Modifications of Own Mothers’ Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial

Abstract

The aim was to investigate the effect of two own mother’s milk (OMM) fortification protocols on (a) IGF-I and ghrelin plasma levels at 35 post-conceptional weeks (PCW, T2) and whether this effect is maintained after elimination of the differences in OMM fortification, and (b) growth until 12 months corrected age. Forty-eight OMM-fed preterm infants (GA 24–32 weeks) were randomly allocated to the fixed-fortification (FF) group (n = 23) and the protein-targeting fortification (PTF) group (n = 25) targeting the recommended daily protein intake (PI). Plasma IGF-I and ghrelin were assessed at 35 (T2) and 40 (T3) PCW while growth was longitudinally assessed until 12 months corrected age. PTF group had lower IGF-I and higher ghrelin than FF group at T2, while receiving lower daily protein and energy amounts. PI correlated positively to T2-IGF-I and inversely to T3-ghrelin while energy intake (EI) correlated inversely to T2- and T3-ghrelin. Group and PI were independent predictors of adjusted T2-IGF-I, while group and EI were predictors of adjusted and T2-ghrelin. Growth parameter z-scores were comparable between groups up to 12 months corrected age. Modifications of OMM fortification have a transient effect on early plasma IGF-I and ghrelin levels in preterm infants in a way consistent with the previously recognized protein-energy/endocrine balance, indicating a potential programming effect.

State of the evidence from clinical trials on human milk fortification for preterm infants*

“…One study found no differences in growth or body mass index from 40 weeks to 12 months corrected age. 12…”

Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants

“…Targeted values for the macronutrient and energy content of enteral feeds are typically based on consensus recommendations for preterm infants, including 3.5-4.5 g/kg/day protein, 4.8-6.6 g/kg/day lipids, 11.6-13.2 g/kg/day carbohydrates, 110-135 kcal/kg/day, and protein/energy ratios of 3.2-4.1 g/100 kcal [2]. Fortification may be achieved through a combination of multicomponent fortifiers, as well as specific modular macronutrient products such as medium-chain triglycerides, safflower oil, whey protein, casein-based liquid protein, maltrodextrin, and glucose polymers [43,[45][46][47][48][49]. A human-milk-derived cream fortifier is also commercially available to provide additional fat, protein, and carbohydrate content [45].…”

“…A human-milk-derived cream fortifier is also commercially available to provide additional fat, protein, and carbohydrate content [45]. The frequency of human milk analysis in studies of targeted fortification has ranged from twice daily to weekly [43,45,46,[48][49][50]. In a study evaluating the effects of differing sampling intervals ranging from daily to weekly, Rochow et al found that twice weekly milk analysis achieved macronutrient intake within 5% of targeted goals [50].…”

“…One study that achieved targeted fortification utilizing the addition of a human milk-based cream also found superior growth velocities for weight and length compared to standardized fortification [45]. In two studies that did not find any growth benefits from targeted fortification, the macronutrient content of analyzed milk was actually greater than assumed reference values, such that infants in the targeted fortification group received less supplementation compared to controls receiving standardized fortification [48,49].…”

Mapping the Evidence on Human Milk Fortification and Cardiovascular Risk Factors and Outcomes among Low Birth Weight Infants: A Scoping Review

“…Current literature indicates that nutrition in early life is associated with long-term growth and neurodevelopment. Among preterm and LBW infants, an HM-based diet may reduce morbidity and mortality [6][7][8][9]. However, HM alone is insufficient to meet the nutritional needs of preterm and LBW infants at regular feeding volumes [10].…”