Do nuclear magnetic resonance (NMR)-based metabolomics improve the prediction of pregnancy-related disorders? Findings from a UK birth cohort with independent validation.

BACKGROUND: Prediction of pregnancy-related disorders is usually done based on established and easily measured risk factors. Recent advances in metabolomics may provide earlier and more accurate prediction of women at risk of pregnancy-related disorders. METHODS: We used data collected from women in the Born in Bradford (BiB; n = 8212) and UK Pregnancies Better Eating and Activity Trial (UPBEAT; n = 859) studies to create and validate prediction models for pregnancy-related disorders. These were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small for gestational age (SGA), large for gestational age (LGA) and preterm birth (PTB). We used ten-fold cross-validation and penalised regression to create prediction models. We compared the predictive performance of (1) risk factors (maternal age, pregnancy smoking, body mass index (BMI), ethnicity and parity) to (2) nuclear magnetic resonance-derived metabolites (N = 156 quantified metabolites, collected at 24-28 weeks gestation) and (3) combined risk factors and metabolites. The multi-ethnic BiB cohort was used for training and testing the models, with independent validation conducted in UPBEAT, a multi-ethnic study of obese pregnant women. RESULTS: Maternal age, pregnancy smoking, BMI, ethnicity and parity were retained in the combined risk factor and metabolite models for all outcomes apart from PTB, which did not include maternal age. In addition, 147, 33, 96, 51 and 14 of the 156 metabolite traits were retained in the combined risk factor and metabolite model for GDM, HDP, SGA, LGA and PTB, respectively. These include cholesterol and triglycerides in very low-density lipoproteins (VLDL) in the models predicting GDM, HDP, SGA and LGA, and monounsaturated fatty acids (MUFA), ratios of MUFA to omega 3 fatty acids and total fatty acids, and a ratio of apolipoprotein B to apolipoprotein A-1 (APOA:APOB1) were retained predictors for GDM and LGA. In BiB, discrimination for GDM, HDP, LGA and SGA was improved in the combined risk factors and metabolites models. Risk factor area under the curve (AUC 95% confidence interval (CI)): GDM (0.69 (0.64, 0.73)), HDP (0.74 (0.70, 0.78)) and LGA (0.71 (0.66, 0.75)), and SGA (0.59 (0.56, 0.63)). Combined risk factor and metabolite models AUC 95% (CI): GDM (0.78 (0.74, 0.81)), HDP (0.76 (0.73, 0.79)) and LGA (0.75 (0.70, 0.79)), and SGA (0.66 (0.63, 0.70)). For GDM, HDP and LGA, but not SGA, calibration was good for a combined risk factor and metabolite model. Prediction of PTB was poor for all models. Independent validation in UPBEAT at 24-28 weeks and 15-18 weeks gestation confirmed similar patterns of results, but AUCs were attenuated. CONCLUSIONS: Our results suggest a combined risk factor and metabolite model improves prediction of GDM, HDP and LGA, and SGA, when compared to risk factors alone. They also highlight the difficulty of predicting PTB, with all models performing poorly.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

Distribution and Function of Prostaglandin E2 Receptors in Mouse Uterus: Translational Value for Human Reproduction.

Prostaglandin (PG) E analogs are used clinically to ripen the cervix and induce labor. However, selective receptor agonists may have potential to improve induction response rates or manage unwanted uterine hypercontractility in conditions such as dysmenorrhea and preterm labor. To characterize their therapeutic value, PGE2 analogs were used to investigate the functional E-type prostanoid (EP) receptor population in isolated human uterus. Responsiveness in mouse tissues was also examined to validate its use as a preclinical model. Uterine samples were obtained from mice at dioestrus (n = 12), term gestation (n = 14), and labor (n = 12) and from the lower uterus of women undergoing hysterectomy (n = 12) or Caesarean section (n = 18). Vehicle and agonist effects were assessed using superfusion and immersion techniques. PGE2 evoked predominant excitatory responses in mouse and relaxation in human tissues. Selective EP4 agonists inhibited tissue activity in both nonpregnant species, while the EP2 mimetic CP533536 also attenuated uterine contractions throughout gestation. The uterotonic effects of the EP3/1 agonist sulprostone were more pronounced than the EP1 agonist ONO-D1-004, corresponding to abundant EP3 receptor expression in all samples. The contractile phenotype in mouse compared with human uteri may relate to regional differences as well as high expression of EP3 receptor transcripts. Similarities in nonpregnant and gestational tissues across species suggest that EP3 may represent a valuable translational drug target for preventing uterine hypercontractility by employing a selective antagonist. SIGNIFICANCE STATEMENT: This research validates the use of nonpregnant mice for preclinical drug discovery of uterine EP receptor targets. To determine the utility of novel drugs and delivery systems at term pregnancy and labor, pharmacological agents interacting with EP3 receptors have clear translational value.

An evaluation of the influence of the publication of the UK National Institute for health and Care Excellence's guidance on hypertension in pregnancy: a retrospective analysis of clinical practice.

BACKGROUND: The UK National Institute for health and Care Excellence (NICE) publish guidance aimed at standardising practice. Evidence regarding how well recommendations are implemented and what clinicians think about guidance is limited. We aimed to establish the extent to which the NICE Hypertension in pregnancy (HIP) guidance has influenced care and assess clinician's attitudes to this guidance. METHODS: Five maternity units in the Midlands and North of England took part in the retrospective evaluation of 2490 birth records from randomly selected dates in 2008-2010 and 2013-2015. The proportion of women where care was adhered to before (2008-2010) and after (2013-2015) guidance publication was examined and differences estimated. Eleven midwives and obstetricians employed by Bradford Hospitals were interviewed. RESULTS: The proportion of high risk women prescribed Aspirin rose (before 14%, after 54%, p = < 0.01 (confidence interval of change (CI) 37, 43%) as well as for moderate risk women (before 3%, after 54%, p = < 0.01, CI 48, 54%) following guidance publication. Three quarters had blood pressure and a third proteinuria measured at every antenatal visit before and after guidance. Early birth < 37 weeks and ≥ 37 weeks gestation was more frequently offered after guidance publication than before (< 37 weeks: before 9%, after 18%, p = 0.01, CI 2, 16% and ≥ 37 weeks before 30%, after 52%, p = < 0.01, CI 9, 35%). Few were informed of future risk of developing a hypertensive disorder or had a documented postnatal review; however there was an increase in women advised to see their GP for this review (58% before and 90% after guidance p = < 0.01, CI 24, 39%). All clinicians said the NICE HIP guidance was informative and provided robust evidence, however they said length of the document made use in practice challenging. They did not always access NICE guidance, preferring to use local guidance at least initially; both obstetricians and midwives said they accessed NICE guidance for in-depth information. CONCLUSIONS: NICE HIP guidance is valued, used by clinicians and has influenced important aspects of care that may help improve outcomes for women who develop hypertension or pre-eclampsia, however some recommendations have had limited impact and therefore interventions are required to improve adherence.

Association of maternal exposures with adiposity at age 4/5 years in white British and Pakistani children: findings from the Born in Bradford study.

AIMS/HYPOTHESIS: There is evidence that, from birth, South Asians are fatter, for a given body mass, than Europeans. The role of developmental overnutrition related to maternal adiposity and circulating glucose in these ethnic differences is unclear. Our aim was to compare associations of maternal gestational adiposity and glucose with adiposity at age 4/5 years in white British and Pakistani children. METHODS: Born in Bradford is a prospective study of children born between 2007 and 2010 in Bradford, UK. Mothers completed an OGTT at 27-28 weeks of gestation. We examined associations between maternal gestational BMI, fasting glucose, post-load glucose and diabetes (GDM) and offspring height, weight, BMI and subscapular skinfold (SSF) and triceps skinfold (TSF) thickness at age 4/5 years, using data from 6060 mother-offspring pairs (2717 [44.8%] white British and 3343 [55.2%] Pakistani). RESULTS: Pakistani mothers had lower BMI and higher fasting and post-load glucose and were twice as likely to have GDM (defined using modified WHO criteria) than white British women (15.8% vs 6.9%). Pakistani children were taller and had lower BMI than white British children; they had similar SSF and lower TSF. Maternal BMI was positively associated with the adiposity of offspring in both ethnic groups, with some evidence of stronger associations in Pakistani mother-offspring pairs. For example, the difference in adjusted mean BMI per 1 kg/m2 greater maternal BMI was 0.07 kg/m2 (95% CI 0.05, 0.08) and 0.10 kg/m2 (95% CI 0.09. 0.11) in white British and Pakistani children, respectively, with equivalent results for SSF being 0.07 mm (95% CI 0.05, 0.08) and 0.09 mm (95% CI 0.08. 0.11) (p for ethnic difference < 0.03 for both). There was no strong evidence of association of fasting and post-load glucose, or GDM, with outcomes in either group. CONCLUSIONS/INTERPRETATION: At age 4/5 years, Pakistani children are taller and lighter than white British children. While maternal BMI is positively associated with offspring adiposity, gestational glycaemia is not clearly related to offspring adiposity in either ethnic group.

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials.

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802.

Different strategies for diagnosing gestational diabetes to improve maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. Use of different tests and different criteria will influence which women are diagnosed with GDM. This is an update of a review published in 2011 and 2015. OBJECTIVES: To evaluate and compare different testing strategies for diagnosis of gestational diabetes mellitus to improve maternal and infant health while assessing their impact on healthcare service costs. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (9 January 2017) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model, cluster-randomised or cross-over trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included a total of seven small trials, with 1420 women. One trial including 726 women was identified by this update and examined the two step versus one step approach. These trials were assessed as having varying risk of bias, with few outcomes reported. We prespecified six outcomes to be assessed for quality using the GRADE approach for one comparison: 75 g oral glucose tolerance test (OGTT) versus 100 g OGTT; data for only one outcome (diagnosis of gestational diabetes) were available for assessment. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50 g glucose polymer drink (40 women) and a 50 g glucose monomer drink (43 women). We have included the results reported by this trial as separate comparisons. No trial reported on measures of costs of health services.We examined six main comparisons. 75 g OGTT versus 100 g OGTT (1 trial, 248 women): women who received 75 g OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75; very-low quality evidence). No data were reported for the following additional outcomes prespecified for GRADE assessment: caesarean section, macrosomia > 4.5 kg or however defined in the trial, long-term type 2 diabetes maternal, long-term type 2 diabetes infant and economic costs. Candy bar versus 50 g glucose monomer drink (1 trial, 60 women): more women receiving the candy bar, rather than glucose monomer, preferred the taste of the candy bar (RR 0.60, 95% CI 0.42 to 0.86) and 1-hour glucose was less with the candy bar. There were no differences in the other outcomes reported (maternal side effects). No infant outcomes were reported or any review primary outcomes. 50 g glucose polymer drink versus 50 g glucose monomer drink (3 trials, 239 women): mean difference (MD) in gestation at birth was -0.80 weeks (1 trial, 100 women; 95% CI -1.69 to 0.09). Total side effects were less common with the glucose polymer drink (1 trial, 63 women; RR 0.21, 95% CI 0.07 to 0.59), and no clear difference in taste acceptability was reported (1 trial, 63 women; RR 0.99, 95% CI 0.76 to 1.29). Fewer women reported nausea following the 50 g glucose polymer drink compared with the 50 g glucose monomer drink (1 trial, 66 women; RR 0.29, 95% CI 0.11 to 0.78). No other measures of maternal morbidity or outcomes for the infant were reported. 50 g glucose food versus 50 g glucose drink (1 trial, 30 women): women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). No clear difference was noted in the number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome were reported for the infant or review primary outcomes. 75 g OGTT World Health Organization (WHO) criteria versus 75 g OGTT American Diabetes Association (ADA) criteria (1 trial, 116 women): no clear differences in included outcomes were observed between women who received the 75 g OGTT and were diagnosed using criteria based on WHO (1999) recommendations and women who received the 75 g OGTT and were diagnosed using criteria recommended by the ADA (1979). Outcomes measured included diagnosis of gestational diabetes (RR 1.47, 95% CI 0.66 to 3.25), caesarean section (RR 1.07, 95% CI 0.85 to 1.35), macrosomia defined as > 90th percentile by ultrasound or birthweight equal to or exceeding 4000 g (RR 0.73, 95% CI 0.19 to 2.79), stillbirth (RR 0.49, 95% CI 0.02 to 11.68) and instrumental birth (RR 0.21, 95% CI 0.01 to 3.94). No other secondary outcomes were reported. Two-step approach (50 g oral glucose challenge test followed by selective 100 g OGTT Carpenter and Coustan criteria) versus one-step approach (universal 75 g OGTT ADA criteria) (1 trial, 726 women): women allocated the two-step approach had a lower risk of being diagnosed with GDM at 11 to 14 weeks' gestation compared to women allocated the one-step approach (RR 0.51, 95% CI 0.28 to 0.95). No other primary or secondary outcomes were reported. AUTHORS' CONCLUSIONS: There is insufficient evidence to suggest which strategy is best for diagnosing GDM. Large randomised trials are required to establish the best strategy for correctly identifying women with GDM.

Lifestyle interventions for the treatment of women with gestational diabetes.

BACKGROUND: Gestational diabetes (GDM) is glucose intolerance, first recognised in pregnancy and usually resolving after birth. GDM is associated with both short- and long-term adverse effects for the mother and her infant. Lifestyle interventions are the primary therapeutic strategy for many women with GDM. OBJECTIVES: To evaluate the effects of combined lifestyle interventions with or without pharmacotherapy in treating women with gestational diabetes. SEARCH METHODS: We searched the Pregnancy and Childbirth Group's Trials Register (14 May 2016), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (14th May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included only randomised controlled trials comparing a lifestyle intervention with usual care or another intervention for the treatment of pregnant women with GDM. Quasi-randomised trials were excluded. Cross-over trials were not eligible for inclusion. Women with pre-existing type 1 or type 2 diabetes were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. All selection of studies, data extraction was conducted independently by two review authors. MAIN RESULTS: Fifteen trials (in 45 reports) are included in this review (4501 women, 3768 infants). None of the trials were funded by a conditional grant from a pharmaceutical company. The lifestyle interventions included a wide variety of components such as education, diet, exercise and self-monitoring of blood glucose. The control group included usual antenatal care or diet alone. Using GRADE methodology, the quality of the evidence ranged from high to very low quality. The main reasons for downgrading evidence were inconsistency and risk of bias. We summarised the following data from the important outcomes of this review. Lifestyle intervention versus control groupFor the mother:There was no clear evidence of a difference between lifestyle intervention and control groups for the risk of hypertensive disorders of pregnancy (pre-eclampsia) (average risk ratio (RR) 0.70; 95% confidence interval (CI) 0.40 to 1.22; four trials, 2796 women; I2 = 79%, Tau2 = 0.23; low-quality evidence); caesarean section (average RR 0.90; 95% CI 0.78 to 1.05; 10 trials, 3545 women; I2 = 48%, Tau2 = 0.02; low-quality evidence); development of type 2 diabetes (up to a maximum of 10 years follow-up) (RR 0.98, 95% CI 0.54 to 1.76; two trials, 486 women; I2 = 16%; low-quality evidence); perineal trauma/tearing (RR 1.04, 95% CI 0.93 to 1.18; one trial, n = 1000 women; moderate-quality evidence) or induction of labour (average RR 1.20, 95% CI 0.99 to 1.46; four trials, n = 2699 women; I2 = 37%; high-quality evidence).More women in the lifestyle intervention group had met postpartum weight goals one year after birth than in the control group (RR 1.75, 95% CI 1.05 to 2.90; 156 women; one trial, low-quality evidence). Lifestyle interventions were associated with a decrease in the risk of postnatal depression compared with the control group (RR 0.49, 95% CI 0.31 to 0.78; one trial, n = 573 women; low-quality evidence).For the infant/child/adult:Lifestyle interventions were associated with a reduction in the risk of being born large-for-gestational age (LGA) (RR 0.60, 95% CI 0.50 to 0.71; six trials, 2994 infants; I2 = 4%; moderate-quality evidence). Birthweight and the incidence of macrosomia were lower in the lifestyle intervention group.Exposure to the lifestyle intervention was associated with decreased neonatal fat mass compared with the control group (mean difference (MD) -37.30 g, 95% CI -63.97 to -10.63; one trial, 958 infants; low-quality evidence). In childhood, there was no clear evidence of a difference between groups for body mass index (BMI) ≥ 85th percentile (RR 0.91, 95% CI 0.75 to 1.11; three trials, 767 children; I2 = 4%; moderate-quality evidence).There was no clear evidence of a difference between lifestyle intervention and control groups for the risk of perinatal death (RR 0.09, 95% CI 0.01 to 1.70; two trials, 1988 infants; low-quality evidence). Of 1988 infants, only five events were reported in total in the control group and there were no events in the lifestyle group. There was no clear evidence of a difference between lifestyle intervention and control groups for a composite of serious infant outcome/s (average RR 0.57, 95% CI 0.21 to 1.55; two trials, 1930 infants; I2 = 82%, Tau2 = 0.44; very low-quality evidence) or neonatal hypoglycaemia (average RR 0.99, 95% CI 0.65 to 1.52; six trials, 3000 infants; I2 = 48%, Tau2 = 0.12; moderate-quality evidence). Diabetes and adiposity in adulthood and neurosensory disability in later childhoodwere not prespecified or reported as outcomes for any of the trials included in this review. AUTHORS' CONCLUSIONS: Lifestyle interventions are the primary therapeutic strategy for women with GDM. Women receiving lifestyle interventions were less likely to have postnatal depression and were more likely to achieve postpartum weight goals. Exposure to lifestyle interventions was associated with a decreased risk of the baby being born LGA and decreased neonatal adiposity. Long-term maternal and childhood/adulthood outcomes were poorly reported.The value of lifestyle interventions in low-and middle-income countries or for different ethnicities remains unclear. The longer-term benefits or harms of lifestyle interventions remains unclear due to limited reporting.The contribution of individual components of lifestyle interventions could not be assessed. Ten per cent of participants also received some form of pharmacological therapy. Lifestyle interventions are useful as the primary therapeutic strategy and most commonly include healthy eating, physical activity and self-monitoring of blood glucose concentrations.Future research could focus on which specific interventions are most useful (as the sole intervention without pharmacological treatment), which health professionals should give them and the optimal format for providing the information. Evaluation of long-term outcomes for the mother and her child should be a priority when planning future trials. There has been no in-depth exploration of the costs 'saved' from reduction in risk of LGA/macrosomia and potential longer-term risks for the infants.

Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.

BACKGROUND: Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin. Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII). OBJECTIVES: To compare CSII with MDI of insulin for pregnant women with pre-existing and gestational diabetes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing CSII with MDI for pregnant women with diabetes. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies and two review authors extracted data. Disagreements were resolved through discussion with the third author. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review.There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability).There was no clear evidence of differences in the maternal secondary outcomes: maternal weight gain during pregnancy, 24 hour mean blood glucose in each trimester, mean maternal HbA1c in each trimester, maternal hypoglycaemia, and maternal hyperglycaemia. The included studies did not report several GRADE outcomes: perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour. Many maternal secondary outcomes were also not reported.In two trials, including a total of 61 infants, CSII was associated with an increase in mean birthweight compared with MDI (mean difference (MD) 220.56 g, 95% CI -2.09 g to 443.20 g; P = 0.05). However, the large CI including anything from a small reduction to an increase in mean birthweight and the lack of a difference in macrosomia rate (RR 3.20, CI 0.14 to 72.62; two trials, 61 infants) suggests uncertainty. Large-for-gestational age (see above), andsmall-for-gestational age also suggests uncertainty of effect. No significant differences were found in: gestation at delivery, preterm birth < 37 weeks' gestation, preterm birth < 32 weeks' gestation, neonatal hypoglycaemia (evidence graded very low), respiratory distress syndrome, neonatal hyperbilirubinaemia, and fetal anomaly. There were no data reported on many important infant outcomes, including the GRADE outcomes adiposity and diabetes. There was no follow-up of infants in childhood or adulthood, so longer-term outcomes were not reported.The only outcome reported for use of health service resources wasmaternal days hospitalised, which did not show a difference between groups in the small number of women included (MD 9.40, CI -6.04 to 24.84; one trial, 10 women).The methods used by the trials were poorly reported, for example although blinding of participants and clinicians regarding intervention allocation is impossible, it is possible to blind assessors and this along with other aspects of trial methods was not reported, which means that the trials are at an unclear or high risk of bias. We do not know if the women who participated were representative, and therefore if the results can be generalised. Most GRADE outcomes were not reported. For the GRADE outcomes that were reported, our assessment was that the evidence is very low quality (caesarean section, large-for-gestational age, perinatal mortality, andneonatal hypoglycaemia). This was due to design limitations in the included trials, small sample sizes in the trials contributing data, wide CIs crossing both the line of no effect and the line of appreciable benefit and/or harm, and often few events. We are therefore uncertain whether CSII or MDI improves outcomes for pregnant women with diabetes and their infants, and the results of further studies may differ substantially from those presented in this review. AUTHORS' CONCLUSIONS: There is no evidence to support the use of one particular form of insulin administration over another for pregnant women with diabetes. There are only a small number of trials appropriate for meta-analysis, a small number of women included and questionable generalisability of the trial population.Pump technology has progressed since these trials were undertaken. Well-designed randomised trials are required to evaluate comparisons such as patch pumps against MDI and more conventional CSII against MDI. These trials should be adequately powered to assess the effect of interventions, and report the core set of outcomes used in Cochrane reviews of diabetes in pregnancy. Trials to assess the effects of pumps on birthweight and macrosomia rates are needed. It would be beneficial for future trials to undertake longer-term follow-up of participants and their infants, assess women's preferences, and conduct an economic evaluation.

The HAPPY (Healthy and Active Parenting Programmme for early Years) feasibility randomised control trial: acceptability and feasibility of an intervention to reduce infant obesity.

BACKGROUND: The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY). METHODS: A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m(2)) were recruited between 10-26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59) or usual care (N = 61). Appropriate outcome measures for a full trial were explored, including: infant's length and weight, woman's BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content. RESULTS: Recruitment targets were met (~20 women/month) with a recruitment rate of 30 % of eligible women (120/396). There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1-12). Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of -0.25 standard deviation scores for infant weight at 12 months (95 % CI: -0.16-0.65) favouring the intervention was observed using intention to treat analyses. No adverse events were reported. CONCLUSIONS: The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it, however attendance was low; adaptations to increase initial attendance are recommended. Whilst the study was not powered to detect a definitive effect, our results suggest a potential to reduce risk of infant obesity. The evidence reported provides valuable lessons to inform progression to a definitive trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56735429.

Different strategies for diagnosing gestational diabetes to improve maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. Use of different tests and different criteria will influence which women are diagnosed with GDM. OBJECTIVES: To evaluate and compare different testing strategies for diagnosis of gestational diabetes mellitus to improve maternal and infant health while assessing their impact on healthcare service costs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We identified six small trials, including 694 women. These trials were assessed as having varying risk of bias, with few outcomes reported. We prespecified six outcomes to be assessed for quality using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach; data for only one outcome (diagnosis of gestational diabetes) were available for assessment. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50-gram glucose polymer drink (40 women) and a 50-gram glucose monomer drink (43 women). We have reported results reported by this trial as separate comparisons. 75-gram oral glucose tolerance test (OGTT) versus 100-gram OGTT (one trial, 248 women): Women given the 75-gram OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75). This difference was borderline in terms of statistical significance, and evidence was considered to be of very low quality when assessed by GRADE. No data were reported for the following additional outcomes prespecified for assessment in GRADE: caesarean section, macrosomia > 4.5 kg or however defined in the trial, long-term type 2 diabetes maternal, long-term type 2 diabetes infant and economic costs. Candy bar versus 50-gram glucose monomer drink (one trial, 60 women): More women receiving the candy bar, rather than glucose monomer, preferred the taste of the candy bar (RR 0.60, 95% CI 0.42 to 0.86). Infant outcomes were not reported. 50-gram glucose polymer drink versus 50-gram glucose monomer drink (three trials, 239 women): Mean difference (MD) in gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09). Total side effects were less common with the glucose polymer drink (one trial, 63 women; RR 0.21, 95% CI 0.07 to 0.59), and no clear difference in taste acceptability was reported (one trial, 63 women; RR 0.99, 95% CI 0.76 to 1.29). Significantly fewer women reported nausea following the 50-gram glucose polymer drink compared with the 50-gram glucose monomer drink (one trial, 66 women; RR 0.29, 95% CI 0.11 to 0.78). No other measures of maternal morbidity or outcomes for the infant were reported. 50-gram glucose food versus 50-gram glucose drink (one trial, 30 women): Women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). No clear difference was noted in the number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome were reported for the infant. 75-gram oral glucose tolerance test (OGTT) World Health Organization (WHO) criteria versus 75-gram OGTT American Diabetes Association (ADA) criteria (one trial, 116 women): No clear differences in included outcomes were observed between women who received the 75-gram OGTT and were diagnosed using criteria based on WHO (1999) recommendations and women who received the 75-gram OGTT and were diagnosed using criteria recommended by the ADA (1979). Outcomes measured included diagnosis of gestational diabetes (RR 1.47, 95% CI 0.66 to 3.25), caesarean birth (RR 1.07, 95% CI 0.85 to 1.35), macrosomia defined as > 90th percentile by ultrasound or birthweight equal to or exceeding 4000 g (RR 0.73, 95% CI 0.19 to 2.79), stillbirth (RR 0.49, 95% CI 0.02 to 11.68) and instrumental birth (RR 0.21, 95% CI 0.01 to 3.94). AUTHORS' CONCLUSIONS: Evidence is insufficient to permit assessment of which strategy is best for diagnosing GDM.

Antenatal dietary education and supplementation to increase energy and protein intake.

BACKGROUND: Gestational weight gain is positively associated with fetal growth, and observational studies of food supplementation in pregnancy have reported increases in gestational weight gain and fetal growth. OBJECTIVES: To assess the effects of education during pregnancy to increase energy and protein intake, or of actual energy and protein supplementation, on energy and protein intake, and the effect on maternal and infant health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), reference lists of retrieved studies and contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials of dietary education to increase energy and protein intake, or of actual energy and protein supplementation, during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and checked for accuracy. Extracted data were supplemented by additional information from the trialists we contacted. MAIN RESULTS: We examined 149 reports corresponding to 65 trials. Of these trials, 17 were included, 46 were excluded, and two are ongoing. Overall, 17 trials involving 9030 women were included. For this update, we assessed methodological quality of the included trials using the standard Cochrane criteria (risk of bias) and the GRADE approach. The overall risk of bias was unclear. Nutritional education (five trials, 1090 women) Women given nutritional education had a lower relative risk of having a preterm birth (two trials, 449 women) (risk ratio (RR) 0.46, 95% CI 0.21 to 0.98, low-quality evidence), and low birthweight (one trial, 300 women) (RR 0.04, 95% CI 0.01 to 0.14). Head circumference at birth was increased in one trial (389 women) (mean difference (MD) 0.99 cm, 95% CI 0.43 to 1.55), while birthweight was significantly increased among undernourished women in two trials (320 women) (MD 489.76 g, 95% CI 427.93 to 551.59, low-quality evidence), but did not significantly increase for adequately nourished women (MD 15.00, 95% CI -76.30 to 106.30, one trial, 406 women). Protein intake increased significantly (three trials, 632 women) (protein intake: MD +6.99 g/day, 95% CI 3.02 to 10.97). No significant differences were observed on any other outcomes such as neonatal death (RR 1.28, 95% CI 0.35 to 4.72, one trial, 448 women, low-quality evidence), stillbirth (RR 0.37, 95% CI 0.07 to 1.90, one trial, 431 women, low-quality evidence), small-for-gestational age (RR 0.97, 95% CI 0.45 to 2.11, one trial, 404 women, low-quality evidence) and total gestational weight gain (MD -0.41, 95% CI -4.41 to 3.59, two trials, 233 women). There were no data on perinatal death. Balanced energy and protein supplementation (12 trials, 6705 women)Risk of stillbirth was significantly reduced for women given balanced energy and protein supplementation (RR 0.60, 95% CI 0.39 to 0.94, five trials, 3408 women, moderate-quality evidence), and the mean birthweight was significantly increased (random-effects MD +40.96 g, 95% CI 4.66 to 77.26, Tau² = 1744, I² = 44%, 11 trials, 5385 women, moderate-quality evidence). There was also a significant reduction in the risk of small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90, I² = 16%, seven trials, 4408 women, moderate-quality evidence). No significant effect was detected for preterm birth (RR 0.96, 95% CI 0.80 to 1.16, five trials, 3384 women, moderate-quality evidence) or neonatal death (RR 0.68, 95% CI 0.43 to 1.07, five trials, 3381 women, low-quality evidence). Weekly gestational weight gain was not significantly increased (MD 18.63, 95% CI -1.81 to 39.07, nine trials, 2391 women, very low quality evidence). There were no data reported on perinatal death and low birthweight. High-protein supplementation (one trial, 1051 women)High-protein supplementation (one trial, 505 women), was associated with a significantly increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to 2.41, moderate-quality evidence). There was no significant effect for stillbirth (RR 0.81, 95% CI 0.31 to 2.15, one trial, 529 women), neonatal death (RR 2.78, 95% CI 0.75 to 10.36, one trial, 529 women), preterm birth (RR 1.14, 95% CI 0.83 to 1.56, one trial, 505 women), birthweight (MD -73.00, 95% CI -171.26 to 25.26, one trial, 504 women) and weekly gestational weight gain (MD 4.50, 95% CI -33.55 to 42.55, one trial, 486 women, low-quality evidence). No data were reported on perinatal death. Isocaloric protein supplementation (two trials, 184 women)Isocaloric protein supplementation (two trials, 184 women) had no significant effect on birthweight (MD 108.25, 95% CI -220.89 to 437.40) and weekly gestational weight gain (MD 110.45, 95% CI -82.87 to 303.76, very low-quality evidence). No data reported on perinatal mortality, stillbirth, neonatal death, small-for-gestational age, and preterm birth. AUTHORS' CONCLUSIONS: This review provides encouraging evidence that antenatal nutritional education with the aim of increasing energy and protein intake in the general obstetric population appears to be effective in reducing the risk of preterm birth, low birthweight, increasing head circumference at birth, increasing birthweight among undernourished women, and increasing protein intake. There was no evidence of benefit or adverse effect for any other outcome reported.Balanced energy and protein supplementation seems to improve fetal growth, and may reduce the risk of stillbirth and infants born small-for-gestational age. High-protein supplementation does not seem to be beneficial and may be harmful to the fetus. Balanced-protein supplementation alone had no significant effects on perinatal outcomes.The results of this review should be interpreted with caution. The risk of bias was either unclear or high for at least one category examined in several of the included trials, and the quality of the evidence was low for several important outcomes. Also, as the anthropometric characteristics of the general obstetric population is changing, those developing interventions aimed at altering energy and protein intake should ensure that only those women likely to benefit are included. Large, well-designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.

Assessment of cognitive function across pregnancy using CANTAB: a longitudinal study.

Significant changes in endogenous plasma hormone levels are required to sustain pregnancy which provides a unique opportunity to study their effect on cognitive function. Four carefully selected tests from the Cambridge Neuropsychological Automated Test Battery (CANTAB) were administered to assess the cognitive function of a group of 23 women during each trimester of pregnancy and at three months following birth. Test scores were compared with a control group of 24 non-pregnant women. The Edinburgh Postnatal Depression Scale was administered to assess anxiety and risk of depression. The National Adult Reading Test (NART) was used as a measure of verbal intelligence. Plasma hormone levels were measured at each time-point. The pregnant group scored significantly lower than the control group on the Spatial Recognition Memory (SRM) test at the second trimester and postpartum assessments (p⩽0.004). A significant pregnant group-time interaction (p=0.005) for SRM performance was demonstrated. Compared to their first trimester assessment, the pregnant group scored on average 11.7% less on each subsequent SRM test. The pregnant group reported more symptoms of anxiety and depression compared to the control group (EPDS-4 point increase in mean score at each assessment, p=0.002). There were no plasma hormone levels and test score associations identified. These data suggest SRM performance is adversely affected by pregnancy. Other aspects of executive function seem to be unaffected. Although the pregnant group reported more symptoms of anxiety and depression compared to the control group, analysis indicates that this confounder is not responsible for the SRM differences.

Interventions for women in subsequent pregnancies following obstetric anal sphincter injury to reduce the risk of recurrent injury and associated harms.

BACKGROUND: Perineal damage occurs frequently during childbirth, with severe damage involving injury to the anal sphincter reported in up to 18% of vaginal births. Women who have sustained anal sphincter damage are more likely to suffer perineal pain, dyspareunia (painful sexual intercourse), defaecatory dysfunction, and urinary and faecal incontinence compared to those without damage. Interventions in a subsequent pregnancy may be beneficial in reducing the risk of further severe trauma and may reduce the risk of associated morbidities. OBJECTIVES: To examine the effects of Interventions for women in subsequent pregnancies following obstetric anal sphincter injury for improving health. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014). SELECTION CRITERIA: Randomised controlled trials, cluster-randomised trials and multi-arm trials assessing the effects of any intervention in subsequent pregnancies following obstetric anal sphincter injury to improve health. Quasi-randomised controlled trials and cross-over trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: No trials were included. In future updates of this review, at least two review authors will extract data and assess the risk of bias of included studies. MAIN RESULTS: No eligible completed trials were identified. One ongoing trial was identified. AUTHORS' CONCLUSIONS: No relevant trials were included. The effectiveness of interventions for women in subsequent pregnancies following obstetric anal sphincter injury for improving health is therefore unknown. Randomised trials to assess the relative effects of interventions are required before clear practice recommendations can be made.

Evaluation of the impact of universal testing for gestational diabetes mellitus on maternal and neonatal health outcomes: a retrospective analysis.

BACKGROUND: Gestational diabetes (GDM) affects a substantial proportion of women in pregnancy and is associated with increased risk of adverse perinatal and long term outcomes. Treatment seems to improve perinatal outcomes, the relative effectiveness of different strategies for identifying women with GDM however is less clear.This paper describes an evaluation of the impact of a change in policy from selective risk factor based offering, to universal offering of an oral glucose tolerance test (OGTT) to identify women with GDM on maternal and neonatal outcomes. METHODS: Retrospective six year analysis of 35,674 births at the Women's and Newborn unit, Bradford Royal Infirmary, United Kingdom. RESULTS: The proportion of the whole obstetric population diagnosed with GDM increased almost fourfold following universal offering of an OGTT compared to selective offering of an OGTT; Rate Ratio (RR) 3.75 (95% CI 3.28 to 4.29), the proportion identified with severe hyperglycaemia doubled following the policy change; 1.96 (1.50 to 2.58). The case detection rate however, for GDM in the whole population and severe hyperglycaemia in those with GDM reduced by 50-60%; 0.40 (0.35 to 0.46) and 0.51 (0.39 to 0.67) respectively. Universally offering an OGTT was associated with an increased induction of labour rate in the whole obstetric population and in women with GDM; 1.43 (1.35 to 1.50) and 1.21 (1.00 to1.49) respectively. Caesarean section, macrosomia and perinatal mortality rates in the whole population were similar. For women with GDM, rate of caesarean section; 0.70 (0.57 to 0.87), macrosomia; 0.22 (0.15 to 0.34) and perinatal mortality 0.12 (0.03 to 0.46) decreased following the policy change. CONCLUSIONS: Universally offering an OGTT was associated with increased identification of women with GDM and severe hyperglycaemia and with neonatal benefits for those with GDM. There was no evidence of benefit or adverse effects in neonatal outcomes in the whole obstetric population.

Nutrition advice in pregnancy.

Being overweight or obese in pregnancy is associated with an increased risk of poor pregnancy outcomes and long-term ill health for both mother and infant. Midwives, obstetricians and healthcare support workers providing care in pregnancy are ideally placed to provide women with nutritional advice and to facilitate the acquisition of a healthy diet. This survey was undertaken to assess the provision of training in nutrition for providers of maternity care at the Bradford Women's and Newborn unit, to evaluate what nutrition information is given and to find out if care providers were satisfied with the knowledge they had. All relevant staff were approached and asked to complete a questionnaire developed by members of the unit's research team. Findings from this survey highlight the wide range of nutrition information provided by care providers at the unit. Education and training needs are being addressed by managers and a dedicated service is being developed for obese women.

Antenatal dietary advice and supplementation to increase energy and protein intake.

BACKGROUND: Gestational weight gain is positively associated with fetal growth, and observational studies of food supplementation in pregnancy have reported increases in gestational weight gain and fetal growth. OBJECTIVES: To assess the effects of advice during pregnancy to increase energy and protein intake, or of actual energy and protein supplementation, on energy and protein intakes, and the effect on maternal and infant health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (22 July 2011) and contacted researchers in the field. We updated the search on 12 July 2012 and added the results to the awaiting classification section of the review. SELECTION CRITERIA: Randomised controlled trials of dietary advice to increase energy and protein intake, or of actual energy and protein supplementation, during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and checked for accuracy. Extracted data were supplemented by additional information from the trialists we contacted. MAIN RESULTS: We examined 110 reports corresponding to 46 trials. Of these trials, 15 were included, 30 were excluded, and one is ongoing. Overall, 15 trials involving 7410 women were included.Nutritional advice (four trials, 790 women)Women given nutritional advice had a lower relative risk of having a preterm birth (two trials, 449 women) (risk ratio (RR) 0.46, 95% CI 0.21 to 0.98 ), head circumference at birth was increased in one trial (389 women) (mean difference (MD) 0.99 cm, 95% CI 0.43 to 1.55) and protein intake increased (three trials, 632 women) (protein intake: MD +6.99 g/day, 95% CI 3.02 to 10.97). No significant differences were observed on any other outcomes.Balanced energy and protein supplementation (11 trials, 5385 women)Risk of stillbirth was significantly reduced for women given balanced energy and protein supplementation (RR 0.62, 95% CI 0.40 to 0.98, five trials, 3408 women), mean birthweight was significantly increased (random-effects MD +40.96 g, 95% CI 4.66 to 77.26 , Tau(2)= 1744, I(2) = 44%, 11 trials, 5385 women). There was also a significant reduction in the risk of small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90, I(2) = 16%, seven trials, 4408 women). No significant effect was detected for preterm birth or neonatal death.High-protein supplementation (one trial, 1051 women)High-protein supplementation (one trial, 505 women), was associated with a significantly increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to 2.41).Isocaloric protein supplementation (two trials, 184 women)Isocaloric protein supplementation (two trials,184 women) had no significant effect on birthweight and weekly gestational weight gain. AUTHORS' CONCLUSIONS: This review provides encouraging evidence that antenatal nutritional advice with the aim of increasing energy and protein intake in the general obstetric population appears to be effective in reducing the risk of preterm birth, increasing head circumference at birth and increasing protein intake, there was no evidence of benefit or adverse effect for any other outcome reported.Balanced energy and protein supplementation seems to improve fetal growth, and may reduce the risk of stillbirth and infants born small-for-gestational age. High-protein supplementation does not seem to be beneficial and may be harmful to the fetus. Balanced-protein supplementation alone had no significant effects on perinatal outcomes.The results of this review should be interpreted with caution, the risk of bias was either unclear or high for at least one category examined in several of the included trials and the quality of the evidence was low for several important outcomes. Also the anthropometric characteristics of the general obstetric population is changing, therefore, those developing interventions aimed at altering energy and protein intake should ensure that only those women likely to benefit are included. Large, well designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.

Different strategies for diagnosing gestational diabetes to improve maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. OBJECTIVES: To evaluate and compare alternative tests for diagnosis of GDM, in terms of maternal and infant health and use of health service resources. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2011). SELECTION CRITERIA: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, trial quality and extracted data. MAIN RESULTS: We identified five small trials, including 578 women. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50 g glucose polymer drink (40 women) and a 50 g glucose monomer drink (43 women). We have reported results for this trial as two separate comparisons.75 g oral glucose tolerance test (OGTT) versus a 100 g OGTT (one trial, 248 women): women given the 75 g OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75).This difference was borderline for statistical significance. No other measures of maternal morbidity, or outcome for the baby were reported.Candy bar versus 50 g glucose monomer drink (one trial, 82 women): women receiving the candy bar, rather than glucose monomer, reported fewer side effects (RR 0.50, 95% CI 0.26 to 0.97) and preferred the taste (RR 0.62, 95% CI 0.44 to 0.87). No outcomes were reported for the baby.50 g glucose polymer versus 50 g glucose monomer (three trials, 259 women): mean difference (MD) in gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09). Side effects were less common with the glucose polymer (one trial 82 women; RR 0.20 95% CI 0.07 to 0.54), with no clear difference in taste acceptability (one trial 83 women; RR 0.96; 95% CI 0.78 to 1.18). Significantly fewer women reported nausea following the 50 g glucose polymer drink compared to the 50 g glucose monomer drink (one trial 66 women; RR 0.29; 95% CI 0.11 to 0.78) and bloatedness (two trials 149 women; RR 0.22; 95% CI 0.08 to 0.60). No other measures of maternal morbidity or outcome for the baby were reported.50 g glucose in food versus 50 g glucose drink (one trial, 30 women): women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). There was no clear difference in number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome for the baby were reported. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess which is the best strategy for diagnosing GDM.

Research midwives: look at the evidence!

Evidence based practice underpins modern healthcare and includes the use of research knowledge, consideration of an individual's circumstances and their personal preferences. Maternal and child health care interventions aim to prevent disease and disability and promote health and wellbeing. Before interventions are brought into practice the benefits and risks should be adequately evaluated to ensure clinicians and those receiving the interventions fully understand the potential effects. A multidisciplinary team approach to the development of research initiatives is advantageous. The team should include clinicians, researchers and service users working together to answer important clinical questions. It is our view that clinical research midwives are pivotal to the success of maternal and child health improvement initiatives. For example they can help reduce the gap between clinical practice and research by making research understandable to clinicians and applicable to practice by working in partnership with academics.