Our results show that in a cohort of VPI fed predominantly HM with standard fortification, those receiving more HM during their first 28 DOL had slower postnatal growth during admission than those who were on PF. In the HM-fed VPI group, both weight and weight z-score at 36 weeks PMA and at discharge were lower, while FZS in weight from birth to 36 weeks GA and to discharge and the percentage of patients showing PGF were higher, as previously reported [9, 19, 20]. In an adjusted analysis, increase in WLR and BMI from birth to discharge was smaller in predominantly HM-fed infants, while head growth showed a trend to be better preserved.
Exclusive HM feeding has been associated with reduced mortality and a decrease in morbidity of VPI [21]. However, artificial formula results in higher rates of weight gain and linear growth than HM due to its greater amount of nutrients, particularly in the case of DM, which may be further compromised by pasteurization [8]. Human milk only provides about 60% of the protein requirements when fed in adequate amounts to sustain energy requirements in preterm infants [1], so that an insufficient protein supply through standard fortification could lead to a low protein-energy ratio resulting in deficient lean mass retention [8]. This is in line with the findings of a study using whole-body MRI for the assessment of body composition [22], but contrary to a recent literature review which suggests that HM feeding in preterm infants, although related to a slower weight gain than formula feeding, is associated with a better promotion of fat free mass (FFM) deposition [20]. Other potential contributors to delayed growth of HM-fed infants in our cohort are feeding volumes at 28 DOL, which did not reach 160 ml/kg/day (lower limit of the recommendation for a stable growing preterm infant) [23], and standard HM fortification. Recent recommendations of the European Milk Bank Association recognized that “Standard Fortification” can fall short in supplying sufficient protein for some VPI and encouraged the use of “Individualized Fortification” to optimize nutrient intake [24], although this practice is not yet widespread.
Apart from measuring growth in terms of increase in weight or length, the quality of body composition is also relevant in relation to future health outcomes. Several studies have shown that body composition of preterm infants when they reach term equivalent age is different from that of their term newborns counterparts [25], with a higher percentage of total body fat [16, 25, 26].
Assessment of body composition in preterm infants is challenging, as most methods used in research settings are difficult to implement into daily clinical practice [27]. Alternative options include using skinfolds or anthropometric ratios (WLR, BMI or ponderal index) to predict body composition [25, 27]. Although at birth the WLR seems to primarily correlate with FFM (R2 0.92) [16], changes in WLR and BMI better reflect an increase in adiposity after the first weeks or months of life, once the postnatal deposition of body fat begins, at least in term infants [28]. Our study showed that preterm infants fed ≥ 75% HM (Group 1) had a lower WLR at birth and discharge than infants in group 2, but a higher increase in WLR and BMI from birth to discharge. This seemed to result from the confounding effect of a higher chronological age, as the adjusted analysis pointed to a protective effect of HM in the sense of a slower deposition of fat mass (FM) as assessed by the increase in body ratios (WLR and BMI). A similar effect on BMI increase, particularly in association with formula protein intake has also been reported in healthy infants [29].
Another difference in the pattern of growth between groups refers to proportionality between head and whole body growth. Head circumference z-score from birth to discharge decreased in both groups, with no difference between them. However, the magnitude of change of HC z-score from birth to discharge tended to be smaller in group 1 with respect to the change in body weight z-score, which suggests that head growth could be somehow prioritized. This could be an explanation of why, in spite of slower weight gain, neurodevelopmental outcomes are better in preterm infants fed OMM [10], although differential patterns of body growth are rarely reflected in the literature, making interpretation difficult.
We have analyzed growth outcomes in a cohort of VPIs in relation to preferential HM or formula-feeding. Although we only considered the source of nutrition up to 28 days, it was recorded in detail (daily for the 1st 14 DOL and then for day 28) at a time point that has been shown to predict EN at discharge [30]. One of the limitations of our study, inherent to the retrospective design, is the available sample size and the baseline differences between groups, which we tried to address by adjusting for potential confounders, as GA and severity of clinical course. There is a moderately high rate of breastfeeding in our sample, and the proportion of DM consumed was under 5% in both groups, so these results reflect mostly OMM. Lastly, we lack follow up data to see the impact of these differences later on.