University of Auckland: Protein boost no advantage for tiny prem babies

The prevailing wisdom that boosting protein would safely help the growth of very preterm babies is questionable, say University of Auckland researchers who have just run the largest study to date on this theory.

The Liggins Institute-led multicentre, blinded and controlled study randomised 217 tiny babies (less than 1kg at birth) to receive an extra 1g of protein per day intravenously for the first five days after birth. Another 217 babies were randomised to a placebo group. See New England Journal of Medicine.

“For many years, international recommendations have suggested we need to give the smallest preterm babies more protein to support their growth and development, because these babies don’t grow very well after birth,” says lead investigator and Liggins director Professor Frank Bloomfield.

“Yet it is actually very challenging, because there’s a limited amount of fluid you can give these babies and they often are quite unwell,” Bloomfield says.

“In this trial, we used a novel way of giving babies some additional protein to determine the effects on an important outcome, which is survival free from disability, rather than just growth, which is what most other smaller studies have looked at.”

Although both survival and survival without neurodisability have improved, internationally up to half of extremely low birthweight babies have some degree of neurodevelopmental impairment.

In this trial, 60 percent of these extremely preterm babies who survived to two years of age were free from any disability, reflecting the excellent standards of neonatal care in New Zealand.

The trial, which received ethics approval, was discussed with parents who gave informed consent.

Of all the babies involved, 94 percent were followed up at two years of age.

In the group that received the extra protein, researchers found no improvement in survival free from neuro-disability – the primary outcome of the trial.

However, secondary outcomes from the trial surprised researchers and raised queries that require further research.

“We found the intervention was associated with an increased risk of moderate-to-severe neuro-disability in those babies who survived and also with a condition called ‘refeeding syndrome’, which has only recently been discovered in preterm babies,” Bloomfield says.

Refeeding syndrome is a serious effect of feeding after an extended period of starvation. It involves shifts in electrolytes that, if not managed, can be harmful.

The Liggins-led researchers recommend international guidelines for protein administration in very preterm babies, which have until now been based only on expert opinion, should not be increased.

“The current administration of protein, which is now lower than when the study began, appears to be sufficient to support a level of growth that is adequate for neurodevelopment,” Bloomfield says.

In addition, he says, very preterm babies need to be monitored for refeeding syndrome.

In New Zealand, the researchers would like to see national guideline recommendations introduced for nutritional care of extremely preterm babies. During the trial, they found there was significant variation in practice across the country’s six neonatal units providing this level of care.

While these findings will help clinicians discuss nutrition with parents of extremely small preterm babies, Bloomfield says the best thing parents can do for their baby’s nutrition is to provide breastmilk.

The Liggins Institute is also conducting research on nutrients that may assist very preterm babies, including phosphate and vitamins.