Fevers in early pregnancy can lead to greater risk of birth defects, UC Berkeley study finds

Chunlei Liu/Courtesy

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A fever early in a woman’s pregnancy can lead to a greater risk of birth defects, according to a study published Tuesday by UC Berkeley and Duke University researchers.

According to Chunlei Liu, a senior author of the study and campus associate professor of electrical engineering and computer sciences, scientists have long known of the correlation between maternal fevers and congenital defects. But the study, which appeared in the journal Science Signaling, reveals that the fever itself causes the birth defects, as opposed to the virus that caused the fever.

The study’s results suggest that higher temperatures disrupt the function of neural crest cells found in early-stage embryos, which are critical for the fetus’s development of the heart, face and jaw.

Liu said despite the fact that congenital heart defects are common, their causes were previously unclear.

The researchers studied zebrafish and chicken embryos to understand how a fever can affect fetal development. Miriam Hernández-Morales, a campus postdoctoral researcher under Liu, said the team found “temperature-sensitive proteins” in neural crest cells, and upon activation, these proteins can negatively affect the function of these cells.

Morales said the results suggest some birth defects could be prevented if first-trimester fevers are taken seriously and treated accordingly. John Balmes, a campus professor of environmental health sciences who is unaffiliated with the study, said in an email that fever-lowering drugs such as Tylenol could also prevent some birth defects.

“There’s always some concerns of whether (a pregnant woman) should take drugs or not,” Liu said. “We know of some drugs that are safe to be used in pregnancy. … It’s always good to talk to physicians and seek advice.”

The researchers used a remote radiofrequency approach, which allowed them to simulate fever-like conditions for specific cells without significantly affecting the rest of the organism — a technique Balmes considers “novel.”

The animal embryos that were observed consistently developed facial deformities and heart defects when the neural crest cells were heated, according to the study. Facial deformities included clefts, whereas heart defects included obstructive lesions, a situation in which the blood flow pathways become narrowed.

The study did not address how the severity or duration of the fever impacts fetal development.

Liu is also a part of a research team that was recently given $13.4 million to build a new MRI brain scanner with greater resolution and image quality than existing scanners. Liu previously told The Daily Californian that this new MRI technology was important because it will improve researchers’ understanding of the brain on a neurological level.

“Just think for a moment (of) the suffering involved with heart and cranial congenital defects,” Morales said. “It is painful for the newborns and their parents. It is not just about interesting and exciting knowledge. It is about valuable knowledge for taking better care of the most vulnerable people we can imagine of: our newborns.”

Contact Anjali Shrivastava at [email protected] and follow her on Twitter at @anjalii_shrivas.

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  • Accumulating evidence shows that acetaminophen causes brain injuries and asthma. It is reckless and unjustified to say that acetaminophen will prevent damage caused by immune activation simply because it reduces fever.

    Acetaminphen is a very dangerous drug. It has never been shown to be safe for pregnant women or infants. Use in pregnancy is in fact associated with neurological and behavioral disorders in children.


    “Given its suppression of the febrile response, one might expect that the general effects of exposure to acetaminophen would be anti-inflammatory in nature. Unfortunately, this expectation is false. Studies in adult humans demonstrate that even low-dose acetaminophen triggers immune system activation and oxidative stress responses.135 Further, medical professionals evaluating immune responses from a biologists’ perspective have warned that the febrile response is both adaptive (beneficial to survival) and ancient in its origins,136 with behaviors which induce fever-like temperatures evident in cold-blooded animals.137 Thus, biologists argue that inhibition of the febrile response is likely not without costs.137 It has even been postulated that the elimination of fevers may be responsible in part for the induction of autism.138 However, the health costs of eliminating low-grade fevers in general are not known. On the other hand, some data regarding the health costs of using acetaminophen are described in the literature. A multinational study with more than 200,000 children found a dose-dependent association between use of acetaminophen in the first year of life and the occurrence of inflammatory diseases such as asthma, rhinoconjunctivitis, and eczema later in life.139 The causal relationship between use of acetaminophen and the occurrence of asthma has been questioned,140 but the consensus is that a relationship exists141,142 and a population-wide increase in asthma of more than 40% may be caused by the use of acetaminophen.143”