ABSTRACT
BACKGROUND: Use of HMG-CoA reductase inhibitors (statins) is becoming increasingly common. However, a recent study based on a series of cases reported to FDA suggests possible teratogenic effects of statins on embryogenesis, such as limb defects and severe central nervous system anomalies. METHODS: In a prospective, observational cohort study with a comparison group to examine a fetal toxicity risk of statins, we followed 64 pregnant women taking statins, and 64 comparison group women without exposure to known teratogens. The statin group women were exposed to atorvastatin (n=46), simvastatin (n=9), pravastatin (n=6), or rosuvastatin (n=3) during the first trimester. RESULTS: There was no difference in the rate of major malformations between the statin group (1/46 live birth: 2.2%) and the comparison group (1/52 live birth: 1.9%, p=0.93). Similarly, there were no statistical differences between the statin and comparison groups in live births (71.9% vs 81.2%), spontaneous abortions (14: 21.9% vs 11: 17.2%), therapeutic abortions (3: 4.7% vs 0: 0%) and stillbirths (1: 1.5% vs 1: 1.6%). Gestational age at birth (38.4+/-2.8 weeks vs 39.3+/-1.3 weeks: M+/-S.D., p=0.04) and birth weight (3.14+/-0.68kg vs 3.45+/-0.42kg, p=0.01) were lower in the statin group. CONCLUSIONS: The absolute risk of teratogenicity of statins, if any, appears relatively small. A large-scale study is needed to further characterize the teratogenic potential.
Subject(s)
Fetal Development/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Pregnancy Outcome , Prenatal Exposure Delayed Effects/chemically induced , Abnormalities, Drug-Induced/epidemiology , Abnormalities, Drug-Induced/etiology , Birth Weight/drug effects , Case-Control Studies , Cohort Studies , Female , Gestational Age , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Infant, Newborn , Pregnancy , Pregnancy Outcome/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Prospective StudiesABSTRACT
BACKGROUND: Breastfeeding is the ideal method of infant nutrition. However, if mothers need medications such as the central nervous system (CNS) acting drugs, infant safety concerns arise. Summarized information on infant exposure levels to drugs in milk and associated side effect profiles will help clinicians to rationalize and justify important drug therapy for a breastfeeding patient. METHODS: Electronic searches of MEDLINE and PsycINFO from 1966-2003, and of EMBASE from 1980-2003, were conducted for studies on breastfeeding or breast milk and medications in the following categories: antidepressants, antipsychotics, antiepileptics (or anticonvulsants) and anxiolytics. The infant exposure level (%) was defined as follows: [Drug concentration in milk (mg/mL)] x [Daily milk intake (mL/kg/d)] x 100 / Maternal dose (mg/kg/d). RESULTS: A total of 129 papers were eligible for analyses. Our findings indicate that the majority of the CNS-acting drugs, if taken by nursing women, result in average exposure levels to their breast-fed infants of less than 10% of the therapeutic doses per kg body weight. Exceptions are lithium, ethosuximide, phenobarbital, primidone, lamotrigine and topiramate. Adverse effect profiles do not always correlate with a higher exposure level. Overall, most reported adverse effect profiles appear benign. Where adverse effects were reported, they were often confounded by intrauterine exposure. CONCLUSIONS: CNS-acting drugs taken by the mother do not appear to pose any major risks of immediate adverse effects to the breastfeeding infant, although with most of the newer drugs further research is needed to be conclusive.
