Caesarean section surgical techniques: 3 year follow-up of the CORONIS fractional, factorial, unmasked, randomised controlled trial.

BACKGROUND: The CORONIS trial reported differences in short-term maternal morbidity when comparing five pairs of alternative surgical techniques for caesarean section. Here we report outcomes at 3 years follow-up. METHODS: The CORONIS trial was a pragmatic international 2 × 2 × 2 × 2× 2 non-regular fractional, factorial, unmasked, randomised controlled trial done at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. In this follow-up study, we compared outcomes at 3 years following blunt versus sharp abdominal entry, exteriorisation of the uterus for repair versus intra-abdominal repair, single versus double layer closure of the uterus, closure versus non-closure of the peritoneum, and chromic catgut versus polyglactin-910 for uterine repair. Outcomes included pelvic pain; deep dyspareunia; hysterectomy and outcomes of subsequent pregnancies. Outcomes were assessed masked to the original trial allocation. This trial is registered with the Current Controlled Trials registry, number ISRCTN31089967. FINDINGS: Between Sept 1, 2011, and Sept 30, 2014, 13,153 (84%) women were followed-up for a mean duration of 3·8 years (SD 0·86). For blunt versus sharp abdominal entry there was no evidence of a difference in risk of abdominal hernias (adjusted RR 0·66; 95% CI 0·39-1·11). We also recorded no evidence of a difference in risk of death or serious morbidity of the children born at the time of trial entry (0·99, 0·83-1·17). For exteriorisation of the uterus versus intra-abdominal repair there was no evidence of a difference in risk of infertility (0·91, 0·71-1·18) or of ectopic pregnancy (0·50, 0·15-1·66). For single versus double layer closure of the uterus there was no evidence of a difference in maternal death (0·78, 0·46-1·32) or a composite of pregnancy complications (1·20, 0·75-1·90). For closure versus non-closure of the peritoneum there was no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions such as infertility (0·80, 0·61-1·06). For chromic catgut versus polyglactin-910 sutures there was no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (3·05, 0·32-29·29). Overall, severe adverse outcomes were uncommon in these settings. INTERPRETATION: Although our study was not powered to detect modest differences in rare but serious events, there was no evidence to favour one technique over another. Other considerations will probably affect clinical practice, such as the time and cost saving of different approaches. FUNDING: UK Medical Research Council and the Department for International Development.

The management and outcomes of placenta accreta, increta, and percreta in the UK: a population-based descriptive study.

OBJECTIVE: To describe the management and outcomes of placenta accreta, increta, and percreta in the UK. DESIGN: A population-based descriptive study using the UK Obstetric Surveillance System (UKOSS). SETTING: All 221 UK hospitals with obstetrician-led maternity units. POPULATION: All women diagnosed with placenta accreta, increta, and percreta in the UK between May 2010 and April 2011. METHODS: Prospective case identification through the monthly mailing of UKOSS. MAIN OUTCOME MEASURES: Median estimated blood loss, transfusion requirements. RESULTS: A cohort of 134 women were identified with placenta accreta, increta, or percreta: 50% (66/133) were suspected to have this condition antenatally. In women with a final diagnosis of placenta increta or percreta, antenatal diagnosis was associated with reduced levels of haemorrhage (median estimated blood loss 2750 versus 6100 ml, P = 0.008) and a reduced need for blood transfusion (59 versus 94%, P = 0.014), possibly because antenatally diagnosed women were more likely to have preventative therapies for haemorrhage (74 versus 52%, P = 0.007), and were less likely to have an attempt made to remove their placenta (59 versus 93%, P < 0.001). Making no attempt to remove any of the placenta, in an attempt to conserve the uterus or prior to hysterectomy, was associated with reduced levels of haemorrhage (median estimated blood loss 1750 versus 3700 ml, P = 0.001) and a reduced need for blood transfusion (57 versus 86%, P < 0.001). CONCLUSIONS: Women with placenta accreta, increta, or percreta who have no attempt to remove any of their placenta, with the aim of conserving their uterus, or prior to hysterectomy, have reduced levels of haemorrhage and a reduced need for blood transfusion, supporting the recommendation of this practice.

Caesarean section surgical techniques (CORONIS): a fractional, factorial, unmasked, randomised controlled trial.

BACKGROUND: Variations exist in the surgical techniques used for caesarean section and many have not been rigorously assessed in randomised controlled trials. We aimed to assess whether any surgical techniques were associated with improved outcomes for women and babies. METHODS: CORONIS was a pragmatic international 2×2×2×2×2 non-regular fractional, factorial, unmasked, randomised controlled trial that examined five elements of the caesarean section technique in intervention pairs. CORONIS was undertaken at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Each site was assigned to three of the five intervention pairs: blunt versus sharp abdominal entry; exteriorisation of the uterus for repair versus intra-abdominal repair; single-layer versus double-layer closure of the uterus; closure versus non-closure of the peritoneum (pelvic and parietal); and chromic catgut versus polyglactin-910 for uterine repair. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based number allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. The primary outcome was the composite of death, maternal infectious morbidity, further operative procedures, or blood transfusion (>1 unit) up to the 6-week follow-up visit. Women were analysed in the groups into which they were allocated. The CORONIS Trial is registered with Current Controlled Trials: ISRCTN31089967. FINDINGS: Between May 20, 2007, and Dec 31, 2010, 15 935 women were recruited. There were no statistically significant differences within any of the intervention pairs for the primary outcome: blunt versus sharp entry risk ratio 1·03 (95% CI 0·91-1·17), exterior versus intra-abdominal repair 0·96 (0·84-1·08), single-layer versus double-layer closure 0·96 (0·85-1·08), closure versus non-closure 1·06 (0·94-1·20), and chromic catgut versus polyglactin-910 0·90 (0·78-1·04). 144 serious adverse events were reported, of which 26 were possibly related to the intervention. Most of the reported serious adverse events were known complications of surgery or complications of the reasons for the caesarean section. INTERPRETATION: These findings suggest that any of these surgical techniques is acceptable. However, longer-term follow-up is needed to assess whether the absence of evidence of short-term effects will translate into an absence of long-term effects. FUNDING: UK Medical Research Council and WHO.

Contemporary management and outcomes for infants born with oesophageal atresia.

BACKGROUND: Reports on the management and outcome of rare conditions, such as oesophageal atresia, are frequently limited to case series reporting single-centre experience over many years. The aim of this study was to identify all infants born with oesophageal atresia in the UK and Ireland to describe current clinical practice and outcomes. METHODS: This was a prospective multicentre cohort study of all infants born with oesophageal atresia and/or tracheo-oesophageal fistula in 2008-2009 in the UK and Ireland to record current clinical management and early outcomes. RESULTS: A total of 151 infants admitted to 28 paediatric surgical units were identified. Some aspects of perioperative management were universal, including oesophageal decompression, operative technique and the use of transanastomotic tubes. However, there were a number of areas where clinical practice varied considerably, including the routine use of perioperative chest drains, postoperative contrast studies and antireflux medication, with each of these being employed in 30-50 per cent of patients. There was a trend towards routine postoperative ventilation. CONCLUSION: The prospective methodology used in this study can help identify practices that all surgeons employ and also those that few surgeons use. Areas of clinical equipoise can be recognized and avenues for further research identified.

Myocardial infarction in pregnancy and postpartum in the UK.

AIM: Cardiac disease is a leading cause of maternal death in the developed world, responsible for one-fifth of all maternal deaths in the UK. The aim of this study was to estimate the incidence of myocardial infarction (MI) in pregnancy and up to one week postpartum in the UK and describe risk factors, management and outcomes. METHODS: A prospective population-based study with nested case control analysis used the UK Obstetric Surveillance System to identify all women in the UK with MI in pregnancy (in the years 2005-2010). A control group of 1360 women was used for comparison. Multivariable unconditional logistic regression was conducted to identify potential risk factors for MI in pregnancy and calculate adjusted odds ratios with 95% confidence intervals. RESULTS: Twenty-five cases of MI in pregnancy were reported, giving an estimated incidence of 0.7 per 100,000 maternities (95%CI 0.5-1.1). Maternal age, smoking, hypertension, twin pregnancy and pre-eclampsia were independently associated with MI in pregnancy. Fifteen (60%) women underwent coronary angiography; nine (60%) had coronary atherosclerosis, three (21%) had coronary artery dissection, one (7%) had a coronary thrombus and two (13%) had normal coronary arteries. Nine women had angioplasty +/- stenting and two were thrombolysed. No women died. CONCLUSIONS: Many risk factors are both recognisable and modifiable. Management of MI in pregnancy was highly variable indicating a clear need for further information regarding the safety and outcomes of different interventions. The addition of pregnancy status as a compulsory field in cardiac audit databases would enable routine collection of this information.

Specific second-line therapies for postpartum haemorrhage: a national cohort study.

OBJECTIVE: To describe the characteristics, management and outcomes of women undergoing specific second-line therapies for postpartum haemorrhage (PPH). DESIGN: A population-based descriptive study. SETTING: All 226 consultant-led maternity units in the UK. POPULATION: All women delivering between September 2007 and March 2009. METHODS: Prospective identification of women with PPH managed with uterine compression sutures, pelvic vessel ligation, interventional radiological techniques and recombinant factor VIIa (rFVIIa) through the UK Obstetric Surveillance System (UKOSS). Women with a PPH successfully treated with an intrauterine balloon where none of the other techniques were used were not included in the study. MAIN OUTCOME MEASURES: Usage and success rates with 95% confidence intervals. RESULTS: A specific second-line treatment was used in 272 women representing an estimated rate of use of 2.2 cases per 10,000 women delivering (95% CI 1.9-2.5/10,000). Sixty-seven women (25%) were managed with intrauterine tamponade to treat PPH prior to the use of one of the specific second-line therapies. As the first second-line therapy, uterine compression sutures were successful in 120 women (75%; 95% CI 67-81%), pelvic vessel ligation was successful in five women (36%; 95% CI 13-65%) interventional radiology was successful in 12 women (86%; 95% CI 57-98%) and rFVIIa was successful in five women (31%; 95% CI 11-59%). Rates of success were not significantly different in cases managed first with intrauterine tamponade. Overall, 71 (26%) women had a hysterectomy. CONCLUSIONS: Overall, a quarter of women treated had a hysterectomy as a rescue therapy. Uterine compression sutures and interventional radiological techniques have higher success rates than rFVIIa and pelvic vessel ligation. However, cases managed with rFVIIa and ligation tend to be more clinically complex.

Planned vaginal delivery or planned caesarean delivery in women with extreme obesity.

OBJECTIVE: To compare the outcomes of planned vaginal versus planned caesarean delivery in a cohort of extremely obese women (body mass index ≥ 50 kg/m(2)). DESIGN: A national cohort study using the UK Obstetric Surveillance System (UKOSS). SETTING: All hospitals with consultant-led maternity units in the UK. POPULATION: Five hundred and ninety-one extremely obese women delivering in the UK between September 2007 and August 2008. METHODS: Prospective cohort identification through UKOSS routine monthly mailings. MAIN OUTCOME MEASURES: Anaesthetic, postnatal and neonatal complication rates. RESULTS: After adjustment, there were no significant differences in anaesthetic, postnatal or neonatal complications between women with planned vaginal delivery and planned caesarean delivery, with the exception of shoulder dystocia (3% versus 0%, P = 0.019). There were no significant differences in any outcomes in the subgroup of women who had no identified medical or antenatal complications. CONCLUSIONS: This study does not provide evidence to support a routine policy of caesarean delivery for extremely obese women on the basis of concern about higher rates of delivery complications, but does support a policy of individualised decision-making on the mode of delivery based on a thorough assessment of potential risk factors for poor delivery outcomes.

Critical illness with AH1N1v influenza in pregnancy: a comparison of two population-based cohorts.

OBJECTIVE: To compare admissions to intensive care units (ICUs) with confirmed AH1N1v influenza in pregnancy in Australia, New Zealand and the UK. DESIGN: National cohort studies. SETTING: ICUs in Australia, New Zealand and the UK. POPULATION: Fifty-nine women admitted to ICUs in Australia and New Zealand in June-August 2009, and 57 women admitted to ICUs in the UK in September 2009-January 2010. METHODS: Comparison of cohort data. MAIN OUTCOME MEASURES: Incidence of ICU admission, comparison of characteristics and outcomes. RESULTS: There was a significantly higher ICU admission risk in Australia and New Zealand than in the UK (risk ratio 2.59, 95% CI 1.75-3.85). Indigenous women from Australia and women with Maori/Pacific Island backgrounds from New Zealand had the highest admission risk (29.7 admissions per 10 000 maternities, 95% CI 17.9-46.3). Women admitted in Australia and New Zealand were significantly more likely to have a pre-existing medical condition (51% versus 21%, P = 0.001), but were less likely to receive antiviral treatment (80% versus 93%, P = 0.038) than women admitted in the UK. Women admitted in the UK had a longer length of hospital stay (median 21 days, range 3-128 days) than women admitted in Australia and New Zealand (median 12 days, range 3-66 days), but there were no other differences in maternal or pregnancy outcomes. CONCLUSIONS: The difference in admission risk may reflect a second phase effect from successful clinical and public health interventions, as well as differences in population characteristics between the countries. The overall severity of the AH1N1v influenza infection in pregnancy is evident, and emphasises the importance of an ongoing immunisation programme in pregnant women in both northern and southern hemispheres.

Influenza A/H1N1v in pregnancy: an investigation of the characteristics and management of affected women and the relationship to pregnancy outcomes for mother and infant.

BACKGROUND: In April 2009 a novel influenza A virus (AH1N1v) of swine origin (swine flu) emerged, spreading rapidly and achieving pandemic status in June 2009. Pregnant women were identified as being at high risk of severe influenza-related complications and as a priority group for vaccination against AH1N1v. Limited information was available about the maternal and fetal risks of AH1N1v infection or of antiviral drug or AH1N1v vaccine use in pregnancy. OBJECTIVES: To assess rates of and risk factors for adverse outcomes following AH1N1v infection in pregnancy and to assess the adverse effects of the antiviral drugs and vaccines used in prevention and management. METHODS: Prospective national cohort studies were conducted to identify pregnant women who were (1) suspected to be infected with AH1N1v or being treated with antiviral medication in primary care; (2) vaccinated against AH1N1v; and (3) admitted to hospital with confirmed AH1N1v. Characteristics of women with influenza-like illness (ILI) in primary care were compared with those of women without symptoms accepting or declining immunisation. Characteristics of women admitted to hospital with confirmed AH1N1v infection in pregnancy were compared with a historical cohort of over 1200 women giving birth in the UK who were uninfected with AH1N1v. Outcomes examined in hospitalised women included maternal death, admission to an intensive care unit, perinatal mortality and preterm birth. Risk factors for hospital and intensive care unit admission were examined in a full regression model. RESULTS: The weekly incidence of ILI among pregnant women averaged 51/100,000 over the study period. Antiviral drugs were offered to 4.8% [95% confidence interval (CI) 4.0% to 5.9%] and vaccination to 64.8% (95% CI 64.7% to 68.9%) of registered pregnant women. Ninety pregnant women with ILI presenting in primary care were reported to the research team, 55 of whom were prescribed antiviral drugs and in 42 (76%) cases this was within 2 days of symptom onset. After comparison with 1329 uninfected pregnant women offered vaccination, pre-existing asthma was the only maternal factor identified as increasing risk of ILI presentation [adjusted odds ratio (OR) 2.0, 95% CI 1.0 to 3.9]. Maternal obesity and smoking during pregnancy were also associated with hospital admission with AH1N1v infection. Overall, 241 pregnant women were admitted to hospital with laboratory-confirmed AH1N1v infection. Eighty-three per cent of these women were treated with antiviral agents, but only 6% received antiviral treatment before hospital admission. Treatment within 2 days of symptom onset was associated with an 84% reduction in the odds of admission to an intensive therapy unit (OR 0.16, 95% CI 0.08 to 0.34). Women admitted to hospital with AH1N1v infection were more likely to deliver preterm; a three times increased risk was suggested compared with an uninfected population cohort (OR 3.1, 95% CI 2.1 to 4.5). CONCLUSIONS: Earlier treatment with antiviral agents is associated with improved outcomes for pregnant women and further actions are needed in future pandemics to ensure that antiviral agents and vaccines are provided promptly to pregnant women, particularly in the primary care setting. Further research is needed on longer-term outcomes for infants exposed to AH1N1v influenza, antiviral drugs or vaccines during pregnancy.

Tuberculosis in pregnancy in the UK.

Tuberculosis (TB) is a globally important cause of morbidity and mortality with an increasing incidence in women of reproductive ages. This descriptive study using the UK Obstetric Surveillance System demonstrates key differences in the presentation of TB during pregnancy compared with the nonpregnant population. The disease is limited to ethnic minority women, most commonly recent immigrants. Presentation may be atypical, with extrapulmonary disease as common as pulmonary. Clinicians should be aware of the potential for nonspecific presentation of the disease in pregnancy and consider the diagnosis in women, especially recently arrived immigrants, presenting with nonspecific symptoms.

A prospective national study of acute fatty liver of pregnancy in the UK.

OBJECTIVES: To identify a national, population-based cohort of women with acute fatty liver of pregnancy (AFLP), to evaluate proposed diagnostic criteria and to document accurately the incidence, management and outcomes of the condition. SUBJECTS AND METHODS: This was a population-based descriptive study using the UK Obstetric Surveillance System, carried out in all 229 hospitals with consultant-led maternity units in the UK. The participants comprised 57 women in the UK diagnosed with AFLP between February 2005 and August 2006 in an estimated cohort of 1 132 964 maternities (women delivering). RESULTS: The estimated incidence of AFLP was 5.0 cases per 100 000 maternities (95% CI 3.8 to 6.5 per 100,000). Fifty-five cases (90%) were confirmed by diagnostic criteria and clinical assessment, two (3%) by clinical assessment alone, representing 97% agreement (kappa statistic = 0.78). 18% of women had twin pregnancies and 20% were underweight (body mass index (BMI) <20). 60% of women were admitted to intensive care and 15% to a specialist liver unit. One woman received a liver transplant. One woman died (case fatality rate 1.8%, 95% CI 0% to 9.4%). There were seven deaths among 67 infants (perinatal mortality rate 104 per 1000 births, 95% CI 43 to 203). CONCLUSIONS: The largest population-based cohort of women with AFLP to date has been identified. Diagnostic criteria previously proposed agree substantially with clinical diagnosis. The incidence estimate from this study is lower than documented by earlier hospital-based studies, but maternal and neonatal outcomes are better than previously reported, possibly related to improved ascertainment. Women with twin pregnancies appear to be at higher risk, but further studies are needed to investigate the risk associated with low BMI.