Abstract
Background:
This study examines the relationship between feeding methods during the first 2 weeks post-birth—mother’s own milk (MOM), donor human milk (DHM), and formula—and the incidence of bronchopulmonary dysplasia (BPD) in preterm infants.
Materials and Methods:
A retrospective cohort study was conducted on preterm infants (<32 weeks gestation or <1,500 g birth weight) admitted to Fujian Maternal and Child Health Hospital from March 2023 to February 2024. Infants were grouped by primary feeding method within the first 2 weeks after birth, defined as MOM, DHM, or formula contributing to ≥50% of total feeding. The primary outcome was BPD incidence; the secondary outcome included necrotizing enterocolitis (NEC) stage II or higher, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and sepsis.
Results:
BPD incidence was lower in the MOM and DHM groups compared with formula (22%, 16% vs. 35%; p = 0.03). Adjusted odds ratios for BPD were 3.35 (95% CI 1.43, 7.85) in the formula group versus MOM and 6.48 (95% CI 1.47, 28.57) versus DHM, with no significant difference between MOM and DHM. NEC incidence was also lower in MOM and DHM groups (7.15%, 9.38% vs. 20.21%; p = 0.016). No significant differences were observed in ROP, PVL, or sepsis rates.
Conclusions:
MOM and DHM reduce the risk of BPD and NEC in preterm infants, with DHM being as safe as MOM.
Introduction
Bronchopulmonary dysplasia (BPD) represents a frequent and serious complication among preterm infants. Studies have shown that the prevalence of BPD in extremely preterm or very low birth weight (VLBW) infants is approximately 22% in developed countries and 29.2% in China.1,2 BPD prolongs hospital stays, raises costs, and increases the risk of long-term complications, including readmissions and neurocognitive impairments. 3 Thus, it is vital to prevent and reduce the incidence of BPD to enhance the survival and prognosis of preterm infants, thereby lessening the burden on families and society.
Intrauterine and postnatal inflammation, high oxygen injury, mechanical ventilation, and inadequate nutrition are risk factors for BPD in preterm infants.4,5 Inadequate nutrition during the first weeks of life can lead to permanent lung development damage in extremely preterm infants, where alveolar development primarily occurs post-birth.6,7 Studies suggest that breastfeeding improves nutritional status, provides antioxidants and immune-active factors, promotes lung development, and thus reduces BPD incidence. 7 However, some infants cannot be fed with mother’s own milk (MOM) due to insufficient lactation or maternal illness. It is reported that the rate of exclusive breastfeeding is lower than 15% in neonatal intensive care units (NICUs), leading to mixed feeding with MOM, donor human milk (DHM), and formula. 6
Formula is devoid of numerous bioactive components found in breast milk, including oligosaccharides, lactoferrin, and immunoglobulins. Even DHM, which is typically from term mothers, differs significantly in composition and efficacy from MOM, especially colostrum. 8 Pasteurization and freezing processes also reduce or eliminate bioactive components such as inositol, antioxidants, lactadherin, mucins, and growth factors. 9 Therefore, it is unclear whether early different feeding methods affect the incidence of BPD. This study seeks to examine the correlation between various feeding methods (MOM, DHM, and formula) within the first 2 weeks of life and the risk of developing BPD in preterm infants.
Materials and Methods
Study design and participants
This retrospective cohort study included neonates admitted to the NICU at Fujian Maternity and Child Health Hospital between March 1, 2023, and February 28, 2024. Data on patient hospitalizations were obtained from the hospital’s electronic medical records. The NICU at Fujian Maternity and Child Health Hospital is a level III unit, admitting about 4,000 patients annually. Inclusion criteria: (1) Gestational age (GA) under 32 weeks or birth weight below 1,500 g. (2) Admission within 12 hours after birth. Exclusion criteria: (1) Congenital malformations. (2) Genetic metabolic diseases. (3) Hospitalization duration less than 28 days. (4) Average daily feeding volume under 20 mL/kg during the initial 2 weeks. (5) Any feeding method contributing to less than 50% of the total feeding volume in the first 2 weeks.
Feeding methods
All preterm infants started feeding as early as possible. Those with sufficient MOM were exclusively MOM feeding. If MOM was unavailable or insufficient, DHM or formula was used to supplement MOM inadequacy with informed consent from the parents. Breast milk fortifier was used when breast milk intake reached 50–100 mL/kg/day. Daily caloric intake was ensured at 100–120 kcal/kg, with parenteral nutrition if enteral nutrition was insufficient. Parenteral nutrition was stopped once enteral caloric intake reached 100 kcal/kg/day. DHM was sourced from a milk bank and pasteurized before use. Infants were categorized based on the predominant feeding method in the first two weeks: MOM group (proportion of feeds from MOM ≥50%), DHM group (proportion of feeds from donor milk ≥50%), and formula group (proportion of feeds from formula ≥50%).
Outcomes
Primary outcome
The incidence of BPD was assessed. BPD diagnosis and severity were determined according to the 2001 NICHD criteria: any oxygen dependency (FiO2 > 21%) lasting more than 28 days was diagnosed with BPD. The severity of BPD is assessed at a corrected GA of 36 weeks or at discharge for infants born before 32 weeks of gestation, and at 56 days after birth or at discharge for infants born at or after 32 weeks of gestation. Severity is classified as: Mild—no need for oxygen; Moderate—oxygen requirement with FiO2 < 30%; and Severe—oxygen requirement with FiO2 ≥ 30% or requiring positive pressure ventilation. 10
Secondary outcomes
Secondary outcome measures included sepsis occurring after the initial 2 weeks of life (diagnosed by clinical signs and confirmed by blood culture), stage II or higher necrotizing enterocolitis (NEC; graded per Bell’s staging system 11 ), retinopathy of prematurity (ROP, classified by the International Classification of Diseases for ROP 12 ), and periventricular leukomalacia (PVL, identified by periventricular cysts observed on cranial ultrasonography or magnetic resonance imaging).
Covariates
GA was determined by prenatal ultrasound, menstrual history, obstetric examination, or a combination of these methods. Antenatal steroids are defined as corticosteroid use within 7 days before birth for pregnancies between 24 and 34 weeks. Neonatal asphyxia was indicated by an Apgar score ≤7 at 1 minute after birth. Mechanical ventilation is defined as invasive ventilation within the first 28 days. Prolonged rupture of membranes (PROM) ≥18 hours refers to the spontaneous rupture of membranes for 18 hours or more before the onset of labor. A hemodynamically significant patent ductus arteriosus (hs-PDA) is characterized by systemic hypoperfusion and specific criteria such as the ratio of the left atrium to the aortic root, the diameter of the internal duct, diastolic flow velocity in the left pulmonary artery, ventricular output on the left side, reduced antegrade flow during either systole or diastole, and reversed or absent diastolic flow in the descending aorta. 13
Statistical analysis
Data analysis utilized IBM SPSS version 19. Categorical variables were presented as counts (percentages) and compared via the χ2 test or Fisher’s exact test. For continuous variables with normal distribution, the mean ± standard deviation was used, and comparisons were made using one-way ANOVA. Continuous variables that were not normally distributed were represented as median with interquartile range and compared using the Kruskal–Wallis test. Multivariate logistic regression was conducted to explore the relationships between feeding methods and BPD, accounting for factors such as GA, birth weight, mechanical ventilation, cesarean delivery, PROM ≥18 hours, hs-PDA, and respiratory distress syndrome (RDS). Results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A p value below 0.05 indicated statistical significance.
Results
We enrolled 287 preterm infants who were admitted within 12 hours of birth, with a GA of less than 32 weeks or a birth weight below 1,500 g. After excluding three cases with congenital malformation, one case with genetic metabolic disease, 26 cases with hospital stays <28 days, 16 cases with an average feeding volume <20 mL/kg/day within the first two weeks, and three cases where any feeding method constituted less than 50% of the total feeding volume within the first two weeks, 238 cases were analyzed. The MOM group included 112 cases, with 25 cases of BPD (22%). The DHM group included 32 cases, with five cases of BPD (16%). The formula group included 94 cases, with 33 cases of BPD (35%) (Fig. 1).

Flowchart. GA, gestational age; BW, birth weight; BPD, bronchopulmonary dysplasia.
The cesarean section rate was significantly lower in the MOM group compared with the DHM and formula groups (52.68% vs. 75.00% and 74.47%, respectively; p < 0.01). No significant differences were observed among the three groups in terms of maternal age, antenatal steroid use, rate of PROM ≥18 hours, GA, birth weight, gender, Apgar at 1 minute after birth ≤7, mechanical ventilation rate, incidence of RDS, and hs-PDA (Table 1).
Maternal and Preterm Infant Epidemiological Characteristics
Kruskal–Wallis test.
The comparison between mother’s own milk, donor human milk, and formula feeding.
hs-PDA, hemodynamically significant patent ductus arteriosus; IQR, interquartile range; PROM, prolonged rupture of membranes; RDS, respiratory distress syndrome; SD, standard deviation.
The incidence of BPD was notably lower in the MOM and DHM groups than in the formula group. Univariate logistic regression analysis indicated that formula feeding increased the risk of BPD by 1.88 times relative to MOM feeding (OR 1.88, 95% CI 1.02, 3.48) and by 2.92 times relative to DHM feeding (OR 2.92, 95% CI 1.03, 8.30). There was no increased risk of BPD with DHM feeding compared with MOM feeding (OR 0.64, 95% CI 0.23, 1.85). After adjusting for GA, birth weight, mechanical ventilation, cesarean section, PROM ≥18 hours, hs-PDA, and RDS in a multivariate logistic regression model, formula feeding still increased the risk of BPD by 3.35 times compared with MOM feeding (OR 3.35, 95% CI 1.43, 7.85) and by 6.48 times compared with DHM feeding (OR 6.48, 95% CI 1.47, 28.57). In the moderate to severe BPD subgroup, the rate of formula feeding was significantly higher than that of MOM and DHM feeding (27.66% vs. 9.82% and 9.38%, respectively; p = 0.001). In a multivariate logistic regression analysis accounting for these confounding factors, formula feeding showed a significantly increased risk of moderate to severe BPD compared with MOM (OR 8.20, 95% CI 2.80, 24.08) and DHM (OR 7.35, 95% CI 1.42, 37.96) (Table 2, Table 3).
Incidence of BPD Under Different Feeding Methods
Fisher’s exact test.
The comparison between mother’s own milk, donor human milk, and formula feeding.
The donor human milk compared with mother’s own milk.
The formula feeding compared to mother’s own milk.
The formula feeding compared with donor human milk.
BPD, bronchopulmonary dysplasia.
Relationship Between Different Feeding Methods and Risk of BPD
The donor human milk compared with mother’s own milk.
The formula feeding compared with mother’s own milk.
The formula feeding compared with donor human milk.
Adjusted for gestational age, birth weight, mechanical ventilation, cesarean, hs-PDA, RDS, and PROM ≥18 hours.
BPD, bronchopulmonary dysplasia; CI, confidence interval; hs-PDA, hemodynamically significant patent ductus arteriosus; PROM, prolonged rupture of membranes; RDS, respiratory distress syndrome.
The incidence of NEC ≥ Stage II was notably lower in the MOM and DHM groups than in the formula feeding group (7.15% and 9.38% vs. 20.21%, respectively, p = 0.016), with no notable distinction between MOM and DHM. However, there were no notable variances in the rates of ROP, late-onset sepsis, and PVL among the three different feeding methods (Table 4).
Incidence of Other Complications in Preterm Infants According to Different Feeding Methods
Fisher’s exact test.
The comparison between mother’s own milk, donor human milk, and formula feeding.
The donor human milk compared with mother’s own milk.
The formula feeding compared with mother’s own milk.
The formula feeding compared to donor human milk.
NEC, necrotizing enterocolitis; PVL, periventricular leukomalacia; ROP, retinopathy of prematurity.
Discussion
In our study, we evaluated the impact of MOM, DHM, and formula as primary feeding methods within the first 2 weeks after birth on the occurrence of BPD in extremely preterm and VLBW infants at 28 days of life. We found that compared with formula feeding, both MOM and DHM feeding decreased the occurrence of BPD, particularly lowering the likelihood of moderate to severe BPD. Cohort studies have consistently shown that breastfeeding in the initial weeks after birth markedly lowers the likelihood of developing BPD. 14 Meta-analyses further support that even partial breastfeeding reduces the risk of BPD compared with exclusive formula feeding.15,16 A multicenter retrospective cohort study found that compared with formula feeding, consuming at least 50 mL/kg of breast milk daily reduced the incidence of moderate to severe BPD. 17 These findings are consistent with our study results.
Current research has demonstrated that breast milk promotes lung development and lowers the occurrence of BPD in preterm infants through multiple mechanisms. Components such as tocopherol, carotenoids, lysozyme, leptin, and lactoferrin in breast milk have anti-inflammatory and antioxidant properties, which help decrease BPD incidence.18–20 Breast milk components such as growth factors, secretory IgA, interleukin-10, and soluble CD14 also regulate immune system development, further reducing BPD. 15 Breast milk provides sufficient nutrition for preterm infants, promoting lung development. 18 Microbial imbalance is linked to the progression and severity of BPD. 21 Early breastfeeding influences gut microbiota composition, enhances intestinal barrier function, supports immune system development, and regulates lung development and inflammation via the gut–lung axis.22,23
When MOM supply is insufficient or direct breastfeeding is not possible due to illness, the American Academy of Pediatrics advises using DHM as the preferred alternative. However, DHM often comes from mothers of term infants and has lower energy, fat, and protein content compared with preterm milk. Pasteurization of DHM also destroys many bioactive substances, potentially reducing its benefits for preterm infants. However, our study found that when HDM intake reached 50% of the total milk intake, it similarly reduced the risk of BPD compared with formula. Compared with MOM, it did not increase the risks of BPD, NEC, ROP, PVL, or sepsis at 14 days after birth. Villamor et al. 24 found that DHM can prevent the occurrence of BPD. Madore et al. 25 showed that BPD rates were similar between infants fed mainly with DHM or MOM. Research also found that gut microbiota characteristics were similar between DHM and MOM feeding, though both differed markedly from formula feeding. 26 Antibodies and protective elements in DHM can help prevent infections and reduce lung inflammation and injury. 27 Therefore, DHM should be prioritized when MOM is insufficient.
In addition, our study observed a lower cesarean section rate in the MOM group compared with the DHM and formula groups. This trend may be attributed to the influence of cesarean sections on lactation, resulting in lower rates of MOM feeding. Previous studies have demonstrated that breastfeeding substantially lowers the risk of NEC.28,29 In the first 4 weeks of life, receiving a daily intake of breast milk of at least 50 mL/kg can reduce the risk of NEC in VLBW infants by approximately threefold. 17 Our study found that both MOM and DHM reduced NEC incidence, and DHM did not elevate NEC risk, consistent with previous research. This may be due to the various active substances in breast milk that maintains intestinal mucosal integrity, inhibit inflammation, regulate immunity, and promote the colonization of probiotics, thereby reducing the incidence of NEC. 30
There is still controversy regarding the potential of breast milk to decrease the incidence of sepsis. Peng et al. 29 suggest that breastfeeding may lower the incidence of sepsis. However, Fleiss et al. 31 found no evidence that breastfeeding reduces the risk of sepsis occurring after 72 hours of life. Our study found that the feeding method during the initial 2 weeks of life did not significantly affect the risk of sepsis occurring after 14 days. The different conclusions may be related to variations in breast milk intake and the timing of sepsis onset in different studies.
The role of breast milk in reducing the incidence of ROP is also disputed. Raghuveer et al. 32 found that MOM significantly reduced the risk of severe ROP compared with DHM and formula feeding. However, Zhou et al. 33 reported that only exclusive breastfeeding significantly reduced the incidence of ROP compared with formula feeding, while partial breastfeeding had no significant effect on ROP incidence. Our study found no significant association between the three different feeding strategies and the incidence of ROP, possibly influenced by the relatively low proportion of breast milk intake in our study.
There are few investigations into how early postnatal feeding methods affect the incidence of PVL. Cortez et al. 34 reported a lower incidence of PVL associated with breastfeeding relative to formula feeding. However, our study found no significant impact of the three different feeding methods on the incidence of PVL. Due to the limited occurrence of PVL in preterm infants, more samples are needed to draw reliable conclusions about the relationship between feeding methods and PVL.
In summary, when more than 50% of the feeding volume during the initial 2 weeks after birth is comprised of MOM or DHM, the incidence of BPD in extremely preterm or VLBW infants is reduced. DHM offers the same protective effect against BPD as MOM and is not associated with an increased risk of sepsis, ROP, NEC, or PVL. Therefore, in cases of insufficient MOM, DHM should be the preferred alternative.
The limitations of this study include: (1) Being a single-center retrospective cohort study conducted at Fujian Maternity and Child Health Hospital, which may introduce selection bias. (2) There is currently no unified standard for the diagnosis and classification of BPD that accurately reflects pulmonary lesions in preterm infants. 4 The diagnostic and classification criteria from the 2001 NICHD used in this study may not fully reflect pulmonary lesions. (3) Patients with a hospital stay of less than 28 days include those discharged due to recovery, transferred, or deceased. Some of these patients may have died from severe lung disease and due to the lack of relevant data, this may lead to bias. (4) Due to the lack of health information on donor mothers, we cannot compare the epidemiological characteristics between donor mothers and biological mothers. Variations in these characteristics could influence the composition of breast milk and, consequently, the incidence of BPD.
Conclusions
In conclusion, our study provides evidence that feeding methods within the first 2 weeks of life, particularly the use of MOM and DHM, are associated with a reduced incidence of BPD and NEC in preterm infants. Formula feeding, in contrast, was linked to a higher risk of BPD, especially moderate to severe BPD. These findings underscore the importance of optimizing early feeding practices to improve neonatal outcomes in preterm infants.
Footnotes
Acknowledgments
The authors are indebted to the milk donors whose generosity made this work possible. The authors also extend our heartfelt gratitude to the clinical physicians for their tireless efforts and dedication.
Authors’ Contributions
Z.L.: Conceptualization (equal) and writing—original draft (lead). W.C.: Conceptualization (supporting) and writing—review and editing (equal). S.L.: Writing—review and editing (equal). Y.H.: Writing—review and editing (equal). W.C.: Conceptualization (lead); writing—original draft (supporting); formal analysis (lead); methodology (lead); software (lead); and writing—review and editing (lead).
Ethics and Informed Consent
Ethical approval for the study was obtained from the Fujian Maternity and Child Health Hospital’s Ethics Committee (Approval number: 2024KY154). All identifying patient information was omitted, and the need for informed consent was exempted. The research adhered to the STROBE guidelines for observational studies to guarantee transparency and thorough reporting.
Disclosure Statement
The authors declare no conflicts of interest relevant to this article.
Funding Information
This work was supported by the Joint Funds for the innovation of science and Technology, Fujian province (Grant number: 2023Y9358).
