Postdischarge Nutrition of Preterm Infants: Breastfeeding, Complementary Foods, Eating Behavior and Feeding Problems

Abstract

In preterm infants, the key goals of nutrition are to establish adequate growth and to contribute to appropriate neurodevelopmental outcome. In this context, the postdischarge period is crucial to establish catch-up growth and avoid wrong metabolic programming caused by overfeeding. Breastfeeding is strongly recommended, and for preterm infants the European Society for Gastroenterology, Hepatology, and Nutrition (ESPGHAN) suggests fortifying breastmilk after discharge up to term in appropriate growing infants and up to 3 months in growth-retarded infants. If breastfeeding is not possible, postdischarge formula should be fed at least up to term. However, the effects of a higher nutrient density and energy administered by breastmilk fortification or postdischarge formula on growth and neurodevelop- mental outcome are limited or missing but might have a positive impact on lung function and vision later in life. Moreover, little is known on the optimal timepoint to introduce solids in preterm infants. Data from observational studies have shown that preterm infants are weaned early in life around 13-15 weeks of corrected age. The degree of prematurity and use of formula are major determinants for early complementary feeding introduction. It is emphasized that there should be a strong focus on the infant's anatomical, physiological, and oral-motor readiness to receive foods other than breast milk or formula. Feeding problems and preterm's eating difficulties are common, and especially in the very immature population approximately 30% show oro-motor dysfunction or avoidant behavior at 3 months. An individualized approach according to the infant's neurological ability and nutritional status seems to be the best practice when introducing complementary feeding in preterm infants especially in the absence of evidence-based guidelines.

The optimal nutrition of preterm infants during their first weeks of life is a difficult task for neonatologists and remains a challenge even after discharge. As a consequence of prematurity, preterm infants have high needs for nutrients on the one hand and an organ immaturity on the other hand, which contributes to the difficulty of achieving dietary intakes that allow these infants to grow adequately.

They are also at high risk for delaying their neurodevelopmental milestones resulting in poor feeding skills and feeding problems. Overall, preterm infants may be sleepier at the time of discharge and may have more difficulties in latching, sucking, and swallowing than full-term infants [1]. Additionally, the preterm population is exceptionally inhomogeneous, primarily because of the variation in gestational age from 22 to 36 weeks but also due to the affection by persistent morbidities retarding normal growth (e.g., chronic lung disease, short bowel syndrome, etc.). These infants have higher nutritional requirements and/ or the need to limit the volume of feeds consumed [2]. Finally, preterm infants tend to be discharged from the hospital earlier than the expected term. For the postdischarge period, it is important to define the nutritional requirements, to individualize the nutritional approach, and to consider feeding skills and emotional factors [2].

Optimal Growth after Discharge

In preterm infants, the key issue of perinatal and postdischarge nutrition is to establish adequate growth and appropriate neurodevelopmental outcome. A few years ago, the optimal growth trajectories of preterm infants during their early postnatal period were redefined: Rochow et al. [3] nicely showed that the “phys-iologic” growth trajectory of preterm infants is 1 SDS below their birth percentile. This is attributed to the fact that preterm infants have a higher body water content than term infants which results in a higher postnatal extracellular water loss [3]. A single chart cannot be used to monitor and plot the growth of infants during their initial hospital course and through the early discharge period, when the risk of growth restriction is greatest. To address this, a combination of the Fenton growth charts [4] and the WHO growth charts [5] is helpful (Fig. 1 [6]). The one-time postnatal contraction of extracellular water spaces occurs after preterm birth, leading to a temporary separation of growth curves by the equivalent of approximately -0.8 z-scores and re-emerging after 42 + 0/7 weeks (Fig. 1) [6].



But what is the optimal postdischarge growth velocity? ESPGHAN classified postdischarge growth into four distinct patterns [7]: (1) neonates adequate for gestational age (AGA) at birth without extrauterine growth retardation (EUGR); (2) neonates AGA at birth but with EUGR; (3) neonates small for gestational age (SGA) at birth without catch-up growth at discharge; (4) neonates SGA at birth but with early catch-up growth at discharge. ESPGHAN recommended that all preterm infants should receive either fortified breastmilk or a special postdischarge formula at least until a postconceptional age of 40 weeks. Infants discharged with a subnormal weight (<10th percentile) for postconceptional age and thus with an increased risk of long-term growth failure should receive fortified breastmilk or postdischarge formula possibly until about 52 weeks. These recommendations were published in 2006 and since then a lot of research on metabolic programming especially in SGA infants has been published which indicates that these recommendations should be updated. Postdischarge studies comparing enriched versus standard nutrition highlighted the ability of some preterm infants - like their term counterparts - to regulate their intake volume to compensate for differences in energy density between formulas [8]. This is only applicable to preterm babies reaching term due date and beyond as it has been reported that many less mature preterm babies are not able to compensate for low nutrient density feedings due to immature feeding skills [9]. Still, there is no doubt that infants with EUGR and a complicated neonatal course need enhanced nutrients for catch up growth.

Postdischarge Nutrition

From the nutritional aspect, the time after hospital discharge up to the end of the first year of life can be divided into 2 parts: the period of exclusive nursing or formula feeding and the period when complementary feeding is started in addition to breast- or formula feeding.

There is no doubt that breastmilk is the best source of nutrition for all infants but especially for those born preterm. So far, 3 randomized controlled trials are available investigating different methods of breastmilk fortification while exclu-sively breastfeeding after discharge and their effect on growth and neurodevel- opmental outcome. In the largest study published by Zachariassen et al. [10], the entire dose of a commercial human milk fortifier (HMF) was added into one bottle of pumped breastmilk per day up to 4 months corrected age. No effect on growth was found at 3 or 12 months of age. However, a follow-up study of the cohort reported a better lung function at 6 years [11]. In a second study, HMF was administered by cup twice a day up to 12 weeks after discharge [12]. The intervention induced better weight, length, head growth, and bone mineral density in babies with birth weight <1,250 g which was persisting up to 1 year of age [13] as well as better visual function [14]. In the third study, preterm infants received HMF added to expressed breastmilk twice a day for 4-6 months of corrected age in otherwise to exclusive breastfeeding [15]. This study mainly focused on neurodevelopmental outcome at 12 months and did not provide anthropometric outcomes. None of the studies reported any adverse effects on breastfeeding behavior, but unfortunately there was no positive effect on neuro- developmental outcome. However, there seems to be an association between exclusive breastfeeding at discharge and improved cognitive outcomes despite suboptimal initial weight gain [16]. Weight gain does not necessarily reflect body composition changes, which can be summarized as the “apparent breastfeeding paradox.” That means that although breastfeeding can be associated with a significantly increased risk of losing one weight z-score during hospitalization, head circumference z-scores are higher than 0.5 at 2 years [17] and at 5 years [18] of age with a significantly decreased risk for suboptimal neurodevel- opmental assessment [16].

If the mother is not able to breastfeed, ESPGHAN recommends to feed post-discharge formula up to at least 40 weeks, and in growth-retarded infants up to 52 weeks [19]. Postdischarge formula has a higher nutrient and energy density (74 kcal/100 mL) ranging between preterm and term formula. A meta-analysis addressed the question if feeding formulas enriched with energy, protein, and micronutrients to preterm infants after hospital discharge would result in catchup growth [20]. Accelerated weight gain and crossing of body mass index percentiles might be associated with altered fat distribution and related “programmed” metabolic consequences that may increase the risk of insulin resistance and cardiovascular disease later in life [20]. However, because preterm infants fed in response to hunger and satiation cues (demand or responsive feeding) can adjust their volume of intake according to the energy density of formula, infants may consume less nutrient-enriched milk than standard formula [20]. Consequently, infants fed responsively with preterm or postdischarge formula may not receive more energy (or other nutrients) than infants fed standard term formula. The meta-analysis did not provide evidence that feeding postdischarge formula versus standard term formula (~67 kcal/100 mL) to preterm infants after hospital discharge affects growth parameters up to 12-18 months or neurodevelopmental outcome [20].

Although there are no effects of postdischarge formula on outcome with 1 year, there seems to be an association of early infant growth and later cognition. Data of a 10-year follow-up study showed that weight gain in the first 3 months was significantly associated with improved intelligence quotient and freedom from distractibility subsets of the Wechsler Intelligence Scale for children, which remained significant even after adjusting for weight gain [21]. These data are in line with other studies in preterm infants indicating that infants with a better weight gain between term and 4 months corrected age have a higher developmental score at 18 months [22] and another study showing that each unit increase in weight SDS between term and 1 year of age was associated with a 1.9-point IQ advantage at 8 years of age [23]. Therefore, it is likely that the 3-4 months after term remain a potentially important period for optimizing brain development through dietary management.

Complementary Feeding in Preterm Infants

In full-term infants, ESPGHAN [24, 25] recommends a stepwise introduction of complementary food (CF) between the 17th and 26th week of life. In preterm in-fants, guidelines on the optimal time for starting solids and the ideal composition of CF meeting their special requirements are missing [26, 27]. Observational studies have shown that in general solids are introduced early to preterm infants [28-30]. An Italian study documented that infants born between 24 and 32 weeks were from exclusive nursing or formula feeding at 13 weeks corrected for term, while more mature infants born between 33 and 36 weeks were weaned at 15 weeks corrected for term [26] indicating that the degree of prematurity is a major determinant for CF introduction. The odds for being weaned before 4 months are 9.9 times higher in infants born between 22 and 32 weeks' gestation, and 6.19 higher in infants born between 33 and 36 weeks' gestation when compared with term infants [31]. Another interesting issue was that in general formula-fed infants are weaned earlier than breastfed infants or infants on mixed feeding [26].

To date, only 2 RCTs have investigated time of introduction and nutritional quality of solids for preterm infants. A study which was published before post-discharge fortification of breastmilk and postdischarge formula were introduced randomized preterm infants either into a “preterm weaning strategy (PWS)” group or to a control group [32]. Infants in the PWS group received high-energy, high-protein, semisolid foods together with a preterm infant formula starting at 13 weeks of uncorrected age, provided they had reached at least 3.5 kg body weight. Infants in the control group were started on CF at 17 weeks of uncorrected age, provided they weighed at least 5 kg, and no specific advice for food quality was given. At 12 months of age, infants in the PWS group had greater length compared to those in the control group, with no differences in weight or head circumference [32]. A more recent RCT from India published in 2017 could not find an effect of CF introduction at 4 versus 6 months on weight for age z-scores, other anthropometric parameters, or neurodevelopmental outcome at 1 year in preterm infants with a GA <34 weeks [33]. Breastfeeding, type of formula or maternal education did not influence results. However, this study was conducted in a lower/middle-income country indicating that setting and results cannot be transferred to high-income countries. In this study, infants in both groups showed a remarkable loss in z-scores of -2.8 around term, which does not correspond to normal growth trajectories in European cohorts [34]. This growth retardation persisted up to 1 year of corrected age, where z-score loss was still -1.6 in both groups (Fig. 2). The results of the study also highlight the importance of quality of solid foods indicating that a nutrient-rich diet is important in these infants. Also, little is known about the timing of introduction of single food groups in preterm infants. In an internet survey among Italian pediatricians, Baldassarre et al. [35] investigated: (1) timing of the introduction of CFs to preterm newborns; (2) type of CFs introduced; (3) vitamin D and iron supplementations. Results showed that the decision to introduce solids was mainly based on the infants' age (44%). 58% of the pediatricians recommended to start at corrected age (mean 5.5 months), and 42% recommended to start at the chronological age (mean 5.6 months), indicating that there is no consensus concerning chronological or corrected age. Only 18% of the pediatricians considered the neurological ability of the infants to accept solids, which is especially important in extremely immature infants. Parents started with fruits, vegetables, oil, and cereals at 5.5 months, followed by meat (5.6 months), gluten (5.8 months) milk products (7 months), fish (7.4 months), and egg (8.7 months) [35]. Approximately 90% of the infants received iron supplements up to 9.3 months, which is important, as preterm infants often have depleted iron stores and require extra iron intake during their first year of life. Vitamin D was provided up to 21.1 months [35]. The introduction of single food groups was strongly af-fected by local availability of aliments as well as cultural habits and practices. Data from high-quality, prospective randomized trials investigating the optimal timepoint for CF introduction under consideration of chronological or corrected age, the optimal composition, and appropriate supplements such as vitamin D or iron are not available so far.


Neurological Ability and Introduction of CF

The key issue for the introduction of CFs is the infant's anatomical, physiological, and oral-motor readiness to receive foods other than breast milk or formula.

Once an infant has developed an apparent interest in non-milk foods and feeding, the changes that are required for progressing from a liquid to a semisolid and solid diet are [36]:

1.    Anatomical changes in the oral cavity
2.    The disappearance or diminishing of reflexes present at birth that coordinate suckling, swallowing and respiration, and protect the infant from aspiration and choking (i.e., the extrusion reflex of the tongue), in favor of more voluntary movements, and
3.    The development of gross motor skills (head and trunk control to allow an improved movement of the jaw) and fine motor skills (lip, tongue, and jaw movements).

The age range at which preterm infants attain these developmental milestones are related to their immaturity, morbidities, and their perinatal course. Furthermore, feeding problems and preterm's eating difficulties are also related to psychological roots caused by the multiple and unpleasant procedures undergone during hospitalization (e.g., tube feeding, intubation, etc.) [2]. In term infants, the earliest gross motor skills indicative of developmental readiness for spoonfeeding of pureed foods (i.e., holding the head in midline when in supine position and to control its head well when pulled to sitting or at aided sitting) can be observed between 3 and 4 months of age [36]. At this age, it can be assumed that the rooting and the extrusion reflexes may have also diminished in some infants. The gross motor skill indicative of developmental readiness for self-feeding finger foods (i.e., sitting without support) can be observed in some infants at 4 months, but more commonly between 5 and 7 months of age. In preterm infants, the necessary developmental milestones for feeding are also reached around the same age range (post-term), depending on the severity of illness experienced during the neonatal period, the degree of prematurity, and any sequelae [36].

A large prospective study in early (GA <34 weeks; n = 319) and late (GA 34-37 weeks; n = 571) preterm infants investigated the incidence of postdischarge feeding dysfunction and hospital/subspecialty visits for feeding problems during the first year of life [37]. Twenty-nine and 17% of the early preterm and late pre-term infants showed oro-motoric dysfunction, respectively. Corresponding per-centages for avoidant behavior at 3 months were 33 and 29% [37]. Formula feed-ing increases the chance of presenting complementary feeding difficulties by 41% (OR; 0.27-7.13) when compared to exclusive breastfeeding and mixed feeding [38]. In most of the infants, the symptoms disappeared during the first year of life, but these results highlight that pediatricians should screen preterm infants for feeding dysfunction during their first year of life [37]. Preterm infants who show oral dysfunctions need a multidisciplinary follow-up that must include a nutritionist and a speech therapist specializing in oral function [2].
An individualized approach according to the infant's neurological ability and nutritional status seems to be the best practice when introducing complementary feeding in preterm infants especially in the absence of evidence-based guidelines.

Conclusion

Preterm infants with EUGR and a complicated neonatal course need food with a higher nutritional density to establish postnatal catch-up growth and proper development. So far, it is not clear what the optimal growth velocity is to guarantee an optimal neurodevelopmental outcome and appropriate metabolic pro-gramming in the period after discharge from hospital, during their first year, and later in life. Fortification of breastmilk after discharge might be an opportunity to improve growth, but studies have shown conflicting results. If breastfeeding is not possible, postdischarge formulas are available but do not affect postnatal growth. The available evidence suggests that there is no specific timing for the introduction of solids. This issue needs more research from high-quality RCTs. Complementary feeding should be introduced following an individualized evaluation which is based on infants' development rather than corrected or postnatal age. Furthermore, preterm infants who have developed oral dysfunction need support by a multidisciplinary team that must include pediatricians, nutritionists, and speech therapists specialized in oral function.

Conflict of Interest Statement

N.H. receives honoraria for lectures from Nestlé, Baxter, Danone, Novalac, and MUM. The author has no other conflicts of interest to declare.

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