Gastrointestinal consequences of cesarean section birth: A systematic review of short- and long-term effects in infancy and beyond

Table 1 Population, intervention, comparison, outcome, inclusion, and exclusion criteria

PICO element	Description
Research question	What are the short- and long-term gastrointestinal effects in infants born via C-section compared to those born via vaginal delivery?
Population (P)	Infants born via C-section (elective or emergency), from term or preterm gestations, across various geographic and ethnic backgrounds
Intervention (I)	Birth by C-section (elective or emergency)
Comparison (C)	Infants born via vaginal delivery (with or without labor)
Outcome (O)	Short- and long-term gastrointestinal outcomes, including gut dysbiosis, functional gastrointestinal disorders, infantile colic, constipation, gastroesophageal reflux, inflammatory bowel disease, food allergies (including cow’s milk protein allergy), and coeliac disease
Study design	Systematic review of observational studies (cohort, case-control, cross-sectional), randomized controlled trials, and relevant systematic reviews/meta-analyses
Other	Inclusion: Human studies, studies reporting delivery mode and gastrointestinal outcomes, studies with clearly defined outcome measures, and English language. Exclusion: Case reports, animal studies, conference abstracts without full data, studies not distinguishing C-section from vaginal delivery or lacking gastrointestinal outcomes

PICO: Population, intervention, comparison, outcome; C-section: Cesarean section.

Table 2 Summary of short-term functional gastrointestinal disorder risk in cesarean section vs vaginally delivered infants

Ref.	Sample size	FGID evaluated	C-section association	Statistical significance	Risk of bias
Salvatore et al[11], 2019	934	Colic, regurgitation, dyschezia, constipation	↑ Colic (RR: 1.23), ↑ dyschezia (RR: 1.20), ↑ any FGID (RR: 1.14)	Significant (P < 0.01 for all)	Low (well-powered, defined FGIDs, adjusted)
Bi et al[12], 2023	988 (preterm)	Colic, regurgitation, dyschezia, constipation	73.4% had ≥ 1 FGID; C-section strongly associated	Significant (P < 0.001)	Moderate (preterm bias, but strong stats)
Pantazi et al[13], 2025	134	FGID + gut microbiota profile	C-section → ↑ dysbiosis, ↓ Bifidobacterium, ↑ E. coli	Significant (P < 0.05 for key microbes)	Moderate (small sample, integrated analysis)
Ziętek et al[14], 2024	82	Colic, regurgitation, constipation	↑ Regurgitation in C-section-born at 3-6 months	Significant (P = 0.0434)	High (small cohort, limited follow-up)
Bekem et al[15], 2021	213	Dyschezia, regurgitation	↑ Dyschezia (C-section: 83.3%), ↑ regurgitation (C-section: 88.9%)	Significant (P = 0.006 and 0.035)	Moderate (retrospective design)
Velasco-Benitez et al[16], 2020	1497	School-age FGIDs (longitudinal)	No significant C-section association in older children	Non-significant (P > 0.05)	Low (large cohort, age-stratified, well-controlled)

P value less than 0.05 is considered significant. C-section: Cesarean section; FGID: Functional gastrointestinal disorder; RR: Relative Risk; E. coli: Escherichia coli.

Table 3 Infantile colic and cesarean section delivery

Ref.	Design & number	C-section vs VD colic prevalence	Main modifiers evaluated	Key findings	Risk of bias
Sommermeyer et al[17], 2022	Cross-sectional, 195 infants	Higher fecal calprotectin in C-section colic	Type of feeding, birth mode	C-section infants had higher calprotectin & lower diagnostic accuracy for IC	Moderate (small sample, limited confounder control)
Salvatore et al[11], 2019	Prospective cohort, 934 infants	C-section: RR 1.23 for IC	Preterm, antibiotics, formula feeding	Strong C-section association with IC; antibiotics further increased the risk	Low (good sample, adjusted)
Bi et al[12], 2023	Retrospective, 988 (preterm)	Higher FGIDs (incl. IC) in C-section	Breastfeeding, smoking, hospitalization, and antibiotics	C-section is significantly associated with IC (P < 0.001)	Moderate (preterm only; confounders considered)
Ziętek et al[14], 2024	Prospective, 82 infants	↑ Colic at 3 months; ↑ regurgitation in C-section	Antibiotics, feeding pattern	GI disorders more frequent in C-section group	High (small size, short follow-up)
Akman et al[18], 2006	Prospective, 78 infants	IC in 64.7% of C-section infants	Maternal depression, attachment style	C-section, depression, and insecure attachment linked with IC	High (tiny cohort, potential bias)
Bekem et al[15], 2021	Cross-sectional, 213 infants	Infant dyschezia higher in C-section (P = 0.006)	Breastfeeding, maternal QoL, depression	IC more common in depressed mothers; C-section linked to GI symptoms	Moderate (retrospective; subjective outcomes)

C-section: Cesarean section; VD: Vaginal delivery; FGID: Functional gastrointestinal disorder; GI: Gastrointestinal; IC: Infant colic; QoL: Quality of life; RR: Relative risk.

Table 4 Key modifiers of effects of cesarean section and delivery on infant colic identified across studies

Modifier	Effect on infant colic
Cesarean section delivery	Consistently associated with a higher risk of colic across most studies
Neonatal antibiotic use	Associated with increased gut dysbiosis, leading to higher colic risk
Feeding type	Formula feeding and a lack of exclusive breastfeeding increased the risk
Maternal psychological status	Maternal postpartum depression and insecure attachment increased colic incidence
Prematurity	Associated with a higher prevalence of IC and other FGIDs
Probiotics	Mixed results—some studies suggest probiotics may worsen symptoms like constipation

Clinical Pearls 1: Infantile colic is more common in Cesarean-delivered infants, likely due to early gut microbiota disruption. Factors such as formula feeding, antibiotic exposure, and maternal stress increase risk. Colic severity often peaks around 6-12 weeks and may be associated with increased gut inflammation. Promoting breastfeeding and judicious use of antibiotics are key modifiable strategies to reduce colic risk in cesarean section-born infants. FGID: Functional gastrointestinal disorder; IC: Infant colic.

Table 5 Summary of key findings on constipation and cesarean section in infants

Ref.	Sample size	Age evaluated	Prevalence of FC	C-section vs VD comparison	Significance	Modifiers	Risk of bias
Yoshida et al[6], 2018	83019	1 year	1.37%	No significant difference (AOR = 0.94)	No	Breastfeeding, GA, BW	Low (large national dataset; adjusted)
Nakamura et al[19], 2021	71878	3 years	12.3%	Higher in C-section (13.1% vs 12.1%; AOR = 1.064)	Yes	Breastfeeding, solid food, maternal BMI	Low (population-based; confounders addressed)
Bi et al[12], 2023	988 (preterm)	0-12 months	19.2%	Strong C-section association (67.1% vs 40.3%)	Yes	Antibiotics, FF, maternal smoking	Moderate (limited to preterms; good stats)
Ziętek et al[14], 2024	82	3, 6, 12 months	Not isolated	C-section is linked to regurgitation only	No	Probiotics ↑ risk (P = 0.045)	High (small sample; limited power)
Salvatore et al[11], 2019	934	0-12 months	26.6%	C-section linked to dyschezia, not FC	No	Preterm, antibiotics, FF	Low (good design and adjustment)
Neves et al[20], 2023	135	12 months	49.6%	C-section infants had more FC, but not significant	No	Feeding method (PLW)	Moderate (small sample; not powered)
Hierink et al[21], 2024	2643 (mothers)	Adults	24.6% maternal constipation	More common in VD mothers	Yes	Perineal trauma	Moderate (maternal outcome; subjective reporting)

AOR: Adjusted odds ratio; BMI: Body mass index; BW: Birth weight; C-section: Cesarean section; FC: Functional constipation; FF: Formula feeding; GA: Gestational age; IC: Infant colic; PLW: Parent-led weaning; VD: Vaginal delivery.

Table 6 Key modifiers of effects of cesarean section on infant constipation identified across studies

Modifier	Effect on constipation	Ref.	Notes
Feeding type	Formula feeding associated with higher risk; exclusive breastfeeding appears protective	Bi et al[12], 2023; Salvatore et al[11], 2019; Yoshida et al[6], 2018	Formula-fed C-section infants are more prone to delayed gut transit and reduced microbiota diversity
Antibiotic exposure	Increased constipation risk via microbiota disruption (in C-section-born, especially)	Bi et al[11], 2023; Salvatore et al[10], 2019	Antibiotics delay colonization by beneficial bacteria such as Bifidobacteria
Prematurity	Preterm C-section infants have a higher risk of functional GI disorders, including constipation	Bi et al[12], 2023; Salvatore et al[11], 2019	May reflect an immature enteric nervous system and altered motility
Probiotic use	Unexpectedly associated with increased constipation at 3 months	Ziętek et al[14], 2024	Possibly due to strain-specific effects; more research needed
Complementary feeding practices	No significant effect overall, but trends show PLW may slightly increase risk	Neves et al[20], 2023	Cultural and dietary factors may influence stool patterns
Maternal depression/smoking	Associated with increased GI symptoms and constipation in C-section-born infants	Bi et al[12], 2023; Bekem et al[15], 2021	May affect breastfeeding success and infant regulatory behavior
Age of evaluation	C-section-related constipation was not apparent at 1 year but was observed at 3 years	Yoshida et al[6], 2018; Nakamura et al[19], 2021	Suggests delayed or progressive impact of delivery mode on GI function

C-section: Cesarean section; GI: Gastrointestinal; PLW: Parent-led weaning. Clinical Pearls 2: The gastrointestinal effects of Cesarean delivery, particularly constipation, are not solely attributable to the delivery mode but are also modulated by early-life exposures, such as feeding type, antibiotics, and gestational maturity. Some effects may emerge only later in early childhood, highlighting the importance of longitudinal follow-up.

Table 7 Summary of gastroesophageal reflux findings in cesarean section-born infants

Ref.	Population	Key findings	C-section association	Modifiable factors	Risk of bias
Dahlen et al[22], 2018	869188 infants	1.1% diagnosed with GER/GERD; higher in C-section births	AOR: 1.13 (P < 0.001)	Maternal psychiatric illness, prematurity, NICU stay	Low (large national dataset, adjusted for multiple confounders)
Pantazi et al[13], 2025	134 infants	Reduced Lactobacillus and Bifidobacterium in GER infants; ↑ E. coli	GER strongly linked with C-section and dysbiosis	Artificial feeding, C-section, antibiotic use	Moderate (small cohort, microbial focus, controlled analysis)
Ziętek et al[14], 2024	82-term infants	Higher regurgitation in C-section group (P = 0.0434)	Significant increase in GER symptoms	Formula feeding, antibiotic use	High (small sample size, limited adjustment)
Salvatore et al[11], 2019	934 infants	40% had regurgitation in year one; C-section increased FGID risk	Associated with dyschezia and diarrhea	Exclusive formula, prolonged hospital stays	Low (well-designed, prospective, controlled)
Bi et al[12], 2023	988 preterm infants	41.6% had GER; C-section among strongest risk factors	Yes (χ2 = 33.13, P < 0.001)	Lack of breastfeeding, antibiotic/probiotic use	Moderate (preterm focus, retrospective, good confounder control)
Guo et al[23], 2002	496 neonates (C-section only)	GER/aspiration prevented with manual intervention	None reported	Early postnatal intervention	High (no comparison group, limited external validity)

A P value less than 0.05 is considered significant. Clinical Pearls 3: Gastroesophageal reflux is reported more frequently in infants born via cesarean section, particularly during the first months of life. The association is likely linked to delayed gut microbiota maturation and reduced exposure to labor-induced hormonal and physiological adaptations. Contributing factors include formula feeding, antibiotic use, and preterm birth. Supporting early breastfeeding and gut microbiota development may help reduce gastroesophageal reflux symptoms in cesarean section-born infants. AOR: Adjusted odds ratio; C-section: Cesarean section; E. coli: Escherichia coli; GER/GERD: Gastroesophageal reflux/Gastroesophageal reflux disease; NICU: Neonatal intensive care unit.

Table 8 Summary of gut microbiota differences by delivery mode

Feature	Vaginal delivery	C-section
Initial colonizers	Lactobacillus, Bifidobacterium, Bacteroides	Enterococcus, Staphylococcus, Klebsiella
Microbial diversity	High	Reduced
Commensal dominance	Yes	Delayed or absent
Opportunistic pathogen presence	Low	High (esp. hospital-acquired)
Persistence of differences	Normalize by 6-12 months	May persist > 12 months
Transmission from mother	Effective vertical transmission	Severely reduced; environmental transmission
Modifiable by breastfeeding	Enhanced commensal colonization	Partially restores microbial balance
Effect of Intrapartum Antibiotics	Reduces vertical transmission in VD	Present in all C-section deliveries
Racial/geographic variation	Present (e.g., Japanese, Korean, United Kingdom cohorts)	Yes, with consistent patterns across populations
Corrective interventions	Less needed	FMT, probiotics, breastfeeding are critical

C-section: Cesarean section; FMT: Fecal microbiota transplant; VD: Vaginal delivery.

Table 9 Summary of included studies on gut microbiota differences by delivery mode

Ref.	Country/population	Key findings	Persistence of difference	Modifiable factors examined	Risk of bias
Nagpal et al[27], 2017	Japan/Healthy full-term infants	VD enriched with Lactobacillus, Bacteroides; C-section infants had reduced colonization	Seen up to 3-6 months	Not specified	Moderate (small sample, unclear confounder control)
Kim et al[25], 2021	Korea/National cohort	C-section associated with lower Bifidobacteria, delayed microbiota maturation	Persisted into infancy (12 months)	Breastfeeding	Low (large cohort, confounders adjusted)
Reyman et al[28], 2019	Netherlands/n = 117	C-section infants had low species richness, delayed Bacteroides	Up to 6 months	Antibiotics, feeding method	Moderate (small sample, well-defined methods)
Shao et al[24], 2019	United Kingdom/Baby Biome Study	C-section disrupted maternal strain transmission; ↑ Klebsiella, Enterococcus	Persistent at 1 year	Antibiotics, feeding, maternal FMT	Low (large, multicenter, robust metagenomics)
Mitchell et al[29], 2020	United States/Israel/Multiethnic cohort	Bacteroides absent in C-section infants for weeks; antibiotic-sensitive	6-12 weeks	Antibiotics, breastfeeding	Moderate (multi-site, antibiotic exposure varied)
Bäckhed et al[26], 2015	Sweden/n = 98	VD infants dominated by Bifidobacterium, Bacteroides; C-section → ↑ Clostridium	Up to 3-4 months	Breastfeeding	Moderate (well-designed but small sample)
Dos Santos et al[33], 2023	Canada/National cohort	C-section disrupted diversity; ↑ Proteobacteria in early life	Up to 12 months	Hospital stay, feeding type	Low (population-wide registry, controlled)
Dominguez-Bello et al[34], 2010	United States/Pilot cohort	VD infants resembled vaginal flora; C-section resembled skin/hospital flora	Neonatal period	FMT, vaginal seeding	High (pilot study, small sample, proof-of-concept only)

C-section: Cesarean section; FMT: Fecal microbiota transplant; VD: Vaginal delivery.

Table 10 Interventions to restore gut microbiota in cesarean section-born infants

Ref.	Intervention	Microbiota composition	Microbial diversity	Duration of effect	Modifiable factors	Population	Risk of bias
Song et al[50], 2021	Vaginal seeding (swab)	Aligned with vaginally born	Improved	Up to 12 months	Maternal microbiota	United States, Hispanic/Latino	Moderate (small cohort, no randomization)
Wilson et al[36], 2021	Oral vaginal seeding	No significant effect	No change	Up to 3 months	Administration method	New Zealand	High (pilot nature, small sample, no control)
Mueller et al[38], 2023	Vaginal seeding (RCT)	↑ Maternal strains	↓ Alpha-diversity	1 month	Delivery timing	United States	Low (RCT, good design)
Lagkouvardos et al[37], 2023	Synbiotic formula (L. fermentum + GOS)	↑ Bifidobacterium, ↓ Blautia	↑ at 4 months	Up to 24 months	Baseline microbiota	European	Low (long follow-up, intervention control)
Chua et al[39], 2017	Synbiotic (scGOS/LcFOS + B. breve)	↑ Bifidobacteria, ↓ Enterobacteriaceae	Improved by week 8	12 weeks post	Feeding method	Multinational (Asia)	Low (RCT, multinational)
Wang et al[40], 2025	Synbiotic (B. breve + scGOS/LcFOS)	↑ Parabacteroides, Bacteroides	↑ Diversity	Up to 12 months	Feeding, birth mode	China	Low (RCT design, stratified by C-section)
Garcia Rodenas et al[41], 2016	L. reuteri-enriched formula	Modulated toward VD profile	↑ Diversity	4 months	Strain selection	Greece	Moderate (no blinding stated)
Yang et al[42], 2021	Probiotics (varied dose)	↑ Bifidobacterium, Lactobacillus	↑ To VD levels	28 days	Dosage	China	Moderate (dose variability, controlled)
Gong et al[43], 2023	Probiotics (B. longum, L. acidophilus)	↑ Faecalibacterium, ↓ Klebsiella	Improved	42 days	Antibiotic exposure	China	Moderate (strain-specific findings)
Hurkala et al[44], 2020	Probiotics (B. breve, L. rhamnosus)	↑ LAB, ↓ pathogens	Significant	30 days	Early start post-C-section	Poland	Moderate (observational, small sample)
Akagawa et al[45], 2019	Breastfeeding vs formula	Restoration by 1 month	Equalized	1 month	Feeding type	Japan	Moderate (observational, controlled)
Wu et al[46], 2023	Breastfeeding in C-section infants	↑ SCFA metabolism stability	Enhanced	3 months	Feeding type	China	Low (well-controlled feeding study)
Korpela et al[47], 2018	Probiotic mixture (4 strains)	Corrected dysbiosis in C-section infants	Improved	3 months	Breastfeeding	Finland	Low (strong probiotic trial, adjusted)
Bellomo et al[48], 2024	B. bifidum only	↑ Bacteroides, ↓ Shigella, ↑ α-diversity	Sustained ↑	12 months	Feeding mode	Italy	Low (well-controlled, single strain tested)
Yang et al[49], 2025	Bovine colostrum vs fortifier	Minor changes	No significant change	1 month	Fortifier type	Denmark	Moderate (neutral result, no microbiome endpoint)
Dominguez-Bello et al[51], 2016	Vaginal swabbing	Partial restoration (Bacteroides)	Mild increase	30 days	Swabbing technique	United States, multiethnic	High (pilot nature, small number)

Clinical Pearls 4: Cesarean section delivery is strongly associated with early gut dysbiosis, characterized by reduced microbial diversity and delayed colonization by beneficial bacteria, such as Bifidobacteria and Bacteroides. This imbalance can persist for up to 12 months and may predispose infants to gastrointestinal and immune-related conditions. Breastfeeding, probiotic/synbiotic supplementation, and limiting perinatal antibiotic exposure are key strategies to support microbiota recovery in cesarean section-born infants. C-section: Cesarean section; LAB: Lactic acid bacteria; L. fermentum: Limosilactobacillus fermentum; SCFA: Short-chain fatty acids; VD: Vaginal delivery; RCT: Randomised controlled trial.

Table 11 Cesarean section and risk of inflammatory bowel disease

Ref.	Country	Sample size	Follow-up duration	Association with IBD	Key notes/modifiable factors	Risk of bias
Bager et al[52], 2012	Denmark	2.1 million	Up to 35 years	↑ IBD (IRR: 1.29 for < 15 years)	Adjusted for family history	Low (large population, long-term, adjusted)
Andersen et al[53], 2020	Denmark	2.7 million	Up to 40 years	↑ IBD and autoimmune diseases	Risk with both elective/emergency C-section	Low (excellent registry data, confounder control)
Hellsing et al[54], 2022	Sweden	1.1 million	17 years	↑ Crohn’s (HR: 1.14)	No effect on UC	Low (well-stratified outcomes, good adjustment)
Zamstein et al[55], 2022	Israel	7337 breech births	18 years	↑ IBD hospitalizations (aHR: 3.18)	Breech delivery as key variable	Moderate (small subgroup, well-controlled)
Malmborg et al[56], 2012	Sweden	> 16000	Not specified	↑ Pediatric Crohn's (boys, OR: 1.25)	Elective C-section more strongly associated	Moderate (good design, duration unclear)
Ponsonby et al[57], 2009	Australia	Not specified	Up to 16 years	↑ Crohn's disease with elective C-section	Trend noted over time	Moderate (ecological component, unclear sample)
Bernstein et al[58], 2016	Canada	12159	Approximately 20 years	No association	Controlled for siblings, urban/rural	Low (sibling matched, good design)
Burnett et al[59], 2020	Canada	262729	Approximately 25 years	No association	Two independent cohorts analyzed	Low (large sample, replication)
Burgess et al[60], 2022	Scotland	2 million	16 years	No association	Controlled for feeding, GA, mode	Low (robust dataset, adjusted)
Sonntag et al[61], 2007	Germany	1859	Retrospective	No association	Preterm birth more influential	Moderate (small sample, retrospective)
Soullane et al[62], 2021	Canada	934873	7.4 years	No IBD association	Pediatric cohort focus	Low (strong national data, pediatric angle)

C-section: Cesarean section; HR: Hazard ratio; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; IRR: Incidence rate ratio; OR: Odds ratio. Clinical Pearls 5: Evidence suggests a modest association between C-section—predominantly elective C-section—and an increased long-term risk of Crohn’s disease. At the same time, no consistent link has been found with ulcerative colitis. Geographic and genetic factors, as well as early-life gut dysbiosis, may contribute to this risk. However, findings are mixed, and Cesarean delivery alone is not considered a definitive risk factor for inflammatory bowel disease.

Table 12 Summary of studies on cesarean delivery and risk of celiac disease

Ref.	Country	Sample size	Follow-up	Association with CD	Notable modifiers	Risk of bias
Andersen et al[53], 2020	Denmark	2.7 million births	40 years	↑ Risk of celiac disease and other inflammatory diseases	Parental autoimmune disease	Low (large national cohort, robust adjustments)
Soullane et al[62], 2021	Canada	934873 children	7.4 years	No increased celiac disease risk (HR = 0.86)	Hospitalization data	Low (large cohort, good registry linkage)
Iorfida et al[63], 2024	Italy	3259 celiac disease patients	40 years	↑ C-section rate in celiac disease group; earlier onset in emergency C-section	Emergency vs elective C-section	Moderate (case-control; retrospective risk)
Mårild et al[64], 2012	Sweden	11749 cases; 53887 controls	35 years	↑ Risk with elective C-section (aOR = 1.15)	SGA status, labor exposure	Low (matched controls, well-powered)
Dydensborg Sander et al[65], 2018	Denmark & Norway	Approximately 1.6 million births	15-18 years	No significant association	Country-level consistency	Low (multinational, controlled)
Emilsson et al[66], 2015	Norway	114500 children	8-10 years	No significant association	Maternal celiac disease, type 1 DM, gluten timing	Low (adjusted for strong confounders)
TEDDY Study (Koletzko et al[67], 2018)	United States, Europe	6087 HLA-positive children	5-10 years	No significant association after adjustments	Genetics, breastfeeding, country	Low (high-quality longitudinal cohort)
Tanpowpong et al[68], 2023	United States	44539 mother-child pairs	> 6 years	↑ Risk in C-section without labor (aHR = 1.56)	Labor status at delivery	Moderate (good follow-up, stratified labor data)
Decker et al[69], 2010	Germany	1950 children	Retrospective	↑ Celiac disease in C-section-born (OR = 1.8)	Breastfeeding, postnatal complications	Moderate (retrospective, smaller size)
Bielik et al[70], 2024	Slovakia	1226 (534 celiac disease patients)	Cross-sectional	No C-section-celiac disease link; breastfeeding protective	Antibiotics, family history	High (cross-sectional design, recall bias)

Clinical Pearls 6: Some studies suggest a slight increase in celiac disease risk following cesarean section, particularly elective cesarean section without labor, possibly due to altered microbial exposure at birth. However, results are inconsistent across populations, and large cohort studies have found no significant association. Feeding practices, genetic predisposition, and perinatal factors may play a more influential role than delivery mode alone. aOR: Adjusted odds ratio; aHR: Adjusted hazard ratio; C-section: Cesarean section; CD: Crohn's disease; DM: Diabetes mellitus; HLA: Human leukocyte antigens; SGA: Small for gestational age.

Table 13 Summary of key studies on cesarean section and food allergy risk

Ref.	Country	Sample size	Follow-up	Association with food allergy	Modifiable factors	Risk of bias
Papathoma et al[71], 2016	Greece	459	3 years	↑ C-section risk (OR: 3.15); higher with parental atopy	Atopic dermatitis, gestational age	Moderate (small sample, good confounder adjustment)
Eggesbø et al[72], 2003	Norway	2803	2.5 years	↑ Risk in allergic mothers (OR: 7.0)	Antibiotics not significant	Low (strong prospective design, adjusted)
Mitselou et al[73], 2018	Sweden	1086378	13 years	HR: 1.21 for C-section	LGA, low Apgar score	Low (large population-based cohort)
Pyrhönen et al[74], 2022	Finland	5564	12 years	RR: 2.41 for elective C-section in non-atopic mothers	Sibling atopy modifies risk	Moderate (targeted subgroup, adjusted analysis)
Polos and Fletcher[75], 2019	United States	150000+	Cross-sectional	↑ Food allergy across racial groups	Race, C-section rate, birth cohort effects	Moderate (large dataset, cross-sectional limitations)
Currell et al[76], 2022	Australia	5276	12 months	No association with C-section (aOR: Approximately 1.0)	Labor, feeding, siblings not modifying	Low (clear methodology and control)
Chua et al[77], 2025	Taiwan	> 1 million	Approximately 14 years	No significant food allergy risk (aHR: 1.13)	↑ Asthma, eczema, obesity	Low (nationwide cohort, adjusted)
Tamai et al[78], 2025	Japan	2114	9 years	No significant association (aRR: 1.1; CI: 0.7-1.7)	Adjusted for child & parental variables	Low (population-based, adjusted with GEE)
Adeyeye et al[79], 2019	United States	Approximately 2900	3 years	↑ Risk with emergency C-section (RR: 3.02)	Breastfeeding (partial mediation)	Moderate (good adjustment, moderate size)
Yang M et al[80], 2019	China	6768	12 months	↑ C-section and formula feeding in CMPA group	High tolerance after 1 year (77%)	Moderate (well-documented, short-term)
Gil et al[81], 2017	Spain	211 cases + controls	Retrospective	C-section + formula (FFH) ↑ risk (OR: 11.82)	FFH and breastfeeding key risk factors	Moderate (case-control, smaller scale)
Metsälä et al[82], 2010	Finland	16237 CMPA cases	2 years	C-section (OR: 1.18); high maternal age ↑ risk	Smoking & low SES ↓ risk	Low (large birth cohort, adjusted)
Toro Monjaraz et al[83], 2015	Mexico	101 CMPA, 90 controls	Retrospective	No C-section effect; antibiotics ↑ risk	Breastfeeding duration ↓ risk	High (small sample, retrospective)
Kuitunen et al[84], 2009	Finland	1018	5 years	Probiotics ↓ allergy in C-section-born infants	Perinatal probiotic supplementation	Moderate (well-executed trial, modest size)

Clinical Pearls 7: Cesarean section, primarily when elective and without labor, is associated with a modestly increased risk of food allergies, including cow’s milk protein allergy. This risk is amplified by factors such as formula feeding, the absence of breastfeeding, and early exposure to antibiotics. Promoting exclusive breastfeeding and early microbial support (e.g., probiotics or synbiotics) may help reduce the development of allergies in cesarean section-born infants. aRR: Adjusted risk ratio; CMPA: Cow’s milk protein allergy; C-section: Cesarean section; FFH: Formula feeding in hospital; GEE: Generalized estimating equations; HR: Hazard ratio; LGA: Large for gestational age; OR: Odds ratio; SES: Socioeconomic status.

Table 14 Summary of risk of bias assessment across included studies

Study domain	No. of studies	Risk of bias assessment	Tools used
Observational studies (cohort, case-control)	54	37 low risk, 14 moderate, 3 high	Newcastle-Ottawa scale
Randomized controlled trials	6	5 low risk, 1 some concerns	RoB 2.0 tool
Cross-sectional studies	12	7 moderate risk, 5 high risk	AXIS appraisal tool (when applicable)
Systematic reviews/meta-analyses	3	2 low risk, 1 Moderate	AMSTAR 2

Total studies reviewed: 75. Overall quality distribution: Low risk of bias: 44 studies (58.6%), moderate risk of bias: 22 studies (29.3%), high risk of bias: 9 studies (12.0%).