Abstract
Objective
To identify clinical factors influencing the time to achieve full enteral feeding (FEF) in preterm infants with respiratory distress syndrome (NRDS) and to provide evidence for optimizing nutritional management.
Methods
We conducted a retrospective cohort study of 110 preterm infants with NRDS admitted to the neonatal intensive care unit of the First Affiliated Hospital of Fujian Medical University between January 2019 and January 2022. Clinical and treatment data, including feeding practices, respiratory support, gastrointestinal symptoms, and laboratory results, were collected. FEF was defined as enteral intake ≥ 150 mL/kg/day. Kaplan-Meier survival analysis and multivariate Cox regression were used to evaluate factors associated with time to FEF.
Results
Among the 110 infants, 67 (60.9%) achieved FEF before discharge, with a median time of 19 days, and the mean time was 21.4 ± 12.0 days. Clinical cure-defined as complete resolution of NRDS symptoms and successful withdrawal of respiratory support-was observed in 41 infants (37.3%), while clinical improvement-defined as partial symptom relief with reduced respiratory support-was seen in 69 infants (62.7%). Univariate analysis identified significant associations between time to FEF and factors such as breastfeeding, invasive ventilation, duration of non-invasive ventilation, initiation time and volume of feeding, gastric retention, constipation, pulmonary surfactant treatment, prolonged caffeine use, and antibiotic therapy (all P < 0.05). Multivariate Cox regression revealed that breastfeeding was independently associated with a shorter time to FEF (HR = 2.80, 95% CI: 1.54–5.11, P = 0.001), whereas non-invasive ventilation > 14 days, constipation, and caffeine therapy > 14 days were associated with feeding delays.
Conclusion
Breastfeeding, shorter duration of non-invasive ventilation, timely management of constipation, and judicious use and timely adjustment of supportive therapies, alongside optimized feeding management, may facilitate earlier achievement of FEF without compromising respiratory stability.
Keywords: Neonatal respiratory distress syndrome, Full enteral feeding, Breastfeeding, Non-invasive ventilation, Caffeine.
Introduction
Neonatal respiratory distress syndrome (NRDS) is a severe respiratory condition primarily characterized by progressive respiratory difficulty and hypoxemia due to pulmonary surfactant deficiency [1]. While more common in preterm infants, the incidence in term neonates has also been rising [2]. This condition is one of the most common critical emergencies in the neonatal intensive care unit (NICU), posing a serious threat to the lives of newborns, particularly preterm infants. Even if they survive, some affected infants may experience long-term complications, imposing significant economic burdens and lifestyle challenges on their families [2]. Thus, timely and accurate diagnosis of NRDS holds great significance for improving neonatal prognosis [3].
In recent decades, advances in neonatal resuscitation and NICU care have significantly improved the survival of infants with NRDS [4]. Comprehensive management strategies have also been gradually optimized, including maintenance of normothermia, proper fluid balance, adequate nutritional support, management of the ductus arteriosus, and circulatory stabilization, all of which play crucial roles in determining overall outcomes [4]. Among these strategies, early and adequate nutritional and fluid support are particularly critical because enteral nutrition promotes gastrointestinal maturation, growth, and functional development. Sufficient nutrition not only facilitates recovery from illness but also has long-term effects on cardiovascular health, neurological development, and overall well-being. Achieving full enteral feeding (FEF), commonly defined as an enteral intake of ≥ 150 mL/kg/day, is often considered a significant milestone for assessing infants’ readiness for discharge and long-term growth potential [5].
Systematic reviews have found that delays in achieving full enteral feeding are associated with longer hospitalization, higher risk of infections, and adverse neurodevelopmental outcomes [6, 7]. Factors such as gestational age, birth weight, breastfeeding, non-invasive ventilation, feeding initiation, and gastrointestinal complications significantly influence the time to FEF. To improve outcomes, recent Cochrane reviews and ESPGHAN guidelines recommend evidence-based strategies to optimize feeding advancement, including the early initiation of minimal enteral nutrition to promote gut adaptation, enhance feeding tolerance, and facilitate earlier achievement of full enteral feeding [8, 9].
However, studies specifically focusing on NRDS infants remain limited, and the determinants of time-to-FEF in this population are not well defined. Therefore, this study aims to identify key clinical factors influencing FEF achievement and to explore modifiable strategies that may optimize nutritional management, promote growth, and improve clinical outcomes.
Materials and methods
Study population
A total of 110 preterm infants admitted to the NICU of the First Affiliated Hospital of Fujian Medical University from January 2019 to January 2022 were enrolled in this study. The study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (MTCA, ECFAH of FMU (2015) 084 − 2). Written informed consent was obtained from the parents or caregivers. This study was conducted in accordance with the ethical principles of the 1964 Declaration of Helsinki and its later amendments. Clinical trial number: not applicable.
All enrolled infants were preterm (< 37 weeks’ gestation). For analysis, gestational age was stratified into two categories: GA < 32 weeks and GA 32-<37 weeks.
Diagnostic criteria for NRDS as referenced from the 5th edition of Practice of Neonatology [10] are as follows: (1) Presence of high-risk factors for morbidity: maternal diabetes during pregnancy, intrauterine infection, premature birth, premature rupture of membranes exceeding 18 h, intrauterine distress, birth asphyxia, etc. (2) Presence of clinical symptoms and signs of NRDS. Symptoms include progressive exacerbation of respiratory distress within 6 h after birth (>60 breaths/minute). Signs include: ① Cyanosis, nasal flaring, inspiratory retractions, and prominent expiratory grunting. ② Severe cases may exhibit shallow rapid breathing, irregular breathing rhythm, respiratory pauses, and limb flaccidity. ③ Reduced breath sounds in both lungs upon auscultation. (3) Presence of typical chest X-ray characteristics, although not mandatory for early diagnosis.
The exclusion criteria for all participants were as follows: (1) Neonates with congenital abnormalities of the digestive system (e.g., congenital megacolon, intestinal malrotation); (2) Neonates with cyanotic congenital heart disease; (3) Neonates with chromosomal abnormalities or inherited metabolic disorders; (4) Neonates who died or were transferred to another facility within 24 h of admission; (5) Neonates requiring surgical intervention.
Clinical data
(1) General information of the patient, including gestational age, mode of delivery, birth weight, gender, Apgar scores (at 1 min and 5 min), etc.; (2) Maternal conditions, including complications during pregnancy, time of premature rupture of membranes, and breastfeeding (defined as feeding with expressed breast milk via bottle), were recorded; (3) Treatment measures during the patient’s hospitalization, including the use of non-invasive and/or invasive ventilation, treatment with Pulmonary Surfactant (PS), sedation, caffeine therapy, nasogastric feeding, antibiotic therapy, time of initiation of feeding, feeding volume; (4) Clinical symptoms of the patient, including abdominal distension, gastric retention, constipation, and the status of enteral nutrition at discharge; detailed records of feeding volume and stool output by the responsible nurse; (5) Laboratory data, including white blood cell (WBC) count, C-reactive protein (CRP), and procalcitonin (PCT), were collected at baseline within 24 h after NICU admission as part of routine infection screening. Follow-up tests were performed only when clinically indicated, such as suspected sepsis, feeding intolerance, or unexplained clinical deterioration.
The primary outcome was the time required to achieve enteral nutrition of 150 mL/kg/day, defined as full enteral feeding (FEF).
Definitions and grouping criteria
(1) Birth asphyxia: Apgar score ≤ 7 at 1 min or 5 min; low birth weight: birth weight less than 2.5 kg; (2) Premature rupture of membranes (PROM): classified into three categories-rupture ≥ 18 h, rupture < 18 h, and no rupture; (3) Early minimal feeding: feeding initiated within 12 h after birth, recommended feeding volume ≤ 10-20mL/kg/day; (4) Abdominal distension: refers to localized or generalized abdominal distension, excluding mild physiological distension after feeding; Gastric retention: gastric residual volume exceeding 30% of the feeding volume or presence of coffee-ground-like material in the stomach; Constipation: defined as no spontaneous bowel movement within 48 h; (5) Elevated non-specific indicators of blood infection: WBC count < 5.0 × 109/L or ≥ 30 × 109/L at 24 h postnatal, CRP > 10 mg/L, PCT > 10 ng/mL.
To analyze the effects of non-invasive ventilation, nasogastric feeding duration, and caffeine therapy on achieving full enteral feeding (FEF), patients were classified into a short-term group (≤ 14 days) and a long-term group (>14 days), based on both published evidence [11–13] and clinical practice considerations.
For analysis, gestational age (GA) was categorized as < 32 weeks versus 32-<37 weeks, reflecting a clinically meaningful boundary between very preterm and moderate/late preterm infants used in neonatal practice.
Feeding advancement strategy for achieving full enteral feeding (150 mL/kg/day)
Feeding was generally advanced according to institutional protocol, beginning with minimal enteral nutrition (10–20 mL/kg/day) and increasing by 10–20 mL/kg/day depending on feeding tolerance. In clinically stable infants, attending neonatologists were permitted to advance feeds slightly more rapidly than the standard protocol, based on individualized assessments of tolerance, gastrointestinal function, and respiratory stability.
Feeding intolerance (e.g., abdominal distension, gastric residuals) was managed by temporarily discontinuing feeds, adjusting feeding volume, or switching to hydrolyzed or elemental formulas as clinically indicated.
Definitions of clinical cure and clinical improvement
Clinical cure was defined as the complete resolution of major NRDS symptoms (e.g., tachypnea, retractions, grunting, cyanosis) and successful withdrawal from all respiratory support, with no further need for supplemental oxygen.
Clinical improvement was defined as partial alleviation of NRDS symptoms, accompanied by a reduction in the level of respiratory support, but without complete resolution of symptoms or full weaning from respiratory assistance.
Statistical analysis
Statistical analyses were conducted using SPSS software, version 23.0 for Mac OS X (SPSS Inc., Chicago, IL, USA). Continuous variables with skewed distributions were summarized as medians with interquartile ranges (IQRs), whereas approximately normally distributed variables were expressed as means ± standard deviations (SD). Because the primary outcome was the time to achieve full enteral feeding (FEF), Kaplan-Meier survival curves were generated, and the log-rank test was applied to compare time-to-event distributions between groups in the univariate analyses. To evaluate the associations between neonatal and maternal factors and the achievement of FEF, univariate analyses were performed using the χ² test for categorical variables. Variables with P < 0.05 in the univariate analyses were included in a multivariate Cox proportional hazards regression model to identify independent predictors of time to FEF. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. GA was included as an independent covariate in both univariate and multivariate models to adjust for its potential confounding effect on feeding outcomes. All statistical tests were two-tailed, and a P value < 0.05 was considered statistically significant.
Results
Clinical characteristics of the enrolled infants
A total of 136 neonates with NRDS were initially screened for eligibility. After applying the exclusion criteria (Fig. 1), 110 infants were included in the final analysis between January 2019 and January 2022. The gestational age ranged from 28 to 36 weeks, with a median of 32.6 weeks (IQR: 30.0–34.0). Of these infants, 69 (62.7%) were male and 41 (37.3%) were female. Among the 110 NRDS cases, 67 (60.9%) achieved full enteral feeding (FEF) before discharge, whereas 43 (39.1%) did not. Of these 43 infants, 8 (18.6%) were transferred to local hospitals at parental request for continued nutritional management after their respiratory status improved, and 35 (81.4%) were discharged early due to family decisions despite not reaching FEF. Importantly, none of these infants developed necrotising enterocolitis (NEC) or severe feeding intolerance during their NICU stay. Clinical cure was observed in 41 cases (37.3%) and clinical improvement in 69 cases (62.7%). The median time to achieve FEF was 19 days, and the mean time was 21.4 ± 12.0 days.
Fig. 1.
Flowchart of patient inclusion and exclusion
Univariate analyses of factors affecting time to achieve FEF
Clinical factors
To assess the associations between neonatal and maternal factors and the achievement of full enteral feeding (FEF), univariate analyses were performed using the chi-square test. Birth weight, gestational age at birth, breastfeeding, invasive ventilation, duration of non-invasive ventilation, timing of feeding initiation, initial feeding volume, gastric retention, and constipation were significantly associated with achieving FEF. In contrast, infant sex, mode of delivery, maternal hypertension during pregnancy, duration of premature rupture of membranes, birth asphyxia, and abdominal distension showed no significant association (Table 1).
Table 1.
Clinical characteristics associated with achieving full enteral feeding (FEF) in preterm infants with NRDS
| Variable | Category | Achieved FEF (n = 67) | Did not achieve FEF (n = 43) | χ² | P-value |
|---|---|---|---|---|---|
| Gender | Male | 38 (56.7%) | 31 (72.1%) | 2.789 | 0.095 |
| Female | 29 (43.3%) | 12 (27.9%) | |||
| Gestational age | 32-<37 weeks | 38 (56.7%) | 12 (27.9%) | 26.015 | < 0.001 |
| < 32 weeks | 29 (43.3%) | 31 (72.1%) | |||
| Birth weight | ≥ 2.5 kg | 21 (31.3%) | 24 (55.8%) | 33.24 | < 0.001 |
| < 2.5 kg | 46 (68.7%) | 19 (44.2%) | |||
| Delivery mode | Cesarean | 10 (14.9%) | 9 (20.9%) | 2.138 | 0.144 |
| Vaginal | 57 (85.1%) | 34 (79.1%) | |||
| Gestational hypertension | Yes | 15 (22.4%) | 7 (16.3%) | 1.914 | 0.167 |
| No | 52 (77.6%) | 36 (83.7%) | |||
| Premature rupture of PROM | ≥ 18 h | 9 (13.4%) | 9 (20.9%) | 2.159 | 0.34 |
| 0–18 h | 10 (14.9%) | 8 (18.6%) | |||
| None | 48 (71.7%) | 26 (60.5%) | |||
| Breastfeeding | Yes | 42 (62.7%) | 16 (37.2%) | 5.417 | 0.02 |
| No | 25 (37.3%) | 27 (62.8%) | |||
| Birth asphyxia | Yes | 28 (41.8%) | 14 (32.6%) | 3.062 | 0.08 |
| No | 39 (58.2%) | 29 (67.4%) | |||
| Invasive ventilation | Yes | 20 (29.9%) | 9 (20.9%) | 11.971 | 0.001 |
| No | 47 (70.1%) | 34 (79.1%) | |||
| Duration of NIV | > 14 days | 28 (41.8%) | 28 (65.1%) | 21.901 | < 0.001 |
| ≤ 14 days | 39 (58.2%) | 15 (34.9%) | |||
| Time to initiate feeding | > 12 h | 15 (22.4%) | 11 (25.6%) | 8.496 | 0.004 |
| ≤ 12 h | 52 (77.6%) | 32 (74.4%) | |||
| Initial feeding volume | ≥ 20 mL/kg/day | 28 (41.8%) | 20 (46.5%) | 15.128 | < 0.001 |
| < 20 mL/kg/day | 39 (58.2%) | 23 (53.5%) | |||
| Gastric retention | Yes | 26 (38.8%) | 27 (62.8%) | 4.218 | 0.04 |
| No | 41 (61.2%) | 16 (37.2%) | |||
| Constipation | Yes | 42 (62.7%) | 35 (81.4%) | 39.825 | < 0.001 |
| No | 25 (37.3%) | 8 (18.6%) |
Values are expressed as n (%). Comparisons between groups were performed using the χ² test. PROM indicates premature rupture of membranes (“≥18 h” = prolonged rupture; “0–18 h” = rupture < 18 h; “None” = no rupture)
NIV non-invasive ventilation, FEF full enteral feeding
Laboratory tests
The log-rank test indicated that elevated peripheral blood WBC, CRP, and PCT levels within 24 h after birth were not significantly associated with the time to achieve FEF (Table 2).
Table 2.
Laboratory test results and their association with time to achieve full enteral feeding (FEF) in neonates with NRDS
| Variable | Category | n (%) | Achieved FEF (n) | Did not achieve FEF (n) | Time to FEF (days, mean ± SD) | χ² | P-value |
|---|---|---|---|---|---|---|---|
| WBC (×10⁹/L) | < 5 or > 30 | 17 (15.5%) | 8 | 9 | 26.0 ± 5.6 | 1.046 | 0.307 |
| 5–30 | 93 (84.5%) | 59 | 34 | 20.4 ± 1.5 | |||
| CRP (mg/L) | > 10 | 37 (33.6%) | 25 | 12 | 23.6 ± 2.4 | 1.275 | 0.286 |
| ≤ 10 | 73 (66.4%) | 42 | 31 | 19.8 ± 1.8 | |||
| PCT (ng/mL) | > 10 | 46 (41.8%) | 29 | 17 | 21.1 ± 2.5 | 0.009 | 0.924 |
| ≤ 10 | 64 (58.2%) | 38 | 26 | 21.6 ± 1.8 |
χ² and P values represent the test statistics and results of the log-rank test, respectively
WBC white blood cell, CRP C-reactive protein, PCT procalcitonin
Treatment interventions
Treatment with pulmonary surfactant, caffeine therapy, antibiotic therapy, and prolonged nasogastric feeding was significantly associated with delayed achievement of full enteral feeding (FEF), whereas sedative therapy showed no significant association (Table 3).
Table 3.
Treatment-related factors associated with time to achieve full enteral feeding (FEF) in neonates with NRDS
| Variable | Category | n (%) | Achieved FEF (n) | Did not achieve FEF (n) | Time to FEF (days, mean ± SD) | χ² | P-value |
|---|---|---|---|---|---|---|---|
| PS treatment | Yes | 46 (41.8%) | 31 | 15 | 24.9 ± 2.4 | 4.714 | 0.030 |
| No | 64 (58.2%) | 36 | 28 | 18.3 ± 1.7 | |||
| Sedation | Yes | 15 (13.6%) | 10 | 5 | 26.5 ± 4.7 | 1.926 | 0.165 |
| No | 95 (86.4%) | 57 | 38 | 20.5 ± 1.5 | |||
| Caffeine treatment | > 14 d | 74 (67.3%) | 42 | 32 | 30.9 ± 2.4 | 26.210 | < 0.001 |
| ≤ 14 d | 36 (32.7%) | 25 | 11 | 15.5 ± 1.2 | |||
| Antibiotic treatment | Yes | 21 (19.1%) | 16 | 5 | 24.3 ± 1.7 | 24.486 | < 0.001 |
| No | 89 (80.9%) | 51 | 38 | 11.8 ± 1.0 | |||
| Nasogastric feeding | > 14 d | 49 (44.5%) | 36 | 13 | 27.3 ± 1.9 | 20.252 | < 0.001 |
| ≤ 14 d | 61 (55.5%) | 31 | 30 | 14.4 ± 1.5 |
χ² and P values represent the test statistics and results of the log-rank test, respectively
PS pulmonary surfactant
Multivariate Cox regression analysis of factors affecting time to achieve FEF
Multivariate Cox regression analysis identified breastfeeding, duration of non-invasive ventilation, constipation, and caffeine therapy as independent predictors of time to achieve FEF (Table 4). Breastfeeding was associated with a shorter time to achieve FEF (HR > 1), whereas prolonged non-invasive ventilation (> 14 days), extended caffeine therapy (> 14 days), and constipation were associated with delayed achievement (HR < 1).
Table 4.
Independent predictors of time to achieve full enteral feeding (FEF) in neonates with NRDS by multivariate Cox regression analysis
| Independent variables | β | SE | Wald | HR (95% CI) | P-value |
|---|---|---|---|---|---|
| Breastfeeding | 1.031 | 0.307 | 11.295 | 2.803 (1.537–5.113) | 0.001 |
| Non-invasive ventilation > 14 d | −0.812 | 0.338 | 5.751 | 0.444 (0.229–0.862) | 0.016 |
| Caffeine therapy > 14 d | −1.686 | 0.368 | 21.029 | 0.185 (0.090–0.381) | < 0.001 |
| Constipation | −1.475 | 0.368 | 16.096 | 0.229 (0.111–0.470) | < 0.001 |
Values are derived from multivariate Cox proportional hazards regression analysis
HR hazard ratio, CI confidence interval, SE standard error
A HR > 1 indicates earlier achievement of FEF, whereas HR < 1 indicates delayed achievement
Kaplan-Meier survival curves were generated to illustrate the impact of these predictors on time to FEF (Fig. 2). After adjusting for other covariates, breastfeeding significantly accelerated the attainment of FEF, while prolonged non-invasive ventilation, extended caffeine therapy, and constipation significantly delayed FEF. All associations were statistically significant.
Fig. 2.
Kaplan-Meier survival curves for time to achieve full enteral feeding (FEF) in neonates with NRDS, stratified by (A) breastfeeding, (B) duration of non-invasive ventilation, (C) duration of caffeine therapy, and (D) presence of constipation. Differences between groups were compared using the log-rank test
Discussion
Early nutritional support plays a pivotal role in the management of neonatal respiratory distress syndrome, facilitating catch-up growth and improving long-term outcomes [4]. Achieving full enteral feeding is a key milestone in the recovery, and understanding the factors that influence the time required to FEF can help guide targeted interventions and improve prognosis.
Evidence from systematic reviews supports our findings. A Cochrane review suggested that early minimal enteral nutrition may promote gastrointestinal adaptation and improve feeding tolerance, and current evidence does not indicate an increased risk of necrotising enterocolitis [8]. Consistently, the ESPGHAN Position Paper (2022) recommends early initiation of small-volume feeds, standardized feeding protocols, and breast milk prioritization to optimize feeding progression in preterm infants [9]. These international guidelines provide strong evidence supporting early, structured nutritional strategies in NRDS management.
Our findings confirm that breastfeeding significantly shortens the time to achieve FEF in infants with NRDS. This is consistent with the results of Corvaglia et al., who reported that very low birth weight infants exclusively fed breast milk achieved FEF 1.4 days earlier than those fed formula [14]. The unique bioactive and immunomodulatory components of breast milk promote maturation and function of the neonatal gastrointestinal tract, thereby enhancing feeding tolerance and reducing complications [15]. Therefore, promoting breastfeeding in NRDS management is therefore crucial, as it may shorten hospitalization, minimize gastrointestinal disturbances, and improve nutritional outcomes.
Constipation also emerged as an important factor delaying FEF. Consistent with the observations of Marcos et al., who found that early establishment of normal bowel habits expedited FEF in preterm infants, our study identified constipation as a significant risk factor for feeding delay [16]. Impaired bowel function can cause fecal retention, rectal distension, and delayed gastric emptying, all of which compromise feeding tolerance. Clinically, timely interventions such as glycerin or saline enemas may facilitate defecation and support earlier attainment of FEF.
Non-invasive ventilation (NIV) is widely used in NICUs as a respiratory support strategy for infants with NRDS [17, 18]. However, prolonged use may adversely affect feeding progression. In our study, infants who required NIV for more than 14 days experienced significant delays in achieving FEF. This finding is supported by recent evidence indicating that nasal continuous positive airway pressure (nCPAP) may interfere with the coordination of swallowing and breathing, potentially increasing the risk of silent aspiration in preterm infants [19]. In addition, NIV may reduce mesenteric perfusion, thereby compromising gastrointestinal function. These results emphasize the importance of timely weaning from NIV to minimize its negative impact on feeding tolerance.
Caffeine therapy, although effective in reducing apnea of prematurity and enhancing respiratory drive, was also associated with delayed attainment of FEF when administered for prolonged durations (>14 days) [20, 21]. In contrast, recent studies have shown that early initiation of caffeine therapy in preterm infants accelerates progression to FEF (median 5 vs. 11 days, P < 0.001) [22], suggesting that delayed initiation or extended treatment may contribute to feeding delays. Possible mechanisms include impaired gastrointestinal motility and reduced mesenteric perfusion, as indicated by studies of caffeine’s effects on mesenteric blood flow [23]. While caffeine remains a cornerstone in neonatal care, clinicians should carefully balance its benefits against potential feeding delays and optimize both the timing and duration of therapy.
Despite the strengths of our analysis, several limitations should be acknowledged. First, this was a single-center retrospective study conducted in a tertiary NICU, which may introduce selection bias and limit generalizability. Multicenter prospective studies are needed to confirm these findings. Second, although GA is a key determinant of feeding tolerance and clinical outcomes, our analysis stratified infants into only two categories (< 32 weeks vs. 32-<37 weeks) rather than the standard four-level classification (< 28, 28–32, 32-<37, and ≥ 37 weeks). This simplified stratification was selected to preserve statistical power and avoid sparse strata given our limited sample size; consequently, residual confounding by finer GA differences could not be fully adjusted for, and future larger multicenter studies are needed to enable more comprehensive risk adjustment across GA subgroups. Third, follow-up data after transfer to local hospitals were unavailable; therefore, we could not assess post-transfer feeding outcomes or late complications. This limitation may have led to underestimation of the time to full enteral feeding among transferred infants. Finally, when interpreting the associations observed, it should be noted that some management variables may reflect illness severity rather than represent direct causal effects on feeding outcomes. Prolonged respiratory or pharmacologic interventions may therefore act as indirect markers of disease severity rather than independent determinants of feeding delay.
In conclusion, breastfeeding was associated with earlier attainment of FEF, whereas prolonged non-invasive ventilation, extended caffeine therapy, and constipation were linked to delays; optimizing feeding strategies, supporting breastfeeding, and adjusting therapies according to illness severity may help preterm infants achieve FEF sooner without compromising respiratory stability.
Acknowledgements
This work was supported by the Joint Funds for the Innovation of Science and Technology of Fujian Province (Grant No. 2023Y9077). The authors thank the parents and caregivers for their participation and cooperation.
Authors’ contributions
Huang HH and Wu B: Data analysis, Manuscript writing; Huang HH and Zhu LH: Data collection; Wu B and Huang HH: Project development, Manuscript editing. All authors critically reviewed the manuscript. The authors read and approved the final manuscript.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (MTCA, ECFAH of FMU (2015) 084 − 2). Written informed consent was obtained from the parents or caregivers. This study was conducted in accordance with the ethical principles of the 1964 Declaration of Helsinki and its later amendments. Clinical trial number: not applicable.
Consent for publication
Consent for publication was obtained from the infants’ parents or legal guardians.
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.
Huanhuan Huang and Longhui Zhu contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.