Shakila Thangaratinam

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence

Objective To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. Design Systematic review and meta-analysis. Data sources Major databases from inception to January 2012 without language restrictions. Study selection Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. Data synthesis Results summarised as relative risks for dichotomous data and mean differences for continuous data. Results We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference −50 g, −100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference −60 g, −120 to −10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. Conclusions Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.

Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence

Objectives To evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, and SCISEARCH (inception-2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth. Study selection Studies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes. Data synthesis Odds ratios from individual studies were pooled separately for cohort and case-control studies with the random effects model. Results 30 articles with 31 studies (19 cohort and 12 case-control) involving 12 126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12 566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P<0.001). For case-control studies the odds ratio for miscarriage was 1.80, 1.25 to 2.60; P=0.002). There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P=0.01). Two randomised studies evaluated the effect of treatment with levothyroxine on miscarriage. Both showed a fall in miscarriage rates, and meta-analysis showed a significant 52% relative risk reduction in miscarriages with levothyroxine (relative risk 0.48, 0.25 to 0.92; P=0.03). One study reported on the effect of levothyroxine on the rate of preterm birth, and noted a 69% relative risk reduction (0.31, 0.11 to 0.90). Conclusion The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.

Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis

BACKGROUND Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. We assessed the performance of pulse oximetry as a screening method for the detection of critical congenital heart defects in asymptomatic newborn babies. METHODS In this systematic review, we searched Medline (1951-2011), Embase (1974-2011), Cochrane Library (2011), and Scisearch (1974-2011) for relevant citations with no language restriction. We selected studies that assessed the accuracy of pulse oximetry for the detection of critical congenital heart defects in asymptomatic newborn babies. Two reviewers selected studies that met the predefined criteria for population, tests, and outcomes. We calculated sensitivity, specificity, and corresponding 95% CIs for individual studies. A hierarchical receiver operating characteristic curve was fitted to generate summary estimates of sensitivity and specificity with a random effects model. FINDINGS We screened 552 studies and identified 13 eligible studies with data for 229,421 newborn babies. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76·5% (95% CI 67·7-83·5). The specificity was 99·9% (99·7-99·9), with a false-positive rate of 0·14% (0·06-0·33). The false-positive rate for detection of critical congenital heart defects was particularly low when newborn pulse oximetry was done after 24 h from birth than when it was done before 24 h (0·05% [0·02-0·12] vs 0·50 [0·29-0·86]; p=0·0017). INTERPRETATION Pulse oximetry is highly specific for detection of critical congenital heart defects with moderate sensitivity, that meets criteria for universal screening. FUNDING None.

Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study

BACKGROUND Screening for congenital heart defects relies on antenatal ultrasonography and postnatal clinical examination; however, life-threatening defects often are not detected. We prospectively assessed the accuracy of pulse oximetry as a screening test for congenital heart defects. METHODS In six maternity units in the UK, asymptomatic newborn babies (gestation >34 weeks) were screened with pulse oximetry before discharge. Infants who did not achieve predetermined oxygen saturation thresholds underwent echocardiography. All other infants were followed up to 12 months of age by use of regional and national registries and clinical follow-up. The main outcome was the sensitivity and specificity of pulse oximetry for detection of critical congenital heart defects (causing death or requiring invasive intervention before 28 days) or major congenital heart disease (causing death or requiring invasive intervention within 12 months of age). FINDINGS 20,055 newborn babies were screened and 53 had major congenital heart disease (24 critical), a prevalence of 2·6 per 1000 livebirths. Analyses were done on all babies for whom a pulse oximetry reading was obtained. Sensitivity of pulse oximetry was 75·00% (95% CI 53·29-90·23) for critical cases and 49·06% (35·06-63·16) for all major congenital heart defects. In 35 cases, congenital heart defects were already suspected after antenatal ultrasonography, and exclusion of these reduced the sensitivity to 58·33% (27·67-84·83) for critical cases and 28·57% (14·64-46·30) for all cases of major congenital heart defects. False-positive results were noted for 169 (0·8%) babies (specificity 99·16%, 99·02-99·28), of which six cases were significant, but not major, congenital heart defects, and 40 were other illnesses that required urgent medical intervention. INTERPRETATION Pulse oximetry is a safe, feasible test that adds value to existing screening. It identifies cases of critical congenital heart defects that go undetected with antenatal ultrasonography. The early detection of other diseases is an additional advantage. FUNDING National Institute for Health Research Health Technology Assessment programme.

Interventions to Reduce or Prevent Obesity in Pregnant Women: A Systematic Review

BACKGROUND Around 50% of women of childbearing age are either overweight [body mass index (BMI) 25-29.9 kg/m(2)] or obese (BMI ≥ 30 kg/m(2)). The antenatal period provides an opportunity to manage weight in pregnancy. This has the potential to reduce maternal and fetal complications associated with excess weight gain and obesity. OBJECTIVES To evaluate the effectiveness of dietary and lifestyle interventions in reducing or preventing obesity in pregnancy and to assess the beneficial and adverse effects of the interventions on obstetric, fetal and neonatal outcomes. DATA SOURCES Major electronic databases including MEDLINE, EMBASE, BIOSIS and Science Citation Index were searched (1950 until March 2011) to identify relevant citations. Language restrictions were not applied. REVIEW METHODS Systematic reviews of the effectiveness and harm of the interventions were carried out using a methodology in line with current recommendations. Studies that evaluated any dietary, physical activity or mixed approach intervention with the potential to influence weight change in pregnancy were included. The quality of the studies was assessed using accepted contemporary standards. Results were summarised as pooled relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous data. Continuous data were summarised as mean difference (MD) with standard deviation. The quality of the overall evidence synthesised for each outcome was summarised using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and reported graphically as a two-dimensional chart. RESULTS A total of 88 studies (40 randomised and 48 non-randomised and observational studies, involving 182,139 women) evaluated the effect of weight management interventions in pregnancy on maternal and fetal outcomes. Twenty-six studies involving 468,858 women reported the adverse effect of the interventions. Meta-analysis of 30 RCTs (4503 women) showed a reduction in weight gain in the intervention group of 0.97 kg compared with the control group (95% CI -1.60 kg to -0.34 kg; p = 0.003). Weight management interventions overall in pregnancy resulted in a significant reduction in the incidence of pre-eclampsia (RR 0.74, 95% CI 0.59 to 0.92; p = 0.008) and shoulder dystocia (RR 0.39, 95% CI 0.22 to 0.70; p = 0.02). Dietary interventions in pregnancy resulted in a significant decrease in the risk of pre-eclampsia (RR 0.67, 95% CI 0.53 to 0.85; p = 0.0009), gestational hypertension (RR 0.30, 95% CI 0.10 to 0.88; p = 0.03) and preterm birth (RR 0.68, 95% CI 0.48 to 0.96; p = 0.03) and showed a trend in reducing the incidence of gestational diabetes (RR 0.52, 95% CI 0.27 to 1.03). There were no differences in the incidence of small-for-gestational-age infants between the groups (RR 0.99, 95% CI 0.76 to 1.29). There were no significant maternal or fetal adverse effects observed for the interventions in the included trials. The overall strength of evidence for weight gain in pregnancy and birthweight was moderate for all interventions considered together. There was high-quality evidence for small-for-gestational-age infants as an outcome. The quality of evidence for all interventions on pregnancy outcomes was very low to moderate. The quality of evidence for all adverse outcomes was very low. LIMITATIONS The included studies varied in the reporting of population, intensity, type and frequency of intervention and patient complience, limiting the interpretation of the findings. There was significant heterogeneity for the beneficial effect of diet on gestational weight gain. CONCLUSIONS Interventions in pregnancy to manage weight result in a significant reduction in weight gain in pregnancy (evidence quality was moderate). Dietary interventions are the most effective type of intervention in pregnancy in reducing gestational weight gain and the risks of pre-eclampsia, gestational hypertension and shoulder dystocia. There is no evidence of harm as a result of the dietary and physical activity-based interventions in pregnancy. Individual patient data meta-analysis is needed to provide robust evidence on the differential effect of intervention in various groups based on BMI, age, parity, socioeconomic status and medical conditions in pregnancy.

Accuracy of serum uric acid in predicting complications of pre‐eclampsia: a systematic review

Background  Pre‐eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre‐eclampsia.

Positron emission tomography/computerised tomography imaging in detecting and managing recurrent cervical cancer: systematic review of evidence, elicitation of subjective probabilities and economic modelling

BACKGROUND Cancer of the uterine cervix is a common cause of mortality in women. After initial treatment women may be symptom free, but the cancer may recur within a few years. It is uncertain whether it is more clinically effective to survey asymptomatic women for signs of recurrence or to await symptoms or signs before using imaging. OBJECTIVES This project compared the diagnostic accuracy of imaging using positron emission tomography/computerised tomography (PET-CT) with that of imaging using CT or magnetic resonance imaging (MRI) alone and evaluated the cost-effectiveness of adding PET-CT as an adjunct to standard practice. DATA SOURCES Standard systematic review methods were used to obtain and evaluate relevant test accuracy and effectiveness studies. Databases searched included MEDLINE, EMBASE, Science Citation Index and The Cochrane Library. All databases were searched from inception to May 2010. REVIEW METHODS Study quality was assessed using appropriately modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. Included were any studies of PET-CT, MRI or CT compared with the reference standard of histopathological findings or clinical follow-up in symptomatic women suspected of having recurrent or persistent cervical cancer and in asymptomatic women a minimum of 3 months after completion of primary treatment. Subjective elicitation of expert opinion was used to supplement diagnostic information needed for the economic evaluation. The effectiveness of treatment with chemotherapy, radiotherapy, chemoradiotherapy, radical hysterectomy and pelvic exenteration was systematically reviewed. Meta-analysis was carried out in RevMan 5.1 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) and Stata version 11 (StataCorp LP, College Station, Texas, USA). A Markov model was developed to compare the relative cost-effectiveness using TreeAge Pro software version 2011 (TreeAge Software Inc., Evanston, IL, USA). RESULTS For the diagnostic review, a total of 7524 citations were identified, of which 12 test accuracy studies were included in the review: six studies evaluated PET-CT, two evaluated MRI, three evaluated CT and one evaluated both MRI and CT. All studies were small and the majority evaluated imaging in women in whom recurrence was suspected on the basis of symptoms. The PET-CT studies evaluated local and distant recurrence and most used methods similar to current practice, whereas five of the six CT and MRI studies evaluated local recurrence only and not all employed currently used methods. Meta-analysis of PET-CT studies gave a sensitivity of 92.2% [95% confidence interval (CI) 85.1% to 96.0%] and a specificity of 88.1% (95% CI 77.9% to 93.9%). MRI sensitivities and specificities varied between 82% and 100% and between 78% and 100%, respectively, and CT sensitivities and specificities varied between 78% and 93% and between 0% and 95%, respectively. One small study directly compared PET-CT with older imaging methods and showed more true-positives and fewer false-negatives with PET-CT. The subjective elicitation from 21 clinical experts gave test accuracy results for asymptomatic and symptomatic women and the results for symptomatic women were similar to those from the published literature. Their combined opinions also suggested that the mean elicited increase in accuracy from the addition of PET-CT to MRI and/or CT was less than the elicited minimum important difference in accuracy required to justify the routine addition of PET-CT for the investigation of women after completion of primary treatment. For the effectiveness review, a total of 24,943 citations were identified, of which 62 studies were included (chemotherapy, 19 randomised controlled trials; radiotherapy or chemoradiotherapy, 16 case series; radical hysterectomy and pelvic exenteration, 27 case series). None provided the effectiveness of cisplatin monotherapy, the most commonly used chemotherapeutic agent in the NHS, compared with supportive care in a background of other treatment such as radiotherapy in recurrent and persistent cervical cancer. The model results showed that adding PET-CT to the current treatment strategy of clinical examination, MRI and/or CT scan was significantly more costly with only a minimal increase in effectiveness, with incremental cost-effectiveness ratios for all models being > £1M per quality-adjusted life-year (QALY) and the additional cost per additional case of recurrence being in the region of £600,000. LIMITATIONS There was considerable uncertainty in many of the parameters used because of a lack of good-quality evidence in recurrent or persistent cervical cancer. The evidence on diagnostic and therapeutic impact incorporated in the economic model was poor and there was little information on surveillance of asymptomatic women. CONCLUSIONS Given the current evidence available, the addition of PET-CT to standard practice was not found to be cost-effective in the diagnosis of recurrent or persistent cervical cancer. However, although probabilistic sensitivity analysis showed that the main conclusion about cost-ineffectiveness of PET-CT was firm given the range of assumptions made, should more reliable information become available on accuracy, therapeutic impact and effectiveness, and the cost of PET-CT reduce, this conclusion may need revision. Current guidelines recommending imaging for diagnosis using expensive methods such as PET-CT need to be reconsidered in the light of the above. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Accuracy of pulse oximetry in screening for congenital heart disease in asymptomatic newborns: a systematic review.

Objective: To evaluate the accuracy of pulse oximetry as a screening tool for congenital heart disease in asymptomatic newborns. Design, data sources and methods: Systematic review of relevant studies identified through MEDLINE, EMBASE, Cochrane Library, MEDION, and bibliographies of retrieved primary and review articles. Two reviewers independently extracted data on study characteristics, quality and results to construct 2×2 tables with congenital heart disease as the reference standard. A random-effects bivariate model was used to meta-analyse estimates of sensitivity and specificity. Logit pairs of sensitivity and specificity of each study were analysed in a single model, accounting for their correlation due to differences in threshold between studies. Results: Eight studies were included with a total of 35 960 newborns. Pulse oximetry was performed on asymptomatic newborns in all studies; three studies excluding newborns with an antenatal diagnosis of congenital heart disease. Either functional or fractional oxygen saturation was measured by pulse oximetry with oxygen saturation below 95% as the cut-off level in most studies. On the basis of the eight studies, the summary estimates of sensitivity and specificity were 63% (95% CI 39% to 83%) and 99.8% (95% CI 99% to 100%), respectively, yielding a false positive rate of 0.2% (95% CI 0% to 1%). Conclusion: Pulse oximetry was found to be highly specific tool with very low false positive rates to detect congenital heart disease. Large, well-conducted prospective studies are needed to assess its sensitivity with higher precision.

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

BackgroundProteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies.MethodsWe conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards.ResultsSixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission.ConclusionMeasure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia.

Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis

OBJECTIVE To conduct a systematic review and metaanalysis of studies evaluating the regression rate of endometrial hyperplasia with oral progestogens and levonorgestrel-releasing intrauterine system. STUDY DESIGN Searches were conducted on Medline, Embase, Cochrane Library, and Web of Science, and reference lists of relevant articles were examined. The methodologic index for nonrandomized studies was used for quality assessment. Metaanalysis was performed with random effects model. RESULTS There were 24 observational studies (1001 women), of low methodologic quality, evaluating the outcome of regression of endometrial hyperplasia with oral progestogens or levonorgestrel-releasing intrauterine system. Metaanalysis showed that oral progestogens achieved a lower pooled regression rate compared with levonorgestrel-releasing intrauterine system for complex (pooled rate, 66% vs 92%; P < .01) and atypical hyperplasia (pooled rate, 69% vs 90%; P = .03). There was no statistical difference in simple hyperplasia (pooled rate, 89% vs 96%; P = .41). CONCLUSION Oral progestogens appear to induce a lower disease regression rate than Levonorgestrel-releasing intrauterine system in the treatment of endometrial hyperplasia.