Interventions for women with premature cervical dilatation and exposed fetal membranes to prevent pregnancy loss and preterm birth - A systematic review and meta-analysis.

INTRODUCTION: The management of women with premature cervical dilatation and exposed unruptured fetal membranes remains uncertain and controversial. Treatment options may include expectant management or emergency cervical cerclage (ECC). Little is known regarding the effectiveness of individual interventions, or additional therapies. This systematic review aims to summarise all existing evidence to improve understanding of the treatment options and pregnancy outcomes for women presenting with premature cervical dilatation. METHODS: Databases were searched using a prospective protocol (CRD42021286275). Studies were eligible for inclusion across five distinct comparison groups if they included women with premature cervical dilatation and reported clinical outcomes. Primary outcome was pregnancy loss (miscarriage, stillbirth, neonatal death and termination of pregnancy). Planned subgroups included singletons and twins, and low-cervical or high-cervical suture. Pairwise random effects meta-analysis calculated in RevMan5.4, single arm random effects proportional meta-analysis calculated using RevMan and R studio. Risk of bias was assessed using Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS: 6781 abstracts were screened, and 177 (four randomised controlled trials) studies included in the five analysis groups. Women receiving ECC were significantly less likely to experience pregnancy loss (combined RR 0.48 95 %CI 0.39-0.59 singleton RR 0.48 95 %CI 0.34-0.67 twin only RR 0.39 95 %CI 0.26-0.58) compared to expectant management. Adjuvant amnioreduction with ECC was not found to reduce pregnancy loss (RR 1.12 (95 % CI 0.73-1.72) or any other outcomes compared to ECC without amnioreduction. Women were significantly more likely to experience pregnancy loss (RR3.85 95 %CI 3.13-4.74) after ECC compared to planned cerclage. The probability of intra-operative rupture of membranes at ECC insertion was 3.3 % (95 %CI 1.8-5.1) and the probability of an ECC attempt being abandoned was 2.6 % (95 %CI 1.1-4.6 %). DISCUSSION: ECC appears to reduce the risk of pregnancy loss for both singletons and twins although the overall quality of evidence is poor. It is important that women are counselled regarding the outcomes following cerclage according to indication. Pregnancy complications are common after ECC although the rates of intra-operative complications are lower than may be anticipated. Randomised trials remain imperative for understanding the role of ECC and adjunctive treatments in preventing pregnancy loss in this condition.

Placental architectural characteristics following laser ablation within monochorionic twins complicated by twin-twin transfusion syndrome: A systematic review and meta-analysis of outcomes.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) complicates approximately 10%-15% of all monochorionic twin pregnancies. The aim of this review was to evaluate the placental architectural characteristics within TTTS twins following laser and elucidate their impact on fetal outcomes and operative success. MATERIAL AND METHODS: Five databases were searched from inception to August 2023. Studies detailing post-delivery placental analysis within TTTS twins post-laser were included. Studies were categorized into two main groups: (1) residual anastomoses following laser and (2) abnormal cord insertion: either velamentous and/or marginal or proximate. The primary outcome was to determine the proportion of TTTS placentas with residual anastomoses and abnormal cord insertions post-laser. Secondary outcomes included assessing residual anastomoses on post-laser fetal outcomes and assessing the relationship between abnormal cord insertion and TTTS development. Study bias was critiqued using the Joanna Briggs Institute checklists and Cochrane risk of bias tool. Random-effects meta-analysis was used, and results were reported as pooled proportions or odds ratio (OR) with 95% confidence interval (CI). PROSPERO registration: CRD42023476875. RESULTS: Twenty-six studies, comprising 4013 monochorionic twins, were included for analysis. The proportion of TTTS placentas with residual anastomoses following laser was 24% (95% CI, 0.12-0.41), with a mean and standard deviation of 4.03 ± 2.95 anastomoses per placenta. Post-laser residual anastomoses were significantly associated with intrauterine fetal death (OR, 2.38 [95% CI, 1.33-4.26]), neonatal death (OR, 3.37 [95% CI, 1.65-6.88]), recurrent TTTS (OR, 24.33 [95% CI, 6.64-89.12]), and twin anemia polycythemia sequence (OR, 13.54 [95% CI, 6.36-28.85]). Combined abnormal cord (velamentous and marginal), velamentous cord, and marginal cord insertions within one or both twins following laser were reported at rates of 49% (95% CI, 0.39-0.59), 27% (95% CI, 0.18-0.38), and 28% (95% CI, 0.21-0.36), respectively. Combined, velamentous and marginal cord insertions were not significantly associated with TTTS twins requiring laser (p = 0.72, p = 0.38, and p = 0.71, respectively) versus non-TTTS monochorionic twins. CONCLUSIONS: To the best of our knowledge, this is the first review to conjointly explore outcomes of residual anastomoses and abnormal cord insertions within TTTS twins following laser. A large prospective study is necessitated to assess the relationship between abnormal cord insertion and residual anastomoses development post-laser.

Childbirth Acquired Perineal Trauma study (CHAPTER): a UK prospective cohort study protocol.

INTRODUCTION: Childbirth-related perineal trauma (CRPT) is the most common complication of childbirth affecting 80% of women overall after vaginal birth. There remains a lack of comprehensive evidence relating to the prevalence of subsequent health problems. Current evidence is related to short-term outcomes, for example, pain, but there is less known about longer-term outcomes such as infection, wound dehiscence, pelvic floor function and psychological outcomes. This is a protocol for a cohort study assessing outcomes of women after CRPT. METHODS AND ANALYSIS: A multicentre, prospective UK cohort study aiming to include 1000 women. All women who have sustained CRPT will be eligible for inclusion and will be followed-up for 12 months after childbirth. The primary outcome will be perineal infection at 6 weeks post-birth. Secondary outcomes will include antibiotic use for perineal infection, wound breakdown, use of analgesia, the requirement for admission or surgical intervention, urinary and faecal incontinence, anxiety and depressive symptoms, sexual function and impact on daily activities. Outcomes will be measured at 6 weeks, 6 months and 12 months post partum, with some outcomes being measured at all time points and others at selected most appropriate time points only. Outcome data will be obtained from a review of clinical notes and from patient questionnaires. Simple descriptive statistics will be used to summarise characteristics and outcomes, with categorical variables expressed as percentages and continuous variables as mean averages, alongside the corresponding standard deviatons. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Research Ethics Council with reference 23/WA/0169. Data collected from the Childbirth Acquired Perineal Trauma (CHAPTER) cohort study will highlight the prevalence and type of complications after CRPT and which women are more at risk. After the conclusion of this study, findings will be used to work with governmental organisations and Royal Colleges to target resources and ultimately improve care.

Induction of labour care in the UK: A cross-sectional survey of maternity units.

OBJECTIVES: To explore local induction of labour pathways in the UK National Health Service to provide insight into current practice. DESIGN: National survey. SETTING: Hospital maternity services in all four nations of the UK. SAMPLE: Convenience sample of 71 UK maternity units. METHODS: An online cross-sectional survey was disseminated and completed via a national network of obstetrics and gynaecology specialist trainees (October 2021-March 2022). Results were analysed descriptively, with associations explored using Fisher's Exact and ANOVA. MAIN OUTCOME MEASURES: Induction rates, criteria, processes, delays, incidents, safety concerns. RESULTS: 54/71 units responded (76%, 35% of UK units). Induction rate range 19.2%-53.4%, median 36.3%. 72% (39/54) had agreed induction criteria: these varied widely and were not all in national guidance. Multidisciplinary booking decision-making was not reported by 38/54 (70%). Delays reported 'often/always' in hospital admission for induction (19%, 10/54) and Delivery Suite transfer once induction in progress (63%, 34/54). Staffing was frequently reported cause of delay (76%, 41/54 'often/always'). Delays triggered incident reports in 36/54 (67%) and resulted in harm in 3/54 (6%). Induction was an area of concern (44%, 24/54); 61% (33/54) reported induction-focused quality improvement work. CONCLUSIONS: There is substantial variation in induction rates, processes and policies across UK maternity services. Delays appear to be common and are a cause of safety concerns. With induction rates likely to increase, improved guidance and pathways are critically needed to improve safety and experience of care.

Mothers working to prevent early stillbirth study (MiNESS 20-28): a case-control study protocol.

INTRODUCTION: In the UK, 1600 babies die every year before, during or immediately after birth at 20-28 weeks' gestation. This bereavement has a similar impact on parental physical and psychological well-being to late stillbirth (>28 weeks' gestation). Improved understanding of potentially modifiable risk factors for late stillbirth (including supine going-to-sleep position) has influenced international clinical practice. Information is now urgently required to similarly inform clinical practice and aid decision-making by expectant mothers/parents, addressing inequalities in pregnancy loss between 20 and 28 weeks. METHODS AND ANALYSIS: This study focuses on what portion of risk of pregnancy loss 20-28 weeks' gestation is associated with exposures amenable to public health campaigns/antenatal care adaptation. A case-control study of non-anomalous singleton baby loss (via miscarriage, stillbirth or early neonatal death) 20+0 to 27+6 (n=316) and randomly selected control pregnancies (2:1 ratio; n=632) at group-matched gestations will be conducted. Data is collected via participant recall (researcher-administered questionnaire) and extraction from contemporaneous medical records. Unadjusted/confounder-adjusted ORs will be calculated. Exposures associated with early stillbirth at OR≥1.5 will be detectable (p<0.05, ß>0.80) assuming exposure prevalence of 30%-60%. ETHICS AND DISSEMINATION: NHS research ethical approval has been obtained from the London-Seasonal research ethics committee (23/LO/0622). The results will be presented at international conferences and published in peer-reviewed open-access journals. Information from this study will enable development of antenatal care and education for healthcare professionals and pregnant people to reduce risk of early stillbirth. TRIAL REGISTRATION NUMBER: NCT06005272.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Pregnancy outcomes in women following the Ross procedure.

INTRODUCTION: The Ross procedure, where a pulmonary autograft (neoaorta) replaces the aortic valve, has excellent long-term outcomes in patients with congenital aortic valve disease. However, there are reports of neoaortic dilatation and dissection. An increasing number of women are wishing to become pregnant following the Ross procedure, but little is known about the occurrence and risks of neoaortic dilatation and complications in pregnancy. We investigated neoaorta function and outcomes in pregnancy following the Ross procedure. METHODS: This retrospective study investigated women post-Ross procedure at a tertiary ACHD unit between 1997 and 2021. Imaging evaluated neoaortic root dimensions and regurgitation pre-, and post- pregnancy, compared with matched non-pregnant controls. Primary endpoints were change in neoaortic dimensions, degree of regurgitation and adverse maternal outcomes. RESULTS: Nineteen pregnancies in 12 women were included. The mean change in neoaortic root diameter post-pregnancy was 1.8 mm (SD 3.4) (p = 0.017). There was no significant change in neoaortic dimensions in matched controls during follow-up. There were no cases of dissection, arrhythmia, acute coronary syndrome, or maternal mortality. Three deliveries were pre-term, including one emergency Caesarean section due to maternal cardiac decompensation, requiring aortic root replacement post-partum but there were no neonatal deaths. CONCLUSIONS: Pregnancy following the Ross procedure is associated with neoaortic dilatation, and pregnancy is generally well tolerated. Although adverse maternal outcomes are uncommon, there are still rare cases of cardiac complications in and around the time of pregnancy. These findings emphasise the need for accessible pre-pregnancy counselling, risk stratification and careful surveillance through pregnancy by specialist cardio-obstetric multi-disciplinary teams.

Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial.

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

Application of a Physiologically Based Pharmacokinetic Model to Predict Cefazolin and Cefuroxime Disposition in Obese Pregnant Women Undergoing Caesarean Section.

Intravenous (IV) cefuroxime and cefazolin are used prophylactically in caesarean sections (CS). Currently, there are concerns regarding sub-optimal dosing in obese pregnant women compared to lean pregnant women prior to CS. The current study used a physiologically based pharmacokinetic (PBPK) approach to predict cefazolin and cefuroxime pharmacokinetics in obese pregnant women at the time of CS as well as the duration that these drug concentrations remain above a target concentration (2, 4 or 8 µg/mL or µg/g) in plasma or adipose tissue. Cefazolin and cefuroxime PBPK models were first built using clinical data in lean and in obese non-pregnant populations. Models were then used to predict cefazolin and cefuroxime pharmacokinetics data in lean and obese pregnant populations. Both cefazolin and cefuroxime models sufficiently described their total and free levels in the plasma and in the adipose interstitial fluid (ISF) in non-pregnant and pregnant populations. The obese pregnant cefazolin model predicted adipose exposure adequately at different reference time points and indicated that an IV dose of 2000 mg can maintain unbound plasma and adipose ISF concentration above 8 µg/mL for 3.5 h post dose. Predictions indicated that an IV 1500 mg cefuroxime dose can achieve unbound plasma and unbound ISF cefuroxime concentration of ≥8 µg/mL up to 2 h post dose in obese pregnant women. Re-dosing should be considered if CS was not completed within 2 h post cefuroxime administration for both lean or obese pregnant if cefuroxime concentrations of ≥8 µg/mL is required. A clinical study to measure cefuroxime adipose concentration in pregnant and obese pregnant women is warranted.

Outcomes in intervention and management of multiple pregnancies trials: A systematic review.

OBJECTIVES: Twin pregnancy has risks of adverse outcomes for mother and baby. Data synthesis is required to gain evidence to aid recommendations but may be hampered by variations in outcome reporting. STUDY DESIGN: Systematically review outcomes reported in twin pregnancy trials (PROSPERO - CRD42019133805). Searches were performed in MEDLINE, EMBASE, CINHAL, Cochrane library (inception-January 2019) for randomised control trials or their follow-up studies reporting prediction, prognosis, intervention or management outcomes in twin pregnancy. The study characteristics, outcomes definitions and measurements were extracted and descriptively analysed. RESULTS: 49 RCTs and 8 follow-up studies evaluated 21 interventions, 1257 outcomes, categorised into 170 unique outcomes. 65 % of trials included all twin pregnancies, 12 % DCDA and 11 % MCDA only or MCMA and MCDA. Five (9 %) papers were prediction/ prognosis RCT's and 52 (91 %) related to an intervention. Of interventions, 40 (77 %) were medical, 34 (85 %) for preterm birth; 12 (23 %) surgical, 6 (50 %) related to TTTS interventions (83 % for monochrorionic studies). Commonest domains were: 'Neonatal' 77 %, 'Delivery' 70 % and 'Survival' 67 %. Least reported were longer term outcomes for 'Infant' or 'Parental'. CONCLUSIONS: Twin pregnancy outcomes are diverse and complex. This is related to the need to address maternal, single and double fetal outcomes and different types of chorionicity. The lack of outcome standardisation in selection, definition and reporting hinders evidence synthesis and the selection of outcomes important to women and health care professionals thus limiting the effectiveness of research.

Aspirin for preventing adverse outcomes in low risk nulliparous women with singleton pregnancies: A systematic review and meta-analysis.

OBJECTIVE: To assess the effects of aspirin in pregnancy for the prevention of adverse outcomes in low risk, nulliparous women with singleton pregnancies. STUDY DESIGN: Medline, Embase, CINAHL, the Cochrane library, Web of Science and clinicaltrials.gov were searched from inception until February 2020. Randomised controlled trials were eligible for inclusion where women were nulliparous, had singleton pregnancies and no other risk factors for pre-eclampsia such as diabetes or pre-existing hypertension. Primary outcomes were pre-eclampsia, gestational hypertension and eclampsia. Secondary outcomes included; pre-term birth, postpartum haemorrhage, antepartum haemorrhage, miscarriage, small for gestational age (SGA), fetal growth restriction (FGR), birthweight and further markers of maternal and neonatal morbidity and mortality. The results were combined into meta-analysis where appropriate. RESULTS: Ten studies were eligible for inclusion involving 23,162 women. Two studies (involving 214 women) used aspirin doses of 100 mg, with the remainder using smaller doses. There was no significant difference found in the risk of developing pre-eclampsia between women receiving aspirin compared to no aspirin (relative risk [RR] 0.70, 95 % confidence interval [CI] 0.47-1.05, p = 0.08). Women receiving aspirin had a reduced risk of having a preterm birth <34 weeks (RR 0.50, 95 % CI 0.26-0.96, p = 0.04), and reduced risk of having a SGA neonate (RR 0.94, 95 % CI 0.89-1.00, p = 0.04). An increase in birthweight was seen when aspirin was received (mean difference 105.17 g, 95 % CI 12.38 g-197.96 g, p = 0.03) and there was no increase in risk of postpartum or antepartum haemorrhage in those receiving aspirin (RR 1.24, 95 % CI 0.90-1.71, p = 0.19 and RR 1.06, 95 % CI 0.66-1.70, p = 0.81 respectively). CONCLUSION: The results did not demonstrate a significant difference amongst low risk nulliparous women in the risks of pre-eclampsia or gestational hypertensive disorders with aspirin administration. Although we found significantly improved fetal growth parameters and prevention of preterm birth in women receiving aspirin, there were few eligible studies, with those included generally providing low quality evidence and many studies using aspirin doses ≤100 mg, commenced late in pregnancy. More research in the form of a high quality randomised controlled trial is needed before recommendations can be made.

Authors' reply to: Letter to the Editor in response to 'Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study'.

In this correspondence we thank the authors for highlighting the importance of our work, and agree with the limitations they have raised regarding performing this study.

Prophylactic perioperative cefuroxime levels in plasma and adipose tissue at the time of caesarean section (C-LACE): a protocol for a pilot experimental, prospective study with non-probability sampling to determine interpatient variability.

BACKGROUND: The aim of the C-LACE study is to measure cefuroxime concentration in plasma and adipose tissue of non-obese and obese pregnant women undergoing caesarean section. METHODS: This study plans to compare maternal cefuroxime concentrations (plasma and adipose tissue), at the time of skin incision and time of skin closure during a caesarean section from non-obese (body mass index BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) pregnant women. The incidence of post-surgical site infection will also be measured. At least 15 participants are required for each arm (non-obese vs obese) with a total of 30 participants. The study participants will be followed up between 30 and 40 days post-caesarean section to record details of any post-caesarean surgical infection to explore correlations between BMI, measured cefuroxime concentrations and post-caesarean infection rates. DISCUSSION: This pilot study will allow the development of a model testing the inter-patient variability in plasma and adipose tissue concentrations of cefuroxime. The results will facilitate the development of a larger study to determine whether differences in cefuroxime plasma and tissue concentration in obese and non-obese women can support the development of a physiologically based pharmacokinetic model. This model can then be used to propose dosing adjustments that can be used in a further trial to optimise cefuroxime dosing for women undergoing caesarean section. TRIAL REGISTRATION: ISRCTN Registry , ISRCTN17527512 . Registered on 26 October 2020.

The incidence, maternal, fetal and neonatal consequences of single intrauterine fetal death in monochorionic twins: A prospective observational UKOSS study.

OBJECTIVE: Report maternal, fetal and neonatal complications associated with single intrauterine fetal death (sIUFD) in monochorionic twin pregnancies. DESIGN: Prospective observational study. SETTING: UK. POPULATION: 81 monochorionic twin pregnancies with sIUFD after 14 weeks gestation, irrespective of cause. METHODS: UKOSS reporters submitted data collection forms using data from hospital records. MAIN OUTCOME MEASURES: Aetiology of sIUFD; surviving co-twin outcomes: perinatal mortality, central nervous system (CNS) imaging, gestation and mode of delivery, neonatal outcomes; post-mortem findings; maternal outcomes. RESULTS: The commonest aetiology was twin-twin transfusion syndrome (38/81, 47%), "spontaneous" sIUFD (22/81, 27%) was second commonest. Death of the co-twin was common (10/70, 14%). Preterm birth (<37 weeks gestation) was the commonest adverse outcome (77%): half were spontaneous and half iatrogenic. Only 46/75 (61%) cases had antenatal CNS imaging, of which 33 cases had known results of which 7/33 (21%) had radiological findings suggestive of neurological damage. Postnatal CNS imaging revealed an additional 7 babies with CNS abnormalities, all born at <36 weeks, including all 4 babies exhibiting abnormal CNS signs. Major maternal morbidity was relatively common, with 6% requiring ITU admission, all related to infection. CONCLUSIONS: Monochorionic twin pregnancies with single IUD are complex and require specialist care. Further research is required regarding optimal gestation at delivery of the surviving co-twin, preterm birth prevention, and classifying the cause of death in twin pregnancies. Awareness of the importance of CNS imaging, and follow-up, needs improvement.

Efficacy of perioperative cefuroxime as a prophylactic antibiotic in women requiring caesarean section: A systematic review.

Intravenous (IV) Cefuroxime (CFX) is widely used in Caesarean Section (CS) as a prophylactic antibiotic. The objective of this systematic review to compare CFX concentration in maternal blood and adipose tissue with the incidence of surgical site infection (SSI) following IV CFX in non-obese and obese women undergoing CS. A search in Medline, EMBASE, Cochrane, Web of Science, CINHAL Plus, Scopus and Google Scholar was conducted without language or date restrictions. Published articles or abstracts reporting CFX concentration or rates of SSI following CFX IV administration in adult women requiring CS were included. Studies were screened by title and abstract. Quality of studies was assessed via the ClinPK Statement checklist (Pharmacokinetics studies), or Joanna Briggs Institute Critical Appraisal Tools (SSI studies). The Cochrane Effective Practice and Organisation of Care checklist evaluated the risk of bias (SSI studies). There were no studies evaluating CFX concentrations in obese women undergoing CS. For non-obese women, CFX plasma concentrations ranged from 9.85 to 95.25 mg/L within 30-60 min of administration (1500 mg dose; 4 articles, n = 108 women). Plasma CFX concentrations were above the minimum inhibitory concentration (8 mg/L) for up to 3 h post-dose. No studies reported on CFX concentration in adipose tissue. Reported rates of SSI were 4.7% and 6.8% after administration of a single 1500 mg dose of CFX administrated after cord clamping (n = 144 women). There is limited data on pharmacokinetics of CFX for CS. There were no studies that reported CFX concentrations or SSI in obese women.

Women's perspectives on caesarean section recovery, infection and the PREPS trial: a qualitative pilot study.

BACKGROUND: In England, 27.8% of all pregnant women undergo caesarean sections (CS) to deliver their babies. Women undergoing CS are at risk of developing sepsis and post-natal infections, which not only contribute significantly to maternal mortality and morbidity, but also negatively impact upon post-natal recovery and wellbeing. This study explores patients' priorities in relation to CS recovery, focusing on their knowledge and experiences of infection prevention. The study formed part of the PREPS (Vaginal Preparation at caesarean section to Reduce Endometritis and Prevent Sepsis - a feasibility study of chlorhexidine) Trial; patients' views on the PREPS Trial were also sought. METHODS: Using qualitative methodology, two focus groups and six telephone interviews were carried out between September and October 2017 with a total of 21 women who had undergone a CS within the preceding six months. Focus groups and individual telephone interviews were audio-recorded and transcribed verbatim; a thematic analysis was conducted using NVivo 11. RESULTS: Women's priorities around CS recovery centred on pain (or the lack thereof), mobility and the ability to resume everyday activities, including caregiving. Those undergoing a CS for the first time reported not feeling confident in their ability to identify signs of infection and sought visiting health professionals' expertise and reassurance. Women were unable to recall whether they had received information regarding infection prevention and felt that they had not received sufficient advice. Some reported receiving general information regarding CS recovery, which ranged in quality. Prevention of womb infection is a major goal of the PREPS trial, however, the majority of women were not aware that womb (as opposed to wound) infection was a post CS risk. CONCLUSIONS: Women undergoing a CS want more information on what constitutes a 'normal' post-operative recovery and specifically would welcome written information and infection prevention advice. This should be a key element of improving post-CS maternal experiences and potentially reducing sepsis and infection rates. CS stigma negatively impacts women's recovery experiences and possibly information provision. The PREPS team incorporated findings regarding consent pathways for recruiting women into intrapartum research and developed two patient reported outcomes to collect in the main trial. TRIAL REGISTRATION: The PREPS trial has been registered with ISRCTN on the 10th July 2017 ( ISRCTN33435996 ).