see our Alternatives to Natural Conception page. If you are looking for information on the personal risks of alloimmunization or information about hemolytic transfusion reactions and how to prevent them, click here.
Recently postpartum
Thank you for interest in our pregnancy tree. To see an outline of the entire tree, please click here. It looks like you are interested in information dealing with the postpartum period for an infant with HDFN. Our neonatal tree is coming soon. Please click here to view tests for infants with HDFN.
Thank you for interest in our pregnancy tree. To see an outline of the entire tree, please click <a href="http://allohopefoundation.org/wp-content/uploads/2021/01/AHF-Prenatal-Tree.pdf" target="_blank">here</a>. It looks like you are interested in information dealing with the postpartum period for an infant with HDFN. Our neonatal tree is coming soon. Please click <a href="/library/infant-testing/">here</a> to view tests for infants with HDFN.
Has the father's antigen phenotype been tested?*
Paternal testing is a vital part of managing an alloimmunized pregnancy. Medical literature says that the father should be tested to determine if he can pass the gene for the antigen on to the fetus ^1, ². If the father is negative, the fetus cannot inherit the antigen and the fetus is safe. If the father cannot be tested, or if his results come back as heterozygous (example: Ee for the partner of a woman with anti-E), then cell free fetal DNA testing can be run.
- Yes
- No
Paternal testing or cffDNA has not been run.
Medical literature says that an antigen phenotype should be run on the father ^1, ², and cffDNA testing from the mother^1, ³. A father who is antigen negative will lead to an antigen negative fetus who is safe from HDFN. For example: If the mother has anti-E, the father will be:
- ee - the father cannot pass on the E antigen, all children with this partner will be safe from HDFN. No further monitoring or testing is needed. The pregnancy can proceed as normal.
- Ee - each child has a 50/50 chance of inheriting the E antigen and being at risk for HDFN.
- EE - all children with this partner will inherit the E antigen and be at risk for HDFN. Pregnancies with this partner will need to be monitored closely.
In the case of a heterozygous (Ee) father, the fetal antigen status can be determined with cffDNA testing. cffDNA testing is available for the D, C, c, E, e, K, and k antigens. If cffDNA testing is not available in your country, labs in the UK and Netherlands allow you to ship blood for testing. See our page on cffDNA testing for more information about this test and how it can influence pregnancy monitoring and treatment. Other options include monitoring as if the fetus is antigen positive or performing an amniocentesis.

Due to the risks, many parents are choosing to avoid amniocentesis as a method of determining fetal antigen status. Some literature show that amnios may increase the titer levels or lead to the development of new antibodies and worsening of alloimmunization, in addition to the risks of fetal loss or infection ⁸.
Medical literature says that an antigen phenotype should be run on the father 1, 2, and cffDNA testing from the mother1, 3. A father who is antigen negative will lead to an antigen negative fetus who is safe from HDFN. For example: If the mother has anti-E, the father will be: <ul> <li>ee - the father cannot pass on the E antigen, all children with this partner will be safe from HDFN. No further monitoring or testing is needed. The pregnancy can proceed as normal. </li> <li>Ee - each child has a 50/50 chance of inheriting the E antigen and being at risk for HDFN.</li> <li>EE - all children with this partner will inherit the E antigen and be at risk for HDFN. Pregnancies with this partner will need to be monitored closely.</li> </ul> In the case of a heterozygous (Ee) father, the fetal antigen status can be determined with cffDNA testing. cffDNA testing is available for the D, C, c, E, e, K, and k antigens. If cffDNA testing is not available in your country, labs in the UK and Netherlands allow you to ship blood for testing. See our page on <a href="/library/cffdna/">cffDNA testing</a> for more information about this test and how it can influence pregnancy monitoring and treatment. Other options include monitoring as if the fetus is antigen positive or performing an amniocentesis. Due to the risks, many parents are choosing to avoid amniocentesis as a method of determining fetal antigen status. Some literature show that amnios may increase the titer levels or lead to the development of new antibodies and worsening of alloimmunization, in addition to the risks of fetal loss or infection 8.
Has the patient had a previous pregnancy or infant affected by maternal alloimmunization?*
It is important to determine if the patient has had a previous pregnancy or infant affected by maternal alloimmunization ². An affected fetus or newborn has a positive DAT (or is antigen positive), and has signs of anemia, hyperbilirubinemia, or some other consequence of HDFN. It is not required that an infant be treated (via transfusion etc) in order for them to be considered affected.
- No, the patient has not had a previous pregnancy or infant affected by maternal alloimmunization.
- Yes, the patient has had a previous pregnancy or infant affected by maternal alloimmunization.
What are the patient's titer levels?*
In a patient's first affected pregnancy, titers are considered an accurate indicator for the risk of fetal anemia ². The critical titer for all antibodies except anti-K is 16 ². The critical titer for anti-K is 4, though severe anemia has occurred at titers of 2 with anti-K. The lower critical titer for anti-K is related to its proposed dual mechanism of action to cause fetal anemia: hemolysis of red cells and suppression of the fetal bone marrow to make new red cells. Some physicians believe that there is no safe titer for anti-K, and titers should not be used to monitor a pregnancy involving anti-K (MCA Dopplers should be used instead) ².
- At or above critical levels.
- Below critical levels.
Titers are below critical.
If the titers are below critical, the risk for moderate-severe fetal anemia is very low. If the titer levels have a 4-fold increase, or reach critical levels, it is indicative of the need for MCA scans ⁴. Titers can rise at any point in the pregnancy and can rise quickly. Dr Moise recommends that titers are drawn every 4 weeks until 24 weeks, then every 2 weeks until delivery ⁵. After 35 weeks, the risks to the fetus increase substantially, even with low titers. At 32 weeks, weekly NST are given and the results can provide another indicator for when it is time for delivery ^6, ⁷. ACOG², SMFM ¹¹, RCOG ³, and Up to Date ⁶ guidelines advocate for delivery at 37-38 weeks. In general alloimmunized women (especially those who are carrying an antigen-positive fetus), are delivered no later than 38 weeks gestation.
For more information about prenatal or newborn monitoring, see our provider page or patient page. After birth, cord blood testing for hemoglobin, bilirubin, and DAT must take place. For a list of necessary newborn lab tests, see the page in our resource library about infant testing.

If the titers are below critical, the risk for moderate-severe fetal anemia is very low. If the titer levels have a 4-fold increase, or reach critical levels, it is indicative of the need for MCA scans 4. Titers can rise at any point in the pregnancy and can rise quickly. Dr Moise recommends that titers are drawn every 4 weeks until 24 weeks, then every 2 weeks until delivery 5. After 35 weeks, the risks to the fetus increase substantially, even with low titers. At 32 weeks, weekly NST are given and the results can provide another indicator for when it is time for delivery 6, 7. ACOG2, SMFM 11, RCOG 3, and Up to Date 6 guidelines advocate for delivery at 37-38 weeks. In general alloimmunized women (especially those who are carrying an antigen-positive fetus), are delivered no later than 38 weeks gestation. For more information about prenatal or newborn monitoring, see our <a href="/providers">provider page</a> or <a href="/patients">patient page</a>. After birth, cord blood testing for hemoglobin, bilirubin, and DAT must take place. For a list of necessary newborn lab tests, see the page in our resource library about <a href="/library/infant-testing/">infant testing</a>.
What is the patient's gestation?*
Monitoring and treatment options change depending on gestation.
- 13 weeks or earlier.
- 14-35 weeks
- 35 weeks or later
Gestation before 14 weeks
Determine if the patient is a candidate for starting IVIG and plasmapheresis. For patients who are at 14 weeks gestation or earlier, who have had a previous pregnancy with an IUT <24 weeks gestation, or a previous loss, or those with a titer level of 1024 or higher, IVIG with or without plasmapheresis is an option ⁵. IVIG with plasmapheresis has been used to successfully lower titers and improve fetal outcomes. IVIG and plasmapheresis are most effective when started before 14 weeks gestation. To read more about these methods, see www.allohopefoundation.org/providers. In addition to plasmapheresis and IVIG, patients have the option of enrolling in a clinical trial. You can view current trials related to alloimmunization and HDFN at www.allohopefoundation.org/trials.
Determine if the patient is a candidate for starting IVIG and plasmapheresis. For patients who are at 14 weeks gestation or earlier, who have had a previous pregnancy with an IUT <24 weeks gestation, or a previous loss, or those with a titer level of 1024 or higher, IVIG with or without plasmapheresis is an option 5. IVIG with plasmapheresis has been used to successfully lower titers and improve fetal outcomes. IVIG and plasmapheresis are most effective when started before 14 weeks gestation. To read more about these methods, see <a href="/providers/">www.allohopefoundation.org/providers.</a> In addition to plasmapheresis and IVIG, patients have the option of enrolling in a clinical trial. You can view current trials related to alloimmunization and HDFN at <a href="/trials/">www.allohopefoundation.org/trials.</a>
What was the patient’s most recent MoM score?*
For women with critical titers or who have had a previously affected pregnancy/infant, weekly MCA scans are usually initiated at 16-18 weeks ⁵. For those with very high titers or past pregnancies which were severely affected by HDFN, scans can be started as early as 14 weeks¹⁰. The MCA scan provides a Peak Systolic Velocity (PSV) number, which is then calculated into a Multiple of the Median (MoM) score. Calculators such as https://medicinafetalbarcelona.org/calc/ are readily available and easy to use.
- 1.5 or higher
- 1.40-1.49
- Below 1.4
What was the patient’s most recent MoM score?*
For women with critical titers or those who have had a previously affected pregnancy/infant, weekly MCA scans are usually initiated at 15-18 weeks ⁵. While rare, severe anemia requiring IUT has been reported as early as 15 weeks in subsequent pregnancies. MCA-PSV determinations are possible and reference values are available as early as 12 weeks gestation ⁹, however it is more common for women with very high titers or past pregnancies which were severely affected by HDFN, to begin scans as early as 14 weeks¹⁰. The MCA scan provides a Peak Systolic Velocity (PSV) number, which is then calculated into a Multiple of the Median (MoM) score. Calculators such as https://medicinafetalbarcelona.org/calc/ are readily available and easy to use.
- 1.5 or higher
- 1.40-1.49
- Below 1.4
MoM 1.5 or higher
Medical literature states that a peak systolic velocity with an MoM of 1.5 or higher indicates moderate to severe anemia ^1, ^6, ^10, ¹¹. An intrauterine transfusion (IUT) or early delivery is recommended. Clinicians should not wait for signs of hydrops to develop before scheduling or performing an IUT. Dr Kenneth Moise recommends performing a cordocentesis when the MoM reaches or exceeds 1.5 and performing an IUT if the fetal hematocrit is <30% ^5, ¹⁰. Some providers will perform a second MCA scan the day after a patient receives a 1.5 MoM to rule out a falsely elevated MoM and then proceed with the cordocentesis & IUT if still elevated. Expert opinion ⁵ holds that steroid administration has been shown to falsely lower MoM values and planned delivery or intrauterine transfusion should not be modified based on MoM values observed after administration of steroids. For more information on the effect of steroids on fetal blood flow, see our additional reading by topic page.
- IUT was scheduled without a rescan.
- 1.5 or higher
- 1.40-1.49
- Below 1.40
Repeat MoM 1.40-1.49
At this point, care is determined on an individual basis at the physician's discretion. If steroids were administered, providers may choose proceed with cordocentesis and base care off of the resulting blood values. If steroids were not administered, physicians may choose to repeat the scan again in 2-3 days.
At this point, care is determined on an individual basis at the physician's discretion. If steroids were administered, providers may choose proceed with cordocentesis and base care off of the resulting blood values. If steroids were not administered, physicians may choose to repeat the scan again in 2-3 days.
MoM 1.40-1.49
An MoM of 1.4-1.49 indicates that the baby may be becoming anemic. Fetal anemia can develop within a matter of days ⁶. An MCA-PSV at or above 1.5 MoM for gestational age (calculator available here), indicates possible severe anemia requiring intervention. Treatment with intrauterine transfusion is initiated once the MoM reaches or exceeds 1.5. As a result, when a patient has an MoM of 1.4-1.49, many providers choose to repeat the scan in 2-3 days. The exact timing of the next scan is determined at the physician's discretion.
An MoM of 1.4-1.49 indicates that the baby may be becoming anemic. Fetal anemia can develop within a matter of days 6. An MCA-PSV at or above 1.5 MoM for gestational age (calculator available here), indicates possible severe anemia requiring intervention. Treatment with intrauterine transfusion is initiated once the MoM reaches or exceeds 1.5. As a result, when a patient has an MoM of 1.4-1.49, many providers choose to repeat the scan in 2-3 days. The exact timing of the next scan is determined at the physician's discretion.
MoM below 1.4
MCA scans are repeated every 1-2 weeks until delivery ⁵.
MCA scans are repeated every 1-2 weeks until delivery 5.
Intrauterine Transfusions and Timing
The goal of an intrauterine transfusion is to maintain the fetal hematocrit above 25% . To this end, some experts will typically transfuse 10 days after the first transfusion, 2 weeks after the second transfusion, and 3 weeks after the third transfusion. You can generally expect a decline in hemoglobin of 0.4 g/dL/day after the first transfusion, 0.3 g/dL/day after the second transfusion, and 0.2 g/dL/day after the third transfusion. Information regarding the accuracy of MCA-PSV for determining the timing of additional transfusions is mixed, and providers must familiarize themselves with the various data available. For additional information regarding IUTs, please see the Up To Date article on Intrauterine Transfusion of Red Blood Cells.
The goal of an intrauterine transfusion is to maintain the fetal hematocrit above 25% . To this end, some experts will typically transfuse 10 days after the first transfusion, 2 weeks after the second transfusion, and 3 weeks after the third transfusion. You can generally expect a decline in hemoglobin of 0.4 g/dL/day after the first transfusion, 0.3 g/dL/day after the second transfusion, and 0.2 g/dL/day after the third transfusion. Information regarding the accuracy of MCA-PSV for determining the timing of additional transfusions is mixed, and providers must familiarize themselves with the various data available. For additional information regarding IUTs, please see the <a href="http://www.uptodate.com/contents/intrauterine-fetal-transfusion-of-red-blood-cells">Up To Date article on Intrauterine Transfusion of Red Blood Cells</a>.
What was the patient’s most recent MoM score?*
It is almost time for delivery. The goal is to prolong the alloimmunized pregnancy to 35 weeks of gestation. Women with critical titers are still receiving weekly MCA scans to check for fetal anemia ⁵. The MCA scan provides a Peak Systolic Velocity (PSV) number, which is then calculated into a Multiple of the Median (MoM) score. Calculators such as https://medicinafetalbarcelona.org/calc/ are readily available and easy to use. If an MoM of 1.5 or higher is found, delivery is induced. IUTs are not performed at or beyond 35 weeks gestation¹⁰. At this point, the IUT has more risk than early delivery and treatment outside of the womb. After 35 weeks, the risks to the fetus increase substantially, even with low titers.
- 1.5 or higher
- Below 1.5
Gestation 35 weeks or greater.
It is almost time for delivery. After 35 weeks, the risks to the fetus increase substantially, even with low titers. Beginning at 32 weeks, weekly NST are given in addition to MCA scans and the results can provide another indicator for when it is time for delivery^6, ⁷. ACOG^2, ¹³, SMFM ¹¹, RCOG ³, and Up to Date ⁶ guidelines advocate for delivery at 37-38 weeks even if titers are low and IUTs have not been necessary. In general alloimmunized women (especially those who are carrying an antigen-positive fetus), are delivered no later than 38 weeks gestation.

After birth, cord blood testing for hemoglobin, bilirubin, and DAT must take place. For additional information on newborn testing, see our provider page or our patients page. If you would like to use our neonatal tree after birth, it can be found here.
It is almost time for delivery. After 35 weeks, the risks to the fetus increase substantially, even with low titers. Beginning at 32 weeks, weekly NST are given in addition to MCA scans and the results can provide another indicator for when it is time for delivery6, 7. ACOG2, 13, SMFM 11, RCOG 3, and Up to Date 6 guidelines advocate for delivery at 37-38 weeks even if titers are low and IUTs have not been necessary. In general alloimmunized women (especially those who are carrying an antigen-positive fetus), are delivered no later than 38 weeks gestation. After birth, cord blood testing for hemoglobin, bilirubin, and DAT must take place. For additional information on newborn testing, see our <a href="/providers/">provider page</a> or our <a href="/patients">patients page</a>. If you would like to use our neonatal tree after birth, it can be found <a href="/neonatal-tree/">here</a>.
Gestation 35 weeks or greater with MoM 1.5 or higher
Medical literature states that if a woman has an MoM of 1.5 or higher after 35 weeks, her providers should strongly consider delivery^2, ^3, ^6, ¹¹. At this point MCA Dopplers indicate potential moderate to severe anemia and early delivery needs to be scheduled. Clinicians should not wait for signs of hydrops or distress to develop before scheduling or performing a delivery. Expert opinion holds that steroids may falsely lower the MoM score. Intervention should not be delayed due to decreased MoM values after administration of steroids. The goal is to prolong the alloimmunized pregnancy to 35 weeks of gestation. IUTs are not performed beyond 35 weeks gestation¹⁰. At this point, the IUT has more risk than early delivery and treatment outside of the womb. After 35 weeks, the risks to the fetus increase substantially, even with low titers.

After birth, cord blood testing for hemoglobin, bilirubin, and DAT must take place. For additional information on newborn testing, see our provider page or our patients page.
Medical literature states that if a woman has an MoM of 1.5 or higher after 35 weeks, her providers should strongly consider delivery2, 3, 6, 11. At this point MCA Dopplers indicate potential moderate to severe anemia and early delivery needs to be scheduled. Clinicians should not wait for signs of hydrops or distress to develop before scheduling or performing a delivery. Expert opinion holds that steroids may falsely lower the MoM score. Intervention should not be delayed due to decreased MoM values after administration of steroids. The goal is to prolong the alloimmunized pregnancy to 35 weeks of gestation. IUTs are not performed beyond 35 weeks gestation10. At this point, the IUT has more risk than early delivery and treatment outside of the womb. After 35 weeks, the risks to the fetus increase substantially, even with low titers. After birth, cord blood testing for hemoglobin, bilirubin, and DAT must take place. For additional information on newborn testing, see our <a href="/providers/">provider page</a> or our <a href="/patients">patients page</a>.
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References