Literature DB >> 30878984

Association between caesarean section delivery and obesity in childhood: a longitudinal cohort study in Ireland.

Gwinyai Masukume1,2, Fergus P McCarthy1,2,3, Philip N Baker4, Louise C Kenny5, Susan Mb Morton6, Deirdre M Murray1,7, Jonathan O'B Hourihane1,7, Ali S Khashan1,8.   

Abstract

OBJECTIVES: To investigate the association between caesarean section (CS) birth and body fat percentage (BF%), body mass index (BMI) and being overweight or obese in early childhood.
DESIGN: Prospective longitudinal cohort study.
SETTING: Babies After Screening for Pregnancy Endpoints: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints cohort. PARTICIPANTS: Infants born to mothers recruited from the Screening for Pregnancy Endpoints study, Cork University Maternity Hospital between November 2007 and February 2011. OUTCOME MEASURE: Overweight or obese defined according to the International Obesity Task Force criteria.
RESULTS: Of the 1305 infants, 362 (27.8%) were delivered by CS. On regression analysis, BF% at 2 months did not differ significantly by delivery mode. Infants born by CS had a higher mean BMI at 6 months compared with those born vaginally (adjusted mean difference=0.24; 95% CI 0.06 to 0.41, p value=0.009). At 2 years, no difference was seen across the exposure groups in the risk of being overweight or obese. At 5 years, the association between prelabour CS and the risk of overweight or obesity was not statistically significant (adjusted relative risk ratio, aRRR=1.37; 95% CI 0.69 to 2.69) and the association remained statistically nonsignificant when children who were macrosomic at birth were excluded from the model (aRRR=0.86; 95% CI 0.36 to 2.08).
CONCLUSION: At 6 months of age, children born by CS had a significantly higher BMI but this did not persist into future childhood. There was no evidence to support an association between mode of delivery and long-term risk of obesity in the child. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Entities:  

Keywords:  Ireland; body composition; body fat; caesarean section; childhood; obesity

Year:  2019        PMID: 30878984      PMCID: PMC6429933          DOI: 10.1136/bmjopen-2018-025051

Source DB:  PubMed          Journal:  BMJ Open        ISSN: 2044-6055            Impact factor:   2.692


Data were obtained from a well-phenotyped contemporary prospective longitudinal cohort study. Body fat percentage was measured by air displacement plethysmography which is regarded as the gold standard method. A limitation was the unavailability of maternal pre-pregnancy body mass index. The number of overweight and obesity cases at 2 and 5 years of age was limited.

Introduction

Over recent decades, caesarean section (CS) rates have risen considerably worldwide and in some countries, CS rates now exceed 50%.1 The aetiology of the global CS rate increase is multifactorial and includes a decline in vaginal births after caesarean, physician fear of litigation, maternal request, more multiple pregnancies resulting from greater assisted reproductive technology use and access to private health insurance.2–7 Although a timely CS can be both necessary and life-saving, for example, in cases of obstructed labour, transverse lie and fetal distress/compromise, it nevertheless conveys complications. For the mother, these include an increased length of hospital stay, infection and haemorrhage, as well as a higher risk of respiratory complications in the infant and consequent admission to the neonatal intensive care unit.8 Birth weight is the most commonly used indicator of in utero growth; however, body composition at birth, the relative proportion of fat and fat-free mass can provide a more accurate picture.9 We have shown retrospectively that neonatal body fat percentage (BF%) is more closely linked to risk of CS than birth weight.10 Therefore, conversely changes in BF% could be an early and more sensitive indicator of future health. It has been hypothesised that the described association between abnormal birth weight and future cardiometabolic disease11 across the life course can be more closely attributed to differences in early life body composition than to birth weight differences.9 CS itself has been consistently associated with an increased risk of obesity later in life, although studies have been inconclusive.12–14 It is also unclear whether this increased risk pertains to elective/prelabour CS or emergency CS/CS in labour. Making this distinction is challenging because of limited literature so much so that the latest systematic review and meta-analysis on the topic (2018) performed an analysis including all CS and did not differentiate.15 Several research papers have been able to distinguish between elective and emergency CS but these have been limited by small sample sizes.16–18 With CS in labour, membranes are more likely to have ruptured, thereby exposing the infant to vaginal microflora.19 However, lack of exposure to the vaginal microflora among infants born by elective CS, where membranes are more likely to be intact, has been suggested as the main causal mechanism for the increased risk of obesity later in life.20–22 Some have disputed this23 24; nevertheless, robust data from animal experiments demonstrate a potential causal role for CS delivery in the development of childhood obesity.25 Given the worldwide increase in nonmedically indicated prelabour CS,8 this type of CS represents a potentially modifiable risk factor for childhood obesity. The aim of this study was to investigate the relationship between CS delivery, particularly prelabour CS, and childhood body composition and growth, using a well-phenotyped prospective longitudinal birth cohort with detailed clinical phenotyping of both mothers and their children. We wanted, in particular, to examine the potential confounding effect of macrosomia, as this is both a risk factor for CS and for long-term obesity.

Methods

Data source and population sampled

Data were obtained from the Irish cohort of the prospective Screening for Pregnancy Endpoints (SCOPE) study of ‘low-risk’ nulliparous women with singleton pregnancies (ACTRN12607000551493, www.scopestudy.net/) and its follow-up prospective Irish birth cohort, the Babies After SCOPE: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints (BASELINE) study (NCT01498965, www.baselinestudy.net/). The SCOPE and BASELINE study methodologies are reported in detail elsewhere.26 27 Briefly, the aim of the SCOPE study was to develop screening approaches, clinical and molecular, to predict fetal growth restriction, pre-eclampsia and spontaneous preterm birth in healthy nulliparous women during early gestation. Exclusion criteria included the following: (1) considered to be at high risk of fetal growth restriction, pre-eclampsia or spontaneous preterm birth due to underlying medical conditions (chronic hypertension, diabetes, renal disease, systemic lupus erythematosus, anti-phospholipid syndrome, sickle cell disease, HIV), previous cervical knife cone biopsy, ≥3 previous terminations or ≥3 miscarriages, current ruptured membranes; (2) had a major uterine anomaly, a known major fetal anomaly or abnormal karyotype or (3) received an intervention that could modify pregnancy outcome (eg, aspirin therapy, cervical suture). In brief, the BASELINE cohort participant’s mothers were recruited at 15±1 weeks of pregnancy from Cork University Maternity Hospital between November 2007 and February 2011. Of the 2579 women approached to participate, 1774 (69%) gave their written informed consent. From those, 1537 (87%) had infants recruited into the BASELINE study. The sociodemographic, lifestyle and physical measurements were collected by trained research midwives. A complete audit trial was available for the data that were entered into a centrally accessed internet database (MedSciNet AB, Stockholm, Sweden).

Exposure and outcome ascertainment

Delivery mode was grouped into four categories, namely unassisted vaginal delivery (VD), operative VD, prelabour lower segment (LS) CS and LSCS in labour. Operative VD constituted delivery by either vacuum extraction or forceps. Whole body density was calculated from naked weight measured by an electronic scale (seca 384; seca, Birmingham, UK) to the nearest gram divided by body volume estimated by the PEA POD air displacement plethysmography system (COSMED, Concord, CA, USA) within the first 4 days of life and also at age 2 months. The PEA POD agrees highly with the gold standard four-compartment model and is noninvasive, fast and safe.10 28 29 Based on body density and a two-compartment model of body composition (fat and fat-free mass), using values established by Fomon,28 BF%, the primary outcome, was calculated as follows: ([fat mass, kg/body mass, kg]×100). The child’s height and weight were measured by a trained interviewer using standardised protocols and medically approved instruments. At birth, 2 months, 6 months, 1 year, 2 years and 5 years of age, body mass index (BMI) in kg/m2 was calculated for each child. At age 2 and 5 years, BMI was classified as thin, normal, overweight or obese, according to the International Obesity Task Force (IOTF) criteria.30 31 The IOTF classification begins at age 2 years. The following potential confounders as reported in the literature12–14 32 33 were included a priori: maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia. For instance, smoking cigarettes is a potential confounder because it is a risk factor for both CS birth34 and for childhood obesity.35

Statistical analysis

Stata V.14SE (StataCorp LP College Station, TX, USA) was used for statistical analysis. Categorical variables were described using frequency (n) and per cent (%). Numeric variables were described using the mean (SD) or median (IQR). Crude and adjusted linear regression models were used to examine the association between mode of delivery and BF%. Linear regression models were also used to evaluate the association between delivery mode and BMI as a continuous measure. Crude and adjusted multinomial logistic regression models were used to examine the association between mode of delivery and the risk of being overweight or obese. Adjusted mean differences and adjusted relative risk ratios (aRRR), for the linear and multinomial logistic regression models, respectively, were calculated with 95% CIs. Unassisted VD was the reference category and normal BMI was the base outcome for the multinomial logistic regression models. Models were stratified by whether infants were macrosomic or not which was defined as a birth weight >4000 g or ≤4000 g, respectively. We also explored interaction by infant sex. Statistical significance was defined as a p < 0.05.

Patient involvement

Participants were not involved in establishing the research question, outcome measures including the study design and interpretation or writing of this paper. The results will be disseminated via the study website, social media, information evenings and by newsletter.

Results

Of the 1305 infants, 943 (72.3%) were delivered vaginally. The remainder of the deliveries (27.8%) were by CS; prelabour LSCS (12.0%) and LSCS in labour (15.8%), respectively (table 1). At birth, 13.0% of infants were macrosomic (>4000 g); 11.0% were large for gestational age (>90th percentile for customised birth weight centiles). At 2 years of age, 116 (10.9%) children were overweight or obese (using IOTF cut-offs). At age 5 years, the respective number was 118 (14.5%). At age 2 months, the mean (SD) BF% was calculated at 21.8% (±4.3%). BF% approximated to the normal distribution.
Table 1

Characteristics of the study population at 2 months

CharacteristicOverall n (%)Unassisted vaginal n (%)Operative vaginal * n (%)Prelabour LSCS n (%)LSCS in labour n (%)
N1305 (100)470 (36.0)473 (36.2)156 (12.0)206 (15.8)
Maternal age (years), median IQR30 (28–33)30 (27–32)30 (28–33)32 (29.5–34)31 (29–33)
 <2019 (1.5)9 (1.9)9 (1.9)1 (0.6)0 (0.0)
 20–24111 (8.5)57 (12.1)38 (8.0)4 (2.6)12 (5.8)
 25–29388 (29.7)157 (33.4)139 (29.4)34 (21.8)58 (28.2)
 30–34615 (47.1)215 (45.7)214 (45.2)85 (54.5)101 (49.0)
 35–39155 (11.9)31 (6.6)66 (14.0)28 (17.9)30 (14.6)
 ≥4017 (1.3)1 (0.2)7 (1.5)4 (2.6)5 (2.4)
Ethnicity
 Caucasian1287 (98.6)463 (98.1)466 (98.5)155 (99.4)203 (98.5)
 Other18 (1.4)7 (1.5)7 (1.5)1 (0.6)3 (1.5)
Schooling (years primary and secondary), median IQR†13 (13–14)13 (13–14)13 (13–14)13 (13–14)13 (13–14)
Marital status
 Single123 (9.4)52 (11.1)49 (10.4)11 (7.1)11 (5.3)
 Married920 (70.5)321 (68.3)330 (69.8)115 (73.7)154 (74.8)
 Stable relationship not married261 (20.0)97 (20.6)94 (19.9)29 (18.6)41 (19.9)
Sex of baby
 Male666 (51.0)221 (47.0)252 (53.3)81 (51.9)112 (54.4)
 Female639 (49.0)249 (53.0)221 (46.7)75 (48.1)94 (45.6)
Pre-eclampsia48 (3.7)17 (3.6)7 (1.5)16 (10.3)9 (4.4)
Maternal BMI at 15 weeks (kg/m2), median IQR24.0 (22.1–26.9)23.9 (21.5–26.4)23.7 (22.1–26.7)24.9 (22.3–28.7)24.7 (23.0–27.9)
Gestational age (weeks), median IQR40.3 (39.3–41.0)40.3 (39.3–41.0)40.6 (39.6–41.1)39.3 (38.6–40.1)40.6 (39.6–41.3)
Number of cigarettes per day at 15 weeks SCOPE visit, mean (±SD)0.5 (±2.1)0.7 (±2.4)0.4 (±2.1)0.5 (±2.3)0.3 (±1.4)
Birth weight (g), median IQR3460 (3160–3770)3400 (3120–3690)3510 (3200–3800)3345 (2915–3670)3650 (3300–4000)
 Macrosomia (>4000 g)169 (13.0)32 (6.8)65 (13.7)21 (13.5)51 (24.8)
Baby size according to customised centile
 SGA<10th centile135 (10.3)59 (12.6)40 (8.5)22 (14.1)14 (6.8)
 AGA ≥10th centile ≤90th centile1027 (78.7)383 (81.5)374 (79.1)110 (70.5)160 (77.7)
 LGA>90th centile143 (11.0)28 (6.0)59 (12.5)24 (15.4)32 (15.5)
Body composition (at 2 months)
 Body fat (%), mean SD21.8 (±4.3)21.8 (±4.3)21.6 (±4.4)22.3 (±4.6)21.6 (±4.2)
 Missing272 (20.8)98 (20.9)93 (19.7)39 (25.0)42 (20.4)
BMI (kg/m2) at 2 years‡
 Thin77 (5.9)28 (6.0)34 (7.2)6 (3.8)9 (4.4)
 Normal812 (62.2)289 (61.5)286 (60.5)101 (64.7)136 (66.0)
 Overweight96 (7.4)29 (6.2)39 (8.2)12 (7.7)16 (7.8)
 Obese10 (0.8)4 (0.9)2 (0.4)3 (1.9)1 (0.5)
 Missing310 (23.8)120 (25.5)112 (23.7)34 (21.8)44 (21.4)
BMI (kg/m2) at 5 years‡
 Thin38 (2.9)13 (2.8)17 (3.6)3 (1.9)5 (2.4)
 Normal656 (50.3)236 (50.2)232 (49.0)83 (53.2)105 (51.0)
 Overweight97 (7.4)22 (4.7)42 (8.9)12 (7.7)21 (10.2)
 Obese21 (1.6)10 (2.1)6 (1.3)3 (1.9)2 (1.0)
 Missing493 (37.8)189 (40.2)176 (37.2)55 (35.3)73 (35.4)

*Vacuum or forceps.

†Total years of schooling (primary and secondary, not preschool or tertiary).

‡International Obesity Task Force age and sex-specific cut-offs.

AGA, appropriate for gestational age; BMI, body mass index; LSCS, lower segment caesarean section; SGA, small for gestational age; LGA, large for gestational age.

Characteristics of the study population at 2 months *Vacuum or forceps. †Total years of schooling (primary and secondary, not preschool or tertiary). ‡International Obesity Task Force age and sex-specific cut-offs. AGA, appropriate for gestational age; BMI, body mass index; LSCS, lower segment caesarean section; SGA, small for gestational age; LGA, large for gestational age. The average BMI, by the four birth modes, at each of the six time points is depicted in figure 1 and for all vaginal and CS births in figure 2. The maximum divergence in BMI by delivery mode occurred at 6 months of age. At 6 months, the mean BMI of infants delivered vaginally and those born by CS was 17.3 kg/m2 and 17.6 kg/m2, respectively.
Figure 1

Mean BMI from birth to 5 years of age: Please note that the time axis has been expanded below age 1 year to permit clearer visualisation. BMI, body mass index; LSCS, lower segment caesarean section.

Figure 2

Mean BMI from birth to 5 years of age with 95% confidence intervals (CIs) around the mean BMI—thin lines. There is no overlap of the 95% CIs at 6 months of age. Please note that the time axis has been expanded below age 1 year to allow clearer visualisation. BMI, body mass index.

Mean BMI from birth to 5 years of age: Please note that the time axis has been expanded below age 1 year to permit clearer visualisation. BMI, body mass index; LSCS, lower segment caesarean section. Mean BMI from birth to 5 years of age with 95% confidence intervals (CIs) around the mean BMI—thin lines. There is no overlap of the 95% CIs at 6 months of age. Please note that the time axis has been expanded below age 1 year to allow clearer visualisation. BMI, body mass index. Across delivery mode, missing data were distributed equally for the primary and secondary outcomes, BF% and BMI, respectively. Thus, missing data were unlikely to have affected the results or conclusions (online supplementary table 1).

Mode of delivery and BF% at age 2 months

At age 2 months, there was no association between prelabour CS and BF% (adjusted BF% mean difference=0.46; 95% CI −0.46 to 1.40) and LSCS in labour (adjusted BF% mean difference=0.07; 95% CI −0.88 to 0.73) in comparison to the reference group of children delivered by unassisted VD (table 2).
Table 2

Mode of delivery and body fat per cent at age 2 months

Delivery modeCasesCoef. (95% CI)P valueAdjCoef. (95% CI)*P value
n
Unassisted vaginal372ReferenceReference
Operative vaginal380−0.16 (−0.78 to 0.46)0.614−0.10 (−0.72 to 0.52)0.743
Prelabour LSCS1170.50 (−0.40 to 1.40)0.2780.46 (−0.46 to 1.40)0.325
LSCS in labour164−0.19 (−0.9 to 0.61)0.6420.07 (−0.88 to 0.73)0.864

N for adjusted model=1033. Linear regression.

*Adjusted for maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia

Adj, adjusted; BMI, body mass index; Coef, β-coefficient; LSCS, lower segment caesarean section.

Mode of delivery and body fat per cent at age 2 months N for adjusted model=1033. Linear regression. *Adjusted for maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia Adj, adjusted; BMI, body mass index; Coef, β-coefficient; LSCS, lower segment caesarean section.

Mode of delivery and BMI at age 6 months, 2 years and 5 years

Infants born by CS had a significantly higher mean BMI at 6 months compared with those born vaginally (adjusted BMI mean difference=0.24; 95% CI 0.06 to 0.41, p value=0.009). Limiting analysis to non-macrosomic infants resulted in an adjusted BMI mean difference=0.26; 95% CI 0.07 to 0.45, p value=0.008. There was, however, no statistically significant differential effect by sex (p value for the interaction term was 0.70; online supplementary figure 1). There was no statistically significant association between prelabour CS (aRRR=1.38; 95% CI 0.73 to 2.62) or LSCS in labour (aRRR=0.88; 95% CI 0.48 to 1.61) and the risk of being overweight or obese at age 2 years, as compared with the reference group (table 3). Limiting analysis to non-macrosomic infants at age 2 years resulted in the association between prelabour CS and the risk of overweight and obesity being (aRRR=0.95; 95% CI 0.44 to 2.05) and for LSCS in labour (aRRR=0.89; 95% CI 0.44 to 1.82) (online supplementary table 2).
Table 3

Mode of delivery and body mass index at age 2 years

BMI category (normal BMI–base outcome)CasesRRR (95% CI)P valueAdjRRR (95% CI)*P value
n
Thin
 Unassisted vaginal30ReferenceReference
 Operative vaginal371.23 (0.74 to 2.05)0.4171.42 (0.83 to 2.41)0.199
 Prelabour LSCS60.59 (0.24 to 1.47)0.2590.65 (0.26 to 1.62)0.352
 LSCS in labour90.65 (0.30 to 1.41)0.2790.86 (0.39 to 1.87)0.696
Overweight or obese
 Unassisted vaginal37ReferenceReference
 Operative vaginal411.11 (0.69 to 1.78)0.670.95 (0.58 to 1.56)0.853
 Prelabour LSCS171.45 (0.79 to 2.65)0.2331.38 (0.73 to 2.62)0.324
 LSCS in labour201.18 (0.66 to 2.10)0.5830.88 (0.48 to 1.61)0.68

N for adjusted model=1062. Multinomial logistic regression.

*Adjusted for maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia.

Adj, adjusted; BMI, body mass index; LSCS, lower segment caesarean section; RRR, relative risk ratio.

Mode of delivery and body mass index at age 2 years N for adjusted model=1062. Multinomial logistic regression. *Adjusted for maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia. Adj, adjusted; BMI, body mass index; LSCS, lower segment caesarean section; RRR, relative risk ratio. At age 5 years, there was a nonsignificant association between prelabour CS and the risk of being overweight or obese (aRRR=1.37; 95% CI 0.69 to 2.69) (table 4). There was also no association between LSCS in labour and the risk of being overweight or obese (aRRR=1.69; 95% CI 0.92 to 3.08). Limiting analysis to non-macrosomic infants at age 5 years resulted in the association between prelabour CS and the risk of overweight and obesity being (aRRR=0.86; 95% CI 0.36 to 2.08) and for LSCS in labour (aRRR=2.37; 95% CI 1.19 to 4.68) (online supplementary table 3).
Table 4

Mode of delivery and body mass index at age 5 years

BMI category (normal BMI–base outcome)CasesRRR (95% CI)P valueAdjRRR (95% CI)*P value
n
Thin
 Unassisted vaginal13ReferenceReference
 Operative vaginal181.45 (0.69 to 3.02)0.3241.82 (0.84 to 3.96)0.131
 Prelabour LSCS30.68 (0.19 to 2.44)0.5530.46 (0.14 to 1.56)0.212
 LSCS in labour50.86 (0.30 to 2.47)0.7771.06 (0.36 to 3.09)0.915
Overweight or obese
 Unassisted vaginal36ReferenceReference
 Operative vaginal521.51 (0.95 to 2.40)0.0791.64 (1.00 to 2.67)0.05
 Prelabour LSCS171.39 (0.74 to 2.60)0.3051.37 (0.69 to 2.69)0.368
 LSCS in labour261.61 (0.93 to 2.80)0.091.69 (0.92 to 3.08)0.09

N for adjusted model=856. Multinomial logistic regression.

*Adjusted for maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia.

Adj, adjusted; BMI, body mass index; LSCS, lower segment caesarean section; RRR, relative risk ratio.

Mode of delivery and body mass index at age 5 years N for adjusted model=856. Multinomial logistic regression. *Adjusted for maternal age, education, ethnicity, marital status, infant sex, maternal smoking during pregnancy, maternal BMI at the first antenatal visit, gestational age (at delivery), birth weight and pre-eclampsia. Adj, adjusted; BMI, body mass index; LSCS, lower segment caesarean section; RRR, relative risk ratio.

Discussion

Main findings

There was no significant difference in BF% at age 2 months between modes of delivery. A statistically significant difference in BMI at age 6 months was observed between infants born by CS and VD. Infants born by CS had a higher mean BMI. There was no evidence to support a link between prelabour CS and our secondary outcome, being overweight or obese, at 2 and 5 years of age.

Strengths and limitations

A major strength was the availability of data from a well-phenotyped prospective longitudinal cohort that is among those with the most data available for BF%. This allowed us to investigate the role of factors such as cigarette smoking prior to conception, which is often not available from prior or extant cohorts. In addition, we used robust measures of body composition obtained by air displacement plethysmography, which is regarded as the gold standard method. A homogeneous sample where 98% of the cohort’s participants were Caucasian, primiparous and ‘low risk’27 could limit the generalisability of these findings to heterogeneous populations. However, the cohort reflected Ireland’s demographics of reproductive age women (15–49 years), where 93% are Caucasian women.36 The variable pre-pregnancy BMI was unavailable; this variable attenuated effect size estimates towards the null12 in previous studies. BMI at 15 weeks’ gestation, a good proxy for pre-pregnancy BMI, was used because 15 weeks is prior to the occurrence of most weight gain in pregnancy. It has been suggested that any association between CS birth and childhood obesity is due to antibiotics administered during CS, with CS delivery serving as a proxy; nonetheless, this proposition has not been supported by evidence.37 38 The major limitation was the low number of cases at 2 and 5 years of age.

Interpretation

The relationship between CS delivery and offspring being overweight or obese has been explored by several systematic reviews and meta-analyses.12 14 15 39 A positive association was the most common finding. Our findings are similar to those of infants, born in 2010, from a Danish prospective cohort study which found that the largest BMI difference by delivery mode, from birth to 5 years of age, occurred at 6 months’ age and that this difference did not track into later childhood at age 5 years.38 In addition, similar to this study, no significant difference in BF% by delivery mode was found. It is worth highlighting that the first 2 years of life have been identified as a critical developmental window during which perturbations in growth and development are more likely to result in lifelong sequelae.40 This Danish study, like ours and also as reported by the systematic reviews and meta-analyses,13 32 did not find a sex-specific growth pattern by mode of birth. This suggests that in humans CS birth might not influence sex-specific growth patterns as has been observed in mouse studies.25 Childhood fat mass index data from a Brazilian longitudinal cohort also showed no significant difference between children born by CS and VD at 6 years of age.41 The declining influence of CS birth on the risk of obesity as children grow older has been attributed to the increasing influence of other risk factors for obesity like physical inactivity, family dietary habits, watching television (and the use of other electronic devices).42 Indeed, a study which utilised a sibling-pair design attributed the observed association between CS birth and childhood obesity to unmeasured confounding.43 Our results are dissimilar to those of children from a Boston, United States (US) cohort study which found a positive association between delivery mode and being overweight or obese at age 5 years.37 The Boston study, unlike ours, did not subclassify CS births into elective and emergency for example, and unusually there were more girls delivered by CS,44 this might indicate reduced external validity for the US study. A few studies have been able to differentiate between elective/prelabour CS and emergency/LSCS in labour and they have been limited by small sample sizes.16 17 However, a higher risk of childhood obesity for infants born by emergency CS than elective CS was reported.17 Finding an association at age 5 years between LSCS in labour, when membranes are more likely to have ruptured, and being overweight or obese, but not with prelabour CS suggests an attenuated role for vaginal flora in the genesis of children being overweight or obese. A possible explanation for the LSCS in labour association is confounding by the indications for CS. The exact indications for CS were not available for this cohort. However, a divergent BMI trajectory in mid-infancy which then converges by age 5 years between VD and CS babies may suggest a transient role for the vaginal microflora. Further exploration, around mid-infancy, of the association between CS birth and BMI is required. The CS rate of 27.8%, in this cohort, is consistent with published national estimates of 27.1% to 28.6% that prevailed during the study’s recruitment period from 2007 to 2011.45 This suggests the generalizability of findings to the Irish population, particularly ‘low-risk’ first-time mothers. A macrosomia (>4000 g) prevalence of 13.0% is almost double that of another high-income country, the USA at 7.5% during a similar time period, and suggests high baseline Irish rates of excess adiposity.46 The general Irish population had at age 3 and 5 years a prevalence of 24% and 20%, respectively, for obesity and being overweight47 which is higher than that observed in this cohort. This cohort’s low-risk population likely explains its lower prevalence of being overweight or obese compared with the general Irish population.

Conclusion

We have found no evidence to support a relationship between prelabour CS and offspring being overweight or obese in early childhood. No significant differences in outcome at 2 months and 2 years, and an increased risk of being overweight or obese in children born by CS in labour, but not prelabour CS at 5 years, suggests that the previously hypothesised causal effects due to vaginal microflora are also unlikely at least in the long term.
  41 in total

1.  Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study.

Authors:  Susanna Y Huh; Sheryl L Rifas-Shiman; Chloe A Zera; Janet W Rich Edwards; Emily Oken; Scott T Weiss; Matthew W Gillman
Journal:  Arch Dis Child       Date:  2012-05-23       Impact factor: 3.791

2.  An obesity-associated gut microbiome with increased capacity for energy harvest.

Authors:  Peter J Turnbaugh; Ruth E Ley; Michael A Mahowald; Vincent Magrini; Elaine R Mardis; Jeffrey I Gordon
Journal:  Nature       Date:  2006-12-21       Impact factor: 49.962

3.  Association Between Cesarean Birth and Risk of Obesity in Offspring in Childhood, Adolescence, and Early Adulthood.

Authors:  Changzheng Yuan; Audrey J Gaskins; Arianna I Blaine; Cuilin Zhang; Matthew W Gillman; Stacey A Missmer; Alison E Field; Jorge E Chavarro
Journal:  JAMA Pediatr       Date:  2016-11-07       Impact factor: 16.193

4.  Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring.

Authors:  Hein M Tun; Sarah L Bridgman; Radha Chari; Catherine J Field; David S Guttman; Allan B Becker; Piush J Mandhane; Stuart E Turvey; Padmaja Subbarao; Malcolm R Sears; James A Scott; Anita L Kozyrskyj
Journal:  JAMA Pediatr       Date:  2018-04-01       Impact factor: 16.193

5.  Private health care coverage and increased risk of obstetric intervention.

Authors:  Jennifer E Lutomski; Michael Murphy; Declan Devane; Sarah Meaney; Richard A Greene
Journal:  BMC Pregnancy Childbirth       Date:  2014-01-13       Impact factor: 3.007

6.  Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery.

Authors:  Derrick M Chu; Jun Ma; Amanda L Prince; Kathleen M Antony; Maxim D Seferovic; Kjersti M Aagaard
Journal:  Nat Med       Date:  2017-01-23       Impact factor: 53.440

Review 7.  Mode of delivery and offspring body mass index, overweight and obesity in adult life: a systematic review and meta-analysis.

Authors:  Karthik Darmasseelane; Matthew J Hyde; Shalini Santhakumaran; Chris Gale; Neena Modi
Journal:  PLoS One       Date:  2014-02-26       Impact factor: 3.240

8.  Mode of delivery at birth and the metabolic syndrome in midlife: the role of the birth environment in a prospective birth cohort study.

Authors:  Béatrice Bouhanick; Virginie Ehlinger; Cyrille Delpierre; Bernard Chamontin; Thierry Lang; Michelle Kelly-Irving
Journal:  BMJ Open       Date:  2014-05-15       Impact factor: 2.692

9.  National Variation in Caesarean Section Rates: A Cross Sectional Study in Ireland.

Authors:  Sarah-Jo Sinnott; Aoife Brick; Richard Layte; Nathan Cunningham; Michael J Turner
Journal:  PLoS One       Date:  2016-06-09       Impact factor: 3.240

10.  The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990-2014.

Authors:  Ana Pilar Betrán; Jianfeng Ye; Anne-Beth Moller; Jun Zhang; A Metin Gülmezoglu; Maria Regina Torloni
Journal:  PLoS One       Date:  2016-02-05       Impact factor: 3.240

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  14 in total

1.  Relationship between caesarean section delivery and risk of overweight/obesity among children aged 6-23 months in the Tamale Metropolis of Ghana.

Authors:  Issahaku Sulley; Mahama Saaka
Journal:  J Nutr Sci       Date:  2022-06-08

2.  Relationship between Obstetric Mode of Delivery and Risk of Overweight/Obesity in 1- to 4-Year-Old Children.

Authors:  Peiying Huang; Xiulin Shi; Fangsen Xiao; Liying Wang; Wei Liu; Jinyang Zeng; Mingzhu Lin; Xuejun Li
Journal:  Obes Facts       Date:  2022-02-10       Impact factor: 4.807

3.  Caesarean delivery is associated with increased blood pressure in young adult offspring.

Authors:  Amaraporn Rerkasem; Sarah E Maessen; Antika Wongthanee; Sakda Pruenglampoo; Ampica Mangklabruks; Patumrat Sripan; José G B Derraik; Kittipan Rerkasem
Journal:  Sci Rep       Date:  2021-05-13       Impact factor: 4.379

4.  The association between caesarean section delivery and later life obesity in 21-24 year olds in an Urban South African birth cohort.

Authors:  Eniola Sogunle; Gwinyai Masukume; Gill Nelson
Journal:  PLoS One       Date:  2019-11-14       Impact factor: 3.240

5.  Elective and nonelective cesarean section and obesity among young adult male offspring: A Swedish population-based cohort study.

Authors:  Viktor H Ahlqvist; Margareta Persson; Cecilia Magnusson; Daniel Berglind
Journal:  PLoS Med       Date:  2019-12-06       Impact factor: 11.069

6.  The impact of cesarean delivery on infant DNA methylation.

Authors:  Qian Chen; Yanhong Ming; Yuexin Gan; Lisu Huang; Yanjun Zhao; Xia Wang; Yongjie Liu; Jun Zhang
Journal:  BMC Pregnancy Childbirth       Date:  2021-03-30       Impact factor: 3.007

Review 7.  Maternal and early life exposures and their potential to influence development of the microbiome.

Authors:  Erin E Bolte; David Moorshead; Kjersti M Aagaard
Journal:  Genome Med       Date:  2022-01-11       Impact factor: 15.266

8.  Effect of Elective Cesarean Section on Children's Obesity From Birth to Adolescence: A Systematic Review and Meta-Analysis.

Authors:  Shanshan Zhang; Xiaoyun Qin; Peixuan Li; Kun Huang
Journal:  Front Pediatr       Date:  2022-01-27       Impact factor: 3.418

9.  Caesarean section delivery and childhood obesity in a British longitudinal cohort study.

Authors:  Gwinyai Masukume; Ali S Khashan; Susan M B Morton; Philip N Baker; Louise C Kenny; Fergus P McCarthy
Journal:  PLoS One       Date:  2019-10-30       Impact factor: 3.240

10.  Delivery mode and altered infant growth at 1 year of life in India.

Authors:  Giridhara R Babu; Noel T Mueller; Melissa Glenda Lewis; Anjaly Krishnan; Eunice Lobo; R Deepa; Sonalini Khetrapal; Sara E Benjamin-Neelon
Journal:  Pediatr Res       Date:  2021-03-02       Impact factor: 3.756

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