Ethics/education

Banking obstetric–related Current uses of CB

tissues and cells: what every CB is collected for various reasons.

maternity unit must know Directed donation of CB

In England, directed donation of CB from a sibling can be
arranged months before delivery with the National Blood Service
Fiona A M Regan if the Consultant of the sick sibling confirms the likely need for a
future CB transplant and funding. CB is collected by the Obstetri-
S Bewley cian or Midwife according to standard written instructions. There
are only about 25 directed CB units collected per year throughout
Ruth Warwick England, so the impact on a single hospital is small.

Unrelated altruistic donation of CB

Abstract
Cord blood (CB) is rich in haemopoietic stem cells, and can be used
instead of bone marrow (BM) for transplantation of patients with leukae-
mia, immunodeficiency or metabolic diseases. Private banking of CB to
treat various degenerative diseases is not evidence based, but regenera-
tive medicine deserves ongoing review of progress. Autologous CB for
treatment of BM disease is very unusual. If hospitals permit private col-
lection of CB, it should be taken by a trained third party. Mesenchymal
stem cells, present in very small numbers in CB and in larger numbers in
cord matrix, may have potential use in regenerative medicine. Ethical is-
sues relating to consent, testing and ownership of CB have largely been
resolved, but timing of cord clamping and private versus public banking
of CB is controversial.
One-third of patients needing HSC transplant have a matching
sibling donor; another one-third find a matched, unrelated, volun-
teer donor of BM or PBSC from worldwide donor registries, which
have ∼11 million donors. Matching for ethnic minority patients is
harder because tissue types vary between populations, and ethnic
minorities are under-represented on BM registries. CB transplants
have been used as an alternative for patients without a BM donor,
particularly in children, where the limited dose of stem cells in
CB collections compared with BM is less of a problem. Many CB
Banks, including the UK NHS Cord Blood Bank (NHSCBB), collect
from hospitals with diverse ethnic mixes to increase the chances
of finding matches. There are advantages and ­ disadvantages
in using CB versus BM or PBSC for transplant (Table 1) and it
has been suggested that, in children, CB transplant results are

Keywords bone marrow transplantation; cord blood; ethics; umbilical

cord Advantages and disadvantages of cord blood versus
transplantation using bone marrow or peripheral
blood stem cells
Cord blood (CB) is rich in haemopoietic stem cells (HSC). It is an
alternative to bone marrow (BM) or peripheral blood stem cells Advantages Disadvantages
(PBSC) to transplant patients with malignancy, including leukae-
Less close tissue type match Lower cell dose (∼1/10th
mia or diseases such as BM failure, inherited immune disorders
required than for BM or PBSC of BM) with slower and less
or metabolic disorders.
certain engraftment
The first CB transplantation was done in 1970 using multiple
unmatched CBs with transient take. A patient with Fanconi’s Greater chance of finding a Increased risk of life-
anaemia was successfully treated with CB In 1989. There have match, particularly for patients threatening post-transplant
been more than 10,000 CB transplants worldwide. from ethnic minorities infections (bacterial, fungal
and some viral)

Reduced risk of GVHD post- Not ethical to obtain second

Fiona A M Regan FRCP FRCPath is a Consultant Haematologist and Medical
transplant donation from same donor
Director for the NHS Cord Blood Bank, London, UK. Conflicts of
Faster to obtain donation for
interest: author works for the UK NHS Cord Bank.
transplant, as ‘off the shelf’,
whereas volunteer BM/PBSC
S Bewley FRCOG is a Consultant in Obstetrics and Maternal–Fetal
donors take 3–4 months to
Medicine at Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
assess fitness and donate
Conflicts of interest: author was Chair of the Ethics Committee of the
Lower incidence of donor to
RCOG from 2004 to 2007, and member of the RCOG Working Party on
recipient viral transmission of e.g.
Umbilical Stem Cell Collection in 2006.
cytomegalovirus, Epstein-Barr virus
from neonates than adult donors
Ruth Warwick FRCP FRCPath is a Consultant Specialist for Tissue Services
at NHS Blood and Transplant, London, UK. Conflicts of interest: author BM: Bone marrow; PBSC: Peripheral blood stem cells; GVHD: Graft versus
is CEO and trustee of Cord Blood Charity from 1997 to 2007, and was host disease.
the Medical Director of the London CB Bank (now known as NHS Cord
Blood Bank) from 1995 to 2004. Table 1

OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 18:3 76 © 2008 Elsevier Ltd. All rights reserved.
 Ethics/education
c­ omparable or superior to BM transplants. The main challenge
in CB transplantation is to improve engraftment. Using reduced-
­intensity conditioning for patients before transplant reduces the
period of low blood count, infections and transplant-related
­mortality, but is riskier for graft rejection and relapse.
CB transplantation for adults increased after the introduction
of double CB transplants to overcome low cell dose. Only one of
the multiple CBs transplanted takes, but a predictor of which unit
predominates has not been identified. Larger cell doses result in
better outcomes, so Banks aim to optimize the volume of CB col-
lections without compromising the wellbeing of mother or baby.
With skilled, experienced, designated collection staff, it is possible
to obtain CB units from an ex utero placenta of comparable vol-
umes to those collected from placentas in situ in utero (assuming
the same time for cord clamping). It is not known how a physi-
ologically managed third stage versus delayed cord clamping of
≤1–3 minutes would affect collection in utero versus ex utero col-
lections, though it must be presumed that total volume collected
is probably less. It is the policy of the NHSCBB not to interfere
with the usual management of labour. Bacterial contamination
rates decrease from 30% to <1% with experienced collectors.
Innovative approaches
Ex vivo expansion of CB stem cells has not resulted in improved
engraftment in clinical trials, partly because the expanded cells
may be too committed, rather than amplifying the number of
truly multipotent HSC. Other manoeuvres being studied to speed
up engraftment include
• intra-BM injection of CB (rather than conventional intra­venous
‘transfusion’)
• co-infusion of mesenchymal stem cells (MSCs)
• upregulation of homing receptors for HSC.
Private banking of CB
Private commercial CB Banks offer families the opportunity to
store the CB of their baby in case that child or a sibling requires
a CB transplant, or for potential regenerative medicine using CB
as a source of multipotent stem cells. The chances of using the CB
for a haemopoietic transplant are extremely low. Larger cell doses
could be obtained from BM from that child at the age of 1–2 years.
The scientific and ethical justification for private banking has been
questioned. An opinion paper in June 2006 from the Scientific Advi-
sory Committee of The Royal College of Obstetricians and Gynae-
cologists (RCOG) recommended that all NHS Trusts or hospitals
develop policies responding to parents’ requests for private storage
of CB. If private collection of CB is permitted, there should be:
• full recovery of economic cost to the NHS
• no alteration to the ‘usual management’ of the third stage
(­itself not uncontroversial)
• ex utero collection by a trained third party (not the attending
Obstetrician or Midwife)
• collection, testing, processing and storage in accordance with
the 2006 European Tissues and Cells Directive.
Future uses of CB and other obstetric-related tissue
CB and/or cord Wharton’s jelly in regenerative medicine
CB contains very small numbers of mesenchymal stem cells
(MSCs). MSCs are present in much greater numbers in the cord
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 18:3
matrix (i.e. Wharton’s jelly) with great expansion potential,
ability to migrate to sites of tissue injury, and strong immuno-
suppressive properties. They can differentiate into various cell
types (Figure 1). Animal studies showed improved cardiac func-
tion when CB stem cells were infused post-myocardial infarc-
tion. Other sources of stem cells have been tested, including
skeletal myoblasts, BM, endothelial precursors and resident car-
diac stem cells. MSCs appear more promising for regenerative
medicine, but few are present in adult BM, and their number
and plasticity decrease markedly with age. Cord matrix can be
used as a source of MSCs by mincing the cord after removing
the CB vessels.
After expansion, MSCs infused into the coronary artery asso-
ciated with the myocardial infarct differentiate into cardiomyo-
cytes, smooth muscle cells and endothelial cells. Several studies
have demonstrated improved cardiac function in patients. In neu-
rological disease, animal studies showed improved performance
in rats with brain ischaemia and a rat model of Parkinson’s dis-
ease after BM and MSCs were infused. Ex vivo-expanded MSCs
transplanted into patients with amyotrophic lateral sclerosis pro-
duced a mild slowing of disease progression; further studies in
neurological disease are in progress.
Allogeneic MSCs are being used in studies of patients under-
going BM/PBSC or CB transplants to see if they improve hom-
ing of HPCs within the marrow to accelerate engraftment. They
are being trialled as a modulator of graft-versus-host-disease
(GVHD), a severe complication of allogeneic HSC transplants.
Some studies have suggested a reduction in GVHD with co-
­infusion of MSCs with HSC. Autologous MSCs have been used
successfully in several studies to delay rejection of skin grafts.
Overall, using non-HSCs for regenerative medicine and immu-
nomodulation appears promising (Table 2), but it is unclear
which source of such cells are preferred. They have the potential
for transmission of donor infections, severe allergic reactions and
serious compromising of the recipient immune system; robust
controlled clinical trials to assess their safety and efficacy are
needed.
Ethical issues relating to banking of CB
CB banking is associated with ethical issues fully discussed in the
literature and summarized below.
Informed consent
To give informed consent, the mother must receive relevant
­information about:
• the risks and benefits of donating CB
• microbiological and other testing of her blood to prevent
­disease transmission by the donated material
• storage, future clinical or research use
• discard of the unit if unsuitable for use.
 Information is also needed on the mother’s health and behav-
ioural risk.
Donation of CB for public use should be voluntary and unpaid
to minimize the chance of mothers failing to disclose relevant
information. Mothers must understand that they will be informed
of testing results with current or future implications for their or
their baby’s health. Permission to store samples for future testing,
including tests for emerging infections, is also relevant. Donor’s
77 © 2008 Elsevier Ltd. All rights reserved.
 Ethics/education

Multipotent adult progenitor cells

Mesenchymal Endothelial progenitor Haemopoeitic

stem cells (MSCs) for cells (EPCs) stem cells (HSCs)

Bone Fat Cartilage Muscle Neural cells Endothelial cells Blood: red cells,
white cells, platelets etc.

Figure 1 Origin and potential differentiation pathways of mesenchymal stem cells.

details are not provided to the recipient or their medical team.
The donation is identified only by a unique identification number
to ensure confidentiality and donor privacy. Mothers cannot be
approached once in active labour to ensure informed consent
is given willingly. A recent change in European law has meant
that CB cannot be collected provisionally and then discarded or
stored according to the mother’s subsequent decision.
Informed consent does not entirely protect mothers and CB col-
lectors from potential criticism regarding ethics. If CB collection
or practices associated with it (e.g. very early clamping) had a
definite adverse effect on the newborn infant, no amount of fully
informed consent would trump the ethical principle of ‘first of all,
do no harm’. There is an obligation to act in the best interests of
the baby, though the relative risks and benefits must be balanced.
Ownership of donated CB
Permission for donation is obtained from the mother because she
is the assumed owner and the person making healthcare decisions
on behalf of the baby. A public CB Bank stores the CB for potential
use for transplanting any patient in need. Could the mother or the
infant have a future claim on their own CB for use in later life, per-
haps even decades later, even through it was voluntarily donated
and entrusted to the CB Bank for the benefit of others? If a sibling
needed a transplant and that CB unit were the best match and had
not already been used, then it would be released for the sibling’s
use. If the mother or infant donor of the CB unit wanted to reclaim
it, their ownership versus the ownership of the CB Bank would
be questionable. It could be argued that the CB Bank is in ‘legal
possession’ of the donation, while the ‘owner’ would remain the
donor. Banks may be obliged to comply with requests for return
of CB and it is unclear who would be the ultimate owner if the
mother and child held different views.
CB banking: public versus private
Ethical concerns regarding the private banking of CB relate to com-
mercial pressure and the fine line between advertising and deceit.
• Is the information given in leaflets and websites and sub-
sequent discussion on the telephone honest and fully truthful
about the benefits and risks of CB collection?
• Is the future uncertainty about treating a range of diseases
explained?
• Are vulnerable parents (and grandparents) convinced that
they have to pay to store CB (referred to in some promotional
literature as ‘the gift of life’) to be good parents?

Uses and sources of non-haemopoeitic stem cells

Uses of non-HSCs Indication Source of expanded non-HSCs

Regenerative Cardiac: post infarct; intracoronary artery infusion; Bone marrow stem cells or MSCs and
endothelial cells
Neurological: amyotrophic lateral sclerosis (infused into Bone marrow MSCs
surgically exposed spinal cord)
Degenerative retinal disease: animal studies promising Cord tissue MSCs

Immunomodulatory–allogeneic Improved homing of HSC by MSCs Bone marrow

Reduce GVHD post-allogeneic HSC transplant (MSCs infused Bone marrow
the same time as HSC transplant)

HSC: haemopoeitic stem cell; MSC: Mesenchymal stem cell; GVHD: Graft versus host disease.

Table 2

OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 18:3 78 © 2008 Elsevier Ltd. All rights reserved.
 Ethics/education
 There is no firm evidence to support the claims for most of the
degenerative diseases cited. Autologous CB transplantation for
acute leukaemia is rare; pre-leukaemic mutations have been
found in CB of patients who later developed leukaemia. The stor-
age of CB for a sibling who by chance develops leukaemia is of
limited benefit because transplanters could harvest larger collec-
tions of BM or PBSC from the sibling than from CB.
Private Banks rarely use their own staff to make collections:
the cost of collection falls on the NHS. This could be resolved
by a charge levied by the NHS and passed onto the consumer.
Of greater concern is that the Midwives or Obstetricians have
a conflicting role if pressurized by the parents (as consumers
or clients) and could theoretically be distracted from caring for
the mother and baby (their patients) at a time of significantly
increased clinical risk immediately post-delivery. Ideally, a third
party collector is required (possibly provided for by the NHS, but
paid for by the private Bank). It is not always clear what would
happen to a privately stored CB unit if the company ceased to
operate.
If private CB banking for families’ own personal use were to
increase prolifically, public Banks could be deprived of dona-
tions, lessening the chances of patients finding suitable matches.
Rampant private commercialization could have an adverse effect
on collective ‘goods’. Fewer babies, children and adults (whom
we should all care about to some degree as a society) will be
helped if donations are limited to use within families rather than
being freely available within a wider group (a country or even
the whole international community because finding matches
requires global collaboration). Several European countries have
recommended that, while private CB Banks are legally permit-
ted, public CB Banks should be actively promoted. Italy banned
private banking of CB in 2002.
Early cord clamping
Early clamping has been widely practised (albeit without proper
assessment of harm or benefit), along with uterotonic prophy-
laxis and controlled cord traction, as part of active management
of the third stage of labour to reduce the risk of post-partum
haemorrhage. There is no evidence that early clamping per se
contributes significantly to reduction in maternal risk. If the cord
is left unclamped, ∼19 ml/kg birthweight of blood is transfused
to the neonate (equating to 21% of the final blood volume of
the neonate); 75% of this occurs within the first minute after
birth. The immediate haematocrit and neonatal iron stores are
increased; the average haemoglobin increases by 1.1 g/dl at
4 months of age. This is more important in countries where anae-
mia is endemic. Iron-deficient anaemic infants have poorer men-
tal and motor development. There is no evidence of increased risk
from neonatal polycythaemia or jaundice from delayed clamping.
Late clamping reduces the volume left in the placenta, and cell
count available for CB collection, but the overriding principle for
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 18:3
public CB Banks is that the wellbeing of the mother and baby are
paramount, and cord clamping should comply with local hospital
policy and evolving data. ◆
Further reading
Armitage S, Warwick R, Fehily D, Navarrete C, Contreras M. Cord
blood banking in London: the first 1000 collections. Bone Marrow
Transplant 1999; 24: 139–45.
Braude P, Minger SL, Warwick RM. Stem cell therapy: hope or hype?
BMJ 2005; 330: 1159–60.
Directive 2004/23/EC of the European Parliament and of the Council
of 31 March 2004 on setting standards for quality and safety
in the donation, procurement, processing, preservation, storage
and distribution of human tissues and cells. Official J Eur Union
L 102/48; 07/04/2004.
Eapen M, Rubenstein P, Zhang M, et al. Cord blood transplant vs. bone
marrow in paediatric acute leukaemia. Lancet 2007; 369: 1947–54.
Giordano A, Galderisi U, Marino R. From the laboratory bench to the
patient’s bedside: an update on clinical trials with mesenchymal
stem cells. J Cell Physiol 2007; 211: 27–35.
Puigolomenech Rossell P, Virt G. Ethical aspects of umbilical CB
banking. Opinion of the European group on ethics in science
and new technologies to the European Commission 2004.
http://Europa.eu/european_group_ethics/docs/avis19_en.pdf
Royal College of Obstetricians and Gynaecologists Scientific Advisory
Committee. Opinion Paper 2, June 2006.
Sarugaser ER, Lickorish D, Bash D, Hosseini M, Davies JE. Human
umbilical perivascular (HUC PV) cells: a source of mesenchymal
progenitors. Stem Cells 2005; 23: 220–9.
Schoemans H, Theunissen K, Maertens J, Boogaerts M, Verfaillie C,
Wagner J. Adult umbilical cord blood transplantation: a
comprehensive review. Bone Marrow Transplant 2006; 38: 83–93.
Weeks A. Umbilical cord clamping after birth. BMJ 2007; 335: 312–3.
Practice points
• Cord blood is a useful source for transplantation of
haemopoietic stem cells. The UK Royal College of Obstetricians
and Gynaecologists strongly support the concept of public
banking of cord blood for altruistic donations.
• Early cord clamping is probably detrimental in babies at risk
of iron deficiency anaemia or who are premature. Collection
of cord blood and cord clamping should comply with the
local policy of the hospital.
• When private collection of cord blood is undertaken, it
should be collected ex utero, by a trained third party, with
full recovery of economic cost.
79 © 2008 Elsevier Ltd. All rights reserved.