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Consider the Source: An interview with Cord Clamping Researcher, Judith Mercer

November 17th, 2009 by avatar

Consider the Source is a new series of interviews with prominent researchers working to improve the health outcomes of women and infants around the time of childbirth.

A member of the faculty at the University Rhode Island, Judith Mercer, PhD, CNM, FACNM, is the Principal Investigator on a randomized controlled trial at Women & Infants Hospital examining the effects of delayed cord clamping on outcomes of preterm, very low birth weight babies. She and her multi-disciplinary research team reported short-term outcomes in 2006 in the journal Pediatrics, and outcomes of infants at 7 months of age appear in an upcoming issue of the Journal of Perinatology.

2ndLeveldo_badge1Dr. Mercer graciously agreed to be the first to participate in our Consider the Source series, answering questions about her research in honor of National Prematurity Awareness Month and the March of Dimes’ Bloggers Unite to Fight for Preemies Event. I especially appreciate Dr. Mercer’s research journey because it started with her observations of physiological birth. Her quest to more deeply understand normal physiology led her to improve care for sick and high-risk babies.  Lamaze International would like to express our gratitude to Dr. Mercer, her research colleagues, and her collaborators at Women & Infants Hospital.

Science & Sensibility: You have studied how timing of umbilical cord clamping affects health outcomes in preterm infants. What compelled you to study this?

Judith Mercer: In 1975, I vividly remember reading Frederick Leboyer’s book Birth Without Violence in which he advocates not cutting the umbilical cord until the infant has successfully completed her transition between her two worlds – the fetal world of water and placental respiration and the neonatal world of air and breathing. He says “For a few minutes the baby straddles two worlds…then, slowly, slowly she can cross the threshold from one to the other peacefully and easily with safety…as long as we don’t interfere [by premature clamping of the cord].”  I adopted the practice of delaying cord clamping to ensure a more gentle birth and have used it for more than 30 years.

I had an epiphany at a home birth in 1979. An infant was born very rapidly with the cord 2 and 1/2 times around his neck. He was as pale as the white sheet his mother had on her bed and limp and breathless. I was very afraid that I would not be able to resuscitate him.  I placed him on the bed and immediately unwrapped the cord from around his neck and dried and stimulated him with no response. His heart rate was well over 100 and the cord was pulsating vigorously.  I noticed that his color was changing from the pale white to pink as his body gained the blood back into it. His heart rate was always over 100. In about 1 and 1/2 minutes, he flexed his extremities, opened his eyes and took a gentle breath.  He looked at us like “What is the fuss?” and never cried.  I tried as hard as I could to get him to cry as I believed at that time that he should do but I could not get him to.  He nursed very well and was a normal child at one year of age when I last saw him.

I knew that I had seen a miracle and one that I would never have seen in the hospital.  In the hospital, we would have cut the cord and taken the infant to a warmer to resuscitate him. In doing so, we would have denied him exactly what he needed – the opportunity for the blood squeezed out of him in the birth process due to the tight cord around his neck to flow back into his body.  This event marked the beginning of my research career.  I vowed that at some point in my life I would research what I had seen but did not fully understand.

So it was my personal clinical experience that lead me into my area of research. When I began to ask colleagues and other practitioner about their cord clamping practices, I found a wide variation in practice and beliefs. When I turned to the literature, I found a general lack of evidence-based recommendations for cord clamping practice. All appeared to be opinion-based or based on flawed or inconsistent research findings. Yet, at the same time, I noticed that the etiology of many newborn problems was not known and remain unknown today.  The symptoms are often the opposite of what happens when one delays cord clamping. I also noticed that these problems rarely occur in settings where the infant has a normal physiologic transition. I wondered if immediate cord clamping may be causing some of these problems.

After midwifery jobs with no opportunity to do research, I joined the faculty at the University of Rhode Island where Dr. Margaret McGrath, a well-funded nurse-scientist, offered to mentor me.  She introduced me to Dr. William Oh at Women and Infants Hospital who agreed to sponsor me. With their excellent support, I was able to build my research program.

In 2001, I published an integrative review of the literature on delayed versus immediate cord clamping and found many controlled trials demonstrating beneficial effects of delayed clamping in both term and preterm babies. These included increased blood volume of up to 40%, reduced likelihood of anemia, increased blood flow to vital organs and higher body temperatures in the delayed clamping groups. None of the studies demonstrated harm from delayed clamping and none replicated findings from a poorly-controlled – but often cited – study done in the 1960’s that showed more jaundice and polycythemia in infants with delayed clamping.

At URI, I developed, with a colleague from Rochester, NY,  the Blood Volume Model for Neonatal Transition and published Neonatal Transitional Physiology: A New Paradigm.  While theoretical, it is entirely based on solid research from many different studies. We sought to develop a cohesive theoretical model that explained the relationships among oxygen transport, red blood cell volume, and initiation of breathing, and predicted the effects of early versus delayed cord clamping. We think that in the first one to two minutes, blood plays a larger role in physiological transition than air and that interrupting the process can harm the infant.

Judith Mercer, DNSc, CNM

Judith Mercer, PhD, CNM

Based on these findings, my colleagues at URI, collaborators at Women and Infants Hospital, and I decided to do a pilot randomized controlled trial of delayed versus immediate cord clamping in babies born between 24 and 32 weeks. We had funding from the University and our local chapter of Sigma Theta Tau. We chose to focus on preterm infants because these infants have many problems after birth.  Prevention or reduction in the occurrence of any of these problems would make a huge impact.  Also, the preterm infants are followed very closely in our developmental follow-up clinic so we could examine their outcomes in a cost-effective manner.

Doing a small pilot allowed us to test the feasibility of a larger trial, develop an appropriate protocol and determine how many mothers we would need to recruit in the larger trial. Our study design proved feasible and findings were promising. We did not detect any harms of delayed clamping and the 16 babies in the delayed clamping group had higher blood pressure, higher initial blood glucose, and were less likely to be discharged on supplemental oxygen. With these initial findings, we were able to secure funding from the National Institute of Nursing Research for a larger clinical trial.

Science & Sensibility: How did you design the randomized controlled trial? What were your findings?  Were there any surprises?

Judith Mercer: All women admitted to Women and Infants’ Hospital between 24 and 31.6 weeks gestation with symptoms of preterm labor were candidates for inclusion in the study.  From these women, 72 very low birth weight (VLBW) infants were delivered and represent the sample. Since gestational age is a major risk factor for preterm infants, we used block stratified randomization to assign the intervention to the subjects above and below 28 weeks with a pre-specified equal probability to help avoid unequal numbers of participants in each gestational age group as the study progressed. Exclusion criteria included: obstetrician’s refusal to participate, prenatally-diagnosed major congenital anomalies or multiple gestations, intent to withhold or withdraw care, frank vaginal bleeding or placenta abruption, placenta previa. Women had to be admitted to the hospital at least 2 hours before delivery to allow time for screening enrollment.

Just prior to birth, eligible patients were randomized to receive either standard care (immediate cord clamping (ICC)) or the intervention (delayed cord clamping (DCC)). For the standard care group, the obstetrician clamped the umbilical cord immediately (< 5-10 seconds) For the intervention group, the obstetrician clamped the cord at 30 to 45 seconds and held the infant in a sterile towel or blanket approximately 10-15 inches below the mother’s introitus or incision.  Care was taken that no tension or traction was placed on the cord. A stopwatch was used to mark the time of birth and then the time elapsed was counted out in ten second intervals to the obstetrician.  At 30 to 45 seconds, the obstetrician clamped and cut the umbilical cord, and the infant was moved to the warmer for neonatology management.

If the baby appeared jeopardized in any way, the obstetrician could alter the protocol for the safety of the infant and a protocol violation form was completed although no protocol violations occurred because of an infant’s appearance.  The subsequent clinical management of the infants was at the discretion of the neonatologists. Because of the obvious nature of the intervention, the study could not be blinded to those at the birth.  Due to safety considerations for the infant, pediatric staff was always in attendance.  However, staff who attended each birth adhered to the principal investigator’s request not to reveal the infant’s grouping in the infants’ medical records.

Research assistants who were registered nurses and the Principle Investigator (PI) shared an on-call schedule to screen potentially eligible women, enroll them, or attend the births of enrolled women. Women had equal probability of assignment to the groups.

The primary outcomes we considered, based on our previous research and that of other researchers, were oxygen use at 36 weeks gestational age and suspected or confirmed necrotizing enterocolitis (NEC). We found no statistically significant differences between the groups in these primary outcomes. But additional planned data analyses revealed the most exciting findings.  Infants in the delayed cord clamping group were found to have fewer incidences of any level of intraventricular hemorrhage (IVH) defined by the reports of cranial ultrasounds routinely ordered during the first 28 days in the NICU.  The incidence of IVH was equally divided between the stratified groups (ICC 7/7, DCC 2/2) although the majority occurred in infants less than 30 weeks gestation.  One infant in the DCC group was a protocol violation, meaning that the cord was clamped prior to 30 seconds in violation of the study protocol. In addition, infants in the DCC group were less likely to have blood culture-proven (confirmed) sepsis during the NICU stay.

For our follow-up study, we saw surviving babies at an average age of 7 months corrected age at our clinic. Trained, certified psychologists administered a validated test for motor and mental development, known as the Bayley Scales of Infant Development-II (BSID-II).  A physician or nurse practitioner also conducted a complete medical history and physical examination. The staff was masked to the assigned study groups. In this phase of the study, we found no overall differences in the BSID scores between the DCC and ICC groups. However, after controlling for several factors, male infants in the DCC group had higher motor scores. Preterm male infants are known to be at higher risk for mortality and developmental delay than female infants, a phenomenon that is not well understood. Our study suggested that delayed cord clamping may be protective against motor delay in preterm male infants.

Science & Sensibility: Immediate cord clamping is the standard of care and is stubbornly defended despite a growing body of evidence of its harms. Did the attitudes of care providers or other staff get in the way of the conduct of your study? Have attitudes changed at your facility since the study began?

Judith Mercer: Due to the excellent cooperation of the obstetricians, fellows and residents, there were only 7 protocol violations.  Six occurred in the DCC group with cord clamping time and were mainly as a result of miscommunication.

This study was a Phase I trial. Phase I trials are generally small and test the safety of a particular intervention. Institutional changes are not usually instituted on the basis of outcomes from a Phase I study.  We used the information gained from this study to design a Phase II study which tests the protocol on a much larger group.  We were awarded a $2.5 million dollar grant from NIH, National Institute for Nursing Research, to carry out this study which is now underway.  Our sample size is 212 infants and we are current almost half-way through. To determine the mechanism of effect, we will measure red cell volume, cytokines, and stem cells, each of which may play a role. We expect that this trial will confirm our findings and we hope it will also help us understand why IVH is more common with immediate clamping.

Science & Sensibility: What other research is needed to improve transitional care of newborns? What studies are you hoping to conduct next?

Judith Mercer: In addition to our Phase II trial, a group of Australian neonatologists and others is beginning a large government-funded multi-center trial on delayed cord clamping in preterm infants.  I serve on there advisory board.  They plan to publish a meta-analysis of their data, my data, and any other data generated in the meantime.

My colleague, Dr. Debra Erickson-Owens and I plan to submit a proposal to fund research on term infants in the near future. Well designed trials and meta-analyses have documented more anemia of infancy at two and three months in full-term infants with immediate cord clamping. Betsy Lozoff, MD, at the University of Michigan has documented a relationship between anemia and poorer developmental outcomes in several publications displaying her body of work. She had found that perinatal iron deficiency harms the developing brain in animal studies interfering with the myelination that must take place in the first few months of life for the brain to develop fully. She was able to demonstrate poorer behavioral and developmental outcome (10 points less IQ when controlling for confounding variables) more than 10 years after treatment for iron deficiency in infancy. She also found evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo in that they had delayed maturation of auditory brainstem responses. These findings raise concern about possible adverse developmental and behavioral effects from immediate cord clamping, but no one has studied these effects, which we are planning to do. As with the preterm study, we plan to conduct a pilot study on full term infants and, later, a funded full study.

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  1. November 18th, 2009 at 10:51 | #1

    What a great study and post!

    I can’t wait to see the outcomes in the larger sample. I am glad this got NIH funding.

    I thought the story about the home birth baby with the cord issue and reperfusion was a chilling story. I am facing a future of being a practitioner in hospital based births, and I will keep that in the back of my mind. I hope I can influence decisions that are made some day in similar situations in the medicalized, non physiological birth setting.

    So, I have a question about the protocol. How did you decide to position the infant 10 to 15 inches below the introitus or incision? The research I did on delayed cord clamping in the past (Consider the Source, however, *wink*, since it was no way as complete as the literature review done prior to this study) seemed to indicate that positioning the baby that far below was asking for those elusive, possibly non-existent complications of overperfusion, like polycythemia, jaundice, etc. But, they may have been people repeating myth rather than data.

    So, the evidence against a lower level may not be good. However, isn’t it more logistically difficult, in most circumstances, to put the newborn a foot below the introitus that say, five inches? I am not sure about an incision. I would guess even then an entire foot below may be difficult than whatever the distance is to the bed. Also, can’t you be limited by cord length? What was the justification for that part of the protocol?

    Can I also say that this is the perfect example of the epitome (in my mind) or participatory medicine and the meta-world between pure scholarly medicine and blogging. Birth activism that leads to changing protocols may need to come in the form of published, peer reviewed research. But, individual anecdotes like the one about the white, limp baby in the bed making med students like me sit up and listen may be just as important for changing attitudes.

  2. November 18th, 2009 at 11:19 | #2

    Fascinating research, and I am eager to see the results of the next phase.

    Do you anticipate providers raising any objections to applying these recommendations to full-term infants? Since your study dealt with premature babies, it would be interesting if someone would attempt to replicate the study in term infants, and see if outcomes are similar.

    I also questioned how you arrived at the 10-15 inches below the introitus protocol. It seems if we are attempting to use physiological birth as the model, a mother giving birth without directives from providers would likely be in a squatting or kneeling position, then sit back and pick the baby up. When I have observed undisturbed and undirected births in my birth center and at home, I saw this behavior many times. The mother initially sits back in somewhat of a cross-legged position and holds the baby on her lap, looking at it and stroking it. This puts the baby approximately level with the placenta.

    I wonder if it’s necessary to put the baby lower than the introitus? As long as the cord is still pulsating, wouldn’t the pressure continue to circulate blood to the newborn, regardless of positioning?

  3. November 18th, 2009 at 11:34 | #3

    10-15 inches is based on Alice Yao and other early work. With preemies, that is about as long the cord is.

    In the most recent meta-analyses (Hutton and Hasson 07), the polycythemia and jaundice did not appear to be an issue. I think many people who do delayed cord clamping also do skin-to-skin so the baby goes up on the abdomen. That is OK as long as the cord is not cut for any reason. If the infant “crashes’, it should be lowered with intact cord and resuscitated at the perineum. That is going to take some time. We are in the process of writing for an RO1 grant to study the issue in term infants.

    On my website there is a 2002 review of the literature that deals with each issue. Am working with a doctoral student right now to update and publish a 2010 version of that.

    Thank you for your thoughtful responses. Hope I have answered your questions.

  4. November 18th, 2009 at 13:44 | #4

    On behalf of the March of Dimes, thanks to Lamaze and Dr. Mercer for participating in Prematurity Awareness Month. Very interesting discussion of the topic and the research.

    With best wishes,
    Pam
    March of Dimes

  5. avatar
    Lisa
    November 18th, 2009 at 20:57 | #5

    I’ve always been baffled by the medical tendency to cut the baby’s oxygen/blood supply when they’re slow to start. It seems extremely counter-intuitive.

    I’m curious what made you decide on 30-45 seconds as ‘delayed’. I would think at least a full minute, or even 2 minutes, with the baby skin to skin would give even better results. Is leaving the cord longer, possibly even until it stops pulsing, a possibility for future study?

  6. November 18th, 2009 at 22:42 | #6

    As a NICU nurse I find this study absolutely fascinating. The preliminary finding of less IVH in the DCC preemies is intriguing. IVH is thought to be caused by the very immature/non-existent auto-regulation functions in the extremely premature infant. Maybe cutting that cord early causes a huge increase or variation in the infant’s blood pressure, thus causing bleeding within the brain. Just a thought.

    I am curious to know if the fetal strip plays any role in the exclusion criteria of the study, and if a cord gas is taken. Can’t wait to hear more.

  7. November 19th, 2009 at 19:43 | #7

    I am so thankful for you and your research. This is so important and it makes so much sense that the baby is being squeezed and therefore needs time to allow the blood to flow back into the baby’s body via the umbilical cord.

    I agree with Lisa- it makes no sense that the cord should be cut immediately for a baby that is compromised or slow to start. Why cut off a baby’s oxygen supply?

  8. November 20th, 2009 at 10:55 | #8

    @Elizabeth Morrison
    “it makes no sense that the cord should be cut immediately for a baby that is compromised or slow to start. Why cut off a baby’s oxygen supply?”

    I think it is important to differentiate what “compromised” is when deciding whether to cut the cord immediately or not. In the example Dr. Mercer gave, I would not have considered that baby compromised with a heart rate of 100, even if he was initially apneic at birth. That baby had great reserve and was just a little “shell-shocked” so to speak.
    Some babies however become compromised due to a severe asphyxia and hypoxemia in utero. It would serve no benefit to keep that oxygen deprived blood flowing to these infants with the cord attached, and it would be dangerous to delay ventilation in these infants.

    Premature infants often are not compromised at delivery and have good heart rates and some attempts at ventilation. That’s why I find Dr. Mercer’s research so interesting in DCC for these babies. It sounds like such a gentle way to bring these fragile infants into the world.

    Great discussion!

  9. November 21st, 2009 at 08:44 | #9

    @RealityRounds I think that the causes of IVH are multifactorial but definitely having a stable blood volume, not interrupted at the time of birth, could play a role in prevention. We think that three factors are important: blood volume loss which may contribute to cardiovascular instability and loss of autoregulation; poorer perfusion of all tissues -especially the fragile germinal matrix; inflammation secondary to blood loss (pro-inflammatory cytokines); and loss of hematopoietic stem cells to heal the site of damage. These are discussed further in our paper. The pdf of the article is at my website, cordclamping.info.

    I don’t think the fetal strip plays much of a role. It is amazing how good these little guys are at birth–by about the third day they are challenged.

    @Lisa We chose 30-45 seconds based on earlier literature and because we thought that it was about all anyone could stand for the very little ones.

  10. November 22nd, 2009 at 09:04 | #10

    This is a great post. I appreciate the fact that you included so much background into study design, etc.

  11. November 22nd, 2009 at 15:06 | #11

    I’ve been meaning to read this for days and am glad I finally did. Fascinating.

    I, too, was very curious about the 30-45 seconds. I was really surprised that such a short time was considered “delayed”. When my daughter was born, it had to have been at least 10-15 minutes, possibly even more (time is a wee bit fuzzy for me here). The placenta had been delivered by then. It’s amazing that a few SECONDS could make a difference!

    Is there any research on what might be *too* long? Would you consider researching this, if not?

  12. December 1st, 2009 at 09:39 | #12

    @Reality Rounds

    I think the issue is why the baby is oxygen starved. If its because of cord compression, demonstrated by deep variable decellerations in the active and second stage, I would think that once the cord is unwrapped it will be excellent and delivering oxygenated blood to the baby, and that letting baby pump some blood through the cord and placenta would be a great idea! If the baby is hypoxic because of chronic uteroplacental insufficiency or abruption, it makes little sense to pump extra blood through that placenta. It still may provide some benefit to the baby to get some blood out of the placenta into the baby, if only for increased oxygen carrying capacity.

    I have often wondered why we clamp the cord on a baby that has a respiratory acidosis secondary to repeated cord compression and variable decels, rushing the baby to the warmer to get blow-by oxygen or even positive pressure ventilation, when the best oxygen delivery device is likely the placenta still in the uterus. This thought is supported by the question “what would happen to all these hypoxic babies without the pediatric intervention? Would they be injured.” Though I am not sure of the answer, I suspect that the natural mechanism of continuing to pump blood through the placenta will naturally resolve the respiratory acidosis and hypoxia quickly.

    Nicholas Fogelson MD

  13. December 1st, 2009 at 10:14 | #13

    Nick, I think you would really appreciate Judy’s article, Neonatal Transitional Physiology: A New Paradigm. It’s the article that made me begin to realize the extent to which we are meddling with a really delicate and important process. She also makes the same point that you do – blood is the only liquid we have available to us that has oxygen carrying capacity. If we chronically deliver hypovolemic babies, and then give IV fluids to those who are hypovolemic enough that they’re symptomatic, we haven’t really fixed the problem.

    You’ve probably heard from reps for cord blood banking companies that cord blood stem cells can be used to treat hypoxic injury. These claims drive me crazy, because it’s ludicrous to deprive the baby of the blood (early clamping is recommended for cord blood banking), send it off to a lab, spin it around in some tubes and such, and then deliver it back to a baby via IV. Seems to me that nature had a pretty good idea about how to repair hypoxic injury in the first place.

    I agree that delayed cord clamping is not appropriate in the presence of known or suspected abruption (and rare other circumstances, such as when there is no palpable pulse in the cord). I know I’ve seen Judy write about this, but I wasn’t able to find it with a quick search through the papers she’s written. Of course, if hypoxic injury is caused by abruption, that would be a situation when replenishment of stem cells may make a lot of sense.

  14. December 1st, 2009 at 10:58 | #14

    @Amy Romano

    Its an interesting and important topic. Its on my list to write about for my blog as well. I’ll review the literature and post what I find, likely similar results.

  15. December 28th, 2011 at 16:41 | #15

    @Amy Romano

    You wrote’…delayed cord clamping is not appropriate…[in] rare other circumstances, such as when there is no palpable pulse in the cord).’

    I am a home birth and birth centre midwife in the UK and have on 3 occasions felt no pulse in a cord immediately after birth only to have it return within about 10 seconds and quickly climb to normal in all three cases. I wonder if anyone else has experienced this and how I might better understand this occurrence? Thank you for all of your work in this area.

  16. November 21st, 2012 at 13:47 | #16

    I am quite bemused by all the fuss and the perceived ‘need’ for so much research. No such studies were conducted before the absurd practice of premature cord cutting was introduced. Clamping becomes a need because the cord is being cut too soon and creates a terrible mess with the blood that should be going into the baby. Once the cord is empty it simply needs to be tied with a bit of dental floss. It is really very simple. We are mammals. No other mammal behaves as we do towards the newborn. They all receive the full placental transfusion as nature has designed. There are laws to protect them from such cruelty. Our Lotus Born babies keep their cords intact until it comes away at the navel naturally 2-7 days after birth. It is a most remarkable.

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