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A study examines the safety of MRI scans during pregnancy. Plus: Researchers at Florida State University identify several compound that could combat Zika.
Results of a cohort study of more than 1.4 million pregnancies show that magnetic resonance imaging (MRI) in the first trimester is safe but that gadolinium-enhance MRI at any time in pregnancy may slightly increase risk of a rare vision problem. Published in JAMA, the findings are from analysis of data in a Canadian universal health care database and the research may be the first controlled study of first-trimester in human pregnancy.
Using the database, births >20 weeks from 2003 to 2015 in Ontario, Canada were identified with the goal of evaluating the long-term safety after first-trimester exposure to MRI or exposure to gadolinium at any time during pregnancy. For the former, the authors looked at risk of stillbirth or neonatal death within 28 days of birth and any congenital anomaly, neoplasm, and hearing or vision loss from birth to age 4 years. For the latter, connective tissue skin disease that resembled nephrogenic systemic fibrosis (NSF-like) and a broader set of rheumatological, inflammatory, or infiltrative skin conditions were identified.
The overall rate of MRI was 3.97 per 1000 pregnancies. In pregnancies with no exposure to first-trimester MRI compared to those with exposure to the testing, the relative risk (RR) was 1.68 (95% CI, 0.97 to 2.90) for an adjusted risk difference of 4.7 per 1,000 person-years. (95% CI, -1.6 to 11.0). The risk was also not significantly higher for congenital anomalies, neoplasm or vision or hearing loss. The adjusted risk difference was 47.5 per 1000 pregnancies (95% CI, 9.7 to 138.2) for stillbirths and neonatal deaths in 7 MRI-exposed pregnancies versus the 9,844 unexposed pregnancies (adjusted RR, 3.70; 95% CI, 1.55 to 8.85).
For gadolinium versus no MRI, the hazard ratio for NSF-like outcomes was not statistically significant. The broader outcome of any rheumatological, inflammatory, or infiltrative skin condition occurred in 123 versus 384,180 births adjusted HR, 1.36; 95% CI, 1.09 to 1.69) for an adjusted risk difference of 45.3 per 1,000 person-years (95% CI, 11.3 to 86.8). When the investigators restricted MRI exposure to 5 to 10 weeks’ gestation, risk of congenital anomalies and hearing loss was unchanged but risk of vision loss was higher: adjusted HR 2.28 (95% CI, 1.09-4.77) or an adjusted risk difference of 2.7 per 1,000 person-years (95% CI, 0.2-7.9)
The authors noted that the study’s large size and population-based sample were strengths but that it was underpowered to assess uncommon outcomes in those exposed to first-trimester MRI. Risk of spontaneous or induced abortion before 21 weeks associated with MRI also is unknown because pregnancies that ended before 21 weeks were excluded.
Given their findings, the researchers said it may be wise to discuss with women who were advertently exposed to MRI in the first trimester or who are planning such exposure the “potentially slightly higher risk of vision loss” in offspring exposed during the first trimester. That risk, however, should be balanced against the finding that MRI exposure is not associated with a higher risk of other adverse outcomes. “It seems prudent,” they said, “to avoid more than 1.5-T MRI for pregnant women. Until further studies are done, these findings suggest that gadolinium contrast should be avoided during pregnancy.”
Small-molecule drugs may protect cells against Zika
A consortium of investigators directed by scientists from the Florida State University have identified more than 10 compounds that have potential to inhibit the Zika virus and the death of neural cells that it produces. Published in Nature Medicine, the findings are the result of screening approximately 600 compounds that included approved drugs, clinical trial drug candidates, and pharmacologically active compounds.
The drug repurposing process used by the investigators focused on compounds that could decrease activation of caspase-3, an enzyme that is upregulated by the Zika virus, leading to cell death. They found that one class of neuroprotective drugs and one class of antiviral drugs had potential to protect neural cells from Zika-induced cell death.
Treatment with emricasan, the investigators said, reduced the number of forebrain-specific human neural progenitor cells (hNPCs) that expressed caspase-3 after exposure to FSS13025, a Cambodian strain of Zika. The drug did not, however, suppress Zika replication.
A US Food and Drug Administration-approved drug and an investigational agent were singled out by the researchers as the antiviral compounds with the most potential in fighting Zika. Both niclosamide, which is FDA-approved to treat worm infections in humans and livestock, and PHA-690509, which is a cyclin-dependent kinase inhibitor (CDKi), were found to inhibit Zika strains from Cambodia, Uganda, and Puerto Rico. The authors said that both niclosamide and PHA-690509 inhibit Zika after its entry into cells, probably during viral RNA replication. Nine other CDKis also were found to have activity against the virus.
The investigators then tested emricasan and PHA-690509 in combination and found that they have an additive effect in inhibiting caspase-3 activity in Zika-infected cells. Interestingly, sequential treatment of cells infected with the Puerto Rican strain of Zike with emricasan for 72 hours followed by 48 hours of treatment with niclosamide led to recovery of Zika-negative hNPCs. The authors said the inhibition of apoptosis might “buy time,” allowing infected cells to recover.