Diagnostic and perinatal outcomes in consanguineous couples with a structural fetal anomaly: A cohort study

Abstract

Introduction Consanguineous unions occur when a couple are related outside marriage and is associated with adverse genetic and perinatal outcomes for affected offspring. The objectives of this study were to evaluate: (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 to 2019. Outcomes were compared using odds ratios (OR). Results Most consanguineous couples were of Pakistani ethnicity (odds ratio [OR] 29, 95% confidence interval [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 was greater (OR 10, 95% CI 3‐34) than in 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 counseling and education from the multidisciplinary team, addressing language barriers as well as religious and cultural beliefs in an attempt to optimize reproductive options.

Evolving fetal phenotypes and clinical impact of progressive prenatal exome sequencing pathways: cohort study

“…Demographic characteristics and outcomes of the study cohort are shown in Table 1. The rates of South Asian ethnicity and consanguinity were above average owing to the underlying demographics of the region, as described previously 13 . All causative pathogenic (Class IV and V) variants and incidental findings with corresponding outcome are shown in Table 2; the reported VUS are displayed in Table 3.…”

Cohort study of intervened functionally univentricular heart in England and Wales (2000–2018)

“…26 A recent study found that couples with consanguinity and Pakistani heritage were less likely to consent to invasive fetal testing and to genetic follow-up, which might make them more vulnerable to the risk of a pregnancy affected by congenital anomalies. 27 Therefore, the higher than expected proportion of children with South Asian heritage in our study could result from a combination of genetic predisposition and also parental views about pregnancy termination. Studies from the USA found lower survival rates with CHD in Black patients, 28 and with poorer socioeconomic circumstances in children with HLHS.…”

Prenatal genomic testing for ultrasound‐detected fetal structural anomalies

“…Incidental findings present ethical challenges as they may detect adult‐onset disorders, such as cancer predisposition genes, which may introduce unanticipated anxiety into the family, as well as potentially leading to stigmatisation and a loss of autonomy for the future child. A trio exome may also uncover non‐paternity, which has an estimated median rate of around 4%, and consanguinity, where the rate is dependent upon regional demographics 41,42 . Consensus recommendations exist to support these challenging circumstances 19,43 .…”

“…A trio exome may also uncover nonpaternity, which has an estimated median rate of around 4%, and consanguinity, where the rate is dependent upon regional demographics. 41,42 Consensus recommendations exist to support these challenging circumstances. 19,43 Another important consideration for counselling is who has ownership of the results, which can pose a concern for the wider family and raise the question of who owns the genetic material as part of the 'joint account'.…”