As a Neonatologist, there is no question that I am supportive of breast milk for preterm infants. When I first meet a family I ask the question “are you planning on breastfeeding” and know that other members of our team do the same. Before I get into the rest of this post, I realize that while breast milk may be optimal for these infants there are mother’s who can’t or won’t for a variety of reasons produce enough breast milk for their infants. Fortunately in Manitoba and many other places in the world breast milk banks have been developed to provide donor milk for supporting these families. Avoidance of formula in the early days to weeks of a ELBWs life carries benefits such as a reduction in NEC which is something we all want to see.
Mother’s own milk though is known to have additional benefits compared to donor milk which requires processing and in so doing removes some important qualities. Mother’s own milk contains more immunologic properties than donor including increased amounts of lactoferrin and contains bioactive cells. Growth on donor human milk is also reduced compared to mothers’ own milk and lastly since donor milk is obtained from mothers producing term milk there will be properties that differ from that of mothers producing fresh breast milk in the preterm period. I have no doubt there are many more detailed differences but for basic differences are these and form the basis for what is to come.
The Dose Response Effect of Mother’s Own Milk
Breast milk is a powerful thing. Previous studies on the impact of mother’s own milk (MOM) have shown that with every increment of 10 mL/kg/d of average intake, the risk of such outcomes as BPD and adverse developmental outcomes are decreased. In the case of BPD the effect is considerable with a 9.5% reduction in the odds of BPD for every 10% increase in MOM dose. With respect to developmental outcome ach 10 mL/kg/day increase in MOM was associated with a 0.35 increase in cognitive index score.
The same group just published another paper on this cohort looking at a different angle. NICU human milk dose and health care use after NICU discharge in very low birth weight infants. This study is as described and again looked at the impact of every 10 mL/kg increase in MOM at two time points; the first 14 and the first 28 days of life. Although the data for the LOVE MOM trial was collected prospectively it is important to recognize how the data for this study was procured. At the first visit after NICU discharge the caregiver was asked about hospitalizations, ED visits and specialized therapies and specialist appointments. These were all tracked at 4 and 8 months of corrected age were added to yield health care utilization in the first year, and the number of visits or provider types at 4, 8, and 20 months of corrected age provided health care utilization through 2 years.
What were the results?
“Each 10 mL/kg/day increase in HM in the first 14 days of life was associated with 0.26 fewer hospitalizations (p =
0.04) at 1 year and 0.21 fewer pediatric subspecialist types (p = 0.04) and 0.20 fewer specialized therapy types (p = 0.04) at 2 years.” The results at 28 days were not statistically significant. The authors reported both unadjusted and adjusted results controlling for many factors such as gestational age, completion of appointments and maternal education to name a few which may have influenced the results. The message therefore is that the more of MOM a VLBW is provided in the first 14 days of life, the better off they are in the first two years of life with respect to health care utilization.
That even makes some sense to me. The highest acuity typically for such infants is the first couple of weeks when they are dealing with RDS, PDA, higher oxygen requirements etc. Could the protective effects of MOM have the greatest bang for your buck during this time. By the time you reach 28 days is the effect less pronounced as you have selected out a different group of infants at that time point?
What is the weakness here though? The biggest risk I see in a study like this is recall bias. Many VLBW infants who leave the NICU have multiple issues requiring many different care providers and services. Some families might keep rigorous records of all appointments in a book while others might document some and not others. The big risk here in this study is that it is possible that some parents overstated the utilization rates and others under-reported. Not intentionally but if you have had 20 appointments in the first eight months could the number really by 18 or 22?
Another possibility is that infants receiving higher doses of MOM were healthier at the outset. Maternal stress may decrease milk production so might mothers who had healthier infants have been able to produce more milk? Are healthier infants in the first 14 days of life less likely to require more health care needs in the long term?
How do we use this information?
In spite of the caveats that I mentioned above there are multiple papers now showing the same thing. With each increment of 10 mL/kg of MOM benefits will be seen. It is not a binary effect meaning breastfed vs not. Rather much like the medications we use to treat a myriad of conditions there appears to be a dose response. It is not enough to ask the question “Are you intending to breastfeed?”. Rather it is incumbent on all of us to ask the follow-up question when a mother says yes; “How can we help you increase your production?” if that is what the family wants>
Much has been written on the topic of cord clamping. There is delayed cord clamping of course but institutions differ on the recommended duration. Thirty seconds, one minute or two or even sometimes three have been advocated for but in the end do we really know what is right? Then there is also the possibility of cord milking which has gained variable traction over the years. A recent review was published here.
Take the Guessing Out of the Picture?
Up until the time of birth there is very little pulmonary blood flow. Typically, about 10% of the cardiac output passes through the lungs and the remained either moves up the ascending aorta or bypasses the lungs via the ductus arteriosus. After birth as the lung expands, pulmonary vascular resistance rapidly decreases allowing cardiac output to take on the familiar pattern which we all live with. Blood returning from the systemic venous circulation no longer bypasses the lung but instead flows through pulmonary capillaries picking up oxygen along the way. One can imagine then that if a baby is born and the cord is clamped right away, blood returning from the systemic circulation continues to bypass the lung which could lead to hypoxemia and reflexive bradycardia. This has been described previously by Blank et al in their paper Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition.
A group of researchers from the Netherlands published a very interesting paper Physiological-based cord clamping in preterm infants using a new purpose-built resuscitation table: a feasibility study this month. The study centres around a resuscitation table called the Concord that is brought to the mother for resuscitation after birth. The intervention here was applied to infants 26 to 35 weeks gestational age. The cord was clamped after each of the following was achieved for an infant indicating successful transition with opening of the lung and establishment of an FRC.
1. Establishment of adequate breathing (average tidal volume ≥4 mL/kg) on CPAP. They used a mask capable of measuring expired tidal volumes.
2. HR above 100 bpm
3. SpO2 above 25th percentile using FiO2 <0.4
In this way, the cord was only clamped once the baby appeared to have physiologically made the transition from dependence on umbilical cord blood flow to ventilation perfusion matching in the lung. Although 82 mothers consented only 37 preterm infants were included in the end. Exclusion criteria were signs of placental abruption or placenta praevia, signs of severe fetal distress determined by the clinician and the necessity for an emergency caesarean section ordered to be executed within 15 min. This really was a proof of concept study but the results are definitely worth looking at.
How Did These Babies Do?
There are many interesting findings from this study. The mean time of cord clamping was 4 minutes and 23 seconds (IQR 3:00 – 5:11). Heart rate was 113 (81–143) and 144 (129–155) bpm at 1 min and 5 min
after birth. Only one patient developed bradycardia to <60 BPM but this was during a mask readjustement. The main issue noted as far as adverse events was hypothermia with a mean temperature of 36.0 degrees at NICU admission. Almost 50% of infants had a temperature below 36 degrees. Although the authors clearly indicate that they took measures to prevent heat loss it would appear that this could be improved upon!
What stands out most to me is the lengthy duration of cord clamping. This study which used a physiologic basis to determine when to clamp a cord has demonstrated that even at 1 minute of waiting that is likely only 1/4 of the time needed to wait for lung expansion to occur to any significant degree. I can’t help but wonder how many of the patients we see between 26-35 weeks who have a low heart rate after delivery might have a higher heart rate if they were given far more time than we currently provide for cord clamping.
I can also see why cord milking may be less effective. Yes, you will increase circulating blood volume which may help with hemodynamic stability but perhaps the key here is lung expansion. You can transfuse all the blood you want but if it has nowhere to go just how effective is it?
As we do more work in this area I have to believe that as a Neonatal community we need to prepare ourselves for the coming of the longer delay for cord clamping. Do we need to really have the “Concord” in every delivery or perhaps it is time to truly look at durations of 3-4 minutes before the team clamps the cord.
As the saying goes, sometimes less is more. In recent years there has been a move towards this in NICUs as the benefits of family centred care have been shown time and time again. Hi tech and new pharmaceutical products continue to develop but getting back to the basics of skin to skin care for many hours and presence of families as an integral team member have become promoted for their benefits. The fetus is a captive audience and hears the mother’s heart beat and voice after the development of hearing sometime between 24-26 weeks gestational age. This is a normal part of development so it would stand to reason that there could be a benefit to hearing this voice especially after hearing has developed and the fetus has grown accustomed to it. Hospital including my own have developed reading programs for our patients and some companies have developed speakers in isolettes designed to limit the maximum decibel to 45 but allowing parents to make recordings of their voices. Music may be played through these speakers as well but today we will focus on the benefit of voice.
Could reading to your baby reduce apnea of prematurity?
This is the question that Scala M et al sought to answer in their paper Effect of reading to preterm infants on measures of cardiorespiratory stability in the neonatal intensive care unit. This was a small prospective study of the impact of parental reading on cardiorespiratory stability in preterm NICU infants. Eighteen patients were enrolled who were born between 23-31 weeks gestation. The study was carried out when the babies were between 8-56 days old at a mean postnatal age of 30 weeks. Each patient served as their own control by comparing episodes of oxygen desaturation to <85% during pre-reading periods (3 hours and 1 hour before) to during reading and then 1 hour post reading. Parents were asked to read or create a recording lasting a minimum of 15 min but up to 60 min of recorded reading. The parents were offered a standard set of books that had a certain rhythm to the text or could choose their own. Recorded reading was played for infants up to twice per day by the bedside nurse. While it was small in number of patients the authors point out that the total exposure was large with 1934 min of parental bedside reading analyzed (range 30–270 min per infant, mean 123, median 94 min). Patients could be on respiratory support ranging from ventilators to nasal cannulae.
Was it effective?
It certainly was. I should mention though that the authors excluded one patient in the end when it was found that they failed their hearing screen. Arguably, since the infant could not have benefited from the intervention effect this makes sense to me. As shown from table 3 there was a statistical reduction in desaturation events during the reading period which was sustained in terms of a downward trend for one hour after the intervention was completed. In case you are asking was the difference related to oxygen use the answer is no. There was no difference in the amount of oxygen provided to patients. While the events were not eliminated they were certainly reduced. The other point worth mentioning is that there appears to be a difference between live (through open portholes) vs prerecorded reading (through a speaker in the isolette).
Now for a little controversy
Does source of the reading matter? The authors found that maternal had a greater effect than paternal voice. As a father who has read countless books to his children I found this a little off-putting. As a more objective critic though I suppose I can buy the biologic plausibility here. I suspect there is an independent effect of voice having a positive impact on development. If we buy the argument though that the voice that the fetus has most been accustomed to is the mothers, then the findings of an augmented effect of the maternal voice over fathers makes some sense. I will have to put my ego aside for a moment and acknowledge that the effect here could be real.
There will no doubt need to be larger studies done to drill down a number of questions such as what is the ideal type of reading, duration, rhythmic or non etc but this is a great start. I also think this falls into the category of “could this really be a bad thing?”. Even if in the end no benefit is shown to this type of intervention, the potential for family bonding with their preterm infant alone I think is cause for embracing this intervention.
It has to be one of the most common questions you will hear uttered in the NICU. What were the cord gases? You have a sick infant in front of you and because we are human and like everything to fit into a nicely packaged box we feel a sense of relief when we are told the cord gases are indeed poor. The congruence fits with our expectation and that makes us feel as if we understand how this baby in front of us looks the way they do.
Take the following case though and think about how you feel after reading it. A term infant is born after fetal distress (late deceleration to as low as 50 BPM) is noted on the fetal monitor. The infant is born flat with no heart rate and after five minutes one is detected. By this point the infant has received chest compressions and epinephrine twice via the endotracheal tube. The cord gases are run as the baby is heading off to the NICU for admission and low and behold you get the following results back; pH 7.21, pCO2 61, HCO3 23, lactate 3.5. You find yourself looking at the infant and scratching your head wondering how the baby in front of you that has left you moist with perspiration looks as bad as they do when the tried and true cord gas seems to be betraying you. To make matters worse at one hour of age you get the following result back; pH 6.99, pCO2 55, HCO3 5, lactate 15. Which do you believe? Is there something wrong with the blood gas analyzer?
How Common Is This Situation
You seem to have an asphyxiated infant but the cord gas isn’t following what you expect as shouldn’t it be low due to the fetal distress that was clearly present? It turns out, a normal or mildly abnormal cord gas may be found in asphyxiated infants just as commonly as what you might expect. In 2012 Yeh P et al looked at this issue in their paper The relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. The authors sampled a very large number of babies over a near 20 year period to come up with a sample of 51519 babies and sought to pair the results with what they knew of the outcome for each baby. This is where things get interesting. When looking at the outcome of encephalopathy with seizures and/or death you will note that only 21.71% of the babies with this outcome had a gas under 7.00. If you include those under 7.10 as still being significantly distressed then this percentage rises to 34.21%. In other words almost 66% of babies who have HIE with seizures and/or death have a arterial cord pH above 7.1! The authors did not look at encephalopathy without seizures but these are the worst infants and almost 2/3 have a cord gas that you wouldn’t much as glance at and say “looks fine”
How do we reconcile this?
The answer lies in the fetal circulation. When an fetus is severely stressed, anaerobic metabolism takes over and produces lactic acid and the metabolic acidosis that we come to expect. For the metabolites to get to the umbilcal artery they must leave the fetal tissues and enter the circulation. If the flow of blood through these tissues is quite poor in the setting of compromised myocardial contractility the acids sit in the tissues. The blood that is therefore sitting in the cord at the time of sampling actually represents blood that was sent to the placenta “when times were good”. When the baby is delivered and we do our job of resuscitating the circulation that is restored then drives the lactic acid into the blood stream and consumes the buffering HCO3 leading to the more typical gases we are accustomed to seeing and reestablishing the congruence our brains so desire. This in fact forms the basis for most HIE protocols which includes a requirement of a cord gas OR arterial blood gas in the first hour of life with a pH < 7.00.
Acidosis May Be Good For the Fetus
To bend your mind just a little further, animal evidence suggests that those fetuses who develop acidosis may benefit from the same and be at an advantage over those infants who don’t get acidemia. Laptook AR et al published Effects of lactic acidinfusions and pH on cerebral blood flow and metabolism. In this study of piglets, infusion of lactic acid improved cerebral blood flow. I would suggest improvement in cerebral blood flow of the stressed fetus would be a good thing. Additionally we know that lactate may be used by the fetus as additional metabolic fuel for the brain which under stress would be another benefit. Finally the acidemic fetus is able to offload O2 to the tissues via the Bohr effect. In case you have forgotten this phenomenon, it is the tendency for oxygen to more readily sever its tie to hemoglobin and move into the tissues.
I hope you have found this as interesting as I have in writing it. The next time you see a good cord gas in a depressed infant, pause for a few seconds and ask yourself is this really a good or a bad thing?
A Mother’s arms are full of tenderness and children sleep soundly in them – Victor Hugo
The NICU is a loud and chaotic place, that can be painful to be in at times. Its hard to get a good nights sleep (especially for the nurses!). When you think about how much our infants are handled and disturbed, poked and prodded, all in almost continual daylight, it’s a wonder they get any sleep.
For normal neurodevelopment the infant needs both active and quiet sleep. Sleep in an infant is divided into REM (active sleep) and NON-REM (quiet sleep). During quiet sleep you see very little movement and a regular breathing pattern, whereas active sleep involves movement with an irregular breathing pattern.
The importance of Quiet Sleep:
• Without it, the infant doesn’t get enough active sleep.
• Provides the infant with a break from the busy NICU environment.
• Lessons the release of glucocorticoids (Increased cortisol can cause neuronal cell death).
• Necessary for brain development.
• Increased quiet sleep = decreased risk of SIDS.
The importance of Active Sleep:
• Active sleep promotes brain maturation (US DHHS, 2003; Mirmiran, 1995).
• Most memory consolidation and learning occurs in this state (Smith, 2003).
• Nerve cell connections are restructured (synaptic plasticity) (Marks et al., 1995).
Due to the NICU environment, the infant ends up having slower sleep organization maturation and with increased cortisol they are more apt to have a disturbed and less restful sleep.
A complete cycle of sleep includes moving from active sleep to quiet sleep and back to active sleep. Full term and preterms >32 weeks postconceptional age will need about 60-70 minutes for a cycle. Infants <32 weeks postconceptional age will need about 90 minutes. So when infants come out for KC, we try to plan for at least that amount of time.
You will see when infants are placed in KC, the infant settles and goes into a deep sleep. To accommodate this, you will need comfortable chairs for the parent and good support for their arms. You also want to make sure they have had something to eat or drink, pumped breast milk, used the washroom and had something for pain if needed. Don’t be surprised if your parent falls asleep as well; oxytocin will end up kicking in (the cuddle hormone) and they often find it hard to stay awake. We also provide warmed blankets for our parents to encourage everyone to get comfortable and rest. Snoring is a common side effect of KC in our unit…
While in KC, the infants have a deep sleep with less arousal and better sleep organization than when not in KC (Ludington-Hoe et al., 2006)
In Scher et al.’s study (2009) they found that infants’ brain maturation was accelerated and brain complexity increased with 1.5 hours of KC/day for 4 days/wk from 32-40wks pma. Enhanced development in five sensory areas of the brain was shown with KC that was not seen in infants who did not get KC (both preterm and full term).
With all the evidence pointing to KC being beneficial for a good night’s sleep, I find it difficult to understand why so many are skeptical of it!
Sleep is that golden chain that ties health and our bodies together – Thomas Dekker