Thr NEW ENGLAND JOURNAL Of MEDICINE in young children,most under 36 months We administered a questionnaire designed to ob ofage,recently occurred in China.On Sep-tain information about demographic characteris- tember 12,2008,the Chinese government an- nounced that the epidemic was most likely relat melamine content,dura ora com 0nofeposure,use on or breas melamine the 3-day period before the visit.Other signs trogen by mass:this covert practice appears to have and symptoms,such as oliguria,unexplained cry- been the cause of the melamine contamination of infant formula.Although an epidemic of rena uarrn ing some occurred i with anin melamine ingestion and urinary stones in hu mans was initially unclear in the recent epidemic Republic of China reported that 22 brands of in among children.The present report details an fant formula were contaminated(with reported investigation of melamine-linked u ary stones concentrations of melamine ranging from 0.1 to in children exposed to contaminated formula. 2500 ppm).On the basis METHODS nt、s00 om)moderate Immediately after the announcement of melamine (150 ppm)and no-melamine formula None of contamination of formula and the government the brands tested contained melamine at a con sponsored screening,we initiated a multidisci centration between 150 and 500 ppm.Children had plinary study.The prespecified pri to have been fed formula for at ast 30 days to be mary was the pre to nave ticle at NEJM.org). We developed a questionnaire that was adminis. tered by several trained investigators.For the other LABORATORY INVESTIGATIONS atory sta to us riaa wer proc aur notra was petb sample 0to19 liter)tra sfarrin (re raphy personnel.The rapid impl erence range,0to 2mg per liter),a-microglobulir tation of this study rendered it likely that some (reference range,0to12mg perliter),and N-acetyl data would be incomplete. B-D-glucosaminidase (reference range,0 to 21 t PATIENTS r urinary stones ber UITRASONOGRAPHY OF THE URINARY TRACT September 17 and October 3.2008.The study was Ultrasonography of the kidneys and lower urinary approved by the hospital's ethics committee.All the tract was performed with the use of an uasono parents or guardians provided written informed raphy system (ProSound SSD-5000SV,Aloka)an consent. an attached scanner monitor (5 to 6 MHz).Assess 1068 N ENGLJ MED 360:11 NEJM.ORG MARCH 12,2006 Downloaded from nejm. The NThe new england journal o f medicine 1068 n engl j med 360;11 nejm.org march 12, 2009 An epidemic of urinary tract stones in young children, most under 36 months of age, recently occurred in China. On Sep￾tember 12, 2008, the Chinese government an￾nounced that the epidemic was most likely related to melamine contamination of powdered-milk for￾mula for infants, and a policy of free screening for urinary stones in children was instituted. The ad￾dition of melamine to food boosts the apparent protein content, since melamine contains 66% ni￾trogen by mass; this covert practice appears to have been the cause of the melamine contamination of infant formula. Although an epidemic of renal failure, including some deaths, had occurred in 2007 in animals exposed to pet food contaminat￾ed with melamine,1 the relationship between melamine ingestion and urinary stones in hu￾mans was initially unclear in the recent epidemic among children. The present report details an investigation of melamine-linked urinary stones in children exposed to contaminated formula. Methods Immediately after the announcement of melamine contamination of formula and the government￾sponsored screening, we initiated a multidisci￾plinary cross-sectional study. The prespecified pri￾mary outcome was the presence of urinary stones. Secondary outcomes were clinical manifestations and laboratory abnormalities, as well as other pos￾sible factors, associated with melamine exposure. We developed a questionnaire that was adminis￾tered by several trained investigators. For the other assessments, all involved investigators, pediatri￾cians, ultrasonographers, and laboratory staff were trained to use uniform criteria and procedures. Identifying information concerning patients and samples was concealed from the laboratory and ultrasonography personnel. The rapid implemen￾tation of this study rendered it likely that some data would be incomplete. Patients We studied all children 36 months of age or young￾er who were brought to Peking University First Hospital for screening for urinary stones between September 17 and October 3, 2008. The study was approved by the hospital’s ethics committee. All the parents or guardians provided written informed consent. Questionnaire We administered a questionnaire designed to ob￾tain information about demographic characteris￾tics, including sex and age; the history of exposure to contaminated formula, including the brand, melamine content, duration of exposure, use of formula alone or a combination of breast milk and formula; birth type (preterm or term); and symptoms such as fever or vomiting and diarrhea within the 3-day period before the visit. Other signs and symptoms, such as oliguria, unexplained cry￾ing (especially on urination), and edema, and any history of passing stones were recorded. Categorization of Contaminated Formula The General Administration of Quality Supervi￾sion, Inspection, and Quarantine of the People’s Republic of China reported that 22 brands of in￾fant formula were contaminated (with reported concentrations of melamine ranging from 0.1 to 2500 ppm). On the basis of the amount of melamine contamination, we grouped the formulas into three categories: high-melamine formula (melamine content, >500 ppm), moderate-melamine formula (<150 ppm), and no-melamine formula. None of the brands tested contained melamine at a con￾centration between 150 and 500 ppm. Children had to have been fed formula for at least 30 days to be considered to have been exposed. The content of individual formulas is listed in the Supplementary Appendix (available with the full text of this ar￾ticle at NEJM.org). Laboratory Investigations Routine serum-chemical measurements included blood urea nitrogen, creatinine, and alanine ami￾notransferase levels. Urinalysis was performed, and we measured levels of urinary microalbumin (ref￾erence range, 0 to 19 mg per liter), transferrin (ref￾erence range, 0 to 2 mg per liter), α1-microglobulin (reference range, 0 to 12 mg per liter), and N-acetyl- β-d-glucosaminidase (reference range, 0 to 21 U per liter). Urinary calcium and creatinine levels were also measured. Detailed methods are found in the Supplementary Appendix. Ultrasonography of the Urinary Tract Ultrasonography of the kidneys and lower urinary tract was performed with the use of an ultrasonog￾raphy system (ProSound SSD-5000SV, Aloka) and an attached scanner monitor (5 to 6 MHz). Assess￾The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved