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Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions

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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: 5 June 2025 | Viewed by 18185

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Prof. Dr. Walter A. Mihatsch

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Guest Editor

1. Department of Pediatrics, Ulm University, 89075 Ulm, Germany
2. Department of Health Management, Neu-Ulm University of Applied Sciences, 89231 Neu-Ulm, Germany
Interests: preterm and term infant enteral and parenteral nutrition; bone mineralization; family integrated care
Special Issues, Collections and Topics in MDPI journals

Dr. Miguel Saenz de Pipaon

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Guest Editor

Department of Neonatology, Hospital Universitario La Paz, Department of Pediatrics, Universidad Autonoma de Madrid, 28046 Madrid, Spain
Interests: preterm and term infant parenteral and enteral nutrition; feeding
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is an increasing body of evidence suggesting that pre-, peri- and postnatal nutrition during the first 1000 days (from conception to two years of age) significantly affects long-term development and neurodevelopmental outcome. In addition, the patients’ survival, especially in the most immature preterm infants, significantly improved during the recent decades. On the other hand, there is still significant postnatal malnutrition and growth failure.

For this upcoming Nutrients Special Issue, it is our pleasure to invite researchers to contribute papers that explore recent developments in fetal, perinatal, preterm, and term-neonatal nutrition or feeding focusing on physiology, new hypothesis, and interventions to improve care and outcome.

Prof. Dr. Walter A. Mihatsch
Dr. Miguel Saenz de Pipaon
Guest Editors

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Keywords

nutrition
preterm infants
term infant
parenteral nutrition
prebiotics
probiotics
symbiotics
oligosaccharides
hydrolyzed protein
amino acids
feeding

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Published Papers (10 papers)

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Research

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11 pages, 1672 KiB

Open AccessArticle

Bioelectrical Impedance Vector Analysis in Extremely Low-Birth-Weight Infants to Assess Nutritional Status: Breakthroughs and Insights

by Raquel Núñez-Ramos, Diana Escuder-Vieco, Carolina Rico Cruz, Cristina De Diego-Poncela, Sara Vázquez-Román, Marta Germán-Díaz, Nadia Raquel García-Lara and Carmen Pallás-Alonso

Nutrients 2024, 16(24), 4348; https://doi.org/10.3390/nu16244348 - 17 Dec 2024

Viewed by 832

Abstract

Background/Objectives: To obtain bioelectrical data to assess nutritional status for extremely low-birth-weight (ELBW) infants upon reaching term-corrected age. Methods: A descriptive, observational, prospective, and single-center study, which included ELBW preterm infants was performed. The study variables collected were gestational age, sex, and anthropometry at birth and at term-corrected age. Bioelectrical impedance vector analysis (BIVA) was performed by a phase-sensitive device (BIA 101 BIVA PRO AKERN srl, Pisa, Italy). The components of the impedance vector—resistance (R) and reactance (Xc)—were normalized for body height (H). For each subject, the measurement was taken between the 36th and 44th weeks of postmenstrual age (PMA). A semi-quantitative analysis of body composition was performed using the vector modality of the BIA. Using the RXc graph method, the bivariate 95% confidence intervals of the mean vectors were constructed. From the bivariate normal distribution of R/H and Xc/H, the bivariate 95%, 75%, and 50% tolerance intervals for this cohort were drawn. The individual impedance vectors were compared with the distribution of the vectors from other populations. Results: 85 ELBW infants (40 male, 45 female) were included, with a mean gestational age at birth of 26 + 6 weeks (±1.76). Mean R/H was 870.33 (±143.21) Ohm/m and Xc/H was 86.84 (±19.05) Ohm/m. We found differences in the bioelectrical data with regard to gender, with resistance values being significantly higher in females. Our ellipses align closely with those from other term neonatal cohorts. Conclusions: Bioelectrical data and the confidence and tolerance ellipses of an ELBW infant cohort are presented and can be used as a reference standard for nutritional assessment at discharge. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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11 pages, 594 KiB

Open AccessArticle

Does the Composition of Breast Milk in the First Week Postpartum Differ Due to Maternal Factors or Neonatal Birth Weight and Percent Fat Body Mass?

by Karolina Karcz, Paulina Gaweł and Barbara Królak-Olejnik

Nutrients 2024, 16(19), 3310; https://doi.org/10.3390/nu16193310 - 30 Sep 2024

Cited by 1 | Viewed by 1472

Abstract

Background: The composition of breast milk is dependent on numerous factors. However, the precise impact of maternal health conditions on breast milk composition remains to be fully elucidated. Similarly, there is a paucity of evidence regarding the correlation between neonatal body composition and human milk. The objective of the study was to evaluate the macronutrient composition of breast milk collected during the first week postpartum from mothers with gestational diabetes and healthy mothers in terms of selected maternal and neonatal factors. Methods: n = 70 breast milk samples were analyzed for fat, protein, carbohydrate, dry matter, true protein, and energy. The results were evaluated in terms of selected maternal factors, as well as neonatal birth weight (BW) and percent fat body mass (%FBM), which was assessed with a bioimpedance method. Results: Energy of breast milk in the study group was as follows: median 55.5 kcal/dL in GDM G1, median 55.5 kcal/dL in GDM G2, and median 65.0 kcal/dL in non-GDM, which differed significantly in Kruskal–Wallis ANOVA. Neonatal %FBM, but not BW, was found to be significantly related to concentrations of protein, true protein and dry matter. Maternal gestational weight gain, history of hypothyroidism, and classification by study group were identified as factors affecting both breast milk and neonatal body composition. Conclusions: The composition of breast milk in the initial week following childbirth is predominantly determined by maternal factors. The relationship between selected macronutrients and neonatal percent fat body mass was found to be weak, yet the significance of this finding is unclear. Further research is required to ascertain the influence of maternal milk composition on early infantile nutritional programming. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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15 pages, 2301 KiB

Open AccessArticle

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study—A Randomized Clinical Trial

by Maria Sanchez-Holgado, Miguel Saenz de Pipaon, Maria Concepcion Jimenez, Gema Crespo Sanchez, Marta Molero-Luis, Maria Teresa Montes, Cristina Segovia, Itsaso Losantos-García, María Jimenez-Gonzalez, Esperanza Escribano and Marta Cabrera-Lafuente

Nutrients 2024, 16(17), 2904; https://doi.org/10.3390/nu16172904 - 30 Aug 2024

Viewed by 1865

Abstract

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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13 pages, 843 KiB

Open AccessArticle

Metabolic and Low-Grade Inflammation Risk in Young Adults with a History of Extrauterine Growth Restriction

by Laura Palomino-Fernández, Belén Pastor-Villaescusa, Inmaculada Velasco, María de la Cruz Rico, Juan Roa, Ángel Gil and Mercedes Gil-Campos

Nutrients 2024, 16(11), 1608; https://doi.org/10.3390/nu16111608 - 24 May 2024

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Abstract

Children with a history of extrauterine growth restriction (EUGR), later at prepubertal age, exhibit an increased metabolic risk including risen insulin resistance and low-grade inflammation. However, the progression of such metabolic changes after puberty and the lasting health implications have not yet been investigated. The objective of this study was to ascertain whether young adults with a history of EUGR faced increased vulnerability to metabolic disorders. A study was conducted comparing a group of adults with a history of EUGR with a healthy reference group. A total of 110 young adults (36 from the EUGR group and 74 from the control group) were included. Anthropometric variables, blood pressure (BP), general biochemical parameters, plasma inflammatory biomarkers, and adipokines were assessed. Compared to the reference group, the EUGR group had a shorter height and body weight with higher lean mass and waist circumference, as well as a greater percentage of individuals with high BP. In addition, EUGR patients had higher values of insulin, HOMA-IR, nerve growth factor, and leptin, and lower levels of adiponectin and resistin. The present study suggests that young adults with a history of EUGR present increased metabolic risk factors therefore, clinical follow-up should be considered. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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13 pages, 288 KiB

Open AccessArticle

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2–3-Year Neurodevelopmental Outcome

by Paolo Massirio, Marcella Battaglini, Irene Bonato, Sara De Crescenzo, Maria Grazia Calevo, Mariya Malova, Samuele Caruggi, Alessandro Parodi, Deborah Preiti, Agata Zoia, Sara Uccella, Domenico Tortora, Mariasavina Severino, Andrea Rossi, Cristina Traggiai, Lino Nobili, Pasquale Striano and Luca Antonio Ramenghi

Nutrients 2024, 16(3), 449; https://doi.org/10.3390/nu16030449 - 3 Feb 2024

Viewed by 1968

Abstract

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59–0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

12 pages, 1903 KiB

Open AccessArticle

The Umbilical Cord Creatine Flux and Time Course of Human Milk Creatine across Lactation

by Walter Alexander Mihatsch, Bernd Stahl and Ulrike Braun

Nutrients 2024, 16(3), 345; https://doi.org/10.3390/nu16030345 - 24 Jan 2024

Cited by 7 | Viewed by 2893

Abstract

(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (−2.07 mmol/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding (p < 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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Review

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27 pages, 571 KiB

Open AccessReview

Complementary Feeding and Infant Gut Microbiota: A Narrative Review

by Danielle L. Noles, Kinzie L. Matzeller, Daniel N. Frank, Nancy F. Krebs and Minghua Tang

Nutrients 2025, 17(5), 743; https://doi.org/10.3390/nu17050743 - 20 Feb 2025

Viewed by 955

Abstract

Background: The complementary feeding period, spanning from 6 to 24 months of age, marks the transition from an exclusive liquid diet in infants to a dietary pattern requiring the introduction of solid foods to meet nutritional demands. Complementary feeding coincides with other critical development windows, including the maturation of the gut microbiome. However, the effects of specific solid foods on gut microbiota and the subsequent influence on health outcomes require further investigation. Methods: This narrative review analyzes published research from January 2004 to October 2024 and aims to summarize the current evidence of the effects of complementary feeding on the infant gut microbiota. Results: A total of 43 studies were included in this review. Overall, multiple studies reported an increase in alpha-diversity after solid food introduction. Bifidobacteriaceae is the predominant bacterial family during the first 6 months of life, shifting to Lachnospiraceae, Ruminococcaceae, and Clostridium spp. after the introduction of solid foods. The timing of solid food introduction may also influence gut microbiota, though results were inconclusive. The effect of individual dietary components on the gut microbiota was conflicting, with limited evidence to make inferences. Conclusions: Because of variations in study design, dietary intake quantification, and minimal follow-up, a lack of conclusive evidence exists describing the relationship between complementary feeding and gut microbiota outcomes in infants. Future research to describe these relationships should focus on the impact of individual foods on microbial diversity and maturation, as well as the relationship between microbiota and infant health outcomes. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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15 pages, 1623 KiB

Open AccessReview

Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition—A Narrative Review

by Wolfgang Bernhard, Katrin A. Böckmann, Michaela Minarski, Cornelia Wiechers, Annegret Busch, Daniela Bach, Christian F. Poets and Axel R. Franz

Nutrients 2024, 16(12), 1873; https://doi.org/10.3390/nu16121873 - 14 Jun 2024

Cited by 1 | Viewed by 3073

Abstract

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms “choline” and “parenteral nutrition”, resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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Other

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7 pages, 526 KiB

Open AccessBrief Report

Nutritional Outcomes of Bowel Lengthening Procedure in Patients with Short Bowel Syndrome

by Tena Niseteo, Mia Šalamon Janečić, Sara Sila, Anuka Torić, Laura Serdar, Stjepan Višnjić, Francisca Tolete Velcek, Marko Mesić and Iva Hojsak

Nutrients 2024, 16(10), 1456; https://doi.org/10.3390/nu16101456 - 12 May 2024

Viewed by 1397

Abstract

Background: Although parenteral nutrition (PN) significantly improves mortality rates in pediatric short bowel syndrome (SBS), long-term PN has many possible complications and impacts quality of life. Bowel lengthening procedures (BLPs) increase the contact surface of food and the intestinal mucosa and enable the better absorption of nutrients and liquids, possibly leading to a PN decrease. Methods: We retrospectively reviewed the data of patients with short bowel syndrome who underwent BLPs in the period from January 2016 to January 2022. Overall, eight patients, four male, five born prematurely, underwent BLPs. Results: There was a significant decrease in the percentage of total caloric intake provided via PN and PN volume after the BLPs. The more evident results were seen 6 months after the procedure and at the last follow-up, which was, on average, 31 months after the procedure. Two patients were weaned off PN after their BLPs. Patients remained well nourished during the follow-up. Conclusions: The BLP led to a significant decrease in PN needs and an increase in the food intake; however, significant changes happened more than 6 months after the procedure. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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19 pages, 864 KiB

Open AccessSystematic Review

Plant-Derived Substances for Prevention of Necrotising Enterocolitis: A Systematic Review of Animal Studies

by Cheryl Anne Mackay, Chandra Rath, Shripada Rao and Sanjay Patole

Nutrients 2024, 16(6), 832; https://doi.org/10.3390/nu16060832 - 14 Mar 2024

Cited by 1 | Viewed by 1617

Abstract

Inflammation, oxidative injury, and gut dysbiosis play an important role in the pathogenesis of necrotising enterocolitis (NEC). Plant-derived substances have historically been used as therapeutic agents due to their anti-inflammatory, antioxidant, and antimicrobial properties. We aimed to review pre-clinical evidence for plant-derived substances in the prevention and treatment of NEC. A systematic review was conducted using the following databases: PubMed, EMBASE, EMCARE, MEDLINE and Cochrane Library (PROSPERO CRD42022365477). Randomized controlled trials (RCTs) and quasi-RCTs that evaluated a plant-derived substance as an intervention for NEC in an animal model of the illness and compared pre-stated outcomes (e.g., clinical severity, severity of intestinal injury, mortality, laboratory markers of inflammation and oxidative injury) were included. Sixteen studies (n = 610) were included in the systematic review. Ten of the sixteen included RCTs (Preterm rat pups: 15, Mice: 1) reported mortality and all reported NEC-related histology. Meta-analysis showed decreased mortality [12/134 vs. 27/135; RR: 0.48 (95% CI: 0.26 to 0.87); p = 0.02, 10 RCTs] and decreased NEC in the experimental group [24/126 vs. 55/79; RR: 0.34 (95% CI: 0.22 to 0.52); p < 0.001, 6 RCTs]. Markers of inflammation (n = 11) and oxidative stress (n = 13) improved in all the studies that have reported this outcome. There was no significant publication bias for the outcome of mortality. Plant-derived substances have the potential to reduce the incidence and severity of histologically diagnosed NEC and mortality in rodent models. These findings are helpful in guiding further pre-clinical studies towards developing a food supplement for the prevention of NEC in preterm infants. Full article

(This article belongs to the Special Issue Recent Developments in Perinatal-Preterm and Term-Neonatal Nutrition—Physiology, New Hypothesis and Interventions)

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