Improving outcomes of Preterm Infants, early post-discharge intervention programs

Posted on 8 August 2012 by Keith Barrington

The history of early intervention programs is rather mixed. Do they actually help to improve outcomes? The most recent cochrane review was published in 2007 by the amazingly productive Lex Doyle and his colleagues, and was followed by an updated review by the same authors in 2009 (Orton J, Spittle A, Doyle LEX, Anderson P, Boyd R: Do early intervention programmes improve cognitive and motor outcomes for preterm infants after discharge? A systematic review. Developmental Medicine & Child Neurology 2009, 51(11):851-859). There are quite a few studies, 18 in all, but several were quasi-randomised, and the quality of several was low. Many were very small studies, but there was one study with nearly 1,000 babies, and another with just over 300, these were both high quality studies with follow up to school age. The largest study, the US Infant Health and Development Program (IHDP), has reported outcomes to 18 years of age, that study included infants less than 2.5 kg and less than 37 weeks; they randomized them 2:1 to get control more frequently than the intervention, I am not sure why. About half of the babies were less than 2 kg. Overall from the meta-analyses it seems that early cognitive scores are improved by around 0.5 of a standard deviation, up to pre-school testing. Scores at school age are not improved. There was some benefit in the larger babies at 18 years in the IHDP study, but not in the smaller ones. One of the higher quality studies in the systematic review was by Karen Koldewijn and her colleagues. In 2009 they had only published the 6 month outcomes, but they have very recently added preschool results. (Verkerk G, Jeukens-Visser M, Houtzager B, Koldewijn K, van Wassenaer A, Nollet F, Kok J: The infant behavioral assessment and intervention program in very low birth weight infants; outcome on executive functioning, behaviour and cognition at preschool age. Early Human Development 2012, 88(8):699-705.) For this publication there was an extensive analysis of the infants, including tests of executive functioning, behavior, visual motor integration and cognition. There were 151 infants of the originally randomized 176 who were examined (2 had died). They also had a number of term controls, about 40. The overall analysis showed no effect of the intervention program at this age. They did perform subgroup analyses which suggested some benefit in more high risk infants (with BPD or less than 28 weeks, or when the mother was of a low SES), but as always you have to take such analyses with a pinch of salt. Why would this be? An effect on cognitive development that does not generally seem to translate into longer term cognitive outcomes? I think that we are seeing is that there is an overall improvement in cognitive scores as these children age, particularly before they start school, as we showed in the CAP 5 year follow up. Some of that is because of the use of different tests. In the CAP 5 year follow up we examined some variables that were associated with improving cognitive scores and the social and educational background of the parents was important. So it seems that having an enriched environment at home after discharge is very important, but when the home environment is already good, then adding an early intervention program doesn’t have much long term effect. For those children with a more limited home environment these types of programs may have a benefit. Such programs are fairly expensive, but I think the data are positive enough that infants from families of lower socioeconomic status do benefit from early intervention and should be targeted. Who will pay is a question for the health care system where you are.

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A life worth living? Who would want a child like that?

Posted on 5 August 2012 by Keith Barrington

A troubling tale from an adult with a handicap has just been published. (Peace WJ: Comfort care as denial of personhood. Hastings Center Report 2012, 42(4):14-17.) When admitted to an acute care hospital with a serious wound the author was offered the option of not treating the infection by a well-meaning physician who assumed that his life was not worth very much, so he might want to die. He discusses his experience in this article and makes a heartfelt plea that the medical community should listen to the voices of the disabled. He was rather shaken by the assumption that he might be better off dead.

But in Pediatrics and Neonatology we make that assumption all the time. We assume that having a developmental delay as a result of an intracranial hemorrhage is worse than being dead, so withdrawing active care is justifiable. Even when we acknowledge that our predictions are very imperfect, and that many infants with very similar findings might have little impairment, we still offer limitation of care to parents with the goal that the infant will not survive.

Annie Janvier was guest editor of an edition of ‘Current Problems in Pediatrics and Adolescent Health Care‘ last year she  asked several parents to write their stories. Many of these stories recount the positive impact of a baby with impairments on their families.

One brief essay was entitled who would want a child like that? (Roy C: Who Would Want a Child Like That? Current Problems in Pediatric and Adolescent Health Care 2011, 41(4):127-127). In response to the question from a doctor which became the title Claire Roy gives an answer which in part is this: ‘A parent wants a child like that … their child … and they want to have every chance to do their job well. They deserve every support medical and social, emotional, and financial that it takes to bring “that child’s” life to fruition, to bring “that child’s” gifts to the world into which “that child,” for whatever reason, chose to enter.’

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Weekly Updates #2

Posted on 29 July 2012 by Keith Barrington

Recent things that I have noted:

Dennington D, Vali P, Finer NN, Kim JH: Ultrasound confirmation of endotracheal tube position in neonates. Neonatology 2012, 102(3):185-189. Bed-side ultrasound by the NICU team can confirm ETT position quickly and without radiation. This could be done out on transport, or in the delivery room as well as in the NICU, using handheld equipment with instant results.

Berry CA, Suki B, Polglase GR, Jane Pillow J: Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome. Pediatr Res 2012. This confirms work in adult dogs, and shows less lung injury if you allow tidal volume to vary around an average value rather than keeping it identical for each breath. I thought of looking at this in babies a long time ago, but I realized that tidal volume already varies a lot, unless you have the baby paralyzed.

Newburger JW, Sleeper LA, Bellinger DC, Goldberg CS, Tabbutt S, Lu M, Mussatto KA, Williams IA, Gustafson KE, Mital S et al: Early developmental outcome in children with hypoplastic left heart syndrome and related anomalies: The single ventricle reconstruction trial. Circulation 2012, 125(17):2081-2091. 14 month follow up of an RCT comparing 2 different ways of doing the Norwood procedure. Bayley scores were not affected very much by how the procedure was done, or by other intra-operative management variables. They were mostly affected by innate patient variables (such as syndromes) and by patient morbidity over the first year of life. Bayley 2 MDI scores at 14 months averaged about 90, with 16% being below 70.

Beal J, Silverman B, Bellant J, Young TE, Klontz K: Late Onset Necrotizing Enterocolitis in Infants following Use of a Xanthan Gum-Containing Thickening Agent. J Pediatr 2012, 161(2):354-356. Even things that you think should be innocuous may be dangerous for preterm babies. This report documents a possible association between NEC and a milk thickening agent used for reflux. As previously noted, very few babies who have reflux need any treatment at all. Please don’t use something that might be toxic.

Parker M, Kamholz K, Brodsky D, Zuckerman B: Neonatal Intensive Care Unit Graduate Home Visit: A Learning Opportunity for Pediatric Interns. The Journal of Pediatrics 2012, 161(2):177-178.e171. What a good idea. Send pediatric residents to do home visits with families who have an ex-preterm infant to see what the home life of such a family is really like. We should do the same thing with families coping with children with impairments as well.

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‘Our children are not a diagnosis’ – what an amazing response!

Posted on 26 July 2012 by Keith Barrington

This blog was initially intended mostly for health professionals (especially neonatologists and pediatricians in training) and others interested in academic neonatology, with the hope that some other people might find it interesting.

The reaction to my post on Annie Janvier’s paper has been humbling; over 1600 page views in 60 hours, and the counter is still mounting.

I would encourage anyone who interacts with families of children with serious chronic medical conditions to read the comments under the post.  I started trying to respond to all the parents’ comments, but then there were so many (and I have also just gone on vacation) that it became impossible, but I have read them all, (and rescued 3 from the automatic spam filter that were not spam, so they appeared out of chronological order). What is very evident is that most of the families who posted comments had very similar, but also very individual experiences. Most of them had negative initial contacts with their doctors, obstetricians, family doctors, pediatricians, or neonatologists; despite this they tried to get for their children what they felt was in the infant’s best interest, and finally most have found someone supportive, positive and helpful, who had made a big difference in their lives. They all report what a positive experience it was (or is) to live with a child with very serious limitations. Unfortunately one or two are still battling doctors who are convinced that their children would be better off dead, but they are a minority.

My sincere hope is that some of the health care providers reading this blog will have their attitudes changed, and that we will all have a deeper appreciation of the love and happiness surrounding children with serious conditions, be they chromosomal, genetic, or multifactorial, and an understanding of what a positive contribution they can make to our society. I don’t think you can read the stories in these comments and not be deeply moved: unless you have a heart of stone, and if so, you shouldn’t be in health care!

Just a brief additional note. If you leave a comment for the first time I have to approve it and  thereafter you can leave comments without approval, but I still read them all, and I will delete anything that is abusive. I have seen some distressing comments on youtube and other sites, and I have no intention of giving a forum to anyone who abuses a parent of a child with impairments, or that child. On the other hand if you want to disagree with me or correct me (or even abuse me;-)) that is OK, and I will approve anything that is on topic. So far I have not had any hesitation in approving any comments.

Posted in Advocating for impaired children | 3 Comments

“Our children are not a diagnosis”: the family experience of trisomy 13 and 18

Posted on 23 July 2012 by Keith Barrington

Annie Janvier, Barb Farlow and Ben Wilfond have just published a rather disturbing study. At least I feel a bit disturbed. (Janvier A, Farlow B, Wilfond BS: The experience of families with children with trisomy 13 and 18 in social networks. Pediatrics 2012.) It is one of those studies that challenges many assumptions. They set up an internet questionnaire and contacted parents of infants with trisomy 18 and trisomy 13 who belonged to various internet-based support groups.

In this new publication; 332 parents completed the questionnaire, some had prenatal diagnosis and others postnatal. Those with prenatal diagnosis may or may not have had access to abortion services, but if they did, they had obviously chosen not to terminate because the study only included parents of infants who had been born alive.

About half of the parents had opted for palliative care and a quarter for limited medical care after birth, the remaining 25% had wanted full intervention. Interestingly, survival duration was not much different between these families.

One of their important findings was that they asked parents if they regretted their choices regarding the extent of medical intervention. The parents who regretted their choices were overwhelmingly those who chose to limit the medical interventions to comfort care only, or less than full intervention.

Also of note the children did show signs of developmental progress, and all were able to communicate with their parents at some level.

The parents report overwhelmingly, that the experience of living with these children had made a positive contribution to their family life, irrespective of the length of their lives, and even though it had created substantial financial costs. They also report their child as being a happy child.

What is most distressing is how negative the families’ interactions with health care providers were. Although 2/3 of the families did meet at least one provider who was helpful; most had received misinformation, and many of those who chose to have active care felt that they were judged negatively by providers for daring to make that decision. Providers also often referred to their baby in de-humanising terms, calling their baby ‘it’ or ‘a T18’. They recount interactions with providers who never learnt their baby’s name, instead referring to the child by their diagnosis.

This study points out the uniqueness of each of these children and the heterogeneity of condition and survival. The emphasize that we cannot be definite about the duration of survival or the capacities of an individual.

They conclude: Parents who engage with parental support groups may discover an alternative, positive, description about children with T13-18.

I conclude; we need to rethink how we present diagnoses of serious conditions to parents.

I must admit to an enhanced interest in this publication, I know Barb Farlow personally, she contacted Annie and me a few years ago, after her family had a distressing interaction with healthcare providers. Her own daughter was born with trisomy 13 and eventually died after a re-admission, when a do not resuscitate order was placed in her baby’s chart without her knowledge or consent (or that of her husband; she has written about the experience here and here and here). Interacting with Barb and then going on to review the websites, youtube videos and personal stories of families who had a child with one or other of these trisomies has really enhanced my understanding of how some families with such children react. One very touching video, which has become quite well known, is 99 balloons, another is here. I encourage anyone who has to care for  families whose children have severe impairments to spend  some time listening to the parent stories, the videos and the websites.

So here are some guidelines to use when talking with parents who have received a diagnosis, prenatal or postnatal, guidelines that you could develop as a result of these families’ reports of their experiences:

1. Don’t say that this is ‘incompatible with life’ or ‘lethal’; anyone can go on the internet and find very quickly that you lied to them.

2. Don’t say that if they survive ‘they will live a life of suffering’, parents do think that their child had more pain than others, but they also had many positive times, and their overall evaluation was positive.

3. Human beings are not vegetables. These children are conscious and interact, even if at very limited levels. Carrots don’t.

4. Don’t predict marital disharmony, or family breakdown. You can’t see the future, there is no evidence at all that this occurs more when a family has a baby with severe impairments, and indeed in this admittedly biased sample the divorce rate was far lower than the US or Canadian average.

4. Families find meaning in the lives of their children. Whether those lives are unimpaired or lived with severe impairments. Whether they are very short or not.

5. Don’t suggest that the child is replaceable. Sometimes parents will bring up the idea that they can have another child, that is fine if they do so, but for you to suggest it really shows that you think this child is worthless.

6. Don’t say that there is nothing you can do for them. There is a lot you can do. Empathy and a positive attitude can be a great help. Finding resources, respite care, enabling appropriate medical care, these are all things that you can do for them.

7. Be very explicit about medical decision making, come to an agreement about the limits of medical interventions (if you can’t, then find them another doctor who can); and be open to changing the plan as time goes on.

8. Refer to the child by name if there is a name. (Annie has often recounted to me that when she sees parents antenatally with a serious diagnosis she will ask them what the baby’s name is. They often become teary and tell her it is the first time anyone has recognized their fetus as being a real potential human being, it is one of the many things she has taught me.)

9. Above all recognize that these babies are human beings who will be loved, who will be cared for, who will leave a positive mark on their families, and who deserve respect.

Posted in Advocating for impaired children | Tagged , , | 104 Comments

Ventilation during Resuscitation, sustained inflations?

Posted on 20 July 2012 by Keith Barrington

I don’t post much about animal studies, but there are some things which are extremely difficult to study in human babies and at least for preliminary studies they may be essential and very informative. That great Melbourne group has been looking at the effects of prolonged inflation time on response to resuscitation. Both in preterm animal models, and in asphyxiated near-term models.

They have shown that in rabbit cage experiments, preterm rabbits using a sustained inflation, of for example 20 seconds achieves an FRC much faster. The publications from 2009 show a fascinating series of images from phase-contrast x-rays showing the difference in lung volumes: I reproduce one here

Phase contrast x-ray images from prematurely delivery newborn rabbit pups ventilated from birth. Top panel are the images from the group with no SI (1 s in duration; images A, B, C, and D). Bottom panel are the images from the group with SI of 20 s (images E, F, G, and H). Images were acquired at 1 (A and E), 5 (B and F), 10 (C and G), and 20 (D and H) s after birth. The double asterisks (**) indicate images acquired at the end of the first inflation. Images acquired after the first inflation were acquired at end inspiration.

One could reasonably ask if that is  a good thing? Does achieving a good FRC faster really help? Well a new study from the group, this time in asphyxiated near-term lambs, would certainly suggest that a clinical benefit is very much a possibility (Klingenberg C, Sobotka KS, Ong T, Allison BJ, Schmölzer GM, Moss TJM, Polglase GR, Dawson JA, Davis PG, Hooper SB: Effect of sustained inflation duration; resuscitation of near-term asphyxiated lambs. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012.) In this study lambs ventilated with  a single ventilation of 30 seconds had a much more rapid recovery of their heart rate and blood pressure than did those with 5 x 3 second inflations with 1 sec expiratory time, or those ventilated at a rate of 60 per min with 0.5 sec inflations. So as well as increasing FRC cardiovascular recovery is faster with sustained inflations.

I must admit, that despite the lack of RCT evidence I have been doing this for many years, often I will take over ventilation when a baby is not responding immediately to the initial attempts (by a resident or someone following NRP guidelines) I will give a long inflation of 20 to 30 seconds (which is very long during a resuscitation) with a gradually increasing pressure. I have been doing this following the research from many years ago of Vyas and Milner. They showed that the apparent opening pressure of the lungs could be eliminated by such an inflation, and the lungs developed an FRC as a result of this maneuver. There has never been any poof that this improves outcomes of resuscitation, but given this physiologic evidence I have tried it many times, and very often a baby who was difficult to ventilate and bradycardic has responded with good chest movements (which I now know are probably excessive tidal volumes!) and improvements in circulation.

The next stage should surely be to examine the use of prolonged inflations in human resuscitation.

But please see Carlos Blanco’s comment on this post.

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Weekly Update #1

Posted on 20 July 2012 by Keith Barrington

There are a number of interesting and/or important publications that I don’t get the time to blog about. I was thinking that maybe a weekly update which lists them with just a little description rather than a full blog post might be interesting.

I will try this out, let me know if you find this helpful. As this is the first one I will go back a few weeks, and try to outline publications since the beginning of June.

van Vonderen JJ, Kleijn TA, Schilleman K, Walther FJ, Hooper SB, te Pas AB: Compressive force applied to a manikin’s head during mask ventilation. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012, 97(4):F254-F258. Around 2 kg of force are applied during mask ventilation of the mannikin, before and after adjusting mask position.

Nijman J, de Vries LS, Koopman-Esseboom C, Uiterwaal CSPM, van Loon AM, Verboon-Maciolek MA: Postnatally acquired cytomegalovirus infection in preterm infants: A prospective study on risk factors and cranial ultrasound findings. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012, 97(4):F259-F263. Around 10% of very preterm babies <32 weeks acquired CMV in the NICU, mostly from breast milk, most remained asymptomatic.

Mirea L, Sankaran K, Seshia M, Ohlsson A, Allen AC, Aziz K, Lee SK, Shah PS, Canadian Neonatal N: Treatment of patent ductus arteriosus and neonatal mortality/morbidities: Adjustment for treatment selection bias. J Pediatr 2012(0). Surgical ligation is associated with increased BPD risk, even after trying to account for all potential confounders, whether it really is possible to correct I am not sure, but they tried hard.

Pineda RG, Stransky KE, Rogers C, Duncan MH, Smith GC, Neil J, Inder T: The single-patient room in the nicu: Maternal and family effects. J Perinatol 2012, 32(7):545-551. Parents whose babies were assigned to single patient rooms visited more, but experienced more stress.

 Tillman S, Brandon DH, Silva SG: Evaluation of human milk fortification from the time of the first feeding: Effects on infants of less than 31 weeks gestational age. J Perinatol 2012, 32(7):525-531. After changing their protocol and fortifying milk from the very first feeding, there was less biochemical evidence of osteopenia, and it was well tolerated.

Caeymaex L, Jousselme C, Vasilescu C, Danan C, Falissard B, Bourrat M-M, Garel M, Speranza M: Perceived role in end-of-life decision making in the nicu affects long-term parental grief response. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012. When interviewed a couple of years after their child’s death, parents who described their involvement in decision making as being “shared decision making” experienced less grief than those who thought it was mostly a medical decision, or those who thought it was mostly their decision.

Lyall AE, Woolson S, Wolfe HM, Goldman BD, Reznick JS, Hamer RM, Lin W, Styner M, Gerig G, Gilmore JH: Prenatal isolated mild ventriculomegaly is associated with persistent ventricle enlargement at ages 1 and 2. Early Human Development 2012, 88(8):691-698. Prenatal mild ventriculomegaly leads to persistent mild postnatal ventriculomegaly. Up to 2 years of age. But there is little effect if any on development.

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Hypotension and cerebral oxygenation

Posted on 18 July 2012 by Keith Barrington

Two recent observational studies have examined how cerebral oxygenation is affected by therapies designed to increase blood pressure.

The first, by Hilde Bonestroo and co-workers, studied 71 infants less than 32 weeks gestation who had a mean arterial blood pressure in mmHg less than their gestational age in weeks (Bonestroo HJ, Lemmers PM, Baerts W, van Bel F. Effect of antihypotensive treatment on cerebral oxygenation of preterm infants without PDA. Pediatrics. 2011;128(6):e1502-10. Epub 2011/11/09). They excluded infants with an open ductus. Infants received a fluid bolus over 30 minutes, and then went on to get dopamine if they remained hypotensive. Treatment decision were not determined by protocol, but by the attending clinical team. This explains why, even though fluid boluses did not affect the blood pressure, there were 33 infants who did not go on to receive dopamine. The other 38 babies started dopamine at 5 microg/kg/min, and a few increased their dose thereafter. There was no effect on cerebral oxygenation as determined by NIRS, either from the fluid bolus or after treatment with dopamine. Even though some of the cerebral saturations were quite low before treatment, the plots show the same distribution of NIRS signals before and after treatment. Fluid boluses did not increase the blood pressure, but dopamine at 5 microg/kg/min increased the average mean BP by 5 mmHg.

The second study from Rachel Garner and David Burchfield (Garner RS, Burchfield DJ. Treatment of presumed hypotension in very low birthweight neonates: effects on regional cerebral oxygenation. Arch Dis Child Fetal Neonatal Ed. 2012. Epub 2012/07/12) had a different treatment threshold. In their institution infants less than 30 weeks gestation and less than 1500 g birth weight receive treatment if their mean BP is less than 30 mmHg. They gave a fluid bolus over 15 to 60 minutes and then started dopamine at 2.5 to 5 microg/kg/min. The differences in entry criteria and treatment probably explain the differences in BP responses to the previous study; this study showed an increase of about 2 mmHg with the fluid bolus, and about 2 mmHg with the dopamine. Cerebral oxygenation was unaffected by either maneuver.

These results are consistent with an older study using a different NIRS device, (Wardle SP, Yoxall CW, Weindling AM. Determinants of Cerebral Fractional Oxygen Extraction Using Near Infrared Spectroscopy in Preterm Neonates. J Cereb Blood Flow Metab. 2000;20(2):272-9). In this study the blood pressure thresholds to define hypotensive were derived from the Watkins charts. They did not examine the effects of treatment. They found no relationship between hypotension and cerebral fractional oxygen extraction.

All of which suggests that most hypotensive preterm babies, using any of these 3 common definitions of hypotension, do not have impaired cerebral oxygenation, or at least if they do, then treating the hypotension does not improve the situation. Is there any effect of treating low blood pressure on outcomes? We will have to wait for the result of randomized trials to answer that one… more later.

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Trying to improve outcomes of preterm infants

Posted on 17 July 2012 by Keith Barrington

Two recent RCTs in high risk newborns of things I would never have thought of.

The first is a trial of Estradiol and Progesterone supplementation (Trotter A, Steinmacher J, Kron M, Pohlandt F. Neurodevelopmental Follow-Up at Five Years Corrected Age of Extremely Low Birth Weight Infants after Postnatal Replacement of 17β-Estradiol and Progesterone. Journal of Clinical Endocrinology & Metabolism. 2012;97(3):1041-7. http://jcem.endojournals.org/content/97/3/1041.abstract). The idea being that fetuses are usually exposed to these hormones at high concentration during the last half of pregnancy and very preterm babies miss out on this exposure, and that these hormones are also are known to have neuroprotective effects in certain model systems. The reasonable conclusion being that abnormalities of brain development in very preterm infants, even those who do not have intracerebral hemorrhages, might in part be due to a lack of these 2 hormones. Babies < 29 weeks and < 1000 g were randomized. The study was clearly very underpowered for a 5 year developmental outcome (n=83, 71 survivors to 5 years, 61 agreed to inclusion in the study), but did have some suggestive results that should be considered for future studies.

The authors previously published a 15 month follow up of extremely low birth weight infants from another pilot study : (Trotter A, Bokelmann B, Sorgo W, Bechinger-Kornhuber D, Heinemann H, Schmücker G, et al. Follow-Up Examination at the Age of 15 Months of Extremely Preterm Infants after Postnatal Estradiol and Progesterone Replacement. Journal of Clinical Endocrinology & Metabolism. 2001;86(2):601-3. http://jcem.endojournals.org/content/84/12/4531.long). That study was even more underpowered, (30 randomized, 25 survivors, 24 evaluated) the hormone treated babies had higher Bayley motor index, 101 vs 71 for the controls, which was not statistically significant. Is there a place for a larger multicenter trial?

The other trial was from the inimitable Paolo Manzoni. Two carotenoids found in breast-milk were studied because of their potential anti-oxidant effects, and the putative role of oxidative injury in the pathogenesis of Necrotizing Enterocolitis, Retinopathy and Bronchopulmonary Dysplasia. (Manzoni P, Guardione R, Bonetti P, Priolo C, Maestri A, Mansoldo C, et al. Lutein and Zeaxanthin Supplementation in Preterm Very Low-Birth-Weight Neonates in Neonatal Intensive Care Units: A Multicenter Randomized Controlled Trial. Am J Perinatol. 2012(EFirst). Epub 2012/07/10.  https://www.thieme-connect.com/DOI/DOI?10.1055/s-0032-1321494). This moderately sized trial (about 115 very low birth weight infants per group) showed non-significant positive effects in all 3 of the target outcomes. As this was a relatively low-risk group (mean gestational age around 30 weeks) the incidence of each of the outcomes was not large (about 10% for RoP and BPD for example) so even 40 to 60% lower incidence (for RoP and BPD respectively) with treatment was not significant. Given the history of carotenoid supplementation for human disease, (beta-carotene led to an increase in lung cancer in adults, rather than the expected decrease Duffield-Lillico AJ, Begg CB. Reflections on the Landmark Studies of β-Carotene Supplementation. Journal of the National Cancer Institute. 2004;96(23):1729-31. http://jnci.oxfordjournals.org/content/96/23/1729.short.) we need to be very careful before widespread use of these agents

These trials point out a few things, that we need much larger trials to find positive results, now that many of our babies have good outcomes, that we need stable funded research networks to be able to quickly mount trials to address questions raised in trials such as these, and that we will have to prioritize which studies to be done in which order.

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More on Probiotics

Posted on 16 July 2012 by Keith Barrington

All of the accumulated evidence regarding probiotics in preterm infants to prevent necrotising enterocolitis (NEC) clearly shows that probiotic bacteria (specifically bifidobacteria and lactobacilli) are effective in reducing the incidence of NEC by more than 50%, they, as a result, reduce mortality in eligible infants.

Do these benefits from randomized controlled trials translate into real benefits in routine use? It seems highly likely that they should, especially as there is no evidence of any harm in any of the randomized trials.

Cohort studies are one way of keeping track of the effects of an intervention when actually introduced into daily use. Such studies are better if designed prospectively (as you can determine definitions etc more precisely) and better if inception cohorts, that is they include all patients who are eligible from the moment they become eligible.

A newly published study was a retrospective cohort, (Bonsante F, Iacobelli S, Gouyon JB. Routine Probiotic Use in Very Preterm Infants: Retrospective Comparison of Two Cohorts. Am J Perinatol. 2012(EFirst). Epub 2012/07/10. https://www.thieme-connect.com/DOI/DOI?10.1055/s-0032-1321498) from an NICU in France. The authors showed that in routine use in infants of 24 to 31 weeks gestation, Lactobacillus rhamnosus was associated with a decrease in NEC of 80%, and a decrease in mortality of 54%. The same order of effect that has been seen in the RCTs.

More confirmation of the benefits of probiotic bacteria in preterm infants, as if more were needed!

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