The four main causes of birth defects are genetic factors, environmental exposures (including medications and toxins), infections during pregnancy, and maternal health conditions. Together, these categories account for roughly half of all known cases. About 1 in 33 babies in the United States is born with a birth defect, and nearly half of all congenital anomalies have no identifiable cause at all.
Understanding these four categories matters because many birth defects occur during a narrow and surprisingly early window: the 3rd through 6th week of embryonic development, when the heart, brain, limbs, and facial structures are actively forming. That’s often before many people even confirm a pregnancy.
Genetic and Chromosomal Abnormalities
Genetic causes are the single largest identifiable category. About 1% of all live births involve a structural abnormality caused by a single-gene mutation, and these mutations collectively account for roughly 40% of congenital defects seen in newborns. The math is striking: each individual genetic disorder is rare, but there are so many possible mutations that they add up quickly.
These genetic defects fall into three patterns of inheritance. Dominant traits, where only one copy of the altered gene is needed to cause a problem, occur in about 7 out of every 1,000 births. Recessive traits, where both parents must carry the gene, account for about 2.5 per 1,000. X-linked disorders, which disproportionately affect males because they only have one X chromosome, add another 0.5 per 1,000.
Chromosomal abnormalities are a related but distinct issue. Instead of a single gene being altered, entire chromosomes are duplicated, deleted, or rearranged. Down syndrome (an extra copy of chromosome 21) is the most widely known example. These errors usually happen randomly during cell division and are not inherited from a parent in the traditional sense, though the risk does increase with maternal age.
Environmental Exposures and Teratogens
A teratogen is any substance that can interfere with normal fetal development. The list includes certain medications, recreational substances, chemical pollutants, and even high doses of some vitamins.
Medications
Several widely prescribed drugs carry serious risks during pregnancy. Certain anti-seizure medications are among the most well-documented. Valproic acid interferes with how the body uses folate and generates harmful reactive oxygen molecules in the embryo. Phenytoin exposure can cause a distinct pattern of problems including growth deficiency, intellectual disability, and characteristic facial features. Carbamazepine can damage DNA and has been linked to craniofacial defects and growth restriction.
Retinoids, which are derivatives of vitamin A used in some acne and skin treatments, are potent teratogens that target developing neural crest cells, the group of cells responsible for forming much of the face, skull, and nervous system. Even high-dose vitamin A supplements can pose a risk.
Alcohol and Tobacco
Alcohol during pregnancy damages the placenta, reducing its weight and impairing the blood vessels that deliver nutrients to the fetus. It also slows cellular growth, increases oxidative stress, and can alter the way genes are expressed through a process called epigenetic reprogramming. These effects are most dangerous during the first six weeks of development but can cause harm throughout pregnancy.
Tobacco smoke contains more than 7,000 chemicals, and hundreds of them can cross the placental barrier. Nicotine and carbon monoxide are direct neurotoxins that reduce blood flow to the fetus and cut off oxygen delivery. Other compounds in cigarette smoke, including nitrosamines and polycyclic aromatic hydrocarbons, cause direct genetic damage and have known teratogenic effects. Studies comparing smokers to non-smokers find significantly higher levels of oxidative stress in smokers’ blood, which translates directly to fetal risk.
Environmental Toxins
Exposure to heavy metals like lead and cadmium during pregnancy has been linked to orofacial clefts (such as cleft lip and palate) in a dose-dependent relationship, meaning the higher the exposure, the greater the risk. Arsenic in soil and water is a recognized teratogen. Pesticide exposure during early pregnancy is associated with increased birth defect risk, and even chemical fertilizers can introduce cadmium and other toxic metals into the food chain.
Infections During Pregnancy
Certain infections can cross the placenta and directly damage a developing fetus. Doctors group these under the acronym TORCH: Toxoplasmosis, Other infections, Rubella, Cytomegalovirus, and Herpes simplex virus. Each pathogen causes a different pattern of harm.
Cytomegalovirus (CMV) is the most common congenital infection. Affected newborns may show growth restriction, an enlarged liver and spleen, microcephaly (an abnormally small head), and hearing loss. Even babies who appear healthy at birth can develop progressive hearing loss during childhood.
Rubella, though now rare in countries with widespread vaccination, causes congenital rubella syndrome: a triad of cataracts, deafness, and heart defects. The full spectrum also includes eye abnormalities, brain calcifications, and low birth weight in about 9% of cases.
Herpes simplex virus during pregnancy raises the risk of miscarriage, premature birth, and stillbirth. When the virus reaches the fetus directly, it can cause brain damage, fluid accumulation in the skull, and microcephaly. Varicella (chickenpox) carries a roughly 1% chance of congenital varicella syndrome if a pregnant person becomes infected, which can include limb deformities, scarring, cataracts, and brain abnormalities. Parvovirus B19, the virus that causes “fifth disease,” can trigger severe fetal anemia, heart inflammation, and brain lesions.
Maternal Health and Nutritional Deficiencies
The mother’s own health before and during pregnancy directly shapes fetal development. Pre-existing diabetes is one of the strongest risk factors: mothers with pregestational diabetes face 2 to 75 times the typical odds of having a baby with a structural birth defect, depending on the specific defect type. The range is enormous because diabetes affects nearly every organ system during development, from the heart to the spine to the kidneys.
Obesity without diabetes also raises risk, though more modestly. Mothers with pregestational obesity face 10% to 50% higher odds of neural tube defects, certain intestinal malformations, kidney abnormalities, and several types of congenital heart defects. When obesity and diabetes occur together, the risks compound.
Nutritional deficiencies play a critical role as well. Insufficient folate (vitamin B9) during the earliest weeks of pregnancy is one of the most preventable causes of neural tube defects like spina bifida and anencephaly. The World Health Organization recommends 400 micrograms of folic acid daily for all pregnant women, started as early as possible and ideally before conception. Women with a history of neural tube defects in a previous pregnancy are typically advised to take a higher dose. Because the neural tube closes by about the 4th week of development, supplementation that starts after a missed period may come too late.
Why Many Cases Have No Clear Cause
Despite these four well-established categories, nearly half of all birth defects remain unexplained. In many cases, the cause is likely a combination of genetic susceptibility and environmental triggers rather than any single factor. A fetus with a mild genetic vulnerability might develop normally unless exposed to a specific toxin at just the wrong moment, or a combination of low-level exposures might push past a threshold that no single one would cross alone. This interaction between genes and environment is one of the hardest areas to study, because it requires tracking both inherited risk and real-world exposures across thousands of pregnancies.
What is clear is that the timing of exposure matters enormously. The 3rd through 6th weeks of embryonic development are when most structural defects originate. The heart, limbs, brain, and face are all actively forming during this period. After the first trimester, the risk of major structural defects drops significantly, though the brain and some other organs remain vulnerable to damage throughout pregnancy.