Cancer diagnosed in a baby at birth or within the first 28 days of life is referred to as neonatal or congenital cancer. This phenomenon is exceedingly rare, occurring in an estimated one in every 27,000 to 33,300 live births worldwide. The presence of cancer at such an early stage suggests that the mechanisms responsible for its formation are closely tied to the complex biological processes of fetal development. Understanding how a tumor can arise during gestation requires examining three main pathways: errors during normal fetal cell growth, the inheritance of specific genetic predispositions, and, in extremely rare instances, transmission from the mother.
Developmental Failures: Errors in Fetal Cell Growth
The most frequent explanation for cancer in a newborn involves a mistake that occurs during the rapid, yet highly regulated, process of fetal development. A developing fetus relies on specialized, immature cells known as embryonal cells to differentiate into all the body’s tissues and organs. Sometimes, a subset of these cells fails to complete its maturation process and remains in an undifferentiated state. If these immature cells acquire spontaneous genetic changes, or de novo somatic mutations, they can begin to proliferate uncontrollably, forming tumors known as blastomas.
This mechanism is responsible for the formation of embryonal tumors, which are the most common malignant tumors seen in neonates. For instance, neuroblastoma, the most common type of neonatal cancer, originates from primitive nerve cells, often appearing in the adrenal glands. Wilms tumor, a type of kidney cancer, arises from precursor kidney cells that fail to mature into functional renal tissue. These tumors are considered accidents of development, where the cancer-causing mutations are acquired by the fetus’s own cells and are not present in the parents’ DNA.
Another example is retinoblastoma, a tumor of the retina, which frequently results from a somatic mutation in the RB1 gene. These developmental tumors highlight that the fetus’s intense cellular activity, involving trillions of cell divisions, carries an inherent risk of miscopying DNA. The sheer speed and scale of cell growth create an environment where random mutations can easily occur and lead to a cancerous growth before or shortly after birth.
The Role of Inherited Genetic Mutations
In a smaller fraction of cases, a baby is born with cancer because they have inherited a genetic mutation that predisposes them to the disease. Unlike the developmental failures that arise de novo in the fetus, these mutations are passed down from one or both parents through germline cells. These inherited defects typically involve faulty tumor suppressor genes or genes responsible for DNA repair mechanisms. When a child inherits one altered copy of such a gene, their cells already have a weakened defense system against cancer.
This means the child is born genetically primed for cancer, though they are not born with the cancer itself. The second, cancer-initiating mutation—the “second hit”—occurs spontaneously later in a susceptible cell during development, leading to tumor formation. Li-Fraumeni syndrome is a well-known example, involving an inherited mutation in the TP53 gene, which severely increases the risk of developing several types of cancer, including some that appear in infancy. Similarly, hereditary retinoblastoma results from inheriting a defective copy of the RB1 gene.
These hereditary syndromes are disproportionately represented in cases of neonatal cancer. The presence of these inherited mutations causes cancer to develop at a much younger age than it would in the general population. While the inheritance of the faulty gene is certain, the development of cancer remains a matter of risk, depending on whether the necessary second genetic event occurs during the fast-paced fetal growth period.
Addressing Rare Transmission Routes
A common concern is whether cancer can pass directly from a pregnant mother to her baby, a phenomenon known as vertical or transplacental transmission. This route is considered exceptionally rare, occurring in an estimated one in 500,000 pregnancies where the mother has cancer. For this transmission to occur, the mother’s malignant cells must successfully navigate a highly complex biological pathway. First, the cancer cells must enter the mother’s bloodstream and then manage to cross the placental barrier, which acts as a robust filter to protect the fetus.
Even after crossing the placenta, the maternal cancer cells must overcome the fetal immune system, which usually recognizes the mother’s cells as foreign and destroys them. Only a few types of cancer are known to have the aggressive characteristics necessary to complete this journey, most notably melanoma, leukemia, and choriocarcinoma. In the instances where transmission is confirmed, genetic sequencing reveals that the tumor in the baby is genetically identical to the mother’s cancer, meaning the baby has a tumor composed of the mother’s cells.
In some instances, particularly with cervical cancer, transmission can also occur during vaginal delivery if the baby aspirates tumor-contaminated fluid from the birth canal. However, the vast majority of cancer cases in newborns originate within the baby’s own cells, making maternal transmission a statistically insignificant cause.
Common Misconceptions About Congenital Cancer
The occurrence of cancer in a newborn often leads to speculation about external factors, but the causes are overwhelmingly internal to the baby’s biology. Many people mistakenly believe that environmental exposures, maternal diet, or common medications taken during pregnancy are responsible for congenital cancer. However, the known causes of these early-onset tumors are rarely linked to these external influences, which are more often implicated in adult cancers that develop over a lifetime of exposure.
Congenital cancer is fundamentally a developmental accident or the consequence of an inherited genetic predisposition, not a result of common lifestyle choices or typical environmental risk factors. The public often attributes childhood cancer to genetics or environment, which are significant factors in adult malignancies but are less frequently the primary cause in newborns. Understanding the intrinsic nature of these developmental errors helps dispel the idea that parents could have prevented the cancer through different actions during pregnancy. The focus remains on the precise mechanisms of cellular differentiation and genetic integrity during the earliest stages of human life.