Low-dose soybean emulsion may avoid newborn cholestasis: Study

A reduced dose of soybean fat emulsion seems to be better than the standard dose at preventing parenteral nutrition-associated cholestasis in newborns undergoing surgery and needing parenteral nutrition, or that given directly into the bloodstream.

That’s according to data from a Phase 3 clinical trial (NCT02357576).

While lower fat, or lipid, intake may adversely affect the newborn brain, “surgical neonates receiving reduced dose soybean lipid emulsion had [reduced cholestasis] trends without significant differences in growth or neurodevelopment,” the researchers wrote.

The study, “Prevention of Parenteral Nutrition-Associated Cholestasis Using Reduced Dose Soybean Lipid Emulsion: A Multicenter Randomized Trial,” was published in the Journal of Pediatric Surgery.

Cholestasis in newborns linked to parenteral nutrition

Cholestasis is marked by the reduced or blocked flow of the digestive fluid bile from the liver to the intestines. Impaired bile flow can damage the liver, resulting in bile leakage into the bloodstream and the onset of symptoms such as itching and yellowing of the skin and white of the eyes.

One of several different causes of the condition is parenteral nutrition, which is part of standard nutrition care for preterm neonates and infants when nutrient requirements cannot be safely provided via a feeding tube immediately after birth.

Because this intervention bypasses the digestive system, normal signaling between the intestines and the liver can become impaired, causing harmful bile buildup.

Several factors have been shown to increase the risk of parenteral nutrition-associated cholestasis, or PNAC, in newborns. These include premature birth, low birth weight, genetic variants, and certain enzyme deficiencies.

Ingredients in parenteral nutrition itself, such as lipids composed primarily of soybean oil, “have been implicated in the development of PNAC,” the researchers wrote.

Previous studies suggest that using SMOFlipid, a mixed soybean and fish oil lipid formulation, and Omegaven, a pure fish oil emulsion, may lower the incidence of cholestasis.

Both SMOFlipid and Omegaven are approved by the U.S. Food and Drug Administration for use in pediatric patients. Still, some patients cannot tolerate fish oil-containing emulsions due to allergic reactions.

Before SMOFlipid was introduced, a reduced dose of soybean lipid emulsion was typically used to lower the risk of PNAC. However, given the essential role of lipids in the newborn brain, a lower intake of lipids may result in a deficiency in a type of lipid called fatty acids, in addition to delayed neurodevelopment.

These concerns prompted researchers at the University of Michigan to conduct a trial to test a reduced dose of soybean lipid emulsion (SLE) against standard SLE in preventing PNAC in babies up to one year old who were undergoing surgery.

Bilirubin levels rose, then fell

A total of 21 newborns from four children’s hospitals across the U.S. were randomly assigned to receive either standard SLE, at 3 g/kg/day (nine newborns), or a reduced SLE dose of 1 g/kg/day (12 newborns) for 12 weeks (about three months).

The study’s primary goal was to evaluate changes in the blood levels of bilirubin, a substance in bile and a marker of liver damage and bile leakage into the bloodstream. PNAC was defined as a bilirubin level greater than 2 mg/dL on two measurements one week apart in newborns undergoing parenteral nutrition for at least 14 days.

Blood bilirubin levels initially rose and then steadily fell in both groups, with a slower initial rise among those who received the reduced SLE dose. Moreover, bilirubin decreased sooner in the low-dose group than in the standard dose group (by 27 days, compared with 63 days). The drop was also faster with the reduced dose.

None of these group differences reached statistical significance.

PNAC and severe PNAC occurred more often in the standard SLE group, but the overall incidence was low and was not significantly different between the groups.

Two infants in the reduced-dose group had biochemical evidence of mild essential fatty acid deficiency, but neither had clinical evidence of such a deficiency or required clinical intervention. No patients in the standard SLE group showed signs of fatty acid deficiency.

Over time, there was no significant difference in body weight or height trajectories between the groups. Members of both groups initially lost weight, then gained weight after day 46.

In terms of neurodevelopmental outcomes, all eight infants who completed a two-year follow-up assessment showed normal gross motor function for their age, as assessed by the Gross Motor Function System Classification. Scores of the Behavior Assessment System for Children were also similar between groups.

Seven of these infants showed no problematic behaviors, deficits, or delays on the Brief Infant Toddler Social Emotional Assessment. However, the remaining child, who received a reduced SLE dose, performed worse in certain cognitive skills and behavioral and emotional control.

This study “adds to the growing body of literature demonstrating that reduced dose SLE strategies results in favorable direct bilirubin trajectories, a low incidence of PNAC while allowing for normal age-related growth,” the scientists wrote.

“While larger studies evaluating the long-term outcomes of this strategy are still needed, our data suggest that neurodevelopmental outcomes are not worse in surgical neonates treated with a reduced SLE dose strategy,” they concluded.

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