After adjusting for key confounders and confirmation with a series of supplemental analyses, no association was observed between the delivery method and the child’s weight status at ages 1, 3, and 6 years. These observations are in contrast to findings of previous studies, including meta-analyses showing that children born by CS are at higher risk of developing obesity in childhood 10,17. However, of consideration is the fact that these meta-analyses comprised studies primarily conducted among populations from western countries, in which circumstances may be different than Japan. The current study represents one of the first thorough epidemiological evaluations of the role of delivery method in influencing weight status in children in East Asians.
One possibility for these contrasting results is that child’s weight status may be influenced by maternal BMI and eating habits which may differ across populations 18,19. A German study, which did not find a significant association with delivery method, described that there may be other dominating risk factors, such as dietary habits and physical activity as children grow up, influencing the risk of obesity in later life more so than the risk conferred by microbial exposures during child birth 11. The mothers in our study population have generally lower BMI during pregnancy compared to the general pregnancy population in Japan (BMI < 18.5; 19.7% vs 11.2%, BMI ≧ 25; 5.3% vs 21.9%) 20. It may be possible that certain lifestyle characteristic of our study population may have offset the negative influences of caesarean delivery that would have otherwise contributed to the risk of overweight in other populations. Another possibility for the inconsistency may be due to differences in the distribution of microbiota among populations across different countries 21. Thus, the association between delivery method and weight status might be different in Japan, and may not be a primary factor effecting obesity risk. However, we did not examine the profile of the infants’ gut microbiota so we were not able to confirm this point.
Previous studies reported that breastfeeding during infancy is associated with differences in the child’s microbiome 7,22. Therefore, postnatal breastfeeding practices may affect the infant’s gut microbiota and modify the association between delivery method and future weight status. There is evidence that cessation of breastfeeding influences the development of adult-like microbiota more than the introduction of solid foods 23. In our stratified evaluations specifically examining the association among exclusive breastfed and non-exclusive breastfed children, no association was observed in both populations. Preterm infants also tend to be born by CS for a variety of reasons and often receive medical care after birth. Considering that the environment is different from that of term infants, we excluded preterm infants in a sensitivity analysis, but observed no marked effect on the results.
We examined the association between delivery method and child’s weight status at three different time points, ages 1, 3, and 6 years. A Danish study reported that caesarean delivery was associated with an increased risk of obesity among men at age 18 24. A systematic review also showed that delivery by CS was associated with an increased risk of obesity not only in early childhood (0–5 years), but also in adolescents (5–18 years), and adulthood 25. While there may be a possibility that an association with delivery method may become apparent with longer follow-up into adolescence, we speculate that this may not be likely as there was no tendency for rising risk estimates with increasing age.
A planned CS is performed prior to labor or membrane rupture and can deprive the vaginal microbiota of exposure. In contrast, a membrane rupture may have already occurred in some cases of emergency CS. Therefore, in additional confirmatory analyses, we excluded children born by emergency CS, but results showed no notable difference. Several studies have examined the association between selective or non-selective CS and obesity in childhood, but have not obtained additional clarity for the association 26–28.
Other mechanistic considerations are necessary to aid the interpretation of results. Delivery method may influence child’s weight trajectories by affecting the maturation of the gut microbiota, but CS is also known to affect feeding patterns due to effects on maternal hormones, and metabolism of fat and glucose. This can have long-term effects on appetite and metabolic regulation 29. Another mechanism that may explain the association between CS and subsequent offspring obesity is through the effects of stress exposure during labor on cell maturation and DNA hypermethylation which in turn affects metabolic function 29,30. Given these biologically plausible mechanisms, the pathways potentially linking delivery method and child weight trajectories appear diverse and may be influenced by other factors related to the child’s environment.
The phenomenon that BMI changes from decreasing to increasing in early childhood is known as adiposity rebound, and it has been shown that the earlier it starts, the higher the risk of developing obesity and lifestyle-related diseases 31–33. A Japanese study reported that children who showed an increase in BMI between the ages of 1.5 and 3 years, which is usually a period of a decreased or stable BMI due to changes in body composition, tended to have higher insulin resistance 34. Other studies have concluded that early adiposity rebound was associated with factors related to metabolic syndrome, including type 2 diabetes 35, elevated blood pressure, and dyslipidemia 32. Evaluation of the phenomenon in our study showed no association between delivery method and early adiposity as a potential predictor of obesity risk later in life.
To the best of our knowledge, this is the first study on the association between delivery method and child’s weight status in Japan. A major strength of this study was the use of two documented measures of weight status, BMI z-score and POW. In addition, detailed data collection allowed us to address potential confounders such as pre-pregnancy BMI and effect modification by early breastfeeding status in a sample of mother-child dyads. Distribution of weight status of this Japanese population enabled us to uniquely examine the effects of delivery method on both overweight and underweight tendencies, and we were able to separate out CS into either planned or emergency by accessing detailed clinical data. These are features that only limited previous studies have been able to address.
There are also several limitations that should be acknowledged. First, there was loss to follow-up over time, which may have affected statistical power and introduced selection bias. While certain analyses may have had reduced precision due to sample size, the risk estimates for the primary analysis and the series of supplemental analyses were null suggesting minimal support for the prevailing hypothesis. In addition, we compared baseline demographics between participants analyzed at age 6 years and those who were lost to follow-up. We confirmed that the overall distribution of characteristics, including delivery method, were similar between those included and excluded. Secondly, there was a lack of information on early life antibiotic exposure, which might be associated with the distribution of microbiota 7. A previous study reported that administration of antibiotics up to 6 months of age increased the risk of overweight in children of normal weight mothers 12. Another limitation was a lack of complete information about the father’s characteristics precluding our ability for a thorough assessment of paternal factors. A previous study has shown that paternal BMI is associated with the child’s obesity risk 36.
Taken together, the current study represents one of the few rigorous studies conducted on this topic, particularly in Japanese, and results do not support the hypothesis of an increased risk of overweight associated with caesarean delivery. It seems likely that exposures manifested through delivery method may not be a major factor contributing to the child’s weight status; however, it is yet unknown whether there are longer-term effects that influence the overweight tendencies in adolescents and into adulthood. Such a finding suggests that there may not be an immediate concern regarding caesarean deliveries and its influence on childhood obesity, and public health efforts should focus on various prevention programs for monitoring, evaluating, and providing education about healthy lifestyle such as consumption of healthy foods and physical activity 37. At the same time, care for women before conception and during pregnancy about healthy dietary and lifestyle factors is also important 38,39.
In conclusion, we found no association between delivery method and child’s weight status at age 1, 3, and 6 years after careful consideration of a broad range of methodological issues. Further studies are needed considering longer observation periods and target population characteristics to confirm our findings and explore the mechanisms for the potential association.