Birth defect risk for children of first cousins is overstated

The failure to account for significant social and cultural differences throws doubt on the study’s results. Shutterstock

Research about the impact of marriage between first cousins on rates of birth defects garnered much media attention when it was published late last week.

Sadly, most of the coverage worked to alarm rather than inform and failed to mention shortcomings in the paper that suggest the effect is exaggerated.

Instead, most headlines said marriage between first cousins doubles the risk of birth defects, creating a false impression of the genetic impacts made by such unions.

The research

Published in The Lancet, the paper is part of the Born in Bradford study that seeks to investigate the impact of consanguineous (close kin) marriage on health in childhood.

The study was based on 11,396 births between 2007 and 2011 and included data on 5,127 births in the local Pakistani community. Overall, 18% of babies were born to first cousin parents.

But there was a distinct ethnic imbalance in this aspect of the research, with fewer than 1% of children in the white British population born to first cousins in comparison with 37% in the Pakistani community.

The researchers found that, on average, the children of first cousins in the Pakistani community had a 3.6% greater risk of being born with a congenital anomaly than children born to unrelated couples, whose risk was 2.6%.

The overall findings are in close agreement with a study published last year, based on a meta-analysis of 17 populations living in six countries. That analysis showed 3.3% excess risk for serious congenital abnormalities in the children of first cousins.

But problems with the data collection in the Bradford study mean that the results may be misleading.

Too broad an umbrella?

The Bradford study is very comprehensive and includes information on a wide range of birth anomalies, such as heart and central nervous system disorders, oral and facial clefts, musculoskeletal disorders and urogenital defects.

The health outcomes of these defects can vary widely, and while some may be life-threatening others are clinically much less serious. For example, ventricular septal defects (a fault in the wall dividing the two vertical parts of the heart) were the single most common form of anomaly, affecting 54 of the 740 children diagnosed with an abnormality.

In many of these cases, the health of the child is little affected. Indeed, an Israeli study found that this form of septal anomaly spontaneously corrected in 89% of children by the time they were 10 months old. So its inclusion inflates the number of “defects”, when whether it is a serious health problem is questionable.

And this isn’t the only issue with the research.

Overlooking culture

A major problem in assessing the effects of close kin unions is that consanguineous marriage has many interacting cultural, demographic, ethnic, religious and socioeconomic aspects. Researchers need to control for a very wide range of variables.

If due allowance is not made for each of these factors, health risks ascribed solely to marriage among first cousins will inevitably be exaggerated.

In a city such as Bradford, where the authors noted 43 different ethnic origins among their subjects, this would be a monumental, and practically impossible, task.

While the researchers made a very creditable attempt to meet this requirement by controlling for nine major variables (including maternal age and education, a measure of social deprivation, smoking and alcohol consumption prior to and during pregnancy, obesity and diabetes), there are other considerations not accounted for that would influence their results.

More than genes

Not all congenital anomalies are genetic in origin. Particularly in low-income countries, maternal infections such as rubella, cytomegalovirus and toxoplasmosis can cross the placenta and cause severe damage to the developing foetus.

This possibility needs to be kept firmly in mind as transnational marriages between UK-born and Pakistani partners are still favoured by many families in the UK Pakistani community, including those who would have been counted in the study.

From a genetic perspective, the UK Pakistani community is notably heterogenous with community members subdivided by biraderi membership. Biraderi, which literally translate as “brotherhoods”, are traditional male lineages that function as kinship, occupational and social networks. They are also strongly involved in marriage partner choice, with a large majority of marriages occurring within the biraderi.

Disappointingly, the authors were unable to collect representative information on biraderi membership.

Not being able to control for this division into genetic and sociocultural sub-communities seriously undermines the claim that 31% of congenital anomalies in the UK Pakistani population are solely due to marriage between first cousins. In such small sub-groups, restricted marriage-partner choice means that mutations can spread rapidly and affect a large, unrepresentative proportion of individuals.

The bigger picture

More generally, in discussing such marriages, attention to and respect for cultural factors is critical, and cooperation with community elders and religious advisors is vital.

In the Bradford Pakistani community, marriage between close family members is widely believed to offer significant benefits to the couple, who often have known each other from childhood, and to strengthen family ties.

For many couples and their respective families, the birth of a child with a congenital anomaly is viewed as an expression of divine will. In such cases, genetic explanations may be irrelevant and thus emotionally loaded.

Data from the Born in Bradford study can provide the basis for further, more wide-ranging research into the health effects of marriage between first cousins. But the perceived social and economic benefits of marriage within extended families can’t be ignored, especially in vulnerable low-income communities.