Descriptive and risk factor analysis of nonsyndromic sacral agenesis: National Birth Defects Prevention Study, 1997–2011

Abstract

Sacral agenesis is a rare birth defect characterized by partial or complete absence of the sacrum. We sought to (a) describe case characteristics, (b) estimate birth prevalence, and (c) identify risk factors for nonsyndromic sacral agenesis using data from the National Birth Defects Prevention Study (NBDPS). The NBDPS was a population-based, case-control study involving pregnancies with estimated dates of delivery from October 1997 through December 2011. We estimated birth prevalence using all NBDPS eligible cases. Using self-reported maternal exposure information, we conducted multivariable logistic regression analysis to identify potential risk factors overall and among women without diabetes. The birth prevalence of sacral agenesis was 2.6/100,000 live births. In the multivariable analysis, multifetal pregnancy, pre-existing Type 1 diabetes, and pre-existing Type 2 diabetes were positively and significantly associated with sacral agenesis, albeit estimates were imprecise. Preexisting Type 1 diabetes was the strongest risk factor (adjusted odds ratio = 96.6, 95% confidence interval = 43.5-214.7). Among women without diabetes, periconceptional smoking was positively and significantly associated with sacral agenesis. Our findings underscore the importance of smoking cessation programs among women planning pregnancy and the importance of better understanding the role of glycemic control before and during pregnancy when designing interventions for primary prevention of sacral agenesis.

Maternal diabetes‐related malformations inUtah: A population study of birth prevalence 2001–2016

“…It is widely acknowledged and known for decades that sacral agenesis and caudal dysgenesis were associated with maternal diabetes in pregnancy. Nalbandyan et al (2019) recently provided additional evidence of this association from the National Birth Defects Prevention Study documenting an adjusted odds ratio of 96 (confidence interval 43.5–214.7). The evidence for femoral hypoplasia being caused by pregestational diabetes is primarily clinical (Laccaruba‐Flores et al, 2018).…”

“…The cases of maternal DRM identified for the estimate of prevalence were the offspring of mothers with pregestational diabetes documented in the UBDN with specific outcomes. To assign the maternal diabetes as the cause, the mother had to have evidence of type 1 or 2 pregestational diabetes mellitus and to have delivered a fetus or infant with one or more of the following selected DRMs based on convincing evidence in the literature (Correa et al, 2008; Miller et al, 2010; Castori, 2013; Oyen et al, 2016;Nasri et al, 2018; Ryan et al, 2019; Chen et al, 2019; Nalbandyan et al, 2019; Tinker et al, 2020): sacral agenesis/caudal dysgenesis, femoral aplasia/hypoplasia, multiple vertebral defects, holoprosencephaly, heterotaxy, conotruncal heart malformations, bilateral renal defects (renal a/dysplasia), microtia, and anencephaly. All cases of sacral agenesis (full or partial) and caudal dysgenesis were lumped together into a single category (Nalbandyan et al, 2019).…”

“…To assign the maternal diabetes as the cause, the mother had to have evidence of type 1 or 2 pregestational diabetes mellitus and to have delivered a fetus or infant with one or more of the following selected DRMs based on convincing evidence in the literature (Correa et al, 2008; Miller et al, 2010; Castori, 2013; Oyen et al, 2016;Nasri et al, 2018; Ryan et al, 2019; Chen et al, 2019; Nalbandyan et al, 2019; Tinker et al, 2020): sacral agenesis/caudal dysgenesis, femoral aplasia/hypoplasia, multiple vertebral defects, holoprosencephaly, heterotaxy, conotruncal heart malformations, bilateral renal defects (renal a/dysplasia), microtia, and anencephaly. All cases of sacral agenesis (full or partial) and caudal dysgenesis were lumped together into a single category (Nalbandyan et al, 2019). In the determination there were seven cases where the mother had apparent gestational diabetes and the infant had the most typical of DRMs, that is, caudal dysgenesis or femoral hypoplasia syndrome (Castori, 2013; Nasri et al, 2018); we elected to include these cases under the assumption that based on the distinctive outcome, these mothers had pregestational diabetes.…”

Exome sequencing identifies variants in infants with sacral agenesis

“…Maternal diabetes mellitus during organogenesis is by far the most important. Maternal smoking has also been reported to be associated with increased risk of SA in the National Birth Defects Prevention Study (NBDPS) (Nalbandyan et al, 2019).…”

Atypical caudal regression syndrome with lumbar agenesis, hypoplastic sacrum without sacro-iliac joints in the Eastern Democratic Republic of Congo: A case report

“…Regarding the most common form of sacral agenesis, it can be syndromic or non-syndromic, it is due to varying degrees of congenital development failures [4,5]. This condition is observed in 1 to 25,000 living births and it is clinically marked by diverses clinical manifestations dependent on the segment concerned [6,7].…”