First, interviews were conducted 6 weeks to 2 years following delivery, which raised the likelihood of recall bias. For example, 25 percent of women could not remember which antibiotic they had taken (Ailes, 2016). Another weakness was that only two thirds of women agreed to participate, and there were diferences in ethnicity and socioeconomic status between cases and controls. These factors potentially led to selection bias (Reefhuis, 2015). In addition, medical records were not reviewed to veriy dosage, and this precluded assessment of dose-response relationships. And a major limitation was that because the NBDPS included only a small number of cases of each birth defect and analyzed them for multiple maternal exposures, it was not possible to adjust for multiple comparisons. As a result, some of the associations observed were likely due to chance (Alwan, 2015). For example, the study of antibiotics and birth defects included 43 comparisons and identiied four signiicant associations, but chance alone predicted that two associations would be identiied (Ailes, 2016). Last, the low absolute risk of an abnormality complicates counseling and prenatal management. In many instances, the risk identiied by the NBDPS was as low as 1 case per 1000 exposed pregnancies.
These studies begin with cohorts of pregnant women who are exposed or unexposed to a particular medication. The percentage of infants or children afected with birth defects is examined in each cohort. Because individual birth defects are rare, cohort studies require a vey large sample size. Medicaid datasets and private insurance claims databases are commonly used for cohort studies of teratogenicity in the United States (Ehrenstein, 2010). Inability to adjust for confounding variables-such as the indication for which the medication was needed-may be an important limitation of this study design.
Potentially harmful agents may be monitored by clinicians who prospectively enroll exposed pregnancies in a registry. he FDA (20 17b) maintains an active list on their webpage titled Pregnancy Registries. As of 2017, this included registries for 100 individual medications and for medication groups used to treat asthma, autoimmune disease, cancer, epilepsy, human immunodeiciency virus (HIV) infection, and transplant rejection. Similar to case series, exposure registries are hampered by lack of a control group. The prevalence of an abnormality identiied through a registry requires knowledge of the baseline prevalence of that anomaly in the population. Investigators typically use a birth defect registry to assess population prevalence. One example is the Metropolitan Atlanta Congenital Defects Program, which is an active surveillance program established in 1967 for fetuses and infants with birth defects.
medications in pregnancy. Five categories-A, B, C, D, and
X-were intended to summarize available evidence from