Weight Gain in Preemies, Neurodevelopmental Outcomes, and Reverse Causation

Since a trial which randomizes premature infants into groups that are well-nourished and poorly-nourished and then following them prospectively is never going to happen, it is difficult to know with certainty the effects of optimal nutrition are with respect to long-term neurodevelopmental outcomes.

An article I enjoyed reading on this subject (MB Belfort et al. J Pediatr 2016; 168: 30-5) pushes back on the correlation between good weight gain, as a surrogate marker for nutritional status, and neurodevelopmental outcomes.

In this study, 1070 infants between 23-27 weeks gestational age were followed with weights on days 7-28 along with weights at 12 and 24 months.  This data was compared with several indices on neurodevelopmental outcome.  Here is the key finding:  “Weight gain in the lowest quartile from 7-28 days was not associated with higher risk of adverse outcomes.”

In commentary on their findings, the authors point out that “we found no evidence to suggest that faster weight gain from 7 to 28 days of life reduced the risk of adverse outcomes…almost all of the associations between low weight gain..were attenuated or eliminated when we restricted our analysis to those children able to walk independently.”

“Overall, it appears that low weight in children with severe neurodevelopmental impairments may be caused by factors closely related to the impairments themselves…reverse causation may be at play.” Thus, underlying brain damage may limit body weight gain, rather than poor nutrition limiting brain development.”

My take: I may be apt to ‘confirmational bias’ as this study reinforces my view that improved nutrition may not change outcomes appreciably.  To be clear, I still believe that efforts to optimize the nutrition of premature infants are a good idea but we need to be skeptical about the magnitude of benefit that we will derive.

Related blog posts:

A Few Years Ago in Yosemite

A Few Years Ago in Yosemite

Improving Outlook in Neonatal Nutrition (Part 1)

I recently had the opportunity to hear a terrific lecture by David Adamkin (University of Louisville) on neonatal nutrition.  Unlike previous lectures that I’ve highlighted on this blog (Neonatal Nutrition Lecture -What We Know Right Now …) which focused on enteral nutrition and breastmilk.  This lecture focused on providing early parenteral nutrition to prevent postnatal growth failure.

"Father" of TPN was Stanley Dudrick (1968)

“Father” of TPN was Stanley Dudrick (1968)

Introduction of TPN dramatically improved survival for many infants.  In disorders like gastroschisis, TPN increased survival from ~10% to 90%.

Extreme premature infants have minimal energy reserves

Extreme premature infants have minimal energy reserves

At 24-28 weeks gestational age, fetuses are ‘bathed in amino acids’ and extreme premature infants need early amino acids.  At University of Louisville, the neonatologists try to deliver ~3 gm/kg/day of amino acids in 1st 1-2 days in order to match intrauterine growth and prevent growth failure. Half of postnatal weight loss is water; other half is related to proteolysis.  To facilitate TPN at all hours, they use a stock solution (4% amino acids at 60 mL/kg/day delivers 2.4 mg/kg/day of protein; 80 mL/kg/day delivers 3.2 mg/kg/day of protein.

Return to Birth Weight Time is Correlated with Growth Failure

Return to Birth Weight Time is Correlated with Growth Failure.  Extreme prematurity has been correlated with slower return to birth weight

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Lack of correlation between BUN and Protein Intake

Lack of correlation between BUN and Protein Intake

BUN increases with any protein intake but not affected by protein intake -issue has to do renal fxn, comorbidity.  Smaller & sicker have higher BUN.

Key points:

  • The more premature, then the longer it takes to return birth weight and more growth failure
  • Poor growth related to neurodevelopment outcomes
  • With higher protein intake, there is better glucose tolerance; protein intake helps with glucose tolerance & lowers chance of hyperkalemia

More tomorrow…