Researchers have known for decades that fever in early pregnancy increases the risk for some heart defects and facial deformities, such as cleft lip or palate, but they have yet to determine whether it’s the underlying antigen or the elevated body temperature that causes the defects — until now.

Fast facts about fever in early pregnancy

• Fever in early pregnancy — the temperature, not necessarily the underlying infection — can cause serious birth defects
• If you have a fever during your first trimester of pregnancy, consult your OB/GYN as soon as possible about taking only acetaminophen (i.e. Tylenol or Paracetamol) to lower your body temperature

A Duke University team now has evidence indicating that the fever itself, not the underlying infectious cause, is what interferes with the development of the heart and jaw during the first three to eight weeks of pregnancy. Their findings, demonstrated in animal embryos, were published last week in the journal Science Signaling.

The results suggest some congenital birth defects could be prevented by lowering the mother’s fever during the first trimester of pregnancy through the careful use of acetaminophen, said senior author Eric Benner, M.D., Ph.D., a neonatologist and assistant professor of pediatrics at Duke.

“My hope is that right now, as women are planning to become pregnant and their doctors advise them to start taking prenatal vitamins and folic acid, their doctor also informs them if they get a fever, they should not hesitate to call and consider taking a fever reducer, specifically acetaminophen (Tylenol/Paracetamol), which has been studied extensively and determined to be safe during the first trimester,” Benner said. “While doctors advise most women to avoid any drug during pregnancy, there may be benefits to taking acetaminophen to reduce fever. Women should discuss all risks and benefits with their doctors.”

Benner cautions that while pain relievers like ibuprofen and aspirin also reduce fevers, these medicines are not safe to use during the later stages of pregnancy. There is also ongoing debate over whether sustained use of acetaminophen is safe during pregnancy to manage ongoing conditions such as arthritis, Benner said.

“However, its judicious use for an acute problem such as fever is considered safe,” he explained. “These findings suggest we can reduce the risk of birth defects that otherwise could lead to serious health complications requiring surgery.”

To observe how fever during pregnancy impacts a developing fetus, the researchers studied zebrafish and chicken embryos. Among their discoveries, the scientists found that neural crest cells — cells that are critical building blocks for the heart, face and jaw — contain temperature-sensitive properties.

“We found that these neural crest cells contain temperature-sensitive ion channels that typically are found in your sensory neurons,” Benner said. “They’re the channels that, when you stick your hand in a hot cup of water, tell your body the temperature has changed.”

The Duke researchers engineered a noninvasive magnet-based technology to create fever-like conditions in two specific temperature-sensitive ion channels called TRPV1 and TRPV4 in the neural crest cells involved in developing the heart and face. When those neural crest cells were subjected to conditions mimicking a transient fever during pregnancy, the embryos developed craniofacial irregularities and heart defects, including double outlet right ventricle, Tetralogy of Fallot and other outflow obstructions.

The type of defect depends on whether the fever occurs during heart development (around four weeks) or head and face development (five to seven weeks). What researchers still do not know is whether or how the severity or duration of a fever in early pregnancy impacts fetal development, Benner said.

“I hope moving forward, we can educate more women about fever as a risk factor for birth defects and let them know they shouldn’t just tough it out if they develop a fever,” Benner said. “They should ask their doctor before getting pregnant whether they may benefit from taking a fever-reducer such as acetaminophen in the event they develop a fever.”