amoxicillin-potassium-clavulanate-combination and Fetal-Membranes--Premature-Rupture

Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection.. To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013).. Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone.. We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors.. We included 22 trials, involving 6872 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found antibiotics seemed to have little effect on the health of children.. Routine prescription of antibiotics for women with preterm rupture of the membranes is associated with prolongation of pregnancy and improvements in a number of short-term neonatal morbidities, but no significant reduction in perinatal mortality. Despite lack of evidence of longer-term benefit in childhood, the advantages on short-term morbidities are such that we would recommend antibiotics are routinely prescribed. The antibiotic of choice is not clear but co-amoxiclav should be avoided in women due to increased risk of neonatal necrotising enterocolitis.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Chorioamnionitis; Developmental Disabilities; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Premature; Length of Stay; Macrolides; Perinatal Mortality; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Randomized Controlled Trials as Topic

Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection.. To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 April 2010).. Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone.. We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors.. We included 22 trials, involving 6800 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found antibiotics seemed to have little effect on the health of children.. The decision to prescribe antibiotics for women with PROM is not clearcut. Benefits in some short-term outcomes (prolongation of pregnancy, infection, less abnormal cerebral ultrasound before discharge from hospital) should be balanced against a lack of evidence of benefit for others, including perinatal mortality, and longer term outcomes. If antibiotics are prescribed it is unclear which would be the antibiotic of choice.Co-amoxiclav should be avoided in women at risk of preterm delivery due to increased risk of neonatal necrotising enterocolitis.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Chorioamnionitis; Developmental Disabilities; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Premature; Length of Stay; Macrolides; Perinatal Mortality; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Randomized Controlled Trials as Topic

Many perinatal interventions are performed to improve long-term neonatal outcome. To evaluate the long-term effect of a perinatal intervention follow-up of the child after discharge from the hospital is necessary because serious sequelae from perinatal complications frequently manifest themselves only after several years. However, long-term follow-up is time-consuming, is not in the awareness of obstetricians, is expensive and falls outside the funding-period of most obstetric studies. Consequently, short-term outcomes are often reported instead of the primary long-term end-point. With this project, we will assess the current state of affairs concerning follow-up after obstetric RCTs and we will develop multivariable prediction models for different long-term health outcomes. Furthermore, we would like to encourage other researchers participating in follow-up studies after large obstetric trials (> 350 women) to inform us about their studies so that we can include their follow-up study in our systematic review. We would invite these researchers also to join our effort and to collaborate with us on the external validation of our prediction models.. A systematic review of neonatal follow-up after obstetric studies will be performed. All reviews of the Cochrane Pregnancy and Childbirth group will be assessed for reviews on interventions that aimed to improve neonatal outcome. Reviews on interventions primary looking at other aspects than neonatal outcome such as labour progress will also be included when these interventions can change the outcome of the neonate on the short or long-term. Our review will be limited to RCTs with more than 350 women. Information that will be extracted from these RCTs will address whether, how and for how long follow-up has been performed. However, in many cases long-term follow-up of the infants will not be feasible. An alternative solution to limited follow-up could be to develop prediction models to estimate long-term health outcomes of the newborn based on specific perinatal outcomes and other covariates. For the development of multivariable prediction models for several health outcomes, we will use data available from a Dutch cohort study of preterm (< 32 weeks) and/or small for gestational age infants (< 1500 g). These infants were born in The Netherlands in 1983 and followed until they reached the age of 19.. The systematic review will provide insight in the extent and methods used for follow-up assessments after obstetric RCTs in the past. The prediction models can be used by future studies to extrapolate short-term outcomes to a long-term horizon or to indicate for which neonates long-term follow-up is required, as their outcomes (either absence or presence of sequelae) cannot be adequately predicted from short-term outcomes and clinical background characteristics.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Fetal Membranes, Premature Rupture; Follow-Up Studies; Health Care Costs; Humans; Infant, Newborn; Models, Theoretical; Multivariate Analysis; Netherlands; Perinatal Care; Pregnancy; Treatment Outcome

In the 'Overview of the role of antibiotics in curtailing labour and early delivery' (ORACLE I)-trial in women with premature rupture of membranes, the use of erythromycin was found to be associated with a decrease in the primary composite outcome (neonatal death, chronic lung disease or major cerebral abnormality on ultrasound; p = 0.08) and in single adverse neonatal outcomes (p = 0.02) when compared to placebo. The positive results were more significant in the singleton group (p = 0.02 for the composite outcome), while no effects were found in twin pregnancies. The combination of amoxycillin and clavulanic acid, with or without erythromycin, was associated with some improvements in outcome, but was also accompanied by a higher rate of neonatal necrotising enterocolitis. Another trial (ORACLE II) found no effects of antibiotic use in women with premature labour with intact membranes. Although both trials were of good quality, the stratification into singleton and twin pregnancies should have been done more consistently. Because premature rupture of membranes in singleton pregnancies is more likely to be associated with a pre-existing infection than in multiple pregnancies, the potential benefit of treatment with antibiotics is larger in singleton pregnancies.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Enterocolitis, Necrotizing; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic

The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate.. The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England.. This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age.. The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Double-Blind Method; Drug Therapy, Combination; Erythromycin; Female; Fetal Membranes, Premature Rupture; Follow-Up Studies; Humans; Obstetric Labor, Premature; Outcome Assessment, Health Care; Pregnancy; Research Design; Surveys and Questionnaires; Treatment Outcome

Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. A large, randomized, multicentre trial was undertaken to try to resolve this issue. In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital. The analysis was undertaken by intention to treat. Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin. In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis.. Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Antibiotic Prophylaxis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Erythromycin; Female; Fetal Membranes, Premature Rupture; Follow-Up Studies; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Reference Values; Risk Assessment; Treatment Outcome

Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue.. 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.. Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis.. Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability. However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis. A follow-up study of childhood development and disability after pPROM is planned.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Enterocolitis, Necrotizing; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Treatment Outcome

To determine whether the use of prophylactic Augmentin in PPROM prolongs gestation and reduces neonatal and maternal morbidity due to sepsis.. Study setting was Harare Maternity Hospital, Zimbabwe. Women with PPROM between 26 and 36 weeks' gestation were randomly allocated either to a group given a course of prophylactic oral Augmentin or another receiving no prophylactic antibiotic treatment. The calculated sample size was 72 women per group. Data were analyzed using the EPI INFO program.. A total of 171 women were recruited into the study, 84 in the Augmentin group and 87 in the No Treatment group. The group receiving prophylactic Augmentin had a significantly longer latency period between rupture of membranes and delivery. There was a trend towards increased neonatal and maternal morbidity due to sepsis in the No Treatment group although no statistical significance was reached.. The use of prophylactic Augmentin in PPROM significantly prolongs gestation. It appears to decrease neonatal and maternal morbidity due to sepsis.

Topics: Administration, Oral; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Third; Reference Values; Treatment Outcome

We have identified an excess of children with cerebral palsy (CP) born to women who received antibiotic treatment for spontaneous preterm labour (SPL). This nested study investigated the profile of impairment among children with CP in the ORACLE Children Study (OCS), and contrasted outcomes with those in 4Child, a population CP registry.. The study group comprised 167 children aged from 7 to 10 years (100 males, 67 females) with CP from the OCS, who were subdivided into a preterm rupture of membranes (PROM) group (87 children) and an SPL group (80 children). The OCS sought follow-up information regarding the health and behaviour of surviving children at 7 years of age in the UK using a parent-report postal questionnaire. Families provided further information to define wider aspects of function and were offered a physiotherapy assessment.. The prevalence of CP was higher among children in the OCS than among those in 4Child (standardized morbidity ratios: SPL group, 3.12 [95% confidence interval {CI} 2.47-3.87); PROM group: 1.56 (CI 1.24-1.92)]. The proportion of children with CP born after 32 weeks of gestation was higher in in the SPL group (73%) than in the PROM group (30%); the prevalence of CP was higher in the SPL group than in the PROM group or 4Child. Children with CP in the OCS tended to have similar distributions of neuroimpairment as children in 4Child, but motor impairment and associated vision and hearing problems were found to be less severe.. The pattern of CP in both the PROM and the SPL groups was similar, but functional outcomes were milder, compared with children with CP in the general population. However, in these groups the risk of CP was increased independently of gestational age. This is consistent with findings that ongoing inflammatory damage can cause CP.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Birth Weight; Cerebral Palsy; Child; Educational Status; Erythromycin; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Male; Morbidity; Mothers; Movement Disorders; Multiple Birth Offspring; Obstetric Labor, Premature; Poverty; Pregnancy; Premature Birth; Severity of Illness Index

How best to provide the findings of research to study participants remains poorly understood.. We aimed to develop, deliver, and evaluate a consultative approach to inform provision of feedback about research findings to participants in the Oracle Children Study (OCS). The OCS had identified adverse outcomes for some children whose mothers had been prescribed antibiotics as part of a trial in pregnancy.. An iterative process, including focus groups with OCS participants and consultation with other OCS stakeholders, was used to inform the development of a feedback package, including a results leaflet, for OCS participants. A questionnaire survey of participants' reactions to receiving the results leaflet was conducted. The Kolmogorov-Smirnov two-sample test was used to compare responses between different groups of respondents. Analysis of open-ended comments on the questionnaire was based on the constant comparative method.. Three focus groups with study participants provided insight into the potential emotional impact of receiving the results and into how the results might most clearly be explained. Negotiations with other stakeholders identified other priorities, including the need for scientific credibility. These multiple needs had to be balanced. The results leaflet was posted to all 4676 UK OCS participants. Survey responses were received from 1124 (25%) of participants. They indicated that the feedback was mostly well received by participants. Those whose children were affected by conditions associated with increased risk from trial participation were more likely to experience emotional distress on receiving the trial results, but there was also evidence of some other unanticipated impacts.. This study is limited by the low response rate to the survey.. Important lessons can be learned from using a consultative approach to developing feedback about research results for study participants. Especially where the findings are unwelcome, feedback development may involve methodological, ethical, emotional, and practical challenges, be resource-intensive, and need early planning.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Disclosure; Erythromycin; Feedback; Female; Fetal Membranes, Premature Rupture; Focus Groups; Humans; Pregnancy; Pregnancy Complications; Referral and Consultation; Research Subjects; Surveys and Questionnaires; Treatment Outcome

The ORACLE I trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study I--was to determine the long-term effects on children of these interventions.. We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England.. Outcome was determined for 3298 (75%) eligible children. There was no difference in the proportion of children with any functional impairment after prescription of erythromycin, with or without co-amoxiclav, compared with those born to mothers who received no erythromycin (594 [38.3%] of 1551 children vs 655 [40.4%] of 1620; odds ratio 0.91, 95% CI 0.79-1.05) or after prescription of co-amoxiclav, with or without erythromycin, compared with those born to mothers who received no co-amoxiclav (645 [40.6%] of 1587 vs 604 [38.1%] of 1584; 1.11, 0.96-1.28). Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced, on specific medical conditions, or on the proportions of children achieving each level in reading, writing, or mathematics at key stage one.. The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age.. UK Medical Research Council.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Antibiotic Prophylaxis; Child; Child Mortality; Child Welfare; Educational Status; England; Erythromycin; Female; Fetal Membranes, Premature Rupture; Follow-Up Studies; Health Status; Humans; Logistic Models; Male; Pelvic Infection; Pregnancy; Pregnancy Complications, Infectious; Treatment Outcome

To estimate the short term effect of the publication of a major clinical trial on clinical practise.. Questionnaire survey of clinical practise.. UK.. All maternity units in the UK.. A self-administered questionnaire completed by lead consultants on delivery suite of maternity units.. Changes in antibiotic prescription.. Within six months of publication, approximately 50% of maternity units had changed their guidelines for the care of women with preterm prelabour rupture of the fetal membranes.. Publication of a major clinical trial does impact on clinical practise but the impact is heterogeneous in terms of time and consistency.

Topics: Amoxicillin-Potassium Clavulanate Combination; Drug Therapy, Combination; Erythromycin; Female; Fetal Membranes, Premature Rupture; Hospitals, Maternity; Humans; Maternal Health Services; Obstetric Labor, Premature; Practice Patterns, Physicians'; Pregnancy; Prenatal Care; Publishing; Randomized Controlled Trials as Topic; Surveys and Questionnaires; United Kingdom

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Double-Blind Method; Drug Therapy, Combination; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Premature, Diseases; Multicenter Studies as Topic; Obstetric Labor, Premature; Pregnancy; Randomized Controlled Trials as Topic

Topics: Amoxicillin-Potassium Clavulanate Combination; Drug Therapy, Combination; Enterocolitis, Necrotizing; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy; Risk Factors

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy

Topics: Amoxicillin-Potassium Clavulanate Combination; Drug Therapy, Combination; Enterocolitis, Necrotizing; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy