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For preterm infants awaiting the chance to breastfeed, none of the common methods of nutritional support emerged a clear winner in head-to-head comparisons in the DIAMOND trial.

For infants born between 32 and 35 weeks 6 days' gestation -- comprising 85% of all preemies worldwide -- mean body-fat percentage at 4 months was similar when comparing parenteral nutrition versus dextrose solution (26.0% vs 26.2%, P=0.72) and milk supplement versus exclusively mother's breast milk (26.3% vs 25.8%, P=0.25).

Exposing infants to taste and smell also didn't impact time to full enteral feeding (5.8 vs 5.7 days with nonexposure, P=0.59), researchers led by Frank H. Bloomfield, PhD, of the University of Auckland, New Zealand, reported in the .

While the benefits of breastfeeding are well established, the researchers noted that "[m]ost moderate-to-late-preterm infants need nutritional support after birth pending a sufficient supply and intake of mother's breast milk."

In the absence of strong evidence or guideline recommendations as to when or how nutritional support beyond breastfeeding should be provided, practice has widely varied.

In theory, the benefits to enriched feeding would be related to "prevention of a nitrogen deficit and protein catabolism," whereas providing taste and smell is believed to "stimulate the cephalic phase response, which would aid gastrointestinal function and the metabolic response to food and lead to reduced time to full enteral feeding," Bloomfield's group noted.

However, in the absence of any difference in early outcomes in DIAMOND, the researchers suggested targeting efforts elsewhere for infants of mothers who intend to breastfeed, even if the milk supply takes several days to become sufficient.

"Our findings support an approach that concentrates on providing mothers with necessary lactation support, thereby maximizing the likelihood of attaining exclusive breast-milk feeding," Bloomfield and colleagues wrote.

They noted that the findings apply to "infants in neonatal nurseries in which there is dedicated lactation support for mothers who intend to breastfeed, as was the case in this trial."

Their DIAMOND (Different Approaches to Moderate and Late Preterm Nutrition: Determinants of Feed Tolerance, Body Composition and Development) trial included 532 infants admitted to a neonatal unit at five hospitals across New Zealand who were born between 32 weeks 0 days' and 35 weeks 6 days' gestation, had IV access for clinical reasons, and whose mothers intended to breastfeed. Exclusions included newborns who needed a specific mode of nutrition and those with a known chromosomal or genetic abnormality or congenital disorder affecting growth, body composition, or neurodevelopment.

The trial used an multifactorial design to randomize infants within 24 hours after birth in a 1:1 ratio to one of eight possible combinations:

• Amino acid solution for parenteral nutrition versus IV dextrose
• Milk supplementation from donor breast milk or infant formula versus only breast milk from the infant's mother as enteral nutrition
• Exposure or no exposure to the taste and smell of milk before each tube feeding (0.2 mL of milk in the mouth with a syringe immediately before and 0.1-0.5 mL milk on a piece of gauze near the nose during feeds)

These interventions occurred until the supply and intake of the mother's breast milk met the goal prescribed by the clinical team, with the aim of reaching full feeds of only mothers' breast milk as quickly as possible. IV lipid emulsion could also be given at the clinician's discretion.

No significant interactions were seen among the interventions with regard to the primary outcome of mean body-fat percentage at 4 months for the parenteral vs dextrose and milk supplementation vs mothers' milk groups. Similarly, there was no interaction in the primary outcome of time to first full enteral feeding for the taste and smell intervention.

Secondary outcomes were similar across interventions, including body composition characteristics, time to full sucking feeds, time to full enteral feeding, breast-milk feeding status at the time of hospital discharge and at 4 months of corrected gestational age, and length of stay in the hospital.

One infant had three serious adverse events (necrotizing enterocolitis, gastrointestinal surgery, and death), which were not considered trial-related. That baby had been assigned to parenteral nutrition, mother's breast milk only, and no smell and taste intervention.

The overall lack of impact of the interventions on body composition "may be due to the short period of time nutritional support was provided, with most infants reaching full enteral feeding within a week after birth," the researchers suggested. "The lack of any discernible effect of smell and taste exposure in this trial may be attributable to the multiple stimuli in a neonatal intensive-care environment, including numerous odors, which might have overcome any potential effect of the smell and taste of milk."

While the large sample size was an advantage, the trial was limited by its unblinded design and by constraints from the COVID-19 pandemic. Although 85% of the infants were assessed at 4 months, "many of these assessments were undertaken in the infants' homes rather than in a clinic, owing to family preference," the researchers noted. Still, 61% had assessment of percentage of fat mass at 4 months, which exceeded the number needed to power the trial for that primary outcome endpoint.

Another limitation was the relatively short-term outcomes assessed in the trial, Bloomfield and colleagues wrote. "Two-year follow-up of the infants enrolled in this trial to assess neurodevelopment is ongoing."

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