Diagnostic and perinatal outcomes in consanguineous couples with a structural fetal anomaly - a cohort study.

Introduction Consanguineous unions occur when a couple are related outside marriage. It is a common practice amongst UK Pakistanis and is associated with adverse genetic and perinatal outcomes for affected offspring. The objectives of this study were to evaluate the; (i) background characteristics; (ii) uptake of prenatal and postnatal investigation and; (iii) diagnostic outcomes of UK consanguineous couples presenting with a fetal structural anomaly. Material and methods This was a retrospective and partly prospective cohort study comparing consanguineous (n=62) and non-consanguineous (n=218) pregnancies with current or previous fetal structural anomalies reviewed in a UK prenatal genetic clinic from 2008-2019. Outcomes were compared using odds ratios (OR). Results Most consanguineous couples were of Pakistani ethnicity OR 29 (95% CI, 13-62) and required use of an interpreter OR 9 (95% CI, 4-20). In the consanguineous group, the uptake of prenatal invasive testing was lower; OR 0.4 (95% CI, 0.2-0.7) and the number declining follow-up OR 10 (95% CI, 3-34) was greater, compared to the non-consanguineous group. This likely explained the lower proportion of consanguineous couples where a final definitive unifying diagnosis to explain the fetal structural anomalies was reached OR 0.3 (95% CI, 0.2-0.6). When a diagnosis was obtained in this group, it was always postnatal and most often using genomic sequencing technologies OR 6 (95% CI, 1-27). The risk of perinatal death was greater OR 3 (95% CI, 1-6) in the consanguineous group, as was the risk of fetal structural anomaly recurrence in a subsequent pregnancy OR 4 (95% CI, 1-13). There was no difference in the uptake of perinatal autopsy or termination of pregnancy between groups. Conclusions Consanguineous couples are a vulnerable group in the prenatal setting. Although adverse perinatal outcomes in this group are more common secondary to congenital anomalies, despite the evolution of genomic sequencing technologies, due to a lower uptake of prenatal testing it is less likely that a unifying diagnosis is obtained and recurrence can occur. There is a need for proactive genetic counselling and education from the multi-disciplinary team, addressing language barriers as well as religious and cultural beliefs in an attempt to optimise reproductive options.