What We Do and Don't Know About Melamine

As details of the melamine contamination scandal continue to emerge, many of our pre- and post-adoptive parents are wondering how potential exposure to this chemical may affect their child. I wish we knew more. But I'd like to start by offering some general information about melamine, and some tentative guidelines about how to manage this issue.

Melamine is a chemical with a number of industrial uses, and an already scandalous history as one of the major contaminants in the 2007 Chinese pet food debacle. It is suspected that it was added to milk at milk collecting stations in China to disguise the fact that milk was being watered down, since melamine artificially increases the testable protein content. We don't yet know how long this has been a problem. According to Sanlu, a popular budget formula manufacturer implicated in this event, contaminated milk was used in the manufacture of infant formula processed before 8/6/08, as well as in other dairy products like liquid milk, frozen yogurt, and coffee creamer.

There is essentially no reliable toxicology information about melamine and human consumption. The animal data suggests that it is not metabolized in the body, and is excreted in urine. At high doses in animals, it can cause bladder stones, and inflammation of the bladder. Over time, this may be carcinogenic, but we have no human studies to evaluate this risk.

The high number of serious kidney complications and deaths in pets exposed to contaminated food has been linked to the particularly toxic combination of melamine and cyanuric acid. We have not seen reports of cyanuric acid in human-consumed milk products, but it can be a contaminant in melamine products.

What is additionally confusing is that in animals, melamine alone can cause bladder stones (a mixture of melamine, protein, uric acid and phosphate), but has not caused kidney stones or kidney failure. The preliminary reports from China, however, do indicate that a small fraction of children who received contaminated formula have been diagnosed with kidney stones, reportedly containing uric acid. We are told that 4 infants have died, perhaps from obstruction of their kidneys from such stones, and 150 children have had renal failure. I don't know what to make of the high number of reported hospitalizations (over 14,000), and suspect that some of those may have been for workup and not because of illness.

Symptoms to Watch For

Please keep in mind that recently adopted children have plenty of more common and benign reasons for crying. That said, here are some things to watch for that would deserve prompt evaluation:

Unexplained crying episodes or abdominal pain, especially with urination
Passing blood, crystals, or particles in urine
Dramatic decrease in urine output
Swelling of the hands, feet, or around the eyes (edema)
Pain when tapped over the kidneys
Unexplained lethargy or vomiting

Our Evolving Approach

What remains unclear is which children deserve what workup. I'll cover our clinic's current approach here (which may be updated as consensus evolves and new information becomes available):

So far, we are checking a urinalysis with microscopy (to look for blood or crystals), and an electrolytes/BUN/creatinine panel (to look for signs of impaired kidney function) on all new Chinese adoptees. We may also add more routine ultrasound of kidneys, ureters, and bladder to look for stones themselves (see below).
Many of our previously adopted children have had some of these tests, but we are asking any symptomatic children (see above) to come in for urine & blood testing, and for an ultrasound, or perhaps CT scan if our suspicion is very high.
Children who came home from China in the past 3 or so years (vague because we don't know how long melamine has been a contaminant) who are asymptomatic should probably have at least a non-urgent urinalysis, if they have not previously had one. If they've been growing well and are asymptomatic, and have no other reason to need a blood draw, I'm not convinced that bloodwork is necessary. But we may start ultrasounding more routinely for this group as well.
A reasonable diagnostic code to use would be V87.39: contact with and (suspected) exposure to other potentially hazardous substances (for asymptomatic children), or codes based on a child's specific symptoms.
As for specific testing for melamine itself in blood or urine, we are not doing that at this time. Such testing is investigational and hard to come by, and given the expected fairly rapid excretion of melamine, may not be of much clinical use. Plus, children may be exposed to insignificant amounts of melamine from other sources, which would complicate interpretation of results.
Treatment of children with stones may involve close observation, IV fluids and urine alkalinization, medical management of acute renal failure if present, and various procedures to break up and remove recalcitrant or obstructing stones.

What is currently controversial is whether ultrasounds should be a routine screening test for asymptomatic Chinese adoptees with normal urinalysis. Thus far, we're not sure, and we have a low threshold to order ultrasounds if we're not sure about the "symptomatic" part, and are happy to order them for concerned parents. There have been several reports of renal stones diagnosed by ultrasound in otherwise asymptomatic children with normal urinalysis and bloodwork. If more of these are confirmed, we probably will start routinely ultrasounding. What remains unanswered is how common are these cases, and what needs to be done if asymptomatic stones are discovered.

We are in discussion with our local kidney and urology specialists, as well as other adoption docs, about the advantages and drawbacks of more universal ultrasound screening for Chinese adoptees. There are other radiographic approaches, such as a CT KUB (non-contrast) or CT urogram (with contrast), which can give better resolution for children in whom we highly suspect stones based on symptoms or labs, but the substantial amount of radiation exposure (and cost) with CT scans makes them unattractive for routine screening.

We've not yet seen any children in our practice with diagnosed kidney stones or other complications. According to informal data from Half the Sky, less than 5% of exposed children in the orphanages they work with have been diagnosed with kidney problems. And without stones and renal complications, we think it unlikely that melamine-exposed children will have significant long-term impacts. But we will keep you posted here as we learn more. And as always, please do involve your child's medical provider. Their opinion on this as-yet-fuzzy issue may not be the same as ours, and they know your child better than the internet does.

Useful Melamine Resources

The World Health Organization (WHO) has an excellent overview of melamine contamination in China
The Hong Kong Journal of Pediatrics has published an excellent melamine overview and editorial (pdf), with new details and thoughtful analysis (link courtesy of Dr Gordina)
The New England Journal of Medicine has a good overview of the global implications of the melamine contamination scandal
JCICS has posted a helpful FAQ, including some reports from Half the Sky about affected children in their orphanages
The Canadian Public Health Agency has a helpful set of melamine resources
Our Centers for Disease Control (CDC) has a good FAQ as well
"China Milk Issue" YahooGroup, an active listserv of concerned parents (and a few docs), with database of their test results
Parent-organized survey collecting preliminary data regarding results of tests on children adopted from China who may have been exposed to melamine. Please consider adding your information here, to better understand the scope of the problem.

Recommendations from the Chinese Ministry of Health:

(via the WHO, as of 10/08 - check here for updates):

The World Health Organization has agreed to circulate the information contained herein regarding the treatment plan that is being implemented in China by the Ministry of Health. The information below does not reflect the rules, regulations, policies and guidelines of the World Health Organization.

The following regimen has been issued by the Ministry of Health, China.
Clinical manifestations

Unexplained crying, especially when urinating, possible vomiting

Macroscopic or microscopic haematuria

Acute obstructive renal failure: oliguria or anuria

Stones discharged while passing urine. For example, a baby boy with urethral obstruction with stones normally has dysuria

High blood pressure, edema, painful when knocked on kidney area

Key diagnostic criteria

Been fed with melamine-contaminated infant milk formula

Having one or more of the above clinical manifestations

Laboratory test results: routine urine tests with macroscopic or microscopic haematuria; blood biochemistry; liver and kidney function tests; urine calcium/creatinine ratio (usually normal); urinary red blood cell morphology shows normal morphology of red blood cells (not glomerular haematuria); parathyroid hormone test (usually normal).

Imaging examination: preferably ultrasound B exam of urinary system. If necessary, abdominal CT scan and intravenous urography (not to be used in case of anuria or renal failure). Kidney radionuclide scans can be used where available to evaluate renal function.

Ultrasound examination features:

General features: bilateral renal enlargement; increased echo on solid tissue; normal parenchyma thickness; slight pyelectasia and calicectasis; blunt renal calyx. If the obstruction locates in the ureter, then the ureter above the obstruction point dilates. Some cases have edema with perinephric fat and soft tissue around the ureter. As the disease develops, the renal pelvis and ureter wall may have secondary edema. A few cases have ascites.

Stone features: most stones affect the collecting system and ureters on both sides. Ureteral stones are mostly at pelviureteral junction, the part where the ureter passes across iliac artery, and ureter-bladder junction. Stones stay collectively, covering massive areas. Lighter echo in the background. Most stones are different from the calcium oxalate stones. Urinary tract is mostly completely obstructed by the stones.

Differential diagnosis

Haematuria differentiation: need to rule out glomerular haematuria.

Stone differentiation: the stones are normally radiolucent and have a negative image on urinary tract x-ray. This feature differentiates the stones from those of radiopaque stones of calcium oxalate and calcium phosphate.

Differentiation of acute renal failure: need to rule out pre-renal and renal failure.

Clinical treatment

Immediately stop using melamine-contaminated infant formula milk powder.

Medical treatment: use infusion and urine alkalinization to dispel the stones. Correct the water, electrolyte and acid-base imbalance. Closely monitor routine urine tests, blood biochemistry, renal functions, ultrasound findings (with particular attention to the renal pelvis, ureter expansion, and the change of the stones in shape and location). If the stones are loose and sand-like, they are very likely to be passed out with urine.

Treatment of complicated acute renal failure: priority should be given to the treatment of life-threatening complications such as hyperkalemia. Measures include the administration of sodium bicarbonate and insulin. If possible, blood dialysis and peritoneal dialysis can be used early. Surgical measures can be taken to remove the obstruction if necessary.

Surgical treatment: if medical treatment is not effective, and hydrocele and kidney damage present, or blood dialysis and peritoneal dialysis are not available in case of renal failure, surgical methods can be considered to remove the obstruction. Stones can be removed by different methods including cystoscope retrograde intubation into the ureter, percutaneous kidney drainage, surgical removal and percutaneous kidney stone removal. Extracorporeal shock wave lithotripter (ESWL) is greatly limited in its application, because the stones are loose and mainly composed of urate, and the patients are infants.

Follow-up
Once the urinary obstruction is relieved, and the general condition and renal function and urination are back to normal, the children can be discharged.
Key issues to follow-up
Urine routine tests; ultrasound of urinary system; renal function tests; IVP (intravenous pyelogram) if necessary.