Search Results (95)

Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut–brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan–serotonin metabolic signalling, hypothalamic–pituitary–adrenal (HPA) axis modulation, and the integrity of intestinal and blood–brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions—including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)—focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial–neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population. Full article

Background: Small for gestational age neonates represent a population at risk of growth failure or deviant growth patterns and long-term metabolic complications. Breastfeeding has been identified as a critical factor in promoting healthier growth and long-term metabolic health in both full-term and preterm appropriate for gestational age infants, but similar studies in small for gestational age infants are limited. The aim of this narrative review is to assess the impact of breastfeeding on growth and body composition in small for gestational age neonates. Methods: The PubMed and Google Scholar databases were screened for the relevant literature. The following terms, were used: “low birth weight”, “in utero growth restriction”, “small for gestational age”, “human milk”, and “growth”. The initial screening identified 57 relevant studies. Thirteen of them fulfilled the eligibility criteria and were included in this narrative review. Results: In preterm small for gestational age neonates, human milk nutrition was associated with healthier catch-up growth without excessive fat accumulation. Fortification strategies were associated with enhanced growth outcomes without increased incidence of neonatal morbidities. In the context of full-term, small for gestational age neonates, exclusive breastfeeding has been demonstrated to be associated with healthy catch-up growth. Furthermore, human milk nutrition has been shown to mitigate the predisposition of these children to obesity and cardiometabolic complications. Conclusions: According to the limited extant literature, human milk feeding has been identified as a potentially protective factor for small for gestational age neonates, promoting healthier growth patterns and long-term cardiometabolic health. However, larger prospective studies are needed to evaluate human milk feeding and human milk fortification in association with growth and long-term outcomes in small for gestational age infants. Full article

Background/Objectives: To prevent nutritional depletion and impaired weight status in infants, targeted public health policies and prevention programs based on scientific evidence are needed. This study provides an overview of the dietary patterns and feeding behavior of infants in Croatia as part of the National Food Consumption Survey on Infants and Children. Methods: This cross-sectional study was conducted following the EU Menu methodology and included 322 healthy infants (54% boys; aged 3 months up to 12 months) from Croatia. Two-day dietary records were collected and analyzed using NutriCro 2.0 software. Results: The daily energy intake of infants was on average 886 ± 219 kcal, mainly from carbohydrates (47.0%), followed by fat (41.6%) and protein (9.9%). The main sources of energy and macronutrients were milk and dairy products, grains, grain products, potatoes and tubers and the fruit food group. One third of infants were breastfed, and more than 70% of infants were introduced to complementary foods. Parents started complementary feeding at the age of 5.37 ± 0.82 months, mostly with vegetables. Breastfeeding was associated with higher energy intake, especially in infants younger than 6 months, while formula feeding was associated with lower energy intake. The multivariate regression models showed age-related interactions that attenuated the patterns for energy and macronutrient intake. Conclusions: The study emphasizes that milk and dairy products are the main source of energy and macronutrients. The study highlights the important role of breastfeeding in promoting higher energy intake in early infancy and the decreasing effect of infant formula consumption with age. These results can be used as a basis for health policies, programs and strategies that address infant feeding habits in Croatia. Full article

Background/Objectives: Pacifier use in infants has both beneficial and harmful implications, and dipping pacifiers in sweeteners is used by some parents to soothe infants. This study aimed to assess pacifier usage among mothers in Jeddah, Saudi Arabia, and to examine its association with child demographics, maternal socioeconomic status (SES), and maternal knowledge of the risks associated with dipping pacifiers in sweeteners. Methods: A cross-sectional study was conducted among mothers of healthy children aged 2 to 4 years during community-awareness events in Jeddah. Participants completed a validated Arabic questionnaire covering pacifier use patterns, feeding practices, SES background, and knowledge regarding the adverse effects of pacifier sweetening. Results: A total of 1438 mothers participated. The mean age of children was 34.3 ± 10.7 months, with 441 children (30.7%) reported as pacifier users. Among them, 202 (45.8%) used pacifiers both during the day and at night. Most children (35.6%) discontinued use between 4 and 6 months of age. Only 6.1% of mothers reported adding sweeteners to pacifiers. Pacifier usage was significantly higher among first-born children (37.6%, p < 0.001), those who received both bottle- and breastfeeding (65.5%, p < 0.001), and children enrolled in nursery (62.1%, p = 0.007). Most mothers (75.6%) were aware of the link between sweetened pacifiers and dental caries, and 69.4% of those who had this knowledge avoided giving their child a pacifier (p = 0.077). Conclusions: Birth order, feeding practices, and nursery attendance are key predictors of pacifier use. Enhancing parental awareness and education may support early interventions to promote healthier oral and feeding habits in young children. Full article

Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously demonstrated that short-duration feeding with cold liquid significantly reduces dysphagia in preterm infants; however, the impact of an entire feeding with cold milk remains unexplored. This study aimed to evaluate the safety of cold milk feedings in preterm infants with uncoordinated feeding patterns and their impact on their feeding performance. Methods: Preterm infants with uncoordinated feeding patterns (n = 26) were randomized to be fed milk at either room temperature (RT) or cold temperature (CT) using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. Results: There were no significant differences in mesenteric blood flow Doppler measurements or axillary body temperatures between the CT and RT feeding conditions. However, a reduction in gastric content temperatures of 3.6 °F and 2.7 °F was observed at one and thirty minutes following CT feeding, respectively. No evidence of cold stress, increased episodes of apnea or bradycardia, gastric residuals, or emesis was noted in infants during or after the CT feeding condition. Feeding performance outcomes did not differ significantly regarding milk transfer rate (p = 0.781) or proficiency (p = 0.425). However, the quality score on the Infant-Driven Feeding Scale (IDFS) showed a significant improvement following CT feeding (p = 0.001). Conclusions: Cold milk feeding can be a safe therapeutic option for preterm infants. This underscores the potential for further comprehensive investigations to evaluate cold milk feeding as an effective therapeutic strategy for managing feeding and swallowing difficulties in preterm infants. The study was registered at clinicaltrials.org under #NCT04421482. Full article

Background: Medium- and long-chain triacylglycerols (MLCTs) and sn-2 palmitate constitute approximately 70~80% of total breast milk fat. The structured lipid MLCTs and sn-2 palmitate, mimicking human milk, have demonstrated improvement in lipid absorption and energy metabolism in vitro and in animal experiments. However, clinical trials on infant formula supplied with MLCTs and sn-2 palmitate have yet to be conducted. Objectives: This study was designed to evaluate the effects on growth and lipid absorption of a novel formula with structured lipid MLCTs and sn-2 palmitate on healthy infants born at term. Methods: Infants were enrolled at 30 d postpartum and assigned to three groups based on their feeding conditions: (1) a novel formula with MLCTs and sn-2 palmitate (Novel-F group, n = 65); (2) a control formula with vegetable oils and no structured lipids (Contr-F group, n = 46); or (3) breastfeeding (BF group, n = 66). Growth measurements (including weight, length, and head circumference), stool characteristics, and fecal lipid composition (both soap and non-soap fatty acids) were analyzed at both baseline (30 d postpartum) and endline visits (90 d postpartum). Results: The Novel-F group had significantly higher weight gains (2195 ± 595 g) during the intervention compared to the Contr-F group (1897 ± 483 g) but similar weight gains to the BF group (2081 ± 614 g), with the changes in Z_w/a following a similar pattern. Z_l/a increased in the Novel-F group (0.04, (95% CI: −0.21 to 0.28)) and decreased in both the Contr-F (−0.23 (95% CI: −0.52 to 0.06)) and BF groups (−0.20 (95% CI: −0.44 to 0.05)). The stools of infants in the Novel-F group had similar undigested triacylglycerols and total fatty acids compared to breastfed infants but had significantly lower levels than infants fed with the control formula at both baseline and endline visits. Conclusions: The novel infant formula with MLCTs and sn-2 palmitate is safe and well tolerated, and supports adequate weight gain and improves lipid absorption. Full article

Background/Objectives: This study aimed to demonstrate the safety and suitability of an infant formula manufactured from partially hydrolysed whey protein (PHF) compared to standard formula manufactured from intact cow’s milk proteins (IPF; whey–casein ratio, 60:40) in healthy term infants. Methods: This multicentre, randomised, double-blinded, placebo-controlled trial included infants of mothers who intended to exclusively formula feed. Infants ≤ 28 days of age received PHF or IPF for at least 90 and up to 180 days. A group of exclusively breastfed infants was included for reference. The safety evaluation consisted of an equivalence analysis of weight gain within +/−3 g/d after 90 days, further growth parameters, and adverse events. Results: Of the 249 infants randomised, 143 (76 IPF; 67 PHF), as well as 45 breastfed infants, completed the study per protocol. The mean difference in daily weight gain between the formula groups was within the equivalence margins (−2.4 g/d (95% CI 0.3–4.5)) with estimated means (SEM) of 34.9 (0.78) g/d (IPF) and 32.5 (0.76) g/d (PHF). No significant differences in weight gain, length, and head circumference or in the number, severity, or type of adverse events were observed. Comparable growth patterns were observed in the breastfed group. Conclusions: The PHF is safe and supports adequate infant growth with a daily weight gain non-inferior to a standard IPF. Full article

Background: Understanding the patterns of milk intake in the neonatal intensive care unit (NICU) will allow opportunities to intervene to improve mother’s milk supply. Objective: To quantify the type and volume of milk intake in premature infants throughout the NICU stay. Methods: This retrospective observational cohort study included infants born and admitted to the NICU at <33 weeks gestation from January 2014 to December 2017 who did not have contraindications for receiving mother’s own milk (MOM). Daily volume of MOM, pasteurized donor milk (PDM), and formula throughout the NICU stay were collected. Infants were categorized as exclusive human milk diet (EHM) if they consumed MOM and PDM or mixed diet if they consumed formula and MOM and/or PDM. Demographics, feeding outcomes, growth outcomes, and neonatal morbidities were collected. Results: Of 195 study infants, 133 (32%) received EHM. Cumulative volume and percent of MOM intake were greater in the EHM group compared to the mixed diet group. Age of first colostrum administration to infant was earlier in the EHM group than the mixed diet group (3.1 vs. 4.9, p = 0.013). By the second week of life, the EHM group received 100% of their feeds as MOM but the maximum MOM received in the mixed diet group was 63%. There was no difference in other feeding or neonatal outcomes between the groups. Conclusion: The EHM group received colostrum earlier than those who received a mixed diet with formula and reached full MOM by the second week of life. This represents the opportunity to address challenges of milk supply of mothers with premature infants in the NICU in the first two weeks after birth. Full article

Background: Preventing neurodevelopmental impairment after extremely preterm birth remains challenging. While breast milk feeding is linked to better neurodevelopment, the underlying mechanisms are unclear. This study explored the association between individual human milk oligosaccharides (HMO) and neurodevelopment at two years of age in extremely preterm children. Methods: Milk samples from mothers of 76 extremely preterm infants collected at two weeks after birth were analyzed for 15 dominant HMOs. Register data from examination and Bayley-III neurodevelopmental assessment at two years’ corrected age was retrieved and categorized into levels of impairment. An exploratory analysis examined associations between the HMO composition and neurodevelopment. Results: Bioinformatic volcano plots revealed associations between specific HMOs and outcomes: 3FL with less neurodevelopmental impairment, LSTb with higher Bayley-III cognitive scores, and LSTa with worse neurodevelopmental impairment outcomes. Spearman correlations indicated LSTa was linked to more neurodevelopmental impairment (p = 0.018), lower language (p = 0.009), and motor (p = 0.02) scores, whereas 3FL correlated with less neurodevelopmental impairment (p = 0.02). Dichotomized analysis showed LSTa was associated with more neurodevelopmental impairment and lower language scores (p < 0.05), 3FL with milder neurodevelopmental impairment (p < 0.05), and LSTb with better cognitive (p < 0.01) and language (p < 0.05) scores. No significant associations were found for HMO diversity, total sialic acid content, or secretor/Lewis patterns. Conclusions: In this explorative hypothesis-generating study, certain HMOs appeared to be associated with both potentially beneficial and adverse neurodevelopmental outcomes in extremely preterm infants. However, these findings should be interpreted with caution, as they do not constitute evidence but rather serve as a preliminary foundation for future hypothesis-driven research. Full article

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

Nowadays, vegetarian diets are present in a solid way in Western countries’ lifestyles. Some families opt for this dietetic pattern for their infants too, during the period of introduction of complementary foods. Many releases have been issued about this subject, with different and often contradictory advice and conclusions. The aim of this work is to provide a comprehensive overview through the analysis of recently published opinions of the implementation of a vegetarian or vegan diet over the course of complementary feeding. The literature agrees about some key points to consider, that is the necessity for the diet to be well-planned, in order to meet energy, macro- and micronutrients requirements, as well as the need to follow the child longitudinally. Also, there is a substantial agreement on the need for fortified foods and/or supplements to be included in the diet. Following these suggestions, most (but not all) of the papers agree that normal growth and development may be achieved. Final considerations, however, are not straightforward to make and more research with better definition of the features of the diet adopted and of supplementation used and long-term follow-up studies are highly warranted. Full article

Background/Objectives: We aimed to identify neonatal circulating metabolic alterations associated with maternal gestational diabetes mellitus (GDM) and to explore whether these altered metabolites could mediate the association of GDM with offspring neurodevelopment. Additionally, we investigated whether neonatal circulating metabolites could improve the prediction of offspring neurodevelopmental disorders over traditional risk factors. Methods: The retrospective cohort study enrolled 1228 mother–child dyads in South China. GDM was diagnosed at 24–28 weeks of gestation. Neonatal circulating amino acids and lipid metabolites (carnitines) were measured from newborn heel blood 3–7 days postpartum. Offspring neurodevelopment was assessed at age 1 year using the Children Neuropsychological and Behavioral Examination Scale. Neurodevelopmental disorders were defined as developmental delay in any domain of the scale. Results: Twenty-one metabolites associated with GDM were identified, consisting of seven amino acids and fourteen carnitines. Among these metabolites, five (glycine, myristicylcarnitine, palmitoylcarnitine, octadecadienoylcarnitine, and 3-hydroxypalmitylcarnitine) mediated the negative association of GDM with offspring neurodevelopment at 1 year (mediation proportions: 3.91–10.66%). Furthermore, six metabolites (glycine, methionine, malonylcarnitine, isovalerylcarnitine, palmitoylcarnitine, and octadecadienoylcarnitine) significantly increased the predictive performance for offspring neurodevelopmental disorders at 1 year over five traditional risk factors including GDM, parity, infant sex, birth weight, and feeding patterns (area under curve: 0.762 vs. 0.718, p = 0.012). Conclusions: GDM was associated with a variety of amino acid and lipid metabolic alterations in neonatal circulation, among which certain metabolites mediated the association of GDM with adverse neurodevelopmental outcomes in offspring. Moreover, some neonatal circulating metabolites may serve as potential biomarkers that improved the prediction of offspring neurodevelopmental disorders over GDM and other traditional risk factors. Full article

The postpartum period represents a critical phase of profound transition for women. This timeframe encompasses the physical recuperation associated with childbirth, the intricate psychosocial adjustments inherent in assuming the role of motherhood and also important alterations in steroid and peptide hormones. Hence, as women navigate the reconfiguration of relationships and strive to address the diverse needs of their infants and family members, they concurrently grapple with dramatic transformations which are characteristic of the postpartum phase. In fact, relevant prevalence ranges are reported for maternity blues, a mild condition characterized by self-limited and transient depressive symptoms, but also a well-established risk factor for more serious postpartum mood disorders, such as depression (PPD), with an incidence of 10–15%. Unlike in the US, at the European level, there are no concrete recommendations for the routine integration of the assessment of the mother’s emotional state by healthcare professionals, with a considerable risk of underdiagnosing or undertreating these conditions. In this regard, there is a growing body of scientific evidence on the important role of breastfeeding in reducing the risk of PPD and also of the importance of mothers’ compliance with this practice. Indeed, sucking the baby regulates the circadian rhythm of the HPA axis and, together with the action of prolactin, the stress response is decreased. In addition, other positive consequences of breastfeeding, which are inversely correlated with the onset of PPD, include the regulation of sleep and waking patterns for mother and baby, the improvement of the mother’s self-efficacy and her emotional involvement. It should also be considered that the request for support for breastfeeding can often conceal a request for support for motherhood itself and for the mother’s emotional well-being. It therefore emerges that the personnel involved in primary pediatric care to provide adequate support in the transition to motherhood must support mothers in their breastfeeding choices, whether breastfeeding or formula feeding, so that each choice is made conscientiously and serenely. Therefore, neonatal feeding assumes a decisive role, since if, on the one hand, it regulates specific neurohormonal pathways that are protective for maternal emotional well-being (breastfeeding), on the other hand, support in mothers’ breastfeeding choices, even in the case of formula feeding, means validating their being mothers in the absence of judgement and counteracting any feelings of inadequacy, conditions that are inversely correlated to DPP. Full article

The long-term efficacy and use of phenylalanine-free infant amino acid formula (PFIF) is understudied. This retrospective, longitudinal study evaluated PFIF (PKU Start: Vitaflo International) in children with phenylketonuria, collecting data on metabolic control, growth, dietary intake, and symptoms and the child’s experience with PFIF. Twenty-five children (12 males, 48%) with a median age of 3.6 years (2.0–6.2 years) were included. During 24 months follow-up, children maintained normal growth and satisfactory metabolic control. The protein intake from protein substitutes increased from 2.7 at 6 months to 2.8 g/kg/day at 24 months, while natural protein decreased from 0.6 to 0.4 g/kg/day. By 24 months, most children (n = 16, 64%) had stopped PFIF, while nine (36%) continued with a median intake of 450 mL/day (Q1:300 mL, Q3: 560 mL). Children who continued PFIF after 24 months of age had higher energy and fat intakes with higher weight/BMI z-scores compared with those who stopped earlier (p < 0.05). Constipation was reported in 44% of infants but improved with age. Initial difficulty with PFIF acceptance was reported in 20% of infants but also improved with time. Prolonged use of PFIF in pre-school children may contribute to poor feeding patterns and overweight; thus, replacing the majority of the protein equivalent provided by PFIF with a weaning protein substitute by 12 months and discontinuing PFIF before 2 years is recommended. Full article

Toddlerhood (aged 13~36 months) is a period of dietary transition, with water intake being significantly influenced by parental feeding patterns, cultural traditions, and the availability of beverages and food. Nevertheless, given the lack of applicable data, it is challenging to guide and evaluate the water intake of toddlers in China. In this study, our objectives were to assess the daily total water intake (TWI), evaluate the consumption patterns of various beverages and food sources contributing to the TWI, determine the conformity of participants to the adequate intake (AI) recommendation of water released by the Chinese Nutrition Society, and analyze the various contributors to the daily total energy intake (TEI). The data for the assessment of water and dietary intake were obtained from the cross-sectional dietary intake survey of infants and young children (DSIYC, 2018–2019). A total of 1360 eligible toddlers were recruited in the analysis. The differences in related variables between two age groups were compared by Mann–Whitney U test and Chi-Square test. The potential correlation between water and energy intake was examined utilizing age-adjusted partial correlation. Toddlers consumed a median daily TWI of 1079 mL, with 670 mL (62.3%, r = 0.752) derived from beverages and 393 mL (37.7%, r = 0.716) from foods. Plain water was the primary beverage source, contributing 300 mL (52.2%, r = 0.823), followed by milk and milk derivatives (MMDs) at 291 mL (45.6%, r = 0.595). Notably, only 28.4% of toddlers managed to reach the recommended AI value. Among these, toddlers obtain more water from beverages than from foods. The median daily TEI of toddlers was 762 kcal, including 272 kcal from beverages (36.4%, r = 0.534) and 492 kcal from foods (63.6%, r = 0.894). Among these, the median daily energy intake from MMDs was 260 kcal, making up 94.6% of the energy intake from beverages (r = 0.959). As the pioneer survey on TWI of toddlers in China based on nationally representative data, attention to the quality and quantity of water intake and actions to better guide parents by both individuals and authorities are eagerly anticipated. Additionally, the revision of the reference value of TWI for Chinese toddlers is urgently required. Full article