CORD CLAMPINGFor some time it has been known that babies benefit from delayed cord clamping.  I have reviewed the research on it here on EP and it’s pretty clear that delayed clamping is superior, even for preterm babies or babies who need resuscitation there are benefits to keeping them attached to the cord for just 30 seconds.  The main findings on the “benefits” of “delayed” cord clamping (as I mentioned in the aforementioned piece, delayed is really more biologically normal and should be considered as such, with early being the deviation, but as the terminology is so set in our culture I stick with it so people will be able to find this work and just add in this caveat to get people to think) are to do with red blood cells and iron.  Babies get more of each the longer the cord is left intact (until it stops pulsing) resulting in more oxygen to vital organs (via red blood cells) and lower risk of anemia (via iron stores) and these effects have been found to hold even six months later.

But what about beyond the first six months or year?  Once you cross that threshold, is there any reason to believe that there are any differences between early or delayed cord clamping?  Well, researchers from Sweden would have you believe there is according to a new study in JAMA Pediatrics[1].

A group of doctors in Sweden decided to test if there were long-term effects of delayed cord clamping on cognitive, social, and emotional domains.  The theory behind the research stems from the known effects of iron deficiency.  Those low or deficient in iron suffer impaired neurodevelopmental abilities and the administration of iron to those deficient is often met with remarkable improvement in cognitive development and a reduction in behavioural problems.  Although many people are aware of how prevalent iron deficiency is in developing nations, few realize that a sizeable minority of children in developed nations suffer iron deficiency, with estimates ranging from 5 to 25%.  Given the link to greater iron stores in infancy associated with delayed cord clamping, the researchers were interested in seeing if there were even longer term effects given iron’s known relationship to neurodevelopment.

The study was a follow-up to an initial examination of delayed cord clamping in which families were randomly assigned either receive early or delayed cord clamping (it was a randomized clinical trial).  The pregnancies that were included were all full-term, healthy, and uncomplicated and mothers also had to be healthy.  There were 382 children involved in the initial study and 263 completed some portion of the follow-up with full data for 243 children.  There were no differences in response rate between the early and delayed cord clamping groups (from the initial randomization).

The children in the follow-up were all four years of age.  The follow-up tests included a full-scale IQ test (and the subcomponents including verbal IQ, performance IQ, processing-speed, and general language), motor skills (including manual dexterity, posting coins in a box, bead threading, and drawing a bicycle trail), and social-emotional skills as measured by the Strengths and Difficulties Questionnaire, a well-validated measure of these skills (it includes a full-score and subscores for communication, motor skills, problem solving and personal-social skills).  Certain covariates known to influence these abilities were also included (i.e., child sex, parents’ level of education, and child’s age).

Of interest were the number of children below the cut-off scores for the various outcome measures (often based on being in the lowest 15th percentile, though certain measures have their own cut-offs).  There were significant differences between the groups on drawing the bicycle trail, fine motor skills, problem solving, and immature pencil grip, with more children in the early cord clamping failing to reach the cut-off for each of these (all adjusted values).  There were trends towards significance for processing-speed and personal-social skills, again with the early cord clamping group having more children failing to reach the cut-off.  Importantly, when these were examined by child sex there were clear differences.  There were no group differences for girls, but strong differences for boys with the trending scores becoming significant for boys only.

Based on these results, the authors conclude that although the findings were generally similar across the groups, when there were differences, they favoured delayed cord clamping.  With no evidence of harm by delayed cord clamping, the authors suggest that future guidelines take into account the benefits identified herein from a randomized clinical trial.

Question and Answers

What possible questions might people have?  I’ll attempt to answer some here and will update this section if more questions in need of answers are posed where this is shared (and I see them).

How do we know the groups didn’t differ on diet or iron status? 

We don’t.  However, the joy of randomized trials is that you get to assume that because people were randomly assigned, the chance of there being one group with more people of a certain type (e.g., not having a diet rich in iron) is incredibly low.  Not impossible, mind you, but very, very, very low.  It is a risk we are willing to take in research.

What is more of issue is whether there were differences in the group that followed up versus those individuals that didn’t and unfortunately we wouldn’t know which direction the influence lay.  Although there were no differences between those who followed up and those who didn’t in the initial birth data, it doesn’t mean that those who followed up were more or less likely to be experiencing problems (cognitive, motor, or social) with their children.  Unfortunately, you can’t make families follow-up so this is a limitation to any long-term research.

How would this relationship work long-term? 

This is the issue – how do iron stores in infancy influence later iron stores?  The mechanism needs to be examined now that findings have emerged, but the authors hypothesize that one way in which this might work is through a vulnerable period in infancy in which motor skills are developed.  Of note, motor skills were the most influenced in this very low-risk group.  The timing around 6 months to a year has been found in previous studies (and a systematic review) to be a vulnerable period for iron deficiency negatively affecting motor development.  Indeed, there are other studies that have found links between infant iron stores and motor skill deficits years later (specifically looking at either umbilical cord iron or skills at a year and then motor skills at 5-6 years of age) and a link between delayed cc and motor skills in very preterm infants.  Thus, it seems that for motor skills, the sensitive period of development is early enough that cord clamping may have an effect.  It is less clear, however, why there might be behavioural differences.

Why would this relationship emerge only in boys?

It is logical to think that something so biological would have the same impact on boys and girls, but this was not the case herein.  Interestingly, this fits with what we know: Boys notoriously have lower iron stores at birth and in infancy and are at higher risk for iron deficiency.  In this case, the delayed cord clamping had a greater positive effect on boys, likely helping to build up their iron to levels that are more equivalent to what girls are born with.

We live in such a resource-rich nation, why should this matter? 

There are very few nations with as many rich resources as Sweden, where the study took place.  This is definitely a case in which we are looking at one of the lowest risk groups for any problems given the sample (healthy, normal birth coupled with living in a nation that is wealthy and has health care and subsidies and everything else).  Yet the researchers still found differences.  Frankly I feel this highlights the very real positive effects of delayed cord clamping as anyone in a less-than-ideal situation should have even greater effects of delayed cord clamping.  Notably, if we’re honest, few other developed nations have the type of support and equality that exists in Sweden, thus few of us are looking at the same type of accessibility to the resources needed to say we really are “resource-rich”.

Why is delayed cord clamping not the norm if there’s all this research suggesting it’s so good?

I can only speculate here, but speculate I will… Unfortunately, doctors and hospitals are often resistant to change, especially in a culture where birth is “on the clock” so to speak.  Letting things happen naturally takes time and that’s something in short supply of in most developed nations, let along hospitals.  There is also resistance to changing the original theories on why early cord clamping was developed (fear of maternal haemorrhage, higher risk of jaundice, respiratory problems, and polycythemia).  Notably, these risks have all been debunked using research, with the one exception of non-clinical jaundice which was found to potentially be still increased in delayed cord clamping according to the most recent Cochrane report, but was found to be no different from early clamping in another meta-analysis.  From a research perspective, the medial fears are unfounded, though there is the potential for fear of non-clinical jaundice.  Oddly, the benefits of red blood cells and higher iron levels seem to not outweigh this fear.

Hopefully people can catch up sooner rather than later and we can see some more research like this that highlights benefits in order to sway the scales towards evidence-based medicine.

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[1] Andersson O, Lindquist B, Lindgren M, Stjernqvist K, Domellöf M, Hellström-Westas L.  Effect  of delayed cord clamping on neurodevelopment of 4 years of age.  JAMA Pediatrics 2015; doi: 10.1001/jamapediatrics.2015.0358