Abstract
Caesarean section (CS) rates are increasing globally and exceed 50% in some countries. Childhood obesity has been linked to CS via lack of exposure to vaginal microflora although the literature is inconsistent. We investigated the association between CS birth and the risk of childhood obesity using the nationally representative Growing-Up-in-Ireland (GUI) cohort. The GUI study recruited randomly 11134 infants. The exposure was categorised into normal vaginal birth (VD) [reference], assisted VD, elective (planned) CS and emergency (unplanned) CS. The primary outcome measure was obesity defined according to the International Obesity Taskforce criteria. Statistical analysis included multinomial logistic regression with adjustment for potential confounders. Infants delivered by elective CS had an adjusted relative risk ratio (aRRR) = 1.32; [95% confidence interval (CI) 1.01–1.74] of being obese at age three years. This association was attenuated when macrosomic children were excluded (aRRR = 0.99; [95% CI 0.67–1.45]). Infants delivered by emergency CS had an increased risk of obesity aRRR = 1.56; [95% CI 1.20–2.03]; this association remained after excluding macrosomic children. We found insufficient evidence to support a causal relationship between elective CS and childhood obesity. An increased risk of obesity in children born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora.
Introduction
Estimates from 121 countries reveal that Caesarean section (CS) rates increased from 6.7% in 1990 to 19.1% in 20141. In 2015 the United States had a 32.0% CS rate2, Brazil 55.5%3 and England 26.5%4. Ireland experienced a similar rise in CS rates with an increase from 10.5%1 in 1990 to 31.4%5 in 2015.
There is no consensus regarding the optimal population-level CS rate, however, a systematic review suggested that rates up to 16% were associated with reduced maternal, neonatal and infant mortality6 and a further review reported reduction in mortality up to a 19% rate7. Multiple factors have driven the CS rate increase, including advanced maternal age at first childbirth, a decrease in vaginal births after Caesarean (VBAC)8, physician fear of litigation, maternal choice and access to private health insurance9–13.
Babies delivered by CS, particularly elective CS, are generally not exposed to their mother’s vaginal and faecal microbiota, which helps to shape the initial composition of an infant’s microbiota including that of the gut14. Infants born by elective CS have been found to have a gut microbiome that has low diversity and richness15. Some studies suggest that infants born by CS might have a gut microbiota that has a tendency to harvest more dietary nutrients, thereby predisposing them to being overweight or obese16–18.
There is epidemiologic evidence of an association between CS birth and subsequent excess body mass index (BMI) across the life course19–22. Although heterogeneity, confounding, publication bias and inability to account for elective versus emergency CS delivery were limitations in trying to unpack this association, a study using a sibling-control design found that those born by CS had significantly higher odds of being obese later in life compared to their siblings born vaginally23. It was, however, not possible in this sibling-control study to completely rule out confounding by the indications for CS, although the observed association was unlikely to be due to familial or genetic confounding24.
Childhood obesity and overweight are at epidemic levels globally25. Although the aetiology of childhood excess adiposity is multifactorial, given its serious complications26, the aim of this study was to investigate the relationship between obstetric mode of delivery and childhood overweight and obesity. We hypothesised that infants born by elective CS, because of the aforementioned reduced exposure to their mother’s vaginal and faecal flora would be at higher risk of being overweight or obese. In the most recent (2018) systematic review and meta-analysis considering the association between CS birth and childhood obesity (six cohorts), distinction between elective and emergency CS was not made27. In addition, small sample sizes have previously limited the evaluation of elective CS28,29. We aimed to investigate the potential confounding effect of macrosomia and/or large for gestational age (LGA) on the association between CS delivery and obesity. To our knowledge one previous study investigated this confounding effect30.
Methods
Data source and population sampled
The Growing Up in Ireland (GUI) study is a nationally representative infant longitudinal cohort (http://www.esri.ie/growing-up-in-ireland/), which recruited randomly 11134 infants born in Ireland from 1st December 2007 to 30th June 200831–33. (Infants born during the months of July to November, inclusive, were not part of the GUI cohort.).
These children and their families had a baseline face-to-face questionnaire-based interview conducted by trained interviewers in participating households when the infants were approximately nine months old. Mother-infant pairs were subsequently followed-up by home interview when infants were three and five years old; follow-up continues. The response rates were as follows relative to most recent contact: at baseline interview (nine months) 64%, second interview (at three years) 91%, and at the third interview (at five years) 87%31–33. Children lost to follow-up tended to have unmarried mothers or mothers with lower educational attainment. In this study, children whose primary caregivers were not their mothers (n = 40, 0.36%) were excluded because the availability of potentially confounding variables such as age, maternal weight gain during pregnancy and health status predominantly pertained to mothers. In addition, children born by vaginal breech delivery (n = 41, 0.37%) and whose mode of delivery was unknown (n = 4, 0.04%) were also excluded, leaving 11,049 (99.2%) mother-infant pairs at baseline. Children born by vaginal breech delivery were excluded as they may differ from those born by vaginal cephalic delivery in important ways, for instance, they have a higher neonatal mortality rate34, moreover, we did not have enough numbers to include them as a separate category. Further details regarding the GUI study have been reported previously31–33.
Exposure and outcome ascertainment
The primary exposure variable was obtained from mothers during the initial face-to-face interview when infants were nine months old by asking them, “What was the final mode of delivery?”, which has been demonstrated to be a robust method35. The delivery mode was grouped into four categories, namely normal vaginal delivery (VD), assisted VD and elective/planned and emergency/unplanned CS. Elective/planned and emergency/unplanned CS were mainly pre-labour or in labour respectively. The onset of labour contractions is significant because offspring microbial colonisation generally begins afterwards36. Children born by pre-labour CS would have had little to no exposure to vaginal microflora while children born by CS in labour were likely to have been exposed. Assisted VD constituted delivery by forceps or vacuum extraction. We used this classification system because it is well accepted clinically, and importantly, it allows us to test the main hypothesis that the association between CS and the increased risk of childhood obesity is due to differential exposure to vaginal microflora by mode of birth. The GUI study did not collect data on individual CS indications. Although the main focus of the present study is CS compared to normal VD, the assisted VD group is included in the analysis for completeness.
The child’s height and weight were measured by a trained interviewer using a validated standard measuring stick (Leicester portable height measure) and a medically approved weighing scale (SECA 835 digital weighing scales)31–33. BMI in kg/m2 was calculated for each child and each child was then classified as thin, normal, overweight or obese, according to the International Obesity Task Force (IOTF) - now World Obesity Policy & Prevention - system for boys and girls at age three and five years (please see Table 1 for the cut-offs for each category)37,38.
Table 1.
International body mass index cut-off values by age and sex.
| 3 years | 5 years | |||
|---|---|---|---|---|
| Boys | Girls | Boys | Girls | |
| Body mass index (kg/m2) | ||||
| Thin | <14.74 | <14.47 | <14.21 | <13.94 |
| Normal | ≥14.74–<17.89 | ≥14.47–<17.56 | ≥14.21–<17.42 | ≥13.94–<17.15 |
| Overweight | ≥17.89–<19.57 | ≥17.56–<19.36 | ≥17.42–<19.30 | ≥17.15–<19.17 |
| Obese | ≥19.57 | ≥19.36 | ≥19.3 | ≥19.17 |
Potential confounders
Data on the following potential confounders as reported in the literature19–23 were collected and included a priori in the analyses as presented in Table 2: maternal age, ethnicity, educational level, marital status, infant sex, birth weight, gestational age, parity, weight gain during pregnancy, preeclampsia and gestational diabetes. Parity defined as the total number of stillbirths and live births a woman has had was not available, however, we used the number of individuals currently in the study household who were a son/daughter of the mother as a proxy for parity. Birth weight centiles, adjusted for sex and gestational age, were calculated using the Bulk Centile Calculator for Ireland (please see Table 2 for the classification criteria into small, appropriate and large for gestational age; SGA, AGA and LGA respectively)39.
Table 2.
Characteristics of the study population.
| Characteristic | Overall n (%) | Normal vaginal delivery n (%) | Assisted vaginal deliverya n (%) | Elective Caesarean section n (%) | Emergency Caesarean section n (%) |
|---|---|---|---|---|---|
| N | 11049 (100) | 6579 (59.5) | 1596 (14.4) | 1402 (12.7) | 1472 (13.3) |
| Maternal | |||||
| Age, (years) median IQR | 32 (28–36) | 32 (28–35) | 31 (27–35) | 35 (31–37) | 32 (28–35) |
| Ethnicity | |||||
| White | 10266 (92.9) | 6060 (92.1) | 1530 (95.9) | 1319 (94.1) | 1357 (92.2) |
| Other | 739 (6.7) | 489 (7.4) | 62 (3.9) | 80 (5.7) | 108 (7.3) |
| Missing | 44 (0.4) | 30 (0.5) | 4 (0.3) | 3 (0.2) | 7 (0.5) |
| Marital status | |||||
| Married and living with husband | 7421 (67.2) | 4317 (65.6) | 1007 (63.1) | 1110 (79.2) | 987 (67.1) |
| Married and separated from husband | 210 (1.9) | 131 (2.0) | 27 (1.7) | 24 (1.7) | 28 (1.9) |
| Divorced/Widowed | 134 (1.2) | 78 (1.2) | 16 (1.0) | 20 (1.4) | 20 (1.4) |
| Never married | 3148 (28.5) | 1955 (29.7) | 534 (33.5) | 235 (16.8) | 424 (28.8) |
| Missing | 136 (1.2) | 98 (1.5) | 12 (0.8) | 13 (0.9) | 13 (0.9) |
| Number of people in the household who are a son/daughter to the mother – ‘Parity’ | |||||
| 1 | 4508 (40.8) | 2104 (32.0) | 1208 (75.7) | 325 (23.2) | 871 (59.2) |
| 2 | 3643 (33.0) | 2424 (36.8) | 274 (17.2) | 583 (41.6) | 362 (24.6) |
| 3+ | 2898 (26.2) | 2051 (31.2) | 114 (7.1) | 494 (35.2) | 239 (16.2) |
| Missing | 14 (0.1) | 12 (0.2) | 0 (0.0) | 2 (0.1) | 0 (0.0) |
| Gestational age, (weeks) mean (±SD) | 39.5 (±2.1) | 39.7 (±1.9) | 40.1 (±1.6) | 38.7 (±1.7) | 38.9 (±3.0) |
| Missing | 37 (0.3) | 24 (0.4) | 4 (0.3) | 3 (0.2) | 6 (0.4) |
| Weight gain during pregnancy, (kg) mean (±SD) | 13.6 (±6.6) | 13.4 (±6.6) | 14.0 (±6.3) | 13.8 (±6.4) | 14.2 (±6.9) |
| Missing | 1500 (13.6) | 884 (13.4) | 236 (14.8) | 178 (12.7) | 202 (13.7) |
| Pre-eclampsia | 765 (6.9) | 354 (5.4) | 127 (8.0) | 107 (7.6) | 177 (12.0) |
| Gestational diabetes | 316 (2.9) | 151 (2.3) | 42 (2.6) | 61 (4.4) | 62 (4.2) |
| Offspring | |||||
| Sex | |||||
| Male | 5644 (51.1) | 3253 (49.4) | 885 (55.5) | 702 (50.1) | 804 (54.6) |
| Female | 5405 (48.9) | 3326 (50.6) | 711 (44.5) | 700 (49.9) | 668 (45.5) |
| Birth weight, (g) mean (±SD) | 3485 (±534) | 3507 (±502) | 3551 (±466) | 3431 (±562) | 3369 (±672) |
| Macrosomia (>4000 g) | 1539 (13.9) | 899 (13.7%) | 228 (14.3%) | 183 (13.1%) | 229 (15.6%) |
| Missing | 124 (1.1) | 70 (1.1) | 12 (0.8) | 26 (1.9) | 16 (1.1) |
| Birth weight centiles adjusted for sex and gestational age | |||||
| SGA < 10th centile | 1552 (14.0) | 910 (13.8) | 236 (14.8) | 175 (12.5) | 231 (15.7) |
| AGA ≥ 10th centile ≤ 90th centile | 8138 (73.7) | 4932 (75.0) | 1214 (76.1) | 983 (70.1) | 1009 (68.5) |
| LGA > 90th centile | 1199 (10.9) | 643 (9.8) | 130 (8.1) | 215 (15.8) | 211 (14.3) |
| Missing | 160 (1.4) | 94 (1.4) | 16 (1.0) | 29 (2.1) | 21 (1.4) |
| Body mass index (kg/m2) at 3 years* | |||||
| Thin | 445 (4.0) | 275 (4.2) | 56 (3.5) | 48 (3.4) | 66 (4.5) |
| Normal | 6748 (61.1) | 4037 (61.4) | 1000 (62.7) | 866 (61.8) | 845 (57.4) |
| Overweight | 1767 (16.0) | 1038 (15.8) | 249 (15.6) | 227 (16.2) | 253 (17.2) |
| Obese | 506 (4.6) | 280 (4.3) | 67 (4.2) | 73 (5.2) | 86 (5.8) |
| Missing | 1583 (14.3) | 949 (14.4) | 224 (14.0) | 188 (13.4) | 222 (15.1) |
| Body mass index (kg/m2) at 5 years* | |||||
| Thin | 534 (4.8) | 318 (4.8) | 78 (4.9) | 55 (3.9) | 83 (5.6) |
| Normal | 6459 (58.5) | 3860 (58.7) | 954 (59.8) | 834 (59.5) | 811 (55.1) |
| Overweight | 1389 (12.6) | 798 (12.1) | 215 (13.5) | 187 (13.3) | 189 (12.8) |
| Obese | 437 (4.0) | 252 (3.8) | 48 (3.0) | 65 (4.6) | 72 (4.9) |
| Missing | 2230 (20.2) | 1351 (20.5) | 301 (18.9) | 261 (18.6) | 317 (21.5) |
SD (Standard deviation), IQR (Interquartile range), SGA (Small for gestational age), AGA (Appropriate for gestational age), LGA (Large for gestational age).
aVacuum or forceps.
*International Obesity Task Force age and sex-specific cut-offs.
Educational level not shown because of up to 14 overlapping categories that were challenging to recode into coherent mutually exclusive groups, missing data 10 (0.1%).
Breast feeding can be considered to be a mediator because mothers who gave birth by CS, particularly elective CS, are less likely to breastfeed40 and babies not breast fed are prone to future excess adiposity41. Variables such as the number of antibiotic courses during the last year, typical time to bed and the presence of a television in the child’s room have been associated with an increased risk of childhood obesity42,43. These variables including breast feeding were, however, not considered as confounders because they came after CS and cannot by definition confound the association between mode of birth and childhood obesity44.
Missing data
Variables with missing data are as depicted in Table 2. The majority of key covariates had a low proportion of missing data. Importantly our outcome variable, BMI, had missing data either due to non-response or loss to follow-up which was equally distributed across the mode of delivery categories. Where a variable had a small amount of missing data (in this study all the key variables had <2% data missing) an extra category was added for example, ‘Ethnicity’ (1 = White; 2 = Other; 3 = Missing). It has been suggested that where missing data is minimal adding it as a missing category has a minimal impact on effect estimates45.
Statistical analysis
Statistical analysis was conducted using Stata version 14SE (StataCorp LP College Station, TX). Frequency (n) and percent (%) were used to report categorical variables. The mean (standard deviation-SD) or median (interquartile range-IQR) were used to report numeric variables.
To evaluate the study hypothesis at ages three and five, we used multinomial logistic regression to calculate the adjusted relative risk ratio (aRRR) with 95% confidence intervals (CIs) with normal VD as the reference category and normal BMI as the base outcome. We also considered the association between mode of birth and transition of IOTF BMI category from three to five years (two time points); 0 = remained normal (base outcome), 1 = remained obese, 2 = became obese, 3 = became non-obese and 4 = other transition. For the multinomial regression models because the IOTF childhood BMI classification starts at two years of age46, we thus did not examine the association between mode of delivery and BMI at nine months age.
To explore if any associations could be explained by other factors we conducted sensitivity analyses by restricting analysis to SGA, AGA, LGA or non-macrosomic infants. Secondly we combined vaginal breech delivery with normal vaginal birth to form the reference category. We also performed subgroup analyses by infant sex, preterm birth (<37 weeks), restricting analysis to infants whose mothers did not have pre-eclampsia and to mothers <35 years old. Statistical significance was defined as a p-value < 0.05.
Ethics statement
The GUI study received independent ethics approval from a Research Ethics Committee convened by the Department of Health and Children. Written informed consent was obtained from parents or guardians. All methods were performed in accordance with the relevant guidelines and regulations.
Results
Descriptive statistics
Of the 11049 infants, 8175 (74.0%) were delivered vaginally; most of these deliveries were by normal VD (59.5%) and the remainder were by assisted VD (14.4%). The rest of the deliveries (26.0%) were by CS; elective CS (12.7%) and emergency CS (13.3%) respectively (Table 2). The cohort had 51.1% boys and 48.9% girls; approximately 55% of deliveries by assisted VD and emergency CS were of boys. Of women who gave birth by elective CS just over half, 50.4%, were 35 years and older.
At birth, 13.9% of children were macrosomic (>4000 g); 10.9% were large for gestational age (population centiles). At three years of age, there were 1767 (18.7%) overweight and 506 (5.3%) obese children. At age five, the respective numbers were 1389 (15.8%) and 437 (5.0%).
Most children (n = 5030, 57.0%) remained within a normal BMI category between age three and five years whilst 175 (2.0%) remained obese. Two hundred and fifty six (2.9%) children who were obese at age three became non-obese (overweight, normal or thin) at age five and 262 (3.0%) children who were not obese at age three became obese at age five. Of the mothers who delivered vaginally, 13.2% were obese and of those who delivered by CS 21.5% were obese.
Mode of delivery and BMI at age three years
There was an association between elective CS (aRRR = 1.32; [95% CI 1.01–1.74]) and emergency CS (aRRR = 1.56; [95% CI 1.20–2.03]) and the risk of obesity at age three years compared to the reference group of children delivered by normal VD (Table 3). The risk of being overweight at age three years was associated with emergency CS (aRRR = 1.23; [95% CI 1.04–1.44]) but not elective CS (aRRR = 1.06; [95% CI 0.90–1.25]).
Table 3.
Mode of delivery and body mass index at age three years.
| BMI category (normal BMI – base outcome) | Cases n (%) | RRR (95% CI) | p-value | AdjRRR (95% CI)** | p-value |
|---|---|---|---|---|---|
| Thin | |||||
| Normal vaginal delivery | 275 (2.9) | reference | reference | ||
| Assisted vaginal delivery | 56 (0.6) | 0.82 (0.61–1.10) | 0.194 | 0.77 (0.56–1.05) | 0.098 |
| Elective Caesarean | 48 (0.5) | 0.81 (0.59–1.11) | 0.2 | 0.84 (0.61–1.16) | 0.299 |
| Emergency Caesarean | 66 (0.7) | 1.15 (0.87–1.52) | 0.336 | 1.11 (0.84–1.48) | 0.456 |
| Overweight | |||||
| Normal vaginal delivery | 1038 (11.0) | reference | reference | ||
| Assisted vaginal delivery | 249 (2.6) | 0.97 (0.83–1.13) | 0.684 | 1.02 (0.87–1.20) | 0.787 |
| Elective Caesarean | 227 (2.4) | 1.02 (0.87–1.20) | 0.815 | 1.06 (0.90–1.25) | 0.467 |
| Emergency Caesarean | 253 (2.7) | 1.17 (1.00–1.36) | 0.056 | 1.23 (1.04–1.44) | 0.013 |
| Obese | |||||
| Normal vaginal delivery | 280 (3.0) | reference | reference | ||
| Assisted vaginal delivery | 67 (0.7) | 0.97 (0.73–1.27) | 0.806 | 1.05 (0.78–1.39) | 0.764 |
| Elective Caesarean | 73 (0.8) | 1.22 (0.93–1.59) | 0.154 | 1.32 (1.01–1.74)*** | 0.045 |
| Emergency Caesarean | 86 (0.9) | 1.47 (1.14–1.89) | 0.003 | 1.56 (1.20–2.03) | 0.001 |
N for adjusted model = 9466. Multinomial logistic regression. BMI – Body mass index, RRR (Relative Risk Ratio), CI (Confidence intervals), Adj (Adjusted).
**Adjusted for maternal age, education, ethnicity, marital status, region, infant sex, gestational age, pre-eclampsia, gestational diabetes, parity. ***1.45 (1.10–1.91) when birth weight added.
There was no statistically significant association between elective CS and the risk of obesity at age three among AGA infants, (aRRR = 1.15; [95% CI 0.81–1.64]) (Supplementary Table S1). The analysis of AGA infants who were not macrosomic suggested that there was no association between elective CS and child obesity at age three years, (aRRR = 0.99; [95% CI 0.67–1.45]) (Supplementary Table S2). Among LGA infants there was an association between elective CS and the risk of obesity at age three years (aRRR = 2.01; [95% CI 1.10–3.67]) (Supplementary Table S3). The median birth weight for these LGA infants was 4200 g and their median birth centile was 97.6. SGA infants also drove the overall association, albeit just falling short of reaching statistical significance, (aRRR = 2.73; [95% CI 0.99–7.51]) (Supplementary Table S4). The median birth weight for these SGA infants was 3000 g and their median birth centile was 7.6. The p-value for the interaction term between delivery mode and birth centile categories in relation to obesity at age three years was <0.001.
There was an association between emergency CS (aRRR = 1.77; [95% CI 1.26–2.47]) and obesity when restricting to AGA non-macrosomic children (Supplementary Table S2).
For the observed elective CS effect, there was no statistically significant differential effect by sex, however, girls tended in the direction of having a greater effect size (p-value for interaction term was 0.093). Combining vaginal breech delivery with normal vaginal birth to form the reference category did not alter the results overall (data not shown). Excluding children of pregnancies complicated by pre-eclampsia or preterm birth and children of mothers less than 35 years of age did not affect the results overall (Supplementary Table S5).
Mode of delivery and BMI at age five years
At age five, the association between elective CS and obesity was of borderline significance (aRRR = 1.30; [95% CI 0.98–1.73]) (Table 4); this association was not changed materially when the analysis was restricted to AGA non-macrosomic infants (aRRR = 1.26; [95% CI 0.86–1.84] (Supplementary Table S6), thus an association cannot be completely ruled out. Furthermore, there was an association between emergency CS and the risk of obesity (aRRR = 1.46; [95% CI 1.10–1.93]) (Table 4). There were no other statistically significant associations between mode of delivery and the remaining BMI categories. Restricting the analysis to AGA non-macrosomic children did not alter the observed association between emergency CS and the risk of obesity (Supplementary Table S6).
Table 4.
Mode of delivery and body mass index at age five years.
| BMI category (normal BMI – base outcome) | Cases n (%) | RRR (95% CI) | p-value | AdjRRR (95% CI)** | p-value |
|---|---|---|---|---|---|
| Thin | |||||
| Normal vaginal delivery | 318 (3.6) | reference | reference | ||
| Assisted vaginal delivery | 78 (0.9) | 0.99 (0.77–1.28) | 0.954 | 0.95 (0.73–1.24) | 0.697 |
| Elective Caesarean | 55 (0.6) | 0.80 (0.60–1.08) | 0.14 | 0.78 (0.57–1.06) | 0.115 |
| Emergency Caesarean | 83 (0.9) | 1.24 (0.96–1.60) | 0.093 | 1.18 (0.90–1.54) | 0.238 |
| Overweight | |||||
| Normal vaginal delivery | 798 (9.0) | reference | reference | ||
| Assisted vaginal delivery | 215 (2.4) | 1.09 (0.92–1.29) | 0.31 | 1.15 (0.97–1.37) | 0.114 |
| Elective Caesarean | 187 (2.1) | 1.08 (0.91–1.29) | 0.366 | 1.13 (0.94–1.35) | 0.19 |
| Emergency Caesarean | 189 (2.1) | 1.13 (0.95–1.34) | 0.181 | 1.18 (0.99–1.42) | 0.066 |
| Obese | |||||
| Normal vaginal delivery | 252 (2.9) | reference | reference | ||
| Assisted vaginal delivery | 48 (0.5) | 0.77 (0.56–1.06) | 0.107 | 0.84 (0.60–1.16) | 0.279 |
| Elective Caesarean | 65 (0.7) | 1.19 (0.90–1.58) | 0.219 | 1.30 (0.98–1.73) | 0.072 |
| Emergency Caesarean | 72 (0.8) | 1.36 (1.04–1.79) | 0.027 | 1.46 (1.10–1.93) | 0.009 |
N for adjusted model = 8819. Multinomial logistic regression. BMI – Body mass index, RRR (Relative Risk Ratio), CI (Confidence intervals), Adj (Adjusted).
**Adjusted for maternal age, education, ethnicity, marital status, region, infant sex, gestational age, pre-eclampsia, gestational diabetes, parity.
Mode of delivery and BMI transition between ages three and five years
There was no association between elective CS and any BMI category transition (Supplementary Table S7). Those born by emergency CS had an increased risk of remaining obese from the age of three to five years (aRRR = 1.74; 95% CI 1.14–2.69]). Infants born by emergency CS also had an increased statistical risk of becoming non-obese (aRRR = 1.74; [95% CI 1.21–2.49]). Finally, emergency CS infants had an increased risk of making any other BMI category transition (aRRR = 1.20; [95% CI 1.04–1.38]).
Adding maternal weight gain in pregnancy (13.6% missing data) did not alter the interpretation of our results materially at age three or five years and transition between these ages.
Discussion
Main Findings
We investigated the association between CS birth, particularly elective CS, and the risk of childhood obesity using a large, prospective, nationally representative, longitudinal cohort study. In the multinomial logistic regression analysis we found insufficient evidence to support a causal relationship between elective CS and childhood obesity. Indications for emergency CS likely explained the increased risk of obesity observed in infants delivered via this mode, but not elective CS, suggesting that there is no causal effect due to vaginal microflora.
Strengths and limitations
Firstly, the GUI study is a large and nationally representative sample due to the application of sampling weights. The major strength was that our main outcome, BMI, based on height and weight was collected prospectively by trained personnel using validated techniques thus minimising measurement error. In addition, BMI was classified using widely accepted international criteria which allows comparison with other populations. We did not assume that once an individual is classified as obese, they remain so at a future time point. This allowed us in addition to evaluate if the mode of delivery was associated with transition into or out of obesity between time points. The availability of an ample suite of variables to adjust for confounding also strengthened our study. For example, we included gestational diabetes which was not included by several previous studies20.
A limitation was the unavailability of maternal pre-pregnancy BMI which has been highlighted to attenuate effect estimates when included in models20. However this limitation was partially ameliorated because we had access to maternal gestational weight gain, an important variable in its own right, which has been suggested to be significantly correlated with maternal pre-pregnancy BMI47. Recall bias remains a concern because some key variables were collected sometimes a year after pregnancy. Our main predictor, mode of delivery, relied on maternal recall nine months post-partum. We can be confident however that this is likely to be accurate in the vast majority of cases given that a similarly designed and conducted population-based study from the United Kingdom, the Millennium Cohort Study reported that 94% of mothers recalled their mode of delivery nine months post-partum when compared to their hospital records35. Another aspect worth mentioning is that infants born during the months of July to November, inclusive, were omitted from the GUI cohort. This is a constraint because month of birth can serve as a proxy for specific seasonal environmental circumstances that can significantly influence future health48.
The classification of CS into elective and emergency, although addressing a limitation of previous studies, did not allow sufficient granularity of issues like whether the CS was purely on maternal request; these may differ from other elective CSs, or if membranes had ruptured prior to surgery (exposure of the fetus to vaginal microbiota). All the women classified in the elective CS group had pre-labour CS. Although it is likely that women in the emergency CS group mostly had in labour CS, we cannot rule out the possibility that some of them had pre-labour CS. This is unlikely to have influenced the elective CS result, especially in terms of our hypothesis which is based on pre-labour CS. Improving CS classification is an ongoing worldwide effort that is only gaining traction during this century49. There was lack of statistical power for some analyses, like the overweight analysis, however the RRRs were similar to previously reported associations. Given the consistency of our results we thus think there is merit in them.
Our proxy measure for parity, the number of individuals in the study household who were a son/daughter of the mother, assumed for instance that the mother had no biologic children outside the household. Despite the assumptions we made, the average number of children a mother had in the GUI cohort, infants born circa 2008, was 1.97 which is close to the 2008 reported total fertility rate for Ireland of 2.0650. Thus the proxy parity variable was likely to be accurate in most cases and capture birth order sufficiently in the models.
Interpretation
The CS rate in this cohort was 26.0%, and is consistent with published national estimates of 25.6%9. This corroborates the national representativeness of the GUI cohort and the likely external validity of our findings. The 13.9% prevalence of macrosomia (>4000 g) however, was almost twice the 7.6% prevalence for the United States, another high-income country, during a similar time period circa 200851. This suggests a highly obesogenic Irish milieu with high baseline levels of excess adiposity from birth.
We found high rates of childhood obesity and overweight, for comparison global obesity rates for girls and boys in 1975 were less than 1%52. The slightly lower prevalence of obesity at age five (5.0%) than at age three (5.3%) was in keeping with the natural obesity prevalence decline observed from approximately age two to 14 years53.
Approximately 80 studies of various designs (cohort, case control, cross sectional) and several systematic reviews have investigated the association between CS and offspring obesity20,21,54. Most of these studies found a positive association, however evaluation of this association was limited by publication bias, potential for residual confounding and moderate heterogeneity20. Studies which accounted for maternal pre-pregnancy weight and adjusted their analyses for a greater number of potential confounders reported effect sizes closer to the null20.
As reported by the previous systematic reviews and meta-analyses, we also found a small effect size (odds ratio/RRR < 1.50) before accounting for macrosomia in the association between CS birth and subsequent overweight and obesity20,22. We too found a greater association between CS birth and being obese than with being overweight22.
Few studies have been able to differentiate between emergency and elective CS20,22,23. However our finding that elective/planned CS is a risk factor for obesity at three years has been found previously in an American prospective cohort from Boston followed up largely during this century55. Nevertheless this study did not explore the potential confounding effect of macrosomia. Inability to account for elective and emergency CS calls into question the findings and conclusions of a sibling-control study23 which suggested a causal link between CS birth and future obesity. Another study with a sibling-control design, albeit also limited by inability to distinguish between elective and emergency CS, did not find an association between CS birth and higher BMI z score at age five years56. Unfortunately, the GUI cohort did not have data that allows sibling-cohort analysis.
The association between CS and obesity generally dissipates with increasing age, which can be attributed to attrition, greater interference by external factors such as antibiotic therapy or because of the natural decline in obesity prevalence from two to 14 years22,23,53. A study with follow-up to age twenty found higher overweight and obesity rates as well as higher concentrations of total and low-density lipoprotein cholesterol, leptin and apolipoprotein B in those born by CS29. It however remained unsettled if these unfavourable rates and markers of cardiometabolic disease could be attributed to CS birth itself or to the underlying reasons that necessitated CS birth.
Most studies have adjusted for birth weight22, however, a Canadian population-based survey is to the best of our knowledge the only study to specifically consider macrosomia, defined in that study as >4080 g30. Although a non-modifiable risk factor, it is important to highlight that emergency CS was associated with being overweight and obese at three years and being obese at five years. In addition, infants delivered by emergency CS were more likely to ‘transition’ between ages three and five, namely: remain obese, become non-obese (normal, overweight or thin), or have any other transition between the IOTF BMI categories.
As mentioned in the introduction, infants born by CS may have a microbiota that is more capable of harvesting dietary nutrients16–18. With emergency CS, membranes are more likely to have ruptured with consequent exposure of the infant to vaginal microbiota resulting in reduced odds of future obesity compared with elective CS infants. However finding a greater effect size for obesity following emergency CS, as previously reported55, suggests other mechanisms may be at play with emergency CS namely confounding by indication. Indeed a recent study suggested that the main mechanism driving the microbiota’s structure and function in infancy is body site and not mode of delivery57. Like we mentioned the natural history and drivers of being overweight or obese differ significantly by age. Although there is literature on adults21, some of which supports our findings, we focused our discussion on childhood at ages comparable to those in our study.
Conclusion
We did not find enough evidence to support a causal relationship between elective CS and childhood obesity. An increased risk of obesity in children born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora and the association is likely to be explained by the underlying indications of emergency CS.
Electronic supplementary material
Acknowledgements
Data for the Growing Up in Ireland cohort is collected under the provisions of 1993 Statistics Act of the Central Statistics Office and funding is provided by the Government of Ireland through the Department of Children and Youth Affairs. The data was accessed via the Irish Social Science Data Archive - www.ucd.ie/issda. The Growing Up in Ireland Study team composed of Economic and Social Research Institute (ESRI) and Trinity College Dublin (TCD) staff designed and implements the project. G.M. is supported by the Irish Centre for Fetal and Neonatal Translational Research (INFANT) (grant no. 12/RC/2272).
Author Contributions
G.M., S.O.N., P.N.B., L.C.K., S.M.B.M., A.S.K. conceived and designed the study. G.M., S.O.N., A.S.K. analysed the data and all authors interpreted the results. G.M. wrote the first draft of the article and S.O.N., P.N.B., L.C.K., S.M.B.M., A.S.K. revised it critically for important intellectual content. All authors approved the final version and agree to be accountable for all aspects of the work.
Data Availability Statement
The data that support the findings of this study are available from the Irish Social Science Data Archive (ISSDA), www.ucd.ie/issda, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Bona fide researchers can apply for the data from ISSDA.
Competing Interests
The authors declare no competing interests.
Footnotes
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Supplementary information accompanies this paper at 10.1038/s41598-018-33482-z.
References
- 1.Betran AP, et al. The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990-2014. PLoS One. 2016;11:e0148343. doi: 10.1371/journal.pone.0148343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: Final Data for 2015. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. 2017;66:1. [PubMed] [Google Scholar]
- 3.Ministério da Saúde (2015).
- 4.Health and Social Care Information Centre. 6 (2015).
- 5.Healthcare Pricing Office. (ed Health Service Executive) (2017).
- 6.Betran AP, et al. What is the optimal rate of caesarean section at population level? A systematic review of ecologic studies. Reproductive health. 2015;12:57. doi: 10.1186/s12978-015-0043-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Molina G, et al. Relationship Between Cesarean Delivery Rate and Maternal and Neonatal Mortality. Jama. 2015;314:2263–2270. doi: 10.1001/jama.2015.15553. [DOI] [PubMed] [Google Scholar]
- 8.Lundgren I, et al. Clinicians’ views of factors of importance for improving the rate of VBAC (vaginal birth after caesarean section): a study from countries with low VBAC rates. BMC pregnancy and childbirth. 2016;16:350. doi: 10.1186/s12884-016-1144-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Betran AP, Torloni MR, Zhang JJ, Gulmezoglu AM. & Section, W. H. O. W. G. o. C. WHO Statement on Caesarean Section Rates. BJOG. 2016;123:667–670. doi: 10.1111/1471-0528.13526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Organisation for Economic Co-operation and Development. Health at a glance: OECD indicators (2015).
- 11.Lutomski JE, Murphy M, Devane D, Meaney S, Greene RA. Private health care coverage and increased risk of obstetric intervention. BMC pregnancy and childbirth. 2014;14:13. doi: 10.1186/1471-2393-14-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kenny LC, et al. Advanced maternal age and adverse pregnancy outcome: evidence from a large contemporary cohort. PLoS One. 2013;8:e56583. doi: 10.1371/journal.pone.0056583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Minkoff H. Fear of litigation and cesarean section rates. Semin Perinatol. 2012;36:390–394. doi: 10.1053/j.semperi.2012.04.025. [DOI] [PubMed] [Google Scholar]
- 14.Dominguez-Bello MG, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences of the United States of America. 2010;107:11971–11975. doi: 10.1073/pnas.1002601107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Azad MB, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013;185:385–394. doi: 10.1503/cmaj.121189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Turnbaugh PJ, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031. doi: 10.1038/nature05414. [DOI] [PubMed] [Google Scholar]
- 17.Jumpertz R, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. The American journal of clinical nutrition. 2011;94:58–65. doi: 10.3945/ajcn.110.010132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Tun Hein M., Bridgman Sarah L., Chari Radha, Field Catherine J., Guttman David S., Becker Allan B., Mandhane Piush J., Turvey Stuart E., Subbarao Padmaja, Sears Malcolm R., Scott James A., Kozyrskyj Anita L. Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring. JAMA Pediatrics. 2018;172(4):368. doi: 10.1001/jamapediatrics.2017.5535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Li HT, Zhou YB, Liu JM. The impact of cesarean section on offspring overweight and obesity: a systematic review and meta-analysis. International journal of obesity (2005) 2013;37:893–899. doi: 10.1038/ijo.2012.195. [DOI] [PubMed] [Google Scholar]
- 20.Kuhle S, Tong OS, Woolcott CG. Association between caesarean section and childhood obesity: a systematic review and meta-analysis. Obesity reviews: an official journal of the International Association for the Study of Obesity. 2015;16:295–303. doi: 10.1111/obr.12267. [DOI] [PubMed] [Google Scholar]
- 21.Darmasseelane K, Hyde MJ, Santhakumaran S, Gale C, Modi N. Mode of delivery and offspring body mass index, overweight and obesity in adult life: a systematic review and meta-analysis. PLoS One. 2014;9:e87896. doi: 10.1371/journal.pone.0087896. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Sutharsan R, Mannan M, Doi SA, Mamun AA. Caesarean delivery and the risk of offspring overweight and obesity over the life course: a systematic review and bias-adjusted meta-analysis. Clinical obesity. 2015;5:293–301. doi: 10.1111/cob.12114. [DOI] [PubMed] [Google Scholar]
- 23.Yuan, C. et al. Association Between Cesarean Birth and Risk of Obesity in Offspring in Childhood, Adolescence, and Early Adulthood. JAMA pediatrics, e162385, 10.1001/jamapediatrics.2016.2385 (2016). [DOI] [PMC free article] [PubMed]
- 24.Joseph KS, Mehrabadi A, Lisonkova S. Confounding by Indication and Related Concepts. Current Epidemiology Reports. 2014;1:1–8. doi: 10.1007/s40471-013-0004-y. [DOI] [Google Scholar]
- 25.Ng M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–781. doi: 10.1016/s0140-6736(14)60460-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Han JC, Lawlor DA, Kimm SY. Childhood obesity. Lancet. 2010;375:1737–1748. doi: 10.1016/s0140-6736(10)60171-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Keag OE, Norman JE, Stock SJ. Long-term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: Systematic review and meta-analysis. PLoS medicine. 2018;15:e1002494. doi: 10.1371/journal.pmed.1002494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Blustein J, et al. Association of caesarean delivery with child adiposity from age 6 weeks to 15 years. International journal of obesity (2005) 2013;37:900–906. doi: 10.1038/ijo.2013.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Hansen S, et al. Birth by cesarean section in relation to adult offspring overweight and biomarkers of cardiometabolic risk. International journal of obesity (2005) 2018;42:15–19. doi: 10.1038/ijo.2017.175. [DOI] [PubMed] [Google Scholar]
- 30.Flemming K, Woolcott CG, Allen AC, Veugelers PJ, Kuhle S. The association between caesarean section and childhood obesity revisited: a cohort study. Archives of disease in childhood. 2013;98:526–532. doi: 10.1136/archdischild-2012-303459. [DOI] [PubMed] [Google Scholar]
- 31.Quail, A. W. J., McCrory, C., Murray, A. & Thornton, M. (ed The Economic and Social Research Institute) (2011).
- 32.Murray, A. Q. A., McCrory, C. & Williams, J. (ed The Economic and Social Research Institute) (2013).
- 33.Murray, A. W. J., Quail, A. & Neary, M. & Thornton, M. A summary guide to wave 3 of the infant cohort (at 5 years) of Growing Up in Ireland (2015).
- 34.Bjellmo S, et al. Is vaginal breech delivery associated with higher risk for perinatal death and cerebral palsy compared with vaginal cephalic birth? Registry-based cohort study in Norway. BMJ Open. 2017;7:e014979. doi: 10.1136/bmjopen-2016-014979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Quigley MA, Hockley C, Davidson LL. Agreement between hospital records and maternal recall of mode of delivery: evidence from 12 391 deliveries in the UK Millennium Cohort Study. BJOG. 2007;114:195–200. doi: 10.1111/j.1471-0528.2006.01203.x. [DOI] [PubMed] [Google Scholar]
- 36.Rehbinder Eva Maria, Lødrup Carlsen Karin C., Staff Anne Cathrine, Angell Inga Leena, Landrø Linn, Hilde Katarina, Gaustad Peter, Rudi Knut. Is amniotic fluid of women with uncomplicated term pregnancies free of bacteria? American Journal of Obstetrics and Gynecology. 2018;219(3):289.e1-289.e12. doi: 10.1016/j.ajog.2018.05.028. [DOI] [PubMed] [Google Scholar]
- 37.Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. Bmj. 2000;320:1240–1243. doi: 10.1136/bmj.320.7244.1240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Cole TJ, Flegal KM, Nicholls D, Jackson AA. Body mass index cut offs to define thinness in children and adolescents: international survey. Bmj. 2007;335:194. doi: 10.1136/bmj.39238.399444.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Gardosi J & Francis A. Customised Weight Centile Calculator. Bulk Centile Calculator (IE). GROW version 6.7.8, 2017, http://www.gestation.net/GROW_documentation.pdf (2017).
- 40.Hobbs AJ, Mannion CA, McDonald SW, Brockway M, Tough SC. The impact of caesarean section on breastfeeding initiation, duration and difficulties in the first four months postpartum. BMC Pregnancy Childbirth. 2016;16:90. doi: 10.1186/s12884-016-0876-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Yan J, Liu L, Zhu Y, Huang G, Wang PP. The association between breastfeeding and childhood obesity: a meta-analysis. BMC Public Health. 2014;14:1267. doi: 10.1186/1471-2458-14-1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Gilbert-Diamond D, Li Z, Adachi-Mejia AM, McClure AC, Sargent JD. Association of a television in the bedroom with increased adiposity gain in a nationally representative sample of children and adolescents. JAMA pediatrics. 2014;168:427–434. doi: 10.1001/jamapediatrics.2013.3921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Anderson SE, Andridge R, Whitaker RC. Bedtime in Preschool-Aged Children and Risk for Adolescent Obesity. The Journal of pediatrics. 2016;176:17–22. doi: 10.1016/j.jpeds.2016.06.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.VanderWeele TJ, Shpitser I. On the definition of a confounder. Annals of statistics. 2013;41:196–220. doi: 10.1214/12-AOS1058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Vach W, Blettner M. Biased estimation of the odds ratio in case-control studies due to the use of ad hoc methods of correcting for missing values for confounding variables. Am J Epidemiol. 1991;134:895–907. doi: 10.1093/oxfordjournals.aje.a116164. [DOI] [PubMed] [Google Scholar]
- 46.Kelly Y., Patalay P., Montgomery S., Sacker A. BMI Development and Early Adolescent Psychosocial Well-Being: UK Millennium Cohort Study. PEDIATRICS. 2016;138(6):e20160967–e20160967. doi: 10.1542/peds.2016-0967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Bogaerts Annick, De Baetselier Elyne, Ameye Lieveke, Dilles Tinne, Van Rompaey Bart, Devlieger Roland. Postpartum weight trajectories in overweight and lean women. Midwifery. 2017;49:134–141. doi: 10.1016/j.midw.2016.08.010. [DOI] [PubMed] [Google Scholar]
- 48.Doblhammer G, Vaupel JW. Lifespan depends on month of birth. Proc Natl Acad Sci USA. 2001;98:2934–2939. doi: 10.1073/pnas.041431898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Robson MS. Classification of caesarean sections. Fetal and Maternal Medicine Review. 2001;12:23–39. doi: 10.1017/S0965539501000122. [DOI] [Google Scholar]
- 50.The World Bank. Fertility rate, total (births per woman), http://data.worldbank.org/indicator/SP.DYN.TFRT.IN?locations=IE (2016).
- 51.Martin JA, et al. Births: final data for 2008. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. 2010;59(1):3–71. [PubMed] [Google Scholar]
- 52.Abarca-Gómez Leandra, Abdeen Ziad A, Hamid Zargar Abdul, Abu-Rmeileh Niveen M, Acosta-Cazares Benjamin, Acuin Cecilia, Adams Robert J, Aekplakorn Wichai, Afsana Kaosar, Aguilar-Salinas Carlos A, Agyemang Charles, Ahmadvand Alireza, Ahrens Wolfgang, Ajlouni Kamel, Akhtaeva Nazgul, Al-Hazzaa Hazzaa M, Al-Othman Amani Rashed, Al-Raddadi Rajaa, Al Buhairan Fadia, Al Dhukair Shahla, Ali Mohamed M, Ali Osman, Alkerwi Ala'a, Alvarez-Pedrerol Mar, Aly Eman, Amarapurkar Deepak N, Amouyel Philippe, Amuzu Antoinette, Andersen Lars Bo, Anderssen Sigmund A, Andrade Dolores S, Ängquist Lars H, Anjana Ranjit Mohan, Aounallah-Skhiri Hajer, Araújo Joana, Ariansen Inger, Aris Tahir, Arlappa Nimmathota, Arveiler Dominique, Aryal Krishna K, Aspelund Thor, Assah Felix K, Assunção Maria Cecília F, Aung May Soe, Avdicová Mária, Azevedo Ana, Azizi Fereidoun, Babu Bontha V, Bahijri Suhad, Baker Jennifer L, Balakrishna Nagalla, Bamoshmoosh Mohamed, Banach Maciej, Bandosz Piotr, Banegas José R, Barbagallo Carlo M, Barceló Alberto, Barkat Amina, Barros Aluisio JD, Barros Mauro VG, Bata Iqbal, Batieha Anwar M, Batista Rosangela L, Batyrbek Assembekov, Baur Louise A, Beaglehole Robert, Romdhane Habiba Ben, Benedics Judith, Benet Mikhail, Bennett James E, Bernabe-Ortiz Antonio, Bernotiene Gailute, Bettiol Heloisa, Bhagyalaxmi Aroor, Bharadwaj Sumit, Bhargava Santosh K, Bhatti Zaid, Bhutta Zulfiqar A, Bi Hongsheng, Bi Yufang, Biehl Anna, Bikbov Mukharram, Bista Bihungum, Bjelica Dusko J, Bjerregaard Peter, Bjertness Espen, Bjertness Marius B, Björkelund Cecilia, Blokstra Anneke, Bo Simona, Bobak Martin, Boddy Lynne M, Boehm Bernhard O, Boeing Heiner, Boggia Jose G, Boissonnet Carlos P, Bonaccio Marialaura, Bongard Vanina, Bovet Pascal, Braeckevelt Lien, Braeckman Lutgart, Bragt Marjolijn CE, Brajkovich Imperia, Branca Francesco, Breckenkamp Juergen, Breda João, Brenner Hermann, Brewster Lizzy M, Brian Garry R, Brinduse Lacramioara, Bruno Graziella, Bueno-de-Mesquita H B(as), Bugge Anna, Buoncristiano Marta, Burazeri Genc, Burns Con, de León Antonio Cabrera, Cacciottolo Joseph, Cai Hui, Cama Tilema, Cameron Christine, Camolas José, Can Günay, Cândido Ana Paula C, Capanzana Mario, Capuano Vincenzo, Cardoso Viviane C, Carlsson Axel C, Carvalho Maria J, Casanueva Felipe F, Casas Juan-Pablo, Caserta Carmelo A, Chamukuttan Snehalatha, Chan Angelique W, Chan Queenie, Chaturvedi Himanshu K, Chaturvedi Nishi, Chen Chien-Jen, Chen Fangfang, Chen Huashuai, Chen Shuohua, Chen Zhengming, Cheng Ching-Yu, Chetrit Angela, Chikova-Iscener Ekaterina, Chiolero Arnaud, Chiou Shu-Ti, Chirita-Emandi Adela, Chirlaque María-Dolores, Cho Belong, Cho Yumi, Christensen Kaare, Christofaro Diego G, Chudek Jerzy, Cifkova Renata, Cinteza Eliza, Claessens Frank, Clays Els, Concin Hans, Confortin Susana C, Cooper Cyrus, Cooper Rachel, Coppinger Tara C, Costanzo Simona, Cottel Dominique, Cowell Chris, Craig Cora L, Crujeiras Ana B, Cucu Alexandra, D'Arrigo Graziella, d'Orsi Eleonora, Dallongeville Jean, Damasceno Albertino, Damsgaard Camilla T, Danaei Goodarz, Dankner Rachel, Dantoft Thomas M, Dastgiri Saeed, Dauchet Luc, Davletov Kairat, De Backer Guy, De Bacquer Dirk, De Curtis Amalia, de Gaetano Giovanni, De Henauw Stefaan, de Oliveira Paula Duarte, De Ridder Karin, De Smedt Delphine, Deepa Mohan, Deev Alexander D, Dehghan Abbas, Delisle Hélène, Delpeuch Francis, Deschamps Valérie, Dhana Klodian, Di Castelnuovo Augusto F, Dias-da-Costa Juvenal Soares, Diaz Alejandro, Dika Zivka, Djalalinia Shirin, Do Ha TP, Dobson Annette J, Donati Maria Benedetta, Donfrancesco Chiara, Donoso Silvana P, Döring Angela, Dorobantu Maria, Dorosty Ahmad Reza, Doua Kouamelan, Drygas Wojciech, Duan Jia Li, Duante Charmaine, Duleva Vesselka, Dulskiene Virginija, Dzerve Vilnis, Dziankowska-Zaborszczyk Elzbieta, Egbagbe Eruke E, Eggertsen Robert, Eiben Gabriele, Ekelund Ulf, El Ati Jalila, Elliott Paul, Engle-Stone Reina, Erasmus Rajiv T, Erem Cihangir, Eriksen Louise, Eriksson Johan G, la Peña Jorge Escobedo-de, Evans Alun, Faeh David, Fall Caroline H, Sant'Angelo Victoria Farrugia, Farzadfar Farshad, Felix-Redondo Francisco J, Ferguson Trevor S, Fernandes Romulo A, Fernández-Bergés Daniel, Ferrante Daniel, Ferrari Marika, Ferreccio Catterina, Ferrieres Jean, Finn Joseph D, Fischer Krista, Flores Eric Monterubio, Föger Bernhard, Foo Leng Huat, Forslund Ann-Sofie, Forsner Maria, Fouad Heba M, Francis Damian K, Franco Maria do Carmo, Franco Oscar H, Frontera Guillermo, Fuchs Flavio D, Fuchs Sandra C, Fujita Yuki, Furusawa Takuro, Gaciong Zbigniew, Gafencu Mihai, Galeone Daniela, Galvano Fabio, Garcia-de-la-Hera Manoli, Gareta Dickman, Garnett Sarah P, Gaspoz Jean-Michel, Gasull Magda, Gates Louise, Geiger Harald, Geleijnse Johanna M, Ghasemian Anoosheh, Giampaoli Simona, Gianfagna Francesco, Gill Tiffany K, Giovannelli Jonathan, Giwercman Aleksander, Godos Justyna, Gogen Sibel, Goldsmith Rebecca A, Goltzman David, Gonçalves Helen, González-Leon Margot, González-Rivas Juan P, Gonzalez-Gross Marcela, Gottrand Frederic, Graça Antonio Pedro, Graff-Iversen Sidsel, Grafnetter Dušan, Grajda Aneta, Grammatikopoulou Maria G, Gregor Ronald D, Grodzicki Tomasz, Grøntved Anders, Grosso Giuseppe, Gruden Gabriella, Grujic Vera, Gu Dongfeng, Gualdi-Russo Emanuela, Guallar-Castillón Pilar, Guan Ong Peng, Gudmundsson Elias F, Gudnason Vilmundur, Guerrero Ramiro, Guessous Idris, Guimaraes Andre L, Gulliford Martin C, Gunnlaugsdottir Johanna, Gunter Marc, Guo Xiuhua, Guo Yin, Gupta Prakash C, Gupta Rajeev, Gureje Oye, Gurzkowska Beata, Gutierrez Laura, Gutzwiller Felix, Hadaegh Farzad, Hadjigeorgiou Charalambos A, Si-Ramlee Khairil, Halkjær Jytte, Hambleton Ian R, Hardy Rebecca, Kumar Rachakulla Hari, Hassapidou Maria, Hata Jun, Hayes Alison J, He Jiang, Heidinger-Felso Regina, Heinen Mirjam, Hendriks Marleen Elisabeth, Henriques Ana, Cadena Leticia Hernandez, Herrala Sauli, Herrera Victor M, Herter-Aeberli Isabelle, Heshmat Ramin, Hihtaniemi Ilpo Tapani, Ho Sai Yin, Ho Suzanne C, Hobbs Michael, Hofman Albert, Hopman Wilma M, Horimoto Andrea RVR, Hormiga Claudia M, Horta Bernardo L, Houti Leila, Howitt Christina, Htay Thein Thein, Htet Aung Soe, Htike Maung Maung Than, Hu Yonghua, Huerta José María, Petrescu Constanta Huidumac, Huisman Martijn, Husseini Abdullatif, Huu Chinh Nguyen, Huybrechts Inge, Hwalla Nahla, Hyska Jolanda, Iacoviello Licia, Iannone Anna G, Ibarluzea Jesús M, Ibrahim Mohsen M, Ikeda Nayu, Ikram M Arfan, Irazola Vilma E, Islam Muhammad, Ismail Aziz al-Safi, Ivkovic Vanja, Iwasaki Masanori, Jackson Rod T, Jacobs Jeremy M, Jaddou Hashem, Jafar Tazeen, Jamil Kazi M, Jamrozik Konrad, Janszky Imre, Jarani Juel, Jasienska Grazyna, Jelakovic Ana, Jelakovic Bojan, Jennings Garry, Jeong Seung-Lyeal, Jiang Chao Qiang, Jiménez-Acosta Santa Magaly, Joffres Michel, Johansson Mattias, Jonas Jost B, Jørgensen Torben, Joshi Pradeep, Jovic Dragana P, Józwiak Jacek, Juolevi Anne, Jurak Gregor, Jureša Vesna, Kaaks Rudolf, Kafatos Anthony, Kajantie Eero O, Kalter-Leibovici Ofra, Kamaruddin Nor Azmi, Kapantais Efthymios, Karki Khem B, Kasaeian Amir, Katz Joanne, Kauhanen Jussi, Kaur Prabhdeep, Kavousi Maryam, Kazakbaeva Gyulli, Keil Ulrich, Boker Lital Keinan, Keinänen-Kiukaanniemi Sirkka, Kelishadi Roya, Kelleher Cecily, Kemper Han CG, Kengne Andre P, Kerimkulova Alina, Kersting Mathilde, Key Timothy, Khader Yousef Saleh, Khalili Davood, Khang Young-Ho, Khateeb Mohammad, Khaw Kay-Tee, Khouw Ilse MSL, Kiechl-Kohlendorfer Ursula, Kiechl Stefan, Killewo Japhet, Kim Jeongseon, Kim Yeon-Yong, Klimont Jeannette, Klumbiene Jurate, Knoflach Michael, Koirala Bhawesh, Kolle Elin, Kolsteren Patrick, Korrovits Paul, Kos Jelena, Koskinen Seppo, Kouda Katsuyasu, Kovacs Viktoria A, Kowlessur Sudhir, Koziel Slawomir, Kratzer Wolfgang, Kriemler Susi, Kristensen Peter Lund, Krokstad Steinar, Kromhout Daan, Kruger Herculina S, Kubinova Ruzena, Kuciene Renata, Kuh Diana, Kujala Urho M, Kulaga Zbigniew, Kumar R Krishna, Kunešová Marie, Kurjata Pawel, Kusuma Yadlapalli S, Kuulasmaa Kari, Kyobutungi Catherine, La Quang Ngoc, Laamiri Fatima Zahra, Laatikainen Tiina, Lachat Carl, Laid Youcef, Lam Tai Hing, Landrove Orlando, Lanska Vera, Lappas Georg, Larijani Bagher, Laugsand Lars E, Lauria Laura, Laxmaiah Avula, Bao Khanh Le Nguyen, Le Tuyen D, Lebanan May Antonnette O, Leclercq Catherine, Lee Jeannette, Lee Jeonghee, Lehtimäki Terho, León-Muñoz Luz M, Levitt Naomi S, Li Yanping, Lilly Christa L, Lim Wei-Yen, Lima-Costa M Fernanda, Lin Hsien-Ho, Lin Xu, Lind Lars, Linneberg Allan, Lissner Lauren, Litwin Mieczyslaw, Liu Jing, Loit Helle-Mai, Lopes Luis, Lorbeer Roberto, Lotufo Paulo A, Lozano José Eugenio, Luksiene Dalia, Lundqvist Annamari, Lunet Nuno, Lytsy Per, Ma Guansheng, Ma Jun, Machado-Coelho George LL, Machado-Rodrigues Aristides M, Machi Suka, Maggi Stefania, Magliano Dianna J, Magriplis Emmanuella, Mahaletchumy Alagappan, Maire Bernard, Majer Marjeta, Makdisse Marcia, Malekzadeh Reza, Malhotra Rahul, Rao Kodavanti Mallikharjuna, Malyutina Sofia, Manios Yannis, Mann Jim I, Manzato Enzo, Margozzini Paula, Markaki Anastasia, Markey Oonagh, Marques Larissa P, Marques-Vidal Pedro, Marrugat Jaume, Martin-Prevel Yves, Martin Rosemarie, Martorell Reynaldo, Martos Eva, Marventano Stefano, Masoodi Shariq R, Mathiesen Ellisiv B, Matijasevich Alicia, Matsha Tandi E, Mazur Artur, Mbanya Jean Claude N, McFarlane Shelly R, McGarvey Stephen T, McKee Martin, McLachlan Stela, McLean Rachael M, McLean Scott B, McNulty Breige A, Yusof Safiah Md, Mediene-Benchekor Sounnia, Medzioniene Jurate, Meirhaeghe Aline, Meisfjord Jørgen, Meisinger Christa, Menezes Ana Maria B, Menon Geetha R, Mensink Gert BM, Meshram Indrapal I, Metspalu Andres, Meyer Haakon E, Mi Jie, Michaelsen Kim F, Michels Nathalie, Mikkel Kairit, Miller Jody C, Minderico Cláudia S, Miquel Juan Francisco, Miranda J Jaime, Mirkopoulou Daphne, Mirrakhimov Erkin, Mišigoj-Durakovic Marjeta, Mistretta Antonio, Mocanu Veronica, Modesti Pietro A, Mohamed Mostafa K, Mohammad Kazem, Mohammadifard Noushin, Mohan Viswanathan, Mohanna Salim, Yusoff Muhammad Fadhli Mohd, Molbo Drude, Møllehave Line T, Møller Niels C, Molnár Dénes, Momenan Amirabbas, Mondo Charles K, Monterrubio Eric A, Monyeki Kotsedi Daniel K, Moon Jin Soo, Moreira Leila B, Morejon Alain, Moreno Luis A, Morgan Karen, Mortensen Erik Lykke, Moschonis George, Mossakowska Malgorzata, Mostafa Aya, Mota Jorge, Mota-Pinto Anabela, Motlagh Mohammad Esmaeel, Motta Jorge, Mu Thet Thet, Muc Magdalena, Muiesan Maria Lorenza, Müller-Nurasyid Martina, Murphy Neil, Mursu Jaakko, Murtagh Elaine M, Musil Vera, Nabipour Iraj, Nagel Gabriele, Naidu Balkish M, Nakamura Harunobu, Námešná Jana, Nang Ei Ei K, Nangia Vinay B, Nankap Martin, Narake Sameer, Nardone Paola, Navarrete-Muñoz Eva Maria, Neal William A, Nenko Ilona, Neovius Martin, Nervi Flavio, Nguyen Chung T, Nguyen Nguyen D, Nguyen Quang Ngoc, Nieto-Martínez Ramfis E, Ning Guang, Ninomiya Toshiharu, Nishtar Sania, Noale Marianna, Noboa Oscar A, Norat Teresa, Norie Sawada, Noto Davide, Nsour Mohannad Al, O'Reilly Dermot, Obreja Galina, Oda Eiji, Oehlers Glenn, Oh Kyungwon, Ohara Kumiko, Olafsson Örn, Olinto Maria Teresa Anselmo, Oliveira Isabel O, Oltarzewski Maciej, Omar Mohd Azahadi, Onat Altan, Ong Sok King, Ono Lariane M, Ordunez Pedro, Ornelas Rui, Ortiz Ana P, Osler Merete, Osmond Clive, Ostojic Sergej M, Ostovar Afshin, Otero Johanna A, Overvad Kim, Owusu-Dabo Ellis, Paccaud Fred Michel, Padez Cristina, Pahomova Elena, Pajak Andrzej, Palli Domenico, Palloni Alberto, Palmieri Luigi, Pan Wen-Harn, Panda-Jonas Songhomitra, Pandey Arvind, Panza Francesco, Papandreou Dimitrios, Park Soon-Woo, Parnell Winsome R, Parsaeian Mahboubeh, Pascanu Ionela M, Patel Nikhil D, Pecin Ivan, Pednekar Mangesh S, Peer Nasheeta, Peeters Petra H, Peixoto Sergio Viana, Peltonen Markku, Pereira Alexandre C, Perez-Farinos Napoleon, Pérez Cynthia M, Peters Annette, Petkeviciene Janina, Petrauskiene Ausra, Peykari Niloofar, Pham Son Thai, Pierannunzio Daniela, Pigeot Iris, Pikhart Hynek, Pilav Aida, Pilotto Lorenza, Pistelli Francesco, Pitakaka Freda, Piwonska Aleksandra, Plans-Rubió Pedro, Poh Bee Koon, Pohlabeln Hermann, Pop Raluca M, Popovic Stevo R, Porta Miquel, Portegies Marileen LP, Posch Georg, Poulimeneas Dimitrios, Pouraram Hamed, Pourshams Akram, Poustchi Hossein, Pradeepa Rajendra, Prashant Mathur, Price Jacqueline F, Puder Jardena J, Pudule Iveta, Puiu Maria, Punab Margus, Qasrawi Radwan F, Qorbani Mostafa, Bao Tran Quoc, Radic Ivana, Radisauskas Ricardas, Rahman Mahfuzar, Rahman Mahmudur, Raitakari Olli, Raj Manu, Rao Sudha Ramachandra, Ramachandran Ambady, Ramke Jacqueline, Ramos Elisabete, Ramos Rafel, Rampal Lekhraj, Rampal Sanjay, Rascon-Pacheco Ramon A, Redon Josep, Reganit Paul Ferdinand M, Ribas-Barba Lourdes, Ribeiro Robespierre, Riboli Elio, Rigo Fernando, de Wit Tobias F Rinke, Rito Ana, Ritti-Dias Raphael M, Rivera Juan A, Robinson Sian M, Robitaille Cynthia, Rodrigues Daniela, Rodríguez-Artalejo Fernando, del Cristo Rodriguez-Perez María, Rodríguez-Villamizar Laura A, Rojas-Martinez Rosalba, Rojroongwasinkul Nipa, Romaguera Dora, Ronkainen Kimmo, Rosengren Annika, Rouse Ian, Roy Joel GR, Rubinstein Adolfo, Rühli Frank J, Ruiz-Betancourt Blanca Sandra, Russo Paola, Rutkowski Marcin, Sabanayagam Charumathi, Sachdev Harshpal S, Saidi Olfa, Salanave Benoit, Martinez Eduardo Salazar, Salmerón Diego, Salomaa Veikko, Salonen Jukka T, Salvetti Massimo, Sánchez-Abanto Jose, Sandjaja, Sans Susana, Marina Loreto Santa, Santos Diana A, Santos Ina S, Santos Osvaldo, dos Santos Renata Nunes, Santos Rute, Saramies Jouko L, Sardinha Luis B, Sarrafzadegan Nizal, Saum Kai-Uwe, Savva Savvas, Savy Mathilde, Scazufca Marcia, Rosario Angelika Schaffrath, Schargrodsky Herman, Schienkiewitz Anja, Schipf Sabine, Schmidt Carsten O, Schmidt Ida Maria, Schultsz Constance, Schutte Aletta E, Sein Aye Aye, Sen Abhijit, Senbanjo Idowu O, Sepanlou Sadaf G, Serra-Majem Luis, Shalnova Svetlana A, Sharma Sanjib K, Shaw Jonathan E, Shibuya Kenji, Shin Dong Wook, Shin Youchan, Shiri Rahman, Siani Alfonso, Siantar Rosalynn, Sibai Abla M, Silva Antonio M, Silva Diego Augusto Santos, Simon Mary, Simons Judith, Simons Leon A, Sjöberg Agneta, Sjöström Michael, Skovbjerg Sine, Slowikowska-Hilczer Jolanta, Slusarczyk Przemyslaw, Smeeth Liam, Smith Margaret C, Snijder Marieke B, So Hung-Kwan, Sobngwi Eugène, Söderberg Stefan, Soekatri Moesijanti YE, Solfrizzi Vincenzo, Sonestedt Emily, Song Yi, Sørensen Thorkild IA, Soric Maroje, Jérome Charles Sossa, Soumare Aicha, Spinelli Angela, Spiroski Igor, Staessen Jan A, Stamm Hanspeter, Starc Gregor, Stathopoulou Maria G, Staub Kaspar, Stavreski Bill, Steene-Johannessen Jostein, Stehle Peter, Stein Aryeh D, Stergiou George S, Stessman Jochanan, Stieber Jutta, Stöckl Doris, Stocks Tanja, Stokwiszewski Jakub, Stratton Gareth, Stronks Karien, Strufaldi Maria Wany, Suárez-Medina Ramón, Sun Chien-An, Sundström Johan, Sung Yn-Tz, Sunyer Jordi, Suriyawongpaisal Paibul, Swinburn Boyd A, Sy Rody G, Szponar Lucjan, Tai E Shyong, Tammesoo Mari-Liis, Tamosiunas Abdonas, Tan Eng Joo, Tang Xun, Tanser Frank, Tao Yong, Tarawneh Mohammed Rasoul, Tarp Jakob, Tarqui-Mamani Carolina B, Tautu Oana-Florentina, Braunerová Radka Taxová, Taylor Anne, Tchibindat Félicité, Theobald Holger, Theodoridis Xenophon, Thijs Lutgarde, Thuesen Betina H, Tjonneland Anne, Tolonen Hanna K, Tolstrup Janne S, Topbas Murat, Topór-Madry Roman, Tormo María José, Tornaritis Michael J, Torrent Maties, Toselli Stefania, Traissac Pierre, Trichopoulos Dimitrios, Trichopoulou Antonia, Trinh Oanh TH, Trivedi Atul, Tshepo Lechaba, Tsigga Maria, Tsugane Shoichiro, Tulloch-Reid Marshall K, Tullu Fikru, Tuomainen Tomi-Pekka, Tuomilehto Jaakko, Turley Maria L, Tynelius Per, Tzotzas Themistoklis, Tzourio Christophe, Ueda Peter, Ugel Eunice E, Ukoli Flora AM, Ulmer Hanno, Unal Belgin, Uusitalo Hannu MT, Valdivia Gonzalo, Vale Susana, Valvi Damaskini, van der Schouw Yvonne T, Van Herck Koen, Van Minh Hoang, van Rossem Lenie, Van Schoor Natasja M, van Valkengoed Irene GM, Vanderschueren Dirk, Vanuzzo Diego, Vatten Lars, Vega Tomas, Veidebaum Toomas, Velasquez-Melendez Gustavo, Velika Biruta, Veronesi Giovanni, Verschuren WM Monique, Victora Cesar G, Viegi Giovanni, Viet Lucie, Viikari-Juntura Eira, Vineis Paolo, Vioque Jesus, Virtanen Jyrki K, Visvikis-Siest Sophie, Viswanathan Bharathi, Vlasoff Tiina, Vollenweider Peter, Völzke Henry, Voutilainen Sari, Vrijheid Martine, Wade Alisha N, Wagner Aline, Waldhör Thomas, Walton Janette, Bebakar Wan Mohamad Wan, Mohamud Wan Nazaimoon Wan, Wanderley Rildo S, Wang Ming-Dong, Wang Qian, Wang Ya Xing, Wang Ying-Wei, Wannamethee S Goya, Wareham Nicholas, Weber Adelheid, Wedderkopp Niels, Weerasekera Deepa, Whincup Peter H, Widhalm Kurt, Widyahening Indah S, Wiecek Andrzej, Wijga Alet H, Wilks Rainford J, Willeit Johann, Willeit Peter, Wilsgaard Tom, Wojtyniak Bogdan, Wong-McClure Roy A, Wong Justin YY, Wong Jyh Eiin, Wong Tien Yin, Woo Jean, Woodward Mark, Wu Frederick C, Wu Jianfeng, Wu Shouling, Xu Haiquan, Xu Liang, Yamborisut Uruwan, Yan Weili, Yang Xiaoguang, Yardim Nazan, Ye Xingwang, Yiallouros Panayiotis K, Yngve Agneta, Yoshihara Akihiro, You Qi Sheng, Younger-Coleman Novie O, Yusoff Faudzi, Yusoff Muhammad Fadhli M, Zaccagni Luciana, Zafiropulos Vassilis, Zainuddin Ahmad A, Zambon Sabina, Zampelas Antonis, Zamrazilová Hana, Zdrojewski Tomasz, Zeng Yi, Zhao Dong, Zhao Wenhua, Zheng Wei, Zheng Yingfeng, Zholdin Bekbolat, Zhou Maigeng, Zhu Dan, Zhussupov Baurzhan, Zimmermann Esther, Cisneros Julio Zuñiga, Bentham James, Di Cesare Mariachiara, Bilano Ver, Bixby Honor, Zhou Bin, Stevens Gretchen A, Riley Leanne M, Taddei Cristina, Hajifathalian Kaveh, Lu Yuan, Savin Stefan, Cowan Melanie J, Paciorek Christopher J, Chirita-Emandi Adela, Hayes Alison J, Katz Joanne, Kelishadi Roya, Kengne Andre Pascal, Khang Young-Ho, Laxmaiah Avula, Li Yanping, Ma Jun, Miranda J Jaime, Mostafa Aya, Neovius Martin, Padez Cristina, Rampal Lekhraj, Zhu Aubrianna, Bennett James E, Danaei Goodarz, Bhutta Zulfiqar A, Ezzati Majid. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. The Lancet. 2017;390(10113):2627–2642. doi: 10.1016/S0140-6736(17)32129-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Afshin A, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. The New England journal of medicine. 2017;377:13–27. doi: 10.1056/NEJMoa1614362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Kuhle S, Woolcott CG. Caesarean section is associated with offspring obesity in childhood and young adulthood. Evidence-based medicine. 2017;22:111. doi: 10.1136/ebmed-2017-110672. [DOI] [PubMed] [Google Scholar]
- 55.Huh SY, et al. Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study. Archives of disease in childhood. 2012;97:610–616. doi: 10.1136/archdischild-2011-301141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Rifas-Shiman Sheryl L., Gillman Matthew W., Hawkins Summer Sherburne, Oken Emily, Taveras Elsie M., Kleinman Ken P. Association of Cesarean Delivery With Body Mass Index z Score at Age 5 Years. JAMA Pediatrics. 2018;172(8):777. doi: 10.1001/jamapediatrics.2018.0674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Chu DM, et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017;23:314–326. doi: 10.1038/nm.4272. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from the Irish Social Science Data Archive (ISSDA), www.ucd.ie/issda, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Bona fide researchers can apply for the data from ISSDA.