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Birth via cesarean section was associated with a higher risk for developing Crohn's disease later in life, a population-based cohort study from Sweden found.

In the study of over 1 million newborns, unadjusted univariate analysis found that certain gastrointestinal disorders were more common among those born via C-section, reported Anna Löf Granström, MD, PhD, of the Karolinska Institutet in Stockholm, and colleagues:

• Diverticulosis: HR 1.57 (95% CI 1.13-2.18)
• Cholecystitis: HR 1.16 (95% CI 1.05-1.28)
• Crohn's disease: HR 1.13 (95% CI 1.02-1.25)

But after adjusting for confounders, the risk only remained higher for Crohn's disease (HR 1.14, 95% CI 1.02-1.27), according to the findings in .

On subgroup analysis, individuals born via elective C-section were at even greater risk for Crohn's disease on both univariate (HR 1.16, 95% CI 1.01-1.34) and multivariate analysis (HR 1.18, 95% CI 1.01-1.37) versus vaginal deliveries. Although emergency C-sections were linked with a greater risk of diverticulosis and cholecystitis on univariate analysis, they both lost significance on adjusted multivariate analysis.

"Our study is the largest in this field, showing new interesting associations between cesarean section and increased risk later in life for Crohn's disease," Granström said in a press release. "We hypothesize that the underlying mechanism could be the gut microbiome, but further studies will have to confirm this."

Multivariate analysis showed no significant relationship between delivery mode and ulcerative colitis, appendicitis, diverticulosis, or cholecystitis.

C-section deliveries have been on the rise, and account for as many as 20% of all worldwide births, Granström's group noted. Prior studies showed C-sections were tied to a greater risk of infection and diseases among infants, as well as other conditions that may arise later in life, especially for females.

"There are observations suggesting that early-life aberrations in gut microbiota may have long-lasting consequences that have been associated with increased risk of asthma, allergies, type 1 diabetes, celiac disease, and immune deficiencies, which may suggest an increased risk for inflammatory-mediated disease," the authors noted.

"Infants born by vaginal delivery are primarily colonized by bacteria from the birth canal, consisting of bacterial flora mainly from the intestinal tract, unlike infants born by CS [C-section], who have an increased prevalence of skin flora at first colonization," they wrote. "Disrupted gut colonization (dysbiosis) of a newborn may be explained by CS delivery, use of perinatal antibiotics, and type of diet (breast milk or formula)."

Granström and colleagues examined medical birth registry data on 1,102,468 newborns who were born at full-term (37-42 gestational weeks) from 1990 to 2000 in Sweden. Of those, 88.4% were delivered via vaginal birth and 11.6% by C-section. C-sections were stratified by emergency (56.2%) or elective procedures (43.8%). Follow-up occurred until the end of 2017. Excluded were children from multiple pregnancies or unknown delivery modes.

Analysis adjusted for birth weight, gestational age, being small for gestational age, perinatal illness, congenital malformations, maternal smoking, and highest parental education.

The C-section group were more often males (53% vs 51%) and born earlier (median gestational age 38 vs 40 weeks) with a predictably lower birth weight (about 7 vs 8 lb), versus the vaginal delivery group. Additionally, the C-section group were born to mothers who were slightly older (mean age 30 vs 28.5) and more often smokers (18.3% vs 17.3%).

Not surprisingly, the C-section group suffered more perinatal illness (19.2% vs 5.2%), congenital malformations (6.3% vs 3.5%), and deaths (1.9% vs 0.8%).

The median time to be diagnosed with gastrointestinal disorders for the C-section and vaginal birth groups, respectively, were: appendicitis (15.1 vs 15.3 years), Crohn's disease (16.9 vs 17.4 years), ulcerative colitis (17.8 vs 18.2 years), and cholecystitis (20.8 vs 21 years).

Study limitations included the fact that registry-based data may be prone to residual confounding. Also, information was unavailable on hereditary factors, BMI, use of perinatal antibiotics, or whether newborns were breastfed or formula fed.

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