Sickle cell conditions include sickle cell trait (SCT) and sickle cell disease (SCD). These are genetic conditions involving the hemoglobin in red blood cells (RBCs), whose job is to carry oxygen to body tissues. If you have SCT, it means that your body cells harbor a defective copy of a gene that carries instructions for what is called the beta chain of the hemoglobin molecule plus you have a normal copy of the gene of the beta chain. Having SCT makes you a carrier for SCD, which is a very serious condition. People with SCD tend to have anemia (low levels of RBCs or hemoglobin), and also can develop blood clots, strokes, and problems with internal organs, called sickle cell crisis, which can be fatal. In contrast, people with SCT usually do not experience symptoms, unless the body is put under stress. Stressful environments that can put people with SCT in danger of developing sickle cell crisis include high altitude, dehydration, and very intense sports, and possibly pregnancy may do the same.
Sickle cell conditions are genetic. SCD is called a recessive genetic disease because you must receive a gene copy for a defective beta chain from each parent. In contrast, having one gene copy for a normal beta chain and one copy for a defective chain makes you a carrier for SCD. If your one sickle cell gene copy gets together with a defective gene copy from the other parent, the child can end up with two copies of the sickle cell gene. But, as noted above, being a carrier means that you have the sickle cell “trait”, meaning that you can have characteristics of SCD when your body is put under stress.
Genes for sickle cell hemoglobin are much more common in places where the disease malaria is a problem or has been a problem in the recent past. Consequently, the gene for sickle cell hemoglobin is common among people with recent origins in Africa, Mediterranean regions, and parts of south Asia.
One per 12 pregnant African American women carry one sickle cell gene copy, and thus has SCT. SCD is more rare, since it occurs only when two copies of the sickle cell gene combine in the same person, but more than 300,000 are born with SCD each year worldwide. On the other hand, more children with SCD have been surviving to adulthood in recent decades, so SCD is more common during pregnancy than it was in the past.
As noted earlier, there is a connection between malaria and the gene for the defective beta chain that produces sickle cell hemoglobin. Malaria is a serious disease that is caused by a parasite called Plasmodium that is delivered to people through a bite from females of a type of mosquito called Anopheles. Malaria can kill, but there is a big range of severities that the disease can take, and people with certain hemoglobin conditions, including SCT, can resist the infection and get only mildly sick or not sick at all. Consequently, if you live in a place where malaria is present, having one copy of the sickle cell gene –meaning having SCT– gives you a survival advantage over people who have two normal genes for the hemoglobin beta chain. Scientists think that the reason is related to the fact that the Plasmodium that causes sickle cell conditions normally thrives inside RBCs. However, the presence of some abnormal hemoglobin changes the shape of RBCs of people with SCT in a way that prevents the Plasmodium from entering or thriving. Now, it’s true that by having SCT you would have some risk of dying from a sickle cell crisis if you were to climb to a high altitude or get extremely dehydrated, but this risk is lower than the risk of dying from malaria if you have two normal beta chain genes.
In a population of people living where the Anopheles mosquito thrives, the gene for sickle cell conditions and the gene for a normal beta chain of hemoglobin both persist over many generations through a phenomenon called balanced polymorphism. The balance is between malaria killing people who don’t have a sickle cell gene, and SCD killing people who have two sickle cell genes. Even though the result of having the sickle cell gene in the population so that some people will have two copies and die in childhood, many more people will have just one copy and survive malaria. In other words, people with SCT are more fit to survive than other people. Thus, natural selection, survival of the fittest, maintains the sickle cell gene in the population even though the gene kills some people.
One per 12 pregnant African American women carry one sickle cell gene copy, and thus has sickle cell trait. Sickle cell disease is more rare, since it occurs only when two copies of the sickle cell gene combine in the same person, but more than 300,000 are born with sickle cell disease each year worldwide.
Now, the question for you is probably how sickle cell conditions will affect your pregnancy. SCD can cause complications, such as preterm delivery and a serious condition called preeclampsia. SCD also can cause blood clots, strokes, and sickle cell crisis as it can do in women who are not pregnant. As for SCT, this increases the risk of infections in the amniotic fluid, although such infections may not affect your pregnancy. The more severe complications listed above for SCD also can happen in SCT if a woman stresses her body during pregnancy, for instance, by ascending to high altitude.
As far as treatment goes, SCD is treated with a drug called hydroxyurea, and there is some concern that not enough is known about its effects on the fetus to be certain that it cannot harm the fetus. The concern is partly related to the fact that hydroxyurea works by turning off the gene of the hemoglobin beta chain in the mother’s bone marrow cells. As a result, the gene for a fetal version of the beta chain, called the gamma chain, is turned on, giving the mother the same kind of hemoglobin as her fetus. Normally, the benefit of the fetal hemoglobin is that it attracts oxygen more strongly than adult hemoglobin does so oxygen moves from the mother to the fetus. The reasoning is that maybe the fetus of a mother who takes hydroxyurea will not receive enough oxygen, but more studies are needed to determine if this really is a problem. At the same time, there is some concern that hydroxyurea has not been studied enough to know whether it is safe for newborns nursing from mothers who take the drug.
