OEIS complex: Prevalence, clinical, and epidemiologic findings in a multicenter Mexican birth defects surveillance program

Abstract

OEIS is the acronym of a malformations complex association including omphalocele, exstrophy of bladder or cloaca, imperforate anus, and spinal defects. It has a very low prevalence, ranging from 1/82,000 to 1/200,000 live births (LB). The etiology of OEIS is unknown. Virtually all cases are sporadic, and specific associated risk factors uncertain.ObjectivesThis study aimed to determine the prevalence, clinical spectrum, possible early pregnancy exposures, and demographic characteristics as potentially associated risk factors in a sample of Mexican cases.MethodsWe conducted a multihospital based case–control study on 12 cases with the OEIS complex identified in 1,195,020 LB born from January 1978 to December 2015. All comparisons performed were matching 1:3 the relation of cases and controls, respectively, considering the p‐value of ≤.05 as statistically significant.ResultsThe prevalence of OEIS was 1.004/100,000 (1/99,585) LB. The frequency of bladder/cloacal exstrophy was 75 and 25%, respectively, omphalocele was 83.3%, and imperforate anus and spinal defects, 75.0% each. Two pairs of twins discordant for the defect exhibited the severest OEIS phenotype. Except for the higher frequency of maternal first pregnancy trimester influenza infection, early perinatal mortality and a twining trend association, none other variable differed significantly.DiscussionThe prevalence of OEIS in our sample is within the highest reported worldwide. First‐trimester pregnancy maternal influenza infection and twining emerge as associated risk factors for OEIS. Although twin zygosity was not defined, the observed severest phenotypes in twins endorse the hypothesis that OEIS and monozygotic twinning are features of disturbances on early blastogenesis.

Recurrent constellations of embryonic malformations re‐conceptualized as an overlapping group of disorders with shared pathogenesis

“…Although the underlying causes for these malformation complexes are not known, prior studies have hypothesized defects in embryonic development (Arteaga‐Vázquez, Luna‐Muñoz, Morales‐Suárez, & Mutchinick, 2019; Jongbloet, 1987; Lubinsky, 2015; Lubinsky, 2017). The similar epidemiology combined with many reports of co‐occurrence suggest a common or at least overlapping etiology, such as defects in blastogenesis or very early in utero hypoxia, the timing of which may lead to a specific constellation of features that fit into one of the discrete groups discussed above.…”

“…The mutual association between RCEM disorders and twins, especially discordant MZ twins (Arteaga-Vázquez et al, 2019;Bartels et al, 2012;Dawson et al, 2016;Keppler-Noreuil et al, 2007;Kunapinun & Treetipsatit, 2017;Solomon et al, 2013;Werler et al, 2004;Wieczorek et al, 2007), separates them from other molecularly unsolved disorders such as Aicardi and Hallermann-Streiff syndromes (Boycott et al, 2018). Further, the few reports of genetic abnormalities have involved singletons and not twins.…”

NAD+ deficiency in human congenital malformations and miscarriage: A new model of pleiotropy

“…Single umbilical artery (SUA) is posited to be caused either due to primary agenesis or atrophy of an existing vessel (Blackburn & Cooley, 2006). SUA has been seen in all the multiple malformation conditions discussed here, along with being an isolated anomaly (Arteaga‐Vázquez et al, 2019; Duncan & Shapiro, 1993; Hunter et al, 2011; Jnah et al, 2015; Suri et al, 2000; Wheeler & Weaver, 2001).…”

“…However, in the original article, 23 of 29 patients detected in a hospital records review had either two or three of the features, but not complete OEIS (Carey et al, 1978). A study of cases in Mexico described the phenotypic spectrum of the 12 cases, of which four were OEIS, four were OES (omphalocele, exstrophy, and spinal defect), two were EIS (exstrophy, imperforate anus, and spinal defect), and two were OEI, (omphalocele, exstrophy, and imperforate anus; Arteaga-Vázquez et al, 2019).…”

“…In summary, the following organ systems have been reported to have defects in patients described to have LBWC, POC, OEIS, sirenomelia, OAVS, and VACTERL: cardiovascular, vertebral/ribs, urogenitary, sensory, limbs/digits, palate, CNS, respiratory, gastrointestinal, skin and lymphatic (Arteaga‐Vázquez et al, 2019; Aslan et al, 2004; Carey et al, 1978, Colpaert et al, 2000; Duncan & Shapiro, 1993; El Mansoury & Mbekeani, 2016; Fernández et al, 1997; Grigore et al, 2018; Hunter et al, 2011; Jensen et al, 1993; Jnah et al, 2015; Keppler‐Noreuil, 2001; Toyama, 1972; van de Putte, van Rooij, Marcelis, et al, 2020).…”