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Shorter Periconception Maternal Telomere Length and the Risk of Congenital Cardiac Outflow Defects in the Offspring: a case control study
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  • Damiat Aoulad Fares,
  • Rosalieke Wiegel,
  • Alex Eggink,
  • Sten Willemsen,
  • Joyce Van Meurs,
  • Regine Steegers-Theunissen
Damiat Aoulad Fares
Erasmus Medical Center
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Rosalieke Wiegel
Erasmus Medical Center
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Alex Eggink
Erasmus MC
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Sten Willemsen
Erasmus Medical Center
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Joyce Van Meurs
Erasmus Medical Center
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Regine Steegers-Theunissen
Erasmus MC, University Medical Centre
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Abstract

Objective: Congenital cardiac outflow defects (COD) are the largest group of congenital heart defects, with ventricular septal defect (VSD) as the most prevalent phenotype. Increased maternal age, excessive oxidative stress and inflammation are involved in the pathophysiology and enhance telomere length (TL) shortening. We aim to study the association between periconception maternal TL, as future predictive biomarker, and the risk of having a child with COD. Design: HAVEN-study, a multicenter case-control triad study conducted in the Netherlands. Setting and population: 306 case mothers of a child with COD and 424 control mothers of a child without a congenital malformation were selected. Methods: TL was estimated, on DNA from venous blood samples, by qPCR. Multivariable logistic regression was used to compute crude and adjusted odds ratios (OR) per standard deviation (SD) decrease between maternal T/S ratio and COD and VSD risk. Main outcome measures: The risk of COD in offspring. Results: A significant association was shown between maternal TL shortening (per standard deviation) and a 29% increased risk of VSD in offspring (OR 1.29(95% CI 1.04-1.61), P= 0,02), which remained significant after additional adjustment for maternal age (adjOR 1.25(95% CI 1.01-1.55), P= 0,04). No association between maternal TL and the risk of overall COD in offspring was observed. Conclusion: Shortening of maternal TL, due to maternal conditions including age, is associated with an approximately 1.3-fold increased risk, per SD in TL-shortening, of VSD in the offspring. These findings need further confirmation in other studies on the predictive value of maternal TL.

Peer review status:UNDER REVIEW

28 Mar 2021Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
07 Apr 2021Assigned to Editor
07 Apr 2021Submission Checks Completed
08 Apr 2021Reviewer(s) Assigned