First-Trimester Exposure to Gadolinium-based Contrast Agents: A Utilization Study of 4.6 Million U.S. Pregnancies.

BackgroundThe safety of gadolinium-based contrast agent (GBCA) exposure during pregnancy has not been established, and the use of GBCAs during pregnancy is not recommended unless it is essential to the health of the woman or fetus.PurposeTo examine the prevalence of GBCA exposure in a large sample of pregnancies resulting in a live birth.Materials and MethodsThe Sentinel Distributed Database was used to retrospectively identify U.S. pregnancies that resulted in live births between 2006 and 2017 from 16 data partners. The main outcome was the prevalence of MRI procedures with and without GBCAs, sorted by anatomic location and trimester, among pregnant and matched comparator women.ResultsAmong 4 692 744 pregnancies resulting in a live birth, we identified 6879 exposures to GBCAs in 5457 pregnancies, representing one contrast-enhanced MRI examination per 860 pregnancies (0.12% of all pregnancies). Most contrast-enhanced MRI examinations were performed in the head (n = 3499), although pelvic and abdominal MRI constituted 22.3% (n = 1536) of all contrast-enhanced MRI examinations during pregnancy. The majority (70.2%) of GBCA exposures occurred during the first trimester, with a 4.3-fold greater prevalence compared with that in the second trimester and a 5.1-fold greater prevalence compared with that in the third trimester.ConclusionThis study identified higher rates of gadolinium-based contrast agent (GBCA) exposure during the first few weeks of pregnancy compared with the later weeks of pregnancy, suggesting inadvertent exposure to GBCAs might occur before pregnancy is recognized.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Kallmes and Watson in this issue.

Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system.

BACKGROUND: Although certain drugs that target the renin- angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited. We assessed the risk for angioedema associated with the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren. METHODS: We conducted a retrospective, observational, inception cohort study of patients 18 years or older from 17 health plans participating in the Mini-Sentinel program who had initiated the use of an ACEI (n = 1 845 138), an ARB (n = 467 313), aliskiren (n = 4867), or a ß-blocker (n = 1 592 278) between January 1, 2001, and December 31, 2010. We calculated the cumulative incidence and incidence rate of angioedema during a maximal 365-day follow-up period. Using ß-blockers as a reference and a propensity score approach, we estimated the hazard ratios of angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex, history of allergic reactions, diabetes mellitus, heart failure, or ischemic heart disease, and the use of prescription nonsteroidal anti-inflammatory drugs. RESULTS: A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren, and 915 for ß-blockers) were observed during the follow-up period. The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96) cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for ß-blockers. The incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for ß-blockers. Compared with the use of ß-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81-3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04) for aliskiren. CONCLUSIONS: Compared with ß-blockers, ACEIs or aliskiren was associated with an approximately 3-fold higher risk for angioedema, although the number of exposed events for aliskiren was small. The risk for angioedema was lower with ARBs than with ACEIs or aliskiren.

Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure.

PURPOSE: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy. MATERIALS AND METHODS: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy. RESULTS: Of the 8,572 survey respondents (71 +/- 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ. CONCLUSIONS: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure.

Postmarketing surveillance for drug safety in pregnancy: the Organization of Teratology Information Services project.

BACKGROUND: Although medications are frequently used during pregnancy, premarketing studies exclude pregnant women, with the result that maternal and fetal risks of medications are largely unknown prior to marketing. METHODS: To demonstrate the feasibility of using Teratology Information Services (TISs) to identify potential subjects who may participate in postmarketing surveillance studies regarding medications taken during pregnancy, maternal characteristics and pregnancy exposure data routinely collected from callers to member agencies of the Organization of Teratology Information Services (OTIS) were pooled for two one-month periods. RESULTS: A total of 3536 calls inquiring about 7746 different agents were received from pregnant women. Of the 40 medications about which pregnant women most frequently asked, the top two were nonprescription acetaminophen and pseudoephedrine, three were prescription drugs with a U.S. Food and Drug Administration pregnancy label category D designation, and five were prescription antidepressants. CONCLUSIONS: TISs are well positioned to prospectively ascertain medication exposures in large numbers of pregnant women and may be an exceptional resource for conducting postmarketing surveillance for the safety of medications taken during pregnancy.