Physical agents such as ionising radiation and hyperthermia can cause birth defects. Ionising radiation, composed of particles, X-rays, or gamma rays, can create charged ions that damage cells. In the 1920s, studies revealed that pregnant women exposed to X-rays had a higher risk of having children with abnormalities like microcephaly (small head) and microphthalmia (small eyes). A survey from 1928–1929 found that 25 out of 74 children exposed to radiation in utero were malformed.

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Hyperthermia can also act as a teratogen, caused by factors like saunas, hot tubs, infections, or experimental methods such as ultrasound and electromagnetic radiation. Animal studies from the 1970s to 1990s showed that hyperthermia led to central nervous system defects, microcephaly, and other malformations. In humans, it is linked to neural tube defects, miscarriages, and heart and intestinal abnormalities.