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. 2025 Jun 9;51:184. doi: 10.1186/s13052-025-02034-3

Citrobacter and Acinetobacter are respectively involved in feeding intolerance in preterm infants of different gestational ages: a prospective case-control study

Chunyan Fu 1,2,#, Jinglin Xu 1,2,#, He Wang 1,2, Dongmei Chen 1,2,✉, Zhiyong Liu 1,2,✉
PMCID: PMC12150512  PMID: 40490820

Abstract

Background

Feeding intolerance (FI) is a common feeding problem in preterm infants. The gut microbiota contributes significantly to its onset, progression, and outcome. In this study, we aimed to understand the differences in gut microbiota among preterm infants with FI of different gestational ages. The goal was to provide a basis for early probiotic intervention.

Methods

We undertook a prospective case-control study in which we enrolled 80 preterm infants at a gestational age < 34 weeks. Participants were divided into four groups of 20 each: early preterm infants with FI (EFI group, gestational age < 32 weeks), early preterm infants with feeding tolerance (FT) (EFT group, gestational age < 32 weeks), moderate preterm infants with FI (MFI group, gestational age ≥ 32 weeks), moderate preterm infants with FT (MFT group, gestational age ≥ 32 weeks). 16 S rDNA high-throughput sequencing was employed to analyze the infants’ fecal microbiota and examine the potential link between gut microbiota and gestational age. Statistical analysis was conducted for the collected data. The Statistical Package for Social Sciences software was used. T-tests or non-parametric tests were performed for comparison between groups of measurement data, and the χ2 test was used to compare between groups of count data. At the genus and species level, the potential association between intestinal microbiota and FI and the relationship with gestational age were explored.

Results

The abundance of Citrobacter in the feces of the EFI group was significantly higher than that in the EFT group. Additionally, the abundance of Acinetobacter in the MFI group was significantly higher than that in the MFT group. The abundance of Clostridium XI was significantly low in the MFT group.

Conclusions

Citrobacter and Acinetobacter genera are implicated in FI in preterm infants with gestational ages < 32 weeks and ≥ 32 weeks, respectively. However, Clostridium XI may be involved in regulating intestinal homeostasis in those with a gestational age ≥ 32 weeks.

Trial registration

ChiCTR, ChiCTR2400086000. Registered 24 June 2024, https://www.chictr.org.cn/showprojEN.html?proj=210,126.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13052-025-02034-3.

Keywords: Feeding intolerance, Gut microbiota, High-throughput sequencing, Preterm infants

Background

Feeding intolerance (FI) is the inability to completely digest food in the gastrointestinal tract (or gut), leading to gastric retention, abdominal distension, and vomiting. FI can prolong enteral nutrition, resulting in extrauterine growth restriction in preterm infants. Additionally, gut function and structural integrity can be disrupted when enteral nutrition is lacking. Subsequently elevating the incidence of necrotizing enterocolitis (NEC) [1], cholestasis, bloodborne infection, and liver impairment, thereby, increasing the length of hospitalization. Hence, it is better to early establish enteral nutrition for preterm infants.

Neonates tolerate enteral nutrition depending on the maturity of their gut, including mechanical and digestive-enzyme functions, hormonal responses, bacterial colonization, and the gut’s local immune maturity [2]. Incomplete structural and functional development of the gut, abnormal bacterial colonization, and local immunodeficiency result in FI in preterm infants. Xu et al. [3] found that the incidence rates of FI in preterm infants born at gestational age < 32 weeks, 32–34 weeks, and 34–37 weeks were 67.6%, 48.8%, and 27.0%, respectively [3]. Reportedly, the onset, progression, and outcome of FI in preterm infants were associated with abnormal distribution of the gut microbiota [4, 5]. In this study, we aimed to understand the differences in gut microbiota among preterm infants with FI of different gestational ages. The goal was to provide a basis for early probiotic intervention.

Methods

Ethics declaration

This study was approved by the Ethics Committee of Quanzhou Children’s Hospital (2021 Ethics Review No. 20).

Participant recruitment

In this observational controlled trial, we recruited preterm infants who were admitted to the Neonatal Intensive Care Unit (NICU) of Quanzhou Children’s Hospital between December 2021 and December 2022 (clinical trial registration number, ChiCTR2400086000). The inclusion criteria were gestational age < 34 weeks at birth, admission within 24 h after birth, and complete perinatal data. We excluded neonates with congenital deformities, inherited metabolic diseases, intestinal infection, NEC, and neonates who received probiotics or lactase intervention during hospitalization. The guardians of the participants who met the inclusion criteria provided signed informed consent.

Diagnostic criteria for feeding intolerance

Following the 2020 guidelines for the diagnosis and treatment of FI in preterm infants in China. A diagnosis of FI was obtained when one of the following criteria was met [6]: (1) gastric residual volume exceeded 50% of the previous feeding volume, accompanied by vomiting and/or abdominal distension; and (2) feeding-plan failure, including decreased, delayed, or interrupted enteral feeding.

Calculation of sample size

This was a prospective case-control study, where we primarily observed the gut microbiota of preterm infants with a gestational age < 34 weeks who experience FI. The incidence of FI among preterm infants with a gestational age < 34 weeks who were admitted to our hospital’s NICU in 2020 was 69.9%, and the margin of error was 10%. Therefore, the sample size was calculated using the formula: n = Z2⋅p⋅(1 − p)​/ d2. The resulting sample size was 80 (40 in the experimental group and 40 in the control group).

Study design

Eighty preterm infants with a gestational age < 34 weeks were included. Participants were divided into four groups of 20 each: early preterm infants with FI (EFI group, gestational age < 32 weeks), early preterm infants with feeding tolerance (FT) (EFT group, gestational age < 32 weeks), moderate preterm infants with FI (MFI group, gestational age ≥ 32 weeks), moderate preterm infants with FT (MFT group, gestational age ≥ 32 weeks). The EFT and MFT groups, comprised preterm infants with FT who were matched with the EFI and MFI groups by gestational ages (± 2 days) during the same admission period. Similarly, 20 participants were recruited in each group. The general clinical data from the preterm infants and their mothers in the four groups were collected and 16 S rRNA high-throughput sequencing was used to analyze the characteristics of the gut microbiota, including the relative abundances and diversity of species involved. We used the Statistical Package for Social Sciences software for statistical analysis of the collected data. T-tests or non-parametric tests were used for intergroup comparison of quantitative data, and the χ2 test was used for intergroup comparing qualitative data. The potential relationship of gut microbiota and FI with gestational age was examined using a pairwise comparison of gut microbiota among the four groups at the genus and species levels.

Sample collection and testing

Fecal samples were collected from the EFI and MFI groups within 24 h of FI, as well as from the EFT and MFT groups at corresponding gestational and postnatal ages (± 2 days). During sampling, the operator wore sterile gloves and used a sterile swab to collect a sample from the middle inner part of fresh stool from the diaper. No less than 5 g of stool were collected. For those who have not defecated, abdominal massage combined with a cotton swab coated with mineral oil was used to stimulate bowel movements. The collected samples were placed in 5 ml sterilized Eppendorf or storage tubes, labeled with numbers, and stored in an ice box. The samples were transferred to a -80 °C refrigerator within 2 h for DNA extraction analysis.

Genomic DNA from samples was extracted using the CTAB method. A polymerase chain reaction (PCR) reaction mixture was prepared with 30 ng of high-quality genomic DNA and corresponding fusion primers, followed by PCR amplification. The PCR products were purified using Agencourt AMPure XP beads and dissolved in an elution buffer, labeled, and the library construction was completed. The fragment size range and concentration of the libraries were detected using an Agilent 2100 Bioanalyzer. Qualified libraries were sequenced based on the size of the inserted fragments.

Results

We enrolled 80 preterm infants at a gestational age < 34 weeks and collected their fecal samples. The gestational ages at birth for the EFI, EFT, MFI, and MFT groups were 30.04 ± 0.31, 29.71 ± 0.31, 32.97 ± 0.14, and 33.01 ± 0.11 weeks, respectively; and their birth weights were 1477.50 ± 304.66 g, 1375.50 ± 297.77 g, 1860.75 ± 336.86 g, and 1953.25 ± 238.74 g respectively. These parameters differed significantly among the four groups (P = 0.001). However, there were no statistically significant differences in sex, Apgar score, delivery method, feeding method, duration of post-delivery antibiotic treatment, incidence of perinatal infection, ventilator usage rate, or other clinical data among the four groups (P > 0.05, Table 1). The gestational ages at birth and birth weights of the EFI and EFT groups were significantly lower than those of the MFI and MFT groups (P < 0.001). Notably, the same indices between the EFI and EFT groups and between the MFI and MFT groups did not differ (P > 0.05; refer to Supplementary Material).

Table 1.

Comparison of general clinical data of premature infants in the four groups

Total infants EFI (n = 20) EFT (n = 20) MFI (n = 20) MFT(n = 20) P
Male/Female 12/8 13/7 10/10 12/8 0.806
Gestational age at birth weeks 30.04 ± 0.31 29.71 ± 0.31 32.97 ± 0.14 33.01 ± 0.11 0.001*
Birth weight g 1477.50 ± 304.66 1375.50 ± 297.77 1860.75 ± 336.86 1953.25 ± 238.74 0.001*
APGAR 1 min, median (IQR) b 8 (2,10) 8 (2,10) 8 (4,10) 8 (4,10) 0.146
APGAR 5 min, median (IQR) 8 (5,10) 9 (6,10) 9 (4,10) 9 (7,10) 0.085
Vaginal birth, n (%)a 11 (55) 12 (60) 8 (40) 7 (35) 0.333
Postnatal
First antibiotic-free day of life b 10.1 ± 1.2 9.9 ± 1.1 9.1 ± 0.7 7.4 ± 0.8 0.532
Human milk use, n (%) 7 (35) 9 (45) 6 (30) 8 (40) 0.785
mechanical ventilation, n (%)a 16 (80) 18 (90) 16 (80) 18 (90) 0.661
SIMV d, bmedian (IQR) 0 (0.7) 0 (0.10) 0 (0.12) 0 (0.1) 0.765
NIPPV d, bmedian (IQR) 3 (0.21) 2 (0.7) 2 (0.5) 1 (0.4) 0.045*
HFNV d, bmedian (IQR) 3 (0.27) 4 (0.20) 1 (0.8) 4 (0.13) 0.095
Mother
Gestational age range (median) 14–43 (29) 15–38 (28) 16–43 (30) 20–38 (33) 0.255
Maternal antibiotic exposure (Yes:,No) 11:9 9:11 6:14 4:16 0.103
Pregnancy comorbidities, n (%)a 7 (35) 6 (30) 3 (15) 2 (10) 0.167
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APGAR (Appearance, Pulse, Grimace, Activity, and Respiration); IQR (Interquartile Range); SIMV (Synchronized Intermittent Mandatory Ventilation); NIPPV (Non-Invasive Positive Pressure Ventilation); HFNV (High-Flow Nasal Ventilation).

APGAR score, a measure of physical condition at birth, scored from 0 to 10: 10 being the highest; a is expressed as a number of cases and percentage (%), and b as mean ± standard deviation or median (interquartile spacing).* P < 0.05.E = Early Preterm Infant (28–32 weeks gestation); M = Moderate Preterm Infant (32–34 weeks gestation).

The UPARSE algorithm was used for operational taxonomic unit (OTU) clustering and the Venn diagram and petal diagram were used to depict OTUs that were common and unique to preterm infants with FI and FT having gestational ages < 34 weeks. We observed 829 OTUs in the EFI group, of which 397 OTUs were unique; 666 OTUs in the EFT group, of which 297 OTUs were unique; 831 OTUs in the MFI group, of which 405 OTUs were unique; and 339 OTUs in the MFT group, of which 94 OTUs were unique. There were also 119 OTUs that were common to all four groups. These results showed that the number of OTUs in preterm infants with FI having a gestational age < 34 weeks was higher than in those with FT, and that this was not affected by gestational age (refer to Supplementary Material).

The alpha-diversity ACE (H = 4.254, P = 0.235), Chao1 (H = 4.145, P = 0.246), or Simpson x(H = 4.039, P = 0.257) indices did not significantly differ among the EFI, EFT, MFI, and MFT groups (refer to Supplementary Material). We used Principal Coordinates Analysis (PCoA) to compare the β-diversity of the four groups and discovered that the diversity of gut microbiota in the MFT group was significantly distinct from the MFI and EFT groups (P = 0.021 and P = 0.000) (Fig. 1).

Fig. 1.

Fig. 1

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Beta diversity calculation of gut microbiota among the four groups using PCoA unweighted UniFrac distance

At the genus level we observed that the relative abundances of Clostridium XI, Acinetobacter, and Citrobacter in the EFI group were 0.336%, 2.774%, and 1.255%, respectively; 0.265%, 0.021%, and 0.845%, respectively, in the EFT group; 1.688%, 0.025%, and 1.947%, respectively, in the MFI group; and 11.976%, 0.004%, and 0.077%, respectively, in the MFT group (Fig. 2).

Fig. 2.

Fig. 2

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Bar graph of the relative abundance of species at the genus level in each group

Using the linear discriminant analysis effect size (LEfSe) results, we found that the abundances of Clostridium XIVa (Linear discriminant analysis (LDA) = 3.713, P = 0.016) and Citrobacter (LDA = 4.165, P = 0.020) in the EFI group were significantly higher than that in the EFT group (Fig. 3a-b). Furthermore, the abundances of Tenericutes (LDA = 4.106, P = 0.039), Veillonella (LDA = 4.171, P = 0.034), Pseudomonas (LDA = 3.679, P = 0.044), and Acinetobacter (LDA = 3.992, P = 0.011) in the MFI group were significantly higher than in the MFT group. In contrast, the abundances of Peptostreptococcaceae (LDA = 4.697, P = 0.021) and Clostridium XI (LDA = 4.709, P = 0.014) were significantly lower than in the MFT group (Fig. 3c-d). Moreover, the abundance of Veillonella (LDA = 4.174, P = 0.033) in the MFI group was significantly higher than that in the EFI group, whereas the abundance of Citrobacter was significantly lower than in the EFI group (LDA = 4.177, P = 0.046) (Fig. 3e-f).

Fig. 3.

Fig. 3

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LDA bar and clade plots of LEfSe evolution. Linear discriminant analysis (LDA) Plot: Primarily displays species with LDA scores exceeding the preset threshold of 2.0; the color of the bars represents their respective groups, while the length of the bars indicates the LDA score, reflecting the impact degree of species significantly different between groups. Cladogram: Different colors represent different groups, and nodes of different colors indicate microbial groups that play significant roles within the corresponding group. A colored circle represents a biomarker, with the legend in the upper right corner showing the names of the biomarkers. Yellow nodes represent microbial taxa that do not play significant roles across the groups. From the innermost to the outermost circles, the levels of classification are phylum, class, order, family, and genus

Discussion

Tang et al., in their meta-analysis on the risk factors for FI in preterm infants showed that birth weight (OR = 0.99) and gestational age (OR = 0.53) were protective factors for FI, whereas birth asphyxia (OR = 2.1), intrauterine infection (OR = 2.09), ventilator use (OR = 4.23), perinatal infection (OR = 7.83), and gender (OR = 2.33) were risk factors for FI [7]. In this study, all participants were treated in the same NICU under identical hospitalization conditions, and none were administered probiotics or lactase. Comparative analysis of the general characteristics of the enrolled preterm infants showed that the four groups (all P > 0.05) did not significantly differ in terms of gender distribution, birth asphyxia, delivery mode, duration of antibiotic use, feeding method, ventilator use, maternal age, prenatal antibiotic exposure, or pregnancy complications. This provides a solid foundation for further analysis of differences in the gut microbiota based on gestational age grouping. Meanwhile, from the general clinical data, we found that the newborns were treated for a long time with antibiotics, and the vast majority of them were intubated and mechanically ventilated (much more than expected). As the Neonatal Critical Care Center of Quanzhou, we are primarily responsible for the transport and treatment of critically ill preterm infants from surrounding counties and cities. With the improvement of clinical diagnostic and treatment capabilities in local county-level hospitals, the majority of patients transferred to our hospital still require advanced respiratory support or suffer from severe infections. Consequently, the proportion of infants on mechanical ventilation is more than the general level, and the incidence of ventilator-associated pneumonia has increased, leading to a corresponding rise in the duration of prophylactic antibiotic use.

The number of OTUs in preterm infants with FI who had gestational age < 34 weeks was increased and unaffected by the gestational age. The reasons why FI causes gut microbiota to increase in preterm infants are as follows. First, in preterm infants, the development of gut motility is incomplete or disorderly, peristalsis is slow, and gut contents and their metabolites accumulate over a long period without moving downward. This kinetic defect causes the localized accumulation of metabolites (such as short-chain fatty acids and ammonia) and creates a microenvironment conducive to pathogenic bacterial proliferation. Second, gastric acid and gut hormonal secretions are still at their nadir, digestive enzymes are not yet activated, and bile acid-binding capacity is low in the early stages after birth in preterm infants. The chemical barrier function is collectively compromised by the aforementioned factors, triggering a surge in pathogenic bacterial proliferation. Huang [8] evaluated the gut microbiota of preterm infants with FI using 16 S rRNA high-throughput sequencing. The results showed a trend of higher OTU abundance in FI cases compared with FT infants across different feeding regimens, including maternal breastfeeding and formula feeding.

The alpha diversity of gut microbiota in preterm infants was not affected by gestational age or FI. Chernikova et al. [9] found that the α-diversity of gut microbiota did not differ between very and moderate-to-late preterm infants after adjusting for age and exposure (P = 0.697). The findings revealed that there was still no disparity in α- diversity of gut microbiota between these same two groups, even at 6 weeks after birth (P = 0.138). In China, findings from a study by Huang [8] also did not show any differences in the gut microbiota diversity between preterm infants with FI and those with FT even when the feeding methodology was distinctly different. Gut microbiota beta-diversity in preterm infants with a gestational age ≥ 32 weeks was statistically different between those with FI and those with FT (P = 0.024); meanwhile, there was no difference in preterm infants with a gestational age < 32 weeks (P = 0.091). These results were consistent with the results of Korpela et al. [10], possibly because gestational age is the main driver of intestinal bacterial colonization, and diversity is lower when gestational age is lower. In contrast, preterm infants with higher gestational age tend to be affected by FI, leading to differences in beta diversity. In preterm infants with FT, the beta diversity significantly differed between those with gestational age ≥ 32 weeks and those with gestational age < 32 weeks (P = 0.000), while beta-diversity between FI preterm infants with a gestational age ≥ 32 weeks and gestational age < 32 weeks did not significantly differ (P = 0.283). This was consistent with a previous study [11] that showed a large inter-individual difference in microbiota diversity in preterm infants before FI occurred but similar diversity changes with FI. Hence, individuals with the same disease are designated as demonstrating identical variation trends in the microbiota diversity of the gut [12, 13].

At the genus level, Citrobacter and Acinetobacter were enriched in our FI group. Citrobacter is a Gram-negative rod in the gut and is often used in laboratories for constructing a colitis model [14, 15], as its pathogenesis is identical to enteropathic and enterohemorrhagic Escherichia coli [15–17]. Citrobacter can precipitate inflammation of the gut mucosa, ulceration, bleeding, and other gut-function disorders. Mshvildadze et al. [18] reported a great abundance of Citrobacter in patients with NEC. Acinetobacter is an obligate aerobic Gram-negative rod that is ubiquitous in the external environment. Li [19] found that preterm infants with a high Acinetobacter count were more prone to NEC and suggested that Acinetobacter could be used as a marker for predicting NEC, as FI is usually an early symptom of NEC. In the present study, Citrobacter and Acinetobacter were increased in preterm infants with FI; however, this was not affected by gestational age. Therefore, an increase in the abundance of Citrobacter and Acinetobacter in gut microbiota might be considered to constitute a predictive marker of FI.

Our results revealed that in preterm infants at gestational age < 32 weeks with FI, the abundance of Citrobacter in the gastrointestinal tracts was significantly elevated compared with preterm infants with FT (LDA = 4.165, P = 0.020). The abundance of Citrobacter in preterm infants with a gestational age < 32 weeks and FI was also higher than in those with a gestational age ≥ 32 weeks and FI (LDA = 4.177, P = 0.046). We therefore suggest that Citrobacter may be a specific species in preterm infants with FI at a gestational age < 32 weeks. The abundance of Acinetobacter in the tracts of our preterm infants with a gestational age ≥ 32 weeks and FI was significantly higher than in those with FT (LDA = 3.992, P = 0.011). Acinetobacter is a gut microorganism that can be used to predict NEC [19], and exacerbation of FI can lead to NEC [20]. Yu et al. [21] conducted a multivariate logistic regression analysis using the clinical data from 194 preterm infants with NEC and at extremely/very low birth weight. The data showed that FI was an independent risk factor for NEC (OR = 4.121, P = 0.006). We found a significant abundance of Acinetobacter in preterm infants at a gestational age ≥ 32 weeks who were feeding intolerant, suggesting that it can be used as a predictor of FI. The relative abundance of Clostridium XI in the gut microbiota of preterm infants with a gestational age ≥ 32 weeks was greater than in infants with a gestational age < 32 weeks. In addition, the abundance of Clostridium XI in the MFT group reached 11.976% and LefSe analysis showed that it was significantly higher than that in the MFI group (with a reduction of 85.6%, LDA = 4.709). Clostridium XI ferments carbohydrates in the gut to produce short-chain fatty acids (SCFAs, such as butyrate), which regulate intestinal pH, competitively inhibit pathogenic colonization (Clostridium difficile, Salmonella spp.), suppress pro-inflammatory cytokines (e.g., IL-6, TNF-α) by inhibiting the NF-κB pathway, and promote regulatory T cell (Treg) differentiation to prevent excessive immune responses [22–25]. This suggests that Clostridium XI may exert antagonistic effects against FI in preterm infants ≥ 32 weeks of gestation.

Yu et al. [21] conducted a multivariate logistic retrospective analysis using clinical data from 194 NEC cases in very/extremely low birth weight preterm infants. The results showed that FI was an independent risk factor for NEC (OR = 4.121, P = 0.006). Reportedly, FI in preterm infants is primarily functional [2]. Long-term lack of enteral nutrition can weaken gastrointestinal function and structural integrity, while milk retained in the gastrointestinal tract can be decomposed by gut microbiota, producing metabolites that increase intestinal mucosal permeability, leading to intestinal injury and predisposing preterm infants to NEC [26]. The mechanisms involved are not entirely clear; nevertheless, our finding significantly contributes to determining or predicting whether a neonate develops NEC or has difficulties with nutritional management due to intolerance to enteral feeding because existing research has shown that alterations in gut microbiota are associated with early NEC [27].

FI is not a specific disease but rather a symptom that can be caused by various factors. For example, congenital genetic defects leading to intestinal malformations [28] and hereditary metabolic disorders [29] can affect the digestive system of premature infants, resulting in FI. Additionally, severe infections such as bacterial infections (sepsis and NEC [1]), viral infections (rotavirus [30]), and fungal infections (Candida [31]) can impact the gastrointestinal function of premature infants, causing acute gastroenteritis and symptoms related to FI, such as vomiting. However, the above factors were not specifically discussed in this study, which is one of the limitations of our study.

Additionally, we used a limited sample size and a single hospital, which may lead to the microbiome profile being influenced by regional environment and medical practices (such as antibiotic usage rates and differences in formula milk brands), making it difficult to reflect the diversity of gut microbiota in preterm infants nationwide or globally. Additionally, the focus of this study was on preterm infants with a gestational age of < 34 weeks, which might introduce a selection bias in case inclusion. Moreover, we did not longitudinally analyze the association between microbial succession and changes in FI phenotypes. In future research, multicenter clinical studies should be organized to explore the relationship between different gestational and postnatal ages, FI in preterm infants, and different bacterial species in the gut microbiota and combine characteristic intestinal metabolites to further elucidate the potential mechanisms of FI.

Conclusions

Our findings reveal that preterm infants with FI born at < 34 weeks exhibit increased gut microbiota diversity. Dynamic monitoring of OTUs serves as a potential early warning indicator for FI. Moreover, Citrobacter and Acinetobacter are implicated in FI among preterm infants born at < 32 weeks and ≥ 32 weeks, respectively, whereas Clostridium XI has potential protective effects in infants born at ≥ 32 weeks. These findings provide a theoretical foundation for personalized microbiota-based interventions in preterm infants. Further validation through functional experiments and clinical cohorts is required to assess the efficacy and safety of targeted microbial modulation.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1 (166.5KB, docx)

Acknowledgements

The authors highly appreciate BGI Genomics for the realization of the figure layout.

Abbreviations

EFI

Early preterm infants with feeding intolerance

EFT

Early preterm infants with feeding tolerance

FI

Feeding intolerance

FT

Feeding tolerance

MFI

Moderate preterm infants with feeding intolerance

MFT

Moderate preterm infants with feeding tolerance

NEC

Necrotizing enterocolitis

NICU

Neonatal intensive care unit

Author contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Chunyan Fu Jinglin Xu and Dongmei Chen. The first draft of the manuscript was written by Chunyan Fu and all authors commented on previous versions of the manuscript. All authors read and approved of the final manuscript. He Wang translated and polished and ty-edited this article.

Funding

This work was supported by research grants from the Quanzhou Science and Technology Bureau Quanzhou City 2021 Guided Science and Technology Program Project in the Medical and Health Field (2021N096S) and the Fujian provincial health technology project (Grant No. 2023GGA085), Joint Innovation Project Funds of Huaqiao University (Grant No. 2023YX002).

Data availability

The datasets used and analyzed in the current study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Quanzhou Children’s Hospital (2021 Ethics Review No. 20), and all procedures involving human participants were carried out following the principles of the Helsinki Declaration. Informed consent was obtained from the patient’s parents before conducting fecal collection, including the patient’s clinical details in the manuscript for publication.

Consent for publication

The written informed consent was waived because of no interventions and the anonymous nature of the data.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Chunyan Fu and Jinglin Xu contributed equally to this work and should be considered co-first authors.

Contributor Information

Dongmei Chen, Email: chendm9090@163.com.

Zhiyong Liu, Email: 274979419@qq.com.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1 (166.5KB, docx)

Data Availability Statement

The datasets used and analyzed in the current study are available from the corresponding author upon reasonable request.

Articles from Italian Journal of Pediatrics are provided here courtesy of BMC

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