The release of a study on congenital birth defects in Iraq has been met with controversy, with some experts questioning its methodology and peer review. Paul C Webster reports.

WHO officials have stepped in to defend an unsigned and sharply criticised report released by the Iraqi Ministry of Health (MOH) on congenital birth defects in areas where US-led coalition forces used toxin-laced munitions.

Although several recent studies from Iraq reported worrying rates of congenital birth defects in areas where highly toxic munitions such as depleted uranium shells were used by British, US, and other coalition forces, the new study, which was cofunded by the Iraqi Government and WHO, found “no clear evidence to suggest an unusually high rate of congenital birth defects in Iraq”. After initially referring questions about the study to Iraqi officials, Jaffar Hussain, WHO's Head of Mission in Iraq, told the The Lancet last week that the report is based on survey techniques that are “renowned worldwide” and on the work of international experts who peer reviewed the data “extensively”.

The study, which is based on a 2012 survey of mothers in 10 800 households from 18 Iraqi districts, relies largely on mothers' memories of the details of spontaneous abortions, stillbirths, and births with congenital defects since the 1980s (43 387 pregnancies). Citing a lack of medical records for older events, the Iraqi Government interviewers were able to view medical files for only 32% of the total reported cases.

Although warning that the surveyed mothers' recollections might not be accurate, the report does note a three-fold increase in reported birth defects between 1988–92 (7·6 per 1000 births) and 2003–07 (26·2 per 1000 births). Nonetheless, it asserts “the rates for spontaneous abortion, stillbirths and congenital birth defects found in the study are consistent with or even lower than international estimates”. The reported stillbirth rate for 2008–12 is considerably lower than WHO-established norms, the study indicates, leading it to suggest “possible underreporting of stillbirths, or that stillbirth rates in Iraq are lower than estimated elsewhere”.

WHO says that since the issue of associating birth defects “with exposure to depleted uranium has not been included in the scope of this particular study, establishing a link between the [congenital birth defects] prevalence and exposure to depleted uranium would require further research”. According to Jaffar, “there is still further room for more detailed analysis” and WHO is discussing producing a more detailed report with the Iraqi MOH.

The study notes that WHO offered technical services to the Ministry, and that WHO convened an “expert peer review meeting” on the study in late July with six experts from the London School of Hygiene and Tropical Medicine (LSHTM), University College London (UCL), the US Centers for Disease Control and Prevention (CDC), and the Norway-based Fafo Research Foundation. WHO says this meeting was organised after “it was determined the work should also undergo the scientific standard of peer review”.

That may not have been fully achieved, however. Simon Cousens, professor of epidemiology and statistics at LSHTM, who was among those invited by WHO to review the study, says he “attended a relatively brief meeting of around one and a half hours, so just gave some comments on an early presentation of the results. I wouldn't classify that as thorough peer review.”

At the CDC in Atlanta, Georgia, spokeswoman Belsie Gonzalez confirmed that CDC officials “did participate in the peer review meeting at the invitation of the WHO Regional Office for the Eastern Mediterranean. CDC did not participate in any aspects of the study. We provided data interpretation advice on the report.”

Several of WHO's expert reviewers raise methodological concerns about the study. Its “main limitation is that it is largely based on what people reported, without any medical examination”, says Cousens. At the Fafo Foundation in Oslo, social anthropologist John Pedersen adds that the study's limited geographical scope (Iraq has more than 100 districts) sharply reduces its relevance in understanding the national pattern and prevalence of birth defects in Iraq. “I wouldn't necessarily have designed the study in the same way as it was designed”, explains Pedersen, who notes that lower rates of birth defects could be expected from mothers' recollections than if doctors had been asked to report them.

Children who were born with birth defects in Fallujah (pictured November, 2009) Copyright © 2013 Getty Images

“I agree with Jon Pedersen that there are limitations in the study design”, says Bernadette Modell, emeritus professor of community genetics at UCL. “However, it is really difficult to conduct epidemiological studies of congenital disorders outside a high-income setting, because many congenital disorders are difficult to diagnose without sophisticated clinical and laboratory facilities and a relatively high proportion of those that occur in lower-income settings may be due to environmental causes.”

Taking these limitations into account, Modell adds, “I think the Iraq study was pretty good, and as objective as was feasible. I was particularly impressed with the efficient organisation of data-collection when the study was underway. The reviewers all agreed that the data provide no evidence to support claims of an epidemic of congenital anomalies either nationally, or in any particular area. However, the study amassed a very large amount of data, which needs further analysis, ideally with expert assistance.”

Keith Baverstock, author of a 2004 UN report that highlighted the potential seriousness of Iraq's legacy of intensive exposure to depleted uranium ordinance employed by British and American troops both during the First Gulf War of 1991, and after the US-led occupation in 2003, says the report's reliance on the term “peer review” does not conform with conventional usage. “It's really misleading”, he charges. “I have to question what the role of WHO is in this study as a whole”, Baverstock adds after noting that the study names no authors from WHO or the Iraqi MOH although a WHO website does explain it did provide “technical assistance on study design, methodology, data collection, data analysis and report writing”. For his part, WHO's Jaffar confirms that “the ownership of study and the authorship of the report is with the MOH from the outset”.

Researchers in Iraq, the UK, and the USA who have probed congenital birth defects and have published recent peer-reviewed studies also express concerns about the methodology employed by the Iraqi MOH and WHO.

Although WHO says that “at this point no effort to neither substantiate nor negate the findings of other studies can be employed because the study is not aiming to establish cause-effect associations between [congenital birth defects] prevalence and environmental risk factors”, the study issued by the Iraqi Government states that “in recent years there have been several anecdotal reports of geographical regions with an unusually high prevalence of congenital birth defects in Iraq. Most of the reports did not meet the norms for an objective study of birth defects, and a review of the published literature could find no clear evidence to support their findings.”

Samira Alaani, a paediatrician in Fallujah, Iraq, who copublished a 2011 study utilising hospital records to conclude that congenital malformations accounted for 15% of all births in Fallujah since 2003, says the new study cofunded by WHO and the Iraqi Government should have employed hospital records more comprehensively.

Muhsin Al-Sabbak of the Basrah Medical School in Basrah, Iraq, who copublished a 2012 study reporting a 17-fold increase in birth defects in the Al Basrah Maternity Hospital since 1994, warns that the data from Basrah in the new study does not match local hospital records.

Alison Alborz is a specialist on learning disabilities in children at the University of Manchester, UK, who published a 2013 study presenting data from a 2010 survey of 6032 households in four Iraqi governates including data for more than 10 000 children and young people showing a prevalence of congenital birth defects more than 2·5 times higher than reported in the Iraqi Government study. She says the new report gives little information about sampling and does not offer any discussion of whether the districts chosen for analysis “reflect the characteristics of the governorate as a whole”.

Mozhgan Savabieasfahani, a toxicologist based in Michigan, USA, who coauthored the Alaani and Al-Sabbak studies, agrees with Alborz that the selection criteria determined by the MOH are not sufficiently explained. “Based on information available in this report, we cannot rule out selection bias issues”, she warns. She also questions the decision not to employ hospital records more comprehensively, and notes that the report suffers from a lack of detail regarding “which areas were exposed to bombardment or heavy fighting and which areas were not. The exposed and unexposed populations remain unidentified throughout.”

Tariq Al-Hadithi of the Hawler Medical University in Erbil, Iraq, who undertook the literature review cited by the Iraqi Government in describing the work of Alaani, Al Sabbak, Alborz, and Savabieasfahani as not meeting objective norms, reached a conclusion that was far more tentative than the Iraqi Government suggests. “As not enough data on pre-1991 Gulf War prevalence of birth defects are available”, Al-Hadithi stresses, “the ranges of birth defects reported in the reviewed studies from Iraq most probably do not provide a clear indication of a possible environmental exposure including [depleted uranium] or other teratogenic agents.”