Caesarean sections, while often lifesaving, carry significant risks. Globally, more than a quarter of deliveries in Europe are performed via caesarean section, and the proportion is even higher in North and Latin America. Caesarean sections, being major surgical procedures, are associated with a markedly increased risk of maternal postpartum infections compared to vaginal deliveries. Postpartum infections can include wound infections, endometritis (infection of the uterine lining), and, in some cases, sepsis, a life-threatening response to infection.
To address these risks, prophylactic antibiotics are routinely administered to mothers undergoing caesarean deliveries. These antibiotics are highly effective at reducing maternal infections, as demonstrated in numerous randomised controlled trials. Furthermore, research has consistently shown that the timing of antibiotic administration plays a critical role in its effectiveness. Administering antibiotics before surgical incision significantly reduces the risk of maternal infections compared to providing them after the baby’s umbilical cord has been clamped. Based on this evidence, the National Institute for Health and Care Excellence (NICE) updated its guidelines in 2011 to recommend administering prophylactic antibiotics before incision for caesarean sections.
Timing of Antibiotics and Neonatal Gut Microbiota
While this policy shift has improved maternal outcomes, it has also raised concerns about the potential long-term effects on children. When antibiotics are administered before incision, they cross the placenta and expose the foetus to the medication at birth. This exposure occurs during a crucial time when the neonatal gut is first colonised by microbes, a process that has significant implications for long-term health.
The mode of delivery is a key determinant of the neonatal gut microbiota. Vaginally delivered infants acquire microbes from their mother’s birth canal, while those born via caesarean section are more likely to acquire skin-associated microbes. The neonatal gut microbiota plays a pivotal role in immune system development, influencing how the body responds to various antigens and inflammation. Disruptions in this early microbial colonisation have been linked to an increased risk of conditions such as asthma, eczema, allergies, and other immune-related diseases later in childhood. Given these concerns, understanding the potential impact of pre-incision antibiotics on the infant gut microbiota and subsequent health outcomes has become a priority for researchers.
Examining the Impact of Pre-Incision Antibiotics
A large population-based study was conducted to assess the potential consequences of the policy change recommending pre-incision antibiotics for caesarean sections. The primary objective of the study was to determine whether this policy change influenced the risk of childhood conditions such as asthma, eczema, and other immune-related diseases. Additionally, the study aimed to evaluate broader health outcomes, including autoimmune diseases, neurodevelopmental disorders, and infections, in children born via caesarean section.
Researchers utilised two extensive mother-baby linked healthcare datasets to explore these outcomes. By comparing children born vaginally (as a control group) with those born via caesarean section, the study accounted for temporal changes in diagnosis patterns and healthcare recordkeeping. This robust design allowed for an in-depth analysis of the effects of pre-incision antibiotics on childhood health outcomes.
Reassurance on Childhood Health Outcomes
The findings of the study provided reassuring evidence. Researchers did not find an increased risk of asthma, eczema, or other allergy-related conditions in children born via caesarean section under the updated antibiotic protocol. Similarly, no convincing evidence was found to suggest a heightened risk of autoimmune diseases, neurodevelopmental conditions, or infections.
The study also examined the timing of antibiotic administration for both emergency and elective caesarean sections. No significant differences in childhood health outcomes were observed between these scenarios. Additionally, sensitivity analyses were conducted to test the robustness of the results, and the findings remained consistent despite variations in data quality and definitions of health outcomes.
Maternal Health Benefits of Pre-Incision Antibiotics
While the study’s findings on childhood outcomes were largely neutral, the benefits for maternal health were significant. The researchers observed a 30% reduction in maternal infectious morbidity following the policy change, primarily due to a decrease in wound infections. This aligns with findings from earlier randomised controlled trials, which reported a 28-43% reduction in maternal infections when antibiotics were administered before incision.
Endometritis, another common postpartum infection, also showed a decline, although the estimates for this condition were less precise. Interestingly, the study noted a relative increase in recorded maternal sepsis rates in secondary care. However, this increase is likely an artifact of heightened clinical vigilance and diagnostic practices over the study period, rather than an actual rise in sepsis cases.
Strengths
One of the study’s major strengths was its use of large population-wide healthcare datasets, which provided comprehensive mother-baby linked data. This allowed researchers to explore a broad range of childhood health conditions and assess their severity. The inclusion of vaginally delivered children as a control group was another strength, as it enabled the study to account for temporal trends and changes in healthcare practices.
The study design also facilitated an examination of potential differences in outcomes based on the timing of antibiotic administration, as well as the specific antibiotics used (such as cefuroxime, metronidazole, and co-amoxiclav). Sensitivity analyses further validated the findings by testing the impact of various factors, including the timing of the policy change and data recording quality.
Limitations
Despite its strengths, the study faced several limitations. Routine healthcare records do not capture the timing of antibiotic administration, meaning that researchers had to rely on surveys of clinical directors for maternity care to estimate when hospitals implemented the pre-incision antibiotic policy. This reliance on recollection may have introduced recall bias. Furthermore, not all women undergoing caesarean sections received pre-incision antibiotics after the policy change, although audits indicated compliance rates of 70-100% in most hospitals.
Another limitation was the lack of detailed data on other antibiotics administered during delivery, such as those given to prevent group B streptococcal infections. While these antibiotics are typically narrow-spectrum and less likely to affect the gut microbiota, their impact was not specifically analysed in this study. Additionally, certain health conditions, such as asthma, are challenging to diagnose in early childhood due to the need for age-appropriate testing. This may have limited the study’s ability to fully assess the long-term effects of pre-incision antibiotics.
The use of vaginally delivered children as a control group, while valuable for adjusting for temporal trends, introduced its own challenges. Differences between the two groups (vaginal vs. caesarean delivery) may have contributed to residual confounding, despite the researchers’ efforts to account for these differences.
Antibiotics and Neonatal Sepsis
While the primary focus of the study was on maternal and child health outcomes, it also touched on the impact of pre-incision antibiotics on neonatal sepsis. Evidence from systematic reviews of randomised controlled trials suggests that administering antibiotics before incision may reduce the risk of neonatal sepsis by 23-24%. In this study, researchers observed reductions of 25% and 12% in early and late neonatal sepsis, respectively. However, these findings should be interpreted cautiously, as sensitivity analyses demonstrated considerable uncertainty around the estimates.
The study also highlighted an overall increase in recorded neonatal sepsis rates over time, regardless of delivery type. This trend is likely due to improved diagnostic capabilities and increased clinical awareness of neonatal infections. Additionally, the observed reductions in neonatal sepsis associated with pre-incision antibiotics may be influenced by the use of culture-based diagnostic methods, which can yield negative results if antibiotics were administered before the onset of symptoms.
Implications for Healthcare Policy and Practice
The findings of this study have important implications for healthcare policy and clinical practice. The evidence suggests that the shift to pre-incision antibiotics is not associated with adverse childhood health outcomes, providing reassurance to clinicians and policymakers. At the same time, the significant reduction in maternal infections highlights the value of this policy in improving maternal health outcomes.
However, the study also highlights the need for continued research. While the findings are reassuring, limitations such as the reliance on routine healthcare records and the challenges of diagnosing certain conditions emphasise the importance of further investigations. Future studies could explore more granular data on antibiotic administration and long-term health outcomes, particularly in subgroups of children who may be at higher risk of certain conditions.
Conclusion
The shift to pre-incision antibiotics for caesarean sections represents a significant advancement in maternal care. By reducing the risk of maternal infections, this policy has improved outcomes for countless women. At the same time, the evidence from this large population-based study suggests that the policy does not pose additional risks to child health, providing much-needed reassurance to healthcare providers and families.
As research continues to shed light on the complex relationships between delivery methods, antibiotic exposure, and long-term health, the findings of this study serve as a reminder of the importance of evidence-based guidelines. By striking a balance between maternal and child health outcomes, the pre-incision antibiotic policy exemplifies the power of evidence-driven decision-making in advancing healthcare quality and safety.
Reference
Šumilo, D., Nirantharakumar, K., Willis, B. H., Rudge, G. M., Martin, J., Gokhale, K., Thayakaran, R., Adderley, N. J., Chandan, J. S., Okoth, K., Harris, I. M., Hewston, R., Skrybant, M., Deeks, J. J., & Brocklehurst, P. (2022). Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records. BMJ (Clinical Research Ed.), 377, e069704. https://doi.org/10.1136/bmj-2021-069704