As there is no way I can catch up after the break, I will post a few ‘neonatal Updates’ to point my readers to things I found interesting over the last couple of months, this first group is all about nutrition.
Impacts of undernutrition
First off two animal studies:
Wedgwood S, et al. Postnatal Growth Restriction Augments Oxygen-Induced Pulmonary Hypertension in a Neonatal Rat Model of Bronchopulmonary Dysplasia. Pediatr Res. 2016. Neonatal rats exposed to room air or 75% oxygen were randomized to either get usual nutrition or to get reduced nutrition. This was done by either putting 10 rats in a litter, or 17. The rats who were 17 to a litter will automatically get less nutrition, as apparently the dam (the mummy rat) produces milk which is larger volume, similar in lactose and protein, but has a lower fat concentration. After 14 days of this they weighed only 24 grams compared to the controls that weighed about 33 g. The growth restricted rats were even smaller if they were also hyperoxic (21 g).
Individually, hyperoxia and growth restriction increased pulmonary arterial pressure, right ventricular wall thickness, and pulmonary arterial medial wall thickness, and led to fewer pulmonary vessels. The rat pups who were both growth restricted and hyperoxic were worse off than either of the comparison groups. They also did some metabolomics and other fancy analyses that I will let you read about yourselves. Basically though undernutrition (in this case specifically too little fat) makes the lungs more susceptible to oxygen toxicity.
Joss-Moore LA, et al. Alveolar formation is dysregulated by restricted nutrition but not excess sedation in preterm lambs managed by noninvasive support. Pediatr Res. 2016. This looks like a great study, unfortunately I found some of it hard to understand. Preterm lambs (we don’t know how preterm as the gestational age at delivery doesn’t seem to be in the manuscript) were intubated at birth and extubated within 3 hours to get non-invasive ventilation. They were then randomized to either have good nutrition and standard sedation, or have reduced nutrition, or excessive sedation (using pentobarbitol in all cases, around about 0.8 mg/kg/d for the usual sedation groups an 6 times as much for the high sedation group). I can’t tell you how much nutrition the restricted group received, the normal nutrition groups got a goal of 150 kcal/kg/d and the restricted group was “based on the volume of milk tolerated by historical preterm lambs managed by invasive ventilation”. In the results, the table 2 notes that the controls received 283 kcal/kg on day 20, but the restricted nutrition group got 211 kcal/kg less than that (I think), and basically didn’t gain any weight at all between birth and day 20.
There were major impacts on lung alveolarization, which is of course an important part of BPD, and which suggests that lungs need nutrition to grow and to repair.
And a human epidemiologic study:
Guellec I, et al. Effect of Intra- and Extrauterine Growth on Long-Term Neurologic Outcomes of Very Preterm Infants. The Journal of pediatrics. 2016;175:93-9 e1. This is an analysis of data from the EPIpage study, which was a regional cohort of babies born between 22 and 32 weeks gestation in 9 regions of France. They report the association between growth, from birth to 6 months of age, and neurologic and developmental outcomes.
They classify babies into appropriate and small for gestational age, and then into whether they gained or lost more than 1 Standard Deviation in weight, between birth and when they reached 6 months.
Babies who were AGA and lost 1 SD had worse outcomes, with much more cerebral palsy, and much more cognitive delay; both evaluated at 5 years of age. Those who stayed in their percentiles or gained weight (relatively) were similar.
Among the SGA babies there were only 5 who lost percentiles, the remainder either stayed on their percentiles or had some “catch-up”; those who had catch-up had in general slightly better outcomes than the SGA babies who remained in their percentiles, although the differences may have been due to chance.
Good postnatal nutrition aiming at staying on the same percentile or improving percentiles if you are SGA should protect against BPD, and is associated with improved long-term neurologic and developmental outcomes. Improving growth outcomes is possible without increasing complications.