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Fevers during the first trimester of pregnancy have been linked to birth defects of the heart and facial deformities for decades.

But now a Duke University team says they’ve pinpointed the cause to two temperature-sensitive ion channels – and have also found a way to prevent the common defects, as described in the latest issue of Science Signaling.

“Maternal infections with associated fevers in the first trimester are linked to clinical important craniofacial and cardiac defects,” they conclude.

“These findings suggest we can reduce the risk of birth defects that otherwise could lead to serious health complications requiring surgery,” adds Eric Benner, a Duke University Medical Center neonatologist, and lead author.

The TRPV1 and TRPV4 channels in the neural crest cells are temperature-sensitive.

The scientists set out to check the thermal effects on the pathways – but in chicken and zebrafish embryos.

They engineered iron-binding modifications to the two channels allowing them to turn them on with electromagnetic fields remotely, they write.

When the pathways were lit up in the way that would be done with a fever, the resulting embryos later showed heart and craniofacial irregularities – the same kind that appear in humans.

“Our analysis revealed the hyperthermia exposure resulted in significant craniofacial defects, including a reduction in upper beak lengths compared to normothermic control chicks with severe beak defects,” they conclude. “Cardiovascular defects were increased in hyperthermia-exposed embryos. These defects included a significant incidence of conotruncal defects including DORV and aortic arch patterning defects.

“All of these defects are directly linked to neural crest cell dysfunction,” they add.

Heart defects affect roughly one percent of babies born in the U.S., according to health statistics. Another several thousand are affected by cleft palate, among other deformities, each year.

The fix could be as simple as a smart – and vigilant – use of acetaminophen with fevers early in pregnancy, they conclude.

“Because hyperthermia is a modifiable risk factor in pregnant women, these fever-associated birth defects may be preventable through public awareness and judicious use of antipyretics in febrile pregnant women,” they write.

 

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