Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK; Department of Genetics, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK.
Lancet. 2013 Oct 19;382(9901):1350-9. doi: 10.1016/S0140-6736(13)61132-0. Epub 2013 Jul 4.
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.
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.
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.
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.
National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care programme.
先天性异常是婴儿死亡和残疾的主要原因，其在英国不同种族群体中的发病率有所不同。巴基斯坦裔儿童的婴儿死亡率最高，在这个族裔群体中，12 岁以下儿童死亡的最常见原因是先天性异常。我们调查了一个大型多种族出生队列中先天性异常的发生率，以确定该社区先天性异常过多的原因。
我们从布拉德福德出生研究中患有一种或多种异常的儿童的母亲那里获得了问卷数据，这是一项针对 13776 名婴儿及其家庭的前瞻性出生队列研究，招募工作于 2007 年至 2011 年进行。异常的详细信息被前瞻性地报告给了研究，并与医疗记录进行了交叉核对。我们将异常数据与作为布拉德福德出生研究一部分收集的母亲问卷和临床数据进行了关联。我们计算了各种母体危险因素的单变量和多变量风险比（RR）和 95%置信区间。
在有问卷数据的 11396 名婴儿中，有 386 名（3%）患有先天性异常。先天性异常的发生率为每 10000 例活产儿中有 305.74 例，而全国的发生率为每 10000 例中有 165.90 例。与英国白人原籍母亲相比，原籍为巴基斯坦的母亲的风险更高（单变量 RR 1.96，95%CI 1.56-2.46）。总体而言，2013 名（18%）婴儿是表亲通婚的后代。这些婴儿主要是巴基斯坦裔——在 5127 名巴基斯坦裔婴儿中，有 1922 名（37%）父母是表亲通婚。近亲通婚使先天性异常的风险增加一倍（多变量 RR 2.19，95%CI 1.67-2.85）；我们没有注意到与贫困程度增加有关的关联。在巴基斯坦裔儿童的所有异常中，有 31%可归因于近亲通婚。我们注意到，34 岁以上的英国白人原籍母亲的风险也有类似的增加（多变量 RR 1.83，95%CI 1.14-3.00）。母亲接受大学教育程度是保护性的（0.53，95%CI 0.38-0.75），与种族无关。
近亲通婚是先天性异常的主要危险因素。即使在调整了贫困程度后，这种风险仍然存在，并且几乎占巴基斯坦裔婴儿异常的三分之一。所有种族群体中，较高的教育程度都与较低的风险相关。我们的研究结果将在健康促进和公共卫生领域以及为那些提供产前、儿科和临床遗传服务的机构中具有重要价值。应向处于高风险的社区以及表亲通婚的夫妇提供有关风险的敏感建议，以协助生殖决策。
国家卫生研究院合作领导应用健康研究和护理计划。
