Postnatal growth of small for gestational age late preterm infants: determinants of catch-up growth

The literature shows that being a late preterm neonate represents a risk factor for adverse short and long-term outcomes compared to full-term newborns.14 However, because of a paucity of data regarding the neonatal variables and the mode of feeding associated with the persistence of postnatal growth restriction, catch-up growth represents one of the main challenges for clinicians.

According to our findings, more than 80% of our late preterm and SGA infants showed a catch-up growth in weight and length at 3 and 6 months of corrected age. On the other hand, weight growth tended to decrease, and almost 60% of children maintained to catch-up growth at 12 and 24 months of corrected age, while the growth trajectory for length remained substantially stable for 70% of children. The decrease in the growth trajectory following the first 6 months of corrected age could be partially explained by the introduction of solid foods between 5 and 8 months of life.15 Indeed, complementary feeding in preemies represents a crucial period that requires the acquisition of specific neurodevelopmental skills and that is linked to the onset of new symptoms related to oromotor dysfunction and avoidant feeding behavior, such as choking and spitting.4,15 Furthermore, two surveys conducted in Italy and UK underlined that many mothers of low birth weight newborns, with the introduction of complementary feeding, didn’t perceive the importance of an adequate energy intake and offered their infants nutritionally inadequate diets.16,17

At 36 months of corrected age, however, only one-third of children showed weight and length values lower than the 10th percentile, highlighting a variety of growth trajectories during early infancy. Moreover, not having reached catch-up growth at 12 months and being born singleton were associated with an increased risk of not reaching both weight and length catch-up growth even at 36 months.

On the other hand, the vast majority of our cohort already achieved head circumference catch-up growth at 12 months. The importance of this result is emphasized by the close relationship between head circumference growth and neurodevelopmental outcome of preterm infants, as described in the literature.18,19

There is a lack of data regarding the weight and length growth trajectory of late preterm infants. Zhang et al. in a recent observational study, evaluated the growth in a cohort of 599 healthy late preterm infants and showed a catch-up growth in length and weight of 30.7% and 46.2%, respectively, at term corrected age, but no data on early childhood growth were available.20 Han et al., in their longitudinal study, assessed a cohort of 10,624 preterm newborns (born before 37 weeks of gestational age) and showed that the vast majority of children reached a weight’s catch-up growth at 24 months of life, especially those who were SGA at birth (90.3%). Moreover, in Han et al.‘s study, catch-up growth was associated with an increased risk of being overweight in later life.21 On the other hand, Santos et al. highlighted a failure to thrive in the first 2 years of life for late preterm infants rather than term ones.22

There is no consensus regarding the proper weight gain pattern for preterm infants.23 Furthermore, an emerging body of evidence suggests that body composition analysis of preterm infants may help optimize infant nutrition.24,25 In a recent study, McLeod et al. evaluated the possibility of monitoring early changes in the body composition of preterm infants in response to specific macronutrient intake. In particular, they highlighted that higher energy and fat intake was positively associated with increased fat mass and higher protein and carbohydrate intake was positively associated with increased fat-free mass.24,26 Moreover, changes in the percentage of fat mass and fat-free mass in children who were preterm born are associated with different growth patterns and could influence neurological and motor long-term outcomes and be related to cardiovascular and metabolic diseases in adulthood.24,27 In their studies, Roggero et al. and Yau and Chang reported that preterm newborns at term corrected age showed a higher percentage of body fat content, measured by an air displacement plethysmography system than full-term infants.27,28 These findings were even more evident for SGA preterm neonates than in SGA term ones, as was shown by Giannì et al., whereas the mean body weight between the two study groups was comparable.29

Moreover, our results showed that having IUGR is associated with a greater chance of achieving catch-up growth per length at 36 months of corrected age. Several studies highlighted that children with IUGR often show a pronounced catch-up growth in the first years of life, getting closer to the genetic growth trajectory.20,30 On the other hand, Kesavan and Devaskar31 underlined that although having IUGR is associated with rapid catch-up growth in early life, the more severe IUGR is, the less these children will reach a standard height in adulthood.

In our study, among the non-modifiable factors, being born singleton represents a risk factor for slower weight and height growth velocity in early life. These data have been confirmed by several studies in the literature.20,32 Therefore, we could speculate that the initial IUGR and SGA births found more frequently in twins than in singletons are due to factors related to pregnancy, and a resulting catch-up growth could be expected in extrauterine life. However, the relationship between twin pregnancy and IUGR or SGA infants still needs further studies to be adequately investigated.

Despite the lack of data in the literature, the postnatal growth of late preterm infants is undoubtedly influenced by several variables, including type and mode of feeding.14 Although Verd et al. in their study, have evaluated the growth pattern of two groups of extremely low birth weight infants divided into exclusive human milk-fed and formula-fed one, no significant differences were found in terms of weight gain in the two groups.33 On the other hand, several studies have evaluated the effect of an exclusively human milk-based diet on preterm infants’ growth, and the vast majority of them found a lower percentage of fat mass deposition when compared to mainly formula-fed infants.34,35,36 Moreover, in a recent study, Mòl et al. compared a cohort of mainly formula-fed preterm infants to a group of term newborns. A more significant deposition of fat mass was highlighted in the group of preterm formula-fed babies rather than term ones37 and this effect could be dose-dependent, as reported by Giannì et al.34 Furthermore, exclusively breastfed preterm infants showed a slower weight gain than term ones.38 The mechanism that links breastfeeding to a slower growth pattern than formula feeding and that ultimately leads to better metabolic and neurodevelopmental outcomes was defined by Rozè et al. as an “apparent paradox of breastfeeding”.39 This “paradox” could be partially explained by higher fat-free mass deposition as a possible breastfeeding protective factor against the risk of obesity in adulthood.38,40 Similarly, in our study, we have shown a protective effect of breastfeeding on preterm infants’ growth. Indeed, infants who were any human milk-fed were protected from not achieving both weight and length catch-up growth at 36 months, showing probably a slower but better growth pattern than formula-fed ones. Regardless of these results, our study showed a very low exclusively breastfeeding rate at discharge, equal to 18%. This finding, despite being widely improvable, appeared to be quite similar to what reported by Davanzo et al. from 13 Italian NICUs.41 The authors classified their population based on birth weight and showed an exclusively breastfeeding rate equal to 25% and 22%, respectively, for newborns with birth weight between 1500 and 2000 g and between 2000 and 2499 g.41 Moreover, our population includes late preterm and SGA infants, for whom breastfeeding rates are generally lower than full-term newborns.41,42 In addition, 55% of our cohort were twins and 88% were born by caesarean section, both factors associated with greater difficulty in starting and continuing breastfeeding.43,44

Being a retrospective study, lots of data relating to the growth of the enrolled children were not available. In our opinion, the main limitations of this study are the lack of infants’ body composition assessment and a more in-depth analysis of the type of feeding and breastfeeding duration to evaluate a possible dose-dependent role of human milk on infants’ growth. Moreover, since the study analyzed a period ranging from 2009 to 2015, the evaluation of anthropometric parameters was performed using the Fenton and WHO charts and the same charts were used for both singleton and twins. Since 2014, new postnatal growth standards for preterm infants by the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH 21st) have been published.7 It could be possible, that using different charts we could have highlighted a different growth trajectory, at least up to 6 months of corrected age.7,45

On the contrary, to the best of our knowledge, this is one of the few studies on assessing late preterm infants’ growth from the hospital discharge and through a long follow-up period.

Our results highlighted that late preterm and SGA infants present a variable growth trajectory during early infancy and that maintaining catch-up growth during the first year of life could be affected by different variables such as being born singleton, having IUGR, and being breastfed. Therefore, identifying these variables, especially the modifiable ones and enhancing the protective factors, is a priority for pediatricians to optimize growth and development and prevent the onset of non-communicable diseases in the short and long term. Moreover, our study confirmed the importance of breastfeeding for its nutritional value and as a protective factor against the risk of failure to thrive for preterm and SGA infants. Consequently, breastfeeding promotion should be strongly supported in neonatal intensive care among preterm infants.

Further studies with larger samples are needed to investigate the late preterm profoundly, SGA neonates’ growth trajectory and to identify possible protective factors both on weight and length gain and long-term health outcomes.

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