Overweight and obesity in mothers during pregnancy increased the risk for colorectal cancer (CRC) in their children later on in life, according to a population-based study.

Compared with underweight/healthy weight during pregnancy, both obesity and overweight were associated with increased risk of CRC in offspring (adjusted HR 2.51, 95% CI 1.05-6.02 and adjusted HR 2.12, 95% CI 1.18-3.82, respectively), reported Caitlin Murphy, PhD, of the University of Texas Health Science Center in Houston, and colleagues.

Weight gain during early pregnancy also increased this risk, but only if weight gain across the entire gestation was low. This suggests that a discordant fetal growth pattern from early to late pregnancy may impact outcomes later in life, the researchers wrote in Gut.

“We are seeing that early life events, or things that happen in the womb, are important risk factors of colorectal cancer in adulthood,” Murphy told MedPage Today. “No one up until this point has really been talking about early-life factors as being important for this disease.”

It was “puzzling” to find that the effect of early pregnancy weight gain on offspring cancer risk was dependent on a mother’s weight gain throughout the entire gestation, Murphy continued. “But it suggests that there’s something about the timing of weight gain that is important here,” she added.

Incidence and mortality rates of CRC have jumped in younger populations across the past few decades, Murphy and colleagues noted. The global disease burden is expected to increase by 60% by the year 2030, totaling 2.2 million new cases and 1.1 million deaths.

Obesity is a known risk factor for CRC, but it’s still uncertain how obesity at pregnancy could predispose a fetus to developing illness later on. The researchers proposed two mechanisms: either maternal obesity establishes obesogenic growth patterns for babies that persist into adulthood, or it causes a sensitivity in fetal gastrointestinal tissue that may effect pathology into adulthood.

Murphy’s group analyzed rates of CRC in adult offspring from the Child Health and Development Studies, a population-based cohort of mother-infant pairs who received prenatal care during the 1960s from Kaiser Permanente in Oakland. Offspring were followed for about 60 years.

Using data from California’s state cancer registry, the researchers linked maternal body mass index (BMI), pregnancy weight gain, and birth weight to diagnoses of CRC up until the year 2019. They controlled for covariates such as race and ethnicity, maternal age at pregnancy, parity, education level, total income, gestational age, and family history of CRC.

More than 18,000 offspring were included in the analysis. Nearly half were born in the early 1960s, and 52% were born into families whose total income was below the median. Around two-thirds of study participants were white.

Over more than 700,000 person-years of follow-up, 68 offspring were diagnosed with CRC. All diagnoses occurred when the patients were between the ages of 18 and 56, with around half of patients being diagnosed before age 50. Most patients were diagnosed with regional (44.1%) or distant (25%) disease, and with tumors in the distal colon (42.4%) or rectum (28.8%). Nearly 20% of patients had a family history of CRC.

For mothers with obesity, the incidence rate of CRC in offspring was 16.2 per 100,000 compared with 14.8 per 100,000 for overweight mothers, and 6.7 per 100,000 for healthy-weight or underweight mothers.

Independently, neither early pregnancy weight gain nor total pregnancy weight gain was significantly associated with CRC risk in offspring. However, when high pregnancy weight gain and low total weight gain occurred, risk of developing CRC for offspring in adulthood became much higher (adjusted HR 4.78, 95% CI 1.45-15.74).

Birth weight was also associated with elevated CRC risk: babies who weighed more than 4,000 g had a higher chance of developing CRC in adulthood (adjusted HR 1.95, 95% CI 0.8-4.38).

Murphy’s group recognized that shared maternal and infant characteristics, including diet and microbiome, were not accounted for and may limit these findings. They also did not control for BMI among offspring throughout adulthood. Finally, gestational diabetes was not a part of routine screening practice during the time of recruitment, and could have impacted these results.