Nicholas Embleton

thanks Vicky, Stefan!

All about me! I qualified MBBS 1990, started paediatrics 1991, & did my first NICU job 1992. I was utterly terrified those first few weeks, but worked with some brilliant nurses who looked after me, and an inspirational consultant Edmund Hey - one of the pioneers of neonatology (seminal work on resuscitation and thermal management in the 1960s!). We worked long hours as SHOs (residents) - 24 hours on, 24 hours off, for 2 weeks, knew the babies and families inside out, and then 5 daytime shifts and a whole weekend free 1:3! Such was neonatology at the time, that within 4 weeks of residency starting we had all learned to intubate and drip most babies and the fear subsided. I remained a bit scared of the nurses (still am), and always a bit uncertain what to say to parents. Surfactant was becoming routine but antenatal steroid administration was inconsistent, so lots of RDS, a Bourns ventilator that sat on top of the incubator, but with no graphics. We got good at transillumination and chest drains. Ed was non-interventional so we rarely did art lines or PICCs, and a strict protocol of always doing what the nurses told us. The maternity hospital was a mile away from the City’s main hospital, so had our own lab for measuring serum sodium, bilirubin & osmolality. Lots of exchange transfusions for Rhesus. Busy busy. Great fun. I was a bit disappointed when, as a registrar (senior resident), I realised I loved neonatology, as my intention had always been to be a General Paediatrician but my borderline ADHD/ASD/INTJ-ness had other plans. I became interested in research, and under Ed’s mentorship I wrote papers on Edward’s syndrome and Group B strep - Ed’s mantra was always to write papers you’d be proud of in 10 years time. They were well cited. I wept when he died unexpectedly in 2009, which took me by surprise as I never realised how much he had meant to me and had to creep out the back of the church funeral so no one saw me. By then I had a moderately successful research interest in nutrition and growth, started planning some big RCTs, and loved my clinical job especially the acute, technical life saving whooshy whooshy echo machines and number stuff. I’ll post another time on why doctors want to be a hero. Just possibly also including me. And why wanting to be a hero can change your attitude and behaviour. At about the same time, 2007/2008, I had a chance meeting with a Ruth, social scientist, Judith, a maternal epidemiologist and Steve, a fetal medicine Prof. They were conducting qualitative work and exploring women’s feelings and experiences of being offered termination of pregnancy, and the option of feticide prior to delivery. Important and heavy. They asked me “how do you think parents feel when you ask them to agree/consent to withdrawal of active intensive care”. We planned and got funding for a qual study where an RA spoke to several bereaved parents, and the staff who cared for them, including me. I was humbled by how little I knew about sociology, psychology and qualitative work, but it changed me personally, my career, and how I behaved. I questioned my personal and professional identity. Are they one and the same? Do you ever stop thinking you’re a neonatologist or neonatal nurse? I questioned why I went to some baby’s funerals, but not others. Did that mean I didn’t care about them as much? After we removed an ET tube, and we sat with parents as the baby passed away, why was it OK for the nurse to cry, but I never felt I should. I would though, sometimes take myself for a ‘lazy wee’ if I felt upset as the washroom stalls were the only place you could get a bit of privacy for a few minutes? [OK, it’s toilet but I’m being inclusive of any north American readers.] My kids would ask me (after I had rushed from the house to tube a baby) “Daddy, did the baby die?” and I always lied and said, no, he’s fine now. I felt bad that children should have to know that babies died. How could I sit with parents, watch the baby slowly become apneic, confirm absent heart sounds, and then get up and meet my colleagues for lunch and laugh about the soccer. Did that make me a psychopath? And how could you find so much reward and enjoyment in looking after a baby so sick he might die. Is it OK to be facebook friends with a parent whose baby died? How long do you have to wait before accepting the request. What do the brothers and sisters think when they’re told their much anticipated baby brother died. What do you feel as a surviving twin when your brother died at a day of age before you ever remembered his face. Do you tell your friends at school you’re a twin. When you see a parent from years back walking towards you down the street, and you can’t you remember if the baby survived? “Hi, um, how are things going?” So genuinely, no one is more surprised than I am, that having been fascinated by the epigenetic correlates of rapid infant growth, I am so interested in feelings and experiences. I didn’t become a neonatologist to do that. Almost the opposite of that? But I gradually became fascinated about how we interact with each other, interact with parents, the furrowed brows and sucking of teeth when a baby is sick. I watched parents hang on to every word and facial expression of the attending consultant. Sometimes I wondered if one consultant made things out to be much worse than they were, so he could look more heroic when he made the baby better. Another consultant telling parents everything would be fine as they slowly became bradycardic. I listened to parents ask if they were allowed to stop one of the consultants from turning the machine off, as they feared that’s what we would decide would happen if they went home from the NICU. Watched parents melt when the nurse on rounds say “he’s had a bad night, his gas is terrible”. And what actually really matters? All those RCTs to see if we can improved the BSID by a few points but that really tell you very little about future life and joy and love. Sadly, we can’t put a number on the importance of ‘meaning’, but maybe that’s a good thing. It took me a while to appreciate that short lives can have immense meaning. Even a life as a twin just a few weeks after conception. There’s something deeply profound and existential about baby loss. I don’t want to make out that neonatal medicine is somehow more important or honourable than other branches. But babies are the most cherished of all beings in society. They’re not supposed to be born early, or get sick and die. Pretty much everyone loves them. We’re even happy to be smeared in their faeces or vomit or blood, awwww he’s just a baby, but smear me with an adult’s sputum and I want to barf. And we all feel terribly uncomfortable and awkward when a baby dies, and don’t know what to say sometimes, so we avoid the topic or become all professional and detached. Residents often ask me, I don’t know what to say to parents when a baby dies, it’s just really sad. You could just say that, I suggest. We try not to mention the baby who died. We forget their names. We dehumanise the babies, and talk about a fetus with Trisomy 18, and not Rita. And in all of this, we forget that the micro-interactions we have with parents all day long that determine whether they trust us and feel supported. Did we smile and say hello, ask them how they were, or what they were worried about today. Did we remember their name, the name of the twin who died, and act as if we had plenty of time to talk. Or did we make out we were terribly busy and important, that we know best, or we somehow magically know what they are going through, because we’ve seen it before. I think we all really care, but sometimes we could show it better. Also posted here on Substack.

I’m still learning about the potential to create an online community of like-minded people interested in improving nutrition and growth in preterm infants, especially in more resource limited settings. But as an introverted academic I struggle to write freely, without constantly over-thinking and feeling the need to continually cite every statement as if writing for academic journals. Anyhow, here goes … Credit to CNN 2023 for the photo - you’ll need to read the follow up post to understand the meaning of this photo!In my first post, I discussed the question about whether it’s possible for a sub-1250g baby to grow on breastmilk alone. This is important for resource limited settings where access to PN and nutritional supplements is limited or absent. The nutritional needs of preterm infants are complex, and they need more nutrients per kg than infants born full term. This is especially true for macronutrients (protein, fat and carbs) and micronutrients such as vitamins, electrolytes, and minerals, and trace elements such as iron, manganese and zinc etc. Given their rapid growth rates, limited stores and excess demands (illness etc.) it isn’t surprising they have high nutrient needs. Defining what is an optimal intake is challenging. In-utero growth and the placentaIn-utero growth is supported by nutrients transported across the placenta. Lots of glucose and amino acids (to make protein) and essential fatty acids, but relatively lower amounts of total fat compared to life ex-utero. As with all mammals, placental transport is perfectly evolved to ensure optimal growth in an environment that is more hypoxic than postnatal life. Large amounts of amino acids are transported across the placenta, and nitrogenous waste products passed back to the mother for her liver and kidneys to detoxify and excrete. Uterine blood flow is around 500 litres/day in the 2nd trimester and >1000 litres/day in the 3rd trimester, most of which goes through the placental inter-villous space from where nutrients can pass into the fetal circulation. Int. J. Mol. Sci. 2014, 15(9), 16153-16185; https://doi.org/10.3390/ijms150916153The concentration of essential nutrients like amino acids and minerals in uterine blood therefore doesn’t need to be that high, as the absolute amount that could potentially be provided at those blood flow volumes even with low concentrations is immense. Minerals such as calcium and phosphate precipitate in solutions when the concentration gets too high, but high uterine blood flows solves that problem. When you are restricted to just a total fluid intake of 150ml/kg/day there are challenges everywhere you look to concentrate the solution and provide the optimal balance. We can never provide enough mineral via PN, and we need to get the amino acid composition just right. Enough to grow, but not so high you place a strain on metabolism (autophagy), renal function, and nitrogen excretion. How do we replicate placental nutrient transport when we use PN or start feeds? Body composition of the reference fetusStudies conducted in the 1970s and 1980s used the factorial method which estimated body composition (fat, minerals, protein etc.) at different weeks of [fetal] development, then used subtraction to work out how much of that nutrient was accreted between one week and the next. When you do this for protein you come up with a figure of around 2g/kg/day. However, simply supplying that amount will not lead to growth as there are metabolic inefficiencies and losses. You can’t convert 2g of dietary protein (breastmilk protein or amino acids in PN) into 2g of muscle protein (or liver protein) as it has to be digested, broken down, transported to the liver (as peptides and amino acids), metabolised and then reformed into muscle protein. The amino acid composition of muscle will differ from that of breastmilk protein. There is also continual re-modelling of body proteins even when you are not growing - like you and me. This results in an inevitable loss of ‘protein’ as nitrogenous compounds in the urine (urea) and stool. Several billion gut epithelial cells are lost every day (the whole gut lining is replaced every 6-7 days). All of these losses and inefficiencies add up to around 1.5g protein equivalent, which is why 3.5g/kg/day seems to be the minimum intake for most very preterm infants to grow. Body composition studies provide a fascinating insight into fetal growth. These early studies show that only 1-2% of body weight is due to mineral in bone, and this is fairly constant over the 3rd trimester. Lipid stores are virtually absent at 24 weeks, although there are lipids in all cell membranes especially neurones, brain tissue and the retina. By 40 weeks, fat content is around 13-14% and double this - 25-30% - by 3 months of age. Protein is fairly constant at 10-12%. If you do the math, you’ll see that most of the weight of a 500g baby is actually just water, so when you care for a 24 week infant, remember there’s only 50g of dry tissue. Parenteral Nutrition (PN) & the shrinking babyIn parenteral nutrition (PN) solutions there is no protein, just amino acids (essential and non-essential) but we talk about ‘protein’ as it makes it simpler to inter-convert. Because PN does not involve gut (splanchnic) metabolism, losses are lower than enteral, and an intake of 3-3.5g/kg/day is usually enough. With enteral nutrition, studies show that lean mass accretion (lean mass is pretty much everything that isn’t fat) is optimal at around 3.5-4g/kg/day, although some extremely preterm infants may need a little more, perhaps up to 4.5g/kg/day. https://www.sfnmjournal.com/article/S1744-165X(25)00029-0/fulltext PN is an essential component of preterm NICU care in high-resource settings, but is unavailable in much of Africa, and other low-income settings. If a baby is not receiving enteral milk in those settings, it is impossible to grow. Furthermore, because of the inevitable recycling of protein, there is still ongoing protein (nitrogen) loss meaning a baby receiving no PN will not simply stay the same weight, but will in fact, shrink. Even when you think you are doing a good job and giving a little PN, if you are only giving 1-2g/kg/day (a good amount to start at) the baby, in all likelihood, is still shrinking. Why extremely low birthweight babies don’t grow optimally on un-fortified breastmilkAssuming an ELBW infant needs around 4g/kg/day protein from enteral sources, the question is, how much can they get from breastmilk. Breastmilk protein of course is the highest quality. Quality means the extent to which the amino acid profile meets needs. Highest quality for breastmilk when casein and whey proteins are considered together, a little lower quality for amino acids in PN, and it would be low quality if we used vegetable protein (which of course, we wouldn't). The real challenge though is quantity - the concentration of protein in most Mothers Own Milk (MOM) after the first few days (when lactation reaches ‘full’ volume) is only around 1g/100mL. In donor human milk (DHM) it may be lower (around 0.8g) although there is considerable variability. If MOM is fed at 200ml/kg/day an ELBW may still only get around 50-60% of what they need to grow optimally. It is possible to add extra calories using supplements (MCT, olive oil etc.) and extra minerals, sodium etc. but protein is challenging as it has to come from another animal. Greek protein only just meets essential needsProtein comes from the Greek meaning the ‘first order’ - the primary, most important constituent of life. No protein, no life. Given how rapidly infants seem to grow, and the primary importance of protein, why is the amount in breastmilk apparently low? Term-born infants need less protein per kg than preterm, up to 1.5g/kg/day. This means that breastmilk (1g/100mL) meets most healthy term infants perfectly if they drink around 120-150ml/kg/day - but there seems to be no room for error! No spare capacity. And the amount of protein the mother eats makes no difference to the protein content of milk. Nature is very conservative. No wastage. Interestingly, a significant proportion (perhaps 15%) of the nitrogen in breastmilk is from urea. This can be metabolised by gut bacteria (especially certain Bifidobacteria spp), and converted into amino acids providing nutrients for infant growth. A likely reason that protein is so low comes from understanding infant and child development in complex society. Growth needs to be slow in healthy infants. Unfortunately, this is far from ideal for a ELBW who is desperately trying to grow as quickly as a fetus. A 24 week infant going from 500g at birth to 2500g at NICU discharge 3 months later is a 400% increase. If a term baby born weighing 3.5kg grew this quickly it would weigh the same as a 5 year old (17.5kg) by 3 months age. Low protein is a necessary component of optimal development. In my next post, I’ll be discussing breast milk protein in different mammals, brain growth and how humans differ from most other mammals. Thanks for the read. I’d be grateful for your help in sharing this, and the Baby Loss project posts, with others interested in NICU nutrition and/or Baby Loss. I’m not interested in getting likes or views on their own; I’m interested in connecting with others to see if we can improve outcomes, through collaboration, raising awareness, sharing innovations and good practice, and education. Thanks for any shares, re-stacks. Also posted here on Substack.

This is my first post. I may be slow to keep posting here as I also focus on the Butterfly Project and work with parents. But, please stick with me, and help me share what you know, and your insights on NICU nutrition, to the Global Majority. I want to share content for all things NICU nutrition related especially with a view for global collaboration. I want YOU to help me make a difference to the sick newborns in LMICs. I want to learn how best to translate knowledge to, and share good practice and evidence with less well resourced settings. I want to find out what works in your settings, and what ideas and solutions you have. Our practice in High-income country (HIC) settings is guided by systematic reviews, RCTs and years of experience, but translating that to resource limited settings is challenging. The risks and benefits of faster/slower feeding is context dependant and impacted by population differences (higher rates of IUGR), baseline infection rates and available resources (e.g. PICCs). Let’s be honest, we are all guided by Cochrane etc. but 90% of what we practice is experiential. Show me a single successful RCT powered on a primary of NEC and I’ll buy you lunch. An intervention that is beneficial in HICs (high quality probiotics) could be lethal in LMICs. My clinical career (qual. MBBS 1990) has been in a well resourced setting - the UK, where we care for babies from 22 weeks and 400g with unrestricted access to PN, intravenous lipids, supplements, minerals and fortifiers, as well as biochemistry, dieticians and high nurse:patient ratios. I’ve published hundreds of papers, many of which individually probably made little difference to clinical care, but cumulatively I hope added to our understanding of nutritional needs and practice. I then imagined that in resource limited settings where I’ve been fortunate to visit, such as Kenya, Latin America, Philippines, most preterm babies <28 weeks or <750g wouldn’t survive. However, even in settings such as Kenya, where there were no ventilators or surfactant, no PN, no fortifiers, I saw babies born at 25-26 weeks weighing 600-800g surviving just on Mother’s Own Milk, MOM and good nursing care (warmth, infection control, Kangaroo and milk). However, a lack of access to routine biochemistry (sodium), supplements (calcium but no phosphate) and fortifiers results in universal growth faltering. Whilst I strongly believe that slower growth on MOM is preferable to faster weight gain on formula, there will be a point at which slow growth is a marker of inadequate nutrients for optimal brain growth. Humans are naturally innovative, and there are many local approaches that have been developed, but most have not been rigorously tested. Studies have explored high volume feedings (200-240ml/kg/day), energy supplements such as olive oil, MCT etc. and in some settings where access to breastmilk fortifiers is expensive, formula milk powder is added although of course the final milk composition given is always sub-optimal. In other settings, in-hospital access to formula and fortifier is effectively prohibited because of rigid adherence to BFI. We can all see the benefits of BFI culture, but the adverse growth impact on individual VLBW feels wrong. There may be many babies 1250-1500g who will do fine with high volume MOM, some extra sodium and lots of KMC, below that I’m not so sure. Is it really possible for a <1000g baby to grow optimally just on breastmilk? Also posted here on Substack.

Hi Nestor, I agree; the trial was inadequate, the 'expert witness' is not credible (not an experienced NICU consultant) and I agree the experts on Shoo's panel are experienced. But, they made some comments that I need to know more about - I don't know the cases - but I do not believe you can say all these cases are "natural" and the deaths are due to poor medical management. Of course, many of the deaths might be 'natural' = 'bad luck' but surely that does not easily explain all cases. There were comments that "you should never use a size 2.0 ETT" - I have used very successfully in difficult cases to stabilise a baby ; Comments that 96% leak means there is not effective ventilation - that is too simple an explanation. Has anyone else ventilated a baby with a large leak successfully? Yes. Of course we want low leak, but just because the expired gas passes out around the tube does not automatically mean you are not ventilating the baby. From what I heard (and there may be more) the conclusions seem too 'black and white' to say "there are no murders". Pro bono is great - but we are all far more bothered by our reputation than money! But pro bono does not equal "no conflict". And confirmation bias works both ways - maybe they started out believing she was probably innocent and then reviewed. I agree - we don't know the truth and we need a review ; but the reporting of the panel conclusions is not clear We need a debate!

This case is hugely concerning, but we do not know the facts. All of us who take part in mortality review meetings know that we can not always explain every death; we sometimes disagree on the primary cause. We all have examples of cases where we thought one cause, but PM revealed another. What is written in the notes, or recorded, does not present the full picture. Sometimes there are 'gaps' because we were too busy to write, or forgot. I listened with interest to the presentation from Shoo Lee; the panel seem 'clear' they have an alternate explanation (other than deliberate harm) for every case. That is quite a brave claim. I do not know the make-up of the panel members, but I would also make the point that neonatologists with strong academic credentials are not necessarily any 'better' at determining clinical management, and working out what might have happened i.e. the sequence, than 'jobbing' neonatologists. If my own baby needed resuscitating I would rather have a neonatologist with zero publications who had intubated 400 babies in the last 10 years, rather than published 400 papers but resuscitated none! I am not saying they are wrong or right; or that Letby is likely innocent or guilty. I don't know, and opinions are cheap. It is clear the 'system' has failed on multiple levels and we need a full enquiry. To fully review a single death on a NICU takes around 2 hours and requires 4-6 (or more) experienced neonatologists; also nurses, pathologists, obstetrics; ideally with at least 1-2 external (non-conflicted) neonatologists. How much time do you all have in your job plans to undertake this activity? Also note, this unit typically had 2 deaths per year until 2015 and 2016 where the annualised rate is closer to 8 - the probability of that happening by chance is less than 1%. Of course if you take 100 neonatal units, then a 1% chance happens to one unit every year (on average). But who in this audience would have watched 8 deaths a year and said "...oh that is bad luck" or "...we used to be very good, why are we now so bad?" [Stefan - can you add me a legal disclaimer !!]

Thanks Kaltirkawi - I agree, I have never been convinced that adding MCT oil to promote growth (as opposed to weight gain) is truly beneficial. I am sure it increases weight gain - there are extra calories and CO2 production is less than glucose; but I would be concerned that the 'weight gain' is primarily fat. Most preterm infants with slow growth are probably getting insufficient protein - very likely to be true if using donor milk, but probably also true with MOM. So adding MCT might appear to improve 'growth' but it might 'hide' the underlying issue. Without access to a pure protein fortifier that allows you to adjust the intake, it is a complex problem. Blood urea is typically low in these babies but variability means the predictive value (for protein intake) of Urea is poor - however if i observed 'slow growth' with a urea of <3mmol/L AND the baby was on fortified 180-200ml/kg I might add extra protein, or if no protein supplement, cautiously increase the amount of fortifier. In Arslanoglu trials this approach improved head growth. Arslanoglu S, Moro GE, Ziegler EE. Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatol. 2006 Oct;26(10):614-21. doi: 10.1038/sj.jp.7211571. Epub 2006 Aug 3. PMID: 16885989.

Everyone has an opinion, and all of these are valid. For me a few random comments - A definitive trial powered on NEC requires n>3,000 and may never be performed; so in 10 years time we will still now know for certain. What will happen is that NICUs that use, will publish cohort studies, and slowly we will get an idea of which combinations appear most effective. The WHO are funding a trial in LMICs which might (or not) provide information for high income settings. But a negative result might simply reflect the context (biomes, risks and benefits are different in Africa v Asia v Europe) - so we might still not know In 2033, another 10 years of observational studies will further prove the safety of probiotics ( 1 death per 10,000s exposed is very low rate). Invasive sepsis is not related to QC/QA (contamination is) - so you can't decrease the risk of invasive sepsis by manufacturing a "better" product. However, the MCT oil in the FDA case is interesting - did the MCFA provide a direct conduit for the Bifido bacteria to enter the blood stream? There are major risks of commercial involvement - investment of $millions to develop and test a product mean they will use very heavy handed legal powers to shut down smaller manufacturers. Beware! The way forward is via parent/public pressure and advocacy. Parents can look at a Cochrane plot and can easily understand the debate - it is not that complex! You don't need to start probiotics day 1-2 it is OK to wait whilst parents consider the options and have a slightly better understanding of NICU. Parents can request their baby is treated in the same way they can request/decline donor milk. In a litigious medico-legal environment (USA) parents could be offered the information and sign an agreement to say they want their baby treated. I have little sympathy for the FDA - their statement will increase deaths. However, I have some sympathy with the AAP statement. I don't agree with it, but it is very difficult for an organisation like the AAP in a US legal environment to be so definitive. As clinicians, we need to stick together. We all want the same thing. None of us is making money out of the debate! So please keep opinions "tempered" - it is through disagreement and respectful discussion that we will improve care. have a nice day! Nick

We use electronic software (Badger) that calculates growth curves using WHO/UK dataset. More importantly than the specific growth chart used is how you interpret and what you do! Of course all growth charts differ based on reference populations and none are a true standard. Growth rates in g/kg/d vary between 24-40 weeks so charting is always best. But ... what to do if growth is slow? Is there any evidence that increasing weight gain is beneficial for an individual infant? Growth is a measure or a marker of nutritional status, not an outcome in itself. Useful for audit and research, but perhaps less useful on it's own for clinical management. Growth is one element of Nutritional status. Aim of nutrition and feeding is to improve Nutritional Status not to achieve weight gain per se. Embleton_ADC_15mins_NutrAssessment_May2021.pdfEmbleton_ADC_15mins_NutrAssessment_May2021.pdfEmbleton_ADC_15mins_NutrAssessment_May2021.pdfDOI: 10.1136/archdischild-2020-320928