Congenital limb deficiencies with vascular etiology: Possible association with maternal thrombophilia

Congenital limb deficiency defects (LDDs) are etiologically heterogeneous. Acquired causes include amniotic bands, teratogens exposure, and chorionic villus sampling before 10 weeks' gestation and intrinsic causes include single-gene disorders and chromosome abnormalities. However, a substantial number of cases, especially terminal transverse deficiency defects, occur without an obvious cause and are ascribed to vascular disruption events. Some studies have found an association between maternal thrombophilia and congenital LDDs. We investigated this association through a review of all prenatally identified LDDs at a major tertiary care center in Toronto, Canada over a 12-year period. Our results showed a higher prevalence of thrombophilias among women with a pregnancy affected with an LDD when compared to the general population [χ² (3) = 54.63, P < 0.01]. Our research was strengthened by the inclusion of affected pregnancies regardless of outcome, and strict criteria to avoid including LDDs with a non-vascular etiology. Most LDDs were identified during the routine 18-20 week anatomy ultrasound, but some were discovered as early as 13 weeks' gestation. We found an excess of left-sided defects among terminal transverse but not longitudinal deficiencies; additionally, all diagnoses of maternal thrombophilia occurred in the terminal transverse group. Our results support thrombophilia screening in all women with a prenatally diagnosed fetal LDD as well as careful evaluation of the fetal extremities during prenatal ultrasounds in women with a known thrombophilia. © 2016 Wiley Periodicals, Inc.