Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries

Abstract

Background The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. Methods and findings We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%–29%) were by CS, of which 727,755 (43%, range 38%–57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09–1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12–1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06–1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. Conclusions In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.

Caesarean section and severe upper and lower respiratory tract infections during infancy: Evidence from two UK cohorts

“…A study from New South Wales [ 9 ] found an increased risk in the magnitude of 12–13% while a study from Western Australia [ 10 ] reported that elective caesarean is associated with 34% increased risk of admission and emergency caesarean with 20% elevated risk. Likewise, an international study pooling data from several high-income countries found 15% elevated risk of admission associated with elective caesarean and a slightly lower risk of 9% associated with emergency caesarean [ 13 ].…”

“…This large international study identified a small increase in the risk for hospital admission for URTI in infants and preschool children born by elective or emergency caesarean section, with risks slightly higher following elective caesarean. Study findings relating to hospital admission due to LRTI or other types of infection were of a similar pattern [ 13 ].…”

“…Caesarean section is a risk factor for hospital admission for lower respiratory infections (LRTIs), both during infancy [ 6 – 9 ] and later in childhood [ 10 – 13 ]. When examining elective and emergency caesareans separately, the available evidence suggests that elective caesareans are associated with an increased risk of infection [ 7 – 11 ], while the evidence for emergency caesarean is less conclusive [ 7 , 8 , 11 ].…”

“…Some studies have examined hospital admissions for any respiratory morbidity combined and found caesarean section to increase the risk of unplanned hospitalisation [ 5 , 14 ]. However, only a single study that we are aware of has specifically examined the effect of mode of birth on severe upper respiratory tract infections (URTIs) [ 13 ]. This large international study identified a small increase in the risk for hospital admission for URTI in infants and preschool children born by elective or emergency caesarean section, with risks slightly higher following elective caesarean.…”

Cesarean section and childhood infections: Causality for concern?

“…While there is extensive information on the short-term associations, the long-term effects on the both the mother and child are less well documented. This week in PLOS Medicine , a cohort study including 7.1 million live births from 4 countries, reported by Jessica Miller and colleagues, provides useful new evidence and raises the possibility that cesarean delivery may be associated with the risk of later childhood infectious disease [ 7 ]. The authors performed a pooled analysis of retrospective cohort studies using data from Denmark, Scotland, England, and Australia.…”