Am I conflicted?

Posted on 25 August 2015 by Keith Barrington

Are conflicts of interest a big deal?

Although many of us, definitely including myself, think that conflicts of interest are a serious issue in medical and academic medical practice, a recent series of puff-pieces editorials in the previously prestigious New England Journal of Medicine (from now on it will be the PPNEJM) proposed that physicians earning huge income from pharmaceutical companies was really not such a big deal after all.

These pathetic, clearly conflicted, nonsensical editorials in the PPNEJM invented new terms to denigrate those of us who want clarity, transparency and accountability (“pharma-scolds” was one). However, I guess, as someone who wants medical practice to be evidence-based, I should also want CoI responses to be evidence-based. Fortunately that is possible, as a new post in the BMJ blogs , by a lawyer and bioethicist points out

So what is surprising to me in my experience teaching ethics & COIs is how frequently people who (correctly) insist on the significance of following rigorous evidence in terms of clinical practice seem to offer opinions on the effects of COIs that IMO do not sufficiently reflect what the best evidence on motivated bias actually shows.

…the literature shows that relationships between commercial industry and physicians or scientists are extremely likely to influence physician/scientist behavior in a variety of ways. The claim that various barriers to such influence—i.e. individual virtue, institutional management, disclosure—are sufficient to prevent such influence is simply not an evidence based view.

Daniel Goldberg, the blogger concerned, presents a CoI Bingo card, which includes most of the excuses and responses to questions about CoI that are commonly heard.

He also has a blog, which is worth visiting, he has a lot of insights into the evidence regarding cognitive bias, and in particular on “motivated bias”. Evidence that was completely ignored in the PPNEJM editorials that I referred to earlier.

One quote from Professor Goldberg

It is not evidence-based to claim that these kinds of entanglements do not have an influence on our behavior.  They do.  We know that they do.  Across a population of actors subjected to these entanglements, a significant percentage of them will modify their behavior in ways favorable to the commercial entity.

His post on the influence of Coca-Cola on professional recommendations and position statements about sugary drinks is a classic.

Indeed he has a whole series on the issue. One point that he makes repeatedly, and which I wholeheartedly endorse, is that simply revealing conflicts of interest is not enough. Transparency about connections with industry, or other financial conflicts is the absolute minimum that we should expect. Reducing conflicts and their undeniable influence on decision-making and policy also needs to be a priority.

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Politeness pays

Posted on 24 August 2015 by Keith Barrington

Does being rude stimulate people to do better, or does it have adverse effects on performance, and team functioning? And how to prove it on way or another?

This really interesting, innovative paper from a team in Israel has performed an RCT to address the problem. Riskin A, et al. The Impact of Rudeness on Medical Team Performance: A Randomized Trial. Pediatrics. 2015. The authors created 24 NICU teams and arranged for them to receive some comments from a supposed visiting expert from the USA. Half of them included some mildly rude comments, which the team received either just before or midway through a simulated resuscitation of a newborn manikin.

Just before the simulation, to the rudeness exposed group, the “expert” stated that he was “not impressed with the quality of medicine in Israel”. Ten minutes later the simulation was stopped and the participants heard that “medical staff like those observed wouldn’t last a week in his department”. He added that he “hoped that he would not get sick while in Israel”.

The study found substantial negative effects of what they refer to as “mild incivility” on both diagnosis of problems during the simulation and on procedural performance. For example the subjects were much less likely to correctly verify the position of a tube when they had been the target of the rudeness.

They also showed that the rude comments affected information sharing within the team, and on whether the team  members sought help from each other.

I must say I have been exposed to rudeness, sometimes much more direct and biting than the comments in this research, at many times during my career, and have, to be honest, also occasionally been rude to others myself. Sometimes a transient irritation or annoyance can lead to comments or attitudes that are negative and to “incivility”. In a very high stress environment like the NICU, making snarky comments when things don’t go well is a common reaction.

I think that we should all try even harder to avoid such responses, not just because they may hurt feelings and harm morale, but because it actually looks like they can have adverse effects on the medical care that our patients receive.

 

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Growth in the VLBW; could do better!

Posted on 24 August 2015 by Keith Barrington

Among over 300,000 VLBW infants in the Vermont Oxford Network database between 200 and 2013, the weights at discharge were plotted against the Fenton percentiles. Horbar JD, et al. Weight Growth Velocity and Postnatal Growth Failure in Infants 501 to 1500 Grams: 2000–2013. Pediatrics. 2015. To be included, babies had to be hospitalized for between 15 and 175 days. Over the period studied the babies had slightly better growth moving from 11.8 to 12.9 g/kg/day. The number with postnatal growth restriction fell significantly, which means I guess that the NICUs included are doing a better job. But. In the last year of the study, 50% of the babies were discharged with a weight below the 10th percentile, and 27% below the 3rd percentile.

Which is not good. And can be improved.

19.9% of the babies were below the Fenton 10th percentile at birth.

The article defines postnatal growth failure (PNGF) as a discharge weight below the 10th percentile, which I don’t think is quite right. If a child is born on the 2nd percentile and discharged on the 9th percentile, you can’t really call that PNGF. We need a better definition of PNGF.

In our study, which we have presented at PAS, we called PNGF being discharged below the 10th percentile if you were born above the 10th percentile, and your z-score decreased by 0.5 or more. I am not sure if that is perfect either, as a baby born at the 60th percentile who falls to the 15th would not be defined as PNGF by either definition, but probably should be.

About 5 years ago we introduced enhanced nutritional protocols. We have examined and presented our outcomes for 2 years worth of babies under 1300g (therefore at slightly higher nutritional risk than the VON data) of whom 19% were under the 10th percentile at birth (using the same Fenton standards) so almost identical as a percentage to the VON data. When I look at our data using the VON definitions, there were 27% discharged below the 10th percentile and 6% below the 3rd percentile at discharge. Which is a substantially lower proportion than the VON data, but still, I think we can do better.

We also calculated the average change in z-scores (again derived from Fenton’s work) which is probably a better overall indicator of nutrition for the whole group. Our new protocols resulted in a reduction of z-score between birth and discharge of 0.39 compared to a reduction of more than 1 with our previous protocols.

We had 13% infants with postnatal growth failure by our definition. Which is still too high, I think. Also these definitions are based on body weight ; length and head circumference should also be measured (although measuring length accurately is a challenge) as indicators of skeletal growth and body composition. Our babies, with our enhanced nutritional protocols, had a head circumference z score change between admission and discharge of only -0.1, much better than the previous -0.6, but had a length z-score change of -1.5 compared to -1.7.

Continuing to improve these outcomes will probably require an increase in protein intakes; a review of our standards revealed that many babies were receiving less than the 4 g/kg/d of enteral protein for a growing preterm which is now recommended. We are in the process of further enhancing our intakes to try to further increase protein administration, with the hope that a further improvement in length outcomes, and in head circumference, but without an increase in adiposity will result.

Interestingly our enhanced protocols are similar to the standards suggested in a recent review article from Germany. Maas C, Poets CF, Franz AR. Avoiding postnatal undernutrition of VLBW infants during neonatal intensive care: evidence and personal view in the absence of evidence. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014. The main difference between their recommendation to start breast milk fortification at “no later than 100 mL/kg/day” and or protocol which starts when the babies receive 25 mL/day (which we chose so as to prepare a whole days feeds with at least one sachet of fortifier, and not throw away breast milk). That review article quotes 5 studies which all had good growth outcomes, and were all quite similar to our results, meaning I think that just about any NICU should be able to achieve similar nutritional/growth outcomes.

 

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Choosing Wisely

Posted on 13 August 2015 by Keith Barrington

Many of you will have heard of the “Choosing Wisely” campaign, an attempt to improve decision making, by clarifying efficacy and risks of common procedures or therapies. Many specialty societies have come up with lists of the Top-5 questionable practices that should be reconsidered. The AAP has just published a list of 5 neonatal practices that they say should be avoided. It is interesting that some of the other societies have made very clear recommendations to not do certain things (“Don’t do….” a particular test, for example). The AAP list instead states to “Avoid Routine…” for each one of the 5 practices. I think for a couple of their practices they could have been more forthright.

  1. Avoid routine use of antireflux medications for treatment of symptomatic GERD or for treatment of apnea and desaturation in preterm infants.

This is one where that prior comment applies. I think this should have been stated “Do not use antireflux medications in the newborn”. The reason being that there is no such animal. There is no medication that has been shown to reduce reflux. There is no way clinically to diagnose abnormal reflux. There is no effect of antireflux medication on apnea or desaturation. All the medications in use are toxic.

Now if by antireflux medications, they include anti-gastric acidity medications (and when you look at the supplemental materials it seems that they do) then I guess you could temper those comments a little. It is possible that sometimes acid-caused reflux disease is an issue, and the agents are effective at reducing gastric acid production, even in the newborn. Whether they improve any acid-related disease findings is less certain, most of the rare small RCTs have shown no clinical benefit. They are also associated with more infections, more NEC and increased mortality. So maybe in a baby after diaphragmatic hernia repair, or after Oesphageal Atresia repair they could be indicated, but it would be great to have some actual data.

  1. Avoid routine continuation of antibiotic therapy beyond 48 hours for initially asymptomatic infants without evidence of bacterial infection.

Again I think this could be a stronger statement, given the 2 provisos that the babies are initially asymptomatic and that they have no evidence of bacterial infection. In other words it is for babies with risk factors for infection, but who develop no clinical signs. In those babies you could appropriately say “Stop antibiotics at 36 hours”.

  1. Avoid routine use of pneumograms for predischarge assessment of ongoing and/or prolonged apnea of prematurity.

I think this is appropriately stated, there may be indications for selective predischarge pneumograms, for diagnostic rather than screening purposes, so “Avoid routine” is about right.

  1. Avoid routine daily chest radiographs without an indication for intubated infants.

I agree with this, I didn’t know it was a common practice in the NICU. Some babies are intubated for months, that would be an awful lot of radiation.

  1. Avoid routine screening term-equivalent or discharge brain MRIs in preterm infants.

Again I agree with this, as many of you will already know! The justification given however, is that there is no evidence that they improve long term outcome. While that is true, I don’t think that is why they are being done, not many people think a few minutes in a magnet will make the babies better. The data show a poor positive predictive value of abnormal findings for long term outcomes, which make them of questionable value.

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For Father’s Day

Posted on 20 June 2015 by Keith Barrington

Two links for Father’s Day, the first a narrated graphic story by a cartoonist whose baby had HIE. A wonderfully told touching story of becoming a Dad in the most difficult circumstances:

http://s.telegraph.co.uk/graphics/projects/fathers-days/index.html

The other is to a website where you can read a couple of poems by an uncle of very preterm twins. There are 3 sample poems, and a link to buy the book, which I have bought, and there are many other moving poems in the volume.

http://www.prematurepoems.com/

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Long term effects of surgery in the infant

Posted on 18 June 2015 by Keith Barrington

To follow on from a study in a recent “neonatal updates”, there is a new publication from an Australian group that have been pursuing a prospective cohort of full term infants who had major surgery in the first 90 days of life.

In contrast to the other study, this was prospective, population based, and only included major surgery (defined by opening of a body cavity). The early developmental results have already been published Walker K, et al. Early developmental outcomes following major noncardiac and cardiac surgery in term infants: a population-based study. The Journal of pediatrics. 2012;161(4):748-52 e1.

Now the authors have been testing the infants at 3 years of age. Walker K, et al. Developmental outcomes at 3 years of age following major non-cardiac and cardiac surgery in term infants: A population-based study. J Paediatr Child Health. 2015. They examined 62 infants who had cardiac and 124 who had non-cardiac surgery, and 162 controls, all from New South Wales. The Bayley scales of infant development, version 3 were used. Basically the non-cardiac surgery babies tested lower than the controls on just about all the subscales, and the cardiac surgery babies tested lower than the controls on just about all the subscales.

The proportion of babies whose scores fell into the mild, moderate and severe delay definitions were also increased. Most, as you would expect, were mildly affected, but nevertheless they were affected, and for expressive language and gross motor delay the proportions affected are substantial, 1/3 of the cardiac, and 1/6 of the non-cardiac surgery infants, compared to 1/20 of the controls (all of which were mild except fro 3 babies in the expressive language subscale who were moderate). With proportions like that these babies should all be followed up in order to identify those who may benefit from intervention. If we could identify them early then follow up could be selective. It seems (from other data) that more than 1 surgery increases the risk (Wilder RT, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110(4):796-804.), and longer anesthesia also seems a risk factor.

Several studies of specific types of surgery usually have shown similar results, (for example for oesophageal atresia and gastroschisis) so it is presumably just the fact of having surgery/anesthesia that is important, and not pre-existing associated CNS anomalies. Although some details of how the surgery is done have been studied, such as circulatory arrest times, and hemodilution (both in cardiac surgery), most of the details of the surgical or anesthetic techniques have not been evaluated.

A good recent review is available Sinner B, et al. General anaesthetics and the developing brain: an overview. Anaesthesia. 2014;69(9):1009-22.

 

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Cannulae for CPAP and nasal ventilation

Posted on 17 June 2015 by Keith Barrington

Mukerji A, Belik J. Neonatal nasal intermittent positive pressure ventilation efficacy and lung pressure transmission. J Perinatol. 2015.

This is a lung model study, in which the authors compared the pressure transmission and CO2 elimination effects of nasal IPPV with 2 different interfaces: the neotech RAM cannula and Fisher-Paykell short binasal prongs.

The model they used was a neonatal intubation model, with a soother in the mouth to reduce oral leaks, and they measured the pressures in the distal “trachea”. A Draeger VN500 was used to deliver ventilation and the pressures were varied with a PEEP of 5 and inspiratory pressures from 14 to 34. They measured CO2 removal from the lungs by filling the balloons (“lungs”) with CO2 and then measuring how much was washed out by the nasal ventilation.  They also measured the resistance of the interfaces.

One of the things that bugs me greatly, and there are many, is that a great deal of medical equipment has never been appropriately evaluated. For example, the neotech RAM cannula was introduced, and is sold, without, as far as I am aware, a single study evaluating whether pressure transmission actually occurs in newborn infants.

This study suggests that the resistance of the RAM particular system is far too high, and there is very little pressure transmission; although they don’t report on the CPAP generated in the pharynx, if any. The ventilator will of course continue to show good pressures, as the ventilator measures what is on the ventilator circuit side of the cannulae. This study shows that when you measure the pressures actually getting to the lung during simulated nasal ventilation, the pressures are much lower than you might think. Especially with the RAM cannula. When the set pip was increased from 14 to 34 cmH2O the ventilator measures pressures (in the circuit) increasing from about 12 to about 25, but the pressure in the lung goes from just under 0.5 cmH2O to just over 0.5 cmH2O.

With the Fisher Paykell prongs the ventilator measures circuit pressures which are significantly lower, due to the much lower resistance of the prongs, but much greater pressures are transmitted to the lung.

With both sets of prongs, the tidal volumes obtained were very small, but were much higher with the Fisher Paykell prongs. Also with both sets of prongs there was some CO2 washed out of the “lungs” despite the very small tidal volumes. The authors suggest that this means that maybe there are “non-conventional gas exchange mechanisms” I suggest that it shows the limitations of this kind of model, the findings are interesting, but you certainly can’t start talking about gas exchange, when you are washing CO2 out of  a balloon. In the discussion the authors state:

Several factors have been suggested as determining the NIPPV-dependent gas exchange. These include an increase in tidal ventilation, improved recruitment of alveoli, a washout effect of anatomical dead space and increasing stimulation of the respiratory center. The fact that effective CO2 clearance could be demonstrated in this study despite a small fraction of delivered VT leads credence to the importance of non-VT-dependent alternate factors postulated by others.

Now increased tidal ventilation, recruitment of alveoli and stimulation of the respiratory center are clearly irrelevant in a patient that looks like this: intubationtrainer

This patient doesn’t have any tidal ventilation, respiratory drive or alveoli!  The only one of those mechanisms which might be important is washing out the dead space.

The study clearly suggests that there is a very limited place for the neotech RAM cannulae, at least for nasal ventilation. It also suggests that the resistance of cannulae should be printed on the packaging, so that we know that what we are buying is fit for purpose.

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Neonatal Updates

Posted on 17 June 2015 by Keith Barrington

Bilgin A, Wolke D. Maternal Sensitivity in Parenting Preterm Children: A Meta-analysis. Pediatrics. 2015. “Mothers of preterm children were not found to be less sensitive or responsive toward their children than mothers of full-term children.” Quite.

Boss RD, et al. Decisions regarding resuscitation of extremely premature infants: Should social context matter? JAMA Pediatrics. 2015;169(6):521-2.
This is a discussion of two cases of extremely preterm infants, and the decision-making surrounding them in 2 different social contexts. An interesting article, and I don’t agree with everything they say, but I certainly do agree with this statement:

Delivering a monologue of medical detail and a menu of treatment options can seem a simpler path…… Yet allowing the delivery of medical information to monopolize conversations with families, even in urgent situations, rarely affects parents’ immediate decisions

Harris DL, et al. Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns. Archives of disease in childhood Fetal and neonatal edition. 2015;100(2):F161-4. The authors measured a ketone (beta-hydroxybutyrate) and lactate in the blood of infants with hypoglycemia. The ketone was very low, and the lactate much higher in most, although low in 17%. They didn’t actually measure whether the brains of the babies were using the lactate, but they note that there is good evidence that brains can use lactate, and will do so if the levels are high enough (including a study in adults where they made them hypoglycemic enough to have symptoms and then infused lactate, showing an improvement in symptoms. Which sounds like a very scary thing to volunteer for!) and that when ketone concentrations are low the brain doesn’t use them much. The supposition that the brain can use the increased lactates found in this study, and wouldn’t get much from the ketones,  seems reasonable.

Mian Q, et al. Spontaneously Breathing Preterm Infants Change in Tidal Volume to Improve Lung Aeration Immediately after Birth. The Journal of pediatrics. 2015. 30 preterm infants receiving face mask CPAP had measurement of tidal volume and CO2 excretion over the first 100 breaths. ETCO2 was at first low, with tidal volumes of 5 to 6 mL/kg. Vt then increased over 30 breaths to 7-8 mL/kg and ETCO2 increased also, then the tidal volumes fell back to 4-6, but ETCO2 continued to increase. Which seems to mean that the babies are initially clearing their lung fluid and establishing an FRC and good aeration, then they can eliminate CO2 with smaller tidal volumes.

Baserga MC, et al. Darbepoetin Administration to Neonates Undergoing Cooling for Encephalopathy (DANCE): A Safety and Pharmacokinetic Trial. Pediatr Res. 2015.30 babies being cooled fro HIE were randomized to darbepoetin, the long acting erythropoietin analogue, or placebo. No adverse effects were noted, and the elimination was very long, meaning you could give a weekly dose, if we can show it actually helps. Maybe a couple or 3 weekly doses might help in cerebral repair, we need to know!

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Recent pain/analgesia articles

Posted on 17 June 2015 by Keith Barrington

Several very recent articles have addressed issues of pain and analgesia in the newborn.

van Ganzewinkel CJ, et al. Chronic pain in the newborn: toward a definition. The Clinical journal of pain. 2014;30(11):970-7. This article describes a consensus building expert-based process, to develop a definition of chronic pain. An interesting process.

Taddio AP, et al. Teaching Parents to Manage Pain During Infant Immunizations: Laying the Foundation for Better Pain Management Practices. Clinical Journal of Pain. 2014;30(11):987-94. Anna Taddio and the group at Sick Kids in Toronto have previously published a parent information tool to help parents understand what they can do to reduce pain associated with vaccination. In this study the 4 groups of parents all receive the pamphlet, but 2 of the groups got the pamphlet after tests evaluating their knowledge. The study showed an improvement in knowledge in the groups that got the pamphlet. They also examined what pain interventions the mothers used around the 2 month vaccination of their infants. The study didn’t have a lot of power for this outcome, and didn’t show any real differences. In fact the major strategies that mothers in all groups used were “acting calm” followed by “”holding”. Other proven strategies such as breast feeding or sugary solutions were little used, which is a real shame as they are cheap, harmless and effective.

Maitra S, et al. Epidural anesthesia and analgesia in the neonate: a review of current evidences. J Anesth. 2014;28(5):768-79. A well done systematic review. Almost no RCTs, so the authors describe and review the other kinds of evidence available. We should probably use regional anaesthesia more frequently, but the potential CNS toxicity of the agents needs more work. Which is also true for “systemic” anaesthetic agents.

As shown in this study: Backeljauw B, et al. Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia. Pediatrics. 2015. In this study children who had an MRI as part of a study of MRIs among “volunteers” who were generally in good neurologic health. MRIs were done between 5 years and 18 years of age, the word “volunteers” therefore presumably refers to the subjects or to their parents. Among the subjects there were 53 who had previously had at least one surgery before the age of 4, many,  where ENT surgeries, a few general surgeries and no cardiac or neurosurgery in this group.  A battery of neuropsychologic tests were performed. The subjects had lower scores on a wide range of tests compared to matched controls. There were no overall differences in MRI volumetric measures between the groups, but there was a correlation between lower IQ scores and smaller grey matter volumes. Almost all of the anesthetics were with inhaled, volatile agents. A study with many limitations, acknowledged by the authors, but which has results consistent with many other studies showing adverse effects of early surgery with anaesthesia, and adding the MRI data.

Valeri BO, et al. Pain reactivity in preterm neonates: examining the sex differences. European Journal of Pain. 2014;18(10):1431-9. A prospective evaluation of pain responses to a skin puncture in preterm infants found little difference between males and females. Boys heart rate responses were a little more marked, but not enough difference to really make much of.

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Neonatal Updates

Posted on 11 June 2015 by Keith Barrington

Deshmukh M, et al. Effect of gastric lavage on feeding in neonates born through meconium-stained liquor: a systematic review. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2015.

When I first went to one of the hospitals I have worked at I discovered that the nurses were routinely performing gastric lavage of infants in the NICU who had meconium aspiration, or a history of meconium in the amniotic fluid. I put a stop to the practice as I couldn’t see any rationale, and I had worked in other hospitals where this was not done, and babies in general seemed fine without it. I now find that this is a not uncommon practice, frequent enough for randomized controlled trials and a systematic review, performed by my friend and colleague Sanjay Patole and his co-workers.  The SR suggests that maybe there is a benefit in terms of reduced feeding intolerance, but most babies did not have significant feeding problems, and the only individual trial which showed a significant benefit was of poor quality, caregivers were unmasked, and allocation was unmasked, and the outcome is rather subjective. Basically this is an unpleasant procedure for the babies, with no reliable evidence that it does anything.

Nobile S, et al. Are Infants with Bronchopulmonary Dysplasia Prone to Gastroesophageal Reflux? A Prospective Observational Study with Esophageal pH-Impedance Monitoring. The Journal of pediatrics. 2015.

No.

OK, I was just going to stop after the “No” but I can’t be that brief, or dismissive. 12 babies with BPD off respiratory support and 34 babies without BPD had esophageal impedance monitoring for an average of about 24 hours. There were no differences in the numbers or characteristics of reflux events. Only when a multivariate regression was performed did the authors find that one of the 5 indices that they calculated was different between groups. Which is pushing it, as they say. The association could easily be due to chance, the authors have really inflated the risk of a type 1 error, and should have been made to tone down their discussion.

They also showed that most “symptoms of reflux” were not temporally related to reflux (even though one of the symptoms was regurgitation, which probably was related!) Which is again not how they report the data.

The authors talk about anti-reflux medication, and the importance of proving reflux before using the medications. I would agree…. if there were any such thing as anti-reflux medication. The only therapies used for reflux in the newborn are toxic placebos. Please stop.

Anti-acid medications, on the other hand, may well be effective for reducing acid production, but the only clearly demonstrated effect of them is to increase sepsis, chest infections and necrotizing enterocolitis.

If you click on gastro-oesophageal reflux on the word cloud to the right, you can see some of my other posts on these agents which are used for reflux.

Kersbergen KJ, et al. Corticospinal Tract Injury Precedes Thalamic Volume Reduction in Preterm Infants with Cystic Periventricular Leukomalacia. The Journal of pediatrics. 2015.

Many of you will know that I think the clinical value of routine MRI imaging of very preterm infants is unproven. Maybe I should say that differently; there is good evidence that routine MRI imaging has very poor positive predictive value for adverse outcomes in very preterm infants.

On the other hand this is the kind of research that can be done with fancy forms of MRI, that can give some indication of the pathophysiology of brain injury in the preterm infant. The authors looked at fractional anisotropy (I guess I am going to have to learn how to say that word) of the cortico-spinal tracts on MRI from babies with cystic PVL and without. FA was higher in the controls than among the PVL babies, and among those PVL babies was not associated with the presence or severity of cerebral palsy (which as you will know is the major long term consequence of cystic PVL). The later a scan was done, in terms of post-menstrual age (that is, if it was done at or after term equivalent age) the smaller was the thalamus. Which suggests that the damage to the corticospinal tracts occurs when the PVL is developing, and the thalamic abnormality is a consequence of that. As usual the babies with cystic PVL were not generally extremely preterm, they were moderately preterm infants who often had perinatal sepsis, or other inflammatory conditions.

Schuurmans J, et al. Neonatal morphine in extremely and very preterm neonates: its effect on the developing brain – a review. The Journal of Maternal-Fetal & Neonatal Medicine. 2015;28(2):222-8. This is an excellent review, the unfortunate thing is that they are unable to reliably address the issue in the title, really, as there is little good quality evidence. They note:

Considering all above-mentioned results together, it can be concluded that morphine does not seem to have a negative effect on neurodevelopmental outcome. None of these studies were prospectively designed to investigate the long-term neurodevelopmental outcome, thus, the power of these studies to show a more specific effect of morphine on neurodevelopment was too low. Also, selection bias and loss to follow up could play a key role in the evaluation of the results, since most studies used a smaller subset from the original population.

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