Effect of Oral Colostrum Administration Duration on Clinical Outcomes in Preterm Infants: A Randomized Controlled Trial

Abstract

Objective:

Oral colostrum administration (OCA) for neonates is easy, simple, and safe. Previous studies have reported that OCA decreases the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants. However, the optimal duration of OCA has not been established. This study aimed to investigate the effect of OCA for different durations on the incidence of NEC (stage ≥2) and other morbidities.

Methods:

This randomized controlled study recruited premature infants born before 32 weeks of gestation. The infants were categorized into the following three groups: noncolostrum group, did not receive OCA; short-term colostrum group, received oral colostrum for 3 days; and extended colostrum group, received oral colostrum for 10 days. For additional analyses, the infants were also classified into two broader categories: colostrum (combining short-term and extended groups) and noncolostrum groups.

Results:

In this study, 138 infants (46 in each group) were recruited. The incidence rates of NEC in the noncolostrum, short-term colostrum, and extended colostrum groups were 10.9% (n = 5), 4.3% (n = 2), and 0% (n = 0), respectively. Infants in the groups receiving colostrum exhibited a decreased incidence of NEC, although the difference was not significant when analyzed according to duration (OR: 0.19; 95% CI: 0.11–0.0.32, p = 0.057). Compared with the noncolostrum group, infants in the colostrum group achieved full enteral feeding earlier, had a shorter antibiotic duration, and exhibited lower rates of LOS (p = 0.004, p < 0.001, p = 0.004, respectively). The extended colostrum group exhibited the highest exclusive breastfeeding rate at discharge (p = 0.003).

Conclusion:

OCA improved feeding tolerance and reduced LOS in preterm infants. Although the effect on NEC was not significant, extended administration enhanced exclusive breastfeeding rates at discharge.

Keywords

oral colostrum administration necrotizing enterocolitis preterm breastfeeding

Introduction

Recent advances in neonatal care have contributed to enhancing the survival rate of severe preterm infants. However, necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are the leading causes of morbidity and mortality among preterm infants.¹ The most common preterm morbidities are underdeveloped and aberrant inflammatory responses. Breastfeeding and oral colostrum administration (OCA) exert beneficial effects on the immune system in this high-risk group.²

Colostrum, produced in small amounts during the first few postnatal days, is rich in immunological components, such as secretory immunoglobulin A, lactoferrin, leukocytes, and growth factors that exhibit antimicrobial, anti-inflammatory, and immunomodulatory properties.^3–7 These bioactive elements support the immature immune system of preterm infants and reduce infection risk. OCA is a simple and safe method that exerts local immunostimulant effects, promotes feeding tolerance, and may help prevent morbidities such as NEC and LOS.^8–10

Recent randomized controlled trials (RCTs) have reported that OCA mitigates LOS and NEC in preterm infants.¹¹ Yang et al. found that OCA decreased the incidence of NEC and LOS in infants born at ≤32 weeks of gestation.¹² Similarly, a meta-analysis by Fu et al. demonstrated that OCA reduced the incidence of NEC, LOS, and mortality; shortened the time to achieve full enteral feeding; and accelerated regaining of birth weight.¹³ However, despite these promising results, the optimal duration and frequency of OCA remain unclear, as previous studies have used varying protocols. This gap in knowledge highlights the need for further research. Therefore, this study aimed to investigate the effects of OCA administered for different durations—and thus different cumulative doses—on the incidence of NEC, feeding outcomes, and other morbidities beyond the gastrointestinal system.

Methodology

Research design

This trial was designed as a single-center randomized controlled study. The rationale for the study design was the limited number of studies for the ideal duration of OCA. This study was performed according to the principles of the Declaration of Helsinki. The study protocols were approved by the Akdeniz University Clinical Research Ethics Committee (Decree No. KAEK-503; publication date July 5, 2023).

Participants

The inclusion criteria were as follows: preterm infants aged <32 gestational weeks and birth weight of <1500 g; infants who were administered colostrum in the first 24 hours of birth; infants whose follow-up was completed in our clinic. The exclusion criteria were as follows: infants who could not receive breast milk and infants with gastrointestinal or congenital anomalies. The infants were classified into the following three groups: noncolostrum group: did not receive oral colostrum; short-term colostrum group: received oral colostrum for 3 days; and extended colostrum group: received oral colostrum for 10 days. For additional analyses, the infants were also classified into two broader categories: colostrum (combining short-term and extended groups) and noncolostrum groups.

Treatment assignment

This study was conducted as an open-label RCT. Therefore, clinicians and parents were aware of group allocation after randomization. Infants were randomized into three groups using computer-generated random numbers in permuted random block sizes of 4 or 6. Allocation concealment was ensured using sequentially numbered, sealed opaque envelopes prepared by an independent researcher who was not involved in participant enrollment.

Oral colostrum administration

The mothers of the infants included in the study were instructed to provide their milk as soon as possible after birth at the neonatal intensive care unit (NICU). Colostrum was freshly administered using sterile 1-mL syringes. In particular, 0.2 mL colostrum was drawn into the syringe, with 0.1 mL gently applied to the inside of each cheek of preterm infants. This protocol was repeated once every 3 hours (8 × 0.2 mL) for 3 days (short-term colostrum group) or 10 days (extended colostrum group). Minimal enteral nutrition was initiated on the first day of life and gradually increased in all preterm infants who were hemodynamically stable and had no contraindications for enteral nutrition. The feeding protocol was not changed in the unit during the study period.

Outcomes

The primary outcome was the incidence of NEC (stage ≥2). The secondary outcomes included LOS, duration of antibiotics, time to full enteral and oral feeding, exclusive breastfeeding at discharge, and other morbidities such as patent ductus arteriosus (PDA) and bronchopulmonary dysplasia. The incidence of ≥stage 2 NEC was recorded based on the modified Bell criteria. Culture-proven sepsis occurring after the third day of life was defined as LOS. Additionally, infants receiving only breast milk, breast milk + formula milk, and only formula milk at discharge were recorded.

Statistical analysis

All statistical analyses were performed using Statistical Package for the Social Sciences 23.0 software (Chicago, IL, USA). Descriptive statistics are presented as frequency and percentage, mean and standard deviation, or median and 25%–75% percentile (Q1–Q3) values. Means between two groups were compared using the independent samples t test for normally distributed data and the Mann–Whitney U test for non-normally distributed data. Meanwhile, means between more than two groups were compared using one-way analysis of variance for normally distributed data and the Kruskal–Wallis test for non-normally distributed data. The correlation between categorical data was analyzed using the chi-square test. Differences were considered significant at p < 0.05. The sample size was determined using G*Power (version 3.1.9.4). Based on 90% power and 0.05 margin of error, the sample size was determined to be 138 (46/group) after assuming that a 20% difference between two groups would be significant.

Results

The demographic data, gestational week, and birth weight were not significantly different between the three groups. Antenatal steroid administration rates in the noncolostrum, short-term colostrum, and extended colostrum groups were 32.6% (n = 15), 60.8% (n = 28), and 58.6% (n = 27), respectively (p = 0.024). The rate of complete antenatal steroid cure in the noncolostrum group was lower than that in the short-term colostrum (p = 0.014) and extended colostrum groups (p = 0.020). Other demographic characteristics and antenatal risk factors were not significantly different between the groups (Table 1).

Table 1.

Comparıson of Baselıne Characterıstıcs of the Groups

	Noncolostrum group	Short-term colostrum group	Extended colostrum group	p Value
Gestational week	27.8 ± 2.5	28.4 ± 2.1	28.2 ± 2.2	0.53
Birth weight, g	1115 ± 316	1140 ± 296	1083 ± 271	0.64
Sex (female) (n, %)	21 (45.7%)	24 (52.2%)	18 (39.1%)	0.45
Cesarean delivery (n, %)	43 (93.5%)	44 (95.7%)	44 (95.7%)	0.86
Five-minute APGAR score	7.2 ± 1.4	7.5 ± 1.4	7.2 ± 1.5	0.59
Antenatal steroid^a
None	20 (43.4%)	9 (19.5%)	9 (19.5%)	0.024
Incomplete treatment group	11 (23.9%)	9 (19.5%)	10 (21.7%)
Complete treatment group	15 (32.6%)	28 (60.8%)	27 (58.6%)
Resuscitation at birth
None	18 (39.1%)	24 (52.2%)	20 (43.5%)	0.6
PPV only	27 (58.7%)	21 (45.7%)	26 (56.5%)
PPV + chest compressions ± epinephrine	1 (2.2%)	1 (2.2%)	0
Chorioamnionitis	4 (8.7%)	0	4 (8.7%)	0.12
Premature membrane rupture	4 (8.7%)	5 (10.9%)	8 (17.4%)	0.41
Preeclampsia	11 (23.9%)	7 (15.2%)	7 (15.2%)	0.45
Respiratory distress syndrome	38 (82.6%)	31 (67.4%)	40 (87%)	0.054

Antenatal steroid rate in the noncolostrum group was significantly lower than in the short-term and extended colostrum groups (p = 0.014, p = 0.020, respectively).

PPV, positive pressure ventilation.

The median time (range) of the first administration of oral colostrum in the short-term colostrum and extended colostrum groups was 16 (11–24) and 12 (5–24) hours, respectively. The total oral colostrum volume administered to the patients in the short-term colostrum and extended colostrum groups was 3.6 (2.5–4.8) and 11.7 (10.4–13.9) mL, respectively.

The incidence rates of NEC in the noncolostrum, short-term colostrum, and extended colostrum groups were 10.9% (n = 5), 4.3% (n = 2), and 0% (n = 0), respectively. The NEC incidence rates were not significantly different between the groups (OR: 0.19; 95% CI: 0.11–0.0.32, p = 0.057). The median (range) total enteral feeding time in the noncolostrum, short-term colostrum, and extended colostrum groups was 12 (9–15), 9 (7–13), and 9.5 (7–12) days, respectively (p = 0.013). The total enteral feeding time in the noncolostrum group was higher than that in the short-term colostrum (p = 0.034) and extended colostrum groups (p = 0.004). The median (range) total oral feeding time in the noncolostrum, short-term colostrum, and extended colostrum groups was 59 (38–80), 40 (26–61), and 59 (44–83) days, respectively (p = 0.008). The total oral feeding time in the noncolostrum and extended colostrum groups was higher than that in the short-term colostrum group (p = 0.007 and p = 0.001, respectively). The proportion of infants fed only breast milk in the noncolostrum, short-term colostrum, and extended colostrum groups was 34.1% (n = 14), 54.5% (n = 24), and 71.4% (n = 30), respectively (p = 0.019). Compared with that in the extended colostrum group, the proportion of infants fed exclusively breast milk was lower in the noncolostrum group (p = 0.003) (Table 2). The rates of exclusive breastfeeding at discharge are shown in Figure 1.

FIG. 1.

Flow diagram of the study population.

Table 2.

Comparıson of Groups ın Terms of Necrotızıng Enterocolıtıs and Nutrıtıonal Parameters

	Noncolostrumgroup	Short-term colostrum group	Extended colostrum group	p	OR (95% CI)
NEC (≥stage 2)	5 (10.9%)	2 (4.3%)	0	0.057	0.19 (0.11–0.32)
Time to reach full enteral feeds, day^a	12 (9–15)	9 (7–13)	9.5 (7–12)	0.013
Time to reach full oral feeds, day^b	59 (38–80)	40 (26–61)	59 (44–83)	0.008
Exclusive breastfeeding at discharge^c
Yes	14 (34.1%)	24 (54.5%)	30 (71.4%)	0.019
No	10 (24.4%)	6 (13.7%)	6 (14.3%)
Breastfeeding and formula	17 (41.5%)	14 (31.8%)	6 (14.3%)

Data are given as n (%), median (IQR).

The transition time to total enteral feeding in the noncolostrum group is longer compared with short-term and extended colostrum groups (p = 0.034, p = 0.004, respectively).

The transition time to total oral feeding is longer in the noncolostrum and extended groups compared with the short-term group (p = 0.007, p = 0.001, respectively).

The rate of exclusive breastfeeding is lower in the noncolostrum group than in the extended group (p = 0.003).

NEC, necrotizing enterocolitis.

The incidence rates of PDA in the noncolostrum, short-term colostrum, and extended colostrum groups were 60% (n = 28), 34.8% (n = 16), and 54.3% (n = 25), respectively. The PDA incidence rates significantly varied between the three groups (p = 0.01). The incidence rate of PDA in the short-term colostrum group was significantly lower than that in the noncolostrum (p = 0.007) and extended colostrum groups (p = 0.022). The rates of invasive respiratory support in the noncolostrum, short-term colostrum, and extended colostrum groups were 73.9% (n = 34), 45.7% (n = 21), and 73.9% (n = 34), respectively (p = 0.005). Compared with those in the noncolostrum and extended colostrum groups, the rates of invasive respiratory support were lower in the short-term colostrum group (p = 0.004 and p = 0.013, respectively). The LOS incidence rates in the noncolostrum, short-term colostrum, and extended colostrum groups were 45% (n = 21), 17.4% (n = 8), and 13% (n = 6), respectively. The incidence rate of LOS in the noncolostrum group was higher than that in the short-term colostrum (p = 0.004) and extended colostrum groups (p < 0.001). The median (range) antibiotic treatment duration in the noncolostrum, short-term colostrum, and extended colostrum groups was 21 (12–41), 10 (7–20), and 17 (10–25) days, respectively (p = 0.003). The total antibiotic duration in the noncolostrum group was higher than that in the short-term colostrum group (p = 0.001). Other morbidities and discharge parameters were not significantly different between the groups (Table 3).

Table 3.

Comparıson of Groups ın Terms of Other Clınıcal Data

	Noncolostrum group	Short-term colostrum group	Extended colostrum group	p	OR (95% CI)
GM-IVK
Stage 1	3 (6.5%)	1 (2.1%)	5 (10.8%)	0.54
Stage 2	4 (8.7%)	2 (4.3%)	2 (4.3%)
Stage 3	2 (4.3%)	1 (2.1%)	0
Periventricular hemorrhagic infarction	4 (8.7%)	1 (2.1%)	1 (2.1%)
PDA^a	28 (60%)	16 (34.8%)	25 (54.3%)	0.01	0.24 (0.09–0.37)
PDA treatment
Paracetamol	13 (44.8%)	7 (43.8%)	18 (66.7%)	0.20
Ibuprofen	15 (51.7%)	9 (56.3%)	7 (25.9%)	0.20
Invasive respiratory support^b	34 (73.9%)	21 (45.7%)	34 (73.9%)	0.005
Noninvasive respiratory support, day	19 (7–35)	12 (3–36)	22 (5–31)	0.72
BPD
Mild	15 (36.6%)	9 (20.5%)	17 (37%)	0.56
Moderate	3 (7.3%)	4 (9.1%)	2 (4.3%)
Severe	4 (9.8%)	3 (6.8%)	3 (6.5%)
Late-onset sepsis^c	21 (45%)	8 (17.4%)	6 (13%)	<0.001	0.31 (0.16–0.45)
Antibiotic duration days^d	21 (12–41)	10 (7–20)	17 (10–25)	0.003
ROP (requiring treatment)	3 (7.1%)	3 (6.8%)	2 (4.8%)	0.88	0.04 (0.02–0.24)
Periventricular leukomalacia	5 (12.1%)	7 (15.9%)	3 (7.1%)	0.21	0.13 (0.03–0.36)
Mortality	5 (10.9%)	2 (4.3%)	4 (8.7%)	0.50
Z score of discharge weight	−0.93 (−1.63–0.18)	−0.83 (−1.86–0.14)	−1,1 (−2.0 to −0.27)	0.75
Z score of discharge head circumference	−0.44 (−1–0.51)	−0.45 (−1.3–0.42)	−0.77 (−1.2 to −0.05)	0.50
Extrauterine growth retardation	10 (21.7%)	12 (26%)	16 (34%)	0.42	0.12 (0.02–0.30)
Length of hospital stay, day	71 (41–118)	47 (33–68)	65 (49–89)	0.12

Data are given as n (%), median (IQR).

PDA frequency in the short-term group is lower compared with the noncolostrum and extended groups (p = 0.007, p = 0.022, respectively).

IMV requirement in the short-term group is lower compared with the noncolostrum and extended groups (p = 0.004, p = 0.013, respectively).

Late sepsis incidence in the noncolostrum group is higher compared with the short-term and extended groups (p = 0.004, p < 0.001, respectively).

Total antibiotic duration in the noncolostrum group is higher compared with the short-term group (p = 0.001).

PDA, patent ductus arteriosus; GM-IVK, germinal matrix hemorrhage-intraventricular hemorrhage; BPD, bronchopulmonary dysplasia; EUBG, extrauterine growth retardation.

Analysis was also performed by classifying preterm infants into the oral colostrum group (n = 92) and the nonoral colostrum group (n = 46). The NEC incidence rates in the oral colostrum and nonoral colostrum groups were 2.2% (n = 2) and 10.9% (n = 5), respectively. The incidence of NEC in the oral colostrum group was lower than that in the nonoral colostrum group (p = 0.028). The median (range) total enteral feeding duration in the oral colostrum and nonoral colostrum groups was 9 (7–12) and 12 (9–15) days, respectively. The total enteral feeding time in the oral colostrum group was lower than that in the nonoral colostrum group (p = 0.004). The total oral feeding time was not significantly different between the groups. In the oral colostrum group, the rate of exclusive breast milk feeding was higher than that of formula milk feeding (p = 0.022) and breast milk + formula milk feeding (p = 0.007) (Table 4).

Table 4.

Comparıson of Feedıng Outcomes and NEC between Patıents wıth and wıthout Oral Colostrum Admınıstratıon

	Noncolostrum group (n: 46)	Oral colostrum group (n: 92)	p Value	OR (95% CI)
NEC (≥stage 2)	5 (10.9%)	2 (2.2%)	0.028	0.27 (0.14–0.39)
Time to reach full enteral feeds, day	12 (9–15)	9 (7–12)	0.004
Time to reach full oral feeds, day	59 (38–80)	50 (32–68)	0.107
Exclusive breastfeeding at discharge^a
Yes	14 (34.1%)	54 (62.7%)	0.01
No	10 (24.3%)	12 (13.9%)
Breastfeeding +formula	17 (41.4%)	20 (23.2%)

Data are given as n (%), median (IQR).

The rate of exclusive breastfeeding was higher in patients receiving oral colostrum compared with those receiving formula milk or breast milk + formula milk (p = 0.022, p = 0.007).

NEC, necrotizing enterocolitis.

The LOS incidence rates in the oral colostrum and nonoral colostrum groups were 15.2% (n = 14) and 45% (n = 21), respectively. The incidence rate of LOS in the oral colostrum group was higher than that in the nonoral colostrum group (p < 0.001). The duration of antibiotic treatment in the oral colostrum group was lower than that in the nonoral colostrum group (p = 0.004). Other clinical characteristics were not significantly different between the groups (Table 5).

Table 5.

Comparison of Groups in Terms of Other Clinical Data between Patients with and without Oral Colostrum Administration

	Noncolostrum group (n = 46)	Oral colostrum group (n = 92)	p Value	OR (95% CI)
GM-IVK
Stage 1	3 (6.5%)	6 (6.5%)	0.054
Stage 2	4 (8.7%)	4 (4.3%)
Stage 3	2 (4.3%)	1 (1%)
Periventricular hemorrhagic infarction	4 (8.7%)	2 (2.1%)
PDA	28 (60%)	41 (44.5%)	0.071	0.15 (0.01–0.29)
Invasive respiratory support	34 (73.9%)	55 (59,8%)	0.102	0.13 (0.01–0.27)
Noninvasive respiratory support, day	19 (7–35)	17 (5–33)	0.71
BPD
Mild	15 (36.6%)	26 (28.2%)	0.66
Moderate	3 (7.3%)	6 (6.5%)
Severe	4 (9.8%)	6 (6.5%)
Late-onset sepsis	21 (45%)	14 (15.2%)	<0.001	0.30 (0.08–0.47)
Antibiotic duration days	21 (12–41)	14 (7–24)	0.004
ROP requiring treatment	3 (7.1%)	5 (5.4%)	0.77	0.04 (0.005–0.27)
Periventricular leukomalacia	5 (12.1%)	10 (11.6%)	0.38	0.07 (0.005–0.30)
Mortality	5 (10.9%)	6 (6.5%)	0.37
Z score of discharge weight	−0.93 (−1.66–0.18)	−0.96 (−1.86–0.14)	0.99
Z score of discharge head circumference	−0.44 (−1–0.51)	−0.68 (−1.3–0.42)	0.29
Extrauterine growth retardation	10 (21.7%)	28 (30.4%)	0.36	0.16 (0.01–0.35)
Length of hospital stay, day	71 (41–118)	62 (38–80)	0.122

Data are given as n (%), median (IQR).

PDA, patent ductus arteriosus; GM-IVK, germinal matrix-intraventricular hemorrhage; BPD, bronchopulmonary dysplasia.

Discussion

In this study, OCA initiated within the first 24 hours of life was associated with a lower incidence of NEC, shorter total enteral feeding time, reduced LOS, and higher rates of exclusive breastfeeding at discharge. The highest rate of exclusive breastfeeding was observed in the extended colostrum group, highlighting the potential benefits of early and sustained OCA. Analysis by administration duration further emphasized that providing colostrum during the first 3 days of life may improve feeding outcomes in preterm infants.

Breast milk, especially colostrum, is a potent initial immune stimulant in infants.¹⁴ The colostrum and mature milk of mothers of preterm infants contain increased concentrations of sIgA and secretory IgM, antimicrobial factors, cytokines, and other growth factors.^3,15–17 These factors enhance local intestinal immunity and promote intestinal growth and differentiation. Enteral feeding is not possible in preterm infants. Thus, OCA can provide these factors to preterm infants and stimulate oropharynx-associated lymphoid tissue.¹⁸ Enteral nutrition management of preterm infants is challenging owing to various factors. For example, flora imbalance can increase NEC, LOS development, and mortality.¹⁹ Therefore, OCA can be a potential immunotherapy to regulate immune function and improve outcomes in preterm infants.²⁰

NEC, an inflammatory bowel disease, can cause necrosis and perforation of the intestinal epithelium, enhancing morbidity and mortality.^21,22 The incidence of NEC in preterm infants fed breast milk is lower than that in preterm infants fed formula milk.²³ Evidence regarding the effect of OCA on NEC and LOS, however, remains mixed. Fu et al. performed a meta-analysis of 16 studies involving 1,736 preterm infants. Oral colostrum (at different frequencies and durations) decreased the incidence of NEC and LOS. The authors established four subgroups (1–3, 4–7, 8–10, and >10 days) based on the neonatal follow-up duration and three subgroups (once every 2, 3, and 4 hours) based on the frequency of OCA. The NEC and LOS rates decreased when the duration of OCA was 8–10 days. The NEC incidence rate between the intervention and control groups was significant when the frequency of OCA was once every 4 hours and the duration was 8–10 days.¹³ Similarly, OuYang et al. and another meta-analysis reported lower NEC rates among OCA recipients, whereas Panchal et al. and Sharma et al. found no significant differences.^1,12,24,25 Such discrepancies may reflect heterogeneity among studies, including variations in gestational age, timing, and duration of OCA. In the present study, the duration of OCA was not significantly associated with the incidence of ≥stage 2 NEC. Although NEC occurred less frequently in the colostrum group, this difference did not reach statistical significance, likely due to the limited sample size. Nevertheless, when the administration duration was not considered, NEC incidence was significantly lower in infants receiving OCA compared with those who did not.

In the meta-analysis by Fu et al., the total enteral feeding time was significantly different when the frequency of OCA was once every 4 hours and the duration of OCA was 1–3 and 4–7 days.¹³Additionally, the time to complete enteral feeding and the time to achieve birth weight in the intervention group were lower than those in the control group (p = 0.002).¹³ In a Cochrane meta-analysis of six studies comparing the efficacies of OCA, water, saline, placebo, or no intervention, the NEC incidence was not significantly different. However, the time to full enteral feeding was short in the OCA group.²⁰

Chen et al. found that OCA was associated with the earlier achievement of full feeding and lower rates of feeding intolerance and NEC.²⁶ Future studies must compare different colostrum administration durations. OCA decreased the total enteral feeding time, which was similar to that reported in the literature. However, further studies are needed to understand the effects of OCA duration on total enteral feeding time.

In a retrospective study by Powers et al., 49.7% (n = 21,327) of patients were exclusively breastfed or fed breast milk + formula milk, while 50.3% (n = 21,564) of patients were exclusively formula milk-fed in postdischarge controls. The rate of breastfeeding was positively correlated with advanced gestational age, increased birth weight, White race, and married parents.²⁷ Dharel et al. examined 6,404 newborns and reported that the proportion of patients receiving only breast milk or breast milk + formula milk at discharge was 70% (n = 4,457). Additionally, advanced gestational age, primiparous mother, and breastfeeding on postnatal day 3 were correlated with a high rate of breastfeeding at discharge.²⁸ In this study, 70% (n = 90) of the infants were fed with breast milk and breast milk + formula milk at discharge. These data are consistent with the data reported in the literature. The rate of exclusive breastfeeding in the noncolostrum group was lower than that in the extended colostrum group. However, the rate of exclusive breastfeeding in the noncolostrum + short-term colostrum group was not significantly different from that in the short-term colostrum + extended colostrum group. Additionally, the rate of exclusive breastfeeding in the oral colostrum group was higher than that in the nonoral colostrum group. The rates of breast milk or formula milk feeding at discharge in preterm infants with and without OCA have not been previously compared. This is the first study to examine the effect of OCA on breast milk-feeding rates.

Fu et al. demonstrated that the incidence of LOS in the OCA group was lower than that in the control group. However, subgroup analysis based on different frequencies and durations revealed that the frequency of administration did not affect LOS incidence.¹³ OuYang et al. examined 252 preterm infants with the gestational age of ≤32 weeks who were followed up in a single-center tertiary NICU in China and revealed that OCA decreased the incidence of culture-positive sepsis.¹² One meta-analysis of 11 RCTs involving 1,173 preterm infants with the gestational age of ≤32 weeks or birth weight of ≤1500 g revealed that OCA decreased LOS incidence (p = 0.002).²⁴ Tao et al. reported that OCA was not associated with a significant reduction in LOS compared with controls.²⁹ In this study, the incidence of LOS in the noncolostrum group was higher than that in the short-term colostrum and extended colostrum groups. The total antibiotic duration in the noncolostrum group was higher than that in the short-term colostrum group. However, previous studies have reported contradicting results on the effects of OCA on the incidence of LOS and duration of antibiotics. These differences may be related to the usage of different durations of initial colostrum administration in different studies.

Antenatal steroids are known to reduce the incidence of perinatal and neonatal mortality, respiratory distress syndrome, severe intraventricular hemorrhage, and NEC.³⁰ Although antenatal steroid administration differed significantly among the study groups, no significant difference was observed in the primary outcome, NEC (≥stage 2). Therefore, a regression analysis to adjust for this potential confounder was not performed. Nevertheless, the possible influence of antenatal steroids on neonatal outcomes should be taken into account when interpreting the results.

The strengths of this study are as follows: prospective design, colostrum administration for different durations, and colostrum administration initiation within the first 24 hours. However, this study has some limitations, including a small sample size for NEC outcomes, imbalance in antenatal steroid administration, and a single-center design. Data on early feeding intolerance were not fully collected, and long-term neurodevelopmental outcomes were not assessed.

Conclusion

Oropharyngeal colostrum administration within the first 24 hours was safe and associated with reduced LOS and improved feeding outcomes. A duration beyond 3 days did not significantly alter NEC or LOS, although extended administration improved exclusive breastfeeding rates. Larger multicenter RCTs are needed to determine the optimal duration.

Authors’ Contributions

E.C.O.: Conceptualization, methodology, formal analysis, writing—original draft, writing—review and editing, and visualization. K.C.: Data curation and writing—review and editing. S.A.: Conceptualization, methodology, data curation, writing—original draft, and writing—review and editing. H.O.: Conceptualization, methodology, and writing—review and editing.

Footnotes

Funding Information

No funding was received for this study.

Disclosure Statement

No competing financial interests exist.

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