Judith Mercer and Debra-Erickson Owens have found positive changes after a short delay in cord clamping, indicating the benefits of umbilical cord blood
When cord clamping is delayed at birth (DCC), an infant receives a placental transfusion and benefits from a 30% increase in blood volume and a 50% increase in red cell volume, resulting in increased iron stores over the first 6 months of life. Red blood cells hold 80% of the iron in our bodies, making this added volume of red blood cells responsible for the observed increase in iron stores. Thus, DCC results in less iron deficiency in early infancy.
Iron deficiency in infancy has been shown to adversely affect cognitive, motor, socio-emotional, and behavioural development. These first 6 months of life coincide with the most critical period of brain growth and myelin development, during which most of the brain’s eloquent neural pathways are established and refined. Iron is an essential component of myelination which is critical for normal brain development and function.
Mercer and Erickson-Owens decided to take the current research a step further and look at the effect of DCC on brain development and myelination over the first 2 years of life in infants receiving either DCC, or immediate cord clamping (ICC) at birth. They wondered if the higher iron stores from DCC would result in greater brain myelin content at 4 months of age.
Significant positive change in brain myelination
Myelin is a fatty white substance that is wrapped around nerve cells in the brain to form an insulating layer and creates the white matter in our brains. Myelinated white matter is a cornerstone of human neurodevelopment, establishing and maintaining efficient communication pathways across specialised neuronal systems. Iron plays an essential role in the formation of the cells responsible for producing myelin. Animal studies clearly link low levels of brain myelin with iron deficiency and neurodevelopmental impairment. Also, abnormal myelination underlies a variety of childhood developmental disorders, including conditions such as dyslexia and autism, thus making it a key area of study. Through their research, Mercer and Erickson-Owens hope to fill the knowledge gap on the effects of cord clamping time, at this critical and dynamic period of infant neurodevelopment.
“We chose to do this study because a high percentage of babies world-wide are anaemic or iron deficient (ID) by 6 to 9 months of age. Cord blood is an excellent source of iron and is readily available to every infant via placental transfusion at the time of birth. Anaemia and ID in infancy are also associated with decreased cognitive abilities, and behavioural problems. And, there is good evidence for the safety and benefits of DCC.”
After receiving US National Institutes of Health funding, Mercer and Erickson-Owens were joined by Dr Sean Deoni to launch their latest study known as the ‘Infant Brain Study’. Deoni brought expertise in using MRI scanning to examine myelin and normal brain development in infants and children. Normal healthy women delivering at term with healthy foetuses were recruited and randomised to either ICC (within 20 seconds) or DCC (5 or more minutes). [If the provider felt that they could not delay cord clamping, they were instructed to milk the cord 3 to 5 times – a safe alternative to DCC]. At 4 months of age, blood samples were collected and MRI quantitative myelin scans were done with accompanying developmental assessments (within one week of scanning). Currently these researchers are reporting the study’s 4-month MRI scan results and are awaiting the 12 and 24-month results to be finished later this year.
Most of the MRI scans were conducted in the evening so infants could be scanned during natural sleep. Mothers put infants to sleep in a comfortable room and they were then placed on the scanner table and inserted into the MRI scanner. Several techniques – ear covers, special headphones, slowing the scanner, and noise insulation – were used to reduce noise. The imaging times ranged from 20 to 30 minutes. Parents were invited stay in the MRI room or wait outside. If the child woke, mothers attempted to get them back to sleep and the scan was restarted.
Haemoglobin higher after delayed clamping
There were no significant differences between the mothers or infants in each group – an important finding in any clinical trial. Drainage of the placental blood showed that infants who had ICC left about 30% more blood in the placenta. Blood levels of haemoglobin were higher in those infants who received DCC, without any adverse effects. Ferritin levels (a proxy for iron stores) at 4 months of age were higher in the DCC infants, as expected.
There was significantly more myelin content in several areas of the brain in the infants with DCC, compared to those with ICC. Differences occurred in the earliest myelinating brain regions such as the cerebellum, the internal capsules, and the motor cortex. As the infants were just 4 months old at the time of scanning and these are the brain areas that are rapidly myelinating during this stage of development, DCC appears to have a significant impact on myelination across the brain. Thus, placental transfusion (DCC & milking) facilitates the transfer of residual placental blood without adverse effects and supports increased brain myelination at 4 months of age.
Umbilical cord blood contains many millions of stem cells that help to protect the infant
This study, in its fifth year, will be completed in December 2017. Currently, Mercer and Erickson-Owens are awaiting the results of the MRI scans of brain myelin content and parallel developmental testing at 12 and 24 months. They expect differences at 2 years of age when data on young infants is more robust. A Swedish study that reported no differences in development at one year for children who had DCC or ICC at birth, found significantly better outcomes at 4 years in fine motor skills and social-emotional functioning.
Dr Mercer began her research examining DCC for preterm infants as they have the most serious life-threatening problems. In 2006, she reported less bleeding in the brains of infants who had only a brief delay in cord clamping (30 to 45 seconds), compared to infants who had immediate cord clamping. Her work has been replicated by others and these findings are the major reason DCC is being adopted at the time of birth of premature infants. Erickson-Owens joined her in 2005 and added her research which examined umbilical cord milking in term infants. Her study showed that milking the cord at caesarean section was safe and resulted in better haematocrit levels at 2 days of age – a marker of better iron levels later in infancy.
Umbilical cord blood and stem cells
In the future, these researchers plan to explore stem cells in umbilical cord blood. Stem cells augment the infant’s own healing system in ways that may benefit the child not only in infancy but over his lifetime. Umbilical cord blood contains many millions of stem cells that help to protect the infant. If the cord is cut right away, the infant will leave about 80 millilitres of blood, containing approximately 1 billion nucleated cells behind in the placenta. However, both human and animals studies demonstrate the immense healing power of stem cells.
Human umbilical cord blood stem cells, used for transplants in human diseases, are remarkably successful in promoting healing. In the United States and Japan, scientists are extracting stem cells after birth and placing them back into the bodies of infants afflicted with a life threatening condition known as hypoxic-ischemic-encephalopathy. They have had some success in reducing mortality. Mercer and Erickson-Owens believe these precious stem cells should be allowed to transfuse into every infant’s body at the time of birth and that they might help prevent or lessen the severity of this devastating disease. There is, however, a dilemma. The infants who may need their stem cells the most often receive ICC. Current neonatal resuscitation policies demand ICC so that infants can be quickly moved to warming tables, denying a placental transfusion to the very babies who may benefit the most.
To address this problem, scientists in the UK and the US are conducting research on resuscitating infants near the mother with the umbilical cord intact to allow the placental transfusion to continue. In order to examine whether obtaining cord blood at birth would help these infants, a team from Virginia is conducting a large trial in which they will resuscitate preterm infants without clamping the cord. If successful, this will encourage transitioning of all infants with an intact cord.
Umbilical cord blood donation is not the answer
But shouldn’t parents be altruistic and donate their infant’s umbilical cord blood? In 2017, experts still do not know how to prevent most newborn diseases, such as cerebral palsy, hypoxic-ischemic-encephalopathy, and persistent pulmonary hypertension. While some treatments such as head cooling for encephalopathy have improved outcomes, still over half the infants who develop this condition are either permanently disabled or die in their first 2 years of life.
Mercer and Erickson-Owens do not support cord blood donation at this time except in rare cases such as blood for a sibling in need. Instead, they urge scientists to continue to learn how to make the umbilical cord stem cells proliferate or expand in the laboratory so they can be used for transplantation. Some modest success has resulted in reproducing stem cells but they are not yet as potent when transplanted as the stem cells from cord blood. The race to find the perfect medium continues. Even after a long delay in cord clamping, there is still a small amount of blood remaining in the placenta, which could provide many stems cells via successful expansion techniques. Meanwhile, scientists have identified stem cells in the umbilical cord tissue itself, in amniotic fluid, and in the placenta. All of the sources are under intense study to develop them as alternatives to cord blood stem cells.
It is true that the usual obstetrical practice of ICC, a practice lacking evidence-based support, denies an infant up to 50% of its iron rich red blood cells and stem cells. The birth setting can influence the timing of cord clamping. Historically, obstetricians delayed cord clamping in hospital. However, in the middle of the last century there was a major shift to ICC. The shift in practice led to institutional policies and the adoption of ICC which we now know does not benefit the infant’s wellbeing. Many midwives have used DCC throughout history, often in birth centres and home birth settings, but institutional policies often prevent this practice.
Mercer and Erickson Owens are passionate about umbilical cord clamping and present their work nationally and internationally. Their ongoing research supports the idea that DCC (or milking) is a low tech, no cost approach that is valuable for all infants of all gestational ages across the globe.
“Our knowledge about the value of cord blood for infants is akin to what we knew about colostrum fifty years ago when most people thought it did not matter and could be discarded! Now we know of its great value to newborns. All babies can benefit from a placental transfusion.”
Judith Mercer PhD
University of Rhode Island
Tel: +1 401 480 1542
Debra-Erickson Owens PhD
University of Rhode Island
Tel: +1 401 874 5344
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