Women who have C-sections are no more likely to have children who develop obesity than women who give birth naturally, according to a large study by researchers at Karolinska Institutet in Sweden, published in the journal PLOS Medicine.
The findings contradict several smaller studies that did find an association between C-section deliveries and offspring obesity but did not consider the numerous maternal and prenatal factors that the researchers did in this study.
Cesarean or C-section deliveries have soared in recent years, from 6.7 percent globally in 1990 to around 19.1 percent in 2014, according to earlier reports.
The jump has sparked intense research into the long-term consequences of C-section on offspring health, and several studies have linked cesarean deliveries with increased risks for asthma, various allergies and obesity.
The association with obesity has, however, mainly been confirmed in smaller studies that were unable to account for a wide array of possible confounders or differentiate between types of C-sections.
The researchers in this study set out to investigate if indeed increased C-section births could explain part of the rise in obesity also seen in the last decades, and whether this potential association held true once they accounted for maternal and prenatal factors known to impact offspring weight.
They compared the body-mass index (BMI) of nearly 100,000 male 18-year-olds and divided them into categories depending on whether they were born through vaginal delivery, elective C-section or non-elective C-section.
According to the data, 5.5 and 5.6 percent of the men delivered through elective and non-elective C-section, respectively, were obese compared to 4.9 percent of the men delivered vaginally.
But after accounting for other factors known to impact offspring weight—including prepregnancy BMI, maternal and gestational age and the presence of diabetes, hypertension, smoking and preeclampsia in the mother—the researchers concluded that the method of childbirth did not play a significant role in determining the risk of obesity in the offspring.
“We found no evidence to support a link between C-sections and the development of obesity,” says Daniel Berglind, researcher at the Department of Global Public Health at Karolinska Institutet.
“This tells us that how women give birth may not be an important factor in the origins of the global obesity epidemic.”
The researchers also identified nearly 10,000 full brothers and concluded that sibling analysis, accounting for genetic and environmental factors, did not alter the overall findings.
The strongest confounder in the association between mode of delivery and obesity was how much the mother weighed before she became pregnant.
This is consistent with previous reports on the heritability of obesity and the influence of maternal obesity on fetal health.
“Most of the association between C-section and obesity could be explained by maternal pre-pregnancy BMI,” says Viktor H. Ahlqvist, researcher at the Department of Global Public Health. “This suggests that heritability and fetal exposure to obese-causing factors in the womb are more important when assessing the risk of obesity in the offspring than the mode of delivery.”
As summarised by several systematic reviews and meta-analyses[1–5], numerous studies have found a consistent association between Caesarean section (CS) birth and subsequent childhood obesity. However, it remains unclear if this association indicates that CS causes obesity in childhood or is indicative of underlying confounding factors. A trial randomising pregnant women to deliver by CS or vaginally (VD) would provide definitive evidence.[6]
In the absence of this clinical trial, data from observational studies, albeit limited by the paucity and small sample size of relevant studies, have been leveraged by controlling for major confounding variables, notably from maternal pre-pregnancy body mass index (BMI),[7] by considering obesity in siblings discordant for birth mode,[8, 9] and by comparing those born by elective and emergency CS.[10–14] Animal[15, 16] and microbial studies[17, 18] have also helped to investigate this question.
Differences in the infant gut microflora, which influence nutrient uptake, is the main hypothesised mechanism by which childhood obesity develops following CS delivery in offspring.[19–21] Differential exposure to the vaginal, perineal and faecal microflora between infants born by CS, particularly elective CS, and those born vaginally is presumed to determine the initial composition of an infant’s gut microflora.[22, 23]
There is the contentious possibility, however, that the putative placental microbiota influences composition too, regardless of delivery mode.[24, 25] Another potential mechanism relates to differences between infants born by CS and VD in the intrapartum concentration of cortisol, noradrenaline and other inflammatory chemicals,[26, 27] which may result in long term neuro-immuno-endocrine, epigenetic and other changes which may influence energy metabolism.
Studying the associations underlying the role of CS with childhood obesity is important, given the global increase in CS rates and the epidemic of childhood obesity.[28–30] We recently performed two studies[10, 31] to address some of the limitations of previous reports, but both studies only followed-up offspring to age five years.
According to the systematic reviews and meta-analyses estimates of the strength of association between birth mode and childhood obesity, albeit with bias favouring positive effects, have been generally less than a relative risk of 1.50.[3, 4]
We aimed to investigate the association between planned/elective CS, a potentially modifiable risk factor, and childhood obesity using a large contemporary prospective longitudinal cohort study. In this study we used a similar approach to our previous work but with a different and larger dataset and much longer follow-up. This included analysis of the link between CS birth and body fat percentage (BF%) as previously performed,[31] on the basis that adiposity may be a more accurate measure of obesity than BMI.[32]
Materials and methods
The Millennium Cohort Study (MCS) is an ongoing multidisciplinary nationally representative longitudinal cohort study. At approximately nine months of age, children born in the United Kingdom (UK) from September 2000 through to January 2002 were recruited into the study, with over-sanpling for ethnic minorities. The overall sample was representative of the population. A total of 18,827 infants were enrolled. To date there have been six major data collection sweeps at nine months, three, five, seven, eleven and fourteen years of age. Data was collected by trained interviewers using validated procedures and instruments. Further comprehensive details about the MCS are available from its cohort profile [33]. Ethical approval for the Millennium Cohort Study surveys was granted by the London Multicentre Research Ethics Committee.
The exposure, mode of birth, was classified as normal or assisted VD and planned or emergency CS. Assisted VD constituted birth by forceps or vacuum extraction. Planned and emergency CS were mainly pre-labour or in labour respectively.[10]
Height was measured using a Leicester height measure. Weight and BF % were measured using TanitaTM scales; the latter was ascertained by the scale’s bioelectric impedance mechanism. BMI in kg/m2 was classified as thin, normal, overweight or obese according to the standard International Obesity Task Force (IOTF) criteria, which are sex and age specific.[34–36]. Of the major BMI classification systems, including those from the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), the IOTF criteria have been the most frequently used for this research topic.[3, 37] Using the 2006 WHO child growth standards, anthropometric z-scores were also calculated.[38]
Statistical analysis
Stata version 14SE (StataCorp LP College Station, TX) was used for statistical analysis. Categorical variables were described using frequencies (n) and percentages (%). Numeric variables were described using the mean (standard deviation-SD) or median (interquartile range-IQR). In the main analysis, to account for the continuous BMI, repeated measures available at age three, five, seven, eleven and fourteen years, crude and adjusted mixed-effects linear regression models were generated. In secondary analysis, to replicate our prior work,[10] multinomial logistic regression models were fitted to investigate the association between birth mode and IOTF BMI category transition between age three and five years; 0 = remained normal (base outcome), 1 = remained obese, 2 = became obese, 3 = became non-obese and 4 = any other transition. Linear regression models were fitted to investigate the association between birth mode and BF%, available at age seven and fourteen years.
Based on prior literature, potential confounders were defined a priori. These included maternal age, ethnicity, education, marital status, couple income, infant sex, birth weight, smoking during pregnancy, gestational age, diabetes mellitus, parity, and pre-pregnancy BMI.
We and other researchers found that infant macrosomia explained significant associations,[10, 31] we thus considered it as a potential confounder. Sub-group analysis was performed for infants with mothers aged > 35 years, born pre-term (< 37 weeks) and by their sex. A p-value < 0.05 was considered to be statistically significant.
Missing data
Multiple imputation was performed for maternal pre-pregnancy BMI and childhood BF% which all had substantial amounts of missing data. We assumed this data to be missing at random.[39] Variables in the main analysis were included in the imputation model. Forty-five imputations were done and the results were pooled according to Rubin’s rules.[40] Imputed values were checked for plausibility in relation to observed values
Results
The final baseline population consisted of 18,116 (96.2%) mother-infant pairs following exclusion of infants with an unknown mode of delivery (143, 0.76%), multiple births (467, 2.48%) and where the main respondent was not the infant’s biologic mother because some potentially confounding variables were available only where mothers were the respondents.
Of the 18,116 infants, 3872 (21.4%) were delivered by CS; planned CS (9.2%), emergency CS (12.2%), normal VD 12,567 (69.4%) and assisted VD 1,677 (9.3%) (Table 1). At birth, 10.8% of the infants were macrosomic (> 4kg). The IOTF prevalence of obesity at ages three, five, seven, eleven and fourteen years of age was 5.4%, 5.7%, 6.5%, 7.1% and 7.6% respectively (S1 Table). According to the WHO criteria overweight and obesity prevalence at age three years was 5.2% and 1.8% respectively (S1 Table).
At age seven years, the mean (SD) BF% was calculated at 19.1% (±5.1%) and 21.5% (±5.6%) for boys and girls respectively. The respective values at age fourteen years were 14.9% (±8.2%) and 26.6% (±7.0%).
Table 1
Characteristics of the study population.
| Characteristic | Overall n (%) | Normal vaginal delivery n (%) | Assisted vaginal delivery a n (%) | Planned Caesarean section n (%) | Emergency Caesarean section n (%) |
|---|---|---|---|---|---|
| N | 18,116 (100) | 12,567 (69.4) | 1677 (9.3) | 1669 (9.2) | 2203 (12.2) |
| Maternal age (years), median IQR | 29 (24–33) | 28 (23–32) | 29 (24–32) | 31 (27–34) | 30 (25–33) |
| < 20 | 1572 (8.7) | 1,214 (9.7) | 171 (10.2) | 42 (2.5) | 145 (6.6) |
| 20–24 | 3491 (19.3) | 2,643 (21.0) | 291 (17.4) | 207 (12.4) | 350 (15.9) |
| 25–29 | 5010 (27.7) | 3,491 (27.8) | 505 (30.1) | 409 (24.5) | 605 (27.5) |
| 30–34 | 5215 (28.8) | 3,447 (27.4) | 479 (28.6) | 605 (36.2) | 684 (31.0) |
| 35–39 | 2443 (13.5) | 1,541 (12.3) | 210 (12.5) | 342 (20.5) | 350 (15.9) |
| ≥ 40 | 382 (2.1) | 228 (1.8) | 21 (1.3) | 64 (3.8) | 69 (3.1) |
| Ethnicity | |||||
| European | 15,180 (83.3) | 10,411 (82.2) | 1,525 (90.9) | 1,426 (85.4) | 1,818 (82.5) |
| Asian | 1,911 (10.5) | 1,424 (11.3) | 101 (6.0) | 163 (9.8) | 223 (10.1) |
| African | 664 (3.7) | 464 (3.7) | 20 (1.2) | 51 (3.1) | 129 (5.9) |
| Mixed | 186 (1.0) | 134 (1.1) | 15 (0.9) | 17 (1.0) | 20 (0.9) |
| Any other background | 146 (0.8) | 107 (0.9) | 15 (0.9) | 11 (0.7) | 13 (0.6) |
| Missing | 29 (0.2) | 27 (0.2) | 1 (0.1) | 1 (0.1) | 0 (0.0) |
| Highest education | |||||
| GCSE grades D-G | 1,944 (10.7) | 1,392 (11.1) | 158 (9.4) | 163 (9.8) | 231 (10.5) |
| O level / GCSE grades A-C | 6,047 (33.4) | 4,202 (33.4) | 567 (33.8) | 570 (34.2) | 708 (32.1) |
| A / AS / S levels | 1,687 (9.3) | 1,153 (9.2) | 183 (10.9) | 137 (8.2) | 214 (9.7) |
| Diplomas in higher education | 1,511 (8.3) | 962 (7.7) | 179 (10.7) | 166 (9.9) | 204 (9.3) |
| First degree | 2,229 (12.3) | 1,369 (10.9) | 302 (18.0) | 218 (13.1) | 340 (15.4) |
| Higher degree | 604 (3.3) | 376 (3.0) | 66 (3.9) | 72 (4.3) | 90 (4.1) |
| Other academic qualifications (including overseas) | 526 (2.9) | 382 (3.0) | 37 (2.2) | 43 (2.6) | 64 (2.9) |
| None of these qualifications | 3,521 (19.4) | 2,691 (21.4) | 184 (11.0) | 299 (17.9) | 347 (15.8) |
| Missing | 47 (0.3) | 40 (0.3) | 1 (0.1) | 1 (0.1) | 5 (0.2) |
| Total net couple income (UK pounds) | |||||
| 0–10399 | 1,858 (10.3) | 1,360 (10.8) | 136 (8.1) | 151 (9.0) | 211 (9.6) |
| 10400–15599 | 2,522 (13.9) | 1,837 (14.6) | 201 (12.0) | 209 (12.5) | 275 (12.5) |
| 15600–19799 | 2,533 (14.0) | 1,762 (14.0) | 241 (14.4) | 226 (13.5) | 304 (13.8) |
| 20800–30199 | 3,185 (17.6) | 2,089 (16.6) | 336 (20.0) | 334 (20.0) | 426 (19.3) |
| 31200–80000+ | 3,198 (17.7) | 1,984 (15.8) | 385 (23.0) | 371 (22.2) | 458 (20.8) |
| Not applicable | 3,525 (19.5) | 2,639 (21.0) | 271 (16.2) | 227 (13.6) | 388 (17.6) |
| Don’t know | 921 (5.1) | 652 (5.2) | 64 (3.8) | 110 (6.6) | 95 (4.3) |
| Refused | 374 (2.1) | 244 (1.9) | 43 (2.6) | 41 (2.5) | 46 (2.1) |
| Marital status | |||||
| Legally separated | 516 (2.8) | 392 (3.1) | 24 (1.4) | 39 (2.3) | 61 (2.8) |
| Married, 1st and only marriage | 10016 (55.3) | 6,741 (53.6) | 958 (57.1) | 1,073 (64.3) | 1,244 (56.5) |
| Remarried, 2nd or later marriage | 730 (4.0) | 484 (3.9) | 46 (2.7) | 98 (5.9) | 102 (4.6) |
| Single never married | 6100 (33.7) | 4,419 (35.2) | 594 (35.4) | 370 (22.2) | 717 (32.5) |
| Divorced | 719 (4.0) | 507 (4.0) | 53 (3.2) | 83 (5.0) | 76 (3.4) |
| Widowed | 33 (0.2) | 22 (0.2) | 2 (0.1) | 6 (0.4) | 3 (0.1) |
| Missing | 2 (0.0) | 2 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Body mass index (kg/m2) pre-pregnancy, median IQR | 22.7 (20.6–25.7) | 22.5 (20.6–25.3) | 22.5 (20.7–25.1) | 23.7 (21.4–27.1) | 23.4 (21.2–26.8) |
| Missing | 1558 (8.6) | 1,110 (8.8) | 96 (5.7) | 159 (9.5) | 193 (8.8) |
| Smoking during pregnancy | |||||
| Non-smoker | 12,927 (71.4) | 8,935 (71.1) | 1,169 (69.7) | 1,244 (74.5) | 1,579 (71.7) |
| Gave up | 2,298 (12.7) | 1,526 (12.1) | 268 (16.0) | 208 (12.5) | 296 (13.4) |
| Smoker | 2,877 (15.9) | 2,094 (16.7) | 239 (14.3) | 216 (12.9) | 328 (14.9) |
| Missing | 14 (0.1) | 12 (0.1) | 1 (0.1) | 1 (0.1) | 0 (0.0) |
| Diabetes mellitus | |||||
| Any kind of diabetes mellitus | 313 (1.7) | 144 (1.1) | 18 (1.1) | 79 (4.7) | 72 (3.3) |
| No diabetes mellitus | 17,802 (98.3) | 12,422 (98.8) | 1,659 (98.9) | 1,590 (95.3) | 2,131 (96.7) |
| Missing | 1 (0.0) | 1 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Number of other children–‘parity’ | |||||
| 1 | 17,474 (96.5) | 12,113 (96.4) | 1,663 (99.2) | 1,571 (94.1) | 2,127 (96.6) |
| 2 | 470 (2.6) | 320 (2.5) | 11 (0.7) | 83 (5.0) | 56 (2.5) |
| 3+ | 168 (0.9) | 131 (1.0) | 3 (0.2) | 15 (0.9) | 19 (0.9) |
| Missing | 4 (0.0) | 3 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.0) |
| Sex | |||||
| Male | 9,322 (51.5) | 6,330 (50.4) | 930 (55.5) | 814 (48.8) | 1,248 (56.7) |
| Female | 8,794 (48.5) | 6,237 (49.6) | 747 (44.5) | 855 (51.2) | 955 (43.3) |
| Gestational age (weeks) | |||||
| Preterm (< 37) | 1708 (9.4) | 978 (7.8) | 100 (6.0) | 178 (10.7) | 452 (20.5) |
| Term (37–41) | 15,992 (88.3) | 11,306 (90.0) | 1,535 (91.5) | 1,467 (87.9) | 1,684 (76.4) |
| Postterm (> 42) | 225 (1.2) | 147 (1.2) | 28 (1.7) | 6 (0.4) | 44 (2.0) |
| Missing | 191 (1.1) | 136 (1.1) | 14 (0.8) | 18 (1.1) | 23 (1.0) |
| Birth weight (kg), median IQR | 3.37 (3.03–3.71) | 3.37 (3.04–3.71) | 3.43 (3.15–3.77) | 3.35 (3–3.69) | 3.36 (2.84–3.80) |
| Missing | 14 (0.1) | 11 (0.1) | 0 (0.0) | 3 (0.2) | 0 (0.0) |
| Macrosomia (> 4kg) | 1,957 (10.8) | 1,264 (10.1) | 184 (11.0) | 177 (10.6) | 332 (15.1) |
UK (United Kingdom), SD (Standard deviation), IQR (Interquartile range), GCSE (General Certificate of Secondary Education).
Vacuum or forceps a
Infants with missing data tended to have mothers that were younger, had General Certificate of Secondary Education grades D-G and an income of 0–10399 UK pounds–S2 Table.
The mean BMI by the four birth modes is depicted at each of the five time points, from age three to fourteen years, in S1 Fig. On average, mean BMI was lowest for normal VD and highest for planned CS. The mean BMI reached its nadir, of 16.3 kg/m2 at age five years. Fig 1 depicts the mean BMI for all VD and CS births; it was highest for the latter. Those born by planned CS had a mean BMI that was similar to those born by normal VD (adjusted mean difference = 0.00; [95% confidence interval (CI) -0.10; 0.11], p-value = 0.97) (Table 2). For those born by emergency CS the adjusted mean difference was 0.08; [95% CI -0.01; 0.17], p-value = 0.09.
Table 2
Mode of birth and body mass index.
| BMI | Coef (95% CI) | p-value | AdjCoef (95% CI)** | p-value |
|---|---|---|---|---|
| Normal vaginal | reference | reference | ||
| Assisted vaginal | -0.08 (-0.18; 0.02) | 0.116 | -0.03 (-0.13; 0.07) | 0.567 |
| Planned Caesarean | 0.18 (0.08; 0.28) | 0.000 | 0.00 (-0.10; 0.10) | 0.971 |
| Emergency Caesarean | 0.18 (0.09; 0.27) | 0.000 | 0.08 (-0.01; 0.17) | 0.091 |
Time points for adjusted model = 50,917 at ages three, five, seven, eleven and fourteen years. Mixed-effects linear regression. BMI–Body mass index, Coef (Coefficient), CI (Confidence intervals), Adj (Adjusted).
**Adjusted for maternal age, ethnicity, education, marital status, couple income, infant sex, birth weight, smoking, gestational age, diabetes mellitus, parity, pre-pregnancy BMI (Non-macrosomic infants).
There was no association between planned CS and any BMI category transition, S3 Table. The adjusted relative risk ratio of remaining obese from the age of three to five years among those born by emergency CS was 1.34; [95% CI 0.98; 1.82], p-value = 0.07.
At age seven years, there was no association between planned CS and BF% (adjusted BF% mean difference = 0.13; [95% CI -0.23; 0.49], p-value = 0.47) and emergency CS (adjusted BF% mean difference = 0.21; [95% CI -0.11; 0.54], p-value = 0.20) in comparison to the reference group of children delivered by unassisted VD (Table 3). At age fourteen years, there was also no association (Table 3). Imputing missing maternal pre-pregnancy BMI and BF% did not alter our results materially (S4 Table). The prevalence of being overweight and obese in the observed data was almost identical to that of the pooled data.
Table 3
Mode of delivery and body fat percent at seven and fourteen years.
| Delivery mode (seven years) | Coef. (95% CI) | p-value | AdjCoef. (95% CI)** | p-value |
| Normal vaginal delivery | reference | reference | ||
| Assisted vaginal | -0.21 (-0.56; 0.14) | 0.248 | 0.03 (-0.31; 0.37) | 0.864 |
| Planned Caesarean | 0.43 (0.08; 0.78) | 0.016 | 0.13 (-0.23; 0.49) | 0.466 |
| Emergency Caesarean | 0.35 (0.03; 0.67) | 0.032 | 0.21 (-0.11; 0.54) | 0.199 |
| Delivery mode (fourteen years) | Coef. (95% CI) | p-value | AdjCoef. (95% CI)** | p-value |
| Normal vaginal delivery | reference | reference | ||
| Assisted vaginal | -1.26 (-1.91; -0.61) | 0.000 | -0.40 (-0.94; -0.13) | 0.139 |
| Planned Caesarean | 0.50 (-0.16; 1.15) | 0.135 | -0.08 (-0.64; 0.47) | 0.769 |
| Emergency Caesarean | -0.04 (-0.62; -0.55) | 0.904 | -0.00 (-0.50; 0.50) | 0.999 |
N for adjusted model = 10,254 and 8,279 at age seven and fourteen respectively. Linear regression. Coef (Coefficient), CI (Confidence intervals), Adj (Adjusted).
**Adjusted for maternal age, ethnicity, education, marital status, couple income, infant sex, birth weight, smoking, gestational age, diabetes mellitus, parity, pre-pregnancy body mass index (Non-macrosomic infants).
Sub-group analysis for infants with mothers > 35 years old, born pre-term or by their sex did not reveal any statistically significant results (S5–S8 Tables).
More information: “Elective and nonelective cesarean section and obesity among young adult male offspring: a Swedish population-based cohort study,” Viktor H. Ahlqvist, Margareta Persson, Cecilia Magnusson, Daniel Berglind, PLOS Medicine, Dec. 6, 2019, DOI: 10.1371/journal.pmed.1002996
