The impact of consanguinity on neonatal and infant health

Abstract

Marriage between biological relatives is widely popular in many parts of the world, with over 1000 million people living in countries where 20–50+% of unions are contracted between couples related as second cousins or closer. Consanguinity is, however, a controversial topic, in part due to public misunderstanding, complicated by often exaggerated past estimates of the adverse health outcomes. While some consanguineous couples are at high risk of conceiving a child with a genetic disorder, they are a small minority. Thus a multi-population meta-analysis has indicated an excess infant death rate of 1.1% in the progeny of first cousins, and even this figure may be compromised by inadequate control for non-genetic variables. The benefits as well as the disadvantages of consanguineous marriage are assessed and discussed, with specific consideration given to the health of migrant communities in Western countries, among whom first cousin marriage remains preferential.

Introduction

For clinical purposes, consanguinity is usually defined as a union between two individuals who are related as second cousins or closer. However, the most common form of consanguineous marriage worldwide is between first cousins, who on average have co-inherited 1/8 of their genes from one or more common ancestors. First cousin offspring will therefore be homozygous at 1/16 of all loci, which is conventionally expressed as a coefficient of inbreeding (F) of 0.0625 [4].

The most recent consanguinity estimate indicated that some 10.4% of the world population are either married to a biological relative or are the progeny of a consanguineous union [6]. In fact, because of a lack of information on consanguinity in many populous South and Southeast Asian countries, and in sub-Saharan Africa, this estimate is deliberately conservative. Furthermore, the data refer only to marriages in the most recent generation, when in many regions of the world consanguineous unions have been a long-standing tradition. For this reason, in a large majority of populations, including communities in which consanguinity previously was considered to have been rare, individuals often exhibit extensive, uninterrupted runs of homozygosity because of close kin marriages in former generations [11].

To a large extent the present-day distribution pattern of consanguineous marriage matches that of adherence to the Islamic faith. But there is no prescription that Muslims should marry within the family, and first cousin marriage is freely permissible in the Jewish, Christian Protestant, Buddhist and Zoroastrian/Parsi religions [7]. The preferred types of consanguineous marriage vary according to tradition, so that in Arab societies first cousin marriage between a man and his father's brother's daughter is most common, whereas in the Dravidian Hindu populations of southern India the strong preference is for a first cousin marriage between a man and his mother's brother's daughter, or more often marriage between an uncle and niece (F = 0.125).

First cousin and other more remote categories of consanguineous marriage are permissible under civil legislation virtually throughout the world. The USA is a notable exception, with varying forms and degrees of restrictive laws on consanguineous unions in 31 of the 50 states. Legislation on the prohibited types of cousin marriage dates back to the mid-19th century in some states, but in the case of Texas the prohibition was only introduced in 2005. Interestingly, equivalent civil law prohibitions on first cousin marriage apply in just two other countries, the People's Republic of China and the People's Democratic Republic of Korea.

In assessing the effects of consanguinity on health it is now accepted that variables such as socioeconomic status, maternal age, maternal education, birth order and birth intervals need to be adequately controlled. An additional factor that to date has not been fully considered is the impact of population subdivision on the expression of genetic disorders, even though intra-community marriage is the norm in regions where consanguineous marriage is favoured. Marriage in these populations is contracted within long-established, usually male lineages, e.g., within caste in India, intra-biraderi (literally brotherhood) in Pakistan, and within the hamula (clan) and tribe in Arab societies.

As inter-community gene flow is restricted in most traditional societies, adjacent villages and even co-resident sub-communities may exhibit different and quite distinctive inherited disease profiles, reflecting the influence of small population size and hence limited marriage partner choice, local founder mutations, and genetic drift [4]. Population stratification may therefore be a major influence in the measurement of consanguinity-associated morbidity and mortality, with straightforward comparisons between the progeny of first cousins and unrelated parents genetically invalid unless both sets of parents are known to be members of the same caste, biraderi, clan or tribe [3].