Elsevier

The Lancet

Volume 382, Issue 9901, 19–25 October 2013, Pages 1350-1359
The Lancet

Articles
Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study

https://doi.org/10.1016/S0140-6736(13)61132-0Get rights and content

Summary

Background

Congenital anomalies are a leading cause of infant death and disability and their incidence varies between ethnic groups in the UK. Rates of infant death are highest in children of Pakistani origin, and congenital anomalies are the most common cause of death in children younger than 12 in this ethnic group. We investigated the incidence of congenital anomalies in a large multiethnic birth cohort to identify the causes of the excess of congenital anomalies in this community.

Methods

We obtained questionnaire data from the mothers of children with one or more anomalies from the Born in Bradford study, a prospective birth cohort study of 13 776 babies and their families in which recruitment was undertaken between 2007 and 2011. Details of anomalies were prospectively reported to the study and we cross checked these details against medical records. We linked data for anomalies to maternal questionnaire and clinical data gathered as part of the Born in Bradford study. We calculated univariate and multivariate risk ratios (RRs) with 95% CIs for various maternal risk factors.

Findings

Of 11 396 babies for whom questionnaire data were available, 386 (3%) had a congenital anomaly. Rates for congenital anomaly were 305·74 per 10 000 livebirths, compared with a national rate of 165·90 per 10 000. The risk was greater for mothers of Pakistani origin than for those of white British origin (univariate RR 1·96, 95% CI 1·56–2·46). Overall, 2013 (18%) babies were the offspring of first-cousin unions. These babies were mainly of Pakistani origin—1922 (37%) of 5127 babies of Pakistani origin had parents in first-cousin unions. Consanguinity was associated with a doubling of risk for congenital anomaly (multivariate RR 2·19, 95% CI 1·67–2·85); we noted no association with increasing deprivation. 31% of all anomalies in children of Pakistani origin could be attributed to consanguinity. We noted a similar increase in risk for mothers of white British origin older than 34 years (multivariate RR 1·83, 95% CI 1·14–3·00). Maternal education to degree level was protective (0·53, 95% CI 0·38–0·75), irrespective of ethnic origin.

Interpretation

Consanguinity is a major risk factor for congenital anomaly. The risk remains even after adjustment for deprivation, and accounts for almost a third of anomalies in babies of Pakistani origin. High levels of educational attainment are associated with reduced risk in all ethnic groups. Our findings will be valuable in health promotion and public health, and to those commissioning antenatal, paediatric, and clinical genetic services. Sensitive advice about the risks should be provided to communities at increased risk, and to couples in consanguineous unions, to assist in reproductive decision making.

Funding

National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care programme.

Introduction

Infant mortality varies substantially between ethnic groups in the UK, with the highest rates noted in babies of Pakistani origin.1 Overall, the most common causes of infant mortality are immaturity-related disorders;1 however, in babies of Pakistani origin, the most common cause is congenital anomaly.1 Every year, about 90 extra deaths occur because of congenital anomalies in infants born to Pakistani mothers in England and Wales than would have been expected in this group if they had the same mortality rate as infants born to white British mothers.2 Causes of this excess are unclear.

Findings from a UK study in 1993 suggested that consanguineous unions were the cause of the excess in congenital anomalies in babies of Pakistani origin,3 but no adjustments were made for deprivation, which has been associated with increased risk.2 Although women of Pakistani origin are more likely to live in regions of high deprivation and to earn less than their white British counterparts,4 the disparity in risk of congenital anomaly cannot be wholly explained by socioeconomic differences between groups. For example, parents of infants of Bangladeshi origin have a similar socioeconomic profile to those of infants of Pakistani origin, but the risk of congenital anomalies is much lower.2 Causes of the excess risk in babies of Pakistani origin continue to be debated in the UK by the Chief Medical Officer,5 in the medical literature,6, 7, 8 and often heatedly in the public press.9, 10 However data to clarify the issue are scarce.

Bradford is an ethnically diverse city in the north of England where levels of deprivation are high. Infant mortality in Bradford has been consistently above the national average, peaking at 9·4 deaths per 1000 livebirths in 2003, when the national average was 5·5 deaths per 1000 livebirths.11 Levels of congenital anomalies and childhood disability in Bradford are among the highest in the UK,12, 13, 14 and an excess of deaths occur in babies of Pakistani origin because of such anomalies.11 We analysed the Born in Bradford dataset, and a separate substudy of babies born with anomalies, to investigate the causes for the excess of congenital anomalies in this community.

Section snippets

Born in Bradford cohort

The Born in Bradford study is an ongoing prospective birth cohort study that recruited 12 453 women with 13 776 pregnancies between 2007 and 2011, and monitors them, their infants, and their partners.15 The dataset contains information about demographics (including deprivation) and clinical outcomes and risk factors. To be eligible for the study, women had to attend the antenatal service in Bradford between March, 2007, and December, 2010, and be booked to give birth in Bradford. Full details

Results

The figure shows a flow diagram for inclusion of cases. 518 babies were reported with an anomaly (figure). The appendix provides details of recorded anomalies. Comparison of rates with other regional registers was based on 740 anomalies noted in the 451 babies remaining after exclusion of those with a minor anomaly (figure). We based all other analyses on the 386 cases for whom Born in Bradford questionnaire data were available. The comparison group were the 11 010 pregnancies for which

Discussion

This is the largest report of contemporary congenital anomaly data for the offspring of consanguineous unions in the UK. Our findings show that consanguinity was a major risk factor for congenital anomaly, independent of deprivation, and accounted for almost a third of anomalies in babies of Pakistani origin. High levels of educational attainment were associated with reduced risk in all ethnic groups, and advanced maternal age was associated with increased risk. The frequency of consanguinity

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