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. 2020 Nov;112(18):1495-1504.
doi: 10.1002/bdr2.1773. Epub 2020 Jul 22.

Maternal risk associated with the VACTERL association: A case-control study

Romy van de Putte  1 , Hermien E K de Walle  2 , Kirsten J M van Hooijdonk  1 , Ivo de Blaauw  3 , Carlo L M Marcelis  4 , Arno van Heijst  5 , Jacques C Giltay  6 , Kirsten Y Renkema  7 , Paul M A Broens  8 , Erwin Brosens  9   10 , Cornelius E J Sloots  10 , Jorieke E H Bergman  2 , Nel Roeleveld  1 , Iris A L M van Rooij  1
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Maternal risk associated with the VACTERL association: A case-control study

Romy van de Putte et al. Birth Defects Res. 2020 Nov.

Abstract

Background: The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors.

Methods: A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).

Results: Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL.

Conclusion: We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL.

Keywords: assisted reproductive techniques; folic acid supplement use; overweight; parity; smoking.

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Conflict of interest statement

The authors declare no potential conflict of interest.

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