The reasons for the rise in cesarean section (CS) deliveries worldwide are complex. Maternal choice is often cited as a major factor, but clearly clinicians play the major role. An understanding of the long-term impact of CS on the offspring is critical to any reevaluation of the increasing rate CS deliveries. This review examined current evidence of long-term outcomes after CS and assessed research strategies to test causality and improve understanding of biologic mechanisms.
Cesarean delivery affects long-term health, particularly in relation to conditions associated with the metabolic syndrome, immune system, dentition, malignancies, and nervous system. Metabolic syndrome includes a constellation of well-known features that are associated with type 2 diabetes and cardiovascular disease. Studies on the relationship between CS and greater body mass index (BMI) or obesity in offspring have provided contradictory results, with some reporting no association between CS and risk of being overweight. One confounding factor for the association between CS and offspring BMI is maternal BMI, a known cause of the increased risk of CS. Reports have suggested that neonates have lower blood pressure following CS as compared with vaginal delivery, with some data indicating that blood pressure may be affected by the interaction between gestational age and mode of delivery. Infants born by CS have greater incidence of type 1 diabetes mellitus and a higher risk of asthma. Asthma is associated with respiratory morbidity at birth, and CS delivery is also associated with short-term changes in lung function at birth. An association between CS and atopy and allergy was found in CS infants compared with infants born by vaginal delivery. An association has also been found between CS and celiac disease but not with Crohn disease or ulcerative colitis. A few reports link CS and increased malignancy, particularly childhood myeloid leukemia and nonseminomatous testicular cancer. These associations may indicate epigenetic changes driven by mode of delivery. For neurodevelopment in CS infants, and without strong evidence of poorer neurodevelopmental outcomes in pre-labor cesarean section-delivered infants, causal mechanisms cannot be completely explained or confirmed.
With the wealth of evidence indicating that CS affects short- and long-term health of offspring, the implications for both personal and public health require further elucidation. The proportion of the population burden of obesity that might be attributable to CS is ~3.7%. Reducing the CS rate could reduce the rates for childhood obesity, asthma, and type 1 diabetes. Observational studies and randomized controlled trials (RCTs) have been the most frequently used study designs to evaluate the associations between CS and the health of offspring. However, many studies have provided conflicting results, were unable to recruit sufficient numbers of patients, or provided no long-term follow-up. Concerns are also voiced about safety or ethical or practical issues in conducting RCTs in this population.
Cesarean delivery is associated with detrimental long-term outcomes for offspring. Many of these associations have plausible biologic mechanisms, but causality remains to be proven. An RCT of mode of delivery in the healthy, term, cephalic pregnancy is feasible, and when linked with evaluation of biomarkers of outcome and long-term follow-up, it is the only reliable means to settle an issue of international importance.
Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London, United Kingdom