Melamine-contaminated Milk Powder Research Articles

Melamine and food safety: a 10-year review

In 2008, a melamine-contaminated milk powder incident occurred in China, which caused many urinary calculi in infants and young children. Some of these children developed kidney injury and even died. This had serious effects in China and the world, causing many people to become concerned about food safety issues. More than 10 years have passed since this incident, but food safety events continue to occur worldwide. We systematically reviewed the melamine incident, the harm caused by melamine to the human body, and its impact as well as the lessons and prospects on food safety.

Melamine-contaminated milk formula and its impact on children.

The melamine contaminated milk powder contamination scandal occurred in China in 2008. Its main consequences so far have been urinary stone formation in children with associated renal damage and increased child mortality. Eight years have passed, but food safety issues still remain of concern in the daily lives of millions of Chinese. Vigilance is required to ensure no recurrence of such food safety problems. Ongoing studies focus on the early detection of food industry malpractice, mechanisms whereby these toxic substances induce disease and how its advent may be prevented and better managed. Melamine undergoes renal excretion, but is metabolized slowly and excreted largely unchanged in the urine. Urinary melamine measurement may provide a rapid and inexpensive way to identify exposure to melamine adulterated food items. Although most patients with melaminerelated urinary stones (MUS) have been responsive to conservative treatment, longer time follow-up is needed to assess chronic effects. Aside from MUS, melamine is a recognized carcinogen and can induce urinary tract tumours. Very little is known about the effects of excessive exposure to melamine contaminated milk powder in infants on growth, adolescent and adult health, although short-term effects have become apparent during the scandal.

Assessment of chronic renal injury from melamine-associated pediatric urolithiasis: an eighteen-month prospective cohort study.

BACKGROUNDThe illegal use of melamine in powdered baby formula resulted in a widespread outbreak of melamine-associated pediatric urolithiasis and kidney damage in China in 2008. We conducted this study because more needs to be known about the long-term effects of melamine-associated urolithiasis and kidney damage.OBJECTIVESTo determine the prognosis and long-term implications of chronic kidney damage in children with urolithiasis resulting from melamine consumption.DESIGNProspective cohort study.SETTINGChildren’s Hospital of Fudan University.PATIENTS AND METHODSChildren six years of age or older with a history of having consumed melamine-contaminated milk powder were voluntarily screened. We measured urinary microprotein profiles [microalbumin (ALBU), immunoglobulin G (IgG), and N-acetyl-β-D-glucosidase (NAG)] and creatinine (CR) results at 6 and 18 months in children with melamine-associated urolithiasis. This study was conducted from September 17 to October 15, 2008.MAIN OUTCOME MEASURESChanges in urinary microprotein profiles.RESULTSOf 8335 children screened, 102 children (1.22%) were diagnosed with melamine-associated urolithiasis. Follow-up rates at 6 and 18 months were 91.4% (96/105) and 89.2% (91/102), respectively. Eighteen months later, 90.3% patients had spontaneously passed a stone. The incidence rates of proteinuria and microscopic hematuria at 6 months were significantly higher than at 18 months (P=.029 and P=.017, respectively). The proportion of patients with abnormal ALBU/CR, IgG/CR and NAG/CR at 6 months (27.6%, 17.1% and 21.1%, respectively) was significantly higher than at 18 months (6.4%, 5.1% and 12.8%, respectively). The high concentration of melamine consumed was the primary factor correlated with the high microprotein levels. Approximately 90% melamine-associated urolithiasis cases can be resolved within 18 months by non-surgical therapy.CONCLUSIONThe long-term presence of stones associated with a previous exposure to melanine can cause chronic kidney glomerular and tubular injuries. Passing these stones as soon as possible can reduce kidney injury and accelerate recovery.LIMITATIONSWe could not control for possible selection bias due to more visits to our hospital or visits to our hospital after diagnosis at other hospitals, which might have increased the rate of diagnosis.

Four years follow-up of 101 children with melamine-related urinary stones

The melamine-contaminated milk powder incidence occurred in China in 2008. Many studies have been published regarding the epidemiology, clinical symptoms, diagnosis and treatment of melamine-related urinary stones. The objective of this study is to follow-up the effects of melamine-contaminated milk powder consumption on kidney and body growth in children with melamine-related urinary stones 4years ago. One hundred and one children with melamine-related urinary stones were followed up by urinalysis, renal function tests and urinary ultrasonography. The data of body weight and height, clinical signs and complications were collected. Eighty normal children without the history of consuming melamine-contaminated milk powder were collected as controls. Eighty-one children with melamine-related urinary stones were successfully followed up. Of 45 cases with melamine-related urinary stones treated conservatively after discharge, 34 disappeared completely, 6 dissolved partially, 1 increased in size and 4 did not change at 4years follow-up. The percentages of under-height and under-weight infants were significantly higher in melamine-related urinary stones group compared to the controls, respectively (p<0.05). Routine blood, renal and bladder function tests as well as urinalysis were normal in all children. No urological tumors were detected. No noticeable impact of melamine-related urinary stones on kidney and bladder was found at 4years follow-up. However, whether or not melamine-related urinary stones had effect on body growth needs follow-up in future.

Four-year follow-up analysis on infants fed with melamine contaminated milk powder

Objective To follow up the effects of melamine contaminated milk powder induced hydronephrosis at 4 years ago on urinary system and body growth and development in infants. Methods Twenty-five infants with hydronephrosis induced by melaminecontaminated milk powder were followed up by urinary ultrasonography, urinalysis and renal function tests.The data of body weight and height were collected.Thirty healthy infants without the history of consuming melamine contaminated milk powder were collected as controls. Results Twenty-five infants were successfully followed up.Fifteen boys and 10 girls were included, and the average age was(67.60±17.22) months.Of the 25 infants with hydronephrosis at the time of discharge, 5 cases decreased in size, and others recovered to normal at the time of follow-up.The percentages of infants with calcium supplementation, body weight and height were not obviously different between the 2 groups. Conclusions After a 4-year follow-up, melamine contaminated milk powder induced hydronephrosis has not been found to leave a noticeable impact on kidney, bladder and body growth.A few of children existed hydronephrosis, but no signs of deterioration. Key words: Melamine; Hydronephrosis; Follow-up; Infant

Minimally invasive percutaneous nephrolithotomy in preschool age children with kidney calculi (including stones induced by melamine-contaminated milk powder)

This study was undertaken to assess the safety and efficacy of minimally invasive percutaneous nephrolithotomy (mini-PCNL) using ureteroscope and pneumatic intracorporeal lithotripsy in preschool age children with kidney calculi. We studied 27 renal units in 20 patients of preschool age (≤ 6 years) who underwent mini-PCNL at our institute. The mean age was 42.6 months (range 14-68 months). The average stone burden was 1.85 cm (range 0.9-2.8 cm). Eight patients aged 14 to 58 months had been exposed to melamine-tainted powdered formula. The mini-PCNL was performed with an X-ray-guided peripheral puncture. Minimal tract dilatation was undertaken to fit a 14-16 Fr peel-away sheath. Ureteroscope and pneumatic intracorporeal lithotripsy were used to fragment the stones. Complete clearance was achieved in 23 renal units (85.2 %) with mini-PCNL monotherapy. This has increased to 92.6 % after adjunctive ESWL. The average fall in hemoglobin was 1.28 g/dL. None of the patients required blood transfusion. The median length of hospital stay was 8.2 days. Patients were followed up every 6 months for 2 years. There has been only one recurrence of stone and no long-term complications. Mini-PCNL is a effective treatment for pediatric kidney stones refractory to extracorporeal shock wave lithotripsy, including stones induced by melamine-contaminated milk powder. The "mini-PCNL" technique, which uses ureteroscope and pneumatic intracorporeal lithotripsy, is a safe and feasible modality for treating renal calculi in preschool age children.

Follow-up results of children with melamine induced urolithiasis: a prospective observational cohort study

Melamine-contaminated milk powder was the cause of the 2008 outbreak of urolithiasis in young children and infants in China, but the prognosis of these children remains unknown. We hypothesized that urolithiasis induced by melamine-contaminated milk powder may be associated with secondary renal injury. A total of 8335 children (≤6 years old) with a history of consuming melamine-contaminated milk powder were screened. Urine analysis and urinary system ultrasonography were performed. For children with urolithiasis, the basic information and the results of examination were recorded, and effective therapy was given. They were followed up for 6 months after the original diagnosis, and urinary microprotein profiles were measured. Of the 8335 children, 105 (1.26%) were diagnosed with melamine-contaminated milk powder-associated urolithiasis. The size of the stone was correlated with the duration of exposure to melamine. Six months later, 69.8% (67) of the children with urolithiasis passed stones (follow-up rate: 91.4%). Of the 67 children, 28 passed stones within 2 months. The higher possibility of passing a stone was correlated with the smaller diameter of the stone (P<0.001). The detection rate of abnormal urinary microprotein excretion (microalbumin, immunoglobulin G, and N-acetyl-β-D-glucosidase) was 52.4% in children with persistent stones and 38.2% in those who passed their stones. The detection rate was lower in children who passed stones within 2 months (31.8%) than in those who passed stones in 2 to 6 months (50.0%). The levels of microalbumin/creatinine and immunoglobulin G/creatinine were significantly higher in children with persistent stones than in those who passed their stones. Early passage of a stone may reduce the renal injury induced by melamine-contaminated milk powder-associated urolithiasis.

Development of an Optical Biosensor Based Immunoassay to Screen Infant Formula Milk Samples for Adulteration with Melamine

The illegal adulteration of milk with melamine in 2008 in China led to adverse kidney and urinary tract effects in hundreds of thousands of children and the reported deaths of six. The milk had been deliberately adulterated to elevate the apparent protein content, and subsequently melamine was detected in many milk-related products which had been exported. This led to the banning of imports of milk and milk products from China intended for the nutritional use of children and to the implementation of analytical methods to test products containing milk products. An optical biosensor inhibition immunoassay has been developed as a rapid and robust method for the analysis of infant formula and infant liquid milk samples. A compound with a chemical structure similar to that of melamine was employed as a hapten to raise a polyclonal antibody and as the immobilized antigen on the surface of a biosensor chip. The sensitivity of the assay, given as an IC(50), was calculated to be 67.9 ng mL(-1) in buffer. The antibody did not cross-react with any of the byproducts of melamine manufacture; however, significant cross-reactivity was observed with the insecticide cyromazine of which melamine is a metabolite. When sample matrix was applied to the assay, a limit of detection of <0.5 μg mL(-1) was determined in both infant formula and infant liquid milk. The development of the immunoassay and validation data for the detection of melamine is presented together with the results obtained following the analysis of melamine-contaminated milk powder.

One year follow up of the outcomes of child patients with melamine‐related kidney stones in Beijing and surrounding provinces in China

To evaluate their prognosis, the damage by melamine on children's kidney and other organs, and its influence on the children's development, was investigated. Nine hundred and sixty-two Chinese children were divided into three groups: group A, 265 children diagnosed with melamine-associated urolithiasis; group B, 197 children with a history of melamine-contaminated milk powder consumption but without urolithiasis; and group C, 500 healthy children. They were examined at 0, 1, 3, 6 and 12 months. The factors influencing the prognosis were investigated. The stone discharge was monitored by ultrasonography. Overt renal and liver damage and underlying renal injury markers were analyzed. The stone discharge rates 1, 3, 6 and 12 months after the diagnoses were 52.5%, 67.2%, 88.3% and 95.5%, respectively. Stone size was a stable influencing factor for the stone discharge rate. Additionally, the values of the potential renal injury markers in children with stones already discharged is equivalent to normal children. This 12 month follow up of early renal injury markers indicated that the damage to the kidney is temporary with no persistent negative outcomes being found till now. Additionally, the gross development of the children seemed not yet jeopardized by melamine. Longer-term follow up will be conducted.

Infrared spectroscopic analysis of urinary stones (including stones induced by melamine-contaminated milk powder) in 189 Chinese children

AimThe aim of the study was to investigate the composition of the stones in Chinese children with urolithiasis, including peculiar stones induced by melamine-contaminated milk powder. Materials and MethodsBetween 1999 and 2009, 189 urinary stones from children of East China were received at our institution. Among them, 12 stones were received from pediatric stone formers with a history of consuming melamine-contaminated milk powder in 2008; and the remaining stones were defined as “natural” stones. All stones were analyzed by Fourier transform infrared spectroscopy. ResultsAmong 177 “natural” stones, whewellite stone (49.72%) was observed most frequently followed by weddellite stone (15.25%), uric acid anhydrous stone (9.6%), carbapatite stone (9.04%), cystine stone (9.04%), ammonium acid urate stone (4.52%), struvite stone (2.26%), and sodium urate stone (0.56%). Twelve young children who consumed melamine-contaminated milk powder were younger than 3 years, and their stones were composed of a mixture of uric acid dihydrate and ammonium acid urate based on Fourier transform infrared spectroscopy. In addition, the stones were radiolucent and could be dissolved by urine alkalinization. ConclusionsOur study emphasizes the relatively high rate of calcium oxalate stones and cystine stones, and the relatively low rate of struvite stones in Chinese children with urolithiasis. The stones caused by melamine-contaminated milk powder are composed of the mixture of uric acid dihydrate and ammonium acid urate.

Application of LIIR Automatic Analysis System of Infrared Spectroscopy in the determination of urinary stone composition

Objective To determine the value of applying LIIR Automatic Analysis System of Infrared Spectroscopy in analyzing urinary stone composition. Methods 1450 samples of urinary stones were collected from 1032 male and 418 female patients. The age of patients ranged from 6 months to 88 years. The mean ages were 41.7±15.3 and 42.0±15.6 years for male and female pa- tients, respectively. Of 1450 stones, 875 cases were located in kidney （60.34%）, 504 cases in ureter （34.76%） and 71 cases in bladder （4.90%）. All stones were analyzed by LIIR Automatic Analysis System of Infrared Spectroscopy （Tianjin）. Analysis results were reevaluated by the artificial analysis of spectrogram, i{ necessary, with polarization microscope, chemical analysis, and X ray diffraction. Results Calcium oxalate monohydrate stones were found in 714 cases （49. 24%）, carbonate apatite stones in 444 cases （30.62%）, anhydrous uric acid stones in 93 cases （6.41%）, calcium oxalate dihydrate stones in 92 cases （6. 34%）, ammonium magnesium phosphate hexahydrate stones in 28 cases （1. 93%）, cystine stones in 23 cases （1.59%）, ammonium urate stones in 20 cases （1.38%）, uric acid dihydrate stones in 16 cases （1.10%）, brushite stones in 12 cases （0. 83%）, sodium urate monohydrate stones in 2 cases （0. 14%）, calcium carbonate stones in 1 cases （0.07%）, and other stone types in 5 cases （0.34%）. Most urinary stones were composed of 2 or more compositions, and purestones were only observed in 397 cases （27.38%）. Most of the mixed stones contained calcium and non-calcium mixed stone was rarely observed. In addition, 15 stones were found in infants who had consumed melamine-contaminated milk powder. These stones were composed of uric acid dihydrate and ammonium urate. The results of reevaluation by artificial analysis showed the following among pure and mixed stones, false detection occurred in 6 cases （0.41%）, of which the composition was ammonium urate or carbonate apatite determined by automatic system but the true composition was an hydrous uric acid. False negative detection occurred in 9 cases （0.62%）, of which the composition was ammonium magnesium phosphate hexahydrate or carbonate apatite in 7 cases, but in other 2 cases the composition could not be determined by artificial analysis. The false negative detection of compo- nents with relatively low content occurred in 6 cases and 10 cases in stones with 2 components and 3 components, respectively. The undetected composition in these cases was ammonium magnesium phosphate hexahydrate or carbonate apatite. Conclusion Automatic Analysis System of Infrared Spectroscopy has many advantages in accuracy, automation and is quick in analyzing the composition of urinary stones, and is worthy of promotion in clinical use. Key words: Urinary calculi; Spectrophotometry, infrared; Calcium oxalate; Apatites

Clinical characteristics of melamine contaminated milk powder induced infant urinary calculi

目的 探讨三聚氰胺污染奶粉致泌尿系统结石的发病特点及预后,为临床诊断和治疗提供参考.方法 参照卫生部下发的诊断标准,对9578例食用三聚氰胺污染奶粉的婴幼儿通过泌尿系统B超及尿常规进行筛查,对11例住院治疗患儿的临床表现、治疗及转归等进行分析.结果 9578例儿童中,筛查出29例患有泌尿系统结石,检出率为0.3%;其中11例患儿需住院治疗.11例住院患儿中5例入院前有间断排尿哭闹,2例有排红色尿史,4例无任何症状,其中4例并发泌尿系感染.11例中右肾单发结石4例,右肾多发结石3例,双肾单发结石3例,双肾多发结石1例,其中1例伴发右肾积水.主要对患儿进行水化治疗和碱化尿液治疗,经2～91 d的治疗,彩色超声检查泌尿系统结石消失.随访1年未再出现临床症状,超声检查未见异常.结论 三聚氰胺污染奶粉致泌尿系统结石为单发或多发性肾结石,如结石直径为4～11mm,经内科综合治疗预后良好。

MP-19.10: Clinical Features of Urinary Tract Calculi Induced Hydronephrosis in Infants Fed Melamine-Contaminated Milk Powder

MP-19.10: Clinical Features of Urinary Tract Calculi Induced Hydronephrosis in Infants Fed Melamine-Contaminated Milk Powder

Rapid analysis of melamine in infant formula by sweeping-micellar electrokinetic chromatography

In the present study, an analytical method using capillary electrophoresis with on-line preconcentration technique was developed for rapid determination of melamine in infant formula. Both stacking and sweeping preconcentration techniques had been investigated for the comparison of their effectiveness in melamine analysis. The limit of detection of melamine standard was 0.5 ng/mL for the field amplified sample stacking (FASS) technique and 9.2 ng/mL for the sweeping technique. Although the FASS technique provided better concentration efficacy than the sweeping technique, the matrix effect was more profound with the former. Matrix effect was evaluated by comparing the enhancement factor (EF) of melamine standard and post-extraction spiked infant formula solution. The EF was changed from 429.86 ± 9.81 to the level less than 133.31 with significant peak distortion in the FASS system, and it was remained unchanged in the sweeping system. Sweeping-micellar electrokinetic chromatography (sweeping-MEKC) was demonstrated to be most suitable for real sample analysis. Under optimum sweeping-MEKC conditions, melamine content in infant formulas could be determined within 6 min. The developed solid phase extraction (SPE) procedures coupled with the sweeping-MEKC method was subjected to method validation. Run-to-run repeatability ( n = 3) and day-to-day reproducibility ( n = 3) of peak area were within 3.6% and 4.8% RSD, respectively. The accuracy was tested by spiking 0.5 and 2 μg/mL of melamine standard in the melamine contaminated milk powder provided by the European Commission, and the recoveries were 93.4 ± 0.5% and 98.7 ± 0.4%, respectively. Results of this study show a great potential for the sweeping-MEKC method as a tool for the fast screening of melamine in infant formulas.

Conservative Management of Pediatric Nephrolithiasis Caused by Melamine-Contaminated Milk Powder

In this article we report our experience with the diagnostic screening and management of children with melamine-induced nephrolithiasis. A total of 1091 children younger than 4 years who had been exposed to melamine-contaminated formula from September 17 to October 12, 2008, were screened for nephrolithiasis at the department of pediatrics at Shenzhen Nanshan Hospital in China. During the clinical examination, each patient's demographic characteristics were recorded together with the details of his or her milk-consumption profile during the contamination scare and any clinical signs of poisoning. Urinary stones were detected by B-ultrasonography, and renal status was examined by a routine urine test panel and a renal function test. When urinary stones were detected, patients were ordered to cease consumption of the suspected formula, and a conservative treatment course was adopted, including infusion of fluids, urinary alkalinization, increased water consumption, and diuresis. Of the 1091 children screened, 12 (1.1%) were diagnosed with kidney stones. They had been exposed to the contaminated milk from 1 to 24 months. Eleven (91.7%) of these 12 patients had consumed milk with a high level of melamine content (955-2563 ppm); 1 patient (8.3%) had consumed milk with a low-level melamine content (6.2-17.0 ppm). Six patients exhibited dysuria; the remaining 6 patients were asymptomatic. All 12 patients had normal renal function, although 4 had proteinuria, and 1 had hematuria. The kidney stones were resolved within 3 to 5 days of commencing treatment in all 12 cases. Nephrolithiasis was associated with high melamine-exposure levels. A combination of B-ultrasonography and urinalysis is suitable for screening for pediatric nephrolithiasis caused by melamine poisoning. The condition can be resolved with a conservative treatment approach in patients without serious clinical symptoms who have normal kidney function.

The Clinical Analysis of Urolithiasis in 165 Infants and Children with History of Feeding Melamine Contaminated Milk Powder

Purpose To investigate the clinical feature of the urolithiasis in infants fed with melamine contaminating milk powder. Material and Methods The clinical data of 165 infants, aged from 50 days to 3 years old (14m±9m), with urinary calculus who had the history of feeding melamine contaminating milk powder were retrospectively analyzed. All cases were divided into mild (25 cases), moderate (122 cases) and severe group (18 cases)) and treated according to the guideline from Chinese Ministry of Health. Results The peak incidence of urolithiasis was found in the age of 6m -12 m. The male and female ratio was 2.59:1. Among these patients, 50.3% showed asymptomatic, 16.9% dysuria, 14.6% infantile colic, 10.9% oliguria or anuria and 7.3%hematuria. Acute urinary retention caused by bladder and urethra stones was found in 5 cases. The mean urinary pH value in 165 cases was (5.5±0.4). The BUN, Scr and SUA in the severe group were significantly higher than those of the control (P Conclusions The melamine calculus occurred mostly in infants at 6 months to 10 months after feeding melamine contaminated milk powder. Multiple stone was most frequently confronted in clinincal practice. Noninvasive management had a good efficacy.

THE CLINICAL ANALYSIS OF UROLITHIASIS IN 165 INFANTS AND CHILDREN WITH HISTORY OF FEEDING MELAMINE CONTAMINATED MILK POWDER

Purpose To investigate the clinical feature of the urolithiasis in infants fed with melamine contaminating milk powder. Material and Methods The clinical data of 165 infants, aged from 50 days to 3 years old (14m±9m), with urinary calculus who had the history of feeding melamine contaminating milk powder were retrospectively analyzed. All cases were divided into mild (25 cases), moderate (122 cases) and severe group (18 cases)) and treated according to the guideline from Chinese Ministry of Health. Results The peak incidence of urolithiasis was found in the age of 6m -12 m. The male and female ratio was 2.59:1. Among these patients, 50.3% showed asymptomatic, 16.9% dysuria, 14.6% infantile colic, 10.9% oliguria or anuria and 7.3%hematuria. Acute urinary retention caused by bladder and urethra stones was found in 5 cases. The mean urinary pH value in 165 cases was (5.5±0.4). The BUN, Scr and SUA in the severe group were significantly higher than those of the control (P Conclusions The melamine calculus occurred mostly in infants at 6 months to 10 months after feeding melamine contaminated milk powder. Multiple stone was most frequently confronted in clinincal practice. Noninvasive management had a good efficacy.