Maternal risk factors for the VACTERL association: a EUROCAT case-control study.

Abstract

The VACTERL association (VACTERL) is a very serious condition that includes at least three of the following congenital anomalies: vertebral, anorectal, cardiac, tracheo-esophageal fistula with or without esophageal atresia (EA/TEF), renal, and limb anomalies1, No major genetic risk factors have been identified yet and in most patients, VACTERL occurs sporadically, but familial inheritance and increased prevalence rates of component features in first-degree relatives are observed. The paper presents the results of a case-control study aimed to identify maternal risk factors for VACTERL association in offspring. The study was based on a large population of VACTERL cases (329 VACTERL cases, and 49,724 controls) retrieved from the JRC-EUROCAT Central Database. Data from 28 EUROCAT registries over the period 1997–2015 with ascertainment through hospital records, birth and death certificates, questionnaires and/or post-mortem examinations were include in the study. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals. The main outcome measure were adjusted ORs for maternal risk factors for VACTERL. The results show that for couples who conceived through assisted reproductive techniques, there is an increased risk of VACTERL (aOR = 2.3) in offspring. Pre-gestational diabetes (aOR=3.1) and chronic lower obstructive pulmonary diseases (aOR=3.9) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL. In conclusion, the study identified several maternal risk factors for VACTERL in offspring befitting a multifactorial aetiology.