We have with great interest read the recent review on cesarean section and immune development in the offspring. Elective cesarean section may affect the gut flora up to 6 years of age. An increased risk of asthma and other immune disorders after elective cesarean section would be consistent with the hygiene hypotheses. However, a number of studies have now indicated a reversed trend of asthma among schoolchildren who were born in the 1990s when the use of cesarean section was still increasing. The findings from epidemiological studies have not been consistent and confounding control is problematic also in large and well-designed observational studies. Sibling-pair analysis is a powerful tool to control for confounding related to familial and genetic factors. We have assessed the risk of asthma medication as a proxy for asthma in relation to mode of delivery in a registry-based national cohort study comprising 199,837 children aged 2-5 and 6-9 years. The conventional analysis with adjustment for relevant sociodemographic and perinatal factors demonstrated that elective cesarean section was associated with a 20% increased risk of asthma in both age groups. When analyzed using discordant sibling pairs (discordant for both mode of delivery and asthma medication outcome), the association between elective cesarean section and asthma medication was reduced in children aged 2-5 years and disappeared completely in children aged 6-9 years. Similarly, another Swedish study of 87,500 sibling pairs could not demonstrate any association between elective cesarean section and asthma medication in children aged 10-12 years. Thus, the sibling-pair analyses indicate that elective cesarean section may contribute to a modestly increased risk of asthma but only in children aged <5 years. Sibling-pair analyses have so far not been used in studies of mode of delivery as a risk factor for diabetes, celiac disease, inflammatory bowel disease, or other autoimmune disorders.

Timing of delivery could be more important than mode of delivery. The risk of asthma has an inverse relationship with gestational age and every week is important. As compared with children born at term, children born at 37-38 gestational weeks have a 10% increased risk of asthma and early term birth accounts for 2% of all cases of childhood asthma. Thus, the importance of gestational duration to prevent the development of asthma should be weighed against other medical risks in the timing of an elective cesarean section.