ABO Incompatibility

Many babies become 'jaundiced' after birth, primarily, as the result of ABO incompatibility. The reader below had a baby who developed severe complications with the same - fortunately a rare event - but gives us reason to discuss this condition as it is now the most common cause of hemolytic disease of the newborn (HDN)....

• At Tue Sep 30, 09:21:00 PM 2008, Zoe said…

Dear Dr,

Blood tests taken at the time of the birth of my first baby showed an ABO incompatibility - our pediatrician informed us that my body had released antibodies that had attacked our baby's immune system. As a result he had jaundice for almost 12 weeks and many many tests. I am O+ and my son is A+.

I am currently pregnant with our second child and am concerned after reading articles that state the severity of the condition is greater with subsequent pregnancies, and can result in serious conditions or even fetal death.
Should we be concerned? Are there tests that can be done during the pregnancy to determine if the baby is at risk?
Many many thanks for your help.

• At Wed Oct 08, 10:37:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Zoe:

All people who have O blood types make antibodies against both the A and the B blood group antigens. These antibodies develop very early in life, usually during the first year after birth, probably as the results of similar antigens carried on certain foods and bacteria that normally colonize the gut. Usually these antibodies are of the class of IgM antibodies that are too large to cross the placenta, so that even if you have a baby with A or B blood, the antibodies won't be able to get on the baby's side of the placenta and cause destruction of the baby's red blood cells. You are someone who has antibodies against these blood groups of the IgG class. IgG antibodies readily cross the placenta to the baby, are actively concentrated from your blood to the baby’s side and, indeed, are a major source of protection against many of the things in the environment that could hurt the baby during the first 3-6 months of life before its own immune system has matured.

Unfortunately, the placenta cannot differentiate which IgG antibodies are there to protect the baby and which might hurt, as is also the case in Rh-disease. Your IgG anti-A antibodies can cross the placenta, attach to the baby’s red blood cells, and then mediate destruction of the baby's red blood cells by the baby's own immune system. Not only can that cause fetal anemia (more common in Rh-isoimmunization than with ABO incompatibility) but it can also release large quantities of hemoglobin from the baby’s blood cells. One of the breakdown products of hemoglobin is bilirubin. Bilirubin is metabolized by the liver, but the fetal liver is not efficient at that until after the baby is born. Indeed, high levels of bilirubin can accumulate in the baby before or, more commonly, after birth and if these are not quickly reduced by phototherapy, exchange transfusion, and simple maturation of the liver’s metabolic pathways, this can accumulate in the baby’s brain and cause brain damage (kernicterus).

ABO incompatibility occurs in approximately 15% of all pregnancies. Indeed, since we implemented prophylactic therapy for Rh-disease, ABO incompatibility has become the major cause of hemolytic disease of the newborn (HDN). Fortunately, less than 5% of ABO incompatibility pregnancies result in babies that develop HDN (less than 1% of all pregnancies) and usually the primary manifestation is hyperbilirubinemia rather than anemia. ABO incompatibity can occur in first pregnancies but severity is not necessarily worse in subsequent pregnancies (unlike the situation with Rh-isoimmunization). Black babies are more likely to have severe complications than Caucasians.

The hyperbilirubinemia can often be recognized by a yellow-orange appearance of the baby’s skin and eyes (jaundice). Usually simple phototherapy (bili lights) during the first few days after delivery is sufficient to manage increased bilirubin levels until the baby’s liver adjusts to life outside the womb. Some babies can have a more severe and prolonged course because of the concentration of the antibodies throughout their bodies. However, exchange transfusion is necessary in only about 0.1% of HMD pregnancies related to ABO incompatibility.

If you have another baby with an A blood type, this could happen again, but the recurrence rate is much lower and the outcome much less predictable with ABO incompatibity than with Rh-isoimmunization. You did not tell me whether your baby’s complications were from severe anemia or from hyperbilirubinemia (or both). However, tests that you could consider having done before and during another pregnancy are the following:

1) Check your husband’s blood type to see if he has one (heterozygote) or two (homozygote) doses of the A gene. If he has two, then all your babies with him MUST end up having the A blood type. If he has only one, then half your babies could have O blood types just like you and not be affected by the antibodies at all

2) If your husband is homozygous, then there would be no sense in testing another baby to find out what its blood type is during the pregnancy since it would have to have an A blood type and would therefore be ‘at risk’. But, if he is heterozygous, that testing could be done (by amniocentesis or direct testing of the baby’s blood by percutaneous umbilical cord blood sampling – PUBS) and if the baby has O blood, then you could rest assured and relax the rest of the pregnancy

3) If fetal anemia is a concern, the degree of fetal anemia caused by the antibodies can be monitored by a noninvasive ultrasound procedure called Doppler flow velocimetry (DFV). Using DFV we can measure the velocity of blood (peak systolic velocity – PSV) in a vessel called the middle cerebral artery in the baby's brain. If that blood flow velocity is higher than expected at a given gestational age, this might indicate the baby is developing severe anemia. PUBS could then be done, the degree of anemia determined precisely (as well as the bilirubin levels), and the baby could be transfused with O blood directly by injection in the umbilical vein

4) For your next pregnancy, if you choose to have one, you should get a consultation with a specialist in Maternal-Fetal Medicine. In fact, you might even want to do that BEFORE you think seriously about getting pregnant again.

Hope this helps. Best wishes! Dr T

Labels: ABO incompatibility, Rh-isoimmunization

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Assessing Fetal Lung Maturity - 2

The fetal lungs are the last organ system to “mature” so that survival outside the womb is possible. Maturity involves several components. First, there must be sufficient surface area within the lung to allow sufficient exchange of gases (oxygen in and carbon dioxide out) to support metabolic functions. This is accomplished by millions of small sacs called alveoli that give the lungs a sponge-like appearance. Second, the alveoli must develop to the point that the inner lining of cells (epithelial cells) that come in contact with inspired air are very thin – gas exchange can only occur over a short distance between the blood vessels in the alveoli and the air that fills the alveoli. Third, the alveoli must be able to remain open so that the air can get into them and gas exchange can take place. The first two events are generally quite complete by about 32-34 weeks, however, the third is the most essential component from that point on and it is the focus of our fetal lung maturity testing as we shall explain.

Alveoli are like little bubbles. The laws of physics predict that because of the high ratio of surface tension to volume of little bubbles, their tendency is to collapse. To prevent this from happening, certain cells in the lungs – the type II alveolar cells – begin to excrete chemicals that can reduce the surface tension in the alveoli. These chemicals are called ‘surfactants’ and they are a complex combination of phospholipids and apoproteins. When sufficient surfactants are produced that the alveoli can remain open to function, the fetal lungs are considered ‘mature’. Prior to this time, the baby is at risk for developing respiratory distress syndrome (RDS). RDS occurs in about 1% of all pregnancies and it can have serious short- and long-term consequences, involving both the lungs and other organs, that can extend beyond the neonatal period in its most severe forms.

When babies are very premature, RDS is the result of a combination of both alveolar epithelial cell immaturity (the lining cells have not yet thinned out) and a deficiency of surfactants. Later in pregnancy (“near term”), severe RDS can sometimes also occur but at this point it is usually the result of insufficient surfactants alone – but the end result can be just as devastating. Certain medical conditions can delay surfactant production in babies, the most common being maternal diabetes with poor blood sugar control and isoimmunization (such as Rh-disease). Large babies (macrosomic) are also at greater risk for RDS even if maternal diabetes is not contributing to the fetal size. Babies who have developed heart failure (hydrops fetalis) for any number of reasons can also have a relative deficiency of surfactants (as well as pulmonary edema). For reasons that are not entirely clear, babies delivered by cesarean section, particularly, when this is done prior to the onset of labor, are also at increased risk for respiratory difficulties.

The amniotic fluid is mostly fetal urine, but it is mixed with effluent from the fetal lungs as well. The fluid from the fetal lungs contains surfactants and other indicators of type II alveolar cell activity. When we perform an amniocentesis to assess fetal lung maturity, we are looking for direct and/or indirect evidence to support the presumption that there is adequate surfactant present to minimize the risk for RDS. One should realize that all of the tests we will discuss have some degree of “false positivity” – an indicator suggesting lung maturity, but the baby still develops respiratory problems – however, there is enough experience with their use that a “mature” value with a test result generally means the baby has at least a 95% chance of not developing RDS.

Having provided this information as background, the actual tests commonly used to evaluate fetal lung maturity will be discussed in our next post….

Labels: amniocentesis, diabetes, fetal lung maturity, fetal macrosomia, Rh-isoimmunization, surfactants

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Amniotic Fluid - 7 - Complications Related to Polyhydramnios

When excessive amniotic fluid (polyhydramnios or, simply, hydramnios) is present, there are increased risks of complications for both mother and baby. Some of the risks to the baby are obvious if there is an identifiable etiology for the hydramnios, such as maternal diabetes, multiple gestation, congenital malformation, chromosomal abnormality, severe fetal anemia secondary to isoimmunization or Parvovirus B19, neuromuscular disorders, or congenital infection. Indeed, past reviews confirm the risk for poor outcomes when an etiology is found. For example, Stoll and colleagues (Community Genet 1999;2:36-42) identified 290 cases of polyhydramnios in 225,669 consecutive pregnancies and diagnosed congenital malformations prenatally in 44.5% of the cases. Among these, 10.3% of the infants were stillborn, 41% had more than one malformation, 14.5% had a chromosomal abnormality.

Similarly, Biggio and colleagues (Obstet Gynecol 1999;94:773-7) compared 370 women with singleton pregnancies beyond 20 weeks' gestation and hydramnios with 36,426 controls who had normal amniotic fluid volumes. “The perinatal mortality rate in all women with hydramnios was 49 per 1000 births, compared with 14 per 1000 births in the control group (P < .001). Women with hydramnios had 25 times more anomalies than controls (8.4% versus 0.3%; P < .001)…the cesarean rate was three times higher in women with hydramnios compared with controls (47.0% versus 16.4%; P < .001).” Interestingly, in their study, the increased risks were concentrated in the nondiabetic women with hydramnios.

However, as we mentioned previously, 50-60% of hydramnios is idiopathic (without an identifiable cause). So the question remains, are there increased risks to the baby if no identifiable etiology for the hydramnios is found? In other words, does the excessive fluid alone seem to contribute to or be associated with poor perinatal outcome. The scientific literature would indicate that it does. For example, Magann and colleagues (Obstet Gynecol Surv 2007;62:795-802) recently presented an extensive review dating back more than 50 years and found that idiopathic hydramnios was linked “to fetal macrosomia (in the absence of diagnosed maternal diabetes), an increase in the risk of adverse pregnancy outcomes, and a 2- to 5-fold increase in the risk of perinatal mortality.” So, what are some of the pregnancy risks, irrespective of the cause of the excessive amniotic fluid.

Common risks secondary to overdistention of the uterus include abdominal pain, premature labor and delivery, and premature rupture of membranes. There is also an increased risk of uterine rupture, although this is rare in the absence of a previous cesarean delivery or other operative uterine procedure. In the presence of severe hydramnios, especially in a woman of small stature, overdistention of the uterus can put so much pressure on the mother’s diaphragm that she has difficulty breathing in ANY position and maternal cardiorespiratory decompensation may occur under these circumstances.

Often under these circumstances, placental perfusion is also reduced, the baby develops relative placental insufficiency, and as a consequence of the baby’s (and probably the placenta’s) unhappiness, the mother develops preeclampsia. Doppler flow studies have shown a greater incidence of fetal blood flow ‘redistribution’ (an indirect indicator of ‘placental insufficiency’) in the presence of hydramnios and this is most likely due to the excessive pressure on the umbilical vessels and the placenta itself resulting in decreased fetal perfusion. Indeed, any fetal condition associated with hydramnios that places the baby in a ‘distressed’ situation, particularly, severe fetal anemia and other causes of hydrops fetalis, increases the risk for maternal preeclampsia.

Indeed, the very first obstetrical patient I ever saw die (30 years ago) had a baby with hydrops secondary to severe maternal Rh-isoimmunization and polyhydramnios. An attempt was made to transfuse the baby in utero and afterwards she was sent to the antepartum unit for monitoring. I noticed her blood pressure was elevated and checked her urine to also find 4+ proteinuria. I remember notifying her attending physician ( I was a second year resident at the time) that she appeared to be developing severe preeclampsia and was brushed off that this was simply the ‘stress of the procedure that she had just been through.’ When I came in to round on her the next morning, she was not in her bed and when I asked if she had been discharged, I was told that she had had a hypertensive crisis in the middle of the night, a cerebrovascular accident, and could not be resuscitated. The occurrence of severe maternal preeclampsia in the presence of fetal hydrops has come to be known as “mirror syndrome” in which the mother’s condition reflects (and is probably driven by) the dire fetal condition (Vidaeff, et al. J Reprod Med 2002;47:770-4). Needless to say, there are some things one NEVER forgets!

Hydramnios can also cause several complications related to the onset and course of labor. Too much fluid often leads to lack of ‘engagement’ of the fetal head in the pelvis and/or an unstable fetal lie (breech or transverse). This can be a special problem when the membranes rupture (spontaneously or artificially) because if there is no ‘presenting part’ obstructing the cervix, the umbilical cord can suddenly prolapse with the gush of fluid through the cervix into the vagina turning a relatively uncomplicated situation into an emergency. Acute release of the fluid and decompression of the uterus can also cause sudden separation of the placenta (placental abruption) from the uterine wall. Stretching of the uterine muscle (myometrium) can also result in abnormal labor patterns secondary to poor contractility (myometrial dysfunction) and at times can result in poor contraction (involution) of the uterus following delivery, a situation that is usually accompanied by post-partum hemorrhage. All of these complications contribute to the increased rate of cesarean deliveries in pregnancies with hydramnios and the increased rate of maternal and fetal complications.

One other complication which occurs frequently (and is often not thought about) in the presence of hydramnios, particularly if this is associated with diabetes or simply, with fetal macrosomia, is immaturity of fetal lung development. As we have pointed out in earlier posts, late preterm (near-term) elective delivery of a baby just because it is “too big” can have tragic consequences. It is not unusual for macrosomic babies to have a 2-3 week lag in the functional ability of their lungs at birth because excessive insulin production (hyperinsulinemia) that often accompanies macrosomia can delay the production of the lung surfactants that reduce surface tension in the alveoli and are necessary for expansion of these so that oxygen exchange can occur normally. There is nothing sadder than seeing a 10 lb baby of a diabetic mother laying in the neonatal intensive care unit struggling to survive with severe respiratory distress syndrome and persistent fetal circulation as a consequence of an elective (often cesarean) delivery.

Having discussed some of the more common complications of polyhydramnios, in our next (and final!?!) post on the topic of amniotic fluid, we will address the evaluation and management of the pregnancy with too much amniotic fluid…

Labels: diabetes, hydramnios, polyhydramnios, Rh-isoimmunization

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Readers' Questions About Rh-negative Blood Types and Complications

Hello again. I apologize to all of you for my recent 'down-time' but the Chairman of our department decided to retire on very short notice and I have been put in the position of 'interim Chair' until we can get someone to replace him. I sincerely hope that will not be a long process. Been there, done that, don't want to do it again! Over the past week or so, I have accumulated MANY questions/comments from readers and my responses to several may be used as posts over the next few days to play catch up! Hope you don't mind. The three comments below pertain to Rh-negative status and complications related to Rh-sensitization. This seems to be an area of ongoing confusion among many of you, and for those of you who understand it completely already, I apologize again!

Anonymous Mon Jan 07, 07:47:00 PM 2008 said…

I am 33 years old and my husband and I are actively trying to conceive. Both my husband and I have been cleared of any complications by our fertility doctor. My concern is that I am B-negative and I was recently informed that in the event of a pregnancy, that I would need to get an antibody (Rh-immune globulin) given to me. This does not concern me, but what does is that when I was 15, I had an abortion at 16 weeks and was not given the antibody and I do not know if the father was Rh-negative or -positiive. Neither do I know if the baby was Rh-negative or -positive. I am now worried that my future pregnancies could be affected. How do I find out if I am sensitized?

Kenneth F. Trofatter, Jr., MD, PhD said...

To anonymous Jan 7: To find out if you were 'sensitized' to Rh-D or any other blood antigen, simply ask your doctor to perform a blood type and antibody screen. If the antibody screen is negative at this time you are probably in good shape, but you will be rescreened early in a pregnancy as part of the routine new OB labs. Odds are you are just fine. Incidentally, the Rh-immune globulin you will receive in pregnancy will help protect you from becoming sensitized in the event the baby is Rh-positive. Good luck to you and thanks for reading. Dr T
Fri Jan 11, 05:33:00 PM 2008


Ditchdoc Tue Jan 08, 01:44:00 AM 2008 said…

I have A+ blood and my husband has B+ blood but our 9 year old daughter has AB-. How is this? My grandfather was B-. Could the negative allele have come from him by succession?

Kenneth F. Trofatter, Jr., MD, PhD said...

To ditchdoc26 Jan 8: If your husband is indeed the baby's father, that simply means that both of you are heterozygous for the D allele - in other words, you each have one D gene and one gene without D and are then D/-. This happened because you each inherited one chromosome from each of your parents. On one chromosome you inherited the Rh-D gene and on the other you did not. That means when you have children, 1/4 will be D/D (Rh-positive; homozygous), 2/4 will be D/-; also Rh-positive but heterozygous like you and your husband - remember the D gene is expressed dominantly, two doses are not required to be Rh-positive), and 1/4 will be -/- (Rh-negative; you must have BOTH negatives to be Rh-negative). Hope that helps. Thanks for reading! Dr T
Fri Jan 11, 05:40:00 PM 2008


Amy & Damon Thu Jan 10, 06:55:00 PM 2008 said...

I am a 26 year old and I developed antibodies in my first pregnancy. The baby had to be induced but was full term. She had phototherapy for 5 days before being discharged.

My second child was monitored using the Doppler flow every 2 weeks. Then had his first fetal transfusion at 23 weeks and had to have one every 3 weeks. He was induced at 36 weeks weighing 3.35kg so in total he had 4 fetal transfusions. After he was born he had phototherapy for 5 days. Then needed another transfusion, at 2 weeks of age. Now he is 7 and a half months old and very healthy, normal and happy boy.

Now I am pregnant with my 3rd child (not planned but we are both happy) and scared what's going to happen? As I understand with each pregnancy it gets worse! I do have an appointment with a specialist in Maternal-Fetal Medicine in a few days but would love to know your opinion.

Yours sincerely
Amy

P.S I have no complaints about the Doppler method. Their was a very close call at 23 weeks as the doctors didn’t think the levels would rise so fast, but it all worked out I am just very greatful, we have such great technology and doctors!
I am very sad to hear about your baby passing away. It’s heart breaking and my biggest fear.

Kenneth F. Trofatter, Jr., MD, PhD said...

To Amy and Damon: Thank you for sharing your story. I am sure many readers will appreciate what you have been through because of your Rh-sensitization. Actually (hopefully!), it usually doesn't get much worse than it did the last time. The MFM doctor will probably recommend at the least starting the Doppler studies (peak systolic velocities in the middle cerebral artery) even earlier and they may recommend serial cord blood sampling, prepared to move directly to transfusion each time, because outcomes are a little less predictable in women who are sensitized and have had severely affected babies previously. As you know by now, there are risks each time that you have the cord blood sampling and a transfusion done, but in your case, all of that will probably be necessary again. Good luck to you and please let us know how things turn out. Regards. Dr T
Fri Jan 11, 05:44:00 PM 2008

Labels: rh-immune globulin, Rh-isoimmunization, Rh-negative blood type

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Readers' Questions Regarding Rh-immune Globulin

Like GBS (see our last post), another common source of questions and confusion in uncomplicated pregnancies is the significance of being an Rh-negative woman. It is another one of those things we screen for routinely, and when found, add to our 'problem lists', but rarely get around to explaining well enough to our patients that they understand why they are being given a 'shot' at 28 weeks and after delivery (and sometimes more often than that). In previous posts we have provided some explanations for all of the above, but questions still arise on a regular basis. Below are two recent comments from readers that include questions many pregnant women may have, but may be afraid to ask their providers, related to the use of Rh-immune globulin to prevent sensitization in pregnancies at risk because a baby may be Rh-positive. Again, to the readers who left the comments, I apologize for editing their posts to the best of my understanding so that others may appreciate their concerns...

• At Tue Dec 04, 01:43:00 PM 2007, Teri said…

I was 2 months along when I found out that I was pregnant. I went to the emergency room after my body rejected my baby (spontaneous miscarriage). They informed that I have Rh-negative blood. They gave me a shot that sounded like 'rogain' and told me it would prevent antibodies from attacking my baby in my next prgnancy. Is that what the shot is for? Will it affect me if my future baby's father is Rh-negative also?

• At Fri Dec 14, 12:50:00 PM 2007, Kenneth F. Trofatter, Jr., MD, PhD said…

To Teri Dec 4: Sorry about your miscarriage. You received Rhogam which is Rh-immune globulin that contains antibodies to Rh-positive blood cells. That helps your body destroy any Rh-positive red blood cells that might have gotten into your blood stream from the pregnancy and helps prevent you from developing antibodies of your own (just as the doctors told you in the ER). If the baby's father is Rh-negative too, then the baby could not be Rh-positive and you did not need the Rhogam, but it will not hurt that you got it either, now or with future pregnancies. In your next pregnancy, tell your doctor that you would like to have the baby's father's blood type tested as well. If he is indeed Rh-negative, then you won't need any 'Rhogam shots' during or after the pregnancy. Just be sure you "know who the Daddy is!" Thanks for your question!
Dr T


• At Thu Dec 06, 05:49:00 PM 2007, HAYAT said…
Hi. I'm 31 weeks pregnant. Today I had the Rhogam shot because I am O-negative. I didn't know what it is. I did search on the net and found out that I should have had it at 28 weeks? I am so worried. Is it too late for this shot? My doctor did take my blood before giving me the shot to perform an antibody screen? She gave me the shot after taking my blood. Does that mean I didn't develop the antibodies against the Rh-D antigen? I'm so confused and so sad. Can you please explain to me and tell me if my baby is at risk? And why didn't they give me the shot at 28 weeks. I'm sorry for my english if I made mistakes.
My name is HAYAT
THANK YOU

• At Fri Dec 14, 12:55:00 PM 2007, Kenneth F. Trofatter, Jr., MD, PhD said…

To Hayat Dec 6: See my explanation above to our first reader. The 'shot' is Rh-immune globulin that contains antibodies against Rh(D)-positive red blood cells. That way, if the baby is Rh-positive and any of its red blood cells get into your circulation, the antibodies will help to destroy those cells before you have a chance to make your own antibodies to them. If you do develop your own antibodies, that is called alloimmunization (or isoimmunization). We frequently refer to that as 'sensitization' as well.

If you had not developed any antibodies before you got the shot, then you can stop worrying. The shot will help protect you from becoming sensitized during the rest of your pregnancy. We generally recommend giving the shot at 28 weeks because very few women will become sensitized before that time and the Rh-antibodies usually hang around until about 40 weeks (full term). The shot does not have to be given right at 28 weeks! Some folks give it a little earlier, and some a little later. Women who have trauma, bleeding, or other invasive procedures (such as an amniocentesis) may receive several 'shots' during there pregnancies. One injection of 'Rhogam 300mcg' will neutralize about 30 cc of whole fetal blood. The important thing is that you did get it in time. You should be fine! After delivery, if your baby does turn out to be Rh-positive, your doctors may check your blood to see how much of the baby's blood got into your circulation and then adjust the amount of Rh-immune globulin to make sure you eliminate the fetal red blood cells. Good luck with the rest of your pregnancy and let us know how things turn out!
Dr T

Labels: rh-immune globulin, Rh-isoimmunization, Rh-negative blood type

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More Queries About Rh-Negative Blood

The following two comments recently appeared on my post addressing Implications of a Negative Blood Type. The first reader's question is worth repeating because MANY readers have asked the same question (in various forms) and the explanation is fairly simple. The second reader's questions revolve around potential complications of Rh-sensitization in someone who is attempting to conceive by in vitro fertilization with donor sperm. Her situation is NOT unique today and many other women may be interested in my responses to her queries as well...

Anonymous said...
Hi,I have a daughter who is
O negative. I also have a son who is O positive.
I am O positive and my wife is O negative. Is this possible?

Kenneth F. Trofatter, Jr., MD, PhD said...
To anonymous Sept 24: Yes, it simply means that you are heterozygous for the Rh D antigen. That means you have one chromosome that carries the gene for D and one that does not. Your wife has two that do not because she is Rh-negative and if she had even one dose of D, she would be phenotypically Rh-positive just like you because D is a dominant allele. Anyway, odds are that half of your kids (male and female) would be expected to be Rh-positive and half Rh-negative based on percentages alone (and no other extenuating circumstances). Sounds like that's what's happened so far in your family. Hope that helps. Thanks for reading! Dr T


lotsofdecisions said...
Hi. I became sensitized to Rh during my pregnancy with my daughter. My questions:

1) Does the fact that I was sensitized at my daughter's birth impact the problems I may have with a future pregnancy? I'm using donor sperm and know that the donor is O+ and heterozygous. How great is the risk? My titers are around 1:4.

2) After 2 unsuccessful IVFs to avoid having a second O+ child, I am about to admit defeat re: giving my daughter a full sibling. My question: should I consider only O- donors? It seems like using an A- or B- donor could result in as great of issues as if I used my daughter's donor.

3) How concerned should I be about CMV? I'm CMV negative. I've lived in the Northeast as well as the South. It seems like I'd have contracted CMV if I were susceptible to it.

Sorry this is so long. Thanks in advance.

Kenneth F. Trofatter, Jr., MD, PhD said...
To lots of decisions Sept 20:
1) Yes, your Rh-isoimmunization could have an impact on a future pregnancy. If your donor is heterozygous for Rh-positivity, there is a 50% chance your babies from that donor will be Rh-positive and potentially at risk for "Rh disease." You are currently at relatively low risk for complications with a titer of only 1:4. The risk begins to rise dramatically once your titer exceeds 1:16. During a pregnancy, I would recommend you have your titer checked every 4-6 weeks, especially if it begins to rise. In fact, if it does rise during a pregnancy, that probably confirms the baby is Rh-positive. We can currently assess risk for fetal anemia by a noninvasive study called Doppler flow velocimetry of the peak systolic velocity in the baby's middle cerebral artery. It's not as hard to do as it is to pronounce!

2) If you are using an Rh-positive donor, you cannot be sure that the baby is not Rh-positive until you test fetal cells by some sort of invasive procedure (chorionic villus sampling, amniocentesis, percutaneous umbilical cord blood sampling). You would be better starting off with an Rh-negative donor because then the baby CANNOT be Rh-positive. It does not matter whether that donor is A-, B-, O-, or AB-. The problem is with Rh, not the major blood group antigens.

3) CMV negativity is a BIG concern to me in your situation. (Check out a couple of my earlier blogs on that subject as well). You may be at risk for contracting that from your donor or you could simply contract it from someone else, especially your daughter, who is VERY likely to pick it up if she spends time around other kids. It is spread by all kinds of body fluids (e.g., blood, urine, and drool) and it is unlikely you are "not susceptible" to catching it; you probably have just been UNLUCKY enough not to have been exposed to it earlier in your life. I say unlucky, because if you did happen to catch it during a pregnancy, the results could be quite devastating to the baby. Thanks for reading and the great questions and BEST of luck to you too! Dr T

Labels: CMV, cytomegalovius, Rh-isoimmunization, Rh-negative blood type, Rhogam

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Readers' Concerns Regarding Rh-immune Globulin and ABO-Incompatibilty

Anonymous said...
Great information! I just miscarried and I want to know why. I am 0- and received a Rhogam shot at 28 weeks with my 1st child. I did not receive a shot after delivery--I checked my records. Did this (not receiving a shot) contribute to my miscarriage? Wendy
Sun Sep 16, 12:10:00 AM 2007

Kenneth F. Trofatter, Jr., MD, PhD said...
To Wendy Sept 16: I am sorry for your recent loss. The most common cause of sporadic miscarriage in women who have had successful pregnancies is a fetal chromosomal abnormality. With regard to your other question, the routine would have been to give you Rhogam after you delivered UNLESS your baby happened to be Rh-negative as well. It is very unlikely that not getting the Rhogam after delivery caused you to miscarry your recent pregnancy. That doesn't even seem to be a problem with individuals who ARE clearly Rh-isoimmunized. It's dealing with those pregnancies after the first trimester that becomes the challenge! Regards, and thanks for your question.
Dr T

Sun Sep 17, Prefering Anonymity said...
My wife just delivered a baby girl 5 days ago who has elevated bilirubin levels with the cause thought to be ABO incompatibility. My wife is O-negative, I am A-positive and our daughter is A-positive/Combs-positive. My wife was not administered rhoGAM at any point during or after her pregnancy/delivery. Our pediatrician caught the jaundice fairly early and daughter is seems to be recovering, but I am also quite concerned with whether my wife and I can now safely have another child, as she did not receive rhoGAM. Is it possible for us to safely have another child and what would we need to do or screen for to do so? My thanks to you in advance.

Kenneth F. Trofatter, Jr., MD, PhD said...
To preferring anonymity Sept 16: Your wife did not NEED Rhogam if your daughter was Rh-negative. ABO incompatibility is another issue. All people with O blood types make antibodies to A and B blood groups. They are exposed to those antigens in the environment (bacteria) and do not even need to be exposed to another human's blood to generate these antibodies. However, usually these antibodies are of the IgM class of antibodies. IgM antibodies are very large and basically contain a pentamer (5 antibodies) joined together. They are TOO BIG to cross the placenta to the baby. Occasionally, individuals also make anti-A or anti-B antibodies that are IgG class antibodies. These CAN cross the placenta and, indeed, IgG antibodies are a major source of 'immunity (passive immunity)' against common pathogens for the baby during the first 3-6 months of life.

Unfortunately, the placenta doesn't differentiate between 'good' (protective) IgG antibodies and antibodies that might harm the baby. This is the same problem with Rh-isoimmunization when it occurs. The antibodies from the mother cross the placenta, attach to the fetal tissues that are foreign (in your baby's case blood group A red blood cells) and that signals the baby's immune system to destroy whatever the antibodies are attached to - at that point the baby's immune system cannot distinguish what uis 'foreign' and what is 'self'! With the destruction of the baby's own red cells, hemoglobin is released and its breakdown product, bilirubin, can cause jaundice and more serious problems if the bilirubin levels get high enough. When the baby has used up all the antibody it has gotten from Mom, it will not have anymore problems.

To answer your other question, yes it is safe to have another baby under these circumstances. Often ABO incompatibility isn't much of a problem until after the baby is born, unlike with severe Rh-isoimmunization. Your doctors can assess the degree of fetal anemia in utero, indirectly, by doing peak systolic velocity of blood flow in the baby's middle cerebral artery by Doppler flow velocimetry if you are worried about fetal anemia during the pregnancy. Let them explain that to you! Best of luck, congratulations on your new baby, and thanks for reading and the great questions.
Dr T

Labels: ABO incompatibility, rh-immune globulin, Rh-isoimmunization, Rhogam

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Readers' Featured Comments/Questions - Why Wait to Conceive after Miscarriage and Rh-negative Concerns

Anonymous has left a new comment on your post "Early Pregnancy Loss - 2":

I found out from my OB today that I miscarried (I found out I was pregnant on 8/22, and began bleeding on 8/29, he ordered a hCG level test which went from 12 to 2 in a 48 hour period, therefore, confirming a miscarriage). I have had only two other pregnancies, which resulted in two healthy children (now 4 years and 21 months). Anyway he said I had to wait for my next menstrual cyle to start trying to conceive again - why do we have to wait?

To Anonymous Sept 2: I am sorry for your loss. Since you have had other normal pregnancies, the overwhelming odds are that this baby you lost was chromosomally abnormal. You lost this pregnancy so early (very low hCGs) that it probably wouldn't make any difference if you "tried again" during the next cycle. But, I too usually suggest that a woman wait for one normal period before trying again, just to give any 'inflammation' that was associated with the recent loss a chance to resolve to improve the probability of successful implantation the next time around. Waiting also gives your hormones and the endometrium a chance to get back in 'synch' and this too might improve the chances for a successful pregnancy. Thanks for reading and for a good question that, I am sure, is on the mind of many women who are in a similar situation! Best of luck on the next go-around! Dr T


Anonymous has left a new comment on your post "Implications of a "Negative" Blood Type":
I was recently pregnant and miscarried at 6 weeks. Since I am Rh-negative, I was given a shot of Rhogam and was told that it would last in my system for three months. I am pregnant again (5 weeks) and know that the Rhogam is no longer in my system. Will I need another shot ASAP?

To Anonymous Sept 2: Your doctor will perform an antibody screen on you as part of the standard 'new OB' labs early in this new pregnancy. If there is no evidence of sensitization, i.e., you haven't developed any antibodies against Rh-antigen (odds are you were entirely protected from becoming sensitized by having gotten Rhogam with your miscarriage), then you will not get another shot of Rhogam until about 28 weeks, unless you have an indication such as bleeding, trauma, or an amniocentesis with this pregnancy before then. Best wishes this time around and thank you for reading! Dr T


Anonymous has left a new comment on your post "Implications of a "Negative" Blood Type":
Hello! I am A- and my husband is O+. Will we have problems conceiving or problems during the pregnancy because of our different blood types?

To Anonymous Sept 3: Your different blood types should not increase difficulty conceiving. Because you are Rh-negative and your husband is Rh-positive, you are at a small risk of becoming 'sensitized' to the Rh-antigen during a pregnancy (if the baby is Rh-positive like your husband) or at the time of delivery. However, getting Rhogam (which contains anti-Rh antibody) during and after the pregnancy greatly reduces the chance of isoimmunization because it helps your body get rid of any fetal blood cells that have gotten into your circulation before your own body makes antibodies to them. In fact, it may actually suppress your immune system from making Rh-specific antibodies! I certainly wouldn't sweat the issue at this point! Go out (or stay in) and get pregnant and don't fret about this. Thanks for reading! Dr T

Labels: blood types and pregnancy complications, early miscarriage, Rh-isoimmunization

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