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Epigenetics and Motherhood

How does epigenetics relate to Nature Vs Nurture?

Epigenetics explains how early experiences can have permanent effects. The genes children inherit from their biological parents provide information that guides their development. For example, how tall they could eventually become or the kind of temperament they could have.

How does epigenetics affect us before birth?

Environmental factors may alter the epigenetic profile of a fetus during early life, specifically in the prenatal period, which may increase vulnerability to diseases later in life, such as obesity, cardiovascular, diabetes, etc.

Donor Eggs Epigenetics and Birth Mother.

Birth mothers using donor eggs have a significant impact on the development and future health of their babies. Since the baby’s DNA only comes from the egg donor and the sperm donor, many women using egg donation worry that they will not share any genetic information with their child.

However, the switches that turn our genes on and off may play an even greater role in health and development. These switches are known as epigenetic controls. Abundant research has shown us that the prenatal uterine environment plays a crucial role in fetal brain development, childhood metabolism, immune health, and numerous other factors.

Given our limited understanding of the processes that affect fetal development, what can a pregnant woman do to improve her prenatal environment? Following the common practice most women use during pregnancy might be the best approach in order to foster a healthy uterine environment for your baby, it is essential that you maintain a good weight, follow healthy diet habits, refrain from drinking alcohol, limit caffeine intake, and take prenatal vitamins. Stress management and maintaining stress-reducing activities during pregnancy are equally important for creating a healthy uterus for your baby.

An emerging concept, fetal adaptation, explains how epigenetic regulation impacts development later on in development, in contrast to embryogenesis and implantation early on in development. Epigenetic modifications allow the fetal genotype to respond to a variety of developmental environmental factors. Even though early gestation is the most susceptible period for the fetus, environmental stimulation in late embryonic development, infancy, and early childhood can also have long-term health effects in later life. It has been shown that a high-fat diet supplemented in adulthood induced large-scale methylation changes in skeletal muscles, as did folic acid supplementation during the peri-pubertal period. All these studies suggest that plasticity of the human epigenome may also persist into adulthood and epigenetic mechanisms are involved in life-long adaptation.

In conclusion:

In contrast to conception, which begins when an egg cell meets a sperm cell, motherhood begins in the womb. The factors influencing childhood begin in the mother’s body long before she becomes pregnant. Your uterine environment will influence your baby’s development in various ways. When you begin taking care of yourself before you become pregnant, and continue doing so as your baby develops inside you, you’ll be able to pass on health benefits to your child, ensuring they have the best possible future.

Delayed Cord Clamping

There is, however, a small risk of increased hyperbilirubinemia/jaundice (because of the additional red blood cells infused during DCC) in some infants after DCC. An estimated 50% of term and 80% of preterm infants develop jaundice.

Delaying cord clamping for one minute or more resulted in only a 6%–21% decrease in the total volume of cord blood collected and a 9%–31% decrease in the pre-processed total nucleated cell. It is estimated that about 60% of DCC collections still meets the upper level for the number of total nucleated cells. However, a prolonged delay will allow the blood in the cord to clot, and the opportunity to collect the blood for stem cells will be lost; therefore, if clamping is delayed, it is recommended not to delay for more than two minutes.

What major myths exist relating to the optimal clamping time?

Myth: If you don’t do DCC, you are robbing the baby of 30% of its blood.

Fact: When the umbilical cord is clamped soon after birth, the infant’s blood volume is the same as its volume in utero (in the womb).

Myth: The longer you wait to clamp the cord, the more blood the baby gets.

Fact: The continued transfusion of cord blood when delaying the clamping in normal birth is reliant on contractions of the uterus, the umbilical arteries close around 45 seconds after birth and the umbilical vein in 1–2 minutes. For c-sections, the blood volume in infants increases till 40 seconds and actually decreases thereafter.

Myth: Delaying the clamping of the cord confirms the advantages observed by researchers.

Fact: Factors affecting the transfusion of additional blood cells include the timing of cord clamping, gravity, the onset of respiration, uterine contractions and drugs affecting it, maternal blood pressure and birth asphyxia.

Facts relating to COVID-19 and delayed cord clamping

The use of delayed cord claping during COVID-19: Most Gynaecological institutions have stated that these procedures should remain according to usual centre practice, while following infection control precautions. They have stated that delayed umbilical cord clamping is extremely improbable to increase the risk of transmitting pathogens from an infected mother to the fetus; however, some institutions have selected to forbid this exercise in term infants, in whom the benefits are modest. This practice they believe will minimise newborn exposure to any virus in the immediate environment and reduce the chances that the newborn will require phototherapy for jaundice. Some institutes also prohibit skin-to-skin contact in these cases, although the Paediatric institutions have not advised against this.

A summary of the pros and cons of cord blood banking

Cord blood banking Pros

1. Painless Process

The process of collecting blood from a newborn is entirely non-practical and painless for the mother as well as the baby.

2. Devoid of Health Risks

The banking of cord blood is a risk-free procedure for the baby and the mother.

3. Increased Effectiveness

Cord blood stem cells have an increased advantage of easier tolerability, reduced rejection and mismatching concerns than bone marrow stem cells.

4. Decreased Chances of Graft Diseases

The chances of graft diseases after transplantation are higher with peripheral blood and bone marrow stem cells as compared to cord blood.

5. Prolong Storage

Apart from the easy collection of cord blood, it can be stored for 20 years or more (given it is stored under the industry approved controlled conditions). When cryopreserved, cord blood has a longer shelf life for usage after many years of collection. Bone marrow blood cannot be preserved for a longer duration.

6. Immune System Reinforcement

Cord blood has the added advantage of being used to boost immunity of patients, during the treatment of cancer. Researchers are using cord blood stem cells to increase the immune system of cancer patients after chemotherapeutic treatment of cancer. This treatment provides for better outcomes and recovery of cancer patients.

7. Increased Proliferation Capability

The stem cells from cord blood have increasing dividing capacity and therefore when transplanted in a recipient will give better results than bone marrow or peripheral blood. The yield of cord stem cells is about 14 times greater than cells from other sources when comparing the volumes collected.

8. Less likely to have infectious agents

Stem cells from cord blood rarely carry any infectious diseases and are half as likely to be rejected as adult stem cells.

9. Future Insurance for Child

The banking of cord blood offers reliable and useful choices to parents for saving their child’s health prospects. This process is like health insurance for your children and direct family, due to the similarity in genetics the probability of being a match for siblings is 25% and 50% for parents. Thus the saving could provide a cost saving in the long run when comparing a transplant from a non-related adult stem cell source.

10. Assisting Humanity

Due to improved chances of donor receipt of stem cells into the foreign body, the cord donor blood could prove to be an extraordinary relief to many sufferers. The donation of cord blood is motivated by the certain health agencies as it can serve as an outstanding transplantation opportunity in many recipients.

11. Helping Family Members

In case of medical problems, providing stem cells from a child could be a source of medical assistance to siblings, parents or any other family member, due to inheritance similarities.

Cord Blood Banking Cons

Although there are disadvantages, there are ways to overcome these challenges and we mention these below.

1. Ineffective Treatment in Adults

Because of the limited volume of cord blood available from the source, most adults cannot be treated with the number of stem cells collected at birth. Therefore the expansion of cord blood and tissue stem cells have now provided an increased usage of cord stem cells in general.

2. Autologous Transplantation

Refers to the treatment of the same child with his/her own stem cells. The only drawback is when a child has a genetic diseases or blood cancer because the stem cells will then carry the same genetic makeup and cannot be used. In this case it is recommended to store sibling cord stem cells in the event that the sibling stem cells can be used.

3. Immediate Collection

Though, the cord blood banking is related with the easier collection but immediate collection at the time of birth of a baby is necessary. It is recommended that parents make informed decisions and plan long before birth. Therefore CryoSave offers Emergency Kits at most hospitals to assist with this “on the spur of the moment” decision in some families.

The cord blood stem cells show slow grafting due to the fact that the white blood cells appear later in grafting from cord blood as compared to stem cells from bone marrow transplantation. This can be improved by double unit transplants or by also expansion of cord stem cell grafts ex vivo (outside the body) to increase the cell dose.

5. Ethical Concerns

The use of cord blood and tissue has restraints due to ethical issues, but these are overcome by clinical trials that are demonstrating the value of these precious stem cells in the treatment of many diseases; i.e. autism, cerebral palsy, multiple sclerosis, diabetes, cardiovascular disease and many more.

Graft-versus-Host Disease

  • The ability to immediately bank these samples in a family (private) stem cell bank, for future use by the child (donor) or a sibling.
  • Cord blood stored in ‘public’ cord blood banks are made available for use by non-related individuals. These cord blood stem cells can be made available for transplant, without delay, and are more ‘naïve’ than the other sources of blood-forming stem cells i.e., bone marrow (BM) and peripheral blood stem cells (PBSCs).

    Defining Graft-versus-Host Disease

    The day-to-day task of a person’s immune system is to protect it from foreign invaders, be it a bacteria, virus or other organisms or cells that are not identified as ‘self’.

    When a person needs a stem cell transplant, a donor, who is a match for the specific patient, must be found. This is what we call Human Leukocyte Antigen (HLA) matching or, in non-medical terms, “flags” that the immune system must look at to determine if something is an invader. With a stem cell transplant, the recipient will receive donor stem cells and these cells will form new blood as well as an immune system in the recipient.

    Higher levels of differences of human leukocyte antigen (HLA) matching can be tolerated with CBT, confers a potential advantage. Also, some studies have shown a lower incidence of graft-versus-host disease (GvHD) with CBTs compared to bone marrow and peripheral blood stem cell transplants.

    These features make a cord blood transplant as a potentially important option in patients from diverse, cultural and ethnic backgrounds as, for these patients, it can often be challenging to locate a matched unrelated donor (MUD).

    With a stem cell transplant, even after HLA matching, the patient/recipient’s body will still see small differences between the new developing immune system and other cells in their body. Therefore, the recipient’s “new” immune system may harm some of the recipient’s cells because they are seen as “different”. This immune attack (on the recipient) is called Graft versus Host Disease (GvHD). The word ‘graft’ referring to the donor’s cells, and the ‘host’, to the patient (recipient).

    The good of Graft-vs-Host-Disease

    GvHD can have a ‘good’ aspect as it indicates that the recipient’s new immune system is working and is likely to be attacking any remaining or returning disease. This type of immune response is called ‘graft versus leukaemia effect’ or ‘graft versus tumour effect’. However, extreme GvHD can cause undesirable problems and side effects which is life threatening.

    The not-so good

    GvHD is complex and cannot be predicted. Approximately, 30-40% % of transplant recipients will show signs of GvHD. In certain cases, it is mild but, in severe cases, may be life-threatening.

    GvHD can be classified as the following:

    • Acute: occurring within the first 100 days after transplant
    • Chronic: usually occurring after 100 days and
    • Overlap: having features of both acute and chronic GvHD.

    GvHD affects organs such as the skin, liver, and gastrointestinal system.

    It usually requires a fine balance of medication to keep the disease under control. Treatment includes localised and/or systemic steroids or immunosuppressive medication. In some cases, acute or chronic GvHD cannot be controlled with these medications and further treatment, such as extracorporeal photopheresis (ECP) (where the white blood cells that cause GvHD are destroyed with medication and ultra-violet (UV) light, is required).

    Several strategies exist to further improve outcomes in CBT and minimise GvHD even further:

    1. The use of double CBT from unrelated donors
    2. The use of HLA-identical sibling CBT
    3. The use of a combination of UCB and bone marrow from the same sibling,
    4. The use of higher cell doses in conjunction with microenvironmental factors and, for example, the combined use of mesenchymal stem cells.

    These strategies are designed to enhance the ‘homing’ and engraftment of the transplanted cells and improve success rates overall.

    Final words

    Parents should consider storing their baby’s stem cells at birth, which would give the Transplant Team an option should a stem cell transplant be needed.

    Did you know

    Since the first cord blood transplant in 1988, more than 40,000 CBTs have been performed, worldwide, over the past three decades.

    Know the difference: Family vs Community Cord Blood Banks

    Private Cord Blood Banks

    When storing umbilical cord blood stem cells in a  (private) cord blood bank, the parent/s pay a fee for the collection, transport, processing, testing and storage of the cord blood and cord tissue.  The storage period is a minimum of 20 years.

    Cord blood and tissue stem cells stored in this setting are RESERVED EXCLUSIVELY FOR USE BY THE FAMILY and are available, without delay.

    The stem cells are available to the family should they be required in clinical trials, such as for the treatment of neurological conditions including autism and cerebral palsy. The parents have full rights and access to the cells during the entire period of storage, should they be required for medical treatment.

    A few other noteworthy considerations:

    • A high probability of a match: The child’s stem cells will be a perfect HLAmatch for themselves and there is a 25% chance of being a perfect match for a sibling.
    • HLA matching is included in the family storage package: Should the stem cells be required for a transplant, HLA matching will be paid for by the Family Cord Blood Bank.
    • No additional charges and the contract is straight forward: If cord blood stem cells are required for treatment from a Family Cord Blood Bank, there are no additional charges or fees for making the cord blood unit available to the patient at the Transplant Centre. Your contract stipulates no additional release charges.
    • Various treatment options available for the family: Autologous and allogeneic stem cell therapy have been used to treat more than 80 types of diseases including haematological and immunological disorders.

    Community Cord Blood Banks

    Donating cord blood to community cord blood banks is not ‘free’.

    Someone must pay for the collection, transport, processing, testing and storage, whether it be the parents, a third party, or the State.

    The collected cord blood stem cells are NOT RESERVED EXCLUSIVELY FOR USE BY THE CHILD OR THE FAMILY (the child or a sibling).  At any time during the storage period, parent/s may be informed of the planned use of the cord blood stem cells for a matched, unrelated patient. Should the parent/s not agree to the release of the stem cells to the unrelated patient, a substantial penalty fee will be applicable. 

    A few other noteworthy considerations:

    First come, first use: Should the cord blood stem cell unit be used for a matched, unrelated patient, it will no longer be available to the child or the family for use for established clinical treatments or in a clinical trial.  

    • No exclusive rights: A family that participates in a community programme gives up certain rights and potential access to the donated cord blood unit. The cord blood unit may be sold to a patient in need, who is granted full rights to use it for an established clinical indication or in a clinical trial.
    • Additional charges and costs: The cord blood unit may be made available to a patient in South Africa or abroad. Cord blood units imported into South Africa  can cost over R350,000 each. 

    Contract is more complex: As with any agreement, it is important to read the fine print and be sure that terms and conditions are fully understood, particularly with regards to the availability (or lack of availability) of the stem cells and additional costs that may be incurred.

    At CryoSave,  we currently only provide private stem cell banking.

    Where to get additional information?

    If you would like additional information or have any questions, please contact the CryoSave Medical or Laboratory Director, by calling 087 808 0170 or email info@cryosave.fintechdesign.co.za.

    Can umbilical cord blood be used to treat autism?

    Founder of the Paediatric Blood and Marrow Transplant Programme, Duke Professor of Paediatrics and Pathology and umbilical cord blood transplantation pioneer, Dr Joanne Kurtzberg, explains that a small percentage of cells in umbilical cord blood are blood stem cells that can rescue damaged bone marrow and can therefore act as a source of stem cells for transplant patients who do not have an appropriately matched donor. Dr Kurtzberg and her Duke teams’ investigations into the use of in umbilical cord blood has most recently focused on its possible use in treating a variety of inherited metabolic diseases, hematologic cancers, cerebral palsy and autism. Having completed an initial safety trial, findings in this regard have been positive and presents an optimistic view for future use for children with autism.

    What about those who do not have stored cord blood available?

    While initially those who did not have their stem cells stored at birth could not undergo treatments requiring stem cells sourced from umbilical cord blood, neuroscientists and neurosurgeons around the world are developing ways to generate a person’s own stem cells to repair the brain. Studies of this new approach, which involves the culturing of a specific type of brain stem cell – called Doublecortinpositive cells, provides widespread optimism of future access to such treatment.

    What’s next?

    Phase II of the clinical trials studying autism spectrum disorder (co-led by Kurtzberg and Geraldine Dawson, director of the Duke Centre for Autism and Brain Development and Professor of Psychiatry and Behavioural Sciences) is currently underway with diagnostic and clinical assessments, as well as examinations on the effect of the therapy on brain activity, are taking place. The team at Duke are also entering into a randomised phase II trial to test if cord blood can be used to treat children with cerebral palsy.

    Determined as safe to use when infused intravenously, Dr Kurtzberg has highlighted that stem cells might not be the only components of umbilical cord blood that trigger a response for body repair and has identified that some of the most active cells that induce repair are believed not to be stem cells.
    The Chief of The Paediatric Neurology Division and Professor of Neurobiology, Mohamad Mikati – who has worked with umbilical cord blood as a potential treatment for cerebral palsy – has added that his group have been investigating the safety and efficacy of this treatment in a very controlled and comprehensive study which he hopes will answer the current questions surrounding its potential.

    Following current trials and investigations, Dr. Kurtzberg and Prof. Mikati will be conducting further tests to confirm their findings and look into other neurological diseases for which umbilical cord blood may have potential in treating.