A desperately ill child is every parent’s worst nightmare. When children are affected with life-threatening, inherited blood disorders like Fanconi anemia, β-thalassemias, Tay-Sachs, or leukemia, their best (and sometimes only) chance at survival is a hematopoietic stem cell transplant (HSCT).
HSCTs require a suitable HLA (Human Leukocyte Antigen) match between donor and recipient. HLA typing is far more complicated than blood typing, and finding a donor for such a transplant can be difficult, especially among ethnic groups underrepresented in public donor banks [*].
Parents who have an existing child who does not carry the disease in question and reaches the level of HLA matching required for the transplant are in a good position to save their sick child — especially if they’ve banked the healthy child’s cord blood.
Parents with only one child that will die without a stem cell transplant from a matched donor cannot simply conceive another child and hope for the best because that child, too, could have the inherited disease. And time may be running out for the sick child. But there are ways to mitigate the risk of the baby inheriting the disease.
Stem cell transplants have higher success rates when the donor is not only an HLA match, but also related to the patient. A sibling has a 1 in 4 chance of being a perfect HLA match and a 2 in 4 chance of being a half-match. This means with one sibling, there is a 75% chance overall of a potential match that would be suitable for a HSCT. Although there are more unrelated donor HSCTs, HLA-matched sibling donors represent 30-40% of all allogeneic transplants [*].
This has led many parents to conceive a child via assisted reproduction for the purpose of saving another: a savior sibling. While successful and legal in the U.S., it is not without controversy, particularly over questions of what can be harvested from the child and for whom, the thorny issue of donor consent, the risks and benefits to the donor child, and long-term psychological effects.
What Is a Savior Sibling?
Savior siblings are children who are conceived with assisted reproduction techniques to save the life of a sibling affected with a fatal disease that is best treated by hematopoietic stem cell transplantation.
Their stem cells are typically harvested from the umbilical cord after birth, as stem cell transplants from cord blood have better outcomes than those from bone marrow, but sometimes both options are employed [*].
How Do Savior Siblings Work?
The key to savior siblings is preimplantation genetic diagnosis (PGD). PGD was introduced in the early 1990s as an alternative to prenatal diagnosis of genetically inherited diseases in couples with increased reproductive risk. PGD offers parents a way to avoid passing on a heritable genetic disease, eliminating the need for elective termination and mitigating the risks of miscarriage.
There are three types of PGD tests:
- PGD-A tests for chromosome abnormalities/aneuploidy (having an abnormal number of chromosomes in a haploid set — a problem that increases with the age of the mother).
- PGD-SR tests for structural chromosomal abnormalities.
- PGD-M tests for single gene diagnosis and HLA typing.
Most patients undergoing fertility treatment are offered PGD-A. The other tests are offered when there is a known genetic issue or structural genetic abnormality among the parents and when HLA typing is needed to ensure a match with the sick child.
Genetic testing of embryos is done for hundreds of different types of diseases at IVF clinics and transplant centers across the country.
The embryo(s) that clear the hurdles of both sidestepping the disease and matching the sick child’s tissue type are implanted via IVF. Other viable embryos can be frozen and stored if another cycle is needed or you wish to have another child via IVF. They can also be donated to other couples, to medical research, or discarded.
Upon the birth of the savior sibling, stem cells are harvested from the newborn’s umbilical cord for use in the transplant.
How Effective Are Savior Siblings?
In the largest study assessing clinical outcomes of both PGD + HLA and HSCT, the European Society of Human Reproduction and Embryology published in 2018 15 years of data covering practice at 14 different centers.
A total of 136 HLA-matched babies were born, and stem cell transplants were performed in 57 cases. 64.9% of the transplants involved combined umbilical cord blood and bone marrow transplantation. There were no complications reported in 77.3% of these transplants. Key factors influencing the success were the age of the mother undergoing the treatment cycle, the number of oocytes (eggs) collected per cycle, and genetic probability. The median age of the mother in this study was 33.5 years.
In the last 30 years, cord blood stem cells (hematopoietic stem cells, or HSCs) have been used in more than 25,000 successful transplants to treat 80+ diseases, with hundreds more in clinical trials.
The first cord blood stem cell transplant was performed in 1988 in Paris, France, for a 5-year-old boy named Matthew Farrow who had Fanconi anemia, a rare genetic syndrome characterized by bone marrow failure, congenital malformations, chromosome fragility, and a predisposition to cancer. Fanconi anemia almost always results in leukemia by age 10. The donor was his newborn sister, whose stem cells were harvested from the umbilical cord. Both siblings are alive and well today. Matthew Farrow is 39, married, and a father, as well as an advocate for cord blood awareness.
Fanconi anemia was also the medical issue in the first savior sibling case, in the U.S. in 2001. Adam Nash was born free of the deadly anemia that plagued his 6-yr-old sister thanks to PGD + HLA, and as a suitable HLA match, his umbilical cord blood stem cells saved her life and cured her condition.
Both Adam and Molly Nash are alive and well today, and the Nashes later had a third healthy child as well using PGD to screen for the disease. Many savior sibling cases followed internationally.
The Challenges of Conceiving A Savior Sibling
What’s noteworthy about the Nash case is that both parents carried the gene for Fanconi anemia. It took several rounds of IVF and tens of thousands of dollars to get an embryo that both cleared the disease and matched Molly’s tissue type [*].
Savior siblings are an option when transplantation is not urgent and parents are of reproductive age, but the success rate drops considerably as the mother nears 40. Part of the problem is that diseases like Fanconi anemia are very rarely diagnosed at birth. The mean age at onset of hematological disease in Fanconi anemia is 7 years, and the majority of patients are diagnosed months or even years after onset [*].
Considering that in 2022 the median age of women giving birth in the U.S. is now 30 years — the highest it has ever been — the window to produce a savior sibling is narrowing [*].
Clinicians and families with Fanconi anemia or similar genetic disorders considering PGD + HLA must take into account that possibly more than 95% of the IVF cycles will not result in a birth and that the probability worsens as the mother approaches age 40 [*].
The techniques used to conduct genetic analysis in the context of reproduction continue to evolve, but it’s important to recognize that PGD cannot correct a genetic issue, it can only diagnose it so prospective parents can sidestep it.
Are There Times When Savior Siblings Cannot Be Conceived?
There are instances when none of the embryos created through IVF is free from an undesirable genetic mutation [*]:
- When one of the parents is homozygous (having inherited the same versions (alleles) of a genomic marker from each biological parent) for a dominant genetic disorder, the risk of transmission to offspring is as high as 100%.
- When both parents are homozygous for a dominant genetic disorder, the risk of transmission is 75%.
- When both parents are homozygous for a recessive genetic disorder, meaning they both carry two variants of the disease-causing gene, there is only a 25% chance the offspring will have two normal genes.
For these parents, PGD may not yield a viable embryo, especially if there is a need to HLA match as well as sidestep a genetic defect. Their future may be in gene editing with a tool such as CRISPR, which could potentially correct a monogenic mutation in the embryo — or even directly onto prospective parents’ gametes prior to fertilization.
Gene editing is far more controversial than savior siblings, even though it avoids the whole ethical conundrum of risk-benefit scenarios to a donor child. You may recall the brouhaha that occurred in 2019 when a Chinese scientist altered the DNA of human embryos using CRISPR (to protect them from HIV) and the embryos were carried to term (twin girls) [*]. As a result, the international community called for a global moratorium on all clinical uses of germline editing, and the scientist was jailed for 3 years for failing to follow the guidelines [*].
Although rapid advances in genome editing are expected to make germline gene correction feasible in a clinical setting, there are many issues that still need to be addressed (ethical, social, evolutionary) before this could occur [*]. As of May 2022, based on concerns about ethics and safety, germline cell and embryo genome editing are currently illegal in the United States and many other countries [*].
Federal funding is prohibited to be used for this research, but privately funded research has shown success in eliminating a form of blindness as well as a fatal heart mutation in embryos that were deliberately not carried to term [*].
Are Savior Siblings Legal?
Yes, savior siblings are legal in the U.S. There is very little federal regulation of PGD and no federal or state laws regulating the non-therapeutic use of PGD. It can be used for any condition for which genetic testing is available at the discretion of fertility treatment clinicians and their patients. By contrast, many European countries have rigid legal structures that determine for what indications PGD is allowed.
For instance, in the U.S., a small number of clinics offer PGD to avoid a disability, such as deafness or achondroplasia [*]. PGD is also widely offered for sex selection; a 2017 study showed that 72.7% of US fertility clinics offer sex selection, and 83.5% of those clinics offer sex selection for couples without infertility, meaning that a couple would only undergo IVF to select their child’s sex [*].
Since its introduction in the U.S. in 1981, IVF and similar techniques have resulted in more than 200,000 babies, according to the Society for Assisted Reproduction Technology. The IVF market was valued at around $628.50 million in 2021 and is projected to reach over $1 billion by 2028 in terms of revenue.
When ruling on the legal issues pertaining to savior siblings, courts look at the best interest standard: whether allowing a child to donate tissue or organs would be in the best interest of the child and the child’s needs. The issue is particularly thorny when the child is too young to provide consent and the parents do not agree on what is in the child’s best interests.
In an Illinois case in 1990, a father (Tamas Bosze) estranged from his partner (Nancy Curran) tried to compel her to HLA test the couple’s 3-½-year-old twins so one or the other, if matched, could provide a bone marrow transplant to the father’s 12-year-old son, Jean-Pierre, from another woman. Jean-Pierre suffered from mixed lineage leukemia and had endured multiple treatments which ultimately failed to cure his condition.
Ms. Curran objected to both the testing and any bone marrow harvesting on the grounds it was not in the best interests of the twins in the absence of an existing, close relationship with Jean-Pierre, whom they had only met twice.
The court placed the burden of proof on Mr. Bosze to prove it was in the twins’ best interests to donate bone marrow if they could. The Illinois Supreme Court ultimately supported the judgment of Ms. Curran, who had custody of the twins under a prior arrangement [*].
Are Savior Siblings Ethical?
The Nashes faced a huge ethical backlash over baby Adam, the first savior sibling. The New York Post headline was “Frankenstein Baby,” as if Adam Nash had been spliced together instead of simply selected to beat the odds.
Critics focused on the Nash's decision to have a child with traits that would benefit someone else and scrutinized their reason for having another child. Did they really want another child or were they just trying to save the one they had?
Arguments that a savior sibling would wrongfully be treated as a means rather than an end lands on shaky ground when you consider some of the reasons people have children now: to save a marriage, to care for the parents when they get old, to carry on the family line or family business, to give an existing child a playmate, or simply because contraception failed.
The argument that savior siblings would lead down a slippery slope to designer babies falls apart when you consider how difficult it can be, when one or both parents carry a genetic anomaly and the mother’s biological clock is ticking, to simply create a disease-free embryo, get it to implant via IVF, and carry it to term.
The argument that the savior siblings would suffer physically or emotionally is also lacking evidence, but one study noted an uptick in sibling rivalry [*].
Depending on what one may consider as life, disposing of the other embryos that don’t match the sick child’s tissue type may be an ethical conundrum for some. Storage can run $600-800 a year for frozen embryos.
To be sure, the issues and lack of industry regulation keep bioethicists very busy [*].
There are four basic principles of Bioethics: (1) respect for autonomy (which includes consent issues), (2) beneficence (the benefit to the patient), (3) non-maleficence (to do no harm), and (4) justice (equitable treatment). Each of these principles has equal importance and complexity when dealing with ethical decision-making [*].
In response to the moral concerns about the use of savior siblings, the American Academy of Pediatrics suggests that tissue harvest should only proceed when the following five criteria are met:
- There is no medically equivalent histo-compatible adult relative who is willing and able to donate;
- There is a strong personal and emotionally positive relationship between the donor and recipient;
- There is some likelihood that the recipient will benefit from the transplantation;
- The clinical, emotional, and psychosocial risks to the donor are minimized and are reasonable in relation to the benefits expected to accrue to the donor and the recipient; and
- Parental permission and, where appropriate, child assent have been obtained [*].
Are Savior Siblings Covered by Insurance?
While genetic counseling is typically covered by insurance and consumers can learn about their genetic profiles in direct-to-consumer platforms like 23andMe or Color Genomics, parents may have limited options for managing their reproductive risk.
The high cost of fertility treatment puts it out of reach for so many people, and this is a key ethical concern. As of 2017, 17 states have laws that require insurance companies to include coverage for infertility diagnosis and treatment in their policies. Of these, only 11 specifically require coverage for IVF, and there may be pre-qualifying conditions [*].
Several major carriers do cover PGD + HLA when it is deemed medically necessary (i.e., a parent is a carrier of a genetic mutation) and no other compatible donor source can be found for a child with a bone marrow disorder. From a purely profit-driven perspective, it makes sense that an insurer would opt to cover PGD screening compared to the far greater costs of claims associated with a child born with a deadly disorder known to be carried by a parent.
But without insurance coverage, the reality is that, for many prospective parents, IVF + PGD is simply cost-prohibitive. In the US, a standard IVF cycle costs about $12,000, a price that doesn’t even include fertility medications (another $3,000–$5,000) or the PGD procedure (another $3,000–$6,000 per cycle). On top of that, many women have to undergo multiple IVF cycles to achieve a successful pregnancy [*].
When trying to manage costs associated with creating a savior sibling, it’s important to consider the success rate of the IVF clinic. The CDC tracks success rates for fertility clinics across the U.S. in an annual report [*]. SART (Society for Assisted Reproductive Technology) also provides success rates [*]. Choose wisely.
There is no easy answer to the ethical dilemma of savior siblings, and as the technology advances so do the implications. But the cat is now out of the bag, so to speak.
Savior siblings may be the only option for parents who cannot find a matched donor for HSCT. But it is a costly process whose success is tempered by a number of hurdles: the age of the mother, the parents’ genetic traits, the age of the recipient and the advancement of their disease, the IVF process, and the transplant procedure.
There are many diseases for which a child cannot use its own cord blood and a sibling is the best option. Because not all HSCTs require a 100% HLA match, it makes sense to bank cord blood for all your children so you have it on hand should the need arise [*].
MiracleCord’s service, technology, and value have earned us “Best Cord Blood Banking Company in the U.S.” from Global Health & Pharma in 2021 and again in 2022. Discover why.