Dataset Information

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.

ABSTRACT:

Objective

To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.

Design

Observational controlled interrupted time series study.

Setting

UK primary and secondary care.

Participants

515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.

Intervention

Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.

Main outcome measures

The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.

Results

Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.

Conclusions

This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.

SUBMITTER: Sumilo D

PROVIDER: S-EPMC9112858 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Šumilo Dana D Nirantharakumar Krishnarajah K Willis Brian H BH Rudge Gavin M GM Martin James J Gokhale Krishna K Thayakaran Rasiah R Adderley Nicola J NJ Chandan Joht Singh JS Okoth Kelvin K Harris Isobel M IM Hewston Ruth R Skrybant Magdalena M Deeks Jonathan J JJ Brocklehurst Peter P

BMJ (Clinical research ed.) 20220517

<h4>Objective</h4>To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.<h4>Design</h4>Observational controlled interrupted time series study.<h4>Setting</h4>UK primary and secondary care.<h4>Participants</h4>515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement N ...[more]

PMID: 35580876

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Project description:IntroductionIn the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health.Methods and analysisA controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006-2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level.Ethics and disseminationEthical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.

Project description:Birth by Caesarean-section (C-section), which increases the risk for metabolic and immune disorders, disrupts the normal initial microbial colonisation of the gut, in addition to preventing early priming of the stress and immune-systems.. Animal studies have shown there are enduring psychological processes in C-section born mice. However, the long-term impact of microbiota-gut-brain axis disruptions due to birth by C-section on psychological processes in humans is unknown. Forty age matched healthy young male university students born vaginally and 36 C-section delivered male students were recruited. Participants underwent an acute stressor, the Trier social stress test (TSST), during a term-time study visit. A subset of participants also completed a study visit during the university exam period, representing a naturalistic stressor. Participants completed a battery of cognitive tests and self-report measures assessing mood, anxiety, and perceived stress. Saliva, blood, and stool samples were collected for analysis of cortisol, peripheral immune profile, and the gut microbiota. Young adults born by C-section exhibit increased psychological vulnerability to acute stress and a prolonged period of exam-related stress. They did not exhibit an altered salivary cortisol awakening response to the TSST, but their measures of positive affect were significantly lower than controls throughout the procedure. Both C-section and vaginally-delivered participants performed equally well on cognitive assessments. Most of the initial effects of delivery mode on the gut microbiome did not persist into adulthood as the gut microbiota profile showed modest changes in composition in adult vaginally-delivered and C-sectioned delivered subjects. From an immune perspective, concentrations of IL-1β and 1L-10 were higher in C-section participants. These data confirm that there is a potential enduring effect of delivery mode on the psychological responses to acute stress during early adulthood. The mental health implications of these observations require further study regarding policies on C-section use.

Project description:The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.

Project description:BackgroundProphylactic antibiotics reduce infectious morbidity from caesarean section. The timing of their administration, however, is a matter of controversy.ObjectivesTo examine maternal and neonatal infectious morbidity in women receiving preoperative prophylaxis compared with those receiving intraoperative administration.Search strategyMedline, Embase, Current Controlled Trials and Cochrane Central were searched from their inception dates to December 2011.Selection criteriaRandomised controlled trials of a single dose of any antibiotic comparing preoperative with intraoperative administration were selected.Data collection and analysisTrial characteristics, outcomes and quality measures, based on the Cochrane tool for risk of bias, were independently extracted. The random effect model of DerSimonian and Laird to estimate relative risks (RRs) for maternal and neonatal outcomes was used.Main resultsSix trials met the inclusion criteria, reporting on 2313 women and 2345 newborns. Preoperative administration was associated with a significant 41% reduction in the rate of endometritis compared with intraoperative administration (RR 0.59; 95% confidence interval [95% CI] 0.37-0.94; I2 0%). In the preoperative group, there were nonsignificant reductions in the rates of wound infection (RR 0.71; 95% CI 0.44-1.14; I2 0%), maternal febrile morbidity (RR 0.94; 95% CI 0.46-1.95; I2 0%), neonatal sepsis (RR 0.81; 95% CI 0.47-1.41; I2 0%), neonatal septic work-up (RR 0.93; 95% CI 0.71-1.21; I2 0%) and neonatal intensive-care unit admission (RR 0.92; 95% CI 0.65-1.28; I2 0%). There were nonsignificant increases in the rates of maternal pyelonephritis (RR 1.09; 95% CI 0.49-2.43; I2 0%) and neonatal pneumonia (RR 3.36; 95% CI 0.55-20.47; I2 0%).ConclusionsCompared with intraoperative administration, preoperative antibiotics significantly reduce the rate of endometritis. The lack of neonatal adverse effects should be cautiously interpreted given the limited power of the trials to detect such effects.

Project description:IntroductionPulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth-in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. We aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth.Methods and analysisWe will perform a multicentre, randomised controlled trial in infants with an isolated left-sided CDH, born at ≥35.0 weeks. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. PBCC will be performed using a purpose-built resuscitation trolley. Cord clamping will be performed when the infant is considered respiratory stable, defined as a heart rate >100 bpm, preductal oxygen saturation >85%, while using a fraction of inspired oxygen of <0.5. The primary outcome is pulmonary hypertension diagnosed in the first 24 hours after birth, based on clinical and echocardiographic parameters. Secondary outcomes include neonatal as well as maternal outcomes.Ethics and disseminationCentral ethical approval was obtained from the Medical Ethical Committee of the Erasmus MC, Rotterdam, The Netherlands (METC 2019-0414). Local ethical approval will be obtained by submitting the protocol to the regulatory bodies and local institutional review boards.Trial registration numberNCT04373902.

Project description:BackgroundMothers giving birth by non-elective cesarean section have considerably higher risk of developing postoperative infection, than mothers giving birth by elective cesarean section. Meta-analyses have shown that the risk of infection is reduced when administering antibiotics at least 30 min prior to skin incision rather than after cord clamping. If given prior to incision, antibiotics are present in the neonatal bloodstream for up to 24 h after delivery, with early exposure to antibiotics potentially disturbing development of the gut microbiome. We aimed to retrospectively assess the prevalence of postoperative infection after non-elective cesarean section at a single labor ward administering antibiotics after cord clamping, additionally investigating risk factors for developing postoperative infections.MethodsIn this retrospective cohort study, we included a total of 2,725 women giving birth by non-elective cesarean section in 2010-2017 with a review of records for prenatal risk factors, labor management, and perinatal outcomes. The primary outcomes were a main composite infection of development of either endometritis, surgical-site infection, or sepsis in conjunction with a relevant antibiotic prescription. Secondary outcomes included infection of unknown focus, mastitis, urinary tract infection, and pneumonia.ResultsA total of 88 patients developed a main composite infection (3.2%). These infections subdivide into endometritis (n = 37/2725, 1.4%), surgical-site infection (n = 35/2725, 1.3%) and sepsis (n = 15/2725, 0.6%). We found a high body mass index (aOR = 3.38, 95%CI 1.93-5.92) and intrapartum fever (aOR = 2.26, 95%CI 1.22-4.59) to be independent risk-factors for developing postoperative infection after non-elective cesarean section. Furthermore, we found delivery by a more expedient emergency grade 2 cesarean section (aOR = 0.61 95%CI 0.37-0.998) compared to grade 3 to be a protective factor for developing postoperative infection after non-elective cesarean section.ConclusionIn a labor ward administering antibiotics after cord clamping at non-elective cesarean births, we find a low prevalence of main composite infections when compared to estimates from meta-analyses on the topic. We conclude that administration of prophylactic antibiotics after cord clamping appears to result in acceptable rates of postoperative infection and avoids transplacental-transmission of antibiotics to the infant.

Dataset Information

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.

Objective

Design

Setting

Participants

Intervention

Main outcome measures

Results

Conclusions

Publications

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.

Similar Datasets

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