Maternal factors, medications, and drug exposure in congenital limb reduction defects.

Abstract

As part of an ongoing study on all limb reduction defects occurring among 1,213,913 consecutive live births in the province of British Columbia, Canada, during 1952-1984, cases with documented maternal drug exposure and chronic maternal diseases were analyzed separately. This population-based study was made possible through the existence of an ongoing Health Surveillance Registry, which documents all infants born with congenital, genetic, or chronically handicapping conditions in the province of British Columbia. Strict rules of confidentiality are obeyed. For this part of the analysis of limb reduction defects, cases with documented maternal illness, drug abuse, and exposure to environmental hazards early in pregnancy were analyzed as a separate group to identify specific, recurring patterns of anomalies. A total of 51 cases with possibly related maternal factors were identified. Among them were five cases with maternal epilepsy, four cases with documented maternal diabetes, and three cases with uterine anomalies. Three infants, all born in 1962, had documented thalidomide exposure. It is rarely possible to identify particular teratogenic factors or specific maternal factors as etiologically related to the pattern of limb reduction defects or a spectrum of congenital malformations. Exposure to environmental factors during pregnancy is not reliably registered and can thus only occasionally be ascertained in retrospective studies. This means that very large numbers of cases and cross-referencing to other family members are required to assess whether a potential teratogen is related to limb defects or not.

Characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov

“…Human teratogens, such as thalidomide and rubella, can exert markedly different effects on the developing fetus. 25,26 In the clinical setting, there is no direct method for determining the extent of fetal exposure to a drug. 24 However, factors that define the extent of fetal exposure are likely to include: the concentration-time profile of the drug in the maternal circulation; the size, solubility, ionization, and protein binding of the drug; transfer of the drug in and out of the placental circulation; the extent of placental first-pass metabolism; and the rate of fetal clearance.…”

Birth prevalence for congenital limb defects in the northern Netherlands: a 30-year population-based study

“…During the gestational period, disruptive events, such as amniotic band or vascular disruptions, may cause amputation or hypoperfusion of the developing limbs [ 4 ]. Various CLD are due to prenatal exposure to different teratogens [ 5 ], the best-known example of which is thalidomide, which caused a wide range of CLD, especially intercalary reductions and preaxial defects, in the 1960s [ 6 ]. To prevent further tragedies, several international registries of congenital defects were established.…”

Phenotype-to-genotype description of prenatal suspected and postnatal discovered upper limb anomalies: a retrospective cohort study.

“…For example, radial polydactylies are more observed in non-isolated cases compared to ulnar polydactylies 24 . Furthermore, it is important to enquire about family history for upper limb anomalies, maternal medication use and intoxication to identify factors related to the anomaly 18,25 .…”