Maternal and fetal outcomes in pregnancies complicated by Marfan syndrome.

OBJECTIVES: Information to guide counselling and management for pregnancy in women with Marfan syndrome (MFS) is limited. We therefore conducted a UK multicentre study. METHODS: Retrospective observational study of women with MFS delivering between January 1998 and March 2018 in 12 UK centres reporting data on maternal and neonatal outcomes. RESULTS: In total, there were 258 pregnancies in 151 women with MFS (19 women had prior aortic root replacements), including 226 pregnancies ≥24 weeks (two sets of twins), 20 miscarriages and 12 pregnancy terminations. Excluding miscarriages and terminations, there were 221 live births in 139 women. Only 50% of women received preconception counselling. There were no deaths, but five women experienced aortic dissection (1.9%; one type A and four type B-one had a type B dissection at 12 weeks and subsequent termination of pregnancy). Five women required cardiac surgery postpartum. No predictors for aortic dissection could be identified. The babies of the 131 (65.8%) women taking beta-blockers were on average 316 g lighter (p<0.001). Caesarean section rates were high (50%), particularly in women with dilated aortic roots. In 55 women, echocardiographic aortic imaging was available prepregnancy and postpregnancy; there was a small but significant average increase in AoR size of 0.84 mm (Median follow-up 2.3 months) CONCLUSION: There were no maternal deaths, and the aortic dissection rate was 1.9% (mainly type B). There with no identifiable factors associated with aortic dissection in our cohort. Preconception counselling rates were low and need improvement. Aortic size measurements increased marginally following pregnancy.

Birth weight in pregnancies complicated by maternal heart disease.

OBJECTIVE: To assess median and percentile birthweight distribution in women with various groups of heart disease relative to a contemporaneous comparison group. METHODS: Data on birth weight and gestational age were collected from 1321 pregnancies ≥24 weeks' gestation in 1053 women with heart disease from seven UK maternity units. Women were assigned to one of 16 groups according to their cardiac lesion. In units where it was possible, data on two births, one delivering before and one after index cases, were collected, giving 2307 comparators. Birthweight percentiles (corrected for gestational age, sex and parity) were calculated using Aberdeen norms. We assessed the association of birth weight with cardiac lesion, maternal hypoxaemia (saturations <90%), systemic ventricular function and beta-blockers. RESULTS: 1321 pregnancies in women with heart disease and 2307 comparators were studied. Almost all groups with heart disease had lower median and percentile birth weights than comparators, significantly in 10 groups, the biggest effect seen in women with Fontan circulation, pulmonary hypertension, prosthetic heart valves, systemic right ventricle, Marfan syndrome, repaired tetralogy of Fallot and cardiomyopathy (in that order). In 307 pregnancies, women took beta-blockers; median birth weight adjusted for maternal age, parity and the effect of the cardiac lesion was 3116.7 g (IQR 790.4) when beta-blockers were used and 3354.3 g (IQR 634.1) when they were not (p<0.001). 17 women had saturations <90%, and median birth weight was significantly lower, 3105.4 g (IQR 1288.9) versus 3387.7 g (IQR 729.8) (p=0.006). CONCLUSION: Our findings identify specific groups of women with heart disease at risk of having a small baby.

Mechanical Mitral Valve Replacement during the 2nd Trimester of Pregnancy.

We report the case of a 44-year-old pregnant woman who was diagnosed with symptomatic severe mitral stenosis that did not respond to optimal medical therapy and balloon valvuloplasty. After a multidisciplinary team discussion on the timing and risks of interventions and postoperative optimization of peripartum anticoagulation, the patient underwent mechanical mitral valve replacement during the 2nd trimester of pregnancy. The outcome was excellent for the mother and the infant. This case emphasizes the importance of a multidisciplinary approach in managing unusual cases.

Induction of labour versus expectant management at term by subgroups of maternal age: an individual patient data meta-analysis.

BACKGROUND: British women are delaying childbirth. Women aged 35 years or over have a higher risk of perinatal death. There is a linear relationship between maternal age and delivery by emergency caesarean in nulliparous women. Many obstetricians induce older women at term attempting to improve perinatal outcomes, others are reluctant for fear of increasing caesarean rates. A recent systematic review of induction of labour versus expectant management in women at term, found induction was associated with a reduction in caesareans (OR 0.83, 95% CI 0.76-0.92). OBJECTIVES: To identify whether induction of labour changes the risk of caesarean section in women aged 35 years or over. SEARCH STRATEGY: Available data sets from RCTs included in the Wood et al. systematic review (31 trials) and suitable RCTs published since week 23, 2012. SELECTION CRITERIA: Studies were included if they were randomised controlled trials comparing induction of labour with expectant management at term with intact membranes with a singleton or multiple pregnancy in a cephalic presentation. DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis of individual patient data (IPD) using a random-effects model to calculate odds ratios. RESULTS: In total 2675 women (five studies) were included in the meta-analysis and 2526 women (four studies) were included in the IPD meta-analysis. There was no statistically significant increase in caesarean section rates seen in either analysis. CONCLUSIONS: Induction of labour in women of advanced maternal age has no statistically significant effect on caesarean section rates.

Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points).

Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial.

BACKGROUND: Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO. METHODS: In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556. FINDINGS: 31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71-4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06-9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function-only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses. INTERPRETATION: Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done. FUNDING: UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).

Effectiveness of interventions for the prevention of small-for-gestational age fetuses and perinatal mortality: a review of systematic reviews.

Previous narrative reviews in this area have concluded that there are few interventions that are likely to be beneficial and that further high-quality research is required. Our objective was to perform a review of systematic reviews of the effectiveness of interventions for the prevention of small-for-gestational age (SGA) fetuses and perinatal mortality, to summarize the most up-to-date evidence and assess quality. Searches were carried out by using Medline, Embase, Cochrane Library and DARE (inception to September 2011), by hand searching of journal and reference lists and by contact with experts. Systematic reviews of randomized controlled trials were selected. Two reviewers independently selected articles and assessed the methodological and reporting quality. Data were extracted on study characteristics, quality and results. Summary data were presented as relative risks (RRs) and 95% confidence intervals (CIs). There were 834 randomized controlled trials (>668 672 participants), reporting on 45 different interventions. The most effective interventions to prevent the SGA fetus were antiplatelets at <16 weeks in women at risk of pre-eclampsia (RR 0.47; CI 0.30-0.74) and progesterone therapy for prevention of preterm birth (RR 0.64; CI 0.49-0.83). For the prevention of perinatal mortality in high-risk women, antiplatelets (RR 0.69; CI 0.53-0.90) and antenatal corticosteroids (RR 0.77; CI 0.67-0.89) were effective interventions. It is concluded that effective interventions are available for reducing the occurrence of SGA fetuses and preventing related perinatal mortality. Some are effective in all women, while others target specific co-morbidities. There is a need to consider a comprehensive approach to primary prevention that targets SGA along with pre-eclampsia and preterm birth.

Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between umbilical cord pH at birth and long term outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline (1966-August 2008), Embase (1980-August 2008), the Cochrane Library (2008 issue 8), and Medion, without language restrictions; reference lists of selected articles; and contact with authors. STUDY SELECTION: Studies in which cord pH at birth was compared with any neonatal or long term outcome. Cohort and case-control designs were included. RESULTS: 51 articles totalling 481 753 infants met the selection criteria. Studies varied in design, quality, outcome definition, and results. Meta-analysis carried out within predefined groups showed that low arterial cord pH was significantly associated with neonatal mortality (odds ratio 16.9, 95% confidence interval 9.7 to 29.5, I(2)=0%), hypoxic ischaemic encephalopathy (13.8, 6.6 to 28.9, I(2)=0%), intraventricular haemorrhage or periventricular leucomalacia (2.9, 2.1 to 4.1, I(2)=0%), and cerebral palsy (2.3, 1.3 to 4.2, I(2)=0%). CONCLUSIONS: Low arterial cord pH showed strong, consistent, and temporal associations with clinically important neonatal outcomes that are biologically plausible. These data can be used to inform clinical management and justify the use of arterial cord pH as an important outcome measure alongside neonatal morbidity and mortality in obstetric trials.

Mary Crosse project: systematic reviews and grading the value of neonatal tests in predicting long term outcomes.

BACKGROUND: Events before birth, condition at birth, events immediately following birth, and condition in early childhood are linked together, and have implications for health and disease in adulthood. At present, there is lack of clarity about the tests that purport to link these various stages. This is partly because there is paucity of collated information about the best strategies for predicting longer-term outcomes before (using tests in fetal period) or after birth (using tests in neonatal period, infancy as well as early childhood). METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, amongst neonates, the ability of various tests and measures to predict infant, childhood and adult outcomes. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Independent reviewers will select studies, extract data and assess study quality according to established criteria. Language restrictions will not be applied. Data synthesis will involve meta-analysis (where appropriate), exploration of heterogeneity and publication bias. Evidence collated will be graded for its quality to support decision making. DISCUSSION: The project will collate, synthesise and evaluate the available evidence concerning the value of tests of neonatal wellbeing to predict long term outcomes. The systematic reviews will assess the quality of available evidence and identify tests with the strongest association with outcomes, and assess their economic value. The output of this project will help formulate practice recommendations.

Patient information following emergency laparoscopy for right iliac fossa pain.

Laparoscopy is increasingly used as a diagnostic and therapeutic tool in the management of emergency surgical admissions. Laparoscopic scars give little clue to the operation performed. Hence, the future assessment of patients re-admitted with abdominal pain, often needs to rely on the patient's own account of the operation performed. This study attempted to evaluate the quality of communication between surgeons and patients regarding the results of their laparoscopy and how much information was retained by the patients on discharge. Seventy-seven patients were identified from computerised medical records. A detailed case note review was undertaken looking at operative findings, procedure performed, and documentation of surgeon-to-patient communication. A questionnaire was posted to patients asking their opinion regarding the quality of communication from surgeons. The questionnaire asked specific questions regarding the patient's understanding of the operation performed and its findings. Overall communication between surgeons and patients was good. However, a small proportion of patients were unsure of their diagnosis and what therapeutic procedure had been performed following laparoscopy. This included one patient (out of 28 who had undergone laparoscopic appendectomy) who was unsure if their appendix had been removed. Two from 12 patients diagnosed with pelvic pathology at laparoscopy who were unclear of their diagnosis and two patients with histologically normal appendices who thought their appendices had been inflamed at removal. Greater effort must be made to inform patients of their laparoscopic findings and any therapeutic procedure performed. We recommend the use of written information leaflets to be sent to the patient's home address to ensure that all patients are fully aware of their laparoscopic findings. For any future emergency admission, the patient's knowledge of any previous surgery and whether their appendix is in situ is of considerable diagnostic value to the assessing clinician. More effort must be made to enable patients to retain such necessary information.