Neonatal Updates

It’s a long time since I did one of these, but there were several publications that I thought warranted a quick comment.

Abbey NV, et al. Electrocardiogram for heart rate evaluation during preterm resuscitation at birth: a randomized trial. Pediatr Res. 2021.

In this RCT of babies of 30 weeks or less, 51 babies were randomized to either what has become standard NRP, i.e. trying to put an ECG in place as quickly as possible after the baby arrives on the resuscitation table, or doing the same thing but hiding the monitor. The study was performed 4 years ago, and the time it took to get the babies to the resusc table is said to be “22” in 1 group and “18” in the other. I have to assume that these are seconds, and I have to assume that delayed cord clamping was not being practiced at that time. The heart rate was visible at just over a minute in both groups, and about 10 seconds earlier in the ECG visible group.

There was no difference in any clinical variable, including time to get a pulse over 100, about half of the babies were bradycardic at first evaluation, and PPV was started at about “36” in each group, i.e. before the heart rate was visible on any monitor, presumably because of auscultation or palpation of a slow heart rate.

This is an OK study, but I hope it isn’t interpreted as showing that the ECG is a waste of time. For most babies, even the very preterm, you don’t need anything other suction or a few puffs of positive pressure to get them going, as in this study, so nothing we do to try and improve resuscitation will likely have much impact in a study of 50 babies. In order to demonstrate whether ECG really makes a difference among those babies who really need resuscitation, you would need a sample size of a few thousand probably. Or at least a few hundred. I don’t know whether adding ECG to our resuscitation standards is a significant improvement or not, we certainly need to be aware that it can be misleading, if there is an ECG but no output (Luong D, et al. Cardiac arrest with pulseless electrical activity rhythm in newborn infants: a case series. Arch Dis Child Fetal Neonatal Ed. 2019). On the other hand if you can have an accurate heart rate faster, I think that is self-evidently a good thing, and will probably occasionally change the resuscitation approach to a more appropriate intervention.

Gehle DB, et al. A predictive model for preterm babies born < 30 weeks gestational age who will not attain full oral feedings. J Perinatol. 2021.

Occasionally I read something, and I wonder if I am on the same neonatology planet as another group. At the University of South Carolina they send about 16% of their babies <30 gestation home with gastrostomies and tube feeding. I found this rather bizarre, I know there are pressures in the US to send babies home that I don’t have to deal with, but that doesn’t seem to be the explanation here. The G-tube babies in this study are not going home early, indeed the major risk factor for not establishing oral feeding seems to be when you first offer oral feeds, which averages 40 weeks in their G-tube babies.

This centre seems to choose gastrostomy over home NG tube feeding, which I think is questionable unless you think the tube feeds are going to last at least several weeks. But we send very few preterm babies home with any kind of tube feeding. The G-tube babies in this study had a mean birth weight of just under 700g and lots of complications, but I am still really stunned by this extremely high frequency of needing home tube feeds. We are often too slow to insert a G-tube I think, when we reach around 42 weeks and babies aren’t feeding very well, and don’t have much sign of improvement then a G-tube may be the best option. I guess without actually doing the calculations that occurs in about 4% of our babies under 28 weeks (we have about 100 a year <28 weeks), almost all of whom are 22 to 24 week babies.

I would like to see some multicentre evaluation of this phenomenon, we should aim to determine whether one can reduce the numbers of babies who need home tube feeds by uniformly introducing oral feeding at different criteria. In South Carolina apparently their “criteria for oral feeding attempts were respiratory support of ≤0.5 LPM NC and PMA of at least 31 w”. This may be part of the difference from our centre, we routinely start oral feeds between 32 and 34 weeks regardless of O2 requirements, babies on high-flow cannulae have oral feeding attempts if they are still dependent on high-flow at 35 weeks, and we have tried to orally feed a few babies who were still on CPAP. We have a standardised feeding competence scale that we developed (and which I am supposed to write up, I will get round to it soon, honestly, maybe) and have just started nutrition rounds, which are mostly oral feeding rounds, with a great team of professionals, including an OT and lactation consultant.

This is something that has a huge impact on babies and their families, and it really needs much more attention.

Takahashi T, et al. Betamethasone phosphate reduces the efficacy of antenatal steroid therapy and is associated with lower birth weights when administered to pregnant sheep in combination with betamethasone acetate. Am J Obstet Gynecol. 2021.

I had forgotten, until reading this article, that the “Celestone” that we use in Canada for antenatal lung maturation is a mixture of 2 different molecules, betamethasone phosphate and betamethasone acetate. I vaguely remember hearing about this years ago, and assumed it was unimportant. Not so. Alan Jobe has been emphasising how little we know about this treatment for years, the dose we use is the same as was originally investigated by Liggins and Howie, which was an arbitrary extrapolation from animal data. What has been shown is that the kinetics of the two molecules are quite different, with the Phosphate having a rapid distribution from IM injection to the blood stream, while the Acetate absorbs more slowly and lasts longer.

In this study, pregnant sheep were randomized in 3 groups to either get placebo, or “celestone” (a mixture of betamethasone phosphate and acetate) just like our patients in threatened preterm labour, or just betamethasone acetate. They thought the acetate alone would give a good response as they have previously shown that prolonged low serum concentrations of betamethasone were effective. The total betamethasone dose was twice as large in the combination group as in the acetate alone group.

Efficacy was similar in terms of induction of surfactant synthesis, but the clinical response rate (determined by CO2 levels after 30 minutes of ventilation) was better with the acetate alone. Lung compliance was better and the pressure volume loops more normal with the acetate alone, the lambs were also smaller after the combination drug. There were much higher serum concentrations in the sheep and fetal lamb with the combination, and evidence of pituitary suppression with the combination compared to the acetate alone.

I think we are rapidly approaching having enough data to perform a clinical trial comparing celestone to the acetate alone.

Rakshasbhuvankar AA, et al. Vitamin A supplementation in very-preterm or very-low-birth-weight infants to prevent morbidity and mortality: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr. 2021.

I have always been a bit sheepish about not giving vitamin A to my very preterm babies, with the data showing a reduction in BPD with routine intramuscular injections. The evidence-based approach should be, I believed, to routinely offer vitamin A. My reticence was based on not knowing what the background vitamin A status of mothers in my region, and not wanting to give multiple intramuscular injections for what seemed to be about a 10% reduction in BPD. Vitamin A in TPN is degraded, and very little gets to the baby, although you might be able to improve that by protecting it from light and giving it separately, or mixing it in with the lipid, as is often done in Europe.

This new SR and meta-analysis confirms that vitamin A is probably effective, with a relative reduction in BPD of about 17%, but if you divide up the studies according to background vitamin A intake, those who had a higher enteral intake in the controls (>1500 units/kg/d) didn’t seem to have a benefit. Although the studies with the higher background intake were quite small with a total of 500 babies in a total of 5 trials, this makes me think that we should be making certain that enteral vitamin A intakes are adequate, and if that is difficult then consider parenteral supplementation.

Singh N, Gray JE. Antibiotic stewardship in NICU: De-implementing routine CRP to reduce antibiotic usage in neonates at risk for early-onset sepsis. J Perinatol. 2021;41(10):2488-94.

The CRP does not adequately differentiate between infected and non-infected babies. We should stop doing them. If you stop measuring CRP them you no longer have to treat raised CRP with antibiotics. This study showed that was true for early onset sepsis, there was a 30% reduction in antibiotic usage for early onset sepsis without any downside. If you do the same thing for Late-onset sepsis, where the data about the uselessness of CRP are equally strong, I am sure you would find the same thing. Less antibiotic use, no downside.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , , , , , , , , . Bookmark the permalink.

1 Response to Neonatal Updates

  1. Colin Morley says:

    Hi Keith, Thank you for introducing me to the ECG study during neonatal resuscitation “Electrocardiogram for heart rate evaluation during preterm resuscitation at birth: a randomized trial”. I have followed this literature over the last few years and been amazed that ECG is now recommended during neonatal resuscitation. The main claim for using it is that it detects the heart rate a bit earlier than pulse oximetry. That may or may not be true depending on how the two devices are used. However, I know of very few neonatal resuscitation stations that have an ECG and recommending it means extra expense for equipment that adds to the things that have to be done. The recent neonatal resuscitation recommendations have not provided evidence that detecting a heart rate a little earlier by ECG has any benefit, as this new study shows. Immediately after birth is a time of transition in cardiorespiratory parameters for many babies. It is possible that detecting the heart rate early during transition may encourage the resuscitation team to institute resuscitative measures that may not be needed if time and simple interventions are given time to help a baby transition.

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