Nutrition and Growth in Preterm and Term Infants (N&G 2024)

Nutrition and Growth in Preterm and Term Infants

Introduction

This year, we decided to address for preterm infants three large trials on neonatal nutrition
and six systematic reviews on enteral nutrition. For term infants, the review addressed six
papers on breastfeeding, one paper on iodine nutrition, and two papers on food allergy.

Preterm Infants
Large Trials on Neonatal Nutrition

Early amino acids in extremely preterm infants and neurodisability at 2 years

Bovine colostrum to supplement the first feeding of very preterm infants: the
PreColos randomized controlled trial

Bovine colostrum as a fortifier to human milk in very preterm infants – a
randomized controlled trial (FortiColos)

Comments: One of the larger trials in neonatology, especially in the field of nutrition, was the Pro-VIDe multicenter randomized controlled trial conducted in New Zealand [1]. The trial included a total of 434 infants with a birth weight <1,000 g and who also had an umbilical arterial catheter in place and aimed to assess whether higher parenteral amino acid intake improves outcomes. The infants in the intervention group no longer received heparinized saline through the umbilical cord, but amino acids (with heparin) instead at a dose of 1 g per day in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability at 2 years. The results showed no significant difference between the intervention and placebo groups regarding this outcome (adjusted relative risk, 0.95; 95% confidence interval, 0.79 to 1.14; p = 0.56). Worrying signals came from the secondary outcomes in that infants in the intervention arm had higher probable or proven sepsis rates, as well as higher patent ductus arteriosus rates. Besides, the surviving infants suffered twice as frequent from moderate or severe neurodisability. Thus, the approach of adding an additional gram of amino acids per day (which would imply an extra 2 g/kg per day for those weighing 500 g) on top of all other regular parenteral nutrition was not beneficial. It must be noted that in this study, protein intakes were very high, amounting on average approximately 4 g/kg per day on day 4 of life from parenteral nutrition only,
but many kids thus also received even higher dosages. Since electrolyte intake was
not controlled, this probably resulted in a high rate of hypophosphatemia due to
refeeding syndrome. Previously, the same phenomenon was presented in a study by
Moltu et al., who also described refeeding syndrome features in premature infants not
being supplemented with sufficient phosphate [2]. In fact, also in the ProVIDe study,
several of the participating sites in the study provide only very minimal amounts of
phosphate in parenteral nutrition during the first few days of life as was shown in a
separate paper [3]. Moreover, a negative correlation was shown between amino acid
intake and serum phosphate concentrations. In addition, those infants with refeeding syndrome in this trial suffered more frequently from sepsis and were three times as
likely to die. Thus, all in all, the very high amino acid intakes in combination with low
phosphate intakes may explain some of the negative outcomes in the infants.

Because human colostrum is so rich in immunoactive compounds, colostrum of bovine origin has also been suggested to be a beneficial supplement for preterm infants. Its use could be potentially advantageous in preterm infants whose mothers are not able to produce sufficient colostrum initially or could even serve as an adjunct to insufficient mother’s own milk (MOM) or as a multinutrient fortifier to human milk. A Danish-Chinese research collaboration has recently investigated these usages in two separate trials, the PreColos and FortiColos trial [4, 5]. In the prior trial, 350 preterm infants (mean gestational age 30 weeks) were included in China [4]. They were randomized between either the standard feeding group, i.e., MOM supplemented with preterm formula, or the bovine colostrum group, which received a combination of MOM supplemented with bovine colostrum and possibly preterm formula in case the protein intake would exceed the maximum limit because of the high protein content
of bovine colostrum. The intervention lasted 14 days in total. No differences were seen in the primary outcome, which was time to achieving 120 mL/kg per day of enteral nutrition. It must be noted, however, that feeding advancements in the study were very low compared to, for example, European practice, a feature described earlier [6]. During the first 2 weeks of life, the infants in both groups had received only 32 mL/kg per day of enteral feeding on average, and the median time to achieving 120 mL/kg per day of enteral nutrition lasted 28 days. After adjusting for confounders, the per protocol analysis even showed a significant delay of 4 days in achieving this goal in those who had received the bovine colostrum. Growth and incidence of clinical morbidities were not different between groups, except for possibly more infants suffering from periventricular hemorrhage in the intervention group. In conclusion, in these preterm infants, in whom enteral nutrition was only slowly advanced, partially replacing preterm formula with bovine colostrum in case of insufficient MOM does not seem to be a beneficial strategy.
In the FortiColos trial, bovine colostrum was used as an alternative to regular human milk fortifier [5]. In this randomized controlled trial, conducted in Denmark, 232 preterm infants (mean gestational age 28.5 weeks) were randomized to either a conventional bovine milk–derived multinutrient fortifier or powdered bovine colostrum, which was added to MOM or donor human milk in case of insufficient MOM. Total protein intake was targeted to be the same in both groups, but upon analysis, the infants in the bovine colostrum group received slightly higher protein intakes. The intervention lasted until 35 weeks postmenstrual age. Growth was the primary outcome, but there were no consistent differences between groups. Regarding secondary outcomes, there were also no clear differences in neonatal morbidities like late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or retinopathy of prematurity. In conclusion, unlike preclinical studies in preterm piglets, in which beneficial effects of bovine colostrum were shown consistently [7–9], studies in human preterm infants have not been positive so far. It could be that this is due to the fact that piglets may absorb the immunoglobulin G intactly, whereas in humans, these either remain undigested or are broken down into smaller peptides, losing their bioactive function locally in the gut.

Systematic Reviews on Enteral Nutrition
Oropharyngeal application of colostrum or mother’s own milk in preterm infants: a
systematic review and meta-analysis

Mother’s own milk compared with formula milk for feeding preterm or low birth
weight infants: systematic review and meta-analysis

Delayed introduction of progressive enteral feeds to prevent necrotising
enterocolitis in very low birth weight infants

Fast feed advancement for preterm and low birth weight infants: a systematic
review and meta-analysis

Routine monitoring of gastric residual for prevention of necrotising enterocolitis in
preterm infants

Enteral nutrition in preterm infants (2022): a position paper from the ESPGHAN
Committee on Nutrition and invited experts

Comments: Several systematic reviews regarding neonatal nutrition in preterm infants have been updated last year and we will shortly discuss a few.

In the previous edition of this yearbook [10], we had also briefly discussed the application of buccal or oropharyngeal colostrum in preterm infants. The theory behind this practice is that this immunologically rich milk might boost the immune system and might aid in preventing several neonatal morbidities. The conclusion last year was that while administration of oropharyngeal colostrum to preterm infants appears safe and theoretically attractive from both an emotional and immunological point of view, no clear clinical benefits have consistently been proven unfortunately, especially in high-resource settings. However, in the last 2 years, several new studies mostly from Asian countries have been published, and this urged Kumar et al. to conduct an updated systematic review with meta-analysis [11]. The authors selected 17 randomized controlled trials (RCTs) in which 1,730 preterm infants were randomized between oropharyngeal colostrum versus placebo or standard care. Meta-analyzing available data suggests there might be a reduction in time to full enteral feeding and sepsis events, although GRADE shows this is with very low certainty of evidence mainly because of high study heterogeneity and inclusion of several nonblinded studies. Nonetheless, despite there is still a need for large multicentric adequately powered high-quality RCTs, buccal colostrum appears safe, is a cheap intervention, might stimulate parental involvement and even milk expression [12], has potential clinical benefits, and may thus be advised in neonatal intensive care units.

The latest Cochrane review assessing RCTs on the use of donor human milk versus (preterm) formula in case of insufficient MOM was published in 2019 [13]. It was concluded with moderate certainty evidence that donor human milk decreased the risk of necrotizing enterocolitis compared with formula. Last year, Strobel et al. published an updated systematic review in which 42 cohort studies were reviewed assessing nearly 90,000 preterm infants [14]. Groups of infants were stratified by whether they had received at least 50% formula or at least 50% MOM, so it must be noted that there was considerable overlap in both groups. Also, there were various study designs included and many studies came with a substantial risk of bias. Yet, it was concluded that infants who had received merely formula versus MOM during the first month of life had a threefold higher chance of suffering from necrotizing enterocolitis. Other morbidities and mortality rate were not significantly different between the groups. Knowledge on the rate of advancing enteral nutrition in preterm infants has received a boost since the SIFT study was published in 2019 [15]. In relation to this, several systematic reviews have been updated. For one, a Cochrane review on the start of progressing enteral nutrition before or after 4 days of life showed that there was no increased risk of necrotizing enterocolitis or death of early progression, also not in subgroups [16]. On the contrary, delayed start of progression increased the risk of late-onset sepsis. Closely related is the rate of advancement hereafter. In an updated systematic review on 12 RCTs in which nearly 4,300 preterm infants were included, outcomes after aiming for a very rapid daily progression of enteral feeds (>30 mL/kg per day) versus slower daily progression (<30 mL/kg per day) were assessed. Faster advancement reduced the time to regain birth weight by almost 4 days and the duration of hospitalization by 3 days when compared with slow advancement rates. In addition, although statistical significance was not shown, slight reductions in the risk
of mortality, necrotizing enterocolitis, and sepsis were demonstrated. Priorly, rapidly advancing enteral nutrition was often delayed because of routine assessment of gastric residuals, which were then interpreted as a sign of feeding intolerance. Based on new trials and physiological understanding, we now know this may be a misunderstanding. An updated Cochrane review on 5 RCTs in 423 preterm infants shows that omitting routine gastric residual assessment reduces time to full enteral feeding with 3 days and reduces sepsis risk by nearly 35%, while it has no effect on the incidence of necrotizing enterocolitis [17]. The conclusions of these systematic reviews are all in line with the recommendations given in the recent ESPGHAN position paper on enteral nutrition for preterm infants [18]. The group of authors in this document summarized many aspects of enteral nutrition (more than here described) and provided several practical recommendations for those working on a neonatal intensive care
unit.

Term Infants
Breastfeeding

Breastfeeding: crucially important, but increasingly challenged in a market-driven
world

Marketing of commercial milk formula: a system to capture parents, communities,
science, and policy

The political economy of infant and young child feeding: confronting corporate
power, overcoming structural barriers, and accelerating progress

Breastmilk or infant formula? Content analysis of infant feeding advice on
breastmilk substitute manufacturer websites

Effectiveness of lactation cookies on human milk production rates: a randomized
controlled trial

Systematic review and meta-analysis of breastfeeding and later overweight or
obesity expands on previous study for World Health Organization

Comments: Public Health Policies, Breast Milk Substitutes Marketing and Breastfeeding. There are many reasons for the low rates and short durations of breastfeeding worldwide. Among these, the impact of breast milk substitute (BMS) industry on parents, care providers, and policymakers plays an important role. It is the topic of the three papers of the “Breastfeeding 2023” series published in the Lancet.

In 1981, the World Health Assembly adopted the International Code of Marketing of BMS, the “Code,” a set of standards to promote and protect breastfeeding [19]. It includes prohibition of advertising of BMS to the public or promotion within healthcare systems; banning provision of free samples to mothers, healthcare workers, and health facilities; no promotion of formula within health services; and no sponsorship of health professionals or scientific meetings by the BMS industry. Of note, WHO is increasingly advocating the use of the term commercial milk formula instead of BMS to highlight the artificial and ultra-processed nature of formula products. Forty-two years later, there is still a long way to go. As of March 2022, a total of 144 (74%) of the 194 WHO Member States (MS) have adopted legal measures to implement at least some of the provisions in the Code [20]. Of these, 32 MS have measures in place that are substantially aligned with the Code. A further 41 MS have measures that are moderately aligned and 71 have included some provisions, while 50 have no legal measures at all. The WHO African, Eastern Mediterranean, and Southeast Asian regions have the highest percentage of countries substantially aligned with the Code.

The first paper of the “Breastfeeding 2023” series from Pérez-Escamilla et al. describes
what policies and interventions are needed to achieve optimal breastfeeding [21]. A synthesis of reviews published between 2016 and 2021 and country-based case studies indicate that breastfeeding practices at a population level can be improved with interventions across the socioecological model and settings. Parents and healthcare providers often misinterpret baby behaviors (e.g., crying, fussiness, posseting, poor nighttime sleep) as signs of milk insufficiency or infant pathology.

The second paper from Rollins et al. addresses how BMS marketing operates as a system to capture parents, communities, science, and policy [22]. This paper summarizes the history of BMS and its marketing, e.g., trends in BMS sales and marketing expenditures, and describes the development of the BMS industry marketing playbook and how BMS marketing takes advantage of deficiencies in public health policies and regulations. The increasing use of digital media and tools for the marketing of BMS is of concern. Digital marketing has become the primary means by which BMS manufacturers and distributors promote their brands and products, representing as much as 70% of total advertising spent on these products. Digital marketing platforms enable advertisers to reach beyond national borders, adding further challenges to enforcement of national laws.

The third paper from Baker et al. examines the social, political, and economic reasons
for this problem [23]. This paper highlights the power of the BMS industry to influence
policy at both national and international levels in ways that grow BMS markets. Baker
et al. propose six recommendations on social, political, and economic reforms.
The United States is one of the few countries that has not adopted any portion of the
International Code of Marketing of BMS into law. Therefore, marketing and labelling
techniques that are not allowed in many other countries are regularly used to sell BMS
in the United States. The study by Pomeranz et al. examines how BMS companies communicate with the public about the benefits and challenges of breastfeeding and
BMS feeding on their US websites directed to consumers [24]. The authors identified
messages and images about breastfeeding/breast milk and BMS feeding, including
benefits or issues associated with each of them, and marketing practices that could discourage breastfeeding. Data were collected for US websites of five BMS manufacturers. Websites contained more screenshots about breastfeeding/breast milk (n =303) than BMS (n = 263), but these screenshots were significantly more likely to mention benefits of BMS (44%) than breastfeeding/breast milk (26%), including significantly more statements that BMS provides brain, neural, and gastrointestinal benefits.

Issues related to breastfeeding appeared on 40% of screenshots mentioning breastfeeding (e.g., breast milk supply, infant latching, sore nipples). Twice as many screenshots compared BMS brands favorably to breast milk than as superior to other brands. Pomeranz et al. concluded that their study corroborates previous research finding that BMS marketing expressly discourages breastfeeding.

Duration of Breastfeeding. A large variety of commercially available products claim
to improve lactation. Lactation cookies (LCs) contain galactagogues, i.e., substances
believed to enhance breast milk production. The objective of the study by Palacios et
al. was to assess the efficiency of commercially available LCs [25]. They performed a
1-month, randomized controlled trial among exclusively lactating mothers (n = 176)
of healthy, term, 2-month-old infants living in the United States. Participants were
randomly assigned to eat daily 56.5 g of either LCs with “galactagogues” (oatmeal,
brewer’s yeast, flax seeds, and fenugreek) or conventional cookies containing similar weight, calories, and presentation but lacking galactagogues. No significant differences were observed on baseline-to-endline changes in human milk production rate (primary outcome), perceived insufficient milk, or breastfeeding self-efficacy (secondary outcomes). Recommendations to consume LCs for increasing objective or subjective milk supply are likely to be misleading.

Breastfeeding and Later Risk for Overweight or Obesity. The primary aim of this systematic review and meta-analysis by Horta et al. was to update the evidence on the association of breastfeeding with a reduced risk for overweight or obesity [26]. They also assessed the likelihood of residual confounding. The review comprised 159 studies published between August 2014 and May 2021, with 169 estimates on the association of breastfeeding with overweight or obesity. Most studies (n = 130) were performed in children aged 1–9 years. Breastfeeding was associated with a protection against overweight or obesity (pooled odds ratio: 0.73, 95% confidence interval: 0.71, 0.76). Among the 19 studies that were less susceptible to publication bias, residual confounding, and misclassification, a benefit was still observed (pooled odds ratio: 0.85, 95% confidence interval: 0.77, 0.93), suggesting that the observed association is causal. Among the studies that were clearly susceptible to positive confounding by socioeconomic status, a benefit of breastfeeding was observed even after adjusting for socioeconomic status (pooled odds ratio: 0.76, 95% confidence interval: 0.69, 0.83). This study by Horta et al. confirmed that breastfeeding reduces the odds of overweight or obesity and that this association is unlikely to be due to publication bias and residual confounding.

Iodine Nutrition

Infant iodine status and associations with maternal iodine nutrition, breastfeeding status and thyroid function

Comments: Iodine is an essential component of thyroid hormones. Iodine deficiency (ID) is particularly of concern in pregnant and lactating women, infants, and young children because of the importance of thyroid hormone for normal growth and neurodevelopment both in in utero and early life. Breast milk iodine concentration (BMIC) is dependent on maternal iodine intake; therefore, in exclusively breastfed infants, iodine intake is dependent entirely on maternal iodine intake.

The study by Næss et al. assessed the iodine status in a cohort of Norwegian infants and its association with maternal iodine nutrition, breastfeeding status, and thyroid function [27]. A total of 113 infants were followed up at ages 3, 6, and 11 months. Mean maternal age was 29.3 years, and mean gestational age was 40 years, with 5% preterms. At age 3 months, 80% of the infants were breastfed (all of them were exclusively breastfed), while 15% were mixed milk fed and 5% exclusively formula fed. Infant and maternal urinary iodine concentration (UIC), maternal iodine intake, breastfeeding status, BMIC, and infant thyroid function tests were assessed. The median infant UIC was 82 μg/L at the age of 3 months, below the recommended WHO cutoff of 100 μg/L, indicating insufficient iodine status at group level. Infant UIC was adequate later in infancy (median 110 μg/L at ages 6 and 11 months). Infant UIC was associated positively with maternal UIC, maternal iodine intake, and BMIC. The associations were strongest at the age of 3 months. Breastfed infants had significantly lower median UIC compared with formula-fed infants at ages 3 months (76 vs. 190 μg/L) and
6 months (105 vs. 315 μg/L) but not at age 11 months. No consequences on thyroid
function were found at any age. In this study, median BMIC at 3 months postpartum was 77 μg/L, which is considerably lower than the iodine concentration in ready-to-use infant formula on the European market (about 130 μg/L). Assuming a breast milk intake of 0·75 L per day at the age of 3 months, a BMIC of 77 μg/L would correspond to an iodine intake of 58 μg per day in fully breastfed infants in the present study. This is much lower than the WHO recommendation of 90 μg per day. Næss et al. concluded that breastfed infants in Norway are at risk of insufficient iodine intake during the first months of life. In Norway, iodine supplementation has been recommended from 2018 for lactating women if intake of the most important iodine sources (dairy products and lean fish) is low.

Of note, the high variability in the dietary iodine intake of individuals results in very high day-to-day variation in UIC. Therefore, UIC from spot samples is not appropriate for the diagnosis of ID in an individual but is considered as a reliable biomarker to evaluate the iodine status at a population level. There is an urgent need for biomarkers that could be used to assess iodine status at the individual level. Two 2017 and 2019 Cochrane systematic reviews found no evidence that iodine supplementation in women before, during, or after pregnancy improved infant and child cognitive development in areas with mild to moderate ID [28]. Likewise, a 2019 Cochrane systematic review concluded that there was no evidence of a positive impact of iodine supplementation on morbidity, including cognitive impairment, and mortality in preterm infants [28].

Food Allergy

Timing of allergenic food introduction and risk of immunoglobulin E-mediated
food allergy

Frequency of infant egg consumption and risk of maternal-reported egg allergy at
6 years

Comments: The prevalence of food allergy (FA) is increasing, especially in high-income countries, where up to 10% of the population may experience FA. Findings from recent studies on dietary interventions for FA prevention have led to revised guidelines, moving from an avoidance approach of allergenic foods to actively recommending introduction of allergenic foods in the first 4 to 6 months of life. It has also been shown that earlier introduction of egg and peanut probably reduces the risk for egg and peanut allergy, respectively. Evidence to support earlier introduction of other food allergens before the age of 4 months is still lacking.

Scarpone et al. performed a meta-analysis of randomized clinical trials (RCTs) assessing the age at introduction of allergenic foods (milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soy) during infancy and immunoglobulin E (IgE)–mediated FA from 1 to 5 years of age [29]. Primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods. The study populations were infants enrolled from birth to 12 months of age. RCTs that compared earlier and later allergenic food introduction and different doses and types of exposure were included, as were RCTs using breastfeeding or breast milk, amino acid formula, other low-allergen exposures, or standard care as the comparator. Non-RCTs, trials of timing of solid food introduction that did not use allergenic foods, and trials in specific populations, such as very preterm infants, were excluded.

Data were extracted from 23 RCTs (56 articles, 13,794 randomized participants). There was moderate certainty evidence from 4 RCTs (3,295 participants) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3–4 months) was associated with reduced risk of FA (risk ratio [RR], 0.49; 95% CI, 0.33–0.74; I2 = 49%). There was moderate certainty evidence from 5 RCTs (4,703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45–3.63; I2 = 89%). There was high-certainty evidence from 9 RCTs (4,811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR,0.60; 95% CI, 0.46–0.77; I2 = 0%) and high-certainty evidence from 4 RCTs (3,796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19–0.51; I2 = 21%). Evidence for timing of introduction of cow milk and risk of cow milk allergy was of very low certainty. The study by Scarpone et al. provides more evidence on the beneficial role of earlier
introduction of egg and peanut on the risk of egg and peanut allergy, respectively [29].
This study also suggests that earlier introduction of multiple allergenic foods may be
beneficial for the risk of FA. However, the high rate of withdrawal from the intervention
precludes to draw firm conclusions and therefore update the current guidelines.

Egg allergy is the second most common FA in early childhood after cow milk allergy, affecting about 2.5% of young children. The egg consumption that is needed to induce the beneficial effect of the earlier introduction of egg is unknown. Wen et al. analyzed data of 1,252 children from the Infant Feeding Practices Study II (2005–2012), a longitudinal prebirth cohort study run by the US Food and Drug Administration in collaboration with the Centers for Disease Control and Prevention [30]. Mothers reported the frequency of infant egg consumption at 2–7, 9, 10, and 12 months of age and the status of their child’s egg allergy at the 6 years of follow-up. The risk of maternal-reported egg allergy at 6 years significantly (p = 0.004) decreased with infant egg consumption frequency at 12 months: 2.05% for infants not consuming eggs, 0.41% for those consuming eggs <2 times per week, and 0.21% for those consuming eggs >2 times per week. A similar but not significant trend was observed at 10 months of age. After adjusting for socioeconomic confounders, breastfeeding, complementary food introduction, and infant eczema, infants who consumed eggs >2 times per week at 12 months had a significantly lower RR of maternal-reported egg allergy at 6 years (confounder-adjusted RR: 0.11; 95% CI: 0.01, 0.88; p = 0.038), whereas those who consumed <2 times per week (confounder adjusted RR: 0.21; 95% CI: 0.03, 1.67; p = 0.141) did not have a significantly lower risk than those who did not consume eggs at all. This study adds another piece of information to the most appropriate feeding patterns regarding the prevention of egg allergy. However, some limitations need to be pointed out. The diagnosis of egg allergy was reported by the mother and not after oral egg challenge or diagnosed by a physician. The preparation method (cooked or baked) of the eggs was not available in the surveys. IFPS II data were relatively old with the last follow-up in 2012, which may limit the generalizability of the results. Particularly, there was a low frequency of egg consumption at 9 months or earlier; both the small sample size and the statistical power did not allow to examine its association with the risk of egg allergy at 6 years.

References

1 Bloomfield FH, Jiang Y, Harding JE, Crowther CA, Cormack BE, Pro VTG. Early amino acids in extremely preterm infants and neurodisability at 2 years. N Engl J Med 2022;387:1661–72.

2 Moltu SJ, Strommen K, Blakstad EW, Almaas AN, Westerberg AC, Brække K, et al. Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia – a randomized, controlled trial. Clin Nutr 2013;32:207–12.

3 Cormack BE, Jiang Y, Harding JE, Crowther CA, Bloomfield FH, Pro VTG. Neonatal refeeding syndrome and clinical outcome in extremely low-birth-weight babies: secondary cohort analysis from the ProVIDe trial. JPEN J Parenter Enteral Nutr 2021;45:65–78.

4 Yan X, Pan X, Ding L, Dai Y, Chen J, Yang Y, et al. Bovine colostrum to supplement the first feeding of very preterm infants: the PreColos randomized controlled trial. Clin Nutr 2023;42:1408–17.

5 Ahnfeldt AM, Aunsholt L, Hansen BM, Hoest B, Jóhannsdóttir V, Kappel SS, et al. Bovine colostrum as a fortifier to human milk in very preterm infants – a randomized controlled trial (FortiColos). Clin Nutr 2023;42:773–83.

6 de Waard M, Li Y, Zhu Y, Ayede AI, Berrington J, Bloomfield FH, et al. Time to full enteral feeding for very low-birth-weight infants varies markedly among hospitals worldwide but may not be associated with incidence of necrotizing enterocolitis: the NEOMUNE-
NeoNutriNet cohort study. JPEN J Parenter Enteral Nutr 2019;43:658–67.

7 Sun J, Li Y, Nguyen DN, Mortensen MS, van den Akker CHP, Skeath T, et al. Nutrient fortification of human donor milk affects intestinal function and protein metabolism in preterm pigs. J Nutr 2018;148:336–47.

8 Yan X, Sangild PT, Peng Y, Li Y, Bering SB, Pan X. Supplementary bovine colostrum feedings to formula-fed preterm pigs improve gut function and reduce necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 2021;73:e39–46.

9 Rasmussen SO, Martin L, Ostergaard MV, Rudloff S, Li Y, Roggenbuck M, et al. Bovine colostrum improves neonatal growth, digestive function, and gut immunity relative to donor human milk and infant formula in preterm pigs. Am J Physiol Gastrointest Liver Physiol 2016;311:G480–91.

10 van den Akker CHP, van Goudoever JB, Turck D. Nutrition and growth in preterm and term infants. World Rev Nutr Diet 2023;126:86–113.

11 Kumar J, Meena J, Ranjan A, Kumar P. Oropharyngeal application of colostrum or mother’s own milk in preterm infants: a systematic review and meta-analysis. Nutr Rev 2023;81:1254–66.

12 Snyder R, Herdt A, Mejias-Cepeda N, Ladino J, Crowley K, Levy P. Early provision of oropharyngeal colostrum leads to sustained breast milk feedings in preterm in-
fants. Pediatr Neonatol 2017;58:534–40.

13 Quigley M, Embleton ND, McGuire W. Formula versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev
2019;7:CD002971.

14 Strobel NA, Adams C, McAullay DR, Edmond KM. Mother’s own milk compared with formula milk for feeding preterm or low birth weight infants: systematic review and meta-analysis. Pediatrics 2022;150(Suppl1):e2022057092D.

15 Dorling J, Abbott J, Berrington J, Bosiak B, Bowler U, Boyle E, et al. Controlled trial of two incremental milk feeding rates in preterm infants. N Engl J Med 2019;381:1434–43.

16 Young L, Oddie SJ, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Data-
base Syst Rev 2022;1:CD001970.

17 Abiramalatha T, Thanigainathan S, Ramaswamy VV, Rajaiah B, Ramakrishnan S. Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev 2023;6:CD012937.

18 Embleton ND, Jennifer Moltu S, Lapillonne A, van den Akker CHP, Carnielli V, Fusch C, et al. Enteral nutrition in preterm infants (2022): a position paper from the ESPGHAN Committee on Nutrition and invited experts. J Pediatr Gastroenterol Nutr 2023;76:248–68.

19 World Health Organization. International code of marketing of breast-milk substitutes. Geneva; 1981. https://www.who.int/publications/i/item/9241541601 (accessed
September 27, 2023).

20 World Health Organization/United Nations International Children’s Emergency Fund/International Baby Food Action Network. Marketing of breast milk substitutes. National implementation of the international code. Status Report 2022. Geneva; 2022. https://www.
who.int/publications/i/item/9789240048799 (accessed September 27, 2023).

21 Pérez-Escamilla R, Tomori C, Hernandez-Cordero S, Baker P, Barros AJD, Bégin F, et al. Breastfeeding: crucially important, but increasingly challenged in a market-driven world. Lancet 2023;401:472–85.

22 Rollins N, Piwoz E, Baker P, Kingston G, Mabaso KM, McCoy D, et al. Marketing of commercial milk formula: a system to capture parents, communities, science, and
policy. Lancet 2023;401:486–502.

23 Baker P, Smith JP, Garde A, Grummer-Strawn LM, Wood B, Sen G, et al. The political economy of infant and young child feeding: confronting corporate power, overcoming structural barriers, and accelerating progress. Lancet 2023;401:503–24.

24 Pomeranz JL, Chu X, Groza O, Cohodes M, Harris JL. Breastmilk or infant formula? Content analysis of infant feeding advice on breastmilk substitute manufacturer websites. Public Health Nutr 2023;26:934–42.

25 Palacios AM, Cardel MI, Parker E, Dickinson S, Houin VR, Young B, et al. Effectiveness of lactation cookies on human milk production rates: a randomized controlled trial. Am J Clin Nutr 2023;117:1035–42.

26 Horta BL, Rollins N, Dias MS, Garcez V, Pérez-Escamilla. Systematic review and meta-analysis of breastfeeding and later overweight or obesity expands on previous study for World Health Organization. Acta Paediatr 2023;112:34–41.

27 Næss S, Aakre I, Strand TA, Dahl L, Kjellevold M, Stokland AM, et al. Infant iodine status and associations with maternal iodine nutrition, breast-feeding status and thyroid function. Br J Nutr 2023;129:854–63.

28 Ley D, Turck D. Iodine supplementation: is there a need? Curr Opin Clin Nutr Metab Care 2021;24:265–70.

29 Scarpone R, Kimkool P, Ierodiakonou D, Leonardi-Bee J, Garcia-Larsen V, Perkin MR, et al. Timing of allergenic food introduction and risk of immunoglobulin E-mediated food allergy. JAMA Pediatr 2023;177:489–97.

30 Wen W, Martone GM, Lehman HK, Rideout TC, Cameron CE, Dashley S, et al. Frequency of infant egg consumption and risk of maternal-reported egg allergy at 6 years. J Nutr 2023;153:364–72.