Bovine colostrum for prevention of recurrent urinary tract infections in susceptible children: A randomized controlled trial

Abstract

BACKGROUND

Recurrent urinary tract infections (UTIs) in children with congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of deterioration of kidney functions and possibly, renal scarring. Rising antimicrobial resistance necessitates alternative preventive strategies. Bovine colostrum (BC), a bioactive prebiotic, has emerged as a promising adjuvant therapy in upper respiratory and gastrointestinal (GIT) infections. Given the shared mucosal immune mechanisms, the urinary tract may represent a suitable target for this preventive strategy to reduce UTI recurrence.

AIM

To evaluate the potential role of oral BC as an adjuvant therapy for preventing recurrent UTIs in children with CAKUT.

METHODS

This randomized, double-blinded, placebo-controlled trial enrolled 60 children (< 18 years) with CAKUT and culture-confirmed recurrent UTIs. Children with urinary stones or endo-urinary devices were excluded. Participants were randomized to receive either oral BC sachets (n = 30) or placebo (n = 30) daily for one month. All patients were followed monthly for six months for UTI symptoms, physical examination, urine analysis, urine culture and sensitivity, complete blood count and C-reactive protein when indicated.

RESULTS

The two study groups were comparable in age, sex, and chronic kidney disease stage (P > 0.05). Colostrum supplementation showed a nonsignificant reduction in the overall incidence of upper and lower UTIs vs placebo over six months [relative risk (RR) = 0.84, 95%CI: 0.63-1.12; P = 0.22]. However, significant reductions of 73%-75% in UTI incidence were observed during the fourth, fifth, and sixth months of follow up (P < 0.05 for each). When stratified by infection type, cystitis incidence was significantly lower in the colostrum group (43.3% vs 70.0%; RR = 0.62; 95%CI: 0.39-0.99; P = 0.037), while no significant difference was observed in pyelonephritis. GTI and respiratory infections were reduced by 34% (RR = 0.66; 95%CI: 0.50-0.87; P = 0.001). No allergic reactions were reported.

CONCLUSION

BC supplementation may reduce cystitis, as well as respiratory and GIT infections, in children with CAKUT. The observed month-specific reduction in UTIs suggests a possible cumulative benefit with continued supplementation, warranting further research.

Key Words: Recurrent urinary tract infections; Respiratory tract infections; Gastrointestinal infections; Children; Bovine colostrum

Core Tip: Recurrent urinary tract infections (UTIs) promote the progression of kidney damage in children with congenital anomalies of the kidney and urinary tract, potentially leading to chronic kidney disease. The rising burden of antimicrobial resistance highlights the need for effective nonantibiotic preventive strategies. This randomized, double-blinded, placebo-controlled trial explores oral bovine colostrum (BC), a bioactive prebiotic with immunomodulatory properties, as an adjuvant therapy in these children. Although overall UTIs reduction was not statistically significant, BC significantly reduced cystitis, and showed delayed, month-specific reductions in UTIs, alongside fewer respiratory and gastrointestinal infections. These findings suggest a potential cumulative immunomodulatory benefit of BC in vulnerable pediatric populations.

INTRODUCTION

Recurrent urinary tract infections (UTIs) represent a major cause of morbidity in children with congenital anomalies of the kidney and urinary tract (CAKUT), frequently leading to renal scarring, progressive deterioration of renal function, and an increased risk of chronic kidney disease (CKD)[1]. Although antibiotic prophylaxis has been widely used to prevent recurrence, its long-term effectiveness is still unclear and increasingly challenged by the occurrence of breakthrough infections, and rising antimicrobial resistance[2]. This has prompted growing interest in nonantibiotic strategies that enhance host immune defenses and reduce infection susceptibility in high-risk pediatric populations[3].

Bovine colostrum (BC), the first milk secreted by mammals after birth, is a biologically specialized fluid that has evolved to provide immune protection and support mucosal development in the newborn. It contains a complex mixture of micronutrients, macronutrients and bioactive components, including immunoglobulins, antimicrobial proteins, bioactive oligosaccharides, cytokines, enzymes, and growth factors, which act synergistically to support innate and adaptive immunity and maintain epithelial barrier integrity[4].

Among its bioactive constituents, lactoferrin is one of the most abundant antimicrobial proteins in BC and plays an important role in host defense. Lactoferrin exhibits bacteriostatic and bactericidal activity through iron sequestration, direct disruption of bacterial membranes, inhibition of pathogen adhesion, and prevention of biofilm formation. In addition, it exerts anti-inflammatory and immunomodulatory effects that contribute to mucosal immune homeostasis[5]. Moreover, colostrum immunoglobulins, predominantly IgG, provide passive immune protection by neutralizing pathogens and facilitating immune clearance, while bioactive oligosaccharides act as prebiotics that promote beneficial microbial populations and competitively inhibit pathogen binding to epithelial surfaces[6,7].

Clinical and experimental studies have demonstrated that BC supplementation can reduce the incidence and severity of respiratory, gastrointestinal (GIT), and viral infections through enhancement of mucosal immune responses[8]. However, direct evidence regarding its effects specifically on UTI in children remains limited. Emerging evidence suggests that BC may reduce GIT carriage of uropathogenic Escherichia coli (UPEC), supporting a potential role in the prevention of recurrent UTIs[9]. Despite this strong biological rationale, the use of BC as an adjuvant preventive therapy for recurrent UTIs in the general pediatric population and in children with CAKUT remains insufficiently studied. Evaluating its efficacy and safety may therefore offer a novel, well-tolerated strategy to reduce infection recurrence and antibiotic exposure in this vulnerable population.

MATERIALS AND METHODS

Study design and setting

This study was a randomized, double-blind, placebo-controlled clinical trial conducted in accordance with the CONSORT 2010 guidelines. It was conducted at the Pediatric Nephrology Clinic, Ain Shams University, Cairo, Egypt. Participants were recruited during routine follow-up visits between August 2024 and August 2025.

Participants

Eligibility criteria: Children younger than 18 years with culture-confirmed recurrent UTI were eligible for inclusion. Recurrent UTI was defined according to the National Institute for Health and Care Excellence guidelines as the presence of at least one of the following: (1) Two or more episodes of acute pyelonephritis; (2) One episode of acute pyelonephritis plus one or more episodes of cystitis; and (3) Three or more episodes of cystitis.

Exclusion criteria included: (1) Known allergy or hypersensitivity to BC or any of its components; (2) Presence of an endo-urinary device (e.g., ureteral stent); and (3) Presence of urinary stones.

Ethical considerations: Ethical approval was obtained from the Institutional Review Board, Faculty of Medicine, Ain Shams University (No. FWA000017585; FMASU MS244/2023). Written informed consent was obtained from all participants’ parents or legal guardians prior to enrollment. Participants were informed of their right to withdraw from the study at any time without affecting their standard medical care. The trial was registered at ClinicalTrials.gov (NCT06164600).

Baseline assessment: At enrollment, all participants underwent a comprehensive baseline evaluation. This included collection of demographic data (age and sex), etiology and stage of CKD, current use of prophylactic antibiotics, and history of prior UTI, abnormal voiding patterns, constipation, and bladder–bowel dysfunction. Information regarding previous urological surgeries and circumcision status was also recorded. A complete physical examination was performed, including anthropometric measurements (weight and height), which were expressed as Z-scores and interpreted according to World Health Organization growth standards[10]. Clinical examination was conducted to exclude evidence of active UTI at the time of enrollment. In addition, baseline urine analysis and urine culture were obtained to rule out active infection. Complete blood count and C-reactive protein were performed when indicated. Estimated glomerular filtration rate was calculated using the modified Schwartz formula[11]. Existing antibiotic prophylaxis was kept unchanged throughout the study period to avoid confounding UTI incidence.

Sample size calculation: Due to limited published data on the expected effect size of BC in preventing recurrent UTIs, a pilot study was conducted. Based on a power calculation with a two-sided alpha of 0.05 and a power of 80%, a total sample size of 60 participants (30 per group) was deemed sufficient to detect a clinically meaningful difference in the primary outcome.

Randomization

Eligible children were enrolled consecutively upon meeting the inclusion criteria. Participants were randomly allocated in a 1:1 ratio to either the BC group or the placebo group. Randomization was performed using a computer-generated block sequence by an independent statistician who was not involved in patient recruitment or outcome assessment.

Allocation concealment

Allocation concealment was ensured by the hospital clinical pharmacy, which dispensed identical, sequentially numbered sachets labeled with anonymized codes corresponding to the randomization sequence.

Blinding

Participants, caregivers, investigators, and outcome assessors were blinded to group allocation until completion of data analysis.

Intervention

BC group: Participants assigned to the intervention group received oral BC sachets (ImmuGuard^®, NMI, London, United Kingdom). Each sachet contained 3 g of BC harvested within the first 6 hours postpartum and standardized to contain: Lactoferrin (65 mg), lactoperoxidase (2.8 units) and immunoglobulins: IgG 350 mg, IgA 35.3 mg, IgM 25.3 mg. Dosage was age-adjusted. Children younger than two years received 1 sachet daily, while children aged two years or more received two sachets daily. The sachets were administered on an empty stomach at least 30 minutes before meals for a duration of one month after enrollment.

Placebo group: Participants in the placebo group received sachets containing an inert powder identical in appearance, taste, and packaging to the BC sachets. Dosage and duration were matched to the intervention group.

Follow up and adherence

Participants received the intervention for one month, followed by a six-month post-intervention follow-up period. Outcome assessments were performed monthly throughout the follow-up, with ‘Month-1’ referring to the first month after completion of the intervention. Monthly follow-up visits were conducted, supplemented by telephone contact as needed. Adherence was assessed through caregiver reporting, sachet counts, and review of administration logs. At each visit, urological and systemic symptoms (e.g., dysuria, suprapubic pain, loin pain, fever ≥ 38 °C) were assessed. Urine samples were collected consistently using the clean-catch method or, when a clean-catch was not feasible-such as in infants or non-toilet-trained children-or when clinically indicated, by catheterization for urinalysis and culture with sensitivity testing.

Outcomes

Primary outcomes: (1) UTI including: Acute pyelonephritis, defined as fever ≥ 38 °C associated with a positive urine culture (≥ 10⁵ CFU/mL for clean-catch specimens or ≥ 5 × 10⁴ CFU/mL for catheterized specimens; (2) Cystitis, defined as lower urinary tract symptoms with a positive urine culture. All UTI diagnoses were made consistently using predefined criteria throughout the study; and (3) Sterile pyuria: ≥ 10 white blood cell/high-power field in the absence of bacterial growth.

Secondary outcomes: (1) Asymptomatic bacteriuria, defined as the presence of ≥ 10⁵ CFU/mL of a uropathogen in two consecutive urine cultures in asymptomatic patients; (2) Incidence of infections at other sites, including GIT and respiratory infections; and (3) Adverse events related to BC supplementation.

Statistical analysis

Data were coded, tabulated, and analyzed using IBM SPSS (Statistical Package for the Social Sciences), (IBM Corp., Armonk, NY, United States). Normality of quantitative variables was assessed using the Shapiro-Wilk test. Normally distributed data were presented as mean ± SD and compared using the independent t-test. Categorical variables were expressed as n (%) and analyzed using the χ² test or Fisher’s exact test, as appropriate. Relative risks (RR) with 95%CI were calculated to estimate effect size. A two-sided P < 0.05 was considered statistically significant.

RESULTS

A total of 78 children were assessed for eligibility. Of these, 18 were excluded-12 did not meet the inclusion criteria, and 6 declined to participate. The remaining 60 eligible participants were randomly assigned in a 1:1 ratio to the intervention group (n = 30) or the placebo group (n = 30). There was no loss to follow-up throughout the study period. All 60 participants were included in the final analysis, as illustrated in Figure 1. Both the colostrum and placebo groups were comparable at baseline in terms of age, sex distribution, CKD stage, and underlying cause of CKD, antibiotic prophylaxis against UTI, (P > 0.5 for all) as shown in Table 1. No adverse events were reported in the colostrum-receiving group.

Figure 1  Study flowchart for study participants.

Table 1 Baseline characteristics in study groups, n (%)/mean ± SD.

Variables	Colostrum group (n = 30)	Placebo group (n = 30)	P value
Age (years)	5.1 ± 3.3	4.8 ± 3.2	0.685
Male	18 (60.0)	20 (66.7)	0.592
Weight	-0.8 ± 1.2	-1.1 ± 1.6	0.454
Height	-1.1 ± 1.5	-1.3 ± 1.9	0.607
Pathology
Posterior urethral valve	14 (46.7)	17 (56.7)	0.438
Pelvi-ureteric junction obstruction	4 (13.3)	2 (6.7)	0.671
Vesicoureteric reflux	7 (23.3)	9 (30.0)	0.559
Single kidney	5 (16.7)	2 (6.7)	0.424
Neurogenic bladder	1 (3.3)	1 (3.3)	0.999
Antibiotic prophylaxis	24 (80.0)	26 (86.7)	0.488
Creatinine (mg/dL)	0.8 ± 0.4	0.9 ± 0.8	0.651
eGFR (mL/minute/1.73 m2)	67.2 ± 28.8	73.2 ± 40.8	0.513
Chronic kidney disease stage
I	4 (13.3)	9 (30.0)	0.292
II	11 (36.7)	8 (26.7)
III	13 (43.3)	9 (30.0)
IV	2 (6.7)	2 (6.7)
V	0 (0.0)	2 (6.7)

eGFR: Estimated glomerular filtration rate.

UTI

Colostrum supplementation was associated with a statistically nonsignificant reduction of 16% in the overall incidence of UTIs over a six-month period with RR = 0.84; 95%CI: 0.63-1.12; P = 0.22). However, a marked RR reduction of 73% to 75% in UTIs was observed specifically at the fourth, fifth, and sixth months of supplementation (P = 0.015, P = 0.007, P = 0.015 respectively) as detailed in Table 2. When stratified by infection type, the overall incidence of cystitis over the six-month period was significantly lower in the colostrum group (43.3%) compared with controls (70.0%) with RR = 0.62; 95%CI: 0.39-0.99; P = 0.037). In contrast, no significant difference was observed in the incidence of pyelonephritis between the two groups over the same period as shown in Table 2. The causative pathogens of UTI were Escherichia coli and Klebsiella species.

Table 2 Frequency of cystitis/pyelonephritis among study groups, n (%).

Time	Colostrum group (n = 30)	Placebo group (n = 30)	P value	RR (95%CI)
Pyelonephritis/cystitis
Month-1	10 (33.3)	14 (46.7)	0.292	0.71 (0.38-1.35)
Month-2	7 (23.3)	12 (40.0)	0.165	0.58 (0.27-1.28)
Month-3	5 (16.7)	9 (30.0)	0.222	0.56 (0.21-1.46)
Month-4	3 (10.0)	11 (36.7)	0.015	0.27 (0.08-0.88)
Month-5	3 (10.0)	12 (40.0)	0.007	0.25 (0.08-0.80)
Month-6	3 (10.0)	11 (36.7)	0.015	0.27 (0.08-0.88)
Incidence	17 (56.7)	23 (76.7)	0.222	0.84 (0.63-1.12)
Cystitis
Month-1	5 (16.7)	8 (26.7)	0.347	0.63 (0.23-1.69)
Month-2	5 (16.7)	7 (23.3)	0.519	0.71 (0.25-2.00)
Month-3	2 (6.7)	5 (16.7)	0.424	0.40 (0.08-1.90)
Month-4	1 (3.3)	7 (23.3)	0.052	0.14 (0.02-1.09)
Month-5	2 (6.7)	7 (23.3)	0.145	0.29 (0.06-1.26)
Month-6	2 (6.7)	7 (23.3)	0.145	0.29 (0.06-1.26)
Incidence	13 (43.3)	21 (70.0)	0.037	0.62 (0.39-0.99)
Pyelonephritis
Month-1	5 (16.7)	6 (20.0)	0.739	0.83 (0.28-2.44)
Month-2	2 (6.7)	5 (16.7)	0.424	0.40 (0.08-1.90)
Month-3	3 (10.0)	4 (13.3)	0.999	0.75 (0.18-3.07)
Month-4	2 (6.7)	4 (13.3)	0.677	0.50 (0.10-2.53)
Month-5	1 (3.3)	5 (16.7)	0.195	0.20 (0.02-1.61)
Month-6	1 (3.3)	4 (13.3)	0.353	0.25 (0.03-2.11)
Incidence	14 (46.7)	14 (46.7)	0.999	1.00 (0.58-1.72)

RR: Relative risk.

Sterile pyuria

Over the six-month study period, the overall incidence of sterile pyuria was lower in the colostrum group (40.0%) compared with the placebo group (63.3%) (r = 0.63; 95%CI: 0.38-1.06; P = 0.071), despite that this difference did not reach statistical significance. At the third month, sterile pyuria was significantly lower in the BC group than the control group (6.7% vs 26.7%, P = 0.038) with (RR = 0.25); however, the 95%CI crossed unity (95%CI: 0.06-1.08), likely reflecting the small sample size as shown in Table 3.

Table 3 Frequency of sterile pyuria among study groups, n (%).

Time	Colostrum group (n = 30)	Placebo group (n = 30)	P value	RR (95%CI)
Month-1	5 (16.7)	6 (20.0)	0.739	0.83 (0.28-2.44)
Month-2	3 (10.0)	6 (20.0)	0.472	0.50 (0.14-1.82)
Month-3	2 (6.7)	8 (26.7)	0.038	0.25 (0.06-1.08)
Month-4	3 (10.0)	7 (23.3)	0.166	0.43 (0.12-1.50)
Month-5	1 (3.3)	6 (20.0)	0.103	0.17 (0.02-1.30)
Month-6	1 (3.3)	5 (16.7)	0.195	0.20 (0.02-1.61)
Incidence	12 (40.0)	19 (63.3)	0.071	0.63 (0.38-1.06)

RR: Relative risk.

Asymptomatic bacteriuria

Over the six-month period, the overall incidence of asymptomatic bacteriuria was significantly lower in the colostrum group (16.7%) than in the placebo group (46.7%) (RR = 0.36; 95%CI: 0.15-0.87; P = 0.012). Although monthly comparisons did not reach statistical significance, a consistent reduction trend was observed, particularly in the third month (3.3% vs 20.0%; P = 0.103), fourth month (0.0% vs 16.7%; P = 0.052), and sixth month (3.3% vs 16.7%; P = 0.195), as shown in Table 4.

Table 4 Frequency of asymptomatic bacteriuria among study groups, n (%).

Time	Colostrum group (n = 30)	Placebo group (n = 30)	P value	RR (95%CI)
Month-1	0 (0.0)	2 (6.7)	0.492	Not applicable
Month-2	3 (10.0)	2 (6.7)	0.999	1.50 (0.27-8.34)
Month-3	1 (3.3)	6 (20.0)	0.103	0.17 (0.02-1.30)
Month-4	0 (0.0)	5 (16.7)	0.052	Not applicable
Month-5	1 (3.3)	2 (6.7)	0.999	0.50 (0.05-5.22)
Month-6	1 (3.3)	5 (16.7)	0.195	0.20 (0.02-1.61)
Incidence	5 (16.7)	14 (46.7)	0.012	0.36 (0.15-0.87)

RR: Relative risk.

GIT and respiratory infections

The overall incidence of combined GIT and respiratory infections was significantly lower in the colostrum group (63.3%) compared to the placebo group (96.7%) (RR = 0.66; 95%CI: 0.50-0.87, P = 0.001). Monthly analyses revealed consistently lower infection rates in the colostrum group, with statistically significant differences observed from the second month onward. The most notable reductions were seen at the second month (10.0% vs 60.0%; RR = 0.17; 95%CI: 0.05-0.51, P < 0.001), third month (13.3% vs 46.7%; RR = 0.29; 95%CI: 0.11-0.77, P = 0.005), and fifth month (10.0% vs 56.7%; RR = 0.18, 95%CI: 0.06-0.54, P < 0.001) as shown in Table 5. When analyzed separately, GIT infections were also significantly less frequent in the colostrum group (30.0%) than in the control group (60.0%) (RR = 0.50; 95%CI: 0.27–0.93; P = 0.02). Significant reductions were observed in the second month (P = 0.020) and fifth month (P = 0.026), with a borderline result at third month (P = 0.052). Similarly, respiratory infections occurred less often in the colostrum group (46.7%) control group (76.7%) (RR = 0.61; 95%CI: 0.40-0.94, P = 0.017) with significant differences noted at the second month (P = 0.006), fourth month (P = 0.038), and fifth month (P = 0.020) as shown in Table 5.

Table 5 Frequency of gastrointestinal and respiratory infection among study groups, n (%).

Time	Colostrum group (n = 30)	Placebo group (n = 30)	P value	RR (95%CI)
GIT/respiratory infections
Month-1	15 (50.0)	12 (40.0)	0.436	1.25 (0.71-2.20)
Month-2	3 (10.0)	18 (60.0)	< 0.001	0.17 (0.05-0.51)
Month-3	4 (13.3)	14 (46.7)	0.005	0.29 (0.11-0.77)
Month-4	4 (13.3)	13 (43.3)	0.010	0.31 (0.11-0.84)
Month-5	3 (10.0)	17 (56.7)	< 0.001	0.18 (0.06-0.54)
Month-6	3 (10.0)	11 (36.7)	0.015	0.27 (0.08-0.88)
Incidence	19 (63.3)	29 (96.7)	0.001	0.66 (0.50-0.87)
GIT infections
Month-1	7 (23.3)	6 (20.0)	0.754	1.17 (0.44-3.06)
Month-2	2 (6.7)	9 (30.0)	0.020	0.22 (0.05-0.94)
Month-3	1 (3.3)	7 (23.3)	0.052	0.14 (0.02-1.09)
Month-4	2 (6.7)	5 (16.7)	0.424	0.40 (0.08-1.90)
Month-5	1 (3.3)	8 (26.7)	0.026	0.13 (0.02-0.94)
Month-6	1 (3.3)	5 (16.7)	0.195	0.20 (0.02-1.61)
Incidence	9 (30.0)	18 (60.0)	0.020	0.50 (0.27-0.93)
Respiratory infection
Month-1	8 (26.7)	6 (20.0)	0.542	1.33 (0.53-3.38)
Month-2	1 (3.3)	9 (30.0)	0.006	0.11 (0.01-0.82)
Month-3	3 (10.0)	7 (23.3)	0.166	0.43 (0.12-1.50)
Month-4	2 (6.7)	8 (26.7)	0.038	0.25 (0.06-1.08)
Month-5	2 (6.7)	9 (30.0)	0.020	0.22 (0.05-0.94)
Month-6	2 (6.7)	6 (20.0)	0.254	0.33 (0.07-1.52)
Incidence	14 (46.7)	23 (76.7)	0.017	0.61 (0.40-0.94)

RR: Relative risk; GIT: Gastrointestinal.

DISCUSSION

UTI continue to pose a significant burden in the pediatric population due to their high recurrence rate and potential long-term complications, including renal parenchymal damage, hypertension, and CKD[12]. In children with CAKUT, the risk of recurrent UTIs is further elevated, warranting effective and sustainable preventive strategies. While antibiotic prophylaxis remains the standard of care, concerns about antimicrobial resistance and adverse effects have prompted investigation into exploring adjunctive approaches.

One such modality is BC, a natural product with immunomodulatory and antimicrobial properties that may offer a safe and effective adjunctive approach for preventing recurrent urinary infections in this vulnerable group. Our study demonstrates that BC supplementation led to a 16% reduction in overall UTI incidence over six months, although this reduction did not reach statistical significance. However, a statistically significant decline in UTI incidence emerged in fourth, fifth, sixth months of supplementation. These findings are consistent with preclinical research showing that BC, especially in hyperimmune forms, can reduce GIT colonization by UPEC, a key factor in recurrent UTIs[9]. The delayed but pronounced protective effect suggests that prolonged exposure to colostrum may be necessary to achieve substantial immunological benefits. The effect of BC observed in this study was predominantly attributable to reducing lower UTI mainly cystitis rather than pyelonephritis. The limited impact of BC on pyelonephritis aligns with colostrum’s likely mechanism of action at the mucosal level. Colostrum contains multiple bioactive components-such as lactoferrin, immunoglobulins, and oligosaccharides-that act at mucosal surfaces to prevent initial colonization and epithelial invasion through competitive inhibition of pathogen binding, strengthening of the epithelial barrier, and modulation of immune responses[13]. Lactoferrin specifically can bind directly to epithelial cell receptors, blocking pathogen attachment and the first phase of colonization, while also enhancing barrier function[14]. Moreover, lactoferrin suppresses biofilm formation thus inhibiting the growth and adhesion of UPEC by sequestering iron and disrupting bacterial membranes[15]. Additionally, colostral IgA antibodies neutralize pathogens and prevent their interaction with epithelial cells, further supporting this mucosal-level mechanism[16].

Beyond the urinary tract, BC supplementation significantly reduced the overall incidence of GIT and respiratory infections, with protective effects evident from the second month and maintained till the sixth month. Enteric infections dropped by 78% in the second month and by 87% in the fifth month with an overall incidence reduction of 50%. Respiratory infections were reduced by 89% in the second month, with sustained significance in the fourth and fifth months (75% and 78% reductions, respectively), and an overall reduction of 39%. The relatively more rapid onset of protection in the enteric and respiratory systems compared with the urinary tract, may reflect differences in microbial exposure, local immune mechanisms, or epithelial turnover rates. The persistence of these effects throughout the later months of follow-up highlights the durability of colostrum’s role as a broad-spectrum mucosal immune enhancer.

To the best of our knowledge, no previous studies have evaluated BC for prophylaxis against recurrent UTI in healthy children or children with CAKUT. Current research has primarily focused on respiratory and GIT infections. Meta-analyses involving over 445 participants across seven trials demonstrate a significant reduction in the incidence of upper respiratory tract infections (URTIs) incidence, with efficacy influenced by duration of supplementation but not by dose or sex; adverse effects were minimal and not significantly different from placebo[17]. Among medical students, supplementation with 0.5-1.0 g/day for 45 days reduced both frequency and severity of URTI symptoms, again with good tolerability[18]. In pre-school children, daily oral administration of dried BC (500-1000 mg) for 6 weeks led to a 31%-50% reduction in URTI symptom frequency and severity, with no significant abdominal or other side effects reported[19]. In formula-fed infants (n = 192), daily colostrum sachets for 3 months reduced the incidence and duration of diarrhea and respiratory infections, with improved fecal immune markers and no reported adverse effects[20]. In children with recurrent URTI or diarrhea (n = 160), 4 weeks of colostrum reduced infection episodes and hospitalizations over 6 months with significant decrease in the total number of infections and hospitalizations in children receiving BC[21].

BC exerts its protective effects through barrier-enhancing, immunomodulatory, and microbiota-modulating mechanisms. Its bioactive components-including immunoglobulins (notably IgG), lactoferrin, antimicrobial peptides, growth factors such as insulin-like growth factor-1 and transforming growth factor-β, and oligosaccharides-reinforce epithelial tight junctions, reduce intestinal permeability, promote epithelial repair, modulate innate and adaptive immunity, and shape beneficial microbiota[13,21].

Although the results are promising, this study has some limitations. The relatively small sample size may have limited statistical power to detect differences in some endpoints. Additionally, these findings are limited to children with CAKUT, restricting generalizability. Moreover, participants recruitment occurred along different seasons, therefore seasonal variation may have influenced infection incidence and represents a potential confounding factor. Finally, the six-month follow-up period may not be sufficient to capture the full therapeutic impact of BC.

CONCLUSION

BC appears to be a safe and well-tolerated adjunct for the prevention of recurrent UTIs in children with CAKUT, particularly cystitis and asymptomatic bacteriuria. Notably, its protective effect against UTIs tends to emerge later in the course of supplementation, whereas benefits in reducing GIT and respiratory infections appear earlier after initiation.

ACKNOWLEDGEMENTS

The authors would like to thank Dr. Hazem El-Hariri for his valuable contribution to the study through conducting the statistical analysis with a high level of expertise and commitment.