Investigating Caesarean Section Birth as a Risk Factor for Childhood Overweight

Abstract

Background:

Caesarean section birth may be associated with overweight in childhood; however, findings to date have been inconsistent. This study explored the association of caesarean section vs. vaginal birth with childhood overweight in Vietnam.

Methods:

This longitudinal cohort study explored the association of delivery mode with overweight, obesity, and overweight/or obesity at 8 years of age in children (n = 1937) across 20 sites in Vietnam, using Young Lives longitudinal cohort study data. Categories were defined using BMI z-scores in relationship to the World Health Organization (WHO) reference median: overweight >1 and <2 standard deviations (SD) above WHO reference median, obese >2 SD, and overweight/or obese >1 SD. Individual questionnaire data collected sociodemographic information and pregnancy/birth information through face-to-face interviews with mothers/caregivers. Anthropometric measurements for mother and child were collected at baseline and at 8 years for children.

Results:

Adjusted multivariable logistic models revealed a twofold increase in odds at age 8 years of overweight [odds ratio (OR) = 1.8, 95% confidence interval (95% CI) 1.03–3.2, p = 0.039], obese (OR = 2.2, 95% CI 1.2–4.0, p = 0.014), or overweight/or obese (OR = 2.1, 95% CI 1.3–3.3, p = 0.002) for children born through caesarean section compared with vaginal birth. Children born through planned caesarean section (adjusted OR = 2.3, 95% CI 1.2–4.1, p < 0.001) and unplanned caesarean section (adjusted OR = 1.9, 95% CI 1.1–3.5, p = 0.03) had similar increased odds of overweight/or obesity compared with children born through vaginal birth.

Conclusions:

These findings suggest that there may be an association between caesarean section and childhood overweight even after adjustment for confounders. Further research is needed to explore the underlying mechanisms of this finding.

Introduction

The prevalence of childhood overweight and obesity in South East Asia has nearly doubled over the past 10 years.¹ In 2010, the estimated prevalence of overweight and obesity in children aged 0–5 years in South East Asia was 4.6%.¹ The reason for this increase is unknown, however, a growing body of evidence suggests that early-life circumstances, including perinatal factors may modulate gut microbiota composition and influence disease later in life.^2,3 One biologically plausible explanation is that caesarean section birth prevents newborn exposure to maternal vaginal and intestinal microbiota having lasting impacts on gut microbiota development and composition, playing an important role in the development of childhood disease.^2,4

Associations between caesarean section birth and childhood allergic disease,⁵ asthma,⁶ and type 1 diabetes⁷ have been previously reported in the published literature in high-income countries, and more recently an association between caesarean section birth and childhood disease, such as asthma, has been observed in low-to-middle-income countries (LMICs).⁸ This suggests that children born through caesarean section in LMICs may also be at increased risk of other conditions observed by similar research in more “Western” countries, although whether such results in high-income nations are largely confounded by low social disadvantage is unclear.

Evidence suggests that gut microbiota plays an important role in the pathophysiology of obesity. The proportion of different bacterial species in the intestine differs between individuals,⁹ and major shifts in the gut microbiota have been shown to play a role in immune function and nutrient absorption.¹⁰

One explanation is that the gut microbiota of obese individuals has increased efficiency in harvesting energy from carbohydrates compared with lean individuals.^4,11 The differences to gut microbial composition at birth for children born through caesarean section persist into childhood and may increase the risk of childhood and adult overweight disease.^2,4 Therefore, exploring the association between caesarean section birth and overweight/obesity in childhood becomes relevant, particularly in South East Asia, where the number of caesarean sections performed has increased considerably over the last decade as well as childhood overweight/obesity rates.^1,12 In South East Asia, caesarean section rates have increased from 4.1% in 1990 to 14.8% in 2014.¹²

Several epidemiological studies in high-income countries have reported increased odds between odds ratio (OR) = 2.1 [95% confidence interval (CI) 1.4–3.2]¹³ to OR = 5.2 (95% CI 1.2–22.0)¹⁴ of overweight or obesity in children (age range 3–7 years) born through caesarean section compared with vaginal birth,^13–16 while others have found no association.¹⁷ A recent meta-analysis of nine studies reported a pooled increased overweight/obesity odds of 32% (OR = 1.32, 95% CI 1.15–1.51, p < 0.001) in children born through caesarean section compared with vaginal delivery.¹⁸ Another recent review on the role of gut microbiota in childhood obesity concluded that it was important to continue exploring the role that gut microbiota plays in obesity as evidence suggests that prenatal, birth, and early nutrition factors may also play a role.³

One challenge faced by studies to date has been accounting for confounding for caesarean section birth. In LMICs, caesarean section rates have increased most rapidly among wealthier women,¹⁹ and obese women are more likely to have caesarean section birth due to medical indication.²⁰ As both maternal obesity and wealth (in LMICs) are predictors for childhood obesity, this presents an issue of possible confounding.^21–23 This may explain why previous studies have reported mixed findings for the association between caesarean section birth and childhood obesity.

The current study explores the association between caesarean section birth and childhood overweight/obesity at age 8 years, using birth cohort data in Vietnam (n = 2000), adjusting for confounding.

Methods

Participants

Young Lives is a multinational longitudinal cohort study investigating the changing nature of childhood poverty from 2002 to 2016 in four countries: Vietnam, India, Ethiopia, and Peru.²⁴ For the current study, data were used from the younger cohort in Vietnam (n = 2000) at baseline [aged 6–18 months (mean = 1 year)] and when the children were 7.5–8.5 years old (mean = 8 years). Attrition across survey time points from 1 to 8 years was low at 2.2% with attrition bias unlikely to lead to significant biases when estimating models.²⁵ Multiple and preterm births (<37 weeks gestation) were excluded due to differences in growth trajectories in early childhood compared with singleton, term births (≥37 weeks).²⁶ The analytical sample was therefore n = 1937.

Sampling and Data Collection

The sampling and recruitment procedures for the Young Lives study are outlined in detail elsewhere.²⁷ Pro-poor sampling was used to sample 20 sites across four regions in Vietnam (Northern Uplands, Red River Delta, Central Coast, and Mekong Delta). At each site, 100 eligible children aged 6–18 months were randomly sampled (total n = 2000),²⁸ with follow-up undertaken at age 8 years. Individual questionnaire data were collected through face-to-face interviews with caregivers. Fieldworkers were trained in questionnaire delivery and data collection. Detailed information on study sites and data collection can be found in Supplementary Data S1 (Supplementary Data are available online at www.liebertpub.com/chi).

The Young Lives study was approved by the London School of Hygiene Ethics Committee and participants provided informed consent before involvement.

Measures

Primary outcome–overweight/obesity age 8 years

BMI relative to the World Health Organization (WHO) international growth standards²⁹ was used to estimate overweight/obesity at age 8 years. Height and weight were measured by trained study personnel at the time of survey (mean of three measurements) and converted into normalized BMI-for-age z-scores using the WHO Anthro Plus software package.³⁰ Overweight was defined as more than one standard deviation (SD) above the reference median,²⁹ and obesity was defined as more than two SDs above the reference median. Analyses included exploring overweight and obese as separate entities. This was also transformed into a dichotomous variable for overweight/obesity (Y/N), referred to as overweight/or obesity hereafter. Children with BMI measures >5 SD above or below the reference median were excluded from analysis due to poor validity, consistent with other Young Lives' studies.³¹

Delivery mode

Mothers of the child (or in the absence of the mother, the child's primary caregiver, referred to as “caregivers” hereafter), were asked at baseline if the child was born through caesarean section (with planned and unplanned category also recorded) or vaginal birth.

Other risk factors

Models were adjusted for confounders and effect modifiers as identified in the published literature.^1,21–23,32 A variable was defined as a confounder if the following criteria were met: (1) the variable is associated with the exposure (delivery mode) and the outcome (childhood BMI); (2) the variable is not on the causal pathway between delivery mode and the outcome childhood BMI; (3) and the variable alters the measure of association by at least 10%. Variables in the data set included wealth index, household primary education level, maternal anthropometry, parity, birthweight, breastfed to 6 months, geographic location, smoker currently lives in household, total number of times child ate in last 24 hours, number of different food groups child ate in last 24 hours, and maternal age. Wealth Index is a proxy for household socioeconomic status used in the Young Lives study and comprised a matrix of three indices: housing quality, consumer durables, and services²⁷ as observed by the data collector. The Index is scored between 0 and 1 where a higher score indicates higher socioeconomic status.²⁷ This was used to categorize households into wealth quartiles within the current sample. Household primary education level was a dichotomous variable (yes/no) on whether the caregiver, partner of caregiver, or household head had completed primary school. Maternal overweight/obesity was based on measured height and weight at baseline and calculated BMI. Asian-derived BMI thresholds were used to define maternal underweight (<18.5 kg/m²), normal weight 18.5–22.9 kg/m²), maternal overweight (23–27.4 kg/m²), and obese (≥27.5 kg/m²) and used as a categorical variable.³³ Parity was defined as number of children born alive before the index child. Birthweight was categorized into three levels: <2500, 2500—4000, and >4000 g,¹⁶ and breastfeeding was defined as breastfed to at least 6 months of age as reported by caregiver (Y/N).¹⁶ Geographic locations (urban/rural) were assessed by the research assistant based on community location as precharacterized by sampling methods. Smoker currently lives in household was based on caregiver-reported information at the 8-year follow-up survey (Y/N). Dietary intake at age 8 years included caregiver-reported total number of meals eaten in the previous 24 hours and number of different food groups eaten in previous 24 hours. Maternal age was self-reported by mother or caregiver and used as continuous variable (years).

Statistical Analyses

Descriptive statistics were performed for all variables. Pearson chi-squared tests and Fishers exact test (i.e., where cell counts of n < 5 existed) were used to determine crude differences in the proportion of response categories for overweight and or obese. Independent t-tests were used to evaluate crude differences in continuous variables such as maternal age between birth mode categories.

Separate multivariable logistic regression models were used to explore the relationship between birth mode (i.e., the study exposure) and each outcome measure separately (overweight, obese, and overweight/or obese at age 8 years). Models were adjusted for confounders to obtain the final model using the following process: (1) a univariate logistic regression model containing only the explanatory variable (birth mode) was used to estimate the odds of each outcome measure in unadjusted models; (2) a logistic regression model containing the explanatory variable (birth mode) and each potential confounder one at a time was used to estimate the odds of each outcome measure; (3) from here a saturated model was developed for each outcome measure, containing the explanatory variable and all confounders. Each covariate met the inclusion for entry into the saturated model, if it was a predictor for the outcome measure (at the p < 0.2 level) or the addition of the covariate changed exposure effect estimate by >10% compared with the unadjusted model (Step 2); (4) A backward stepwise variable selection method was used with progressive removal of covariates until the most parsimonious model was achieved. Covariates were only removed from the final model if they met all three of the following criteria: (a) were not a significant predictor of the outcome (p > 0.05); (b) the model was a better fit with the covariate removed (using the likelihood-ratio statistic with α 0.05); (c) the removal of the covariate did not result in a >10% in the outcome estimate; and (5) biologically plausible interactions were tested. No significant interactions were observed, and therefore, the final models did not include any interaction terms.

A linear regression model was also used to estimate the impact caesarean section had on continuous BMI z-score at age 8 years. This model was adjusted for maternal BMI, breastfed to 6 months, geographic location, parity, child's sex, birthweight, number of different foods child ate in last 24 hours, and number of times child ate in last 24 hours.

All data were analyzed using SPSS version 22 statistical software.

Results

A total of 178 (9.2%) women had caesarean section birth. Of these, the majority were from the highest wealth quartile (n = 103; 57.9%), were primipara (n = 99; 55.6%) and were from urban locations (n = 91; 51.1%). Over one-third of caesarean section births were in overweight/obese women (n = 61; 34.2%), despite this group representing only 18.7% of women in the study.

Characteristics of Children Who Are Overweight or Obese

The characteristics of children who were overweight and obese at age 8 years are presented in Table 1.

Table 1.

Sociodemographic Characteristics of Respondents and Children Who Are Overweight in Vietnam (N = 1937)

	All Respondents		Overweight age 8		Obese age 8
Characteristic	n	%	n	%	n	%
All			110		79
Delivery mode
Vaginal	1759	90.8	86	78.2^*	52^*	65.8^*
Caesarean section (all)	178	9.2	24	21.8 ^*	27 ^*	34.2 ^*
Planned caesarean section	81	4.2	10	9.1	16	20.3
Unplanned caesarean section	97	5.0	14	12.7	11	13.9
Wealth index
Lowest quartile (Q1)	496	24.8	13	11.8^*	5	6.3^*
Lower middle quartile (Q2)	508	25.4	20	18.2^*	7	8.9^*
Upper middle quartile (Q3)	489	24.5	17	15.5^*	10	12.7^*
Highest quartile (Q4)	506	25.3	60	54.4^*	57	72.2^*
Child's sex (female)	970	48.5	16	20.3^*	46	41.8^*
Parity
Primipara	885	44.3	55	50^*	47	59.5^*
Multipara	1114	55.7	55	50^*	32	40.5^*
Not breastfed to 6 months of age	48	2.4	5	4.7^*	6	7.9^*
Geographic location
Urban	400	20	53	48.2^*	53	67.1^*
Rural	1600	80	57	51.8^*	26	32.9^*
Maternal anthropometry
Normal	1540	81.1	77	70^*	45	57^*
Overweight	316	16.6	29	26.4^*	29	36.7^*
Obese	43	2.3	4	3.6^*	5	6.3^*
Smoker lives in household (yes)	1041	54.9	61	55.5	38	48.1
Birth weight (kg) (n = 296 missing)
<2500 g	56	3.3	2	1.9	2	2.5
2500–4000 g	1558	92.8	98	92.5	71	89.9
>4000 g	65	3.9	6	5.7	6	7.6
Age mother (years) (mean ± SD)	27.2 (5.7)		28.1 (4.8)		29.7 (5.7)
Number of times child ate in last 24 hours (mean ± SD)	4.6 (1.2)		5.3 (1.2)		5.4 (0.9)
Number of different food groups eaten in last 24 hours (mean ± SD)	6.9 (2.0)		8.2 (1.9)		8.6 (1.6)

p < 0.05 pearson's chi-square and Fishers exact (where n < 5) tests for categorical variables; independent student t-tests for continuous variables.

Bold highlights that this is the outcome measure or measure of interest.

SD, standard deviation.

Caesarean Section Birth and BMI z-Score

Linear regression revealed that caesarean section birth predicted increasing BMI with birth through caesarean section associated with a 1.06-unit (95% CI 0.85–1.28, p < 0.001) increase in childhood BMI-z-score. Adjusted models showed a 0.64-unit (95% CI 0.41–0.86, p < 0.001) increase.

Odds of Overweight/Obesity

The logistic regression models revealed that caesarean section was associated with childhood overweight (unadjusted OR 3.6, 95% CI 2.2–5.8, p < 0.001), obesity (unadjusted OR 6.6, 95% CI 4.0–10.9, p < 0.001), and overweight/or obesity (unadjusted OR 4.8, 95% CI 3.4–7.0, p < 0.001) (Table 2). After adjustment for confounders these effects were attenuated to OR 1.8 (95% CI 1.03–3.2, p = 0.039), OR 2.2 (95% CI 1.2–4.0, p = 0.014), and OR 2.1 (95% CI 1.3–3.3, p = 0.002), respectively. Wealth, primary education, breastfed to 6 months, birthweight, and smoker living in household were not significant predictors of any outcome measure. Increasing maternal BMI predicted overweight, obese, or overweight/or obese at age 8 years. Both planned and unplanned caesarean section had similar odds of childhood overweight compared with vaginal birth [planned: unadjusted OR 5.6 (95% CI 3.4–9.1, p < 0.001), adjusted OR 2.3 (95% CI 1.2–4.1, p < 0.01); unplanned: unadjusted OR 4.3 (95% CI 2.6–6.9, p < 0.001), adjusted OR 1.9 (95% CI 1.1–3.5, p < 0.03)].

Table 2.

Odds of Overweight (n = 1527), Obese (n = 1744), and Overweight/or Obesity (n = 1937) (BMI z-Score) at Age 8 Years

	Overweight^a				Obese^b				Overweight/or obese^c
Variables	OR	95% CI		p	OR	95% CI		p	OR	95% CI		p
Unadjusted model
Delivery mode
Vaginal	1				1				1
Caesarean section	3.6	2.2	5.8	<0.001	6.6	4.0	10.9	<0.001	4.8	3.4	7.0	<0.001
Adjusted model
Delivery mode
Vaginal	1				1				1
Caesarean section (all)	1.8	1.03	3.2	0.039	2.2	1.2	4.0	0.014	2.1	1.3	3.3	0.002
Maternal BMI
Underweight	1
Normal	5.4	1.7	17.6	0.005	5.1	1.2	22.3	0.029	5.2	2.0	13.2	<0.001
Overweight	7.3	2.2	25.0	0.001	11.7	2.6	52.9	0.001	9.5	3.6	25.0	<0.002
Obese	9.5	2.0	46.6	0.005	14.5	2.3	90.6	0.004	13.1	3.8	45.0	<0.003
Breastfed to 6 months	0.7	0.3	2.0	0.524	—				1.2	0.5	2.9	0.600
Geographic location (rural)	0.4	0.3	0.6	<0.001	0.2	0.1	0.4	<0.001	0.3	0.2	0.4	<0.001
Parity (multipara)	—				0.3	0.2	0.6	<0.001	0.6	0.4	0.8	0.004
Child's sex (female)	0.6	0.4	1.0	0.033	0.2	0.1	0.4	<0.001	0.4	0.3	0.6	<0.001
Birthweight
<2500 g	1				—				1
2500–4000 g	1.1	0.3	5.0	0.860					1.2	0.4	3.8	0.774
>4000 g	1.3	0.2	7.3	0.802					1.5	0.4	6.2	0.541
Number of different food child ate in last 24 hours	1.3	1.2	1.5	<0.001	1.4	1.2	1.6	<0.001	1.3	1.2	1.5	<0.001
Number of times child ate in last 24 hours	—				—				1.1	0.9	1.3	0.259
Maternal age	—				1.1	1.0	1.1	0.019	—

Overweight model: wealth index, parity, household primary school education, number of times eaten in last 24 hours, smoker lives in household removed from model.

Obese model: wealth index, parity, birthweight, number of times child ate in last 24 hours, smoker lives in household removed from model.

Overweight/or obese model: wealth index, number of times child ate in last 24 hours, smoker lives in household removed from model.

—, denotes not included in final model as model is better fit with variable removed and variable does not change estimate by >10%.

CI, confidence interval; OR, odds ratio.

Discussion

The current study found that children born through caesarean section were twice as likely to be overweight or obese at age 8 years than children born through vaginal birth, even after adjusting for confounders. Previous published studies report an increased odds of overweight/obesity for children born through caesarean section between 2.1- and 5.2-times^13–16 that of vaginal birth. This is comparable to the increased odds observed in the current study. This provides further evidence that there may be an association between caesarean section birth and childhood overweight even after considering that maternal obesity and wealth influence decision for caesarean section birth and are also predictors for childhood overweight in LMICs.^19–22

The precise reason for this observed association is currently unclear, however, a growing body of evidence suggests that caesarean section birth may predispose infants to overweight/obesity later in life.^18,34 Microbiota dysbiosis has been observed between infants born through vaginal and caesarean section birth,³⁵ with newborns born through vaginal birth exposed to maternal vaginal and fecal microbiota and newborns born through caesarean section being exposed to maternal cutaneous microbiota as well as nonmaternally derived environmental bacteria.¹⁸ This may result in lasting changes to gut microbiota.¹⁸ During the first year of life, there is a rapid increase in the number and diversity of gut microbes, continuing the microbiota dysbiosis.^35,36 Early studies have shown that children born through caesarean have higher stool quantities of bacteria from the Firmicutes phylum or lower quantities of the Bacteroidetes phylum.^37,38 It may be possible that the ratio of these intestinal microbiota plays a role in childhood obesity. It has been observed that the intestines of obese children contain an increased proportion of Firmicutes and a lower proportion of Bacteroidetes than leaner children,^39,40 which has also been observed in adults.⁴¹ The ratio of Firmicutes and Bacteroidetes as an underlying mechanism behind the increased risk of childhood obesity for children born through caesarean warrants further investigation.

While gut microbiota is thought to play an important role in pathophysiology of obesity, other underlying mechanisms independent of the intestinal microbiota composition are also possible. For example, caesarean section may influence inflammation, immune, and endocrine function increasing the potential for long-term obesity risk.^42,43 Labor induces changes in levels of maternal and placental hormones as well as inflammatory cytokines, which do not occur in caesarean section birth, which has been hypothesized to influence obesity risk.^44,45

The current study also found that children born through elective/planned caesarean section had similar odds for overweight compared with children born through vaginal birth. This is consistent with other published studies, which show no difference in odds for unplanned and planned caesarean section and childhood overweight.^13,43 It is hypothesized that planned caesarean section may further prevent exposure to maternal microbiota as the newborn does not begin descending the vaginal canal compared with newborns who are born through unplanned caesarean section after labor has started.⁴⁶ However, current evidence is not strong to support an increased association between planned and childhood obesity compared with unplanned caesarean section.

While we were able to adjust for some potential confounders such as birth weight³² and breastfeeding,³⁸ we were unable to explore the role of other early-life exposures that may influence obesity risk later in life such as prepregnancy BMI,¹³ exposure to antibiotics,⁴⁸ or maternal weight gain during pregnancy.⁴² Antibiotic use, in particular, appears to play an important role, as antibiotics can change gut microbiota⁴⁷ and may have its greatest influence during pregnancy and early postnatal life. Several studies have shown prenatal and perinatal antibiotic use to be an independent risk factor for childhood overweight.^48,49 One study found that maternal antibiotic use during the second and third trimesters increased risk of childhood obesity by 84% compared with children not exposed to maternal antibiotics.⁴⁸ In the same study, the risk for childhood obesity was 46% for children born through caesarean section compared with vaginal birth.⁴⁸ Postnatal antibiotic use,⁵⁰ particularly in the first 6 months of life, has also been associated with higher body mass in early life and childhood.^48,49 Furthermore, the use of prophylactic antibiotics in caesarean section births may also disrupt the colonization of the newborn gut.^51,52

The current study findings suggest that there may be an association between caesarean section birth and childhood overweight. This is unlikely to be an artefact of confounding based on clinical decision-making or maternal sociodemographic characteristics. This may be due to decreased exposure to maternal microbiota at the time of birth, thus predisposing the child to overweight later in life, or due to other unknown reasons. Further research is needed to explore the underlying biological mechanisms of this finding, particularly in LMICs where little research has been conducted, despite increasing rates of caesarean section birth and childhood obesity.

Footnotes

Acknowledgments

We thank the Young Lives team and women and children who participated in this study. Young Lives is funded by UK aid from the Department for International Development (DFID), with cofunding from 2010 to 2014 by the Netherlands Ministry of Foreign Affairs, and from 2014 to 2015 by Irish Aid. The views expressed in this study are those of the author(s). They are not necessarily those of Young Lives, the University of Oxford, DFID, or other funders.

This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the London School of Hygiene Ethics Committee and an ethics exemption granted by the University of Western Australia for secondary analysis of the unidentifiable data. Written informed consent was obtained from all subjects/patients.

Author Disclosure Statement

No competing financial interests exist.

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