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

Romy van de Putte1, Hermien E K de Walle2, Kirsten J M van Hooijdonk1

  • 1Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center (Radboudumc), Nijmegen, the Netherlands.

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Invasive assisted reproductive techniques (ART), maternal obesity, and smoking increase VACTERL risk. Folic acid use may reduce congenital anomaly risk in newborns.

Keywords:
assisted reproductive techniquesfolic acid supplement useoverweightparitysmoking

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Area of Science:

  • Reproductive Medicine
  • Pediatric Genetics
  • Public Health

Background:

  • VACTERL association is a complex condition involving multiple congenital anomalies.
  • Previous studies linked VACTERL to assisted reproductive techniques (ART), pregestational diabetes, and chronic lower obstructive pulmonary disorders (CLOPD).
  • Further investigation into maternal risk factors is crucial for understanding VACTERL etiology.

Purpose of the Study:

  • To replicate previous findings on ART, pregestational diabetes, and CLOPD in relation to VACTERL.
  • To identify additional maternal risk factors associated with VACTERL.
  • To assess the impact of folic acid supplementation and smoking on VACTERL risk.

Main Methods:

  • A case-control study involving 142 VACTERL cases and 2,135 healthy controls.
  • Data collected via self-administered questionnaires.
  • Multivariable logistic regression analyses used to determine adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).

Main Results:

  • Invasive ART was associated with a significantly increased risk of VACTERL (aOR 4.4).
  • Primiparity and maternal pregestational overweight/obesity were identified as risk factors (aORs 1.5 and 1.8, respectively).
  • Maternal smoking nearly doubled the risk of VACTERL, while consistent folic acid use showed a potential protective effect (aOR 0.5).

Conclusions:

  • Invasive ART, primiparity, pregestational overweight/obesity, smoking, and lack of folic acid supplementation are key risk factors for VACTERL.
  • Findings highlight modifiable maternal factors influencing VACTERL risk.
  • Consistent folic acid use may mitigate the risk of these congenital anomalies.