Recently in Pediatrics Category
As just about everyone knows by now, the Special Masters of the US Court of Federal Claims handed down their decisions on Friday, which deny a causative link between the vaccine preservative thimerosal and autism in 3 test cases.
Among the many opinions rendered in the decisions from the Special Masters (see here, here, and here) are discussions of the autism studies published by Mark and David Geier—whose work has been criticized sharply and at length at this blog and in my 2009 letter to the Journal of the Neurological Sciences.
The court's Special Master George Hastings, for instance, writes in his decision re King v Secretary of Health and Human Services:
[M]ost of the epidemiologic studies that have addressed the thimerosal/autism causation issue have failed to find any association between thimerosal-containing vaccines and autism, but there have been certain exceptions. Those exceptions were studies published by the research team of Dr. Mark Geier and his son David Geier[*]...To be sure, the petitioners in this case have not cited or relied upon those Geier studies in their post-hearing briefs, because, as I will discuss below...the petitioners argue that all of the epidemiologic studies done to date are irrelevant to the petitioners' causation theory in this case. However, since I find that the epidemiologic studies are of relevance, I have found it reasonable to examine those Geier studies, to see if they afford any significant counterweight to the many contrary studies...
After careful consideration, I conclude that the Geiers' studies cannot be given any weight. A number of those studies were considered by the Institute of Medicine (IOM) committee that fully studied the entire thimerosal/autism causation issue in 2004. That committee concluded that the studies were so flawed as to be "uninterpretable," and that the studies contributed nothing meaningful ("noncontributory") concerning the causation issue...The committee noted that the studies were based on databases that themselves had "significant limitations"...and that the studies had "serious methodological problems"...or "serious methodological limitations"...The committee added that the Geiers' articles describing their analytical methods were "not transparent" and omitted "important details," so that it was impossible to evaluate the studies...Other specific deficiencies in the studies were also discussed, including the fact that the Geiers incorrectly used several epidemiologic terms and measures.
In addition, Dr. Fombonne [respondent's expert] agreed with the IOM's criticisms of the Geier studies, and testified that the Geier studies in general failed to use accepted epidemiologic methods...Dr. Rutter [respondent's expert] was critical of the Geier studies as well...Further, petitioners' own expert witness concerning epidemiology, Dr. Greenland, agreed with the criticisms of the Geier articles, acknowledging that those studies are "deficient in methodology"...And none of the expert witnesses for the petitioners vouched for the reliability of the Geier studies.
I have reviewed the published Geier studies discussed in the 2004 IOM report, and I agree with the analysis of those studies set forth in that IOM report. Further, I have reviewed the additional studies published by the Geiers since the 2004 IOM report, and find that those studies suffer from the same type of flaws as the earlier Geier studies. That view includes a study published in 2008 by the Geiers, along with Young as the third author. Two of respondent's experts, Drs. Fombonne and Rutter, testified that that 2008 study was again deeply flawed, and those experts provided a number of specific examples of deficiencies in the study...And, again, none of the petitioners' experts testified in support of that 2008 Young, Geier, and Geier study.
In summary, I conclude that all of the Geier epidemiologic studies are not reliable, and cannot be accorded any weight.
In a lengthy footnote from the decision handed down in the case of Mead v Secretary of HHS, Special Master Patricia Campbell-Smith writes,
Although the studies conducted by Dr. Mark Geier and his son purport to find an association between thimerosal-containing vaccines and autism, their studies have been criticized consistently by various reviewers, including petitioners' own expert epidemiologist, as methodologically deficient...(Dr. Rutter [characterized] the 2008 Young study—that was conducted in part by Dr. Geier and his son...as a poorly designed study for the following reasons: (1) the researchers used a "strange" study design that is both a cohort study [a controlled study] and a time-trend analysis of the available database information [an ecological study] and (2) the researchers included emotional disturbance as one of the neurodevelopmental disorders observed following exposure to thimerosal-containing vaccines even though emotional disorders are not included in any of the official psychiatric classifications systems for neurodevelopmental disorders). The undersigned has reviewed carefully the presented studies conducted by the Geiers and has considered the criticisms leveled against the Geiers' studies. Persuaded that the studies are flawed methodologically in critical respects, the undersigned, without addressing the studies in extensive detail here, declines to accord any evidentiary weight to the studies. The undersigned notes that other researchers have been unable to verify the validity of the Geiers' statistical analysis on a number of occasions and a number of courts have expressed concerns about the reliability of their work.
Campbell-Smith goes on to cite 8 court cases in which the Geiers' work was called, among other things, "unintelligible," or in which Dr. Geier's testimony was described as "not reliable."
In her decision for the third test case, Special Master Denise Vowell affords special attention to the Young, Geier, and Geier study of 2008—which was specifically pulled apart at this blog and by Epi Wonk.
The only studies demonstrating a relationship between TCVs [thimerosal-containing vaccines] and ASD [autism spectrum disorder] are those in which Dr. and Mr. Geier appear as co-authors, including the Young study published in May, 2008, and funded by the OAP PSC [Omnibus Autism Proceeding Petitioners' Steering Committee]...Because petitioners’ own expert commented that the Geier studies were not reliable as evidence... and they were thus not addressed by respondent’s experts, I do not discuss the earlier Geier studies any further. In view of the numerous criticisms of the earlier Geier studies and petitioners' own expert’s dismissal of them, I have placed no reliance on them.
The Young study was an ecological analysis using the VSD database...Doctor Greenland [petitioners' expert] did not comment on this study during his testimony, as the article was introduced after his appearance and excusal. The study found an increased risk of ASD, based on increasing exposure to TCVs. Doctor Fombonne offered several criticisms of this study. In a critique common to many of the studies performed by Dr. and Mr. Geier, Dr. Fombonne commented that the Young article did not provide the data that would allow others to verify the calculations performed.
Doctor Fombonne reproduced one chart from the article...Using the chart, he explained that the birth cohorts used in the study did not all contain the same number of individuals, with most representing 40,000 children...One birth cohort, that of children born in 1990, contains only 2,000 children...When this "outlier" is removed, the purported statistical relationship between ASD and TCVs during the first four years of the sample disappears.
Doctor Fombonne was also highly critical of the authors' addition of invented numbers to the 1995 and 1996 data from the VSD...If the adjustments are removed, there is no correlation at all between the increase in thimerosal exposure and increase in autism cases per 10,000...Doctor Fombonne commented: "It’s dishonest to impute like 45 new cases which are just invented to top up the prevalence in a way which is supportive of their hypothesis. It’s clear that these investigators have a clear track record to do with the data that supports their hypothesis. And I’ve seen that in their previous papers."
Doctor Rutter offered similar criticisms of the Young study...calling it "a poor study for several different reasons"...It began with a cohort design, but ended up being analyzed as a time trend study. That required the authors to make adjustments to the first and last cohorts. Doctor Rutter described this as "putting together chalk and cheese in the hope of gazpacho soup coming out"...The "analytic design and strategy was not a satisfactory one."
He pointed to Table 3 as a striking example of the poor design...Table 3 compares "neurodevelopmental disorders" to several control disorders, measuring the difference in rates of the disorder developing in the cohorts that received 100 micrograms more mercury. The table shows higher rate ratios for autism, ASD, ADD/ADHD, developmental or learning disorders, disturbance of emotions, and tics...Doctor Rutter called this table an example of demonstrating a statistical effect without showing a causal effect...If the neuroinflammation hypothesis is correct, it is difficult to explain how neuroinflammation causes tics or disturbance of emotions. The study reported TCV effects across a very broad range of unconnected disorders having different ages of onset, different genetic factors, and different disease courses...The broad range of effects in these diverse disorders caused Dr. Rutter to be "immediately skeptical as to what [the study] shows."
He also questioned why "disturbance of emotions" was listed in the category of neurodevelopmental disorders, noting that anyone knowledgeable about the field of neurodevelopmental disorders would not have categorized it as one, and would have placed it with the control disorders...To prove their hypothesis that increased mercury exposure causes increases in neurodevelopmental disorders but not control disorders, the authors have to demonstrate that mercury is associated with increased rates of one but not the other. If "disturbance of emotions" was properly placed with the list of control disorders, it would undercut the authors' hypothesis. Their comparison between the two groups is therefore invalid.
Vowell also comments on a reanalysis of the Young et al data by Young herself, who found no association between birth year (which was purported to be associated with exposure to TCVs) and ASD when the imputed cases were removed.
Doctor Young’s subsequently-filed letter indicated that she reanalyzed the data to respond to Dr. Fombonne's criticisms. After she removed the 1990 birth cohort (the one containing only 2,000 cases) and the notional cases for 1995 and 1996, the results for autism, ASD, and unspecified developmental disorders lost statistical significance...She nevertheless defended the use of the 1990 birth cohort and her adjustments to the numbers for 1995 and 1996.
Vowell also dismisses the study of Young et al on the basis of its funding source.
For the reasons indicated in the criticisms proffered by Drs. Fombonne and Rutter, I have accorded the Young study little weight. An additional reason for viewing this study as unreliable is the conflict of interest generated by the PSC’s funding of the study. In its opinion on remand in Daubert, the Ninth Circuit considered whether the matters an expert proposed to testify about flowed from research conducted independently of involvement in the litigation in question, noting that this factor provides objective proof that the research was conducted for scientific purposes.
Yet, despite these unequivocal, disparaging opinions on the work of Geier and Geier, they continue to find sympathetic medical publishers. Their latest article (pdf here) can be found in the Journal of Toxicology and Environmental Health, Part A, which has now published the Geiers' work on 5 occasions.
In their latest article, the Geiers (along with Janet Kern of the Genetic Consultants of Dallas) again try to link the excretion of some urinary porphyrins (their dubious pet marker for mercury toxicity) with ASD severity. The study is very similar to their previously published work in the JNS, and one wonders if there isn't substantial overlap in the study subjects (26 vs 28 children).
Despite the suspicion, the tabulated presentation of the Geiers' urinary porphyrin data in JNS (nanomoles per gram of creatinine) makes it virtually impossible to compare these numbers with their urinary porphyrin values in the latest article (which are presented in "normalized" uP levels). Similar objections can be raised of their graphed data, primarily because of differences in the presentations of the x-axes.
N.B.--The Geier studies reviewed by Special Master Hastings included the following:
The most common, identifiable form of pediatric epilepsy, absence seizures (formerly known as petit mal seizures) were first described in the early 18th century by (you guessed it) a French guy. Effective and relatively safe pharmacologic treatment for the condition has been available since 1960, when ethosuximide (Zarontin) was introduced by Parke-Davis (now a subsidiary of Pfizer, like just about every other drug company).
Absence seizures are also responsive to valproic acid (aka Depakene or Depakote; Abbott), which was FDA approved for treatment of the disorder in 1978, and lamotrigine (Lamictal; GSK), which has been studied for the treatment of absence seizures since at least the late 1990s.*
Despite our extensive clinical experience with these drugs, it was unknown which provided the best empirical therapy for absence epilepsy. In fact, Glauser and other neurologists at the University of Cincinnati concluded in 2006 that it was "impossible to develop an evidence-based guideline" for the initial, monotherapy treatment of generalized seizures and specifically those in children, because of the "alarming lack of well-designed, properly conducted" randomized, controlled trials. This finding evidently prompted Glauser and his colleagues to conduct a randomized, double-blind multicenter trial of the 3 drugs in children with newly diagnosed absence seizures—the results of which are available in today's issue of the NEJM.
Among 453 children with new-onset absence epilepsy, Glauser et al found that ethosuximide or valproic acid were significantly more likely to result in a primary composite outcome of seizure control and tolerability (~50%-60% of patients) than lamotrigine (~30% of patients) after 4 months. Attentional deficit, a secondary outcome measure, was significantly more likely with valproic acid than ethosuximide (49% vs 33%).
Commenting at MedPage Today, Glauser said, "[E]thosuximide gave the child the best chance to get the combination of seizure control without side effects or [adverse] effects on attention."
So ethosuximide, it is; then valproic acid; then lamotrigine.
* Although lamotrigine is not FDA approved for the treatment of absence seizures specifically.
The characteristic 3-per-second spike-and-wave EEG pattern of absence epilepsy from An Introduction to Epilepsy.
The continuing mumps outbreak in New York and New Jersey—which has affected more than 1500 individuals, most of them Orthodox Jewish boys—is traced to an 11-year-old who visited Britain in June of last year, reports the CDC.
More than 7400 laboratory-confirmed cases of mumps were recorded in the United Kingdom in 2009. The case number is lower than those seen during the epidemic of 2004 and 2005, the UK Health Protection Agency reports, but greater than cases reported during 2007 and 2008.*
The US mumps outbreak continues despite the relatively high rate of vaccination among the infected—88% had received at least 1 vaccine dose; 75%, 2 doses. However, the mumps component of the MMR vaccine provides less protection than the measles or rubella components. The CDC provides an estimated mumps-vaccine efficacy of 73%-91% after 1 dose and 79%-95% after 2 doses.
Among the most common symptoms of mumps among boys is orchitis, or testicular inflammation. According to one source, about 20% of prepubertal boys will develop this painful condition. Consequent risks include testicular atrophy and sterility.
* A resurgence of mumps and measles cases in the United Kingdom is blamed on reduced vaccination rates--which are believed to be (at least partly) the result of the 1998 study of Andrew Wakefield et al linking the MMR vaccine with autism. The discredited study was recently retracted by The Lancet.
Photo of child with parotid gland swelling due to mumps from the CDC/NIP/Barbara Rice.
That rang 12 years ago.
Yesterday, editors of The Lancet officially retracted publication of a 12-year-old debunked study that linked the MMR vaccine to autism, according to the journal's web site, numerous news sources, and countless blogs. The study is believed to be responsible for declining vaccination rates among children in the United Kingdom and the resurgence of measles.
The journal's decision comes on the heels of an announcement last week from the UK's General Medical Council, which found that 3 of the article's authors—Andrew Wakefield, John Walker-Smith, and Simon Murch—did not act in the best interests of the study's 12 pediatric enrollees. Wakefield, in particular, was cited for "callous disregard" toward his subjects, by plying them with a few pounds in exchange for blood samples at a birthday party. The GMC's report is provided courtesy of Kathleen Siedel at her neurodiversity blog.
The Council's investigation of Wakefield and others was prompted by the investigative reporting of Brian Deer from The Sunday Times. Beginning in 2004, Deer alleged that Wakefield not only held significant financial conflicts of interest, but that he actually manufactured data. Responding to Deer's initial investigation, 10 of the study's 13 authors (including Walker-Smith and Murch) retracted their "interpretation" in a letter to The Lancet.
So where does a discredited UK doctor go? Austin, Texas, evidently. Wakefield is Executive Director of The Thoughtful House Center for Children, a questionable research and treatment center for children with autism. However, Wakefield does not have a license to practice medicine in the state, according to the online database of the Texas Medical Board.
A London pediatrician's diary shows that Haiti desperately needs, more than surgeons, supplies and coordination.
Writing for the Evening Standard, Dr. Nathaniel Segaren of the Caris Foundation, logs his week of guilt, frustration, appall, effort, and anguish among the mayhem. He concludes, "I realise we can be of most help with our knowledge of the city's geography and our ability to speak a combination of French, English and Creole." The ultimate intent becomes to select, with exceptional agony, those patients for transfer to a floating US Navy hospital—which is already beyond capacity.
"There are lots of egos here and mini power struggles," Segaren observes, "People are desperate to claim credit and get maximum media coverage."
From the UN via Flickr: Photo of 18-year-old Haitian girl with head trauma being transported to USS Comfort, a floating hospital.
In an apparent effort to atone for every Microsoft error message, the Gateses are committing $10 billion USD over the next 10 years for the research, development, and delivery of mortality-reducing vaccines to "the world's poorest countries." Some details of the financial pledge are available in today's press release from the couple's philanthropic foundation. The donated money is in addition to the foundation's already committed $4.5 billion for vaccine R&D.
The foundation's new support is motivated by recent data from the Johns Hopkins Bloomberg School of Public Health, which showed that a 90% vaccination-coverage level* in developing countries would prevent the deaths of about 7.6 million young children during the next decade. The number of lives saved could be ramped up to 8.7 million, if a malaria vaccine is introduced in the year 2014.
Another inspiration for the Gateses' pledge is the success of the rotavirus vaccine. In this week's NEJM, pooled results of a randomized, multicenter trial in South Africa (n = 3166 infants) and Malawi (n = 1733 infants) showed that a live, oral rotavirus vaccine (Rotarix; GSK) reduced cases of severe gastroenteritis due to the organism by 61% (4.9% vs 1.9%).**
Also reported in this week's issue, the recent introduction of rotavirus vaccines in Mexico reduced diarrhea-related deaths by 35% among children younger than 5 years of age (18.1 vs 11.8 deaths per 100,000 children). The life-saving benefit of vaccination was even more apparent among infants younger than 11 months (41% mortality reduction).
Vaccine researchers looking for a chunk of the Gateses' big money can start here. But the foundation only accepts letters of inquiry (LOIs) from 501(c)(3) organizations and other nonprofits. Individuals need not apply.
* Which would include new vaccines for diarrheal illnesses and pneumonia.
** Although there was no significant difference in mortality, 2.5% vs 2.6%.
While the FDA and Allergan remain at an impasse on how to disseminate off-label safety information for Botox, the American Academy of Neurology (AAN) just published its recommendations for use of the toxin in children with spasticity due to cerebral palsy (CP).*
On the basis of 14 20 controlled studies (N = 573) in which botulinum toxin A was assessed in children with CP-related limb spasticity, the AAN recommends injections for localized arm or leg spasticity "that warrants treatment." Although, the Academy writes, "There is insufficient evidence to support or refute the use of [botulinum toxin A] to improve motor function in this population."
In its safety assessment, the AAN found the most common treatment-related adverse events to be localized pain, excessive weakness, unsteadiness, increased falls, and fatigue. A few patients experienced urinary incontinence (n = 5) or dysphagia (n = 2). All adverse events were transient and did not require hospitalization or cause death—despite the fact that, last year, the FDA announced postmarketing reports of toxin spread, which compromised breathing and possibly led to death. The agency continues to investigate these cases.
According to lead author of the AAN guidelines, Mauricio Delgado, CP is the most common cause of spasticity in children, and most children with CP have spasticity. In Western nations, the prevalence of CP among 8-year-olds is 0.36%.
* An unapproved use.
No. 1: Pandemic H1N1
You were expecting something else?
Coming out of left field (ie, Mexico)* in April, the novel 2009 H1N1 ("swine flu") virus caused an official global pandemic in June, according to the World Health Organization. Cases mounted rapidly, but fear of disease was mitigated by its relatively low mortality rate.** Drawing on their experience from the swine-flu epidemic of 1976, leading US neurologists first believed that a government-led vaccination campaign would be unlikely because of 1) low mortality and 2) the possibility of vaccine-associated Guillain-Barre syndrome (GBS). Boy, were they wrong.
In August, the CDC released its recommendations for the administration of developing H1N1 vaccines to 5 groups. The surprise: Instead of the historically targeted elderly, the CDC prioritized vaccination for children, young adults, and pregnant women because of their emerging risks of disease-related complications and death. Consequently vaccination was recommended for an estimated 159 million Americans as soon as vaccines became available, sometime in mid-October.
In May, the DHHS had contracted with 5 companies—CSL Biotherapies, GSK, MedImmune, Novartis, and sanofi-pasteur—to produce either injectable or nasally administered vaccines for pandemic H1N1 to the tune of $932 million. Government orders for another $883,977,920 and $438,143,025 were placed in July and September, respectively. The total amounted to about 9 bucks per vaccine, which was being produced by the traditional method of viral incubation in fertilized chicken eggs.
This tried-and-true method ultimately led to a delay in vaccine production for 2 primary reasons: the fastidious nature of the 2009 H1N1 virus (when compared with seasonal influenza viruses) and limited chicken eggs. Turns out the pandemic virus required 2 eggs to create a single vaccine dose, instead of the usual one. By October, the federally contracted companies had only cranked out about 10% of the promised 120 million vaccine doses for US residents. Time was a-wastin'.
In October, the CDC investigators estimated that about 3 million citizens had already experienced symptomatic pandemic flu between April and July, on the basis of a probabilistic model. Confirming previous assessments, the incidence of disease and disease-related hospitalizations were considerably higher in children and young adults. Pandemic flu, overall, had necessitated about 14,000 hospitalizations and had caused about 800 deaths in the United States.
The following month, the CDC estimated that up to 34 million Americans had been infected between April and mid-October. Respective hospitalizations and deaths now ranged from 63,000 to 153,000 and from 2500 to 6000. Another age breakdown revealed that disproportionate numbers of younger adults (and to a lesser extent, children) remained susceptible to pandemic flu generally and severe disease specifically. About 45% of Americans who had died from pandemic flu had been healthy.
And then disease began to wane. Earlier this month, only 25 states reported widespread activity. At the same time, data showed that the pandemic flu vaccines (the supplies of which were up) remained effective and were comparably safe. Specifically the risk of GBS appeared no higher than the typical background rate.
The latest recommendations: More than 30 "major health care provider organizations," including the American Medical Association, the American Academy of Pediatrics, and the American Red Cross, are encouraging all US residents to receive a pandemic flu vaccine in anticipation of another wave of infection. An "open letter" to the American people states,
The H1N1 flu vaccine is safe, effective, and the best way to protect yourself and your family from the H1N1 flu. Over 110 million doses...are now available, with more coming every day. Now is the time to protect yourself and those around you by getting vaccinated against the H1N1 flu.
Links to selected Pathophilia posts on pandemic flu (and a few on seasonal flu) are provided here in chronological order.
* Instead of the historically expected East Asia.
** Estimated in the United States at 0.007%-0.032%.
Depiction of H1N1 virus from Wikipedia.
From 2002 to 2006, the prevalence of autism spectrum disorders (ASDs) increased significantly among 8-year-old American boys and girls.* This conclusion is based on a newly published, retrospective review from the CDC's Autism and Developmental Disabilities Monitoring (ADDM) Network. The CDC investigators ascribe the increased prevalence of ASDs to improved recognition and documentation, but they cannot dismiss a concomitant "true" increase in ASDs.
On the basis of an examination of health and education records at 11 US sites participating in the ADDM Network, the average prevalence of ASDs among 8-year-olds in 2006 was 9.0 per 1000 children (range, 4.2-12.1), or nearly 1%. Among the 10 US sites that provided data for both 2002 and 2006, the overall prevalence of ASDs increased significantly, by 57%. This finding contrasts with a comparison of data from 2000 and 2002, which revealed no significant increase in the overall prevalence of ASDs.
Below are the tabulated prevalence values for ASD at the 10 common sites, stratified by sex, ethnicity, and IQ. These data show consistent across-the-board increases in ASD among the assessed pediatric subgroups.
|
Group |
ASD Prevalence, |
Statistically Significant Increase, % | |
|
2002 |
2006 | ||
|
Overall |
6.0 |
9.4 |
57 |
|
Boys |
9.5 |
15.2 |
60 |
|
Girls |
2.3 |
3.4 |
48 |
|
Non-Hispanic white children |
6.6 |
10.2 |
55 |
|
Non-Hispanic black children |
5.4 |
7.6 |
41 |
|
Hispanic children |
3.2 |
6.1 |
91** |
|
IQ ≤70 |
2.6 |
3.5 |
35 |
|
IQ 71-85 |
1.0 |
1.4 |
90 |
|
IQ >85 |
1.8 |
3.1 |
72 |
The CDC investigators note that the average prevalence of ASDs was higher at sites that had access to health and education records (10.0) than at sites with only health records (7.5). This observation suggests that more opportunities for ASD documentation increase the prevalence of the condition (artificially). Investigators also found that, generally, ASDs were recognized at younger ages in 2006 than in 2002. (And if I'm correctly reading the CDC data, they indicate that significantly more children with below-normal IQs are being classified as having ASDs—a phenomenon that may also explain an increased prevalence of ASDs.)
Most of the children identified as having ASDs in 2006 (70%-90%) displayed developmental problems (eg, language delay) before the age of 3 years; however, the average age at diagnosis was considerably later, at about 4½ years (suggesting lost time for crucial behavioral interventions). In 2006 assessment, most 8-year-olds with ASDs (76%-96%) were receiving special education through public-school programs, under a wide variety of rationales (eg, autism, emotional disturbance, learning disability, language impairment, etc).
The CDC advises that the ADDM Network surveillance sites were selected "on the basis of their ability to conduct active ASD records-based surveillance," and were not intended to be a nationally representative sample. However, the Network accessed the records of more than 300,000 children, representing nearly 8% of all 8-year-olds in the United States.
Data supporting the approximate 1% prevalence of ASDs include a 2007 parent survey and several contemporary international studies, says the CDC.
* ASDs are defined on the basis of documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder; pervasive development disorder, not otherwise specified; and Asperger disorder. The age of 8 years is identified as a "reasonable index age at which to monitor peak prevalence for ASDs." ASD symptoms are usually observed before the age of 3 years.
** The whopping increased prevalence of ASDs in Hispanic children is attributed to the increase in the Hispanic population overall and a prevalence increase of 144% in Arizona. The other Network sites did not reveal an increased prevalence of ASD among Hispanic children.
Fifty-four of 57 Nigerian children died between October 2008 and January 2009 after receiving a liquid acetaminophen preparation that was tainted with diethylene glycol (DEG). Exposure to the branded teething product, My Pikin,* was determined in 96% of the identified cases of unexplained acute renal failure (ARF) in the 57 children, according to a retrospective surveillance study performed by Nigerian officials, the CDC, and the US FDA. Their report is available in the latest issue of the MMWR.
The surveillance study was prompted by clusters of unexplained ARF cases in very young children (≤3 years of age) among hospitals in Lagos, Kadun, and Osun in the fall of last year. Initial reports led to the identification of the DEG-tainted product, a full product recall, and the shutting down of the responsible manufacturer in Lagos, Barewa Pharmaceuticals. Despite a nationwide recall and a press release in November of last year, which resulted in the confiscation of 7616 of 15,000 bottles of the contaminated drug, more than a quarter of the affected children received the product after the recall was announced.
Among children for whom data were available, the median time from drug exposure to ARF was 5.6 days (range, 0-24 days), and the mean time between the onset of ARF and death was 6.8 days (range, 1-19 days). Treatments with dialysis, received by 24 children, and the ethylene-glycol antidote fomepizole, received by 2 children, did not appear to prolong survival.
The MMWR editors report at least 12 episodes of DEG contamination in oral or topical medications during the last 70 years, which have caused at least 450 deaths. (Most of these episodes are described here and here.) The contamination was almost always due to the intentional economic-driven substitution of DEG for the more expensive solvents of glycerin or propylene glycol. (An account of the US deaths that occurred in 1937 due to a DEG-tainted antibiotic solution has been provided in numerous serial posts at this blog [search for "sulfanilamide" or "Massengill," for example], and the deceased are listed on this page.)
Prevention of DEG-contaminated drugs is easy and cheap, according to the editors. "Simple, rapid, and low-cost assays" that use thin-layer chromatography are available to detect and measure DEG at levels of 2% in liquid acetaminophen products and 6% in glycerin, they report.
* DEG accounted for 17%-21% of the My Pikin liquid medication by weight in sampled bottles. According to the MMWR, another contaminated acetaminophen-based syrup, made by a different manufacturer, was discovered to contain 0.5% DEG.
Photo of My Pikin Baby Teething Formula from Vanguard.
