The “Breastfeeding Paradox” as a Guide for the Assessment of Premature Infants Growth: It Is More Than Just Weigh-Ins

One of the most significant challenges for the neonatologist is to ensure that the preterm newborn achieves an adequate postnatal growth by providing the right amount and type of nutrients after birth. The extrauterine environment per se, organ immaturity, and frequent comorbidities often make it doubly, if not triply, challenging to ensure adequate nutrition in this frail population. ¹ Furthermore, impaired growth in early life is accompanied by altered body composition development, which may negatively affect health outcomes, particularly metabolic and neurodevelopmental outcomes. ²

Traditionally, it has been recommended that the growth of preterm infants should match that of healthy fetuses of equal gestational age, ³ resulting in increasingly aggressive nutrition practices, especially with regard to energy and protein intake. However, despite “aggressive nutrition,” such a goal is rarely achieved, and many preterm infants end up being classified as extrauterine growth restricted (EUGR) at discharge. ⁴

With the development of INTERGROWTH-21st Preterm Postnatal Growth Standards, it has become clear that a premature newborn will never be able to grow like a fetus because of the inherently different environment in which it lives and its unique postnatal metabolic and nutritional mechanisms. The INTERGROWTH-21st Preterm Postnatal Growth Standards are based solely on the growth of healthy preterm infants fed according to the current nutritional guidelines and, therefore, represent the most useful tool to monitor postnatal preterm infants' growth. ⁵

Furthermore, unlike previous reference curves derived from cross-sectional data and retrospective approaches, the INTERGROWTH-21st standard curves derive from a prospective longitudinal evaluation, documenting how preterm infants grow under ideal nutritional and clinical conditions. The use of these curves should minimize the improper overdiagnosis of EUGR.

However, using the proper charts is often not enough to adequately assess the growth of preterm infants.

It is not uncommon in Neonatal Intensive Care Units to give great significance to the newborn's weight gain while assessing the adequacy of nutrition and growth. This is understandable as weight is a variable that can be easily measured even in the critically ill patient. However, what would be needed is the analysis of premature infants' growth by considering the critical role played by body composition development in the modulation of health outcomes. ² The quality of growth, determined by the fat-free mass and fat-mass ratio, should also be evaluated in addition to weight gain.

To date, numerous techniques, such as plicometry, isotope dilution, dual-energy X-ray absorptiometry, magnetic resonance imaging, and air plethysmography, can determine neonatal body composition. In the clinical setting, such measurements are not always feasible and thus, they are often used only for research purposes. However, a growing body of literature has demonstrated that the accurate measurement of length and head circumference may nonetheless provide reliable information on fat-free mass deposition and brain growth, respectively. ⁶

Aggressive nutrition may not always be the appropriate approach to ensure adequate postnatal growth in preterm infants, as protein excess may alter the development of fat mass, worsening their well-known predisposition to deposit fat mass at a higher rate than term infants until 50 weeks postmenstrual age. ⁷

Of note, in 2012, Rozè et al. ⁸ introduced the concept of “the apparent breastfeeding paradox” that describes the observation of a more favorable neurodevelopmental outcome in breastfed preterm infants despite the suboptimal weight gain characterizing their initial growth pattern. Several authors had previously documented an association between poor weight gain during hospitalization and later cognitive dysfunction. ⁹ In contrast, Rozè et al. ⁸ observed better neurodevelopmental outcomes in the breastfed preterm group regardless of a lesser weight gain during hospitalization.

From this perspective, the lower postnatal growth rate shown by breastfed preterm infants can be interpreted as reflecting the ability of breast milk to promote an increased fat-free mass acquisition, which is correlated with better long-term metabolic and neurodevelopmental outcomes. ²

Consequently, the “breastfeeding paradox” should be taken into consideration when implementing a nutritional approach that does not rely solely on immediate and measurable data such as daily weight gain but rather trusts the synergistic mechanisms through which nature has selected substances in mother's milk (MOM) that promote the metabolic balance and the development of organs and systems of the premature newborn. We should also keep in mind that, although the introduction of donor human milk (DHM) has undoubtedly brought significant advantages to the preterm population, DHM cannot be considered an equal substitute for MOM, since pasteurization reduces its functional components. ¹⁰

The preterm nutritional challenge continues after discharge from the NICU. Frequently, preterm infants are discharged earlier than term equivalent age, growth restricted, and still with a certain degree of neurological and gastrointestinal immaturity. ¹¹ To this day, it is a widespread practice in different NICUs to suspend HM fortification before discharge in light of the lack of robust scientific evidence ¹² indicating the growth and neurodevelopmental benefit of fortification supplementation after discharge. This could be due to the infant's ability to increase breast milk intake, mainly because of breast milk's tolerability and digestibility.

Once clinically stable and discharged, the breastfed preterm infant would seem to be able to adapt and increase his/her breast milk intake, thus regulating the intake of macro- and micronutrients and benefiting from the “breastfeeding paradox” that seems to be the key to more promising development.

It is essential to keep closely monitoring auxological parameters even after discharge, aiming above all at identifying both a lack of and, conversely, also an excess of weight recovery mainly in fat mass, typical of formula-fed babies, given the higher risk of adverse metabolic outcomes, which are already characteristic of preterm infants. ¹³

In conclusion, given the available scientific evidence already mentioned, breastfeeding promotion seems the most promising route to optimize preterm nutrition and growth from an auxological point of view and, foremost, from a metabolic and developmental perspective. DHM can be considered the second-best option while acting as a bridge toward exclusive MOM feeding. Meanwhile, the premature infant must be monitored with growth curves that reflect the standards built on its population, such as the INTERGROWTH-21st Preterm Postnatal Growth Standards, and should be closely monitored in all its three auxological parameters, considering length and head circumference as reliable indicators of fat-free mass deposition.

When addressing the faltering growth of a premature infant fed with HM, it is advisable to bear in mind the “breastfeeding paradox” in order not to rely on an unjustified or excessive supplementation of formula milk, both during the hospital stay and after discharge.