What’s Happening on the Edge of Viability

A study (N Younge et al. NEJM 2017; 376: 617-28) provides some data on the slowly changing survival and neurodevelopmental outcomes among periviable infants (22-24 weeks gestation).

From epoch 1 (2000-2003), to epoch 3 (2008-2011), there has been some improvements. Overall survival increased from 30% to 36% and the percentage without neurodevelopmental impairment increased from 16% to 20%.

Mortality and Neurodevelopmental Outcomes at ~18 months of age (combined data and 11 centers)

Mortality and Neurodevelopmental Outcomes at ~18 months of age (combined data and 11 centers)

The insightful commentary (pgs 694-6) notes that there has not been improvement in survival in infants born at 22 weeks.  Furthermore, in reviewing multiple studies on outcomes, neurodevelopmental impairment was >94% in patients born at 22 weeks and between 80-90% for infants born at 23 weeks.  At 24 weeks, neurodevelopmental impairment was present between 51-72%

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Related blog posts:

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…

Does necrotizing enterocolitis cause neurologic deficits?

Quite possibly (J Pediatr 2012; 160: 409-14).

There have been recent reports that surgery in preterm and even term infants can affect neurodevelopmental outcomes.  This report, which looked at infants born at <30 weeks or birth weight of <1250 g, adds more information in this area.  The surgery group (n=30) had more white matter injury on MRI and lower developmental scores at 2 years than the nonsurgical group (n=178).  Infants requiring bowel surgery had the worst outcomes.  The exact reasons for these outcomes and the significance are unclear, in part due to the small number of infants with bowel surgery.  Potential factors include inflammatory mediators/cytokines, and anesthesia effects.

The article notes that the FDA has issued warnings regarding anesthetic use in neonates and young children.  These agents may cause abnormalities in the developing brain, particularly in the thalamus.

This study has a number of limitations including the lack of preoperative comparative imaging studies.  Nevertheless, despite unresolved issues regarding causality, it is clear that infants who have necrotizing enterocolitis remain at high risk for poor neurodevelopmental outcomes.

Additional references:

  • -Anesth Analg 2007; 104: 509-20.  Anesthetics in neonates and young children.
  • -J Pediatr 2008; 153: 170-5. Adverse neurodevelopmental outcomes in infants with sepsis or NEC.