Maternal factors increase odds of congenital vertebral malformations by 6x

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Image: PD

1.  Individuals with congenital vertebral malformations (CVM) are six times more likely to have had maternal exposure factors (MEF) compared to individuals with normal spine morphology.

2.  Maternal exposure factors include maternal insulin-dependent diabetes, alcohol, valproic acid, twins, hyperthermia, cigarette smoking, clomiphene, and assisted reproductive technology.

Mothers with a MEF during pregnancy are at enhanced risk for having children with a CVM.  The child is 6x as likely to have isolated CVMs and 7.6x as likely to have a CVM with additional CMs.  A positive dose-response relationship between MEFs and CVMs suggests that MEFs pose an additive risk for CVM.  The translational significance of these findings is two-fold.  First, it allows spine practitioners to identify causes of CVMs for families looking for answers.  Second, it outlines MEFs that should be avoided during pregnancy in order to prevent CVMs.

This study’s case-control nature limits the ability to identify possible MEFs as it relies on medical record notes.  Additional unobserved confounders could therefore be present.    A significant difference in mean age existed between the CVM and control groups, however a separate analysis restricted to patients under 20 years of age also showed statistically significant elevated odds ratios.  This is the first analysis of the association between MEFs and CVM development.  Future studies will serve to identify additional MEFs and quantify the risk of CVM for specific MEFs.

Click to read the study in Spine

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Image: PD

1. Individuals with congenital vertebral malformations (CVM) are six times more likely to have had maternal exposure factors (MEF) compared to individuals with normal spine morphology.

2.  Maternal exposure factors include maternal insulin-dependent diabetes, alcohol, valproic acid, twins, hyperthermia, cigarette smoking, clomiphene, and assisted reproductive technology.

This [case-control] study  reviewed 229 cases of congenital vertebral malformations (CVM) and 267 controls with normal spine morphology.  Subjects ranged in age from 1 to 50 years and were enrolled from three separate institutions.  CVM’s were identified by ICD-9 codes for the following: congenital scoliosis, anomalies of the spine, congenital absence of vertebra, hemivertebrae, Klippel-Feil syndrome, and supernumerary vertebra.  CVMs caused by a known genetic mutation were excluded.  Medical records of all cases were reviewed for documentation of significant maternal exposure factors MEFs that could be associated with CVM including: maternal insulin-dependent diabetes, alcohol, valproic acid, twins, hyperthermia, cigarette smoking, clomiphene, and assisted reproductive technology.

A maternal risk factor was identified in 18% of CVM cases as compared to just 2.6% in the control group.  An odds ratio (OR) of 6.0 (p<0.001) was found for CVM without additional congenital malformations (CM) and this increased to 20.2 when adjusted for age, sex, and institution. The OR for all CVMs including additional CMs was 7.6 with an adjusted value of 16.8.  Logistic regression analysis showed a positive dose-response correlation between the number of MEFs and risk for CVMs.

In sum: Mothers with a MEF during pregnancy are at enhanced risk for having children with a CVM.  The child is 6x as likely to have isolated CVMs and 7.6x as likely to have a CVM with additional CMs.  A positive dose-response relationship between MEFs and CVMs suggests that MEFs pose an additive risk for CVM.  The translational significance of these findings is two-fold.  First, it allows spine practitioners to identify causes of CVMs for families looking for answers.  Second, it outlines MEFs that should be avoided during pregnancy in order to prevent CVMs.

This study’s case-control nature limits the ability to identify possible MEFs as it relies on medical record notes.  Additional unobserved confounders could therefore be present.    A significant difference in mean age existed between the CVM and control groups, however a separate analysis restricted to patients under 20 years of age also showed statistically significant elevated ORs.  This is the first analysis of the association between MEFs and CVM development.  Future studies will serve to identify additional MEFs and quantify the risk of CVM for specific MEFs.

Click to read the study in Spine

By Chaz Carrier and Allen Ho

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