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Nutrition Management in Neonatal Health

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Pediatric Nutrition".

Deadline for manuscript submissions: 15 October 2025 | Viewed by 11676

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Special Issue Editors

Dr. Silvia Salvatore

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Pediatric Unit, Hospital “F. Del Ponte”, Department of Medicine and Surgery, University of Insubria, I-21100 Varese, Italy
Interests: pediatrics; gastroenterology; immunology; food allergy; probiotics
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Dr. Maria Elisabetta Baldassarre

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Department of Biomedical Science and Human Oncology, Section of Neonatology and Neonatal Intensive Care Unit, University of Bari “Aldo Moro”, 70100 Bari, Italy
Interests: preterm newborns; nutrition; microbiota; neonatal gastroenterology; gastroesophageal reflux
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Dr. Maria Lorella Gianni

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Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 20122 Milan, Italy
Interests: nutrition; neonatal care; microbiota; probiotics; preterm infants; human milk
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Prof. Dr. Massimo Agosti

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Neonatal and Pediatric Unit, Hospital “F. Del Ponte”, Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy
Interests: neonates; neonatal care; preterm infants; nutrition; food allergy; microbiota; human milk
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Special Issue Information

Dear Colleagues,

Neonatal period and early life events are increasingly emerging as major determinants of human health. The first one thousand days of life have a pivotal influence on brain development, behaviour, mood, and vascular, metabolic, allergic, autoimmune, inflammatory and gastrointestinal disorders. The interaction between genes, nutrition, the environment, microbiota, exposure to stress, different substances and drugs, the occurrence of infections and traumatic events may have a great impact on an individual’s predisposition to diseases. A number of interventions and preventive strategies have recently been explored and current research is focusing on personalised and precision medicine starting from early ages. This Special Issue aims to collect the most recent evidence, original studies and new developments in medicine for this vulnerable and crucial period of life, focusing particularly on the role of nutrition in this period.

Dr. Silvia Salvatore
Dr. Maria Elisabetta Baldassarre
Dr. Maria Lorella Gianni
Prof. Dr. Massimo Agosti
Guest Editors

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Keywords

early life
the first 1000 days
neonatal nutrition
microbiota
genes
precison nutrition and medicine

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Published Papers (10 papers)

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Research

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13 pages, 253 KiB

Open AccessArticle

Is Iron Supplementation Associated with Infant Mortality in Sub-Saharan Africa and Does Birth Weight Modify These Associations?

by Yibeltal Bekele, Bircan Erbas and Mehak Batra

Nutrients 2025, 17(10), 1696; https://doi.org/10.3390/nu17101696 - 16 May 2025

Cited by 1 | Viewed by 380

Abstract

Background: Iron supplementation during pregnancy is associated with several health benefits, including a reduced risk of maternal anaemia and improved neonatal outcomes such as lower rates of low birth weight, infection, and anaemia in infancy. However, its impact on neonatal and post-neonatal mortality remains unclear in resource-limited settings, where adherence to maternal iron supplementation is low. This study examined the association between maternal iron supplementation and neonatal and post-neonatal mortality and explored whether low birth weight (LBW) modifies those associations. Methods: This cross-sectional study utilised Demographic and Health Survey data collected between 2015 and 2023 from 26 sub-Saharan countries, including 287,642 neonates and 279,819 post-neonates. The primary outcomes were neonatal deaths (within 28 days) and post-neonatal deaths (between 29 days and 12 months). These outcomes and the exposure variables of iron supplementation and its duration were based on maternal recall. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using generalised linear mixed models, with stratification by LBW. Results: There was no significant association between maternal iron supplementation and neonatal mortality (aOR = 1.07; 95% CI: 0.86, 1.34). However, the interaction between LBW and iron supplementation was statistically significant (p = 0.04). Among the LBW infants, the absence of iron supplementation increased the odds of neonatal mortality by 68% (aOR = 1.68; 95% CI: 1.14, 2.47), while supplementation for ≥90 days reduced the odds by 45% (aOR = 0.55; 95% CI: 0.35, 0.84). For post-neonatal mortality, lack of iron supplementation increased the odds by 25% (aOR = 1.25; 95% CI: 1.01, 1.56), whereas supplementation for ≥90 days reduced the odds by 27% (aOR = 0.73; 95% CI: 0.57, 0.93). Conclusions: Maternal iron supplementation was associated with lower post-neonatal mortality and improved neonatal survival among LBW infants. These findings suggest that iron intake may support infant survival, particularly in vulnerable populations. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

14 pages, 645 KiB

Open AccessArticle

Fetal Distress as a Determinant for Refeeding Syndrome in Preterm Neonates

by Maria Di Chiara, Caterina Spiriti, Flavia Gloria, Gianluigi Laccetta, Lucia Dito, Magda Gharbiya, Giuseppe Rizzo and Gianluca Terrin

Nutrients 2025, 17(9), 1417; https://doi.org/10.3390/nu17091417 - 23 Apr 2025

Viewed by 431

Abstract

Background/Objectives: Preterm neonates receiving parenteral nutrition (PN) are at risk of developing refeeding syndrome (RS). Risk factors and the related consequences remain largely undefined. In particular, the reason why only some preterm neonates out of a group receiving the same nutritional protocol will develop RS is yet to be fully understood. The aims of this study were to explore the clinical and nutritional factors contributing to RS and to assess the clinical consequences of this condition. Methods: A retrospective study was conducted, including all newborns with gestational age ≤ 34 weeks and/or body birth weight ≤ 1500 g who were consecutively admitted to the neonatal intensive care unit (NICU) of “Umberto I” Hospital, Sapienza University of Rome, from 2015 to 2022. The population was divided into two groups comprising newborns who developed RS (cases) and infants who did not develop the condition (controls) up to the first 2 weeks of life. The enrolled newborns were compared for clinical and nutritional factors and main morbidities. Results: A total of 412 neonates were enrolled, consisting of 53 cases and 359 controls. The main prenatal risk factor for RS was found to be fetal distress (p = 0.028). The occurrence of RS was identified as statistically significantly associated (p = 0.010; p = 0.007) with the development of extrauterine growth restriction (EUGR) and retinopathy of prematurity (ROP). Conclusions: Fetal distress is the predominant perinatal risk factor associated with the development of RS in preterm neonates managed with early currently recommended PN. These findings suggest an increased risk of ROP and EUGR in preterm neonates with RS. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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16 pages, 301 KiB

Open AccessArticle

Does Maternal Diet Vary During the Postpartum Period According to Infant Feeding Type? The Observational Study GREEN MOTHER

by Rosa Cabedo-Ferreiro, Azahara Reyes-Lacalle, Judit Cos-Busquets, Margalida Colldeforns-Vidal, Liudmila Liutsko, Rosa García-Sierra, Mª-Mercedes Vicente-Hernández, Miriam Gómez-Masvidal, Laura Montero-Pons, Gemma Cazorla-Ortiz, Pere Torán-Monserrat, Gemma Falguera-Puig and The GREEN MOTHER Group

Nutrients 2025, 17(7), 1136; https://doi.org/10.3390/nu17071136 - 25 Mar 2025

Viewed by 1215

Abstract

Background: Breastfeeding mothers have an increased demand for nutrients, including increased intake of certain nutrients, and are recommended to consume a theoretical 500 extra kilocalories (kcal), follow a varied diet, and increase protein, carbohydrate, omega-3, iron, and vitamin D intake. Objectives: We sought to analyze mothers’ energy and nutrient intake and food habits during the postpartum period 6 weeks after delivery and to identify whether there are any differences between breastfeeding and non-breastfeeding mothers. Methods: This was a cross-sectional, multicenter observational study at seven sexual and reproductive healthcare centers in the Metropolitan North area of Barcelona (Spain). The sample comprised 393 women who responded to an infant feeding questionnaire and 24 h diet recall (24 HR). We used frequencies and medians for descriptive analysis as well as the chi-squared and Kruskal–Wallis tests for the bivariate analysis. Results: Mean energy intake was lower than the recommendations in 57% of participants. Mothers who exclusively breastfed consumed a median of 201 kcal more than non-breastfeeding mothers, although this was not significant. The intake of fatty acids and micronutrients, such as iron, calcium, magnesium, and especially vitamin D, was insufficient. Breastfeeding mothers consumed significantly more polyunsaturated fatty acids (PUFAs) (p = 0.0297): 15.4 g vs. 12.7 g per day. Conclusions: There are no significant differences between the diet of breastfeeding and non-breastfeeding women, except for PUFA intake. A general insufficient intake of the analyzed micronutrients was observed. Educational campaigns and dietary guidance from health professionals are a priority. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

13 pages, 405 KiB

Open AccessArticle

Prolonged Parenteral Nutrition Increases the Risk of Comorbidities in Very-Low-Birth-Weight Infants: A Prospective National Cohort Study in South Korea

by Seong Wan Kim, Yoong-A Suh, Seoheui Choi, Moon Sung Park and Jang Hoon Lee

Nutrients 2025, 17(6), 996; https://doi.org/10.3390/nu17060996 - 12 Mar 2025

Viewed by 744

Abstract

Background/Objectives: There has been an increase in the incidence of comorbidities among very-low-birth-weight infants (VLBWIs), including periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). Parenteral nutrition is essential for very-low-birth-weight infants (VLBWIs) who are born with a birth weight of less than 1500 g, but a longer duration of parenteral nutrition is known to have a risk of comorbidity, such as ROP. This study aims to investigate the relationship between the duration of parenteral nutrition and the comorbidities of the VLBWIs. Methods: Using the prospective cohort of Korean neonatal network, we analyzed the perinatal and postnatal data before discharge of the total 2490 subjects born in 2021 and 2022. The primary outcomes were the diagnoses of PVL, BPD, and ROP. The secondary outcomes were the severity of BPD and ROP, treatment of ROP, and proposing the predictive model of comorbidities using the duration of parenteral nutrition. Results: This study found that prolonged parenteral nutrition exceeding 28 days was associated with a higher risk of PVL (odds ratio [OR] 1.71, 95% confidence interval [CI] [1.11, 2.64], p = 0.002) and BPD (OR 1.51, 95% CI [1.10, 2.08], p = 0.011). Furthermore, an intermediate duration of parenteral nutrition was found to be significantly associated with an increased risk of ROP in male subjects. Additionally, a prolonged duration of parenteral nutrition was observed to be linked to greater severity of BPD. Predictive models incorporating the duration of parenteral nutrition demonstrated a high degree of explanatory power in relation to both BPD and ROP. Conclusions: Longer duration of parenteral nutrition has a risk of critical comorbidities in VLBWIs. The nutrition strategy for shorter parenteral nutrition should be encouraged for the prevention of comorbidities. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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13 pages, 1375 KiB

Open AccessArticle

Breastfeeding Shapes the Gut Microbiota and Its Structure Is Associated with Weight Gain Trajectories in Mexican Infants

by Alejandra Arguelles-Lopez, Sandra V. Aguayo-Patrón and Ana M. Calderón de la Barca

Nutrients 2025, 17(5), 826; https://doi.org/10.3390/nu17050826 - 27 Feb 2025

Cited by 1 | Viewed by 1101

Abstract

Background: Rapid weight gain in early infancy increases the risk of childhood obesity, while exclusive breastfeeding can protect against it, depending on breastmilk composition, maternal diet, and infant gut microbiota. Objective: The objective of this study was to analyze the association between maternal diet, breastmilk components, infant gut microbiota, and weight gain in the first year of life of Mexican breastfed infants. Methods: This longitudinal study included 27 mothers with exclusively breastfed infants (≥5 months of age). We evaluated maternal diet and breastmilk composition at 5 months postpartum (pp), the infant fecal microbiota at 5 and 12 months pp using 16S rRNA gene sequencing, and weight gain as normal, rapid or slow weight gain (NWG, RWG or SWG) in periods 1 (0–5.5 months) and 2 (5.5–12 months). Results: Infants with NWG in periods 1 and 2 made up 51% and 56%, respectively. In period 1, ingested breastmilk protein content was higher for NWG infants than for infants with SWG (p = 0.01), and the protein content was negatively correlated with maternal BMI (r = −0.42, p = 0.02). The genera Veillonella (19.5%), Bifidobacterium (19.5%), and Escherichia-Shigella (16.8%) dominated the microbiota at 5 months. At 12 months, Bacteroides predominated, and the first two genera remained. Breastmilk fat correlated with Veillonella abundance (r = −0.50, p = 0.02) and oligosaccharides with Lachnospiraceae (r = 0.73, p = 0.03) at 5 months. There was a trend of a higher abundance of Bifidobacterium in NWG infants than in other infants in period 1, while infants with RWG and SWG had a higher abundance of Ruminococcus gnavus (p = 0.03) in period 1 and Alistipes in period 2 (p = 0.01), respectively. Conclusions: Breastfeeding shaped the gut microbiota of exclusively breastfed infants, and its structure was associated with infant weight gain trajectories. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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19 pages, 1528 KiB

Open AccessArticle

Maternal Folate and Vitamin B 12 Concentrations During Pregnancy Influence Neonatal Nutritional Status and Adiposity: Results from the OBESO Cohort

by Isabel González-Ludlow, Ameyalli M. Rodríguez-Cano, Jonatan A. Mendoza-Ortega, Carolina Rodríguez-Hernández, Blanca V. Suárez-Rico, Guadalupe Estrada-Gutierrez, Maricruz Tolentino-Dolores, Sandra B. Parra-Hernández, Maribel Sánchez-Martínez, Sandra Acevedo-Gallegos and Otilia Perichart-Perera

Nutrients 2025, 17(3), 372; https://doi.org/10.3390/nu17030372 - 21 Jan 2025

Cited by 1 | Viewed by 1881

Abstract

Background/Objectives: Folate and B12, among other B vitamins, are methyl donors and contribute to multiple DNA methylation processes. Maternal deficiency of these nutrients may be associated with impaired fetal growth, affecting the nutritional status and adiposity of the newborn. This study aimed to describe maternal folate and B12 status throughout pregnancy and evaluate its association with neonatal nutritional status. Methods: We studied 90 healthy pregnant women and their babies from the prospective OBESO cohort (Mexico City). Serum folate and B12 concentrations were measured (ELISA) in the first and third trimesters of pregnancy. Deficiency was considered if serum folate was <4 ng/mL, red blood cell folate (RBC) < 151 ng/mL, active B12 < 40 pmol/L, and total B12 < 203 pg/mL). Maternal supplementation of these nutrients was recorded. Newborn assessment (24–72 h) included weight (BW), length (L), waist circumference (WC), and fat mass percentage (%FM; air-displacement plethysmography). Newborn nutritional status indexes were computed and interpreted (BMI/age and length/age) (term-WHO, preterm-Intergrowth). Mean differences, correlations, and multiple linear and logistic regressions were performed (SPSS v. 29). Results: One-third of women had total vitamin B12 deficiency at the end of pregnancy; no folate deficiency was observed. High doses for both folic acid and B12 supplementation were identified in the third trimester (2057.04 ± 2100.74 μg/d and 7.35 ± 4.56 μg/d). Higher first- and third-trimester maternal active B12 concentrations predicted higher WC and reduced the risk of LBW. Higher first-trimester Thcy levels increased the risk of stunting. Higher third-trimester total B12 and folate concentrations predicted higher WC; the latter was associated with higher FM% at birth. Conclusions: Maternal folate, B12, and Thcy levels influence newborn nutritional status alterations, including adiposity markers. It is vital to guarantee an optimal and balanced maternal B-complex status throughout pregnancy. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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13 pages, 255 KiB

Open AccessArticle

Hour of Life at Enteral Feeding Initiation and Associated Clinical Morbidity in Extremely Low-Birth-Weight Infants

by Melissa Thoene, Lauren Ridgway, Elizabeth Lyden and Ann Anderson-Berry

Nutrients 2024, 16(23), 4041; https://doi.org/10.3390/nu16234041 - 26 Nov 2024

Viewed by 1041

Abstract

Background/Objectives: Identifying nutritional interventions in extremely low-birth-weight (ELBW) infants (<1000 g) that are associated with favorable clinical outcomes is important. Delayed enteral feeding initiation (>3 days) has been associated with increased odds of developing morbidity. Therefore, the aim of this study is to evaluate the relationship between hour of life at enteral feeding initiation and associated clinical outcomes. Methods: An IRB-approved retrospective chart review evaluated ELBW infants. Birth acuity was evaluated using CRIB II scoring and incidence of various morbidities (bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and spontaneous intestinal perforation (SIP)) and mortality was assessed after adjustment. p < 0.05 was statistically significant. Results: A total of 27/61 (44.3%) initiated enteral feeding <12 h of life. CRIB II scores were lower in infants with earlier enteral feeding initiation. There were no statistical differences in NEC, SIP, or death between categories of hour of life at enteral feeding initiation. After adjusting for CRIB II scores, enteral feeding initiation ≥12 h of life was associated with more days receiving oxygen >21% inspired air (β = 32.7; p = 0.040), approximately 7-fold higher odds of developing moderate/severe BPD (95% CI 1.2.8–38.28; p = 0.025), and 9-fold higher odds of being discharged home while receiving oxygen therapy (95% CI 1.03–79.81; p = 0.047). Conclusions: Timing of enteral feeding initiation may be delayed in ELBW infants with higher clinical acuity, yet later initiation by hour of life is associated with worsened clinical respiratory outcomes. Early initiation within the first 12 h of life is feasible and was not associated with gastrointestinal morbidity in this single-center cohort of ELBW infants. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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20 pages, 951 KiB

Open AccessReview

Nutritional Management for Preterm Infants with Common Comorbidities: A Narrative Review

by Cheng-Yen Chen, Mei-Yin Lai, Cheng-Han Lee and Ming-Chou Chiang

Nutrients 2025, 17(12), 1959; https://doi.org/10.3390/nu17121959 - 9 Jun 2025

Viewed by 547

Abstract

The complications observed in preterm infants are largely attributable to underdeveloped organ systems and inadequate nutritional stores at birth. Insufficient nutritional support can further exacerbate persistent sequelae, such as bronchopulmonary dysplasia (BPD), metabolic bone disease of prematurity (MBDP), and retinopathy of prematurity (ROP). As a result, clinicians have collaborated to develop optimal nutrition strategies for preterm neonates. However, these clinical nutrition plans may be hindered by several factors, including fluid restrictions due to patent ductus arteriosus (PDA) and delayed enteral nutrition following necrotizing enterocolitis (NEC). Modified strategies for specific conditions can help prevent further deterioration, but inadequate nutritional support may limit organ growth and contribute to additional complications. Achieving an optimal balance between nutritional support and managing specific medical conditions varies across institutions. In addition to fluid balance and energy intake, supplementary nutrition—such as vitamins and probiotics—plays a crucial role in disease prevention. Drawing on recent evidence and our clinical experiences with neonatal nutritional strategies, this review article summarizes the specialized nutritional management required for preterm neonates with conditions such as BPD, NEC, MBDP, PDA, and ROP. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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21 pages, 1742 KiB

Open AccessReview

Macronutrients, Micronutrients, and Malnutrition: Effects of Nutrition on Immune Function in Infants and Young Children

by R. J. Joost van Neerven

Nutrients 2025, 17(9), 1469; https://doi.org/10.3390/nu17091469 - 26 Apr 2025

Viewed by 940

Abstract

The function of the immune system is not only dependent on factors like genetics, age, the environment, and exposure to infectious agents and allergens but also on our microbiota and our diet. It has been known for centuries that food can influence health and vulnerability to infection. This is especially true for infants, young children, and the elderly. This review focuses on how nutrition can support immune function from gestation to school-aged children. Immune support begins during pregnancy by the mother’s diet and transfer of nutritional components as well as antibodies to her fetus. After birth, breastfeeding is of crucial importance for immune development as well as for the development of the intestinal microbiota of an infant. If breastfeeding is not possible, early-life formulas are an alternative. These can provide several of the functionalities of breastmilk, as well as the key nutrients a child needs. New foods are introduced during and after weaning, and after this period, children switch to consuming a normal diet. However, due to circumstances, children can be malnourished. This can range from severe protein/energy malnutrition to micronutrient deficiencies and obesity, all of which can affect the function of the immune system. This narrative review describes the immune challenges in early life, explores breastfeeding and early life nutrition, and provides mechanistic insight into the relative contribution of macronutrients, micronutrients and other immunomodulatory food components that can support immune function in early life. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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18 pages, 992 KiB

Open AccessReview

“OMICS” in Human Milk: Focus on Biological Effects on Bone Homeostasis

by Ilaria Farella, Gabriele D’Amato, Andrea Orellana-Manzano, Yaritza Segura, Rossella Vitale, Maria Lisa Clodoveo, Filomena Corbo and Maria Felicia Faienza

Nutrients 2024, 16(22), 3921; https://doi.org/10.3390/nu16223921 - 17 Nov 2024

Cited by 4 | Viewed by 2532

Abstract

Human milk (HM) is a complex biofluid rich in nutrients and bioactive compounds essential for infant health. Recent advances in omics technologies—such as proteomics, metabolomics, and transcriptomics—have shed light on the influence of HM on bone development and health. This review discusses the impact of various HM components, including proteins, lipids, carbohydrates, and hormones, on bone metabolism and skeletal growth. Proteins like casein and whey promote calcium absorption and osteoblast differentiation, supporting bone mineralization. Long-chain polyunsaturated fatty acids like docosahexaenoic acid (DHA) contribute to bone health by modulating inflammatory pathways and regulating osteoclast activity. Additionally, human milk oligosaccharides (HMOs) act as prebiotics, improving gut health and calcium bioavailability while influencing bone mineralization. Hormones present in HM, such as insulin-like growth factor 1 (IGF-1), leptin, and adiponectin, have been linked to infant growth, body composition, and bone density. Research has shown that higher IGF-1 levels in breast milk are associated with increased weight gain, while leptin and adiponectin influence fat mass and bone metabolism. Emerging studies have also highlighted the role of microRNAs (miRNAs) in regulating key processes like adipogenesis and bone homeostasis. Furthermore, microbiome-focused techniques reveal HM’s role in establishing a balanced infant gut microbiota, indirectly influencing bone development by enhancing nutrient absorption. Although current findings are promising, comprehensive longitudinal studies integrating omics approaches are needed to fully understand the intricate relationships among maternal diet, HM composition, and infant bone health. Bridging these gaps could offer novel dietary strategies to optimize skeletal health during infancy, advancing early-life nutrition science. Full article

(This article belongs to the Special Issue Nutrition Management in Neonatal Health)

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