Risk Factors And Prevalence Of Limb Deficiencies Associated With Amniotic Band Sequence: A Population-Based Case-Control Study

Background: Limb deficiencies associated with amniotic bands comprise a wide range of congenital anomalies. The association of maternal medication and the risk of amniotic band sequence (ABS) has not yet been addressed. Methods: This nationwide population-based case-control study used national registers on congenital anomalies, births and induced abortions, cross-linked with information on maternal prescription medicine use obtained from the registers on Reimbursed Drug Purchases and Medical Special Reimbursements. All cases with congenital limb deficiency associated with amniotic bands born between 1996 and 2008 were included in the study. Five controls without limb deficiency matched for residency and time of conception were randomly selected from the Medical Birth Register. Results: In total, 106 children with limb deficiency associated with ABS were identified and compared with 530 matched controls. Young maternal age (less than 25 y) increased the risk of limb deficiencies [odds ratio=1.72; 95% confidence interval (CI): 1.06, 2.80]. Primiparity was also associated with increased risk [adjusted odds ratio (aOR)=2.42; 95% CI: 1.52, 3.88]. After adjusting for maternal age, pregestational diabetes, and parity, maternal use of beta-blockers (adjusted OR=24.2; 95% CI: 2.57, 228) and progestogens (adjusted OR=3.79; 95% CI: 1.38, 10.4) during the first trimester of pregnancy significantly increased the risk of limb deficiencies associated with amniotic bands. Conclusions: Primiparity significantly increased the risk of limb defects associated with amniotic bands. Also, a novel association on increased risk of ABS with maternal use of progestogens or beta-blockers during the first trimester of pregnancy was observed.