Gl Malin

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, I2=0%), hypoxic ischaemic encephalopathy (13.8, 6.6 to 28.9, I2=0%), intraventricular haemorrhage or periventricular leucomalacia (2.9, 2.1 to 4.1, I2=0%), and cerebral palsy (2.3, 1.3 to 4.2, I2=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.

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

Summary 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 Childrens Hospital Charity).

Systematic review of the effectiveness of antenatal intervention for the treatment of congenital lower urinary tract obstruction

Please cite this paper as: Morris R, Malin G, Khan K, Kilby M. Systematic review of the effectiveness of antenatal intervention for the treatment of congenital lower urinary tract obstruction. BJOG 2010;117:382–390.

Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy

Background  Congenital urinary tract obstruction can lead to perinatal mortality and morbidity. Assessing antenatal ultrasound features may help identify fetuses likely to suffer complications.

Congenital lower urinary tract obstruction: a population-based epidemiological study.

Please cite this paper as: Malin G, Tonks A, Morris R, Gardosi J, Kilby M. Congenital lower urinary tract obstruction: a population‐based epidemiological study. BJOG 2012;119:1455–1464.

Fetal umbilical artery Doppler to predict compromise of fetal/neonatal wellbeing in a high‐risk population: systematic review and bivariate meta‐analysis

We investigated the accuracy of fetal umbilical artery Doppler to predict the risk of compromise of fetal/neonatal wellbeing in a high‐risk population.

When is birthweight at term abnormally low? A systematic review and meta-analysis of the association and predictive ability of current birthweight standards for neonatal outcomes.

Intrauterine growth restriction is a cause of neonatal morbidity and mortality. A variety of definitions of low birthweight are used in clinical practice, with a lack of consensus regarding which definitions best predict adverse outcomes.

The Percutaneous shunting in Lower Urinary Tract Obstruction (PLUTO) study and randomised controlled trial: evaluation of the effectiveness, cost-effectiveness and acceptability of percutaneous vesicoamniotic shunting for lower urinary tract obstruction.

BACKGROUND Congenital lower urinary tract obstruction (LUTO) is a disease associated with high perinatal mortality and childhood morbidity. Fetal vesicoamniotic shunting (VAS) bypasses the obstruction with the potential to improve outcome. OBJECTIVE To determine the effectiveness, cost-effectiveness and patient acceptability of VAS for fetal LUTO. DESIGN A multicentre, randomised controlled trial incorporating a prospective registry, decision-analytic health economic model and preplanned Bayesian analysis using elicited opinions. Patient acceptability was evaluated by interview in a qualitative study. SETTING Fetal medicine departments in the UK, Ireland and the Netherlands. PARTICIPANTS Pregnant women with a male singleton fetus with LUTO. INTERVENTIONS In utero percutaneous VAS compared with conservative care. MAIN OUTCOME MEASURES The primary outcome was survival to 28 days. Secondary outcome measures were survival and renal function at 1 year of age, cost of care and cost per additional life-year and per disability-free survival at the end of 1 year. RESULTS The trial stopped early with 31 women randomised because of difficulties in recruitment. Of those randomised to VAS and conservative management, 3/16 (19%) and 2/15 (13%), respectively, did not receive their allocated intervention. Based on intention-to-treat analysis, survival at 28 days was higher if allocated VAS (50%) than conservative management (27%) [relative risk (RR) 1.88, 95% confidence interval (CI) 0.71 to 4.96, p = 0.27]. At 12 months survival was 44% in the VAS arm and 20% in the conservative arm (RR 2.19, 95% CI 0.69 to 6.94, p = 0.25). Neither difference was statistically significant. Of survivors at 1 year, two in the VAS arm had no evidence of renal impairment and four in the VAS arm and two in the conservative arm required medical management. One baby in the conservative arm had end-stage renal failure at 1 year. VAS was more expensive because of additional surgery and intensive care. VAS cost £15,500 per survivor at 1 year and £43,900 per disability-free year. Elicited expert opinions showed uncertainty in the effect of VAS at 28 days. In a Bayesian analysis combining elicited opinion with the results, uncertainty of the benefit of VAS remained (RR 1.31, 95% credible interval 0.84 to 2.18). The acceptability study identified visualisation of the fetus during ultrasound scanning, perceiving a personal benefit, and altruism as positive influences on recruitment. Fear of the VAS procedure and the perceived severity of LUTO influenced non-participation. The need for more detailed information about the condition and its implications during pregnancy and following delivery was a further important finding of this research. Recruitment was hampered by logistical and regulatory difficulties, a lower incidence of LUTO and lower antenatal diagnosis rate [estimated to be 3.34 (95% CI 2.95 to 3.72) per 10,000 total births and 47%, respectively, in an associated epidemiological study] and high termination of pregnancy rates. In the registry women also demonstrated a clear preference for conservative management. CONCLUSIONS Survival to 28 days and 1 year appears to be higher with VAS than with conservative management, but it is not possible to prove benefit beyond reasonable doubt. Notably, prognosis in both arms for survival and renal function is poor. VAS was substantially more costly and unlikely to be regarded as cost-effective based on the 1-year data. Parents should be counselled about the risks of pregnancy loss with or without VAS insertion. The National Institute for Health and Care Excellence interventional procedures guidance (IPG 202) should be updated to reflect this new evidence. Babies in the PLUTO trial should be followed up long term for the different outcomes. TRIAL REGISTRATION ISRCTN53328556. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 17, No. 59. See the NIHR Journals Library website for further project information.

Antenatal magnetic resonance imaging versus ultrasound for predicting neonatal macrosomia: a systematic review and meta‐analysis

Fetal macrosomia is associated with an increased risk of adverse maternal and neonatal outcomes.

Outcome in fetal lower urinary tract obstruction: a prospective registry study

To describe influences on decision‐making and prognostic variables in the prenatal management of fetal lower urinary tract obstruction (LUTO).